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MINISTRY OF PUBLIC HEALTH OF THE REPUBLIC OF
KAZAKHSTAN
EDUCATIONAL-METHODICAL SECTION
OF KAZAKH STATE MEDICAL ACADEMY
ON SPECIALITIES OF HIGHER AND POST GRADUATE EDUCATION
KARAGANDA STATE MEDICAL ACADEMY
Taijanova D.J., Yevseyenko L.V., Kotlyarova O.A.
SPECIAL LECTURES OF PULMONOLOGY
Educational manual
KARAGANDA 2007
UDK 616.24
BBK 54.12 .я 7
Т 15
ISBN
Taijanova D.J.,Yevseenko L.V., Kotlyarova O.A, the educational manual “Special lectures of
pulmonology". Karaganda, 2007.
Reviewers:
Umbetalina N.S. – d.m.s., professor, the head of department of internal diseases EIF and SPE.
Molotov – Luchanskiy V. B. - c.m.s., assistant professor, the head of department for the
assistant professors’ course of nursing management at KSMA
Seisenbekov T.Z.- professor of the internal disease department of FPDME of Kazak Medical
Academy, professor
Brief performance characteristic: In this educational methodical manual, are presented the
contemporary concepts about etiology, classification and pathogenesis of frequently meeting
diseases of pulmonology, the contemporary diagnostics methods, the criteria of diagnostics and
differential diagnostics of diseases, contemporary approaches to the treatments. Educational
methodical manual is intended for the foreign students of High Medical School - Institute of
Higher Education and interns.
Confirmed and recommended for edition of Academic Council of KSMA
Protocol № _9___ of _29.03.2007 г._
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Introduction
The lungs, as the portal of entry into the body of the oxygen needed for tissue
respiration, almost imperceptibly shift in excess of 10000 litres of air a day.
Inevitably inhaled at the same time are noxious chemicals in various forms,
allergens, and microbes. Yet for most individuals the lungs remain clear and
healthy. Only excessive ‘pollution’ or faults (that may include ‘exuberant’
response) in the normally robust defence mechanisms of the lungs will result in
lung damage and disease. Whatever technological advantages occur in the future,
those concerned with respiratory health, as well as disease, will need to be alert to
dangers in the air we breathe. Infections, industrial and personal pollution, and
allergens are all known hazards-what is yet to come?
Epidemiological trends in the pattern of respiratory diseases can be an early
warning system as well as a tool for investigating causes. The association between
smoking and lung cancer raises one of the most notable contributions in the field of
respiratory medicine.
At least one-third of the population in developed countries continue to smoke
cigarettes and lung cancer and disabling chronic airflow obstruction will remain
prevalent in the foreseeable future. Tobacco manufacturers have launched a major
and cynical advertising campaign in developing countries.
Infection will continue to play a major role in respiratory disease and human
health. In developing countries where living conditions and nutrition are poor,
measles, whooping cough, and infection by Haemophilus influenzae and the
pneumococcus cause more than million deaths annually in children under the age
of 5. Tuberculosis causes 3million deaths annually worldwide. This mortality is
principally in the developing countries, but there are strong indications that the
prevalence of tuberculosis is increasing in North America and Europe in the wake
of the acquired immunodeficiency syndrome (AIDS) epidemic, and that multiply
resistant drug strains are being increasingly encountered. There is an epidemic of
pneumonia due to the opportunistic fungal pathogen Pneumocystis carinii in the
AIDS population, in whom it is a leading cause of illness and death.
Asthma affects at least 5 per cent of most populations; it is the commonest chronic
disease of children, causing more absence from school than any other condition in
many countries. It is a heterogeneous disorder resulting from the interaction of
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genetic and environmental factors. There has been a significant increase in its
prevalence over the past 20 years; the reasons for this are unclear, except that they
must be “environmental” changes of some kind.
Respiratory medicine will need to meet the challenge of new disease as well as to
deal with existing pathology by increased research effort. Here, advances in
molecular medicine and investigative techniques, and novel therapeutic approaches
offer new hope.
List of abbreviations
AIDS- Acquired immunodeficiency syndrome
ARF- Acute respiratory failure
BA- Bronchial asthma
CMV- Cytomegalovirus
COPD- Cchronic obstructive pulmonary disease
DIC- Disseminated intravascular clotting
ECG- electrocardiography
EchoCG-echocardiography
ERS- Erythrocytes segmentation rate
FEV- Forced expiratory volume
FEV1- Force expiratory volume in 1 second
FVC- Forced vital capacity
IC- Inspiratory capacity
IgE- Immunoglobulin E
PEF- Peak expiratory flow
RNA-Ribosomal ribonucleic acid
RSV- Respiratory syncytial virus
NSAID- Non-steroid anti-inflammatory drug
VC- Vital capacity
WHO-World health organization
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CHRONIC BRONCHITIS
Definition
Chronic bronchitis – is a chronic inflammatory disease accompanied by the
constant cough with sputum not less than for three months of a year during two or
more years. Mentioned above symptoms are not associated with any other diseases
of the broncho-pulmonary system, upper respiratory tract or other organs and
systems.
Etiology
chronic tonsillitis, rhinitis, sinusitis, pharyngitis, dental carious;
damage of nasal breathing of any reason (for example, polyposis of the
nose);
congenital phenomena in the lungs of any genesis;
alcohol abuse (used alcohol is secreted by the mucous membrane of bronchi
and influences on its damaging action);
chronic renal failure (secreting products of nitrogen metabolism by the
mucous membrane cause its damage).
Classification
1.
The character of the bronchial process in bronchi:
1.1. Simple bronchitis.
1.2. Purulent bronchitis with purulent sputum.
1.3. Muco-purulent bronchitis with muco-purulent sputum.
1.4. Specific forms:
1.4.1.
Hemorrhagic bronchitis with the secretion of mucous with the content of
blood.
1.4.2.
Fibrinous bronchitis – with viscous sputum rich in fibrin in the form of a
cast of small bronchi.
2.
Presence or absence of the bronchial obstruction syndrome:
2.1. Nonobstructive bronchitis.
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2.2. Obstructive bronchitis.
3.
The level of bronchial tree damage:
3.1. With primary damage of large bronchi (proximal).
3.2. With primary damage of small bronchi and bronchioles (distal).
4.
The course:
4.1. Latent.
4.2. With rare exacerbations.
4.3. With often exacerbations.
4.4. Continuous recidative.
5.
Phase:
5.1. Exacerbation.
5.2. Remission.
6.
Complications:
6.1. Emphysema of lungs.
6.2. Hemoptosis.
6.3. Respyratory failure.
The degree of the severity of the chronic respiratory failure:
I degree – obstructive damages of ventilation without arterial hypoxemia.
II degree – moderate arterial hypercapnia.
III degree – expressed arterial hypoxemia or hypercapnia.
Clinical picture
The principle subjective manifestations of chronic bronchitis are: cough with the
discharge of sputum, general weakness, perspiration.
At the beginning of the disease cough troubles usually in the morning soon after
awakening; the amount of sputum is minimal. Cough in the morning is mostly
caused by the daily rhythm of fibrillary epithelium functioning.
At first patients suffer with cough only during the period of exacerbation; during
remission it almost is not marked.
Cough at night in the lying position is caused with the sputum coming fro small
bronchi.
In small bronchi cough receptors are absent and that’s why in mainly distal
bronchitis cough may be absent; the chief complaint of the patients in this case is
dyspnea.
The attacks of cough in chronic bronchitis may be provoked by cold, frosty air; by
returning in cold weather to the warm place; by smoke, motor gases and by
different exiting substances in the air. Other factors may be too.
The discharge of sputum is the most important sign of chronic bronchitis. Sputum
may be mucous, purulent, muco-purulent and sometimes with traces of blood. In
exacerbated chronic bronchitis the amount of sputum is increased, but while the
damp weather and after the alcohol use it may be diminished. Daily amount of
sputum in most cases of patients is 50-70 ml; while the development of
bronchiectasis it markedly increased.
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With hemoptysis careful differential diagnoses is reguired; with lung tuberculosis,
pulmonary cancer, bronchoectasis. Hemoptysis may be in thromboembolia of the
pulmonary artery, in mitral stenosis, congestive cardiacfailure and in hemorrhagic
diathesises.
In incomplicated chronic bronchitis dyspnea doesn’t troble the patient. But it
becomes the characteristic sign of the disease in the development of the bronchial
obstruction and emphysema of the lungs. On physical examination of the patients
with chronic nonobstructive bronchitisessencial changes are not reveled. In the
stage of exacerbation, especially in purulent bronchitis, perspiration, possible
elevation of the body temperature (to subfebrile) may be observed.
On percussion of the lungs in this case percutative sound is clear. Vocal fremitus
and bronchophony usually are not changed.
On auscultation of the lungs prolonged expiration is marked (the normal
inspiration and expiration duration is 1:1,2). For chronic bronchitis hard respiration
is typical (unequality, roughness of the vesicular respiration).
Usually in chronic bronchitis such dry rales due to viscous sputum in the lumen of
bronchi are heard.
Moist rales are heard also when there is liquid sputum in bronchi and their
character depend on caliber of bronchi.
Any other important changes on examination of organs and systems in patients
with chronic bronchitis are not reveled as a rule.
Investigation
1.
Bronchoscopy (to determine diffuse and organic bronchitis and the degree of
bronchi inflammation).
Intensivity of the inflammation is accessed as the following:
I – degree – the bronchial mucous membrane is pale pink, covered with mucous;
doesn’t bleed. Under thinned mucous membrane translucent vessels are seen.
II – degree – the bronchial mucous membrane is brightly red, thickened,
sometimes bleeding, covered with pus.
III – degree – the bronchial and tracheal mucous membranes are thickened; they
are of purple blue color; slightly bleed and covered with purulent secretion.
2.
Bronchography (after the sanation of bronchial tree).
3.
Roentgenoscopy and roentgenography of the lungs.
X-ray signs of chronic bronchitis are reveled only in patients with a long history of
a disease. And it is typical for them to have strengthening and deformation of
pulmonary film on cellular loop type, increasing of transparence of pulmonary
trees. In some cases we can see thickening of bronchial walls due to peribronchial
pneumosclerosis.
4.
The examination of external respiration function.
Spirrographyc examination as well as pneumotachometria and pick flow
mesurement do not reveal the damage of bronchial conduction in chronic
nonobstructive bronchitis. But about in 30% of patients the increase of the residual
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volume of lungs, decreasing of FEV50 and FEV75 (maximal volume rate on the
level 50 or 75 of forced vital capacity) in normal data of vital capacity of the pick
volume rate.
5.
Examination of the gas blood components.
Blood gases are often normal. In the advanced case there is evidence of
hypoxaemia and hypercapnia.
The diagnosis of exacerbation
The following signs in the process of bronchi are typical for the inflammatory
process:
the increase of the general weakness, ailment, the decrease of the general
work ability;
the appearance of the marked sweating, especially at night;
increased cough;
the increase of the amount and “purulency” of the sputum;
subfebrile temperature;
tachycardia with normal body temperature;
biochemical signs of inflammation;
deviation to the left and increasing of ESR to moderate;
the increase of acid and alkali phosphotase of leucocytes.
Differential diagnosis
Chronic nonobstructive bronchitis should be differentiated with:
acute prolonged and reccurencive bronchitis;
bronchoectasis;
tuberculosis of bronchi;
bronchial cancer;
expirative collapse of the tracheum and large bronchi.
CHRONIC OBSTRUCTIVE BRONCHITIS
Definition
Chronic obstructive bronchitis is a chronic diffuse unallergic inflammation of
bronchi leading to the progressive damage of pulmonary ventilation and gas
exchange on obstructive type and appearing cough, sputum discharge and dyspnea,
not associated with damage of other organs and systems.
Epidemiology
The high prevalence of chronic cough and expectoration in the United Kingdom
was recognized long before cigarette smoking was widely adopted, but only
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became a subject for medical research after the smog disasters in London in the
1950s. At that time 20 to 30 per cent of middle-aged men had chronic cough and
phlegm; with the reduction in active smoking and environmental SO2; and
particulate pollution, this had dropped to about 15 to 20 per cent of middle-aged
men and about 8 per cent of middle-aged women by the late 1980s.
COPD is the commonest cause of impaired spirometry in the population; by
middle age about 18 per cent of male and 14 per cent of female smokers have
FEV1; values more than two standard deviations below the mean predicted values,
in contrast with rates of about 7 per cent in men and women who have never
smoked. These rates are probably somewhat higher than those observed in the
United States. Although the rates for spirometric impairment are broadly similar to
those for chronic cough, as already discussed, both changes are not necessarily
found in the same individual smokers.
Etiology
The major risk factor in Westernized countries is cigarette smoking, but there is a
wide variation in the susceptibility of individual smokers to develop progressive
airflow obstruction, suggesting that other important risk factors remain to be
identified. In the United States, mortality rates for COPD in cigarette smokers are
at least 10 times those in never-smokers at all ages below 80 years; COPD is
estimated to cause about 15 per cent of smoking-related deaths compared with 28
per cent attributed to lung cancer. Smoking promotes inflammation in the
periphery of the lung; it is uncertain whether this is a direct toxic effect of tobacco
smoke (e.g. oxidants) or is due to smoke recruiting neutrophils and other
inflammatory cells into the airways and airspaces. α1;-Antitrypsin deficiency, a
rare genetic disorder, is the strongest single risk factor. Occupational risks have
been a subject of much controversy, particularly in coal miners. It has been
difficult to distinguish changes due to dust exposure and to smoking. In general,
many dusty occupations cause mucus hypersecretion, but few have been proven to
lead to airways obstruction. In some countries domestic environmental factors may
be of great importance; for instance in New Guinea household pollution due to
heating and cooking within a small space is important, and COPD is more common
in women than men. Two popular hypotheses are that repeated bronchopulmonary
infections lead to permanent airways damage and hence to COPD (British
hypothesis), and that the susceptible smoker has a pre-existing asthmatic
constitution with airways hyper-responsiveness which accentuates the effects of
smoking (Dutch hypothesis). Both are entirely reasonable; neither has been proven.
Pathogenesis
Early changes in the evolution of smoking-related COPD are the development of
cough (associated with hypertrophy of mucous glands and mucus hypersecretion)
and inflammatory changes in the respiratory bronchioles. These changes may
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develop in young adults early in their smoking history. In never-smokers
spirometry shows little change in early adult life; age-related decline begins at
about 30 years. In many smokers, however, some decline in FEV1; occurs through
the twenties. Early changes in lung function are due to inflammatory and occlusive
changes in the peripheral airways. By middle age the FEV1; may be significantly
reduced (this is often associated with hyper-responsiveness of the airways to
inhaled histamine and other agents) and the early changes of emphysema are
developing, functionally revealed by reductions in lung recoil and carbon
monoxide transfer coefficient. Because of the enormous total cross-sectional area
of the peripheral airways, breathlessness on exertion does not develop until there is
considerable pathological change and FEV1; may be 50 per cent or less of the
expected values. As the disease advances ventilation becomes uneven, reducing the
efficiency of the lungs as gas exchangers and leading to falls in PaO2; and
increasing ventilatory requirements on exercise. To overcome the airway
narrowing the resting end-tidal volume (functional residual capacity) increases;
although this widens the airways it increases the work of the inspiratory muscles,
which are less able to generate inspiratory pressures because of their shorter length
at the start of inspiration. Until FEV1; drops below about one-third of predicted
values there is hypoxaemia but not hypercapnia; this is because the inefficiency of
the lungs as gas exchangers for carbon dioxide is overcome by a modest increase
in resting ventilation. In advanced disease, this compensation is insufficient and
hypercapnia often develops; this is related to a combination of the severity of
airways obstruction and impaired ability of the inspiratory muscles to generate
pressure. With advanced disease, moderate rises in pulmonary artery pressure are
found; the precise contributions of loss of pulmonary vascular bed, hypoxaemia,
structural changes in the pulmonary vessels, and increased blood viscosity
associated with a high haematocrit are uncertain.
Airways obstruction and impaired gas exchange in patients with advanced COPD
result from varying combinations of obstructive changes in the peripheral
conducting airways (intrinsic airways disease) and destructive changes in
respiratory bronchioles, alveolar ducts, and alveoli (emphysema). Many attempts
have been made to characterize different patterns of clinical presentation or
pulmonary function in COPD and to relate them to the presence and severity of
emphysema. The best established contrast is between pink and puffing patients
(type A, fighters), who are underweight with severe breathlessness, relatively
normal blood gases, and without oedema, and blue and bloated patients (type B,
non-fighters) with severe hypoxaemia and hypercapnia, polycythaemia, and
oedema, but without such severe breathlessness. Type A was originally thought to
be associated with severe emphysema but this has not been confirmed in
subsequent studies; retained ventilatory responsiveness to hypoxia is now thought
to be a more important factor. There are distinct functional changes associated with
emphysema which all reflect the airspace changes: an enlarged total lung capacity,
a severely reduced carbon monoxide transfer coefficient, and loss of lung recoil.
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The enlargement in total lung capacity is responsible for the low flat position of the
diaphragm on full-inflation chest radiographs.
Clinical features
Patients may present either with chronic productive cough and recurrent bronchial
infections, or with insidious breathlessness on exercise, or a combination of the
two types of symptoms.
The tendency to bronchial infections is associated with impaired mucociliary
clearance and chronic bacterial colonization of the normally sterile
tracheobronchial tree. Diagnosis of chronic bronchitis requires a normal chest
radiograph which effectively excludes tuberculosis, bronchiectasis, neoplasms, and
many other lung diseases which cause cough. Other possibilities such as postnasal
drip, aspiration, asthma, and immune deficiency may have to be excluded by
appropriate investigations. Although lung function deteriorates during acute
infections and takes several weeks to recover, there is no evidence that the
progression of airways obstruction is related to the occurrence of recurrent
infections in otherwise healthy smokers.
Airways obstruction leads to breathlessness on exertion and the insidious
development of a reduced exercise capacity. A temporary exacerbation due to
infection often triggers seeking medical advice. Some patients first present at a
very advanced stage and give a short history, but prospective population studies
have failed to identify subjects who show rapid and catastrophic falls in FEV1.
Examination
There are no abnormalities on clinical examination in the earlier stages; diagnosis
then depends on spirometry. With progression of the disease signs of
hyperinflation (barrel-shaped chest, low position of the laryngeal prominence, loss
of cardiac dullness, and lowering of hepatic dullness) develop and there may be
increased frequency of breathing, use of accessory muscles, loss of the normal
outward movement of the abdomen during inspiration, and wheeze, particularly in
the second half of expiration. At the most advanced stage there is often pursed lip
breathing, cyanosis (detected reliably only when oxygen saturation is below 85 per
cent), and indrawing of the lateral rib cage (Hoover's sign) on inspiration. Clubbing
is not a feature. Ankle oedema may develop, often without any detectable
abnormality of the heart or pulmonary circulation. A few patients develop gross
cardiac enlargement, gallop rhythm, signs of tricuspid incompetence, raised jugular
venous pressure, and hepatic engorgement. Signs of advancing respiratory failure
(apart from cyanosis) are restlessness and confusion, a coarse tremor, and warm
peripheries. In hypercapnic ventilatory failure, papilloedema occasionally develops
if diagnosis and treatment are grossly delayed.
Investigation
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Chest radiograph
The chest radiograph is a relatively insensitive indicator of COPD; it is possible to
die from COPD with a normal chest radiograph. The most striking changes are
those due to enlargement of total lung capacity, which is found with emphysema
but not usually when obstruction is due to intrinsic airway disease. The domes of
the diaphragm are then low with loss of the normal curvature (often seen best on
the lateral radiograph); with severe hyperinflation the insertions of the diaphragm
into the ribs may be revealed due to loss of the normal area of apposition between
diaphragm and rib cage at total lung capacity. A further sign of hyperinflation is an
increased retrosternal airspace. Generalized emphysema is often difficult to
diagnose with confidence; local differences in transradiancy and paucity of
medium-size vascular markings, such as the characteristic bilateral basal
transradiancy of α1-antitrypsin deficiency, are more obvious. Bullae and
panlobular emphysema are detected more easily than centrilobular emphysema.
Signs of airway disease are few; airway wall thickening is not obvious, but a few
patients with recurrent infections with COPD may have bronchiectatic changes.
Secondary effects on the circulation may develop with advanced disease, resulting
in upper-zone prominence of medium-size pulmonary vessels, enlargement of the
main branches of the pulmonary arteries (a standard measurement is right main
descending artery more than 16mm in diameter), and eventual enlargement of the
heart.
Computerized tomography has significantly improved the ability to diagnose
generalized emphysema and bullae compared with conventional chest radiographs.
Scans of regional ventilation and perfusion become patchily abnormal with the
development of relatively mild airways obstruction. The coarse moth-eaten defects
seen are usually matched, affecting ventilation and blood flow similarly, but
inevitably make it more difficult to detect additional vascular defects due to
pulmonary embolism.
EchoCG
Electrocardiographic signs of right heart disease are usually modest, probably in
part because they are masked by hyperinflated lung. Right-bundle branch block
and P pulmonale in leads 2, 3, and aVf are common but do not bear a close relation
to pulmonary artery and right-ventricular pressures. Evidence of right-ventricular
hypertrophy is uncommon. Atrial fibrillation is the commonest arrhythmia.
Echocardiographic assessment is also impeded by the hyperinflation, but some
indirect estimate of pulmonary artery pressure and of the ejection fraction of the
right ventricle can be achieved.
Blood test
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The major change is a raised haematocrit (secondary polycythaemia) in
hypoxaemic patients. Smokers have about a 25 per cent rise in all elements of the
white blood cell count; a rise in the percentage of eosinophils suggests an
asthmatic component. Biochemical tests show a raised venous bicarbonate level in
patients with established hypercapnia.
Sputum examination
Many physicians believe that sputum culture is redundant unless the patient fails to
respond to a course of antibiotics. Three main bacteria are cultured: Haemophilus
influenzae, Streptococcus pneumoniae, and Moraxella catarrhalis. At present most
infections respond to a wide range of antibiotics, but ampicillin-resistant H.
influenzae is becoming increasingly common (15 per cent or more in some areas).
So far, penicillin-resistant Strep. pneumoniae is very rare (less than 1 per cent) in
many countries, including the United Kingdom, but isolated multiple-antibioticresistant organisms have been found in New Guinea, the Republic of South Africa,
and Spain. After repeated courses of antibiotics Pseudomonas species may be
predominant. Staphylococcus aureus is important during epidemics of influenza.
The commonest organism causing a lobar pneumonia is Strep. pneumoniae, but
smokers with COPD are at increased risk of Legionella pneumophila infections.
Tuberculosis is relatively common in the elderly smoker, particularly if there is
also alcohol abuse.
Spirometry
A low FEV1 and FEV1/VC ratio are essential to the diagnosis; values of both
depend on age, gender, and height. If the result is not clear cut (e.g. low FEV1 and
vital capacity (VC) without reduction in FEV1/VC), finding convexity to the
volume axis of the expiratory limb of the maximum expiratory flow-volume curve
is useful because this change occurs early in the development of obstruction.
The response to an inhaled α-adrenoceptor agonist and/or muscarinic antagonist
should also be measured; a large increase immediately raises the prospect of a
reversible (asthmatic) component. Absence of an immediate bronchodilator
response, while disappointing, should not prevent a full trial of corticosteroid
treatment (see below).
Once the diagnosis is established, peak expiratory flow can be used to monitor
progress and to assess diurnal variation, which is relatively small in typical COPD,
but because peak expiratory flow is better preserved than FEV1 in COPD, an
initial assessment with full spirometric tests is essential.
Other tests of airways function, such as airways resistance measured by body
plethysmography and tests of the inequality of airways narrowing, are useful
adjuncts but not central to diagnosis.
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Blood gases
Resting PaO2 falls as airways obstruction increases. Oximetry has made it easy to
monitor oxygen saturation during outpatient visits and to assess the need for longterm oxygen at home. Hypercapnia can be suspected from elevation of venous
blood bicarbonate. PaCO2 is usually normal until FEV1 is reduced below 1.2
litres. The chronicity of any elevated PaCO2 can be judged from the pH, which
tends to remain at about 7.40 in the steady state, particularly when the patient is on
diuretics.
The degrees of chronic obstructive bronchitis severity we can determine according
the standard of FRV1 (table 1)
Table 1. Degrees of severity of chronic obstructive bronchitis according the
standard of FRV1
Degree of severity
Slight
Middle
Severe
FEV1 ( in % from standard)
More than 69
50-69
Less than 50
Chronic obstructive bronchitis can be classified according degree of severity
(table 2).
Table 2. Degree of obstructive bronchitis according to clinical signs
Signs
Cough
Sputum
Dyspnea
XR-signs
Mild degree
Present
Possible
Absent
Absent
ECG
Without changes
PEF (in % from Normal
standard PO2 mm
Hg)
The content of Normal
erythrocytes
in
peripheral blood
Hemoglobine
Normal
content in blood
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Moderate degree
Present
Present
Present
Peribronchial
infiltration
Severe degree
Present
Present
At rest
Diffuse
pneumosclerosis,
emphysema
Tachicardia, signs Chronic
of
chronic pulmonary heart
pulmonary heart
50-69%
>60 mm Hg
< 60 mm Hg
Tendency
for Erythrocytosis
erythrocytosis
Tendency
increasing
for High
Diagnostic criteria of chronic obstructive bronchitis
Vermeire (1996) suggest the following criteria of chronic obstructive bronchitis:
- real bronchial obstruction;
- uninverible or partial inversibility of bronchial obstruction, variability of
FEV1 less than 84% and/or decreasing of Tiffno index lower than 80% from
necessary standard;
- stable determined bronchial obstruction at least to 3 times during
observation period of one year;
- age, as a rule, more than 50;
- determining of the disease in smoking persons or in those who are under the
influence of industrial airopolutants;
- physical and X-ray signs of pulmonary emphysema.
Management of chronic stable disease
Disability and prognosis in COPD are dominated by the severity of airways
obstruction. While symptoms can be ameliorated by a large variety of treatments,
radically improved prognosis is unlikely unless obstruction can be relieved or at
least future decline aborted. Generally available options are to stop smoking and to
be certain that the reversible component of airways obstruction is adequately
recognized and treated.
Stopping smoking
In young smokers with minor airways obstruction there may be an improvement in
FEV1 on stopping smoking, but in middle age the major effect is to slow
subsequent decline in FEV1, nearly to that of healthy never-smokers. In advanced
COPD it is less certain that further decline in FEV1 is slowed, so that there is a
strong case for early intervention. Stopping smoking consistently results in a
reduction in cough, expectoration, and acute respiratory infections, but patients
should not expect improvement in breathlessness. Low tar cigarettes are associated
with less cough but any slowing of decline in FEV1 is slight. The benefits of
stopping smoking on the subsequent development of cardiovascular disease and
lung cancer apply equally to patients with COPD as to the rest of the population.
Response to bronchodilator and corticosteroid treatment
Virtually all patients with chronic airways obstruction show some immediate
response to treatment with β-adrenergic agonists, muscarinic antagonists, and
theophylline, but these improvements are usually small. If the response is large, the
possibility of further improvement with corticosteroids is evident. The patient at
risk of undertreatment is the heavy smoker with a small immediate bronchodilator
response, particularly if there is evidence of emphysema. Conventional
management is to make a 2 to 3 week trial of 30 to 40mg of prednisolone daily,
monitoring peak expiratory flow daily and spirometry at least at the beginning and
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end of a trial. In the great majority of responders, improvement can be sustained
subsequently by inhaled corticosteroids. If there is a large improvement in airways
obstruction, the prognosis should be dramatically improved.
A more difficult question is whether long-term treatment is beneficial even when
immediate effects are negligible. Several large-scale trials of inhaled
corticosteroids are currently in progress to see if these can attenuate the
progression of airways obstruction in subjects with mild to moderate COPD. Five
years of treatment with an inhaled muscarinic antagonist failed to attenuate decline
in FEV1 in a large North American Study. Trials of continuous versus on-demand
treatment with β-agonists are also being made to exclude the possibility of
deleterious effects of continuous treatment. In the meantime it seems reasonable to
decide the usage of all these drugs on the basis of short-term benefit.
In contrast with asthma, where β-agonists are clearly superior to muscarinic
antagonists as bronchodilators, muscarinic antagonists are overall as effective as βagonists in COPD. A combination of two or three types of bronchodilators is
commonly used, but addition of effects is uncertain. Patients with severe COPD
often claim more sustained relief from use of β-agonists and muscarinic
antagonists via home nebulizers instead of conventional metered dose inhalers.
Whether this is because of the increased dosage (there can be a 10-fold difference
between the doses given by conventional inhalers and by nebulizers), the
sequential inhalation, the more impressive mode of treatment, or the mimicry of
crisis management in accident and emergency departments is uncertain, but several
studies have suggested reduced hospital admissions in disabled patients.
Apart from relaxation of airways smooth muscle, β-agonists may have some antiinflammatory effects, aid ciliary clearance, and increase mucus secretion; they are
pulmonary vasodilators and modulate cholinergic neurotransmission.
Theophyllines also have anti-inflammatory actions, increase ciliary clearance, and
are mild ventilatory stimulants and diuretics; their ability to improve respiratory
muscle performance is disputed.
Other drugs
Mucolytic drugs have been shown to reduce slightly the number and length of
bronchopulmonary infections. Trials of long-term antibiotics in the 1960s,
admittedly with small doses and less effective drugs than now available, failed to
attenuate decline in FEV1. Trials of α1-antitrypsin replacement, either
intravenously or by inhalation, are under way for patients with severe deficiency.
Oral ventilatory stimulants (such as medroxyprogesterone, carbonic anhydrase
inhibitors, or almitrine) can improve PaO2; and PaCO2; by 0.5-1.0 kPa but are not
widely used.
Sedative drugs should almost always be avoided, although they may have a place
under carefully monitored conditions in a few patients with distressing dyspnoea.
β-Blocker drugs, even when relatively cardioselective or given as eye drops, can
worsen airways obstruction.
Immunization
16
Immunization against influenza and pneumococcal infection seems sensible,
although the protective effect in patients with COPD may be less than in the
general population.
Long-term oxygen treatment
When oxygen is administered for more than 15 of each 24h to hypoxaemic patients
with advanced disease, survival is enhanced and hospital admissions are reduced.
The precise reasons are unclear; the treatment was introduced in the expectation
that it would reduce pulmonary hypertension but this is not achieved consistently.
Present United Kingdom guidelines recommend long-term home oxygen when
PaO2 is less than 7.3 kPa (55 mmHg) in the chronic stable state, but it is arguable
that earlier intervention could be useful. Only a small proportion of potential
subjects in the United Kingdom receive this treatment. Spirometry is unchanged
and exercise capacity remains very limited during long-term oxygen treatment, but
there is no evidence that it damages the lungs or precipitates hypercapnic
ventilatory failure. Portable oxygen therapy has a place in improving exercise
tolerance for instance allowing a patient to walk the distance between home and
car but logistic difficulties limit its use. Intermittent use of home oxygen in patients
not on long-term oxygen is commonly used for relief of short breathless episodes.
Nutrition
Many patients with advanced COPD lose weight. There is an increased resting
energy expenditure, only part of which can be attributed to the increased work of
the respiratory muscles. Skeletal and diaphragmatic mass and strength are related
to body weight, so that cachexia reduces the ability of the muscles to deal with the
requirements of exercise. In contrast with these trends, a subgroup of patients with
COPD are overweight and may develop obstructive sleep apnoea.
Physical therapy and rehabilitation
Conventional physiotherapy emphasizes trying to breathe at a slow frequency and
with a large tidal volume, but patients with advanced COPD often cannot breathe
with a normal tidal volume because of expiratory flow limitation. Assistance for
the respiratory muscles can be obtained by leaning forward and leaning on the
elbows to allow use of the pectoral and shoulder girdle muscles. Training
programmes may aim to increase general exercise performance or specifically
increase the strength and endurance of the respiratory muscles by regular periods
of breathing through a resistance at the mouth. Undoubtedly, some patients benefit
considerably, particularly those who are depressed and feel that their problems are
neglected and intractable. Recently there have been attempts to provide noninvasive ventilatory support either at night or during the day with nasal positive
pressure ventilation or pressure support with nasal continuous positive airways
pressure; the precise benefit and selection of patients is not yet established.
17
REFERENCES
1. The assessment of alfa-1-proteinase inhibitor form and function in lung lavage
fluid from healthy subjects. Hoppe-Seyler's Zeitschrift / Afford, S.C., Burnett, D.,
Campbell, E.J., Cury, J.D., and Stockley, R.A. // Biologische Chemische. 1988. №369. – Р. 1065-1074.
2. Effects of smoking intervention and the use of an inhaled anticholinergic
bronchodilator on the rate of decline of FEV1. The Lung Health Study./
Anthonisen, N.R., Connett, J.E., Kiley, J.P. et al. // Journal of the American
Medical Association. – 1994. - № 272. – Р.1497-1505.
3. Relation of birth weight and childhood respiratory infection to adult lung
function and death from chronic obstructive lung disease./ Barker, D.J.P., Godfrey,
K.M., Fall, C., Osmond, C., Winter, P.D., and Shaheen, S.O.// British Medical
Journal . – 1991. - № 303. – Р.671-675.
4. Becklake, M.R. Occupational exposures: evidence for a causal association with
chronic obstructive pulmonary disease American //Review of Respiratory Disease.
– 1989. - V 140. – Р.85-91.
5. Begin, P. and Grassino, A. Inspiratory muscle dysfunction and chronic
hypercapnia in chronic obstructive pulmonary disease. //American Review of
Respiratory Disease. – 1991. – Vol.143. – Р.905-912.
6. Belman, M.J. Exercise in patients with chronic obstructive pulmonary disease. //
Thorax. 1993. - Vol. 48. – Р.936-946.
7. Burrows, B. Airways obstructive diseases: pathogenetic mechanisms and natural
histories of the disorders.// Medical Clinics of North America. – 1990. - Vol. 74. –
Р. 547-549.
Burrows, B. Predictors of loss of lung function and mortality in obstructive lung
diseases // European Respiratory Review. 1991. - № 1. – Р.340-345.
8. The course and prognosis of different forms of chronic airways obstruction in a
sample from the general population. / Burrows, B., Bloom, J.W., Traver, G.A., and
Cline, M.G. // New England Journal of Medicine. – 1987. - № 317. – Р.1309-1314.
9. Chronic obstructive pulmonary disease. / Calverley, P.M.A. and Pride, N.B.
(eds.). Chapman and Hall, London. – 1995 – P.23-36
10. Proteolysis by neutrophils. Relative importance of cell-substrate contact and
oxidative inactivation of proteinase inhibitors in vitro./ Campbell, E.J., Senior,
R.M., McDonald, J.A., and Cox, D.W. Journal of Clinical Investigation. – 1982. Vol. 70. – Р.845-852.
18
PNEUMONIA
Introduction
Pneumonia has been recognized for many centuries. “Peripneumonia” was
described by Hippocrates in the fourth century BC. The erroneous concepts of
anatomy and physiology which prevailed up to the last century hampered any real
understanding of the nature of pneumonia, although it was regarded as some sort of
inflammation of the lung. Treatment included leeches, cupping, and stupes applied
to the chest, together with emetics, tonics, and purges to draw the inflammation
away from the chest. Vigorous blood-letting was popular, particularly in Britain.
In 1834 Laennec paved the way for our modern understanding of lobar
pneumonia by describing the three stages of consolidation that are still recognized
today. Pathologically, these include a first state of engorgement: the lung, when
cut, is wet, oedematous, and congested. In the second stage of red hepatization, the
lung is dry, red, friable, and solid like liver. Thirdly, grey hepatization occurs with
softening of the cut lung and exudation of yellow purulent fluid which denotes
resolution. Laennec also perfected the use of the stethoscope and described the
crepitous rattle (crepitation) as a pathognomonic sign of the first stage of
peripneumonia. Red hepatization was heralded by the development of bronchial
breathing, and resolution by the return of crepitations (rhonchus crepitous redux).
Towards the end of the nineteenth century the cause of pneumonia became a
matter of hot debate, with some expounding atmospheric conditions and others
infection as the cause. Friedlander, between 1881 and 1884, first found bacteria in
the lungs of fatal cases of pneumonia using the staining techniques of his colleague
Gram, and Fraenkel, in 1884, first isolated an organism which he called
“pneumoniemikroccus” (pneumococcus) from a 30-year-old man dying of
pneumonia. The identification of the pneumococcus rapidly led to a realization of
its importance as a cause of pneumonia and to the production of specific antisera
for treatment. By the early twentieth century microbiologists had become expert
and quick at typing and isolating pneumococci as a guide to specific serum
therapy.
With the discovery of penicillin and other antibiotics the problem of pneumonia
seemed to be conquered and interest in the condition waned. However, it was
recognized that there was a group of pneumonias, which did not behave like lobar
pneumococcal pneumonia, in that they were generally not severe and did not
19
respond to penicillin. These ‘atypical’ pneumonias were subsequently identified as
being caused by Chlamydia psittaci (psittacosis), Coxiella burnetii (Q fever), and
Mycoplasma pneumoniae (Eaton's agent).
The next major event in the history of pneumonia was the first outbreak of
legionnaires' disease in Philadelphia in 1976. This was followed just a few years
later by the increasing recognition of unusual and opportunistic lung infections in
patients with AIDS, and the increasing importance of pneumonia in patients
receiving immunosuppression therapy for inflammatory disease and cancer, and
following organ transplantation.
The most recent event has been the description, in 1986, of a pneumonia
caused by a new atypical pathogen Chlamydia pneumoniae. In contrast with
psittacosis, this Chlamydia species has man as its only host and appears to be a
significant cause of sporadic and epidemic lower respiratory infections. These
changes have generated an increasing awareness that pneumonia of all types is still
a common cause of morbidity and mortality, even in the days of readily available
antibiotics.
Definition
Definition of pneumonia was changed many times according to new moments of
etiology, pathogenesis, pathomorphology.
So, the last definition now sounds like
Pneumonia may be defined as inflammation of the parenchyma, caused by acute
infection and is characterized by recently developed signs of consolidation, both
clinically and radiologically, with the must involvement of all structural elements
of lung tissues, with inflammation of alveoli and production of exudate.
According to the international classification of diseases and trauma and death
causes No. 10 (1992), from the subdivision of pneumonia other non- infectioous
diseases (caused by other physical factors, radiation, chemicals, patrol and
vascular) are excluded.
Epidemyology
Morbidity of acute pneumonia comprises about 10- 13.8 of 1000 of the population.
Morbidity of individuals aged more than 50 years increase up to 17 of 1000
population. Pneumonia is on 4th place in between the diseases causing death, after
cardiovascular diseases, malignant tumors, trauma and intoxication. Pneumonia is
one of the leading causes of death both the in United Kingdom and in North
America. Around 30&nbsp;000 patients died of pneumonia in England and Wales
in 1991. Pneumonia accounts for about ten times as many deaths in the United
Kingdom as all other infectious diseases together. The mortality in those admitted
to hospital with pneumonia ranges from 6 to 24 per cent, with rates between 10 and
50 per cent being reported for patients with pneumococcal bacteraemia.
20
Pneumonia is the most common cause of hospital attendance for both adults and
children in developing countries, and it is estimated that 5 million children under
the age of 5 years die of pneumonia each year. The impact on health service
resources is also substantial. Respiratory infections are the commonest reason for
general practitioner consultation, with the incidence for adult lower respiratory
infections being around 40 per 1000 population per year and 2 to 3 per 1000 for
community-acquired pneumonia. Pneumonia acquired in hospital ranks as the third
most common nosocomial infection, has a considerable mortality and morbidity,
and considerably prolongs hospital stay and costs.
Etiology
Acute pneumonias are caused by different infecting agents mostly they are caused
by bacteria, rare by viruses, fungus, protozoa, and rickettsia.
Bacteria are the most common causes of pneumonia, but these infections con also
be caused by other microbial organisms, It is often impossible to identify the
specific culprit. bacteria.
Many bacteria are categorized by the staining procedure used to visualize bacteria
under a microscope. The stains determine if they gram- negative or gram- positive
bacteria. This gives the physician an idea to the severity of the pneumonia and how
to treat it.
Gram- Positive Bacteria. These bacteria appear blue on the stain. The following
are common gram- positive bacteria.
The most common cause of pneumonia is the gram- positive bacterium.
 Streptococcus pneumoniae ( also called S,pneumoniae or pneumococcal
pneumonia). It was thought to cause 95 % of community-acquired bacterial
infection, but research now indicates it is far less, accounting for about half
of all cases. (Some studies suggest it may account for even fewer, 10% to
30% of cases).
 Staphylococcus aureus, the other major gram –positive bacterium
responsible for pneumonia, accounts for about 10% of bacterial cases. It is
one of the main causes of pneumonia that occurs in the hospital (
nosocomial pneumonia) . It is uncommon in healthy adults but can develop
about five days after viral influenza, usually in susceptible individuals, such
as people with weakened immune systems, very young children,
hospitalized patients, and drug abusers who use needles.
 Streptococcus pyogenes or Group A Streptococcus.
Gram- negative Bacteria. These bacteria stain pink. Gram-negative bacteria are
common infectious agents in hospitalizes or nursing home patients, children with
cystic fibrosis, and people with chronic lung conditions.
 The most common gram-negative species pneumonia is Haemophilis
influensae ( generally occurring in patients with chronic lung disease, older
patients and alcoholics).
21
 Klebsiella pneumoniae may be responsible for pneumonia in alcoholics and
in other people physically debilitated.
 Pseudomonas aeruginosa is a major cause of pneumonia that occurs in the
hospital ( nosocomial pneumonia).It is common in pneumonia patients with
chronic or severe lung diseases.
 Moraxella catarrhalis is found in everyone’s nasal and oral passages.
Experts have identified that bacteria as a cause of certain pneumonias,
particularly in people with lung problems, such as asthma or emphysema.
 Neisseria meningitidis is one of the most common cause of meningitis, but
the organism has been reported in pneumonia, particularly in epidemics of
military recruits.
 Other gram-negative bacteria causing pneumonia include E. coli (a cause of
newborn), Proteus (found in several damaged lung tissue), and Enterobacter
Atypical Pneumonia
Atypical pneumonia are generally caused by tiny nonbacterial organisms called
Mycoplasma or Chlamydia pneumoniae and produce mild symptoms with a dry
cough. Hospitalization is uncommon with pneumonia form these organisms.
 Mycoplasma pneumoniae (M. pneumoniae) is the most common
nonbacterial pneumonia. Mycoplasma is a very small organism that lacks a
cell wall. It has a prolonged, from by close contact and is most often found
in school-aged children and young adults. The condition is usually mild and
commonly known as walking pneumonia. Estimating its prevalence in
community acquired pneumonias in adults range form 1.9% to 30%. In one
study, it accounted for over a third of pneumonia cases in children.
 Another small non-bacterial organism, Chlamydia pneumoniae (C.
pneumoniae),is not thought to cause 10% of all community- acquired cases
of pneumonia. It is most common in young adults and children, where it is
usually mild. In one study, it was the cause of 14%of cases in a group of
children with pneumonia. Though it is common in the elderly, it can be very
severe in this population.
 Legionnaire’s disease, first diagnosed in 1976, is caused by the organism
Legionella pneumophila, and is acquired by breathing droplets of
contaminated water. Outbreaks have most often been reported in hotels,
cruise ships, and office buildings where people are exposed to contaminated
droplets form cooling towers and evaporative condensers. They have also
reported after exposure to whirlpools and saunas. Legionella is not passed
from person to person, but it may be much more common than once thought.
Some experts even believe it causes 29% to 47% of all pneumonia cases.
(Legionella is sometimes categorized as an atypical pneumonia).
22
Viruses what can cause orliead to pneumonia include influenza, respiratory
syncytial virus (RSV), herpes somplex virus, varicella-zoster ( the cause of
chicken pox), and adenovirus. Outbreaks usually occur between January and
April.
 Influenza is associated with pneumonia directly or by altering the mucous
blanket and making a person susceptible to bacteria pneumonia.
 Respiratory syncytial virus (RSV) is a major cause of pneumonia in infants
and people with damaged immune systems. Studies indicate that RSV
pneumonia may also be more common than previously thought in adults,
especially the elderly.
 Adenovuruses have been implicated in about 10% of childhood pneumonia.
 In adults, herpes simplex virus, adenoviruses, and varicella-zoster ( the
cause of chicken pox) are generally causes of pneumonia only in people with
impaired immune systems.
Aspiration Pneumonia and Anaerobic Bacteria
The mouth harbors a mixture of bacteria that is harmless in its normal location
but can cause a serious condition called aspiration pneumonia if it reaches the
lung. This can happen during periods of altered consciousness, often when a
patient is affected by drugs or alcohol, or after head injury or anesthesia. In
such cases, the gag reflex is diminished, allowing these bacteria to enter the
airways to the lung. These organisms are generally different from the usual
microbes that enter the lung by inhalation. Many are often anaerobic ( meaning
they can live in the absence of oxygen).
Opportunistic Pneumonia
Impaired immunity leaves patients vulnerable to serious, even life-threatening,
pneumonias known as opportunistic pneumonias. They are caused by microbes
that are harmless to people with healthy immune systems. Infecting organisms
include the following : Pneumocystis carinii, an atypical organism that is very
common and generally harmless in people with healthy immune systems.
 Fungi, such as Mycobacterium avium.
 Viruses, such as cytomegalovirus (CMV). AIDS is a major risk factor for
opportunistic pneumonia, as are other conditions including lymphomas,
leukemias, and other cancers. Long- term use of corticosteroids and other
medications that suppress the immune increase of the susceptibility to these
pneumonias.
Pathogenesis
23
Mechanism of development of pneumonia is very complicated and unknown to the
end. Virulence of the microorganisms plays also some role in the pathogenesis of
the pneumonia. Viruses damage the mucous membrane of the airways and lead
into its ulceration and develop to the immune disorders. Disorders of defense
mechanisms of respiratory organs play also the role in the pathogenesis of
pneumonia. Change in the immuno- biological reactivity of the macro-organism
and disorders of local immunity of the broncho- respiratory system, play role in
pathogenesis of the disease. Predisposing factors: factors leading to the secondary
immunocopmromising situations as diabetes mellitus, alcoholism and other. In last
researches it is confirmed that immunity system plays a great role in the
development of acute pneumonia, often occurring in the patients with acquired
immunodificieny (AIDS).
There are 3 ways of transmission of infection: bronchogenic way (most
common), haematogenic and lymphogenic way of transmissions.
Bronchogenic way is observed by the inspiration of infecting agents, contributed
by the congenital and acquired disorders of eliminations of the agents: disorders of
the muco- cilliary clearance, disorders of lungs surfactants, insufficient functional
activities of neutophils and alveolar macrophages. Haematogenic and lymphatic
ways of transmission are more characterized for secondary pneumonias.
Significant hyperergic reaction of the pulmonary tissues in croup pneumonia lead
into ateletasis of lobs or several segments of lungs, caused by the significant edema
of the mucous membrane of bronchi and infection is spread rapid in here.
Pneumonia is characterized by the filling of alveolar gas spaces by cellular debris
or edema fluid. Most of these diseases states are acute processes of one kind or
another and a large number of etiological agents may be involved. Alveolar filling
with cellular debris is commonly the result of pneumonias caused by infection. The
classical example is streptococcal pneumonia causing intense packing of all alveoli
of one or more lobes by inflammatory cells and their debris. More diversely
distributed forms of non-streptococcal pneumonia showing local areas subject to
similar changes are more common than lobar pneumonia since the advent of
penicillin. Edema is the other major category of alveolar-filling disease where
largely cell-free collections of fluid, transudative or exudative, collect and thus fill
alveoli, usually more in the dependent than in the non-dependent lung regions.
Such edema may be the result of left heart failure or pulmonary capillary
permeability increases due to any of a variety of cytokine-associated inflammatory
processes.
Classification
European respiratory consol 1993, divide acute pneumonia into following
groups, based on the clinic- pathogenetic and epidemical principles.
European respiratory consol 1993
24
1st. Community acquired pneumonia (primary pneumonia).
2nd. Hospital acquired pneumonia (nosocomial pneumonia).
3rd. Pneumonia in the immunocompromised host including AIDS.
4th. Atypical pneumonia.
In our country classification of WHO 10th addition is used. According to this
classification, acute pneumonia is sub divided according to 3 basic characteristics:
etiology, clinical and morphological signs and progress of the AP.
During the last years, some additions are made to the classification of AP
(complications). The most wide spread classification of AP is by V.P.Silvesterova
(1987).
Classification of AP (V.P. Silvesterov, 1987)
I.
II.
By etiology
By clinical and pharmacological signs:
1. Parenchymal:
a) Lobular
b) Central
III. By spread and localization:
1. one sided (left or right):
a) total;
b) lobular;
c) segmental;
d) sub- lobular;
e) central;
2. Double sided (with indication of spread of the process)
IV. By severity:
1. severe;
2. moderate;
3. mild;
V.
By progression:
1. acute;
2. persistent.
VI. By the presence of functional disorders of external respiration and
circulation:
1. without functional disorders;
2. with functional disorders (characteristic and spread).
VII. By the presence of complications:
1. non- complicated;
2. complicated (with its indications).
In the classifications, pneumonia is divided on the basis of etiological factors
(pneumococcal, staphylococcal, legionella and others), clinical and morphological
signs: first parenchymal, subdivided into lobular and central and second interstitial
pneumonias. The localization and spread of the process are also shown in the
25
diagnosis: one sided (left or right, total, lobular, segmental, sub-lobular and
central). By severity of the process, it is divided into mild, moderate and severe.
By progress into acute and protracting, also functional disorders of respiration,
blood circulation and complications must be shown in the diagnosis also.
Pneumonia is also some times divided into primary (occurs for the first time) and
secondary pneumonia, after other chronic diseases of the respiratory organs and
other organs and systems, predisposing to the development of pneumonia.
Community-acquired pneumonia
Community-acquired pneumonia continues to be a common cause of acute hospital
admission. There are few studies of the incidence in the community of patients not
requiring hospital admission, but studies in a large group health practice in Seattle
suggested an annual rate of 10 to 15 cases per 1000 population of all ages with the
highest rates in the very young and the in very old. Only 16 per cent of cases
required hospital admission. Community studies in Nottingham suggest that a
general practitioner will see about eight to ten cases of pneumonia each year in
adults between 16 and 79 years, and will manage three-quarters of them at home.
Those with pneumonia constitute only about 6 per cent of all the patients that they
treat for respiratory infections with antibiotics. In the United Kingdom around 30
million prescriptions for antibiotics are written each year for new episodes of
respiratory illness (all ages). Therefore a substantial number of patients are being
treated for pneumonia and chest infections in the community. Pneumonia is twice
as common in the winter months. It has been suggested that the winter air of low
humidity dries the nasopharyngeal mucosa and impairs local defenses. Viral
respiratory infections prevalent in winter also increase the risk of secondary
bacterial pneumonia.
Types of community-acquired pneumonia
Community-acquired pneumonia can occur in a number of different settings
important to consider as they affect the likely cause and severity of the infection.
Pneumonia can affect the previously healthy individual or the patient with
underlying disease, particularly chronic lung disease. The latter is associated with
increased colonization of the respiratory tract with pathogenic bacteria together
with impaired local defense mechanisms.
Infection can result either from bacteria already colonizing the upper airways or by
direct spread from other infected individuals (e.g. droplet transmission of
respiratory viruses), animals (e.g. Q fever, tularaemia, psittacosis), or infected
water droplets (e.g. legionella infection). The age of the patient will also influence
likely pathogens.
26
Clinical features
It is not possible to guess the cause of pneumonia correctly from the history and
signs on presentation as no pathogen has an unique pattern.
Symptoms
Males are affected more commonly than females in a ratio of 2-3 to 1. General
symptoms include those of any febrile illness- malaise, anorexia, sweating, aches
and pains, and headache. There may be a preceding history of upper respiratory
tract symptoms, particularly with viral and mycoplasma infections. Respiratory
symptoms are variable, but classically include cough, sputum, dyspnoea, pleural
pain, and, less commonly, haemoptysis
Sputum is usually mucoid, scanty, or absent on the early stage in the illness,
particularly with legionella and atypical pneumonias. Purulent sputum develops
later, and can be pinkish coloured in classic pneumococcal infection.
Non-respiratory symptoms sometimes dominate the picture and mask the
diagnosis. Lower-lobe pneumonia may be present with abdominal pain, rigidity,
and ileus, and should be excluded in anyone with an “acute” abdomen. Marked
confusion may also be seen in patients with any severe pneumonia, and it is a
feature of legionella pneumonia in less seriously ill patients. Meningitis, hypoxia,
and metabolic upset must also be considered in the confused patient. Severe
headache, cerebellar dysfunction, memory loss, and myalgia also occur with
legionella pneumonia. Vomiting and diarrhoea are prominent in some cases,
although they may be the result of initial antibiotic therapy.
The duration of symptoms before hospital presentation varies with the severity of
the illness, but is usually 3 to 7 days. However, 10 to 14 days is not unusual with
atypical pneumonia, particularly mycoplasma infection, and patients will often
have received a course of a b-lactam antibiotic without improvement.
Pneumococcal and staphylococcal pneumonias may present abruptly with fever,
rigors, cough, and pleural pain. Adults with influenza or chicken pox who develop
lower respiratory symptoms may deteriorate quickly, and should be assessed and
treated as a matter of urgency.
Physical signs
The patient usually looks flushed and unwell with tachypnoea and a tachycardia.
High body temperatures (more than 39.5 C) and rigors occur in young people,
particularly with pneumococcal, staphylococcal, and legionella pneumonia. Elderly
or debilitated patients may have little or no rise of temperature; the main sign is a
raised respiratory rate. Herpes labialis is a particular feature of pneumococcal
infection, and is found in a third of cases. Examination of the chest will show
reduced movement of the affected side, particularly if pleural pain is prominent,
and the patient may splint that side by shallow breathing and hand holding of the
chest. Classic signs of lobar consolidation are uncommon and bronchial breathing
occurs in less than a quarter of cases; inspiratory crepitations are the most common
focal sign. A pleural rub may be heard even in the absence of pleural pain. On
occasion, chest examination appears normal and the extent of radiographic
27
shadowing comes as a surprise, a given feature said is more common with atypical
and viral pneumonias.
Signs outside the chest may be found. Upper abdominal tenderness and confusion
are not uncommon in more severely ill patients. A rash is unusual with
community-acquired pneumonias, but has been reported with mycoplasma and
psittacosis pneumonia. More commonly, a rash is a reaction to antibiotic therapy.
It is important to emphasize that respiratory symptoms may not be elicited even in
the presence of extensive pneumonia. This is particularly the case in the very
young, elderly, or debilitated patient, and the diagnosis may be missed without
careful chest examination and a chest radiograph.
Investigation
Investigations are performed for a number of reasons and should be tailored to fit
the individual clinical situation. Investigations are necessary to assess the severity
and cause of the infection, to identify complications, and sometimes for
epidemiological purposes.
General
The total white cell count is over 15.0 x10/dl in the majority of patients with
pneumococcal pneumonia, with the differential showing a neutrophila . However,
in legionella pneumonia the total white cell count is usually not above 15.0 x10;/dl
and sometimes there is a lymphopenia. In patients with uncomplicated atypical or
viral pneumonia about the normal white cell count is usual. A low or very high
white cell count can be found in the very ill and is a poor prognostic sign is poor.
Abnormal liver function tests are common, and may be found in a third of patients
with pneumococcal pneumonia and half with legionella pneumonia. Raised blood
urea and creatinine, hyponatraemia, hypoalbuminaemia, proteinuria, and
haematuria can be seen with any severe pneumonia. Marked hypoalbuminaemia
can develop quickly, probably due to a combination of sequestration of plasma
protein into the lung and generalized increased vascular permeability from
toxaemia.
Specific
For patients who are ill enough to require hospital treatment, the aim is to identify
the cause of pneumonia and the severity of the infection as soon as possible.
Blood, any pleural fluid, and sputum, if possible, should be collected for culture
before antibiotics are started because a single dose can interfere with the culture of
common pathogens such as S. pneumoniae and H. influenzae. However, antibiotic
treatment should not be delayed if sputum cannot be obtained quickly, as a third of
patients will not be able to produce sputum in the early stages.
Gram staining of sputum (and pleural fluid) sometimes gives a quick and accurate
indication of the pathogen if predominant numbers of one pathogen are seen in a
good sputum specimen. Although the specificity of the Gram stain is high, the
28
sensitivity is low. Predominant numbers of Gram-positive diplococci on Gram
stains are seen in only 10 to 20 per cent of patients with pneumococcal pneumonia.
If more than 10 squamous epithelial cells are seen in each low-powered field, the
specimen is probably of oropharyngeal origin and is of little use. Because the
bacterial flora of sputum represents a mixture of organisms from the lower
respiratory tract and those acquired during passage through the mouth, isolation of
a pathogen may not reflect what is occurring in the lung itself. The specificity of
the culture may be improved by washing or diluting the sputum. Even then sputum
culture is a relatively insensitive method of diagnosis for bacterial pneumonia.
Less than a half of patients with untreated bacteraemic pneumococcal pneumonia
have pneumococci isolated from their sputum. Isolation of a pathogen from blood
(or pleural fluid) culture provides certain evidence of its importance and identifies
those bacteraemic patients who have a worse prognosis.
The most common practical problem is over a half the patients have received an
antibiotic before hospital admission and this greatly reduces the usefulness of
Gram stain and culture of secretions and body fluids. The detection of bacterial
antigen can partially overcome this problem and is particularly helpful in
pneumococcal infection.
The diagnosis of non-pneumococcal bacterial pneumonia raises similar problems
to those encountered with pneumococcal pneumonia. Potential pathogens like
staphylococci, meningococci, and streptococci can be part of the normal
respiratory flora. H. influenzae can be cultured in mucoid sputum in over half of
patients with chronic bronchitis. Over a quarter of patients in hospital may carry
Gram-negative organisms in their upper respiratory tract, particularly if they are
receiving broad-spectrum antibiotics. There are no tests available for detecting
antigens from these other bacteria, and serological testing for bacterial
precipitating antibodies is of no value in diagnosing acute infections.
The major limitation of diagnostic virology is the length of time required for
isolating and identifying a particular virus. The direct fluor- escent antibody
staining technique for detecting viral antigens in respiratory secretions has been
useful in the rapid diagnosis of respiratory syncytial virus bronchiolitis in children,
producing a sensitivity of 90 per cent or over, and is being developed for other
respiratory viruses, including influenza, parainfluenza types 1 and 3, and
adenoviruses. Recently, similar techniques have been successfully used for
detecting chlamydial antigens in respiratory secretions of patients with cultureproven Chlamydia pneumoniae pneumonia. Of the organisms causing atypical
pneumonia, only M. pneumoniae can be grown with any ease, although even here
the growth may take several weeks despite using a special diphasic medium.
To diagnose viral and atypical pneumonias by serological methods, blood should
be collected the early stage of the illness and again 10 to 14 days later or during
convalescence. A fourfold or greater change in specific antibody titer is accepted
as evidence of recent infection. Unfortunately, the result often arrives too late to
influence on the management of the patient. A single sample taken late while the
illness showing a high titer does not help to find out the different between a recent
29
or past infection. The detection of a raised specific IgM antibody by the indirect
fluorescent antibody test can overcome this problem, and is also used for the early
detection of M. pneumoniae infection.
The majority of cases of legionella pneumonia are diagnosed serologically by
repeated indirect fluorescent antibody testing. Only about 10 to 15 per cent are
identified in the acute phase of the illness by culture of the organism or by direct
fluorescent antibody staining for organisms in lower respiratory secretions or lung
biopsy material. About a third of cases will have detectable antibody levels (titres
above 16) on admission, and this may be a pointer to the diagnosis in populations
with a low background of seropositivity, such as in the United Kingdom.
Diagnostic seroconversion can be very slow and a proportion of cases of legionella
infection, proven by culture of the organism, never seroconvert. Detection of
legionella antigen in concentrated urine has proved a valuable early diagnostic tool
in some epidemic outbreaks and this technique should be more widely available for
clinical use.
Invasive techniques for investigating pneumonia
Two problems inhibit further advances in sputum diagnosis. Contamination of
sputum by oropharyngeal organisms has already been mentioned. In addition,
about a quarter to a third of patients with pneumonia cannot produce sputum for
testing. Therefore, various invasive techniques have been developed to overcome
these problems. They are usually reserved for patients with severe infection. Close
interaction between the clinicians and the microbiologist is essential in this stage
so that the correct specimens are collected in the optimum manner and transported
rapidly to the laboratory where they are processed immediately.
Induced sputum
Although not strictly “invasive”, induced sputum has proved valuable in
experienced hands for the early diagnosis of infection, particularly pneumocytic
pneumonia in AIDS patients. Inhalation of a 3 per cent saline mist from an
ultrasonic nebulizer can induce coughing and good specimens of bronchoalveolar
material.
Bronchoscopy
Fibreoptic bronchoscopy will provide bronchial secretions, bronchoalveolar lavage
fluid, and transbronchial biopsies from specified areas of the lung. Some
contamination of equipment by passage through the nasopharynx is inevitable.
Protected specimen brush catheters partially overcome this problem/
Bronchoscopy is rarely needed for patients with community-acquired pneumonia,
except to exclude a bronchial obstruction, but is increasingly used for investigating
nosocomial and ventilator associated pneumonia and pneumonia in the
immunocompromised patient. Protected brush specimens cultured with a
quantitative method produce the best results in ventilator-associated pneumonia. A
high diagnostic yield is reported from bronchoalveolar lavage in patients with lung
infections and AIDS, particularly from those with pneumocystis pneumonia.
30
Radiographic features
The initial radiographic pattern is not particularly helpful in differentiating types of
community-acquired pneumonia. Homogeneous lobar or segmental shadows are
more common than patchy shadows in bacterial pneumonia but they are also seen
in over a half of the patients with atypical pneumonia. Multilobe involvement is
common with severe infection. The lower lobes are most often affected in all types
of pneumonia. Pleural effusions are seen in about a quarter of all cases, and more
will be revealed by lateral decubitus films. Although some degree of pulmonary
collapse should raise the possibility of an endobronchial obstruction (e.g. tumour,
foreign body, mucus plug), it occurs in a quarter of otherwise uncomplicated cases
of community-acquired pneumonia. Hilar lymphadenopathy is seen in mycoplasma
pneumonia and occasionally in psittacosis. Lung cavitation is unusual except with
staphylococcal and pneumococcal serotype 3 pneumonia or in immunosuppressed
patients. Pneumatoceles are only seen with staphylococcal infection . An intense
inflammatory and exudative response may produce a swollen lobe with a displaced
interlobar fissure. This is said to be a feature of klebsiella pneumonia but is also
seen inother severe infections.
The rate of radiographic resolution can be surprisingly slow, and lags considerably
behind clinical recovery. It is related to the cause of the pneumonia, the age of the
patient, and the presence of any underlying chronic lung disease. Atypical
pneumonias clear quickly. In the majority of cases radiographs return to normal
within 2 months following mycoplasma pneumonia. At the other extreme,
radiographs may not clear for several months after legionella and bacteraemic
pneumococcal pneumonia.
Nosocomial pneumonia
Introduction
Nosocomial pneumonia is a new episode of pneumonia developing more than 48h
after a patient has entered hospital for whatever reason. The infection is usually
identified by the development of fever, purulent respiratory secretions, elevated
white cell count, and a new pulmonary infiltrate on the chest radiograph.
Nosocomial respiratory infections have been estimated to occur in 0.5 to 5 per cent
of patients in hospital and to rank third after urinary infections and wound
infections in the frequency of hospital-acquired infections.
Pathogenesis
The infection usually arises from aspiration of nasopharyngeal contents, inhalation
of bacteria from contaminated equipment, or, rarely, by haematogenous spread.
Some aspiration of nasopharyngeal secretions is common even in healthy people,
particularly during sleep. The normal lung copes easily with this, because both the
31
bacteria are relatively non-pathogenic and because the local pulmonary defences
are working normally. However, colonization of the nasopharynx with Gramnegative bacilli occurs in 30 to 40 per cent of patients in hospital. The frequency
can be even higher in patients receiving broad-spectrum antibiotics or those who
are seriously ill. These bacilli arise by the direct contamination of the nasopharynx
from the hospital environment and from the patient's own gastrointestinal tract.
Patients who are ill, bed-bound, have impaired consciousness from their illness or
from drugs, or who has a neurological disease will be more likely to aspirate such
pathogens. Reduced ability to clear bronchial secretions after a general anaesthetic
and impaired coughing after thoracic or abdominal surgery are further risk factors,
and occasionally impaired general antimicrobial defenses provoke to the
development of these infections. The presence of malignancy and the prior use of
antibiotics, steroids, or cytotoxic drugs increase the risk of nosocomial pneumonia.
The risk of postoperative pneumonia is associated with increasing age, smoking
habit, obesity, the presence of chronic illness, long preoperative stay, prolonged
anaesthesia, use of intubation, and thoracic and upper abdominal operations.
Inhalation of bacteria from contaminated respiratory equipment such as ventilators,
nebulizers, intubation and suction equipment, humidifiers, and nasogastric tubes is
a particular problem in ventilated patients. Spread of pathogens via the hands of
the personnel must be remembered.
Pneumonia caused by haematogenous spread of infection from a distant site is
uncommon, but may arise after intra-abdominal infection or as a result of infected
pulmonary emboli. Intravenous cannulae left in situ for long periods is a potential
source of bloodstream infection.
Aspiration and anaerobic pneumonia
The most frequent conditions associated with aspiration pneumonia are impaired
consciousness and dysphagia. The resulting insult to the lung can involve gastric
acid, particulate matter, and contamination of the lower respiratory tract with a
complex bacterial flora.
Anaerobes from the oropharynx and teeth crevices usually predominate in
community cases, and these are mostly penicillin sensitive. In contrast, in hospitalacquired infections aerobic bacteria, particularly Gram-negative enterobacteriaceae
and Pseudomonas aeruginosa related to nasopharyngeal colonization, become
increasingly important.
Anaerobic infection in the lung is usually caused by two or more bacteria acting
synergistically and results broadly in four syndromes including anaerobic bacterial
pneumonia, necrotizing pneumonia , lung abscess, and empyema.
Diagnosis
32
The diagnosis of anaerobic infection is difficult, but there should be a clue from
likely predisposing factors such as poor dental hygiene, aspiration, or impaired
consciousness. Foul smelling and purulent sputum appears only when necrosis
occurs, when multiple cavities will be seen on the chest radiograph. The presence
of multiple Gram-positive cocci and Gram-negative bacilli in the sputum that are
negative on aerobic culture is suggestive.
A parenteral penicillin with or without metronidazole, or clindamycin, is
appropriate for community-acquired cases. Gram-negative bacillary cover obtained
by adding a third-generation cephalosporin, an aminoglycoside, or a quinolone is
necessary for hospital-acquired cases. Quinolones alone have no anaerobic activity.
Prolonged therapy is usually necessary.
In spite of different clinical sings of pneumonias it is possible to mark out the main
syndromes of pneumonias:
1. Syndrome of pulmonary consolidation is manifested by:
 reduce elasticity and increase of vocal fremitus in the mostly cases
(decrease vocal fremitus when pneumonia complicated by liquid in pleural
cavity);
 shortening of percussion sound;
 bronchial breathing occurs in less than a quarter of cases of lobar
consolidation;
 fine rales, inspiratory crepitations are the commonest focal sign. A pleural
rub may be heard even in the absence of pleural pain
 X- ray sings of focal lobar, subtotal, total shadowing. On occasion, chest
examination appears normal and the extent of radiographic shadowing
comes as a surprise, a feature said to be more common with atypical and
viral pneumonias.
All theses symptoms are revealed on:
 Examination ( inspection, palpation, percussion, auscultation).
 Chest radiography in direct and side view.
If it is necessary:
 chest tomography;
 ultrasonic investigation of the pleural cavity.
2. Toxic- inflammatory syndrome manifests by:
 fever;
 rigor;
 malaise;
 anorexia;
 sweating;
 aches and pains;
 headache.
All theses symptoms are revealed by:
 conversation with a patient ( gathering complains, anamnesis morbi and
vitae);
33
 thermometry;
 blood test – leucocytosis, ESR increase, neutrophylesis, fibrinogen increase.
3. Pain syndrome manifests by:
 chest pain in affected side, which increases during cough and deep
respiration;
 reduced movement of the affected side, particularly if pleural pain is
prominent, and the patient may splint that side by shallow breathing and
hand holding of the chest.
All theses symptoms revealed at:
 conversation with a patient;
 examination (inspection and palpation).
4. Syndrome of pulmonary failure
 tachypnoe ( more that 18 per minute) at usually physical activity or in severe
case at rest;
 decrease ration PaO2/ FiO2 ( in severe cases PaO2/ FiO2< 250 Hg mm).
5. Cough is a typical clinical sings of pneumonia.
Sputum is usually mucoid, scanty, or absent early on in the illness, particularly
with legionella and atypical pneumonias. Purulent sputum develops later, and can
be pinkish coloured in classic pneumococcal infection.
Diagnostic criteria’s
Diagnosis pneumonia is definite in the presence of radiographic affirmed
the consolidation of pulmonary tissue and two clinical sings from the
following:
 fever ( febrial) on the onset of pneumonia;
 cough with sputum;
 physical sings: percussion – shortening of the sound, at auscultation- fine
rales, crepitation, bronchial breathing;
 leucocytosis- the total white cell count is over 15.0 x10/dl.
The absence of radiographic affirmed consolidation of pulmonary tissue
makes diagnosis of pneumonia is indefinite.
Differentinal diagnosis
When there is a classic history of fever, malaise, sweats, cough, discoloured
sputum, pleural pain, and dyspnoea, together with the clinical and radiographic
signs of lung consolidation, a diagnosis of pneumonia is usually obvious. The
commonest diagnostic confusion is with pulmonary infarction or atypical
pulmonary edema. A source of pulmonary emboli or evidence of valvular disease
or cardiac failure should be sought by physical examination. On occasions the
distinction is very difficult, and treatment may have to be given for more than one
condition until the true diagnosis becomes clearer. Less common conditions that
34
enter the differential diagnosis include alveolitis, pulmonary eosinophilia,
cryptogenic organizing pneumonitis, bronchoalveolar lung tumours, and more
chronic lung conditions Subdiaphragmatic conditions such as subphrenic or
hepatic abscess or acute pancreatitis may present like lower-lobe pneumonia, often
with an accompanying pleural effusion. Ultrasound examination can be very
helpful in such conditions.
Acute pneumonia must be verified with some diseases which have the same
clinical picture like caseous pneumonia in pulmonary tuberculosis, .lung cancer,
pulmonary infarction and others
Pulmonary tuberculosis
You should remember that patients with pulmonary tuberculosis have less
complains, can’t say the exact day of disease and very often don’t know if they
are ill with tuberculosis. Changes in the lungs can be X-ray ; usual sites of
lesions are the apical and posterior segments of the upper lobe or the superior
segments of the lower lobe, which may appear dense and homogenous with more
slow X-ray dynamics than in acute pulmonary. Besides, Mycobacterium
tuberculosis may be found by bacteriologic examination.
Lung cancer
Very often the first diagnosis at the patients with lung cancer is Acute
pneumonia. It is explained by similar symptoms of lung cancer and acute
pneumonia and significant frequency of paracankrous pneumonia. For verified it
is important to determinate the disease onset. For acute pneumonia it is typical
suddenly onset. For lung cancer it is prolonged onset. The main tools the
diagnosis of the lung cancer are radiology, bronchoscopy and cytology.
Cytological examination of sputum must be repeated. A solitary, circumscribed
nodule, or coin lesion , on the chest radiograph is of particular importance and
may be the earliest indication of bronchogenic carcinoma, although it may also
occur in many other conditions. Bronchoscopy with biopsy may be of further
help in differentiating of squmous cell. So for differentiating of lung cancer must
be spent tomography, cytological examination, bronchoscopy with biopsy.
Data of blood test and X-ray investigation are very important in diagnostics.
Criteria of severe pneumonia
( American Thoracic Society)
Clinical features
 respiratory rate is more than 30 per minute;
 confusion;
 diastolic blood pressure < 60 mm Hg;
 new arterial fibrillation;
Laboratory features
 arterial oxygen < 8 kPa;
 serum albumin 25g/l;
35
 multilobe involvement on chest radiograph;
 blood urea> 7mmol/l or less than 20ml/h, acute renal failure required
dialysis;
 white cell count < 4,0x10/dl or leucocytosis more than 30.0x 10/dl .
Native scientifics mark out three degrees of pneumonia severe ( B.A.Anabekova
2002) (Table 3).
Table 3. Severity of pneumonia
Main signs
Mild
Body temperature Till 38
Respiration rate
Till 25
Cyanosis
Absent
Intoxication
Absent
Consciousness
Clear
Distribution
of 1-2 segments.
pneumonia
according to X-ray
examination
Complications
Absent
Decompensation
Absent
of
concomitant
diseases
Blood test
Fibrinogen
blood
36
Moderate
leukocytosis,
increasing ESR
in Till 5
Severity
Middle
38-39
25-30
Moderate
Moderate
Clear or euphoria
Much part of lobe,
all lobe or several
segments in the
both lungs.
Exudate in the
pleura
Exacerbation
of
branchial asthma,
CAD
Severy
More 39
More 30
Intrinsic
Intrinsic
Obtunded
Two lobes of
polysegmental
lesion of the both
lungs.
Abscess,
toxic
shock
Increasing
heart
failure
dysrhythmia,
decompensation of
heat failure
Leukosytosis with Intrinsic
displacement
to leukocytosis with
young form
displacement
to
young
form,
lympopenia,
eosinopenia,
sometimes
leucopenia, anemia
greatly
ESR
increasing
5-10
More than10
Complications of pneumonia
Development of pathological processes in the broncho- pulmonary system,
etiopathogenetically related to pneumonia are called as complications of the
pneumonia.
 Pleurisy;
 abscess;
 acute respiratory failure;
 toxic shock;
 circulatory collapse;
 myocarditis;
 acute renal failure;
 polyorganic failure;
 pulmonary edema.
Acute respiratory failure (ARF)
Acute disorders of respiratory function with insufficient providing O2 to the
organs and tissues (hypoxemia) and delaying CO2 in the organism (hypercapnia)
is called as ARF.
Clinical signs of ARF in pneumonia are: dyspnoea, disorders of respiratory
rhythm as tachypnoea, which may transfer into apnoea. Cyanosis is the
characteristic sign of ARF, occurs in the significant severe cases of ARF. In ARF
hyperhydrosis is typical functional disorders of cardiovascular system, headache,
sleep disorders, anorexia, and may be cramps may happen. There are 4 stages of
ARF.
First stage
There are no significant signs of ARF in this stage. Basic signs are the increase of
the respiratory rate, dyspnoea, and feeling of insufficiency of O2 during physical
activities.
Second stage (stage of sub compensation)
Dyspnoea in rest, constant feelings of O2 insufficiency, participation of subsidiary
muscles in the act of respiration, cyanosis of lips, tachycardia, tendency to
hypertension, and confusion.
Third stage (stage of decompensation)
Significant dyspnoea, compelled position of the patients, significant participation
of subsidiary muscles in act of respiration, hypoxia, psycho- motor stimulation,
tachycardia, diffused cyanosis, and significant decrease of BP.
Fourth stage (terminal stage)
Has the following symptoms:
37
- Depressed consciousness, coma may happen, often develops hypoxiemic edema
of the brain is developing.
- Diffused cyanosis and cold sweat.
- Increased respiratory rate, surface arrhythmic respiration, may develop
respiration of Chain- Stocks or Biot’s respiration. Development of acidosis,
respiration of Kusmaule.
- Pulse is thin, often extra systoles on the base of bradycardia.
- Significant low BP.
- Significant increase of tracheo- bronchial secretion, edema of mucous
membrane of bronchi, and the development of the syndrome of expiratory
obstruction of the airways.
- Oligo- anuria.
Result of the terminal stage is hypoxiemic and hypercapnic coma.
In development of ARF of the patient with AP, intense antibacterial therapy
should be continued and also i/v of bronchodilators should be administered
(euphylline in system 10-20ml, in 2.4 solution of NaCl, 10% 10ml NaI, and
Amoxol 15-30mg, therapeutic bronchoscopy with drainage of bronchial tree) and
oxygen therapy. In severe cases artificial ventilation is necessary.
Pulmonary edema
It develops as a result of saturation and accumulation of liquid part of the blood
from the capillaries of the minor circulatory system in the interstitials of the lungs.
It may be the cause of pneumonia, inflammatory process in pulmonary tissues,
which causes secretion of the vasoactive substances and thus increases the
permeability of vascular membranes and as a result saturation of occurs liquids in
the alveoli. Phase of interstitial edema is characterized by the increase in dyspnoea
attacks, cyanosis, feelings of compression in the chest, insufficiency of O2, and
confusion. When interstitial phase transfers into alveolar, characterized by
orthopnoea, and by significant cyanosis, the patients are covered by cold sweat,
have terrible cough with the secretion of abundant foamy sputum of pinkish color,
BP is lowered, pulse is slow, in lungs moistened rales may be heard, heart tones
are lowered, and the rhythm of gallop may be.
In such cases the venous recur to heart should be decreased as: in bowed sitting
position, putting tight bandages on the limbs, and in the absence of hypertension
Nitroglycerine 2ml 1% solution i/v in 200ml 5% solution of glucose under control
of BP, i/v Furosemide 60-80mg should be administered . For the removal of
stimulation and to lower the dyspnoea i/v 1ml 0.005% solution of Phentanil and
1ml 0.25% solution of Droperidol in 10ml physiological solution under control of
BP, are used. To decrease foam formation in the airways used inhalation of O2 is
used passed through 70% of spirit or 10% spirituous solution of Antifoamsilan. To
decrease the pressure in the minor circulatory system Nitroglycerine and 10ml
2.4% solution of Euphyllin under control of BP. For the decrease of alveolar
permeability 90-120mg Pridnisolone is used, if no affect, repeated after 3-4hours.
If all these procedures give no result artificial ventilation of lungs should be done.
38
Septic shock (infectious toxic shock)
Research works data of Z. Abovsky show that about 10% of patients with
pneumonia suffer septic shock and 12% of them have lethal results. Septic shock is
observed in patients with severe progression of the disease, mostly of Legionella
etiology. Basic mechanism of the development of septic shock is acute toxic
vascular insufficiency with progressive decrease in venous blood return, disorders
of micro- circulation with the development of metabolic acidosis, DIC syndrome
(disseminated intravascular clotting) and poly organic disorders. Shock occurs on
the peak of intoxication and is characterized by hectic fever and shivering. In
septic shock redistribution of blood occurs in the vascular network and thus it
damages the adequate perfusion of tissues. The development of shock is mostly
caused by bacterial infection, rare in viral infection. In the organization of medical
help to the patients, need to remember 3 satges of the development of the shock
(V.P. Silvesterov, V.E. Martsinovsky 1986) is necessary:
1st stage- characterized by significant raise of temperature, shivering, nausea,
vomiting, diarrhea, headache, confusion and dyspnoea. BP is normal, may be
slightly lowered or high.
2nd stage- characterized by paleness of the skin with acrocyanosis, dyspnoea,
tachycardia, oliguria, and arterial hypotension.
3rd stage- differentiated from other stages that, patients are often in state of coma,
significant oliguria, cold and pale skin, BP is lowered or may be absent.
Treatment
To maintain the volume of blood circulation colloids and crystalloids, salline are
administered in dose of 10ml/kg weight of the body. Also plasma and albumin
should be given in severe cases. Infusion of physiological, glucose or Ringer
solutions have also therapeutic affects. Infusion of plasma should be under strict
control of central venous pressure and hourly count of diuresis. Infusion of liquid
should not be more than 25-30ml/kg daily. In significant lower blood pressure
refractory to the procedures, Dopamin in dose of 2-3Mg/kg.min should be
administered i/v. Also recommended i/v infusion of Prednisolone 120-240mg is
recommended, and further if needed is repeated every 3-4hours. To increase heart
pumping activity, give 0.3ml 0.05% solution of Strophantin in 20ml 40% solution
of glucose or physiologic solution and also oxygenation are used. For the
correction of metabolic acidosis under control of pH infusion of 200-400ml 4%
solution of NaH2CO3 (sodium bicarbonate) is used.
Management of pneumonia
1.
2.
3.
4.
Medical regime.
Medical nutrition.
Etiotropic treatment
Pathogenetic treatment: rehabilitation of bronchial drainage, gas
change, immunomodulating, antioxidant therapy.
5. Anti-toxic therapy.
39
6. Symptomatic therapy.
7. Prevention of complications.
8. Physical therapy- massage, respiratory gymnastic
Medical regime and nutrition
Many patients with mild pneumonia, treated successfully in the community, will
not need any investigations, except for a chest radiograph after clinical recovery to
confirm resolution.
Patients ill enough to require hospital admission will often be hypoxic, and
sometimes acidotic. Hypercapnia denotes the onset of ventilatory failure. Signs of
multisystem involvement are less than usual with mycoplasma or viral pneumonia.
Patients with acute pneumonia should be in bed. Fever and pleuritic pain can often
be relieved by regular analgesia. Adequate hydration is essential. For patients
managed at home, the severity of the illness and the need for hospital admission
should be assessed regularly (see discussion of prognostic factors below). On
occasions this will be influenced by psychological and social factors. Pneumonia
developing in someone with influenza or chickenpox is particularly worrying.
Patients with severe pneumonia should be admitted urgently to a hospital which
has facilities for assisted ventilation. For patients ill enough to be in hospital,
correction of fluid balance and hypoxia is very important. An arterial oxygen
tension of 8 kPa or less on added inspired oxygen or rising arterial carbon dioxide
is an indication of severe pneumonia, and assisted ventilation may well be required
for advancing respiratory failure. This can be life-saving and should be started
early. Therefore patients with severe pneumonia are best managed in an intensive
care unit or similar high dependency area where they can be carefully monitored.
Although the outlook of patients with pneumococcal and staphylococcal
pneumonia who require assisted ventilation is poor, those with legionella infection,
atypical pneumonia, and varicella pneumonia have a recovery rate of over 50 per
cent. Chest physiotherapy and postural drainage are rarely helpful in the acute
stage, and may exhaust a toxic and ill patient. When there is increased sputum
production during recovery, physiotherapy can be useful. In patients with severe
infection and those in whom recovery is slow and prolonged, adequate enteral or
parenteral nutrition is important.
Introductions for hospital admission.
1.Physiological- social introductions
 Elderly patient ( age more than 70 years old);
 leucopenia less than 4,0x10/dl or leucocytosis more than 20.0x 10/dl with
neutrophylesis;
 mental confusion;
 possible aspiration;
 respiratory rate is more than 30 per minute;
40
 non-stable hemodynamics;
 toxic shock;
 multilobar affection;
 pulmonary abscess;
 social needs;
 pregnancy;
 non-effective treatment in community.
2. Concomitant diseases
 COPD;
 congestive heart failure;
 chronic hepatitis;
 chronic nephritis;
 alcoholism;
 immunodeficiency;
 acute or chronic renal failure.
Introduction for ICQ admission





respiratory rate is more than 30 per minute;
necessity of artificial ventilation;
severe respiratory failure ( PaO2/ FiO2< 250 Hg mm);
both-sided, multilobar or pulmonary abscess according chest radiography;
rapid progress of process ( increasing size of pulmonary infiltration more
than 50% during 48 hours);
 systolic pressure less than 90Hg mm;
 diuresis less than 20ml/h, acute renal failure required dialysis.
Specific measures (Etiotropic treatment)
Antibiotics
Principles of etiologic treatment.
 Treatment must be administrated as early as possible, before agent
indicating.
 Treatment must provide clinical and bacterial control with determination
of agent and its sensitivity to antibiotic.
 Antibiotic drugs must be administrated in adequate doze and with
adequate intervals.
 Treatment is continued till disappearance of intoxication, fever, physical
data in the lung, pulmonary consolidation according X-ray examination (
41
3-4 days after disappearance). Presence of clinical and X-ray residual
signs is not a reason for antibiotic therapy prolongation. Duration of
antibiotic treatment determine by an agent.
Pneumonia without
complications is treated 3-4 days more after normalization of body
temperature and blood test and 5 days if you use azitromycin. Duration
Mycoplasma and Chlamidia pneumonias is 10-14 days. Legionalla
pneumonia is 14 days (with AIDS -21 days).
 Change antibiotic if there is no effect during 2-3 days, and combine two
drugs if it is necessary.
 Inadmissibly using antibiotic without control as it can be a reason for
steady agents rise.
Duration of antibiotic therapy
Patients with uncomplicated pneumonia are usually treated with antibiotics for 7 to
10days. This may be unnecessarily long in some cases. Studies in Africa have
shown equally good results when treating pneumonia for 1, 3, and 7days. The
duration of therapy for those with more severe pneumonia is judged on clinical
response. In the presence of lung cavitation, treatment may be needed for 3 to 4
weeks. Criteria of antibiotic therapy effect are as under:
Clinical sings: Normalization of body temperature, decrease of intoxication, in
general the patient feels good, normal white blood cell, pus is decreased in the
sputum and positive dynamics of auscultation and X rays. Effect of the therapy is
noted in 24-72hours and it is not changed if there is no negative dynamics
Criteria of effectiveness of antibacterial treatment:
- lower body temperature;
-
intoxication relief;
- mend of condition;
- normalization of leucocytes formula;
- decrease in sputum with pus;
- positive dynamics of auscultation and on chest radiograph data.
For the highest effective of antibiotic therapy and decrease cost of treatment “stepdown therapy” is used now. Using this method antibiotic therapy is began with
intravenous dropping and in2-3 days after achievement of good effect intravenous
antibiotics is replaced with oral antibiotics.
Taking into account etiological classification of antibiotic therapy is different for
community-acquired, nosocomial, aspiration pneumonia.
42
Community –acquired pneumonia
The cause of the pneumonia is not usually known when the patient is first seen and
therefore lists of pathogens matched to ideal antibiotics are of little help. In
practice, a “best guess” of antibiotic choice has to be made, depending on the type
of patient, severity of infection, and any etiological clues from the clinical picture.
The small number of likely causes of community-acquired pneumonia makes this
relatively easy.
Mild or moderate pneumonia
In most previously fit patients with mild pneumonia the most likely infecting agent
is the pneumococcus or, less commonly, an atypical organism. Therefore the
choice lies between b;-lactam antibiotic, such as a penicillin, and erythromycin. An
aminopenicillin such as oral amoxicillin is well tolerated, cheap, and effective.
Erythromycin is appropriate for penicillin-allergic individuals or during a
mycoplasma epidemic or if an atypical infection is suspected. Gastrointestinal
intolerance is a less problem with the newer macrolides. Tetracycline, although
helpful for atypical organisms, is often no longer effective for the pneumococcus.
In those with chronic lung disease an antibiotic which is also effective against H.
influenzae is required. Amoxicillin is usually suitable. However, around 10 per
cent of H. influenzae are ampicillin resistant in the United Kingdom, with higher
figures being reported from some countries such as Spain and some parts of the
United States. If the patient has failed to respond to amoxicillin or is moderately
ill, b-lactamase-stable alternatives include co-amoxiclav, co-trimoxazole (but
beware of skin rashes and blood dyscrasias in the elderly), newer generation
cephalosporins, and chloramphenicol. Currently available quinolones, such as
ciprofloxacin, are highly effective against H. influenzae, M. catarrhalis, and some
atypical pathogens, but their expense and questionable activity against the
pneumococcus argues against their routine use as first line agents.
Severe pneumonia
The physician needs to be on the alert for any signs of deterioration (see discussion
of prognostic factors below). Severe pneumonia can evolve rapidly even in
previously fit people, and the mortality remains high despite apparently effective
antibiotics. Antibiotics should be given parenterally without delay, and must cover
all likely pathogens. Any antibiotic must provide effective cover against
pneumococcal infection. Penicillin-resistant pneumococci are a significant problem
in only a few countries so far but this worrying situation is changing progressively.
Other likely causes of severe community-acquired pneumonia include L.
pneumophila, Staph. aureus (particularly during influenza epidemics), H.
influenzae (particularly in those with chronic lung disease), and occasionally
atypical and varicella pneumonias . High doses of intravenous ampicillin (500 mg43
1 g 6 hourly) or cefuroxime (750 mg-1.5 g 8 hourly) together with erythromycin
(as erythromycin lactobionate 500-1000 mg 6 hourly) provide good initial cover
for all these pathogens. Patients allergic to penicillins can be given erythromycin
alone in high doses or combined (cautiously) with a cephalosporin such as
cefuroxime which has the advantage of being b-lactamase stable. Phlebitis in the
cannula site with intravenous erythromycin can be reduced by a slow dilute
infusion. During a period of influenza, or where there is a chance of secondary
staphylococcal pneumonia, flucloxacillin should be used as well. The antibiotics
are adjusted appropriately as soon as investigations identify a specific pathogen.
Nosocomial pneumonia
A mild early postoperative pneumonia in a previously fit person can usually be
treated like a community-acquired infection. Because of the variety of potential
pathogens in other types of nosocomial pneumonia, it is advisable to use broadspectrum or combination antibiotics as initial therapy, pending the results of tests.
These may include a broad-spectrum third-generation cephalosporin such as
cefotaxime with or without an aminoglycoside such as gentamicin. If there is a
high probability of pseudomonas infection, an appropriate penicillin derivative
such as azlocillin or ticarcillin or a cephalosporin such as ceftazidime should be
used. For suspected anaerobic infection, penicillin and metronidazole, or
clindamycin, will have advantages. Newer antibiotics such as the quinolones are
likely to have an expanding role in nosocomial infections. Physiotherapy aids the
clearance of infected secretions and, used postoperatively, may help to prevent
nosocomial pneumonia. Despite therapy the mortality is high, ranging from 25 to
50 per cent, largely dictated by the underlying condition of the patient, and in
survivors there is a considerable prolongation of hospital stay.
Etiological treatment of the AP
I.
II.
III.
IV.
Community acquired pneumonia- Penicillin, polusynthetic Penicillin, Blactamase, Flourquinolones, Macrolides, and Cephalosporines of I- II
generations.
Hospital acquired pneumonia- Polusynthetic Penicillin, inhibitors of BLactam, Aminoglycsides, Flouquinolones, Cephalosporines of III and IV
generation, and Metronidzol.
Immunocompromised pneumonia- Cephalosporines of III- IV generation,
inhibitors of B- lactam, IV Sulphanyl amides and anti viral drugs
(Acyclovir).
Atypical pneumonia- Macrolides.
Choice of antibiotics of the most common agent of pneumonia.you can find in
talbe 4.
Table 4. Selection of antibiotics of the most common agent of pneumonia
44
Agent
Pneumococcus
Streptococcus
Staphylococcus
Haemophilus
influenza
Mycoplasma
Legionella
Klebsiella
Pseudomonas
Anaerobes
Chlamydia
First drugs
Penicillin
Ampicillin
Penicillin
Oxacillin
Lincomycin
Ampicillin
Alternative drug
Erythomicin
Ftorchinolones
Cephalosporin’s
Erythromycin and
other macrolids
Erythromycin and
other macrolids
Gentamicin
Gentamicin
carbencillin
Trichopol
Ftorchinolones
Rifampicin
Ftorchinolones
Rifampicin
Ftorchinolones
Azlocillin
Cephalosporin’s
imipenem
Penicillin
Tetracycline
Macrolids
Ciprofloxacin
Erythromycin and Ftorchinolones
other macrolids
Reserve drug
Cephalosporin
imipiem
Cephalosporin’s
Tetracycline
Selection of antibiotics and different clinical situations-table 5.
Table 5. Selection of antibiotics and different clinical situations
Clinical situation
Primary
lobar
pneumonia
Primary atypical
pneumonia
Possible agent
Pneumococcus
First drug
Penicillin
Alternative drug
Erythromycin
Mycoplasma
Legionella
Klebsiella
Pneumonia against Haemophilus
a
background influenza
chronic bronchitis Streptococcus
Pneumonia against Staphylococcus,
a background a flu Pneumococcus,
Haemophilus
influenza
Aspiration
Enteric bacilli,
pneumonia
anaerobes
Erythromycin,
other macrolids
Azitromycin
Ampicillin
Macrolids
Azitromycin
Ampiox, penicillin
Amynoglecosids+
metronidazol
Ftorchinalones,
Cephalosporin’s
Artificial
ventilation
Amynoglecosids
Imipiem
Enteric bacilli,
Haemophilus
Laevomycetin
Ftorchinolones
Cephalosporin’s
Ftorchinalones,
Cephalosporin’s
45
penumonia
Pneumonia
AIDS
influenza
with Enteric bacilli,
Staphylococcus,
Penicillin, ampiox, Ftorchinalones,
aminoglicisids
Cephalosporin’s
Pathogenetic, symptomatic therapy, prevention of complications
Analgesics are used in significant high temperature and pleural pains, as they can
interact with the immunity system of the patients. In fit of cough used nonnarcotic drugs, which lower coughing and also it have mucolytic action and don’t
decrease the bronchial drainage function (Intussin, Stoptussin). Also described
vitamin therapy for the correction of oxidation of lipids. In acute period in the peak
of intoxication used water- soluble antioxidants (Ascorbinic acid and Unithol) are
used.
For the prophylaxis of circulatory disorders used Analeptics and Glycosides,
often Corglycon are used. AP is characterized by different disorders of immunity
system. There are observed functional depression of cellular immunity, humeral
immunity, depression of immune reactions and factors of natural defense.
Transitory disorders of immunity system does not need the administration of
immunomodulators. In significant disorders of immunity system lympholized
Endobulin in dose of 100mg/kg body weight is used, till the removal of symptoms
may be repeated after the interval of a week.
For the prophylaxis of DIC syndrome Heparin intercutaneous (IC) in the phase
of high temperature is prescribed. Severe forms of pneumonia complicated by
septic shock, pulmonary edema, DIC syndrome, acute vascular insufficiency, and
respiratory distress syndrome of adults due to be treated in the department of
intense care. In persistent pneumonias, antibiotics should be recommended
according to its sensitivity to it, results of bacteriological analysis of the sputum.
Also is necessery to maintain the drainage function of the bronchi, rational use of
mucolytics, bronchodilators, fibrobronchoscopy.
Prognosis
The majority of patients will recover quickly a few days after starting treatment. If
the recovery is unsatisfactory the causes should be fund out.
Prognosis is related to the pathogen, the host, and the interplay between the two. A
positive blood culture is a bad prognostic sign in bacterial pneumonias; the
mortality of bacteraemic pneumococcal pneumonia is 25 to 33 per cent compared
with 5 per cent for non-bacteraemic cases. There were reported 2500 reported
deaths for pneumococcal pneumonia in England and Wales in 1991, but many
46
were probably not reported. Pulmonary infections with Staph. aureus, H.
influenzae, or Gram-negative bacilli lead to a poor prognosis. However, patients
with atypical pneumonia generally do well. The mortality from communityacquired legionella pneumonia is 5 to 15 per cent.
Mortality and morbidity rise with increasing age of the patient and with the
presence of coexisting chronic illness (such as cardiac or respiratory disease or
diabetes). Other factors associated with a poor prognosis for pneumonia are
summarized in and can be used for early identification of those with severe
disease.
Prevention of pneumonia
Better housing and working conditions and better community health have
contributed greatly to the reduced incidence of community-acquired pneumonia.
Vaccination has been helpful in specific instances and may have a greater role to
play. Post-measles pneumonia, a common occurrence in children in developing
countries, can be reduced by a measles vaccination campaign, and pertussis
immunization reduces the frequency of respiratory complications of whooping
cough. Pneumococcal vaccination has been shown to be effective in reducing
serious pneumococcal pneumonia. It is recommended to patients who are
particularly liable to severe pneumococcal infection, such as those with chronic
respiratory and cardiac disease or sickle-cell disease, and in those due to have a
planned splenectomy. Some authorities recommend its use in all adults over the
age of 60 years. Influenza vaccination in autumn gives some protection to patients
who are debilitated and in whom an attack of influenza or its complications could
be serious.
Prevention of nosocomial pneumonia
The frequency of nosocomial respiratory infection can be reduced by such
measures as prevention of smoking preoperatively, early postoperative
mobilization, hospital staff hygiene, scrupulous care of respiratory equipment, and
infection control in high risk areas such as intensive care units. Selective
decontaminations of the gastrointestinal tract and direct applications of
antimicrobial agents to the respiratory tract have been used with some success to
prevent Gram-negative colonization of the respiratory tract and pneumonia in the
intensive care unit.
REFERENCES
1. American Thoracic Society. Guidelines for the initial management of adults with
community acquired pneumonia. //American Reviews of Respiratory Disease. –
1993. – Vol. 148. – Р.1418-1426.
2. Anon. Lower respiratory tract infections. // Medical Record Bulletin. – 1994. №
5. – Р.5-8.
47
3. Ausina, V. Rapid laboratory diagnostic methods in respiratory infections. //
Current Opinion in Infectious Diseases. – 1989. - № 2. – Р.541-546.
4. British Thoracic Society, Public Health Laboratory Service. Community
acquired pneumonia in adults in British hospitals in 1982-83: a survey of
aetiology, mortality, prognostic factors and outcome. Quarterly // Journal of
Medicine. – 1987. Vol. – 239. Р.195-200.
5. Dosmagombetova R.S. Methodic guide “ Pneumonia. Diagnosis and Treatment.
6. British Thoracic Society. Guidelines for the management of community
acquired pneumonia in adults admitted to hospital. //British Journal of Hospital
Medicine. – 1993. - № 49. Р.346-350.
7. Glynn, J.R. and Jones, A.C. Atypical respiratory infections, including
Chlamydia TWAR infection and legionella infection. //Current Opinion in
Infectious Diseases. – 1990. - № 3. – Р.169-175.
8. Kauffman, R.S. Viral respiratory infections. // Current Opinion in Infectious
Diseases. – 1988. - № 1. – Р.575-579.
9. Macfarlane, J.T. Community acquired pneumonia. // Recent Advances in
Respiratory Medicine ed D M Mitchell. Churchill Livingstone, London, 1991. –
Vol. 5. - Chapter 7. P.109-124
10. Macfarlane, J.T. An overview of community acquired pneumonia with lessons
learned from the British Thoracic Society Study. //Seminars in Respiratory
Infections. – 1994. - № 9. – Р.152-164.
11. Prospective study of aetiology and outcome of adult lower respiratory tract
infections in the community. // Macfarlane, J.T., Colville, A., Guion, A.,
Macfarlane, R.M., and Rose, D.H. Lancet. 1993. – V ol. 341. – Р.511-514.
12. Manresa, F. Rapid clinical diagnostic methods in respiratory infections //
Current Opinion in Infectious Diseases. – 1989. - № 2. – Р.536-540.
Community acquired pneumonia // Marrie, T.J. (ed.) //Seminars in Respiratory
Infections. – 1994. - № 9. – Р.129-219.
13. Marrie, T.J., Durant, H., and Yates, L. Community acquired pneumonia
requiring hospitalisation: 5 years prospective study. //Reviews of Infectious
Diseases. – 1989. - № 11. – Р.586-599.
14. Noah, N.D. Cyclical patterns and predictability in infection. // Epidemiology
and Infection. – 1989. Vol. – 102. – Р.175-190.
15. Niederman, M.S., Sarosi, G.A., Glassroth, J. Respiratory infections. A
scientific basis for management. - W.B. Saunders: Philadelphia, 1994 Respiratory infections: diagnosis and management Pennington, J.E. (ed). (2nd
edn.) - Raven Press: New York, 1989. 16. Santoro, J. Nosocomial respiratory tract infections. // The pneumonias (ed M.E.
Levison). - John Wright: Boston, MA, 1984. - P. 182-196.
17. A new diagnostic approach to the patient with severe pneumonia. Scandinavian
/ Sorensen, J., Forsberg, P., Hakanson, E. et al. // Journal of Infectious Diseases. –
1989. - № 21. – Р.33-41.
48
18. Torres, A. Accuracy of diagnostic tools for the management of nosocomial
respiratory infections in mechanically ventilated patients. //European Respiratory
Journal. – 1991. - № 4. – Р.1010-1019.
19. Verghese, A., and Berk, S.L. (1983). Bacterial pneumonia in the elderly.//
Medicine (Baltimore). – 1983. V ol. – 62. – Р.271-285.
20. Woodhead, M.A. Management of pneumonia. //Respiratory Medicine. – 1992.
- № 86. – Р.459-469.
PLEURISY
The pleural surfaces form the interface between the lung parenchyma and the chest
wall. The parietal pleura is closely applied to the chest wall and the surfaces of the
ribs. There is a thin layer of connective tissue separating it from the periosteum of
the ribs. Medially, the parietal pleura is adjacent to the pericardium and
mediastinal structures. At the hilum, the pleura forms a sleeve-like structure
encompassing the major vessels and bronchi. The visceral pleura covers the
surface of the lungs and extends into the major fissures which separates the lobes
of the lung. The pleura consists of a membranous structure, the surface of which is
covered with a single layer of mesothelial cells. These cells have microvilli over
their surface which facilitate the absorbtion of pleural fluid.
The pleura is not essential for adequate functioning of the lungs, although the
smooth surfaces do permit movement of the lungs within the thorax with minimal
energy loss. Obliteration of the pleural space either following surgery or as a result
of inflammatory disease does not result in significant respiratory impairment.
Between the two layers of pleura there is a potential space, the surfaces of which
are lubricated by a thin layer of fluid. The pressures within the pleural cavity are
generated by the difference between the elastic forces of the lungs and the chest
wall. The functional residual capacity the outward recoil of the chest wall is equal
to the inward recoil of the lung parenchyma. A number of pathological processes
can affect the pleura. Inflammation of the pleura results in characteristic pleuritic
pain which is aggravated by deep inspiration, coughing, or sneezing. It is often
accompanied by the pleural rub. The accumulation of fluid in the pleural space
results in a pleural effusion ( cause of pleural effustion see in table 6). Air can also
enter the pleural space resulting in a pneumothorax. Primary tumours of the
mediastinum are relatively uncommon. Involvement of pleura by metastatic
malignant disease is much more frequent.
Table 6. Causes of pleural effusion
49
Type of effusion
Transudates
Exudates
Inflammatory
Common
Cardiac failure.
Less common
Nephrotic
syndrome
(glomerulonephritis,
renal
amyloidosis,);
cirrhosis;
myxoedema.
Peritoneal dialysis
Subpleural abscess,intrahepatic
abscess; viral; fungal
Parapneumonic;
tuberculosis,
( infective)
Exudates
Inflammatory
(non- infective)
Exudate
neoplastic
Hemothorax
Chylothrax
Pulmonary emboli
Metastatic
lymphoma
Collage
vascular
disease,
pancreatitis,
Drug reaction, asbestos exposure,
Dressler’s syndrome, yellow nail
syndrome
carcinoma, Methelioma, Meig’s syndrome
Trauma, cancer metastasis, Sponteneous, bleeding disorders,
pleural carcinomatosis.
the ruoture of vessel in pleural
adhesions
in
spontaneous
pneumothorax; the break of the
aortic aneurysm into pleural
cavity
Lymphoma,
trauma, Lymphagioleomyomatosis
carcinoma
Epidemiology
All pathological processes in the pleura at appointed moment of development can
result in the formation pleural effusion and its clinical displays become conducting
in a picture of disease. The syndrome of an accumulation of fluid in the pleural
cavity is observed at inflammatory processes in the pleura and adjoining organs
(exsudate), . On data of Р.У. Laity in USA pleural effusion of various etiology is
diagnosed during one year more than at 1 million patients, and as principal causes
of involving in pathological process of the pleura are chronic circulatory
Insufficiency (37,7 %), bacterial (22,5%) .и virus-bacterial pneumonia(7,5%),
cancer (15,1%) pulmonary artery thromboembolism (11,3%). Existence of
appointed distinctions in the etiologic structure of pleurisies depends on the age of
patients. In children and teenagers the dominant role belongs to tuberculosis and a
bacterial pneumonia, in persons of more than 60 years - to tumor, diseases of heart,
pulmonary infarct.
50
The pleurisy as a rule is not an independent disease. It represents a pathological
condition complicating current of various processes in the lungs and adjoining to
the pleura structures (a chest wall, the diaphragm, subdiaphragmatic space).
Sometimes pleurisy is the display of the general (common) system diseases
proceeding without distinct (clear) defeat of fabrics adjoining with the pleura.
The purpose of the work: to seize theoretic knowledge of the principal causes
and mechanisms of the development of syndromes, an accumulation of liquid and
air in a pleural cavity; principles of diagnostics.
Definition
Pleurisy is an inflammation of the pleura with formation of fibrinous masses on
the pleura or pleural effusion. It is always secondary disease but sometime
clinical signs of the pleurisy dominate and mask the primary disease.
The pleural effusion results from an accumulation of fluid in the pleural space.
It is traditional by to divide effusions into transudates and exudates, although
blood, pus, or chyle may also present as collections of pleural fluid.
Pleural fluid formation
The two layers of the pleura allow the chest wall and lung to move together,
with lubrication of the pleural surfaces ensuring that this occurs with minimum
loss of energy. Normally lubrication is provided by a thin layer of fluid
representing an ultrafiltrate of plasma, although surfactant may also be present
and play a role. Although turnover of pleural fluid is probably of the order of 12 l/day, the volume of fluid present at any one time is only a few millilitres.
Under normal circumstances two factors operate to prevent the accumulation of
fluid in the pleural space: the pleura itself acts as a semipermeable membrane,
and the flux of fluid across the pleural space is accounted for by the forces
involved in Starling's law of transcapilliary exchange. The hydrostatic gradient
from the capillaries of the parietal pleura favours fluid efflux into the pleural
space. Pressure in the capillaries in the visceral pleura is close to that of the
pulmonary capillaries, and this lower pressure favours reabsorption of fluid
from the visceral surface . The lymphatic system provides a second method of
preventing excess fluid accumulation. In addition, it enables proteins to be
recovered from the pleural space and returned to the circulating plasma.
Factors likely to result in excess of fluid accumulation in the pleural space can
now be indentified. They include the following.
1.An imbalance between the hydrostatic and oncotic forces as defined in
Starling's equation. Such fluid is usually a transudate.
2.An alteration in the permeability of pleural capillaries resulting in an exudate.
3.Impaired lymphatic drainage.
4.Abnormal sites of entry (e.g. transdiaphragmatic passage of fluid in patients
with ascites).
51
Classification of pleurisy
І.Etiology:
1. infectious pleurisy;
2. aseptic pleurisy.
ІІ. Character of pathological process:
1. dry pleurisy;
2. pleural effusion.
ІІІ. Character of effusion:
1. serous;
2. serous-fibrinous;
3. purulent;
4. putrid;
5. hemorrhagic;
6. cholesterol;
7. chylous;
8. mixed.
ІV. Course:
1. acute;
2. subacute;
3. chronic.
V. Location :
1. diffuse;
2. encysted;
2.1 apical;
2.2 parietal.
2.3 Osteodiaphragmatic.
2.4 Diaphragmatic.
2.5 Paramediastinal.
2.6 Introlobular.
Clinical features
Symptoms specifically related to pleural disease are pain and breathlessness.
The extent to which these occur is likely to vary and clinical presentation will at
least in part be determined by the underlying pathogenesis. Pleuritic pain which
causes severe discomfort whill coughing or deep inspiration is more typical of
for “dry” pleurisy. It tends to improve when fluid is accumulated, separating the
inflamed pleural surfaces. The other major symptom is breathlessness which
becomes apparent only if there is a large effusion or in patients who already
have had impaired respiratory reserve. Abnormal physical signs may be absent
if the effusion is relatively small but are often diagnosed if the effusion is large.
Chest wall movement may be normal although it will tend to be limited,
particularly if there is pain. There can also be a lag of chest wall motion on the
52
affected side. The percussion sound is very dull and Demurazo’s line is
determined. If dullness is determined on IV ribs there is about 1-1,5 l of liquid.
Rising of dullness for one rib means increasing volume of liquid about to 500
ml. Breath sounds will be diminished or absent. Similarly, vocal resonance and
tactile vocal fremitus will be absent. Compression of the lung above the
effusion can result in signs of consolidation with bronchial breathing and an
increased vocal resonance. The position of the mediastinum as judged by the
trachea and apex beat will help in distinguishing between a large effusion and a
collapsed lung. In the former the mediastinum is central or displaced away from
the side of the effusion, whereas in the latter deviation is towards the affected
side.
Features of pleural friction rub
1. Auscultation during inspiration and expirationе.
2. Course rub.
3. No changes after coughing.
4. Auscultation on a distance .
5. Increase at pressure of stethoscope or thumb.
6. On auscultation it seems near the ear.
7. A patient feels the friction of pleural rub.
Diagnosis
1. Forced position – on the affected site больные предпочитают лежать на
больном боку, it limits displacement of the mediastinum to the healthy
side and it allows the healthy lung to take active part in respiration; if effuse
large position of patient is semirecumbent.
2. Diagnosis and jugular venous distention (a lot of liquid in the pleura cavity
embarrasses blood output of jugular venous ).
3. Dyspnoe.
4. Increasing size of the affected side, smooth or bulging intercostals spaces;
5. Lag of affected side in respiration.
6. Edema of skin on the affected side.
7. Dull sound above effusion.
8. Upper border is Demurazo’s line. Zenith of the line is on the scapular or
axillaries posterior line and then down to both sides to the column and to
anterior part of the thoracic cage.
9. Dullness of the percussion sounds on the healthy side like a triangle –
Rauhfus’s triangle, because of the displacement of the aorta to the healthy
side .
10.Disappearance of Traube’s space in a case of the left side pleural effusion;
11.Displacement of the heart to the healthy side;
53
12. Breath sounds will be diminished or absent.. Compression of the lung above
the effusion can result in signs of consolidation with bronchial breathing and
an increased vocal resonance.
13.Near the upper border of exudation the pleural friction rub are auscultated
Similarly, vocal resonance and tactile vocal fremitus will be absent.
Differential diagnosis
Differential diagnosis of dry pleurisy and intercostals neuralgia is in table 7.
54
Table 7. Differentiation dry pleurisy and intercostal neuralgia
Signs
Reason of pain in
the thoracic cage
Increase of pain
Dry pleurisy
Pain
connected
with
respiration
On bending of body to non
affected side
Palpation
of On palpation moderate pain
intercostals space in the area of pleural friction
rub
Pleural
friction Present
rub
Increase of ESR
Typical
Fever
Typical
Intercostal neuralgia.
Pain connected with motion of
the trunk and physical activity.
On bending of body to affected
side.
On palpation acute intensive
pain ,especialy near the column,
the sternum, and axillaries media
line
Absent
Not typical
Not typical
Differential diagnosis the left side paramedistenal pleurisy and angina pectoris is
in talbe 8
Talbe 8. Differentiation of the left side paramedistenal pleurisy and angina pectoris
Sings
Left side paramedistenal Angina pectoris
pleurisy
Mainly on the left side of Behind the sternum
relative cardiac dullness
Respiration, cough
Physical activity.
Location of pain
Reason of pain
Not typical
Irradiation of pain
Pleural friction rub
Effect
nitroglycerin.
ECG
of
In the left hand, left shoulder,
left scapula.
Typical, often pleuracardial Not typical
friction rub
Absent
Very tipical
No changes
Ishemia
Investigation of pleural effusion
The presence of the pleural effusion should be suspected on clinical
examination and can be confirmed by using radiographic imaging or
55
ultrasound. Whilst clinical features play an important part in identifying the
pathogenesis, examination of the pleural fluid or pleural biopsy material is most
likely to lead to a definitive diagnosis.
Radiographic techniques
Radiographic techniques are helpful in identifying the presence of an effusion
but are of limited value in determining the pathogenesis. A conventional
posteroanterior chest radiograph is usually adequate in confirming the presence
of the clinically significant effusion. Fluid tends to accumulate in dependent
parts of the thorax, and small effusions of the order of 500ml will be in blunting
of the costophrenic angle. Larger effusions result in increased opacification and
may produce mediastinal shift. Variations of the normal appearance will result
if the fluid is loculated, a situation which is more likely to occur with an
empyema or if there are pleural adhesions.
Ultrasound can be helpful in confirming the presence and site of an effusion.
Pleural fluid is identified as an echo-free space between chest wall and lung.
The presence of echoes within the fluid may indicate an empyema or
haemothorax, and ultrasound can also demonstrate the presence of septation
and loculi.
CT can detect very small effusions which may not be apparent using standard
radiograph imaging. It can also be the complement to ultrasound examination in
demonstrating the site of a pleural collection and has the additional advantage
of imaging the underlying lung. However, its role in routine evaluation of
pleural effusions is limited.
Thoracentesis
Percutaneous aspiration of pleural fluid is a relatively simple procedure which
can be undertaken for diagnostic purposes and, in the case of larger effusions,
can relieve breathlessness. It is usually performed with the patient upright in a
comfortable position with the arms and head supported on a pillow. Unless the
fluid is loculated, a conventional site for aspiration is posteriorally about 10cm
lateral to the spine and one intercostal space below the upper level of the fluid
as detected by percussion. A common error is an attempt to make aspiration as
low as possible, but this often yields a dry tap since it is impossible on clinical
grounds to determine the level of the diaphragm. The procedure is performed
under strict aseptic technique. The skin and underlying tissues are infiltrated
with local anaesthetic taking care to avoid the intercostal nerves and vessels
which run immediately beneath the rib. For diagnostic purposes it is usually
adequate to remove 50-100 ml of fluid. If therapeutic aspiration of large
amounts of fluid is being undertaken, the best way is to introduce a small
plastic canula into the pleural space to minimize the risk of damage to the
underlying lung.
Failure to obtain fluid can arise for a number of reasons including misdiagnosis
of the presence of fluid, incorrect site of aspiration, and the presence of viscid
fluid. Ultrasound examination can help to identify the reason for a failed tap
and guide further attempts if fluid is present.
56
Examination of pleural fluid
Biochemical, cytological, and microbiological examination of the pleural fluid
can help to determine the underlying cause if this is not apparent on clinical
grounds .
Macroscopic appearance
Transudates are clear straw-coloured fluids which do not clot on standing.
Many exudates are similar in appearance but can be somewhat turbid owing to
the presence of cells. Blood-tinged fluid is of little diagnostic significance, but a
uniformly bloody effusion is likely to be associated with an underlying
malignancy. Pus can sometimes be very viscid and difficult to aspirate. It is
turbid in appearance, yellow in colour, and often foul smelling. Chyle is
odourless and milky in appearance.
Biochemistry
Exudates will generally have a higher protein content than transudates and,
although a level of 30g/l has traditionally been used to help differentiation,
there is a significant overlap and results should be interpreted with caution.
Better differentiation may be obtained by comparing concentrations of protein
and lactic dehydrogenase in the pleural fluid with those of blood. The criteria
which can prove helpful in identifying an exudate are as follows:
(1)A fluid-to-serum ratio of total protein above 0.5;
(2)A fluid lactic dehydrogenase concentration above 200IU;
(3)A fluid-to-serum ratio of lactic dehydrogenase above 0.6.
Differentiation of exudates and transudate is talbe 9.
The concentration of glucose in the pleural fluid is normally equal to that in
serum. However, glucose concentration in the pleural fluid is consistently low
in rheumatoid-related effusions. Reduced concentrations of glucose are also
found in association with tuberculosis, empyemas, and malignancy. One rare
cause of a left-sided pleural effusion is pancreatitis, when pancreatic amylase
measurements of the pleural fluid will be elevated.
Talbe 9. Differentiation of exudates and transudate
Signs
Onset of disease
Exudate
Acute
Present of the chest Typical
pain during onset of
disease
Fever
Present
Typical
of Typical and significant
Transudate
Gradual
Not typical
Not typical
Not typical
57
inflammatory sings in
tests ( increase of
ESR, leukocytosis and
others)
Transudates are clear
Many exudates are similar coloured fluids which
in appearance but can be clot while standing. No
somewhat turbid owing to
the presence of cells.
Blood-tinged fluid is of
little
diagnostic
significance,
but
a
uniformly bloody effusion
is likely to be associated
with
an
underlying
malignancy.
Pus
can
sometimes be very viscid
and difficult to aspirate. It
is turbid in appearance,
yellow in colour, and often
has foul smelling. Chyle is
odourless and milky in
appearance.
Transudates are clear
Changes
of Turbid, fibrin like flakes.. coloured fluids which
macroscopic
seropurulent exudates is clot on standing. .
appearance
on divided into two layers:
standing.
upper- serous, lower –
purulent. Clot in standing
< 20 g/l
Protein concentration
> 30 g/l
< 0,5
Protein F:S ration
> 0,5
< 200 IU > 1,6 g/l
LDH
> 200 IU > 1,6 g/l
< 0,6
LDH F:S ration
> 0,6
< 1,015 kg/l
Density of pleural > 1,018 kg/l
liquid
< 0,3
Cholesterol F:S ration > 0,3
Negative
Rivalt’s test
Positive
Microscopic
appearance
58
strawdo not
smell
strawdo not
Cell counts
Cytological
examination
Most transudates have low cell
counts of less than 1000/mm3;,
with the cells being a mixture
of lymphocytes, polymorphs,
and mesothelial cells.
A small amount of clotted
Exudates tend to have mesothelia.
higher
white
counts,
although this in itself is of
little diagnostic value. A
polymorphonuclear
leucocytosis is indicative
of a bacterial infection but
can also be seen in
association
with
a
pulmonary
infarct
or
pancreatitis.
The
predominance
of
lymphocytes raises the
possibility of tuberculosis
or a lymphoma but may
also occur in association
with other malignancies.
The presence of excess
eosinophils is not in itself
diagnostic but tends to be
associated with benign
inflammation.
> 1000 в 1 мм 3.
Microscopic and cytological examination
Most transudates have low cell counts of less than 1000/mm with the cells
being a mixture of lymphocytes, polymorphs, and mesothelial cells. Exudates
tend to have higher white counts, although this itself is of little diagnostic
value. A polymorphonuclear leucocytosis is indicative of a bacterial infection
but can also be seen in association with a pulmonary infarct or pancreatitis. A
predominance of lymphocytes raises the possibility of tuberculosis or a
lymphoma but may also occur in association with other malignancies. The
presence of excess eosinophils is not itself diagnostic but tends to be associated
with benign inflammation.
For adequate cytology, a sample of 50ml of fluid in a heparinized bottle should
be sent for immediate examination. The finding of malignant cells is likely to
be diagnostic, although occasionally actively dividing mesothelial cells may
59
mimic to adenocarcinoma. The cytological diagnosis of a malignant
mesothelioma presents particular difficulties but can be helped by cytogenetic
studies.
Microbiology
Gram stain and culture of the pleural fluid is of diagnostic value if an infective
aetiology is suspected. Identification of an organism confirms the diagnosis and
sensitivity testing will assist in the appropriate choice of antibiotics. Stains for
acid-fast organisms are often unhelpful even if tuberculosis is suspected.
Cultures are more likely to be positive if a reasonable volume of fluid is
concentrated and then examined.
Pleural biopsy
Pleural biopsy may be indicated if initial analysis of pleural fluid fails to
determine the diagnosis. It is of particular value if there is a suspicion of an
underlying malignancy or tuberculosis. Closed-needle biopsy is usually
performed using an Abraham's or Cope's needle. Both of these are large blunttipped needles with a hook to catch a sample of parietal pleura. The technique is
similar to that used for pleural aspiration except whena small incision is made
in the skin and subcutaneous tissues to enable ease of insertion of the needle.
The Abraham's needle consists of an outer trocar with a side-hole and an inner
cannula with a cutting edge. Once in the pleural space, the side-hole is opened
by rotating the inner cannula and withdrawing it slightly. Fluid is then aspirated
to confirm the position of needle in the pleural space. The needle is withdrawn
at an angle to the chest wall such that the side-hole gently catches on to the
parietal pleura. At this point to the inner cannula is advanced and a biopsy is
obtained. Several samples can be obtained using this technique, but care must
be taken to avoid damage of intercostal nerves and vessels. Samples for
histological examination should be put into formalin and those for culture for
mycobacteria should be put into saline.
Needle biopsy undoubtedly increases the diagnostic yield in patients with
tuberculosis of the pleura. Aspiration alone gives positive results in
approximately 25 per cent of cases, and culture of biopsy material increases this
to 50 per cent. The additional diagnostic yield in malignant disease is less
dramatic, with only a small percentage of biopsies being positive when
cytology has been negative.
Thoracoscopy
Direct visualization of the pleura is technically possible using a thoracoscope. A
diagnosis results in more than 90 per cent of patients with tuberculosis or a
pleural malignancy since biopsies can be taken from areas which are
macroscopically abnormal. Although thoracoscopy was originally introduced in
1910 and is widely used in parts of Europe and North America, it is relatively
60
underused in the United Kingdom. However, technological advances have
improved ease of use and made it likely it become an increasingly valuable
diagnostic and therapeutic instrument which can be used under both local and
general anaesthesia.
Management of pleurisy
1. Etiological treatment .
2. Atntiinflammatory therapy by NSAIDs –aspirin, voltaren, indomethacine
3. Aspiration .
Palliative treatment is only necessary if the size of the effusion results in
significant breathlessness. If the patient is comfortable, no action may be
necessary. Percutaneous needle aspiration of 1 to 2 litres of fluid is a simple
outpatient procedure and often results in considerable symptomatic benefit. The
fluid is likely to recur but repeated aspiration may be an appropriate therapeutic
option. Intercostal tube drainage can be used to remove the majority of the fluid,
although this is also likely to be of temporary benefit unless combined with
pleurodesis. A number of sclerosing agents have been used with varying degrees of
success. Currently, tetracycline (500 mg in 100ml saline) is popular but adequate
analgesia is necessary using both local anaesthetic into the pleural cavity and
systemic analgesics. The pleural space is drained as completely as possible, the
tetracycline is then injected, and the tube is clamped for 1 to 2 h. Any residual fluid
is drained and the tube is removed after 24 h. An alternative approach is to
insufflate iodized talc into the pleural space at thoracoscopy. Surgery with either
pleurectomy or pleural abrasion is very effective in preventing recurrence,
although it is rarely regarded as an appropriate option.
4. Detoxication
Physical therapy, massage.
REFERENCES
1. American Thoracic Society. Guidelines for the initial management of adults with
community acquired pneumonia. //American Reviews of Respiratory Disease. –
1993. – Vol. 148. – Р.1418-1426.
2. Anon. Lower respiratory tract infections. // Medical Record Bulletin. – 1994. №
5. – Р.5-8.
3. Ausina, V. Rapid laboratory diagnostic methods in respiratory infections. //
Current Opinion in Infectious Diseases. – 1989. - № 2. – Р.541-546.
4. British Thoracic Society, Public Health Laboratory Service. Community
acquired pneumonia in adults in British hospitals in 1982-83: a survey of
aetiology, mortality, prognostic factors and outcome. Quarterly // Journal of
Medicine. – 1987. Vol. – 239. Р.195-200.
5 .Dosmagombetova R.S. Methodic guide “ Pneumonia. Diagnosis and Treatment.
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6. British Thoracic Society. Guidelines for the management of community
acquired pneumonia in adults admitted to hospital. //British Journal of Hospital
Medicine. – 1993. - № 49. Р.346-350.
7. Glynn, J.R. and Jones, A.C. Atypical respiratory infections, including
Chlamydia TWAR infection and legionella infection. //Current Opinion in
Infectious Diseases. – 1990. - № 3. – Р.169-175.
8. Kauffman, R.S. Viral respiratory infections. // Current Opinion in Infectious
Diseases. – 1988. - № 1. – Р.575-579.
9. Macfarlane, J.T. Community acquired pneumonia. // Recent Advances in
Respiratory Medicine ed D M Mitchell. Churchill Livingstone, London, 1991. –
Vol. 5. - Chapter 7. P.109-124
10. Macfarlane, J.T. An overview of community acquired pneumonia with lessons
learned from the British Thoracic Society Study. //Seminars in Respiratory
Infections. – 1994. - № 9. – Р.152-164.
11. Prospective study of aetiology and outcome of adult lower respiratory tract
infections in the community. // Macfarlane, J.T., Colville, A., Guion, A.,
Macfarlane, R.M., and Rose, D.H. Lancet. 1993. – V ol. 341. – Р.511-514.
12. Manresa, F. Rapid clinical diagnostic methods in respiratory infections //
Current Opinion in Infectious Diseases. – 1989. - № 2. – Р.536-540.
Community acquired pneumonia // Marrie, T.J. (ed.) //Seminars in Respiratory
Infections. – 1994. - № 9. – Р.129-219.
13. Marrie, T.J., Durant, H., and Yates, L. Community acquired pneumonia
requiring hospitalisation: 5 years prospective study. //Reviews of Infectious
Diseases. – 1989. - № 11. – Р.586-599.
14. Noah, N.D. Cyclical patterns and predictability in infection. // Epidemiology
and Infection. – 1989. V ol. – 102. – Р.175-190.
15. Niederman, M.S., Sarosi, G.A., Glassroth, J. Respiratory infections. A
scientific basis for management. - W.B. Saunders: Philadelphia, 1994 Respiratory infections: diagnosis and management Pennington, J.E. (ed). (2nd
edn.) - Raven Press: New York, 1989. 16. Santoro, J. Nosocomial respiratory tract infections. // The pneumonias (ed M.E.
Levison). - John Wright: Boston, MA, 1984. - P. 182-196.
17. A new diagnostic approach to the patient with severe pneumonia. Scandinavian
/ Sorensen, J., Forsberg, P., Hakanson, E. et al. // Journal of Infectious Diseases. –
1989. - № 21. – Р.33-41.
18. Torres, A. Accuracy of diagnostic tools for the management of nosocomial
respiratory infections in mechanically ventilated patients. //European Respiratory
Journal. – 1991. - № 4. – Р.1010-1019.
19. Verghese, A., and Berk, S.L. (1983). Bacterial pneumonia in the elderly.//
Medicine (Baltimore). – 1983. V ol. – 62. – Р.271-285.
20. Woodhead, M.A. Management of pneumonia. //Respiratory Medicine. – 1992.
- № 86. – Р.459-469.
62
BRONCHIAL ASTHMA
Definition
Bronchial asthma is a chronic inflammatory disease of respiratory ways with
taking part of blood cells( eosinphilis, T-lymphocytes) mediators of allergy and
inflammation, according to preasthmatic persons with bronchial hyperreactivity
obstruction of bronchi, which results in asthmatic attack with wheezes, or
cough with difficulty of breath, especially at night or early in the morning.
This determination corresponds to basic positions of the combined report of
National institute of the Heart, Lungs and Blood (USA) and WHO
“Bronchial asthma”. Global strategy – GINA (1993).
According the modern conception in the base of BA is chronic inflammation
in bronchi, which connect with4 components (forms) of bronchial obstruction:
 Acute obstruction- due to spasm of smooth muscle;
 subacute obstruction- due to mucosal edema;
 chronic obstruction- occlusion of medium-sized bronchi and
bronchioles;
 irreversible obstruction ( sclerotic)- due to sclerotic changes in bronchial
wall during long clinical course.
Epidemiology
Bronchial asthma is a common clinical condition which affects individuals in
almost any age and is an important cause of respiratory morbidity and mortality.
Recent epidemiological surveys suggest that the prevalence of asthma is steadily
increasing, while death rates attributed to asthma have remained stable or have
slightly increased over the past 30 years. The cause of these temporal trends to
asthma prevalence is unclear: in part they represent changes in diagnostic labelling,
but there appears to have been a real increase in prevalence. A number of
explanations have been proposed, including increased environmental pollution
from motor vehicles, dietary changes associated with affluence, and the increased
use of bottle feeding with cow's milk in infancy. Increased mortality rates from
asthma may also be partly due to changes in diagnostic labelling, but the
widespread use of b-adrenergic agonists has also been implicated.
BA is a common malady and affects all ages about 5%of the American
population; the same figure in Europe and Canada. About 2 billion of people die
annually and the figure is increasing, especially among children. According to
German doctors’ data not less than one third coughing people are affected by
asthma. It is possible to suppose we have the same amount of persons suffering
asthma. Living and working conditions, nutrition and environment play
considerable role. There are a lot of episodes of BA in biotechnological factories.
Now days mortality is increasing because of unpractical treatment and late
hospitalization. Unpractical treatment in the result of diagnostic mistakes on one
63
side and the lack of knowledge of moderns methods of therapy depending on
malady currency. Knowledge of diagnosis criteria and therapy principles let to
determine the disease in time and administer rational treatment.
The result of the last epidemiological research is: about 4-10 % of population
in the world affect by bronchial asthma of different severity.
Etiology
Much new information on the pathophysiology of asthma has been obtained in the
past 15 years, and the recent advent of fibreoptic bronchoscopy as a research tool
has allowed detailed examination of the respiratory tract in mild asthma. This has
led to a fundamental reappraisal of the pathophysiological mechanisms of this
disease and has provided a firm scientific basis for treatment strategies in this
condition. Asthma can arise in any age, but there are peaks of onset in childhood
and in middle life. Childhood asthma is usually associated with atopic allergy,
whereas adult onset of asthma often (but not always) arises in non-atopic
individuals. Both allergic and non-allergic asthma appear to have significant
inherited components.
Predisposing factors:
 heredity;
 atopy;
 bronchial hyperactivity.
Heredity
Hereditary predisposition to BA was found in 46,3 % of patients. According to
investigations if father has BA probability BA’s developing is 20-30 %; but if both
parents have BA it increases till 75 %. As a whole they consider that risk of BA
appearance in a child whose parents have atopy is 2-3 time higher than in a child
whose parents don’t have it.
The inheritance of asthma per se does not obey simple Mendelian laws, and family
studies suggest that genetic and environmental components at be required before
asthma becomes evident. Several lines of evidence suggest that the ability to make
large amounts of IgE directed against environmental allergens (atopy) is
genetically controlled. IgE responses to highly purified allergen fragments are
often restricted to individuals bearing a particular major histocompatibility
complex (MHC) class II haplotype, but IgE responses to more complex allergens
(e.g. house dust mite and animal danders) are not MHC restricted.
Correspondingly, there are no clear associations of atopic asthma with particular
HLA types. Genetic linkage studies have suggested that atopy (defined as one or
more skin tests to a common aeroallergen, clinical asthma, rhinitis, or
conjunctivitis) is strongly linked through direct maternal transmission to the gene
for the b-chain of the FcsRI molecule on the long arm of chromosome 11 in some
families. It is important to recognize that development of atopy is not sufficient to
64
cause allergic asthma since many individuals have allergic rhinitis or allergic
conjunctivitis without clinical asthma or any evidence of increased bronchial
irritability. Nevertheless, atopic allergy is an important cause of asthma and is an
important inducer of episodic symptoms in those who are already sensitized to
airborn allergens.
At present they suppose polygenic type inheritance predisposition to bronchial
asthma. Genetic markers of predisposition to BA are certain HLA-antigens.
The patients with BA more often have antigens B13, B21,B35 and DR5. There is
information about frequent popularity of antigens A2,B7,B12, B27 DR2. in
patients with BA. Presence of these antigens increases risk of BA developing. On
the contrary, antigens A28,B14,BW41,DR1 are “ protective” antigens in the
developing of BA.
Atopy
Atopy is the capacity of the organism to produce increased amount of IgE as a
reaction to allergens influence of environment. At the same time there is a high
level of IgE in blood, positive skin test, present allergy manifestation in history in
such patients.
Patients with BA and their relatives extremely often have atopy. The capacity
to IgE synthesis is under genetic control and hand down.
When asthma arises in adult life, it may represent reactivation of childhood
asthma, in which case atopic allergy is usually demonstrable. Asthma arising de
novo in adulthood is less frequently associated with atopy. The serum IgE
concentration is usually within the normal range and skin tests to common airborne
allergens are negative. Many individuals with late-onset of asthma appear to
develop the condition for the first time following upper respiratory tract infections.
Rhinovirus infection has been linked with the development of asthma on both
clinical and epidemiological grounds. Moreover, most individuals with asthma
experience acute exacerbations when they have upper respiratory tract infections.
Respiratory viruses are also important in childhood asthma, and an
epidemiological survey of asthma in schoolchildren found virus infection in nearly
80 per cent of exacerbations when sensitive isolation techniques based on the
polymerase chain reaction were used.
Occupational asthma is an important cause of ill health in the workplace. A wide
range of organic and inorganic materials have been implicated as causes of
occupational asthma. These can be loosely divided into high molecular weight and
low molecular weight agents. High molecular weight occupational agents (e.g. rat
urinary protein) cause asthma through the same mechanisms as other airborne
protein allergens such as grass pollen and house dust mite antigens. IgE is usually
demonstrable and there is strong association with atopic status. In contrast,
occupational asthma due to low molecular weight agents (isocyanates, acid
anhydrides, platinum salts, plicatic acid) is less clearly linked to IgE, except the
65
case of platinum salts, and pre-existent atopy is not a risk factor for low molecular
weight occupational asthma.
While withdrawal from exposure often leads to clinical improvement, it is quite
common for occupational asthma to persist despite cessation of exposure, and in
these cases the clinical picture gradually comes to resemble intrinsic asthma.
Bronchial hyper-responsiveness
Asthma is characterized by marked variation in the calibre of the intrapulmonary
airways over short periods of time. In addition, asthmatic individuals often report
acute episodes of asthma on exposure to non-specific irritants such as cold air,
inorganic dusts, cigarette smoke, perfumes, paint, etc. These are not allergic
responses, but are exaggerated responses of the airways to the non-specific irritant.
This phenomenon is termed as non-specific bronchial hyper-responsiveness and
can be formally documented by the response to the non-specific
bronchoconstrictors methacholine or histamine.
In experimental studies, a wide range of non-specific stimuli have been used to
induce bronchospasm in asthmatic patients; some agents act directly on the
airways smooth muscle (histamine, methacholine, etc.), while others act indirectly
either by inducing the release of mast cell mediators (adenosine etc.) or through
neural reflex mechanisms. Some of these agents will also induce
bronchoconstriction in non-asthmatic individuals, but this increased non-specific
responsiveness is characteristic of asthma and correlates with disease severity .
Other pharmacological agents have no direct bronchoconstrictor effect but increase
bronchial responsiveness by increasing epithelial permeability or increasing
postreceptor sensitivity of smooth muscle. Several mechanisms have been
proposed to explain bronchial hyper-responsiveness. Originally it was thought that
the abnormality might be in the bronchial smooth muscle, but the accumulated
evidence indicates that bronchial smooth muscle behaves no differently in
asthmatics in comparison with normal subjects when studied in vitro. Current
thinking emphasizes the importance of changes in the geometry of the airways in
the response to bronchoconstriction. Thickening of the airways mucosa due to
inflammation and oedema has little influence on baseline airways resistance, but
when the bronchial smooth muscle contracts the swollen mucosa continues to
occupy the same absolute volume and thus the airways lumen is decreased by a
much greater proportion than if the mucosa was not swollen. Since resistance is
inversely proportional to the fourth power of the radius (Poiseuille's law), a small
increase in the thickness of the airways mucosa will have a marked effect on
airways resistance in response to a given contraction of the bronchial smooth
muscle. Intraluminal secretion of mucus and cells will also narrow the lumen and,
like mucosal swelling, will have a disproportionate effect on airways resistance
when the bronchial smooth muscle contracts. Finally, peribronchial oedema
reduces the elastic recoil of the airways and this in turn allows a greater degree of
airways narrowing to a given dose of a bronchoconstricting agonist.
66
There is more to bronchial asthma than bronchial hyper-responsiveness, but
symptoms such as exercise-induced asthma, nocturnal asthma, cough, and
variability of peak flow measurement are largely manifestations of different types
of bronchial hyper-responsiveness. Measurements of bronchial hyperresponsiveness by inhalation challenge have been widely used in epidemiological
studies of asthma but are not usually required in clinical management, except in
cases where there is doubt about the diagnosis of asthma or in the assessment of
occupational asthma. Finally, it is worth noting that b-adrenergic agonists have no
effect on bronchial responsiveness, while inhaled corticosteroids significantly
reduce hyper-responsiveness when used regularly over 4 to 6 weeks.
Causal factors
Realization of predisposing factors and other biological defects occur under
the influence of causal factors that result in bronchial asthma.
Allergens
Allergens are basic etiological factor of BA.
Household allergens
Household allergen is usual household dust.
Epidermal allergens
These are epidermal elements, dandruff, animal hair ( dogs, cows, pigs, horses,
and others), birds, and human.
Insect allergens.
Insect allergens are allergens of insects ( bees, bumblebee, wasps, mosquitos,
cockroaches).
Grass pollen antigen
Pollen has allergic properties and causes allergosis- pollinosis ( allergic rhinitis,
conjunctivitis<BA).Antigenic properties are conditioned by proteins in them. 200
types of plants can be reasons of pollinosis. Size of pollen is 30 mcm and it can
come deep inside of respiratory ways causing bronchial asthma.
Fungoid allergens
About 70-75 % of patients with BA have allergy to fungi. ( G.B. Fedoseyev
1996). The most allergenic fungi of Penicillium, Aspergillus, Mucor, Altepmaria,
Candida.
Food allergens
Food allergens is the reason of BA in 1-4- adults. The most allergenic products
are milk, eggs, fish and meet, wheat flour.
Drug allergens
Drugs can be the reason of exacerbation and deterioration of BA about in 10%
of patients. ( Hunt, 1992) Sometimes drugs can be the reason of BA developing.
Professional allergens
According to Bardana ( 1992), Broors (1993) in 2-15% patients professional
factors are reasons of BA. Today about 200 substances can be reason of
professional bronchial asthma.
67
Endogenous etiological factors
Endogenous factors are not allergens and reasons of intrinsic bronchial asthma.
Endogenous factors:
 metabolism disorder of arachidonic acid because of aspirin influence;
 bronchial hyper- responsiveness to physical activity (exercise- induced
asthma);
 mental factor can be the reason rather seldom of mental bronchial
asthma;
 dyshormonal disorders. Dysfunction of the ovaries and failure of adrenal
glands can be the reason of BA.
Factors which have promoting action: cold, smoking, pollutions.
Pathogeny
The pathology of asthma
Until quite recently, virtually all the available information on the histology of
asthma was based on postmortem studies. When individuals die from acute severe
asthma, their lungs show widespread obstruction of the small airways with mucus
plugs containing fibrin and eosinophils. Death in such cases is primarily due to
asphyxiation secondary to endobronchial plugging rather than bronchoconstriction.
The bronchial epithelium is often damaged and may be shed into the airway. The
basement membrane is thickened with subepithelial fibrosis and there is bronchial
inflammation with oedema, vasodilatation, and a mixed cellular infiltrate
consisting of eosinophils, neutrophils, and T lymphocytes. Ten years ago, it was
thought that these changes reflected severe fatal asthma and were not present in
milder forms of the disease.
This view has radically changed following a series of studies which have used
fibreoptic bronchoscopy to obtain biopsies from asthmatic airways for histological
examination. It turns out that bronchial biopsies from mild asthmatics show
inflammatory changes similar to those found in asthma deaths, with fragility of the
bronchial epithelium and subepithelial fibrosis with deposition of types III and V
collagen. Light and electron microscopy reveal mast-cell degranulation and
infiltration by eosinophils and mononuclear cells (Figs. 4 and 5) 1968,1969. The
eosinophils present in such biopsies are activated as shown by monoclonal
antibody staining for the secreted form of eosinophil cationic protein on their
surface.
The lymphocyte content is slightly increased in bronchial biopsies from asthmatic
subjects but the principal difference from control subjects is that the T
lymphocytes present in asthmatic biopsies activated as shown by expression of the
IL-2 receptor (CD25) and the presence of mRNA for the cytokines IL-5 and
granulocyte-macrophage colony-stimulating factor. These changes are clinically
relevant in the opinion that there is an association between eosinophil infiltration,
68
T-cell activation, and the degree of bronchial hyper-responsiveness. Treatment
with inhaled corticosteroids for 4 weeks leads to a reduction in all inflammatory
parameters, which parallels the reduction in non-specific bronchial responsiveness.
These findings have led to the reclassification of asthma as an inflammatory
disorder of airways mucosa, with bronchial hyper-responsiveness and other
associated features being viewed as consequences of inflammation rather than
primary phenomena.
Histological studies of intrinsic non-allergic asthma and occupational asthma show
very similar findings to the biopsy appearances of allergic asthma. In fact,
eosinophil and lymphocyte activation are, if anything, rather more prominent in
intrinsic asthma, emphasizing the importance of cellular inflammation as a
common feature of all forms of asthma and raising the possibility that intrinsic
asthma may represent a form of autoimmune disease.
Inflammatory events in the bronchial mucosa
In patients with allergic asthma, exposure to a relevant allergen causes
degranulation of mast cells present in the airway lumen and airway mucosa. This
leads to the release of histamine and a range of newly formed mediators which
induce bronchoconstriction, oedema, mucus secretion, and vasodilatation. Acute
bronchospasm due to allergen exposure usually resolves within 1 to 2h, but 3 to
12h after allergen exposure there may be a recurrence of bronchoconstriction
which is much more persistent and much more difficult to reverse with
bronchodilating drugs than the acute asthmatic response to allergens. This latephase of asthmatic response is associated with an increase of non-specific
bronchial responsiveness and with the accumulation of neutrophils, eosinophils,
and other leucocytes. Eosinophils are a characteristic feature of asthmatic
inflammation and are capable to cause considerable damage to the bronchial
epithelium. They contain several basic proteins (major basic protein, eosinophil
cationic protein, eosinophil-derived neurotoxin, and eosinophil peroxidase) which
induce detachment of the bronchial epithelium in experimental models and which
can induce degranulation of mast cells directly. Mast-cell and eosinophil-derived
growth factors can induce the proliferation of myofibroblasts which in turn are
probably responsible for the deposition of interstitial collagens beneath the
basement membrane. In addition to their effect on epithelial growth and integrity,
the eosinophil basic proteins may damage the epithelium by direct effects on the
basement membrane which may in turn alter the ability of the epithelium to
regulate the water and ion content of the fluid lining the bronchial tree. Exposure
of autonomic nerve endings beneath and within the epithelium appears to enhance
the inflammatory response through the release of the neuropeptides substance P,
neurokinin A, and calcitonin-gene-related peptide.
Eosinophil growth and differentiation are controlled by the cytokines IL-3, IL-5,
and granulocyte-macrophage colony-stimulating factor. These cytokineses are
principally produced by T lymphocytes, but mRNA for granulocyte-macrophage
69
colony-stimulating factor can also be identified in macrophages and bronchial
epithelial cells. Colabelling studies have demonstrated that the mRNA
hybridization signals for IL-3, IL-5, and granulocyte-macrophage colonystimulating factor in bronchial lavage cells are confined to T cells. Consequently,
there has been considerable interest to the role of T lymphocytes in atopic allergy.
T cells have long been implicated in the regulation of IgE production, principally
through the production of IL-4, which promotes isotype switching of B cells to IgE
and facilitates differentiation into IgE-producing plasma cells. Interestingly, IL-4
protein has been localized to mast cells in bronchial biopsies using
immunocytochemical methods. This may reflect de novo synthesis or storage of
IL-4 produced by other cells.
While regulation of IgE induction is clearly important in the development of
asthma, it appears to be less relevant to the pathophysiology of established disease.
It has been clearly demonstrated that allergen challenge of the skin or airways
leads to recruitment of CD4+T cells. This process has mainly been studied in the
skin where it is easier to control the allergen dose and to obtain serial samples. In
the skin model, the recruited T cells are mainly of the CD45RO+ (memory)
phenotype and, as the reaction develops over 12 to 24h, activated T cells can be
identified by increased expression of the IL-2 receptor (CD25) and production of
the cytokines IL-3, IL-4, IL-5, tumour necrosis factor-alfa and granulocytemacrophage colony-stimulating factor as shown by in situ hybridization.
Histological studies of allergen challenge in asthmatic airways have been less
detailed, but are broadly consistent with the skin model. Based on these patterns of
cellular recruitment and activation, the T cells recruited after allergen exposure
appear to be the human homologue of the murine TH-2 cell. Other studies have
demonstrated an excess of TH;-2 cells in the blood of atopic individuals and
preferential activation of TH-2 cells on exposure to allergens as compared with
non-allergenic proteins. T cells in BAL and bronchial biopsies are generally of the
CD45RO+memory subset phenotype and are more often “activated” than
peripheral blood T cells, as shown by increased expression of the IL-2 receptor
CD25. To date there has been no convincing evidence that T cells in asthmatic
airways mucosa differ in their T-cell antigen receptor family usage, although there
are some preliminary data which suggest that there may be a reduced usage of Tcell receptor V; n-alfa gene families in asthmatic lungs.
Further evidence supporting the importance of eosinophils and T cells in the
pathogenesis of asthma comes from histological studies performed before and after
a course of inhaled corticosteroids. This form of treatment is very effective for the
most forms of asthma, and reduces both non-specific bronchial responsiveness and
airways inflammation. When given over a 6-week period, beclomethasone
dipropionate substantially reduces the numbers of eosinophils and activates T-cells
present in asthmatic airways. Additional evidence comes from a 6-month doubleblind placebo-controlled clinical trial of cyclosporin A (a specific inhibitor of Tcell activation) which showed a clear beneficial effect on spirometric measures in
patients with chronic severe asthma.
70
Interest to the mechanisms of cellular recruitment in asthma has also attracted
attention towards the vascular endothelium as a potential site for therapeutic
intervention. Allergen exposure leads to upregulation of ICAM-1, E-selectin, and
VCAM-1, and it seems highly likely that these endothelial changes are important
in inducing the influx of inflammatory cells to the site of allergic reactions. In a
primate model of asthma, administration of a monoclonal antibody directed against
ICAM-1 has been shown to attenuate the development of bronchial responsiveness
on subsequent exposure to allergen. This area is now the subject of intense
research with a view to modulating cellular recruitment in human asthma.
Physiology of asthma
In the presence of airways inflammation and bronchial irritability, a wide range of
specific and non-specific insults lead to transient smooth muscle contraction. More
prolonged bronchoconstriction and airflow obstruction arise when a chronic
inflammatory process is set in train, with mucosal oedema, mucus secretion, and
epithelial damage. These changes in airways calibre affect both large and small
airways and lead to an overall increase in airflow resistance. Because of the
relative numbers of large and small airways and the relationship of resistance of
flow to airways diameter, most of the airways resistance in health and disease is
due to small airways. Thus it is principally the obstruction of small bronchioles
which leads to increased airflow resistance in asthma. Measures of expiratory flow
rates (forced expiratory volume in 1&nbsp;s (FEV1;) and peak expiratory flow
rate) are decreased and disturbed airflow patterns are clinically audible as wheeze.
Air is trapped in the lungs, leading to an increase in functional residual volume,
usually without any change in total lung capacity. As a direct consequence of the
increase in airways resistance the work of breathing is increased, leading to the
subjective sensation of breathlessness. Arterial blood gases are usually normal in
stable asthma. In acute exacerbations, some bronchioles become completely
obstructed by mucus plugs, leading to ventilatory perfusion mismatch and hence to
arterial hypoxaemia. To compensate the patient hyperventilation; this blows off
carbon dioxide but is unable to restore a normal PaO2. In very severe
exacerbations, the patient may eventually fail to sustain the increased respiratory
effort, and will then present with a relatively quiet chest, hypoxaemia, and a
normal or rising PaCO2;. This represents a life-threatening deterioration and
requires urgent treatment and ventilatory support, otherwise respiratory arrest and
death by asphyxiation will follow.
In summary: asthma is a chronic inflammatory condition of the airways which has
a complex etiology. There is undoubtedly a genetic component, but the inheritance
pattern is not simple. Development of asthma appears to require a susceptible
airway, upon which one or more environmental inciting agents act to induce a
chronic mucosal inflammation, characterized by eosinophil and T-cell infiltration.
Once established, this chronic inflammatory process leads to the development of
the clinical symptoms of asthma. This inflammation allows a wide variety of non71
specific irritants to cause bronchoconstriction (bronchial hyper-responsiveness).
Acute episodes of asthma may be precipitated by mast-cell degranulation via
sensitizing IgE antibody. Once established, the airways of all asthmatics, mild or
severe, show chronic inflammatory changes with a characteristic infiltration by
eosinophils and T lymphocytes. Unlike classical delayed-type hypersensitivity, the
T cells present express cytokines of the TH-2 subset which are probably important
in perpetuating the eosinophilic tissue response and may contribute to the
continued induction and production of IgE. Chronic asthma is associated with the
continued influx of inflammatory leucocytes (particularly eosinophils and T cells)
and further damage of the bronchial epithelium. Recognition of the inflammatory
basis of asthma has led to a reappraisal of treatment strategies in asthma and to the
identification of several possible future therapeutic targets. The current rationale of
treatment is to try to suppress the inflammatory component of asthma using
prophylactic anti-inflammatory drugs. Direct-acting bronchodilators ply an
important role as first-aid relief for smooth muscle spasm but do not influence on
the inflammatory process and therefore should not be regarded as first-line
maintenance treatment. Acute exacerbations of asthma are associated with
increased inflammatory changes and mucus plugging of the airways; these require
systemic anti-inflammatory therapy as inhaled medication will not be able to
penetrate the blocked airways and reach the affected site.
With this new understanding of the cellular and molecular mechanisms of asthma,
there is also the potential for the development of new therapeutic interventions.
Such treatments may not replace conventional medication for the majority of
patients but might relieve those who are not helped by current treatments.
Mediator’s role in developing of pathophisiological
manifestations of BA is in
the talbe 10
Table 10. Mediator’s role in developing of pathophisiological
BA.(Kaliner,1987)
Pathophysiologic changes
Bronchospasm
manifestations of
Mediators
Histamine
Leuditriene C4,D4,E4
Prostaglandin D2,F2a
Tromboxane A2
Plataletactive factor
Mucosal edema
Histamine
Leuditriene C4,D4,E4
Prostaglandin E2
Bradykinin
Plataletactive factor
Prostacyclin
Cell infiltration of bronchial wall (by Eosinophil chemotaxis factor
eosinophils, neutrophils,
Neutrophil chemotaxis factor
72
Bronchial hypersecretion
Epithelial desquamation
Basal membrane thickening
Prostaglandin D2, E2
Leuditriene B4
Histamine
Leuditriene C4,D4,E4
Prostaglandin A2,D2,F2a
Acetylcholine
Tumor necrosis factor
Proteolytic ferments
Peroxides
Proteolytic ferments
Classification
Today there are two methods of classifications.
The first classification of BA is according etiology. The second one is according to
the severity of BA. ( table 11)
Table 11. Classification of Bronchial asthma ( IDC- 10)
Class X. Respiratory system disoders
J45
J45.0
Block name
Asthma
Extrinsic (allergic asthma)
Allergic bronchitis
Allergic rhinitis with asthma
Exogenic allergic asthma
Hay fever
J45.1
Instrinic asthma
Idiosyncrative asthma
Endogenic non- allergic asthma
J45.8
Mixed asthma
J45.9
Unspecified asthma
Asthmatic bronchitis
Late originated asthma
J46
Status asthmaticus
Acute grave asthma
Other classification is clinical classification according to the severity of
bronchial asthma which is used practically for management of asthma. (table
12).
73
Table 12. Severity of bronchial asthma
Severity
Slight episodic current
Slight persistent asthma
Middle persistent asthma
Grave persistent asthma
Clinical manifastations
- short time symptoms not more
than once a week;
- short exacerbations (several hours
to several days);
- night symptoms 2 times a month
or less;
- absent of symptoms and normal
ventilatory function between
exacerbations;
- FEV>80%;
- daily variations of FEV< 20%
- symptoms 1 time a week or more
often but not every day;
- exacerbations destroy physical
activity and sleep;
- night symptoms 2 times a month
or more often;
- FEV>80%;
- daily variations of FEV< 20-30%
- everyday symptoms;
- exacerbations destroy physical;
activity and sleep;
- FEV>60-80%;
- daily variations of FEV>30%;
- constant symptoms;
- frequent exacerbations;
- physical activity is limited by
bronchial asthma;
- FEV>60%;
- daily variations of FEV>30%;
Clinical features
There are three periods in the development of bronchial asthma: presage, height
(asthmatic attack), and inverse.
Presage period – the onset of the disease can be several minutes, hours and even
days before asthmatic attack and develop the next symptoms: vasomotor reaction
of the nose mucosa ( plentiful watery secretion), sneezing, inching of eyes and
74
skin, attack of cough, difficulty of breathing, headache, fatigue, excessive diuresis,
changes of mood (displeasure, depression).
Height period ( asthmatic attack). Patients feel shortness of breath, suffocating,
expiratory dyspnea. Inhalation becomes short, exhalation is slow 2-4 time longer
than inspiration with laud, long, distant wheezes (prolonged wheezing expiration).
Patients must stand or sit up and give all their energy to breathing (forced positionorthopnea with fixed shoulder girdle), speech is almost impossible. Face of a
patient is pale with acrocyanosis, damp with perspiration. The chest assumes a
position of maximum inspiration, muscles of shoulder and body take part in
breathing. There are interspaces in breath. Cervical veins are swollen. Chough with
viscous sputum appears. After allocation of sputum respiration becomes easer. On
percussion resonance with tympanic shade are determined, lower borders come
down, diaphragmatic excursion is decreased. On auscultation decreasing vesicular
breath sounds and a lot of wheezes during respiration especially during expiration
are determined. Pulsus frequens et vacuus. Heart sounds are decreased. Asthmatic
attack can result in status asthmaticus which can result on coma or even in
patient’s death.
Inverse period .can be different in duration. Sometimes attack finishes quickly and
without any complications, but sometimes duration of this period can be some
hours and even days with difficult breathing and fatigue. Sometimes after the
attack patients are thirsty or hungry.
You should remember that rarely, “ dry cough may be the only evident
manifestation of asthma especially at night without typical asthmatic attack. For
diagnostics of such type of BA it is necessary to spend pick flow measurement
monitoring, taking into account positive effect of evening (prophylactic) using
bronchodilator drugs.
The cardinal symptom of asthma is generally thought to be wheezing. However, a
few asthmatics say that they never wheeze, and many describe other airways
symptoms such as cough with or without sputum production, chest tightness, or
simply shortness of breath.
Asthmatic wheezing is polyphonic; it is present on inspiration as well as
expiration, and is often not detectable at rest and therefore only heard on exercise
or forced expiration. It is produced by vibrations set up in small airways that are
almost closed off. Most asthmatics sense that it is coming from the lower
respiratory tract. Although there is plenty of noise to be heard with the stethoscope
over the central airways, this is a transmitted sound. Just as wheeze signifies
narrowing of the airways, so does the sensation of tightness. It is not a pain and so
should be distinguishable from angina pectoris and oesophageal spasm, both of
which may be described by patients as tightness. In asthma, the sensation partly
reflects the effort required to breathe and partly arises from the central airways,
with those deeper in the lungs being devoided of sensation. Asthmatics generally
find it more difficult to breathe in than out, although doctors usually assume that
the reverse is true.
75
Exertional shortness of breath for the asthmatic has both a variable component,
which tallies with the waxing and waning of their airways narrowing, and a
persistent more fixed component. Indeed, patients will sometimes comment: “It's
not my asthma: I'm just short of breath”.
Cough is insufficiently emphasized as a symptom of asthma. However, it is one of
the commonest symptoms of asthma in children and can be a lone symptom of the
condition in adults. Whilst asthmatic cough may be non-productive, it is frequently
accompanied by the expectoration of mucoid sputum. At times this may be quite
frothy and liquid, although more often it is sticky and difficult to expectorate. The
asthmatic's sputum may contain cylindrical or branched casts in the shape of the
small airways from where they are presumed to have originated.
Diagnosis
The main clinical syndrome of bronchial asthma is
Syndrome reversible disturbance of bronchial passability manifested by:
 sudden expiratory dyspnea
 wheezing respiration ( dry rales)
 “dry” cough
LABORATORY TESTS.
1. Hematocrit ( packed cell volume, PVC) increases.
2. Blood gas analysis -grave arterial hypoxemia (Pa O2 40-55mm), and highgrave hypercapnia Pa CO2- 80-90 mm)
3. Metabolic acidosis.
Skin test must be spent out for determination of extrinsic asthma and allergens. It
is typical eosinophilia for blood test and in sputum Sharko-Leiden’s crystals and
Kurshman’s spirals for extrinsic bronchial asthma. For instrinic there are
leucocytes in sputum. Decreasing suppressor T-lymphocyte activity and
increasing IgE amount at immunological tests.
Investigations
Lung function tests
Pick flow measurements
These tests are mandatory and determine the degree of functional disturbance. A
single set of tests, except complex, provides only a snapshot of a rapidly moving
target. Repeated tests are essential and therefore should be simple. Measurement
of PEF using a portable meter satisfies these aims. Qualitative evaluation of peak
flow charts provides almost all the information required. Quantitative evaluation
with respect to predicted values based on height, age, and sex is important. Care
needs to be taken in recording percentage change. In a patient with a predicted
PEF of 600min, a figure of 400min represents a value 33 per cent below that
predicted, whereas improving the same patient's peak flow from 400 to 600 min
using a bronchodilator is a 50 per cent change. A series of PEF values recorded
76
over a period of time may be analysed as an overall mean, mean values morning
and evening, or a 7-day running mean.
There is little need for more complex tests. Serial FEV1+or- FVC (functional vital
capacity) readings are possible with recently introduced miniaturized electronic
spirometers, but add little to the information given using the pick-flow
mwasurement.
Plethysmographic and flow volume loop measurements of airflow obstruction add
more sensitivity when lung function is only minimally disturbed, and lung volume
measurements add a dimension to understanding of the nature of the functional
disturbance. Breathing at high lung volumes is uncomfortable whatever the degree
of airflow obstruction. These types of assessment are only applicable to short-term
challenge or therapeutic trial situations.
Typical changes of PEF in patients with bronchial asthma:
 Increased PEF more than 15% after B-2 stimulator inhalation;
 Daily variations of PEF is 20% and more in a patient who takes
bronchodilators and 10% and more in a patient without bronchililator
therapy;
Daily variations= PEF min+ PEF max x100%
PEF middle
 Reduction PEF 15% and more after physical loading.
Spirography is graphical registration of lung volumes.
Typical spirgraphical sings of ventilatory destroys in patients with bronchial
asthma:
 Reduction of forced vita capacity (FVC) and Forced expiratory volume
for the first second (FEV1) – is the important sign
 Reduction of FEV1/VC (vital capacity) ratio ( Tiffno’s index), as a rule
it is less than 75%, there is a greater reduction in FEV1 Then VC, so the
 FEV/FVC ration is less than 80%.
Chest radiology
Chest radiology reveals nothing of asthmatic airways per se and is frequently
normal in asthma. Its use is confined to patients presenting diagnostic problems,
usually for the exclusion of other disorders. In an acute attack, beyond reflecting
the hyperinflation secondary to severe airflow obstruction, the plain radiograph
will pick up a pneumothorax and segmental or lobar collapse or consolidation.
Diagnostic creameries of bronchial asthma
Shortness of breath attack with difficult wheezing, distant expiration and wheezes
on auscultation.
 Equivalent of typical asthmatic attack: night with sleep destroy;
wheezing respiration again; difficulty of breathing; cough appearance at
77




night time and contact with allergens( animal, smoke) or after physical
loading.
Obstructive respiratory failure while spirography (reduction FEV1,
Tiffno’s index and PEF.
Daily variations of PEF is 20% and more in a patient who takes
bronchodilators and 10% and more in a patient without bronchililator
therapy.
Disappearance or meaningful relief and increasing PEF about 20% and
more after bronchodilators drugs.
Tresent biological marker of bronchial asthma – high level of nitric oxide
(NO) in expired air.
Differential diagnosis
The physical signs of asthma are those described for airways obstruction with
special features (described below) that reflect severity in the acute severe attack.
Objective confirmation of airways narrowing in asthma can be carried out using
any of the tests of airways function described. In practice, because of its simplicity
of use, portability, and reliability, the device generally used in clinical practice is a
peak expiratory flow rate meter. The test results reflect changing levels of airflow
obstruction with ease and accuracy, can be a more subtle indicator of change than
symptoms, and are nearly always more reliable than chest physical signs.
All the features described so far are commonplace in cardiorespiratory disease.
Therefore what aspects of them does asthma suggest? It is chiefly their variability,
pattern, and timing. First, there is a classic diurnal pattern with symptoms
awakening sufferers in the small hours of the morning (3-5 a.m.) or, if sleep is not
broken, being most obvious on awakening at the natural time. Improvement
follows later in the day, with late afternoon often being the most trouble-free time,
with possibly some hint of deterioration again late in the evening. This diurnal
pattern is disrupted by episodic attacks of asthma, initiated by triggers which are
described more fully below. Some will act transiently over minutes, others set up a
wheezy attack lasting for an hour or so, and yet others create a more prolonged
deterioration lasting for days on end. Conversely, asthmatic symptoms, both
diurnal and episodic, can be abolished with effective treatment.
This pattern of symptomatic variability is reflected in a parallel variability in serial
peak expiratory flow measurements. Thus diurnal variability gives a sawtooth
pattern over several days whereas a triggered attack produces either a short-lived
deterioration in function over minutes or hours, or a much more prolonged episode
if there is a severe attack .
An appropriate history backed up by characteristic serial lung function
measurements will enable asthma to be recognized in many, but not all,
individuals. For the diagnosis of asthma in these other cases and for a better
understanding of asthma as a whole, it is necessary to examine how the
78
mechanisms underlying the bronchial pathophysiology of asthma detailed in the
last chapter translate themselves into the clinical features of this disorder.
The main clinical symptom of BA is attack of shortness of breath which is a sign
of bronchoobstructive syndrome . More often BA must be differentiated with
chronic obstructive pulmonary disease (talbe 13).
Table 13. Differences of BA and COPD
Sings
Bronchial asthma
Chronic
obstructive
disease (bronchitis)
Age of patietns
Usually young
Elderly
Sudden onset
Often
Seldom
Smoking
Seldom
Very often ( almost
always)
Allergy
Often
Seldom
Dyspnea
Attack
Almost all the time
Cough
Paroxymal
(
during Permanent of different
attack)
intensity
Cough with sputum
Seldom
Always
PEF
All time about 10-15%
No
Reversibility of bronchial Increasing PEF about15% Partial or irreversible
obstruction
after in15-20 minutes
bronchodilarotors
Eosinophilia
Typical
Not typical
Bronchial hyperreactivity Typical
Not typical
Cor pulmonale
Appears late seldom
Appears early often
Progress of disease
Episodic
Permanently
Elevated white blood cell Not typical
Typical at exacerbation
count and ESR
X-ray
Pulmonary emphysema
Reticular pneumosclerosis
At auscultation
Whiizing
during A lot of wheezes and rales
asthmatic attack
Sputum
Viscous with eosinophils Mucosal- purulent
Skin tests
Positive
Negative
At trachibronchial dyskinesia because of bowing membranous wall tracheal
lumen are closed during inspiration and while coughing results of cough attack
and expiratory dyspnea. Physical loading, laugh, changed position can be the
reason of cough attack and following by passing out sometimes.
Compression of the trachea and the main bronchi by tumors, increased lymph
nodes, aortic aneurysm can be a reason of difficulty of breath especially during
expiration. At theses disorders wheezing expiration is determined only on the
affected side but at BA wheezing expiration is determined above all the chest.
79
Moreover in the case of mediastinum tumor is a typical syndrome of v.cava
superior ( cyanosis, edema of a face and a neck swelling of the cervical veins).
To be precise X-ray of the chest is done as well as, bronchoscopy, and
tomography.
Cardiac asthma is the manifestation of the left atrium failure and is accompanied
by inspiratory dyspnea. There is heart disease in past history; often patients are
elderly, on auscultation fine rales are marked, sputum is foamy with blood,
dysrhythmia, high BP are present.
Inpulmonary thrombosis a patient has sudden, severe chest pain, inspiratory or
mixed dyspnea. Vesicular breath sounds are decreased.
Complication
Status asthmaticus
Status asthmaticus is severe asthma which has persisted for at least 24 hours
and is not substantially benefited by optimal doses of bronchodilator drugs.
I stage ( stage of relative compensation).
Basic clinical symptoms
1. Frequent prolonged not spot asthmatic attacks in interictal time
bronchospasm is present.
2. Painful, dry cough attack.
3. Forced position, tachypnea till 40 per minute, subsidiary muscles take
part in respiration.
4. Distant wheezing
5. Skin is pale, cyanosis.
6. On percussion – tympanic, on auscultation mosaic respiration – no
reparation in lower part of the lungs; in the upper part – course
respiration with wheezes.
7. Tachycardia till 120 beats per minute, BP is normal or slightly increases;
cervical veins swelling.
1. II stage ( stage of decompensation “silent lung”, progressive ventilatory
disorder).
Basic clinical symptoms
1. Very grave condition of patients.
2. Severe dyspnea, superficial respiration.
3. Forced position – orthopnea.
4. Cervical veins swelling.
5. Skin is pale- gray, damp with perspiration.
6. Excitation is changed by indifference ( apathy)
7. On auscultation silence about most part of the both lungs is determined
(“silent lung” due to bronchi and bronchial obstruction).
8. Pulse till140 beats per minute, dysrhythmia, arterial hypotension,
“gallop” rhythm
80
III stage ( hypercapnia coma)
Basic clinical symptoms
1. Patient is out, before passing out can be cramps
2. Diffuse ‘red” cyanosis, cold perspiration.
3. Superficial respiration ( Cheyne- Stokes respiration is possible)/
4. On auscultation respiration is severe decreased or absent.
5. Thready pulse, BP distinctly decreased or is not determined- collapse,
heart sounds are decreased, “ gallop” rhythm.
Management
Main goals of treatment
 Control determination and maintenance under bronchial
manifestations;
 Prevention of exacerbations;
 Maintenance of normal or close to normal ventilatory function;
 Prevention side effects of drugs;
 Prevention irreversible bronchial obsrution;
 Death prevention.
asthma
Control criterions of bronchial asthma:
 Minimal symptoms of their absence including night asthma;
 Seldom exacerbations;
 Absent urgent summons of physician;
 Minimal need of B-2 antagonist ( bronchodilator drugs);
 No activity limitation , including physical activity;
 Daily variations of PEF ( forced expiratory volume)< 20%;
 Minimal or no side effect of drugs;
 Normal or close to normal PEF.
Long-term ( graduated) treatment
Although asthma can, and often does, remit spontaneously in individuals, there is
no known way of enhancing or encouraging this process, except, when a
recognized allergen entirely responsible for asthma can be eliminated from the
environment. Even so, allergen avoidance must remain a primary principle in
management strategies for asthma. Control of the condition by effective
prophylactic medication follows next, and relief of symptoms is required when
other measures have failed.
Allergen avoidance
The best examples are from occupational asthma where adaptation of the
environment to contain or eliminate the allergen is often possible; of failing - the
affected individual can be removed to a safer environment. An essentially
occupational phenomenon sometimes has secondary effects on the population at
81
large. A fascinating and still unfolding story relates to epidemics of acute asthma
encountered in the Spanish city of Barcelona in recent years. Careful
epidemiological research revealed that high admission rates for acute asthma
coincided with days on which soya bean was being unloaded at the port into one
particular silo and when the wind was blowing towards the city. IgE antibodies to
soya bean were detected in the blood of affected individuals, making this seem
like a typical atopic asthma. The age distribution suggested the possibility of an
interaction with cigarette smoking.
Domestic pets should be banished if possible, but, failing that, weekly washing
combined with antidust measures will help the sufferer but perhaps is not
appreciated by the animal! Items of food that give obviously violent allergic
reactions are easy enough to avoid, but elaborate diets which aim to eliminate
common foodstuffs such as milk, eggs, wheat, etc. should be avoided unless
rigorous double-blind elimination trials have proved positive. No asthmatic should
take a b- blocker by any route (including eye drops). Aspirin and NSAIDs should
be treated with caution, but many asthmatics are unaffected by these drugs. Safe
drugs for simple analgesia in asthmatics are paracetamol and usually trilisate.
Asthmatics should not smoke tobacco actively or passively and have the right of a
smoke-free environment at work. Asthma is twice as common in the children of
smoking parents as it is in those from non-smoking households, and smoking
aggravates the harmful effects of many occupational causes of asthma.
Prophylaxis
The foundation of present-day treatment of asthma is prophylactic regular therapy
to control symptoms. A scheme is outlined. Treatment is begun simply and built up
until satisfactory control is achieved. Control means freedom from symptoms,
particularly nocturnal awakening, lung function within the normal range and
varying by less than 20 per cent within 24h, and normal quality of life. The
attainment of these aims is limited by treatment side-effects and patient
compliance. Maintenance oral corticosteroids give well-recognized side-effects,
but even aerosol corticosteroids are not free from toxicity. With doses of inhaled
beclomethasone or budesonide of 1000mg or more daily, skin bruising is common,
bone density may be reduced and hypothalamus-pituitary-adrenal axis function can
be impaired. Taking regular treatment is demanding and can appear unrewarding
when it gives no immediate benefit. Patients recent relying on medication, and may
have real or imagined fears about it or culturally determined resistance to taking
inhaled drugs. All these concerns must be met if prophylactic therapy is to achieve
clinically all it promises pharmacologically, and at the end the level of treatment
accepted will be a mutually agreed between benefit, side-effects and acceptability.
82
Alternative prophylactics
The choice of inhaled prophylactics is not wide and can essentially be divided into
steroids and non-steroids. In children, in young atopic adults, in those with mild
disease, and in those with an aversion to steroids, disodium cromoglycate (Intal) or
nedocromil (Tilade) should be tried first. Disodium cromoglycate needs to be
given four times a day, at least initially, which is an impediment to compliance,
and at full dose (20 mg on each occasion). This is best achieved with the Spincaps:
the metered dose inhaler contains only 5 mg per puff. Nedocromil is recommended
for twice daily dosage, but needs to be at a quantity of 8mg each time.
If, after a 2 to 3 month trial, response is inadequate, a change should be made to a
steroid inhaler. The current standard beclomethasone and budesonide are being
challenged by the new generation of inhaled steroids which are absorbed even less
and rapidly metabolized. Fluticasone is the first on the market. All steroid aerosols
can be given in a patient-friendly twice daily regimen.
Devices for inhaled therapy
One central feature of asthma treatment is route and method of delivery. The
inhaled route is preferred whenever possible. The device chosen should be that
which the individual can use most effectively illustrates the types of device
available. It will remain usual to try the metered dose inhaler first (at least until it
becomes unacceptable to use chlorofluorocarbons (CFCs) even in medication). The
technique needs to be taught carefully and checked regularly, and an alternative
device prescribed if use of the metered dose inhaler cannot be mastered. Large
spacer devices reduce local side-effects in the mouth because the aerosol is no
longer forced into the back of the throat, reduce systemic side-effects because less
drug is deposited on the buccal mucosa, allow the propellant to evaporate in the
spacer, and overall deliver a greater percentage dose to the lungs. Dry powder
devices are generally more expensive, more complex to use, and still suffer from
problems of deposition in the oropharynx, but do not use CFC propellants.
Nebulizers should be reserved for patients who requires larger doses, cannot use
any other device, or are likely to need unexpected emergency treatment for an
acute attack. Because delivery from a nebulizer is very wasteful and much solution
is left in the chamber, side-effects dose for dose are significantly less than those
with the metered dose inhaler.
Oral bronchodilators
Inhaled b2- agonists are so effective that there should be minimal need to use the
larger doses required for the oral route with their attendant systemic side-effects.
Methylxanthine bronchodilators, such as theophylline and aminophylline, cannot
be given by inhalation, but have a time-honoured place in asthma therapy. Their
mechanism of action is complex, probably involving adenosine pathways as well
83
as phosphodiesterase inhibition. Taken long term they may have additional
advantageous of immune-modulating activity. Slow-release preparations allow
these drugs to be administered twice daily. They are widely favoured in North
America but are less popular in the United Kingdom, where British stomachs seem
unduly prone to the gastrointestinal disturbance (nausea, dyspepsia, and even
vomiting) which is their chief use-limiting side-effect. They also relax the lower
oesophageal sphincter, and so they should not be used when reflux is thought to be
present, and they cause cerebral stimulation and wakefulness in some individuals.
Oral corticosteroids
Short courses of oral corticosteroids are indicated in asthma as a diagnostic test, to
gain good control when initiating treatment in more severe cases, when inhaled
treatment proves unsatisfactory, and when intercurrent infection or allergen
exposure produces a sharp decline in function. Prednisolone is the standard steroid
usually prescribed. The daily dose required varies from 20mg/day in a child or
small female to 40 mg/day in a heavy muscular male. Larger doses are not
infrequently used and become more necessary as the disease becomes more
chronic due to fixed inflammatory airways narrowing. The duration of the course
depends on clinical and functional indices of recovery. The once favourite regimen
of 30mg on the first day, followed by 5 mg less on each of five subsequent days,
had no good trials to support its use. A simple recommendation suitable for many
cases is to maintain the starting dose until previous or best function is restored, and
then to give a half of that dose for an equal number of days. Individuals will differ
in their responses, however, and side-effects may prevent a predetermined plan
from being carried through. Aerosol steroids should not be stopped during a course
of prednisolone, and should be kept at a higher dose than before the oral drug was
used until continued good control signifies that it can be reduced.
Maintenance of oral corticosteroid therapy should be avoided whenever possible.
Long-acting inhaled bronchodilators (theb2-agonist salmeterol and the
anticholinergic oxitropium), slow-release methylxanthines (theophylline and
aminophylline SR), and antihistamines (including the more broadly antiallergic
agent ketotifen) should all undergo a trial before taking this step, despite
considerations discussed below about the possible dangers of regular
bronchodilator therapy. If maintenance steroid therapy is started, every effort
should be made to keep the dose below 10 mg of prednisolone a day and to use an
alternate day regimen if this proves clinically satisfactory. Patients should be
monitored for long-term side-effects, particularly remembering diabetes and
osteoporosis. In postmenopausal women on maintenant oral corticosteroids,
cyclical diphosphonates (e.g. etidronate 200mg daily for 2 weeks in 13) and
calcium supplements (for the remaining 11 weeks of the 13) may halt the progress
towards osteoporosis, but it is not known whether this treatment is equal to or
could be supplemented with oestrogen hormone replacement therapy.
84
In those instances where prednisolone is required in a dose of more than 10&mg,
daily consideration should be given to trials of other immunosuppressive agents.
Those under study at present include methotrexate 10mg weekly and cyclosporin;
other cytotoxic immunosuppressives such as cyclophosphamide and azathioprine
have also been tried, as have intramuscular gold. All these agents carry their own
side-effects which must be balanced against those of the corticosteroid; most give a
degree of steroid sparing, but rarely allow prednisolone to be withdrawn
altogether.Graduated therapy of BA approach to severe asthma is in table 14.
Table 14. Graduated therapy of BA( approach to severe asthma)
Grade
Slight episodic current
Slight persistent asthma
Middle persistent asthma
Grave persistent asthma
Treatment
- short term bronchodilators (aerosol) if
necessary, but not more than once a
week
-Everyday
administration
for
prophylactics;
- inhaled corticosteroids 200-500 mcg or
cromoly sodium and nedocro;mil or
theophylline;
- during asthmatic attack- bete2 –
adrenergic not more than 3-4 times per
day;
- it is possible antichlinergic drug using
- everyday preventive using antiinflammatory drugs for asthma
control; inhaled corticosteroids
800-2000mcg;
- prolonged
bronchodilators,
especially for night ( beta2 adrenergic like tablets, inhalation
or theophilline);
- for rapid relief of symptoms short
term beta2 –adrenergic not more
that 3-4 per day, it is possible
antichlinergic drug using
Every day using:
- - inhaled corticosteroids 8002000mcg;
- prolonged
bronchodilators,
especially for night ( beta2 adrenergic like tablets, inhalation
or theophilline);
- glucocorticoids per os;
85
for rapid relief of symptoms short term
beta2 –adrenergic not more that 3-4 per
day, it is possible inhaled antichlinergic
drug using
Relief of symptoms
Even with the best control, asthmatic symptoms occur spontaneously or in
response to challenge. Inhaled b2;-agonist bronchodilators give the most
immediate relief (detectable improvement in airways calibre within a minute). The
more selective b2;-agonists (e.g. salbutamol and terbutaline) should be used from a
metered dose inhaler or dry powder device. The dose can be repeated within 10min
if required or it can be increased. High doses can be achieved either by using
multiple actuations (10-12) in a large spacer or with prepacked nebulizer solutions.
Both devices minimize side-effects. Failure at this point means that therapy for an
acute attack should be instituted.
Status asthmaticus treatment
Corticosteroids therapy is necessary if there is threat to patient’s life.
The approach to the acute attack is therapeutically simple but managerially
complex to manage. In essence therapy consists of adequate doses of b2--agonist
bronchodilators, systemic steroids, and oxygen. Only a few attacks will fail to
respond to this scheme. For those, additional tactics include additional
bronchodilators and ventilatory support.
Some attacks are dramatically sudden in onset and seem to include an element of
anaphylaxis with laryngeal as well as bronchial narrowing so that a rapidly acting
non-selective b2 -agonist is indicated. Subcutaneous adrenaline (0.5-1.0 ml of
1:1000 solution) is advised. It is available in a prepacked syringe as Mini Jet
adrenaline, and in this form can be used directly by patients or carers. Nebulized
anticholinergics (250-500 mg ipratropium) can quick recovery in the first 24h if
given (up to 4 hourly) with b2-agonists. The position of the methylxanthines is
insecure. Once a mainstay of treatment (it was commonplace to give an
intravenous bolus of 250mg of aminophylline), they fell out of favour because of
reported acute cardiovascular toxicity, even deaths, with the effect being enhanced
in those already taking slow-release form oral methylxanthines. On the difficult
attack or in the rare patients sensitive to b2-agonists, they can be given effectively
as a slow intravenous infusion (0.5 mg aminophylline/kg body weight/hour).
Gastrointestinal upset, as well as tachycardia and dysrhythmias, limit the use of
higher doses. An intravenous infusion for fluid replacement (caused by
hyperventilation and being too breathless to drink) is important in severe attacks,
to which potassium should be added to counteract the metabolic effects of high
dose of b2-agonist therapy.
86
Prognosis
A combination of increased awareness enabling the early recognition of the
disorder, sensible application of excellent prophylactic therapies, and education to
ensure that management has succeeded in reducing much the terror to the condition
and has made it controllable in most sufferers. However, it cannot be cured.
Although remissions occur, relapse is also frequent and continuous treatment over
many years as a sentence for many unfortunately. The genetic approach offers a
hope for new forms of treatment, but success is in some way over the horizon and
at present can only be envisaged for atopic asthmatics. There are so many potential
mediators of asthmatic inflammation that it seems to bea forlorn hope to find a
mediator blocker that will prove therapeutically successful alone. However,
research of inflammatory and other mechanisms, must remain an essential
ingredient of future endeavour. Clinicians are in the firm belief onto the security
with the successes of current therapy, and this has stifled any interest to dissecting
different forms of asthma and hence tailor-made types of treatment. The
epidemiological approach is ideally placed to solve outbreaks traced to industrial
processes or specific pollutants, but if it reveals rising prevalence to be related to
living conditions and/or more general pollution, such as that due to car exhaust, it
will require great personal and political resolve to do the tide turn.
1.
2.
3.
4.
5.
6.
7.
8.
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Sensitivity to heat and water loss at rest and during exercise in asthmatic
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E., and Kendall M et. at. // European Journal of Respiratory Disease. – 1982.
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Anonymous Guidelines on the management of asthma. //Thorax. – 1993. –
Vol. 48, №2. – Suppl. – Р. – 125-138
Community outbreaks of asthma associated with inhalation of soya bean
dust. // Anto J., Sunyer J., Rodriguez-Roison, R., Suarez-Cervera, M., and
Vazquez, L. et. at. New England Journal of Medicine. – 1989. - V ol. 320. –
Р.1097-1101.
Asthma in the elderly: an epidemiological survey. / Burr, M. L., Charles, T.
J., Roy, K., and Seaton, A. //British Medical Journal. – 1979. – Р.1041-1044.
Changes in asthma prevalence: two surveys 15 years apart. / Burr, M.L.,
Butland, B.K., King, S., and Vaughan-Williams, E. // Archives of Disease in
Childhood. – 1989. - № 64. – Р.1452-1456.
Terminology, definitions and classification of chronic pulmonary
emphysema and related conditions. / CIBA Foundation Guest Symposium
//Thorax. – 1959. - № 14. – Р.286-299.
Clark, T.J.H. and Hetzel, M.R. Diurnal variation of asthma. //British Journal
of Diseases of the Chest. – 1977. - Vol. 71. – Р.87-92.
Falls in peripheral eosinophil counts parallel the late asthmatic reaction. /
Cookson, W.O.C.M., Craddock, C.E., Benson, M.K., and Durham S.R.
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//American Review of Respiratory Diseases. – 1989. - Vol. 139. – Р.458462.
9. Bronchoconstrictor effects of a deep inspiration in patients with asthma. /
Gaynard, P., Orehek, J., Grimaud, C., and Charpin C. //American Review of
Respiratory Diseases. – 1975. - Vol. 111. – Р.433-439.
10. Goldman, J. Muers, M. Vocal cord dysfunction and wheezing. // Thorax. –
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11.Prescribed fenoterol and death from asthma in New Zealand 1981-7: a
further case-control study. / Grainger, J., Woodman, K., Pearce, N., Crane,
J., Burgess, C., Keane, A., Beasley, R. et. at. // Thorax. – 1991. - № 46. –
Р.105-111.
12.Asthma, wheezing and school absence in primary schools. // Hill, R.A.,
Standen, P.J., Tattersfield, A.E. Archives of Diseases of Children. – 1989. № 64. – Р.246-251.
13. Keeley, D.J., Neill, P., Gallivan, S. Comparison of the prevalence of
reversible airways obstruction in rural and urban Zimbabwean children.
//Thorax. – 1991. - № 46. – Р.549-553.
14.Effect of low concentrations of ozone and inhaled allergen responses in
asthmatic subjects. // Molfino, N.A., Wright, S.C., Katz, I., Tarlo, S.,
Silverman, F., McClean, P.A., et al. // Lancet. – 1991. - № 338. – Р.199-203.
15.Page, C.P. One explanation of the asthma paradox: inhibition of natural antiinflammatory mechanism by beta-agonists. // Lancet. – 1991. - № 337. –
Р.717-720.
16.Reduction of bronchial hyperreactivity during prolonged allergen avoidance.
/ Platts-Mills, T.A.E., Tovey, U.R., Mitchell E.B., et al. Lancet. – 1982. Р.675-678.
17.Rackemann F.M. A clinical classification of asthma. //American Journal of
Medical Science. – 1921. - Vol. 162. – Р. 802.
18.Regular inhaled beta-agonist treatment in bronchial asthma. / Sears, M.R.,
Taylor, D.R., Print, C.G., Lake, D.C., Li, Q., Flannery, E.M., et al. Lancet.
– 1990. - № 336. – Р.1391-1396.
19.Most asthmatics have gastro-oesophageal reflux with or without
bronchodilator therapy. / Sontag, S.J., O'Connell, S., Khandelwal, S., Miller,
T., Nemchausky, B., Schnell, T.G., and Serlovsky, R. // Gastroenterology. –
1990. - Vol. 99. – Р.613-620.
20.The use of beta-agonists and the risk of death and near death from asthma. /
Spitzer, W.O., Suissa, S., Ernst, P., Horwitz, R.I., Habbick, B., Cockcroft,
D., et al. //New England Journal of Medicine. – 1992. - Vol. 326. – Р.501506.
21.Sterk, P.J. Virus-induced airway hyperresponsiveness in man. //European
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Bennett, J.E., Vogel, C.L. et al. // Medicine. 1970. - № 49. – Р.147-173.
88
23.Bronchodilator treatment in moderate asthma or chronic bronchitis:
continuous or on demand? A randomised controlled study. / van Schayck,
C.P., Dompeling, E., van Herwaarden, C.L.A., Folgering, H., Verbeek,
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Journal. – 1991. - Vol. 303. – Р.1426-1431.
24.Predictive value of respiratory syncytial virus-specific IgE response for
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Р.776-780.
Test control
1. The most frequent reason of acute pneumonia is :
A). pneumococcus
B). klebsuella
C). staphylococcus
D). virus
E). legionella
2. Select primary pneumonia
A). aspirative
B). pancancerative
C). hypostatic
D). croupous
E). infarct-pneumonia
3. Select what is not sign of croupous pneumonia
A). chest pain
B). physical data about lobar affection
C). acute manifestation
D). mosaic percussion sounds
E). “rusty sputum”
4. Treatment of choice for pneumococcus pneumonia is:
A). gentamicin
B). penicicllin
C). tetracycline
D). kefzol
E). erythromycin
5. What are not complications of pneumonia:
A). toxic shock
89
B). pulmonary edema
C). pulmonary bleeding
D). long current
E). acute respiratory failure
6. What is not sign of pulmonary consolidation syndrome:
A). resonance sound of percussion
B). bronchial breath sounds
C). local increasing vocal fremitus
D). discontinuous sounds
E). local increasing bronchophony
7. What is not sign of toxic shock:
A). BP fall
B). oligouria
C). change level of consciousness
D). respiratory distress syndrome
E). hypertension
8. After operation the patient has high temperature, cough with mucouspurulent sputum, local fine moist rales at auscultation. Your dianosis?
A). acute bronchitis
B). acute primary pneumonia
C). acute secondary focal pneumonia
D). pulmonary abscess
E). pulmonary edema
9. Select change of laboratory tests what is not typical for croupous
pneumonia:
A). neutrophill displacement
B). increasing ESR
C). proteinuria
D). neutropenia
E). limphocytosis
10.After overcooling the patient has suddenly high temperature till 39 degrees,
chest pain at the right side, dyspnea at rest, rusty sputum. Your prior
diagnosis?
A). bronchopneumonia
B). croupous pneumonia
C). pulmonary tubeculosis
D). lung cancer
E). infarct-pneumonia
90
11.The main criterion of bronchial asthma diagnosis is :
A). chest radiograph changes
B). bronchoscopy
C). spirography
D). attacks of dyspnea
E). allergy in history
12.What of biological active substance does not result to bronchospasm:
A). acetylcholine
B). serotonin
C). bradicinin
D). histamine
E). adrenalin
13.What is a clinical symptom typical for attack of shortness of breath at
bronchial asthma:
A). difficulty of inspiration and expiration
B). inspiratory dyspnea
C). expiratory dyspnea
D). cough with foamy sputum
E). chest pain
14.Appearance of area of silent lung speaks about :
A). asthmatic attack
B). I- degree of status asthmaticus
C). II- degree of status asthmaticus
D). III- degree of status asthmaticus
E). cardiac asthma
15.For treatment of BA is not used:
A) adrenomimetic (ephedrine)
B) cholinolitic (solutan)
C) beta- blockage ( anaprylin)
D) metylxanitin (euphyllin)
E) corticosteroid (prednisone}
16.For verification of BA all methods are informative except :
A). allergic history
B). skin test
C). provocative test
D). pick flow measurement
E). sowing sputum
91
17.For treatment of status asthmaticus is not used:
A). sympathmymitic
B). corticosteriod
C). oxygen inhalation
D). heparin
E). artificial pulmonary ventilation
18.It is not symptom of attack of BA:
A). dull sound on percussion
B). increasing percussion sounds
C). dry rales ( wheezes)
D). respiratory failure
E). forced position
19.Intal is used at:
A). status asthmaticus
B). preventive measures of extrinsic(allergic) asthma
C). asthmatic attack
D). cardiac asthma
E). chronic bronchitis
20.What is not typical for BA in X-ray examination:
A). increasing transparency of the lungs
B). increasing pulmonary picture
C). widening interspaces
D). infiltration of pulmonary tissue
E). increasing right border of the heart
21. Infectious pleurisy may complicated all disease, except:
A). acute pneumonia
B). pulmonary tuberculosis
C). chronic bronchitis
D). pulmonary abscess
E). suppurative bronchiectasis
22. Non – infectious pleurisy may be observed at all diseases, except:
A). ovary cancer
B). systemic lupus erythematosus, rheumatic fever
C). pulmonary infarction
D). ulcerative disease
E). rheumatoid arthritis
23. The main syndrome of dry pleurisy is:
A). chest pain
92
B). dull sound above affective area
C). fatigue
D). fever
E). cough
24. For pain syndrome of dry pleurisy is not typical:
A). inspirative pain
B). expirative pain
C). pain durig cough
D). pain relief at bending to healthy side
E). more often location is in inferior- lateral
25. For exudative pleurisy is not typical:
A). forsed position of patient
B). dyspnea
C). cyanosis, jugular venous distention
D). intercostals retraction of affected side
E). lag of affected side
26.For exudative pleurisy in X-ray is not typical:
A). intensive homogeneous dark patch
B). oblique stroke of upper border
C). mediastinum is displaced away from the side of the effusion
D). mediastinum is displaced to the side of the effusion
E). smoothed of the diaphragm
27. For exudates is not typical:
A). turbid, yellow color
B). at standing fibrin like flakes
C). protein concentration > 30g/l
D). neutrophilic leukocytes
E). Rivalt’s test is negative
28. What does not has value in pathogenesis of exudative pleurisy:
A). increase of pleural capillary permeability
B). decrease of oncotic pressure in the pleural cavity
C). increase of oncotic pressure in the pleural cavity
D). Impaired lymphatic drainage.
E). An imbalance between the hydrostatic and oncotic forces as defined in
Starling's low
29. What is not typical for dry pleurisy and not typical for intercostal neuralgia:
A). pain increase in inspiration and cough
B). at bending of body to non affected side.
93
C). at bending of body to affected side.
D). pleural friction rub
E). intoxication
30. What is not typical for syndrome of liquid in the plural cavity:
A). dull sound above effusion
B). the upper border go up from the spine
C). mediastinum is displaced away from the side of the effusion
D). mediastinum is displaced to the side of the effusion
E). significant decreasing of vesicular breath sounds above the affected area
Answer standards
1-A; 2-D; 3-D; 4-B; 5-C; 6-A; 7-D; 8-C; 9-C; 10-B; 11-C; 12- E; 13-C; 14-C;
15-C; 16-D; 17-D; 18-A; 19-B; 20-D; 21-C; 22-D; 23-A; 24-D; 25-D; 26-D;
27-E; 28—B; 29-B; 30-D.
94
о
Contents
1. Introduction
2. List of abbreviation
3. Chronic bronchitis
3.1. Definition.
3.2. Etiology
3.3. Classification
3.4. Clinical picture
3.5. Investigations
3.6. Differential diagnosis
4. Chronic obstructive bronchitis
4.1.Definition
4.2. Epidemiology
4.3. Etiology
4.4. Pathogenesis
4.5. Clinical picture
4.6. Examination
4.7. Investigation
4.8. Diagnostic criteria
4.9. Management
4.10. Reference
5. Pneumonia
5.1. Introduction
5.2. Definition
5.3. Etiology
5.4. Pathogenesis
5.5. Classification
5.6. Community-acquired pneumonia
5.6.1 Clinical feature
5.6.2. Investigations
5.7. Nosocomial pneumonia
5.8. Aspiration and anaerobic pneumonia
5.9. Diagnosis
5.10. Diagnostic criteria’s
5.11. Criteria’s of severe pneumonia
5.11. Complications of pneumonia
5.12. Management of pneumonias
5.12.1. Introductions for hospital admission
5.12.2. Antibiotics
5.13. Prognosis
5.14. Prevention of pneumonia
5.15. References
3
4
5
5
5
6
7
8
8
8
8
9
9
9
10
11
11
14
14
18
19
19
20
21
23
24
25
26
27
31
31
32
33
35
36
39
40
40
46
46
48
95
6. Pleurisy
6.1. Introduction
6.1. Epidemiology
6.2. Definition
6.3. Pleural fluid formation
6.4. Classification
6.5. Clinical features
6.6. Diagnosis
6.7. Differential diagnosis
6.8. Investigations
6.9. Examination of pleural fluid
6.10. Management
6.11. References
7. Bronchial asthma
7.1. Definition
7.2. Epidemiology
7.3. Etiology
7.4. Pathogenesis
7.5. Physiology of asthma
7.6. Classification
7.7. Clinical features
7.8. Diagnosis
7.9. Investigations
7.10. Differential diagnosis
7.11. Complications
7.12. Management
7.13. References
8. Test control
9. Answer standards
10. Contents
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Отпечатано в типографии КГМА.
г. Караганда,
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ул. Гоголя 40
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