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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._ 2 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 3 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 4 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. 5 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. 6 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 7 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 8 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 9 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. 10 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 11 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 12 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. 13 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 14 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 15 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 30 000 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. 61 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 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. REFERENCES Sensitivity to heat and water loss at rest and during exercise in asthmatic patients. / Anderson, S.D., Schoeffel, R.E., Follet, R., Perry, C.P., Daviskas, E., and Kendall M et. at. // European Journal of Respiratory Disease. – 1982. - № 63. – Р.459-471. 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. 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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. – 1961. - № 46. – Р.401-404. 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. 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A randomised controlled study. / van Schayck, C.P., Dompeling, E., van Herwaarden, C.L.A., Folgering, H., Verbeek, A.L.M., van der Horgen, H.J.M., and van Weel, C. et al. //British Medical Journal. – 1991. - Vol. 303. – Р.1426-1431. 24.Predictive value of respiratory syncytial virus-specific IgE response for recurrent wheezing following bronchiolitis. / Welliver, R.C., Sun, M., Rinaldo, D., and Ogra, P.L. // Journal of Paediatrics. 1986. - Vol. 109. – 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 96 50 51 51 51 52 52 53 54 54 55 56 60 62 64 64 65 69 72 74 75 76 77 78 78 80 81 88 90 95 96 Отпечатано в типографии КГМА. г. Караганда, 97 ул. Гоголя 40 98