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COPD
Dr. Tanvir us Salam, FCCP
Associate Professor of Medicine
Post Graduate Medical Institute/LGH Lahore
Chronic Obstructive Pulmonary Diseases
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Asthma
Chronic Bronchitis
Emphysema
Bronchiectasis
Cystic fibrosis
Definition
• Asthma
– Chronic inflammatory disorder of the airways
– Airway obstruction
– Recurrent and reversible
• Atopy
– Production of abnormal amounts of IgE antibodies
in response to contact with aeroallergens
• Airway Hyperresponsiveness
– This is an abnormality of the airways that allows
them to narrow too easily and too much
COPD
• Chronic Bronchitis is defined by the presence
of a productive cough for more than three
months' duration in two successive years
• Emphysema is a pathological definition, with
enlargement of air spaces and destruction of
lung parenchyma, loss of lung elasticity distal
to terminal airways
Asthma
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Chronic inflammatory disease of airway
Most common chronic disease of childhood
5-10% of population are affected
More common in developed countries
2:1 male/female ratio in childhood
Is asthma increasing?
Causing restricted activity and hospitalization
Death rate on the rise
COPD
• 14 million people in the united states have COPD
• 14 percent of white male smokers, as compared with
approximately 3 percent of white male nonsmokers
• COPD is now the sixth leading cause of death and it
is the only common cause of death that is increasing
in incidence
• The world health organization predicts that by 2020
COPD will rise from its current ranking as the 12th
most prevalent disease worldwide to the 5th and from
the 6th most common cause of death to the 3rd
Relationship of Wheeze, Asthma,
AHR
Atopy
wheeze
Current
asthma
AHR
RV-Induced Airway Inflammation
Plasma
leakage
Inflammatory
cell recruitment
and activation
Mucus
hypersecretion
Virus-infected
epithelium
Airway
Hyperresponsiveness
Neural activation
Types
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Persistent asthma
Obstructed asthma
Episodic asthma
Asthma in remission
Potential asthma
Trivial wheeze
Extrinsic/Atopic asthma
Occupational asthma
Intrinsic asthma
Risk Factors
• Inducers
– Allergens
– House dust mites
– Respiratory infections
– Passive smoking
– Genetics
• Trigger
– Allergens
– Exercise
– Infections
– Air pollution
– Weather
– Smells and irritants
– Emotional factors
– Food
Causes of Asthma Exacerbations
Pathological Features
• Macroscopic features
– Over inflated lungs
– Wide spread plugging of the airways with thick
secretions
– Normal lung parenchyma
Pathologic Features
• Microscopic features
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Infiltration of epithelium with inflammatory cells
Shedding of the epithelium
Thickened basement membrane
Increased cells in lamina propria
Smooth muscle and mucous glands are
hypertrophied
Cellular Mechanisms Involved in
Airway Inflammation
ANTIGEN
IgE
Mast cell
B cell
Bronchospasm
Macrophage
T cell
Eosinophil
Neutrophils
Macrophage
INFLAMATION
Pathophysiology
• Reduction in airway diameter
– Contraction of smooth muscles
– Vascular congestion and edema of bronchial walls
– Tenacious secretions
• Increased airway resistance
– Decreased forced expiratory volumes
• Hyperinflation
• Mismatched V/P
Molecular Genetics in COPD
• In patients with (alpha)1-antitrypsin deficiency
– Early emphysema develops that is exacerbated by
smoking, indicating a clear genetic predisposition
to COPD
– However, less than 1 percent of patients with
COPD have (alpha)1-antitrypsin deficiency
Molecular Genetics in COPD
• A polymorphic variant of microsomal epoxide
hydrolase, an enzyme involved in the
metabolism of epoxides that may be
generated in tobacco smoke, has been
associated with a quintupling of the risk of
COPD.
Risk Factors
• In industrialized countries, cigarette smoking
accounts for most cases of COPD
• In developing countries other environmental
pollutants, such as particulates associated
with cooking in confined spaces, are
important causes
• Air pollution (particularly with sulfur dioxide
and particulates), exposure to certain
occupational chemicals (such as cadmium),
and passive smoking may all be risk factors
Inflammation
• Now apparent that there is a chronic
inflammatory process in COPD
– But it differs markedly from that seen in asthma,
with different inflammatory cells, mediators,
inflammatory effects, and responses to treatment
– In contrast to the situation with asthma, eosinophils
are not prominent except during exacerbations or
in patients with concomitant asthma
– Most inflammation in COPD occurs in the
peripheral airways (bronchioles) and lung
parenchyma.
– The bronchioles are obstructed by fibrosis and
infiltration with macrophages and T lymphocytes.
– Destruction of lung parenchyma and an increased
number of macrophages and T lymphocytes, which
are predominantly CD8+ (cytotoxic) T cells.
Acute Exacerbations
• It is now evident that many exacerbations in COPD,
as in asthma, are due to upper respiratory tract viral
infections (such as rhinovirus infection) and to
environmental factors, such as air pollution and
temperature.
• There is an increase in neutrophils and in the
concentrations of interleukin-6 and interleukin-8 in
sputum during an exacerbation, and patients who
have frequent exacerbations have higher levels of
interleukin-6, even when COPD is stable.
Acute Exacerbations
• Bronchial biopsies show no increase in
sputum eosinophils during exacerbations in
patients with severe COPD.
• An increase in markers of oxidative stress
and exhaled nitric oxide, presumably
reflecting increased airway inflammation, is
observed during exacerbations.
Medical History in Asthma
• Development of disease
– Age of onset and
diagnosis
– History of early life injury
– Progress of disease
– Present management
– Co-morbid condition
• Family history
– History of asthma, allergy,
sinusitis, rhinitis, or nasal
polyps in close relatives
• Social history
– Characteristics of home
– Smoking
– School characteristics
– Work place
– Level of education
Medical History in COPD
Aggravating factors
Aggravating factors
• All smokers!
• Viral respiratory
infection
• Environmental
allergens, indoor and
out door
• Exercise
• Occupational chemicals
• Irritants
• Emotional expressions
• Drugs
• Food, food additives and
preservatives
• Change in weather,
exposure to cold air
• Endocrine factors
Medical History both
• Symptoms
– Cough
– Wheezing
– Shortness of breath
– Chest tightness
– Fever
– Sputum production
Physical Examination
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Tachypnoea
Tachycardia
Pulsus Paradoxus
Cyanosis
Accessory muscle use
Prolonged expiration
Wheeze
Anxious look
Position and diaphoresis
Investigations
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Chest x-ray
Sinuses x-ray
ECG
DLC (eosinophilia)
Sputum examination
Pulmonary function test
– Spirometry
– ABG
– Pulse oximetery
Classification of Asthma Severity
Symptoms
Nighttime
symptoms
Lung
Function
Mild Intermittent
 Symptoms < 2/ wk
 Exacerbations brief
< 2/ month
FEV 1 > 80%
PEF variability <20%
Mild persistent
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> 2/ month
FEV 1 > 80%
PEF variability 20-30
> 1/ wk
FEV 1 >60%, <80%
PEF variability >30%
Frequent
FEV 1 < 60%
PEF variability >30%
Moderate
Persistent
Severe Persistent
Symptoms> 2/ wk
But > 1/ day
May affect activity
Daily symptoms
Affect activity
Daily use of  agonist
Continual symptoms
Limited activity
Frequent exacerbations
Treatment of Asthma
• Beta2-agonist
– Inhaled
• Short acting
• Long acting
– Oral
• Anticholinergics
• Methylxanthines
• Mast cell stabilizer
– Cromlyn sodium
– Nedocromil
• Corticosteroids
– Inhaled
– Systemic
• Leukotrine modifiers
Therapeutic Measures in COPD
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Antismoking Measures
Bronchodilators
Antibiotics
Oxygen
Corticosteroids
Noninvasive Ventilation
Pulmonary Rehabilitation
Lung-Volume-Reduction Surgery
Short Acting Inhaled Β2 Agonist
• Indications
– Relief of acute symptoms
– Preventive prior to exercise
• Mechanism
– Smooth muscle relaxation
• Adverse effects
– Tachycardia, Skeletal muscle tremor, Hypokalemia,
headache, increased lactic acid
• Therapeutic issues
– Drug of choice for acute spasm
– Mild intermittent asthma
Long Acting Β2 Agonist
• Indications
– Long term prevention of symptoms, nocturnal
– Not to be used to treat acute attack
• Mechanisms
– Smooth muscle relaxation
– Inhibit mast cell mediator release
– Onset ( 15-30 min.), Duration (>12 hours)
• Adverse effects
– QT prolongation
– Other same as short acting
• Therapeutic issues
– Added to standard treatment with inhaled Corticosteroids
Systemic Β2 Agonist
• Inhaled beta agonist are preferred because they have fewer side
effect
Anticholinergics
• Indication
– Relief of acute symptoms
• Mechanisms
– Competitive inhibition of muscarinic cholinergic receptors
– Reduces intrinsic vagal tone to the airways
– Decrease mucus gland secretions
• Adverse effects
– Dry mouth and respiratory secretions
• Therapeutic issues
– Reverses only cholinergically mediated bronchospasm
– Additive effect to β agonist
– Treatment of choice for spasm induced by beta-blocker
Methylxanthines
• Indications
– Long tern control and prevention of symptoms, especially
nocturnal symptoms
• Mechanisms
– Smooth muscle relaxation from phosphodiestrase inhibition
– Increase diaphragm contractility and mucocilliary clearance
• Adverse effects
– Dose related toxiicities include tachycardia, nausea, vomiting
SVT, headache, seizures
– Usual doses include insomnia, gastric upset, increase in
hyperactivity in children, difficulty in urination in elderly
Therapeutic Measures in COPD
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Antismoking Measures
Bronchodilators
Antibiotics
Oxygen
Corticosteroids
Noninvasive Ventilation
Pulmonary Rehabilitation
Lung-Volume-Reduction Surgery
Antismoking Measures
• Smoking cessation is the only measure that will slow
the progression of COPD
• Nicotine-replacement therapy (by gum, transdermal
patch, or inhaler) provides help to patients in quitting
smoking
• The use of the recently introduced drug bupropion, a
noradrenergic antidepressant, has proved to be the
most effective strategy to date
– A recent controlled trial showed that after a 9-week course of
bupropion, abstinence rates were 30 percent at 12 months,
as compared with only 15 percent with placebo
– The abstinence rate was slightly improved with the addition
of a nicotine patch.
Bronchodilators
are the
mainstay of
current drug
therapy for
COPD.
Bronchodilators
• Bronchodilators cause only a small (<10
percent) increase in FEV1 in patients with
COPD
• These drugs may improve symptoms by
reducing hyperinflation and thus dyspnea
• They may improve exercise tolerance, despite
the fact that there is little improvement in
spirometric measurements
Bronchodilators
• Several studies have demonstrated the
usefulness of the long-acting inhaled (beta)2agonists salmeterol and formoterol in COPD.
• An additional benefit of long-acting (beta)2agonists in COPD may be a reduction in
infective exacerbations, since these drugs
reduce the adhesion of bacteria such as
Haemophilus influenzae to airway epithelial
cells.
Bronchodilators
• COPD appears to be more effectively treated
by anticholinergic drugs than by (beta)2agonists, in sharp contrast to asthma, for
which (beta)2-agonists are more effective.
• A new anticholinergic drug, tiotropium
bromide, which is not yet available for
prescription, has a prolonged duration of
action and is suitable for once-daily inhalation
in COPD.
Antibiotics
• Acute exacerbations of COPD are commonly
assumed to be due to bacterial infection,
since they may be associated with increased
volume and purulence of the sputum.
• Exacerbations may be due to viral infections
of the upper respiratory tract or may be
noninfective, so that antibiotic treatment is
not always warranted.
Antibiotics
• A meta-analysis of controlled trials of
antibiotics in COPD showed a statistically
significant but small benefit of antibiotics in
terms of clinical outcome and lung function.
• There is no evidence that prophylactic
antibiotics prevent acute exacerbations
Oxygen
• Long-term oxygen therapy:
– reduced mortality
– improvement in quality of life in patients with
severe COPD and chronic hypoxemia (partial
pressure of arterial oxygen, <55 mm Hg).
– Oxygen does not increase survival in patients with
less severe hypoxemia
– The selection of patients is important in prescribing
this expensive therapy.
In patients with COPD who have
nocturnal hypoxemia, nocturnal
treatment with oxygen does not
appear to increase survival or
delay the prescription of
continuous oxygen therapy
Corticosteroids
• Inhaled corticosteroids are now the mainstay
of therapy for chronic asthma
• However, the inflammation in COPD is not
suppressed by inhaled or oral corticosteroids,
even at high doses.
• This lack of effect may be due to the fact that
corticosteroids prolong the survival of
neutrophils and do not suppress neutrophilic
inflammation in COPD.
• Approximately 10 percent of patients with
stable COPD have some symptomatic and
objective improvement with oral
corticosteroids. It is likely that these patients
have concomitant asthma, since both
diseases are very common. Indeed, airway
hyperresponsiveness, a characteristic of
asthma, may predict an accelerated decline in
FEV1 in patients with COPD.
• long-term treatment with high doses of inhaled
corticosteroids reduced the progression of COPD,
even when treatment was started before the disease
became symptomatic.
• Inhaled corticosteroids may slightly reduce the
severity of acute exacerbations, but it is unlikely that
their use can be justified in view of the risk of
systemic side effects in these susceptible patients
and the expense of using high-dose inhaled
corticosteroids for several years.
• By contrast, two recent studies have demonstrated a
beneficial effect of systemic corticosteroids in treating
acute exacerbations of COPD, with improved clinical
outcome and reduced length of hospitalization.
• The reasons for this discrepancy between the
responses to corticosteroids in acute and chronic
COPD may be related to differences in the
inflammatory response (such as increased numbers
of eosinophils) or airway edema in exacerbations.
Noninvasive Ventilation
Noninvasive positive-pressure ventilation
with a simple nasal mask
• Which eliminates the necessity for endotracheal
intubation,
• Reduces the need for mechanical ventilation in acute
exacerbations of COPD in the hospital,
• used at home may improve oxygenation and reduce
hospital admissions in patients with severe COPD
and hypercapnia
• The combination of noninvasive positive-pressure
ventilation and long-term oxygen therapy may be
more effective,
Pulmonary Rehabilitation
• Pulmonary rehabilitation consisting of a
structured program of education, exercise,
and physiotherapy has been shown in
controlled trials to improve exercise capacity
and quality of life among patients with severe
COPD and to reduce the amount of health
care needed
Lung-Volume-Reduction Surgery
• The reduction in hyperinflation improves the
mechanical efficiency of the inspiratory
muscles
• Careful selection of patients after a period of
pulmonary rehabilitation is essential.
• Patients with localized upper-lobe
emphysema appear to do best; relatively low
lung resistance during inspiration appears to
be a good predictor of improved FEV1 after
surgery.
Functional improvements
• increased FEV1,
• reduced total lung capacity and functional
residual capacity,
• improved function of respiratory muscles,
• improved exercise capacity, and
• improved quality of life.
Thankyou