Chronic Obstructive Pul monary Disease (COPD) M Farooq Saeed University of Health Sciences Lahore

Objectives
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Explain the importance of elastic recoil in keeping respiratory bronchioles patent during exhalation. Explain how this relates to the classic definition of emphysema as "an abnormal, permanent dilatation of part of all of the acinus, with destruction of alveolar walls." Distinguish the two "classic" types of emphysema, and mention their alleged causes. Tell what we think causes emphysema in cigarette smokers and alpha-1 antitrypsin deficient patients. Tell what a "pink puffer" looks like clinically, and how emphysematous lungs look at autopsy. Describe the complication of "bullous emphysema".
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Chronic Obstructive Pulmonary Disease (COPD)

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called chronic obstructi ve lung disease (COLD) l Major cause of bed defining disability l Major symptom is dyspnea (shortness of breath) l Usually due to cigarette smoking l Site of disease: bronchi -chronic bronchitis, bronchiectasis, asthma; l Bronchioles -bronchiolitis l Acini-emphysema
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Obstructive airway disease : Increase in resistance to airflow due to obstructi on at any level; includes emphysema, chro nic bronchitis, bronchiectasis, asthma, tumo r, foreign body; reduced maxi mal airflow rates (FEV1) Restrictive airway disease : Reduced expansion of lung parenchyma wi th decrease i n total lung capacity; normal FEV1; due to chest wall disorders (polio, obesity, pleural disease, kyphoscoliosis), interstitial / infiltrative diseases (ARDS, dust di seases, interstitial fibrosis)
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Obstructive Airway Disease:

Localised Mechanical Tumors, Trauma, Foreign body collapse Diffuse Distal airway diseases COPD chronic COPD Definition: Progressive irreversible airway obstruction with destruction of parenchyma Chronic Bronchitis Emphysema Asthma Chronic Slow ly progressive Stable over several months 25% of smokers likely to develop COPD

Chronic Bronc hitis Chronic bronchitis is a clinic ally defined syndrome of chronic excessive mucus production in the airways Mucus is mainl y produced by the bronchial glands. The pathologic hallmark of c hronic bronchitis is mucous gl and enlargement.
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CLASSIFICATION
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Simple Bronchitis l Chronic Obstructive Bronchitis l Chronic Asthmatic Bronchitis l Constrictive Bronchiolitis

Pathogenesis
1.Smoking / pollution - major cause. 2.Acute & Chroni c mucosal infl ammation 3.The walls get thicker and this narro ws the bronchial lumens. 4.Lack of cilia - retention of sec retions 5.Increased muc ous glands & vi scid mucous. 6.Frequent secondar y infections 7.Inflammation retention infection obstruction cycle.
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Reid index , the ratio of the bronchial mucous gland layer to bronchial wall thickness (from perichondrium to basement membrane), ser ves as an indicator of mucous gland hypertrophy. l Approximate Reid index less than 0.36 to 0.55 l In general, a Reid index of 0.4 or greater is consistent w ith mucous gland hypertrophy.
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CHRONIC BRONCHITIS "smoker's cough"

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The "classic chronic bronchitis patient" is a "blue bloater", with increased PaCO 2, obese, edematous (cor pul monale), cyanotic, producing purulent sputum.

Distinguishing feature ; acquired tolerance for the hypercarbia that poor venti lation (i.e., from emphysema) ul timately causes. l Unlike "pink puffers" (who retain their hypercarbic drive), these pati ents no longer really struggle to breathe, so l ong as they have ade quate O 2
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l "Coarse

breath sounds" / "coarse

rhonchi" l Clubbing of fingers l Despite elabor ate systems of testing pulmonary function, the ultimate diagnosis of "COPD" is made on histor y and physical exam. l This applies to most other dis eases too.

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COMPLICATIONS
l Pulmonary

hypertension super venes earlier in "chronic bronchitis" patients than in emphysema patients l At autopsy we find copious secretions in the airways, even in the absence of pneumonia. l The trachea itself may be almost filled with yellow slime ( slippery) .
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The chest cavi ty is opened at autopsy to reveal numerous large b ullae apparent on the surface of the lungs in a patient dying with emphysema.Bull ae are large dilated airspaces that bulge out fr om beneath the pleura.Emphysema is characterized by a loss of lung parenchyma by destruction of alveoli so that ther e is by permanent dilation of airspaces.
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Emphysema
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Emphysema is defined as "permanent enlargement of airspaces accompanie d by destruction of alveolar walls and capillary bed". In pulmonary emphysema there is loss of alveolar septal tissue and corresponding enlargement of airspaces. Interstitial fibrosis is not seen histologicall y, if present, is the result of additional lung i njury due to some other process.
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Pathogenesis
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The current concept of the of pulmonary e mphysema is that of a protease- antiprotease imbalance, w ith the resultant enzyma tic destruction of the lung structural protein, elastin Cigarette smoke functions in several w ays as a mediator of tissue destruction. It stimulates pulmonar y inflammator y cells ( macrophages and neutrophils) to accumulate in the lung Both macrophages and neutrophils release elastase, although neutrophil elastase is considered to be more important in the degradation of lung elastin.
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the same time oxidants in cigarette smoke are thought to inhibit the activit y of alpha -1-antitrypsin, the most important serum protease inhibitor. is additional e vidence that these oxidants can directly injure lung tissue as well as can impair elastin synthesis. alveolar septa are destroyed, lung elastic recoil is reduced.
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l There

l As

l Elasticity

& normal aging &

smoking. l Both emphysema and chronic bronchitis are most commonly caused by cigarette smoking . l Most smokers with one have the other, too
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Emphysema d ue to A-1-ATD
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Genetic deficiency Alpha-1-antitrypsin (AAT) inhibits proteases, particularly elastase (which digests lung tissue), which is secreted by neutrophils during inflammation PiMM: normal phenotype; 90% of population PiZZ: associated with AAT deficiency; 80% develop symptomatic emphysema; occurs earlier and is more severe in smokers Neutrophils are normally present in lung and alveolar space; when stimulated, neutrophils and macrophages increase in number and release elastase and oxygen free radicals, which causes emphysem a unless counteracted by antiproteases such as AAT Smokers have more neutrophils and macrophages in alveoli, tobacco use enhances release of elastase from neutroph ils, enhances elastase activity, oxidants in tobacco smoke inhibit AAT

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Anatomic Cl assification of Emphysema

l Emphysema

c an be classified anatomically into four subt ypes: l Centriacinar (centrilobular) l Panacinar (panlobular) l Paracicatricial (irregular) l Paraseptal (dis tal acinar) l Others

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Frequently there is a mixture of types within the same l ung. There is no evidence at present to suggest that one subtype evol ves into another. The factors whi ch lead to each of these anatomic forms of emphysema ar e unclear. Each type has i ts own clinical correlates and should be considered as a disti nct entity.
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Centriacinar Emph ysema

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95% of emphysema cases Causes signif icant airflow obstruction, Affects central part of acini, sparing distal alveoli. Worse in upper lobes, particularly apices Men more prone Walls are anthracotic with parabronchial inflammation Seen in heavy smokers, coal worker pneumoconiosis Clinically significant at age 40+ in smokers, although ventilatory deficits seen earlier

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Panlobular Emphysema
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of cases l Acini uniformly enlarged from respiratory bronchiole to terminal alveoli l Usually lower lungs l More common in women below 40 years l Associated with A-1AT deficiency l Lungs usually voluminous
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Paraseptal (Distal Acinar) Emphysema

Involve the distal periphery of the acinus adjacent to pleura, interlobular sept a or bronchovascular bundles. Minor clinically ; Rare Emphysema is next to pleura Near areas of fibrosis, scarring or atelectasis Multiple continuous airspaces affected May be source of spontaneous pneumothorax in young adults
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Senile emphysema :
Due to age -related alterations in internal geometry of alveoli leading to larger alveolar ducts, smaller alveoli, but no loss of elastic tissue or destruction of lung substance
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Paracicatricial emphysema
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Dilated airspaces are of ten seen on the edge of pulmonary scars. This form of emphysema bears no uniform relationship to the acinus & is some times called " irregular" emphysema. It is probably, in part, the result of traction on surrounding lung tissue by the contracting fibrous scar. Usually, paracicatricial emphysema is an inci dental finding without clinical signif icance. However, in severely scarred lungs associated with granulomatous disorders such as tuberculosis, extensive paracicatricial emphysema can produce airf low obstruction.
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Obstructive emphysema
Due to tumor, foreign body or congenital lobar over inflation (infants, perhaps due to hypoplasia of bronchial cart ilage; associated with other) cardiopulmonar y anomalies Due to ball-valve effect with inhalation via collaterals (pores of Kohn, canals of Lambert) Compress normal lung, may be life-threatening
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Interstitial emphyse ma
Air into connective tissue stroma of lung, mediastinum or subcutaneous tissue, due to alveol ar tears, chest wounds, coughing, whooping cough Compensatory emphysema
Response to loss of l ung elsewhere, such as post -lobectomy
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Bullous emphysema
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Produces air -filled blebs (called " bullae if >1 cm) containing little or no lung tissue located immediately adjacent to the visceral pleura. Usually at the apices Sometimes at the sites of old TB scars. Most cases probably r esult from common emphysema, with the inelastic lung "collapsing under its own wei ght"; the upper lobes have more contact more tobacco smoke because they are better ventilated.

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The blebs may be removed s urgically, with improvement in the "pink puffer"'s puffing. Blebs are also prone to ruptur e, causing pneumothorax and sudden death Iatrogenic disease: "IPPB breathing treatments" are irrational therapy for uncomplicated emphysema, and kill patients by blowing out blebs

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Pulmonary Vascular Changes

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The small pulmonary arteries and arterioles in emphysema show increased medial smooth muscle, abnormal muscle which has extended into normally non-muscular arteries & longitudinal muscle bundles in the intima. The strongest stimulus for this arterial muscularization in emphysema appears to be chronic hypoxia. The net effect of the increased mural musculat ure is to compromise vascular lumens and possibly increase vascular tone.

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l The

pulmonary capillary bed is extensively destroyed along with alveoli in emphysema. right ventricul ar hypertrophy is regularly seen in patients with severe (high grade) emphysema (either panacinar or centriaci nar) and unusual in thos e with minimal emphysema
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l Anatomic

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Clinical Pic ture

lNo symptoms until 1/3 of func tional capacity is lost lThe only consistent finding on phys ical exam is slowing of forced expiration lShortness of br eath, coughing, wheezing, weight loss lBarrel chest, pursed li ps, dyspneic, tachypneic, thin lThe classic "emphysema" patient is a "pink puffer", with normal Pa -CO2
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COMPLICATIONS
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Exacerbations and death often follow infection with S. pneum or H. influen Death may also result from cor pulmonale or from apnea brought about by breathing oxygen (remember, hypercarbia no longer stimulates respiration in these patients.) May cause secondary pulmonary vascular hypertension, cor pulmonale, congestive heart failure, death due to respiratory acidosis and coma, pneumothorax Best to assess based on morphometr y, not lung function data At autopsy, the lungs are hyperinflated and relatively bloodless
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Blue Bloater
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Pink Puffer
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Mild dyspnoea, late Infections common Cor-pulmonale Increased resistance Prominent BV, large heart Infrequent wt loss Sputum & Ronchi Maximal Cyanosis Normal ABG Episodic, recurrent

Dyspnoea severe, early Occassional Rare, late Mild increase Hyperinflation small heart Severe wt loss Sputum & Ronchi Minimal Severe Hypoxemia Prognosis, terminal
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Smokers Pathology
Tobacco pigment in the lungs (brow n stuff) l Carbon pigment in the lungs "anthracosis l Loss of ciliar y motility l Goblet cell proliferation in remaining columnar epithelium l Hypertrophy and hyperplasia of mucous glands l Thickening of the respirator y epithelial basement membrane ("subepithelial collagen deposition") l Increased numbers of pol ys in the lungs, 4X l Increased numbers of alveolar macrophages (x6 or so)
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l Impaired

ability of alveolar macrophage to function usefully l Increased neutro and macro elastase production and release l Impaired ability of alveolar macrophage to function usefully l Squamous metaplasia of respiratory epithelium l Loss of elasticity of alveolar walls l Eventual destruction of alveolar walls
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l Smokers

have a greater number of neutrophils and macrophages in their alveoli. l Smoking irritates alveolar macrophages, which in turn release neutrophil chemotactic factors, such as interleukin 8, thus recruiting neutrophils. l Nicotine is chemotactic for neutrophils l Activate the alternative complement pathway l Proteases, particularly elastase, are secreted by these neutrophils and macrophages l Proteases are enzymes that are capable of digesting lung tissue and these chemicals are responsible for the damage seen in emphysema.
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l Oxidants

and free radicals in smoke also inhibit the alpha -1-antitrypsin circulating in t he lung that protects alveoli from proteases. l Chronic irritation by smoke also can lead to chronic bronchitis with excess production of mucus. l Smoke interfer es with the ciliary action of the respiratory epithelium and the mucus cannot be cleared. This predisposes the smoker to secondary and repeated infections
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Diagnosis
History l Physical Examination l Radiological Examination l Laboratory Examination of sputum, bl ood l Pulmonary Func Tests:
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Inc Expirator y Phase Mismatch Ventilation Perfusion Inc FVC Dec FEV 1 Inc RV Inc TLC
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3 Investigations: Spirometry (FEV1/VC), PaO2, P CO2. 3 grades Mild 69-80 FEV1 cough, exerti onal dysp. Mod 40-60 FEV1 - + Wheeze, cough, sputum. Sev - < 40 FEV1 - + Right Heart Failure.

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TREATMENT
Palliative Non Pharmacol ogical Therapy:
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Counselling and prevention Check sputum Feed modification Breathing Exercises Bronchodilators ( adrenergic, anticholinergic) Theophylline Corticosteroids ? O2 Therapy (1 -2 Lit/min; PO 2= 55-65 mm Hg) Surgery
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Pharmacological Therapy:
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