COPD & EMPHYSEMA

·         A disease state characterized by chronic airflow limitation which is not fully reversible.

·         COPD includes-

1.       Emphysema

2.       Chronic bronchitis

3.       Small airways disease

·         Risk factors

1.       Smoking (both active & passive)

§  Expressed as pack-years (i.e. average no. of cigarette packs smoked/day × 365)

§  ↓ in FEV₁ α pack-years of smoking.

2.       Airway hyper-responsiveness

3.       Respiratory infections (mainly responsible for exacerbations of COPD)

4.       Occupational exposures

§  ↓ in FEV₁, FEV₁/FVC, DLco (esp. cadmium)

5.       Air pollution

6.       Genetic predisposition

§  α₁-Antitrypsin Deficiency (α₁ AT)

·         α₁ AT gene is located on protease inhibitor (PI/SERPINA 1) locus

·         3 alleles-

o   M allele- normal α₁ AT levels

o   S allele- slightly reduced α₁ AT levels

o   Null allele- absent α₁ AT levels

·         Pi^ZZ/Pi^Z- most common form of severe α₁ AT deficiency

o   ZZ-homozygous Z allele

o   Z- Z allele + Null allele

·         Pathophysiology

·         3 mechanisms occur simultaneously-

1.       Airway obstruction/limitation

·         ↓ FEV₁ (only slightly responsive to inhaled bronchodilators, a contrast to asthma)

·         ↓ FEV₁/ FVC

·         Maximum inspiratory flow rate preserved

2.       Hyperinflation

·         ↑ RV (Residual Volume)

·         ↑RV:TLC (“air trapping”)

·         ↑TLC (“progressive hyperinflation”) [Hyperinflation helps to compensate for airflow obstruction by enlarging the airways]

3.       Impaired Gas exchange

·         When FEV₁ < 50% of predicted- Pa_O2 ↓ during exertion (due to ventilation/perfusion mismatch)

·         When FEV₁ < 25% of predicted- Pa_CO2↑

·         When FEV₁ < 25% of predicted + Pa_O2 < 55 mm Hg (chronic hypoxemia)- Pulmonary hypertension & cor pulmonale

Non-uniform ventilation & ventilation-perfusion mismatch are characteristic of COPD.

·         Pathology

·         Cigarette smoke may affect large airways, small (<2 mm) airways & alveolar space

·         Large airways-

·         Smoking causes mucous gland hypertrophy & goblet cell hyperplasia.

·         Bronchi undergo squamous metaplasia predisposing to carcinogenesis & disrupting mucociliary clearance.

·         Smooth-muscle hypertrophy & bronchial hyper-reactivity cause airflow limitation.

·         Neutrophil influx in URTI with purulent sputum.

·         Small airways-

·         Major site of increased resistance in COPD is airways ≥2 mm diameter.

·         Smoking causes

·         Goblet cell metaplasia

·         Replacement of surfactant secreting Clara cells with mucous secreting & mononuclear inflammatory cells.

·         Luminal narrowing results from excess mucous, edema & cellular infiltration.

·         Loss bronchial attachments due to extracellular matrix destruction results into airway collapse & airway distortion.

·         Alveolar space-

·         In emphysema-

·         Destruction of gas-exchanging airspaces i.e. respiratory bronchioles, alveolar ducts & alveoli.

·         Accumulation of macrophages in respiratory bronchioles of young smokers.

·         Classification of emphysema-

CENTRIACINAR EMPHYSEMA	PANACINAR EMPHYSEMA
·         Involves respiratory bronchioles while distal part of acinus (alveolar duct & alveolus) are spared	·         Involves distal part of acinus (alveolar duct & alveolus) while respiratory bronchioles are spared
·         Associated with smoking	·         α1 AT deficiency
·         Most prominent in upper lobes & superior segments of lower lobes	·         Lower lobes usually involved

 

·         Clinical presentation

o   Symptoms

§  Cough

§  Sputum production

§  Exertional dyspnoea

o   Signs

§  Prolonged expiratory phase & expiratory wheezing

§  Signs of hyperventilation- barrel-shaped chest, ↑ lung volume, ↓ diaphragmatic excursions

§  Use of accessory muscles of respiration with ‘tripod’ posture

§  Cyanosis

§  Advanced disease signs-

·         Systemic wasting, weight loss, diffuse subcutaneous tissue atrophy

·         Hoover’s sign- paradoxical inward movement of rib cage with inspiration

·         Signs of cor pulmonale.

§  ‘pink puffers’- predominant emphysema (thin & non-cyanotic at rest)

§  ‘blue bloaters’- predominant chronic bronchitis (heavy & cyanotic)

§  Clubbing is not a sign of COPD.

·         Lab investigations-

o   Spirometry (forced expiratory maneuvers) & Plethysmography

§  Degree of airflow obstruction is a prognostic factor in COPD & basis for the GOLD disease classification.

o   Arterial blood gas & oximetry- demonstrate resting/ exertional hypoxemia

o   Radiographic studies-

§  Plain chest X-ray- bullae, ↓ parenchymal markings, hyperlucency (in emphysema)- ↑ lung volume & flattening of diaphragm (hyperinflation)

§  HRCT Scan- definitive test

o   Serum α₁ AT levels

·         Treatment

o   Stable phase COPD

§  Smoking cessation ***

·         Two pharmacological approaches- bupropion & nicotine replacement

§  Bronchodilators

§  Oxygen ***

·         Continual O2- patients with resting hypoxemia

·         Supplemental O2- patients with exertional hypoxemia/nocturnal hypoxemia

§  N-acetyl cysteine

§  α₁ AT augmentation i.v. therapy

§  Inhaled/oral glucocorticoids

§  Lung volume reduction surgery

§  Lung transplantation

o   Acute exacerbation of COPD

§  Bronchodilators (inhaled)

§  Antibiotics- to treat associated infections causing exacerbation.