Chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease (COPD) is a group of diseases—chronic bronchitis, small-airway disease (obstructive bronchiolitis), and emphysema. These should be considered in patients over the age of 35 who have (1) exposure to risk factors, usually tobacco smoke; (2) a history of chronic progressive symptoms—cough, wheeze, and/or breathlessness; (3) airflow limitation that is not fully reversible, confirmed by spirometry. They are slowly progressive conditions characterized by airflow limitation that is largely irreversible and which produce considerable morbidity and mortality: COPD is the sixth commonest cause of death worldwide.

Definition

Chronic bronchitis—defined clinically as the presence of a chronic productive cough on most days for 3 months, in each of two consecutive years, in a patient in whom other causes of chronic cough have been excluded.

Emphysema—defined pathologically as abnormal, permanent enlargement of the distal air spaces, distal to the terminal bronchioles, accompanied by destruction of their walls and without obvious fibrosis.

Aetiology

Cigarette smoking—this is the single most important identifiable aetiological factor, with at least 10 to 20% of smokers developing clinically significant disease. The greater the total tobacco exposure, the greater the risk of developing COPD, although about 10% of cases occur in patients who have never smoked.

Genetic factors—there is significant familial risk for developing airflow limitation in smoking siblings of patients with severe COPD, but apart from α₁-antitrypsin deficiency other functional genetic variances which may influence the development of COPD have not been proven.

Pathology and pathophysiology

Pathology—this is complex, with changes affecting both large and small airways and the alveolar compartment. (1) Chronic bronchitis—hypersecretion of mucus is associated with an increase in the volume of the submucosal glands, and an increase in the number and a change in the distribution of goblet cells in the surface epithelium. (2) Obstructive bronchiolitis or small-airways disease—this results from inflammation, squamous cell metaplasia and/or fibrosis in airways less than 2 mm in diameter; bronchiolitis is present in the peripheral airways at an early stage of the disease, with changes in inflammatory response as the disease progresses that are thought to represent innate and adaptive immune responses to long-term exposure to noxious particles and gases. (3) Emphysema—two main types are recognized: (a) centriacinar (or centrilobular) emphysema, in which enlarged air spaces are initially clustered around the terminal bronchiole; and (b) panacinar (or panlobular) emphysema, where the enlarged air spaces are distributed throughout the acinar unit.

Pathophysiology—the characteristic finding in COPD is a decrease in maximum expiratory flow, which can be reduced by two factors—(1) loss of lung elasticity, and (2) an increase in airways resistance in small and/or large airways. There is no consensus on whether the fixed airway obstruction in COPD is largely due to inflammation and scarring in the small airways, resulting in narrowing of the airway lumen, or to loss of support for the airways due to loss of alveolar walls, as in emphysema. Ventilation–perfusion (V/Q) mismatching is the main cause of impaired gas exchange. A combination of pulmonary overinflation and malnutrition, resulting in muscle weakness, reduces the capacity of the respiratory muscles in patients with severe COPD.

Clinical features

History—details of current smoking status and number of pack years smoked (pack years = number of cigarettes smoked/day × number of years smoked/20) are essential, as are those of previous and present occupations, particularly exposure to dusts and chemicals. Breathlessness can be assessed on the Medical Research Council and Borg Visual Analogue scales.

Examination—signs of airflow limitation may not be present until there is significant impairment of lung function, but the breathing pattern in COPD is often characteristic, with a prolonged expiratory phase, and there may be signs of overinflation of the chest.

Investigation

Spirometry—this is the most robust test of airflow limitation in patients with COPD. A post-bronchodilator FEV₁ less than 80% predicted, together with a forced expiratory volume in 1 s/forced vital capacity (FEV₁/FVC) ratio less than 0.70, confirms the presence of airflow limitation that is not fully reversible and is a diagnostic criterion for COPD. Depending largely on the degree of impairment of FEV₁, the severity of COPD can be graded (Global Initiative for Obstructive Lung Disease, GOLD) as mild, moderate, severe, or very severe. The rate of decline of the FEV₁ can be used to assess susceptibility in cigarette smokers and progression of disease.

Lung function tests—static lung volumes such as total lung capacity (TLC), residual volume (RV), and functional residual capacity (FRC) are measured to assess the degree of overinflation and gas trapping. Dynamic overinflation occurs particularly during exercise and may be an important determinant of breathlessness in patients with COPD.

Arterial blood gases—these are needed to confirm the degree of hypoxaemia and hypercapnia in stable patients with an FEV₁ less than 50% predicted, or those with clinical signs of respiratory or right heart failure.

Exercise testing—the 6-min walk is most commonly employed, but is only useful in patients with moderately severe COPD (FEV₁ <1.5 litres) who would be expected to have an exercise tolerance of less than 600 m in 6 min.

Imaging—(1) posterior–anterior chest radiograph—findings are not specific for COPD; there may be no abnormalities, even in patients with very appreciable disability; emphysema produces signs of overinflation (low flat diaphragm, increased retrosternal air space, obtuse costophrenic angle), vascular changes (reduction in size and number of pulmonary vessels, vessel distortion, and areas of transradiency), and bullae. (2) CT scanning—a variety of techniques (visual assessment of low-density areas; CT lung density methods) can be used to quantitate emphysema and bullous disease.

Other tests—α₁-antitrypsin levels and phenotype should be measured in all patients under the age of 45 years, and in those with a family history of emphysema at an early age.

Prevention

Cessation of cigarette smoking—this is the single most important issue, and the ‘five As’ of smoking cessation should form a routine component of health care delivery: (1) Ask about tobacco use; (2) Advise quitting smoking; (3) Assess willingness to make an attempt; (4) Assist in quit attempt; and (5) Arrange follow-up.

Management

Stable COPD—treatment depends on severity. (1) Mild disease—active reduction of risk factors (e.g. stopping smoking, influenza vaccination); add short-acting bronchodilator as needed. (2) Moderate disease—add regular treatment with one or more long acting bronchodilators when needed; add pulmonary rehabilitation. (3) Severe disease—add inhaled glucocorticosteroids if repeated exacerbations. (4) Very severe disease—add long-term oxygen if chronic respiratory failure; consider surgical treatments.

Acute exacerbations—most of these can be managed in the community, but severe exacerbations require admission to hospital for (1) oxygen therapy to achieve Pao₂ greater than 8 kPa (60 mmHg) or Sao₂ >90%, without inducing significant CO₂ retention; (2) nebulized bronchodilators; (3) antibiotics—if two of the following are present, (a) increase in dyspnoea, (b) increase in sputum volume, and (c) increase in sputum purulence; (4) corticosteroids—prednisolone 30 to 40 mg daily for 7 to 14 days; and (5) ventilatory support—usually noninvasive, if required and if appropriate.

Surgical treatments—(1) bullae—the only treatment possible for large bullae is surgical obliteration, which may allow re-expansion of adjacent compressed lung. Best results are obtained in younger patients with mild symptoms, large bullae, relatively well-preserved pulmonary function, and normal surrounding lung: patients with small bullae, FEV₁ less than 1 litre, or hypercapnia, tend to do badly. (2) lung volume reduction surgery—this aims to reduce the volume of overinflated emphysematous lung by 20 to 30%: it can be recommended only in very carefully selected patients. (3) Lung transplantation—should be considered in selected patients with very advanced COPD.