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Chronic obstructive pulmonary disease 

Chronic obstructive pulmonary disease

Chronic obstructive pulmonary disease

William MacNee


August 28, 2014: This chapter has been re-evaluated and remains up-to-date. No changes have been necessary.


This chapter has been extensively revised.

Aetiology—expanded discussion of environmental (indoor air pollution) and genetic factors, and the role of ageing.

Epidemiology—worldwide prevalence described by Burden of Obstructive Lung Disease (BOLD) study; worldwide estimates of deaths and disability; mortality related to severity of airflow limitation.

Clinical features—expanded discussions of systemic features and comorbidities; use of the COPD assessment test (CAT); assessment of risk of exacerbations; differential diagnosis; combined assessments in COPD (BODE index, GOLD classification).

Management—updates on newer pharmacological treatments, including phosphodiesterase 4 inhibitors, and recommendations regarding combined treatments. Enhanced discussion of treatment of comorbidities and of surgical approaches, including resection of bullae and lung volume reduction surgery.

Relevant case histories from Oxford Case Histories in Respiratory Medicine have been added to this chapter.

Updated on 30 May 2013. The previous version of this content can be found here.
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date: 23 April 2017


Chronic obstructive pulmonary disease (COPD) is a slowly progressive condition that produces considerable morbidity and mortality. It is characterized by airflow limitation that is not fully reversible and is associated with an enhanced inflammatory response in the airways and the lungs to noxious particles or gases. COPD is a group of lung conditions—chronic bronchitis (a chronic productive cough on most days for 3 months, in each of two consecutive years), small-airway disease (obstructive bronchiolitis), and emphysema (abnormal, permanent enlargement of the air spaces, distal to the terminal bronchioles, accompanied by destruction of their walls) that are present to a variable extent in different individuals resulting in heterogeneous presentations of the condition. Exacerbations and comorbidities contribute to the overall severity of the condition in individual patients.

COPD should be considered in individuals over the age of 35 who have (1) exposure to risk factors, usually, but not exclusively, tobacco smoke; and (2) a history of chronic progressive symptoms—cough, wheeze, and/or breathlessness.

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.


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) centrilobular (or centriacina) emphysema, in which enlarged air spaces are initially clustered around the terminal bronchiole and is the predominant type in smokers; and (b) panlobular (or panacinar) emphysema, where the enlarged air spaces are distributed throughout the acinar unit and is predominant in alpha-1-antitrypsin deficiency.

Pathophysiology—the characteristic finding in COPD is a decrease in maximum expiratory flow, which can be reduced by two factors—(1) loss of lung elasticic recoil, 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. COPD is associated with a number of comorbidities: among those that are common are cardiovascular disease, osteoporosis, metabolic syndrome, depression, and lung cancer.

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 scales. Exacerbation frequency can be assessed by patient recall. Comorbidities should be actively sought.

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.


Spirometry—this is the most robust test of airflow limitation in patients with COPD. A post-bronchodilator 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. The severity of airflow limitation in COPD can be graded according to the Global Initiative for Obstructive Lung Disease (GOLD) as mild (≥80% predicted), moderate (50–79% predicted), severe (30–49% predicted), or very severe (<30% predicted). However, other factors contribute to disease severity and require assessment of symptoms (MRC dyspnoea score or CAT) and exacerbation frequency. 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) can be measured to assess the degree of overinflation and gas trapping. Dynamic overinflation occurs particularly during exercise and is 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 the most commonly employed test, 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 can produce 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.


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.

Influenza vaccination can prevent serious illness associated with influenza in patients with COPD and is given annually. Pneumococcal vaccination can prevent community acquired pneumonia in COPD patients and is recommended every five years in those >65 years, or <65 years with significant comorbidities or with more severe airflow limitation (FEV1 <40% predicted).


Stable COPD—treatment depends on an assessment of symptoms, severity of airflow limitation, and the risk of exacerbations.

Pharmacologic therapy—inhaled bronchodilators (beta agonists and/or anticholinergics) are central to the symptom management in COPD. Short-acting bronchodilators are prescribed on an as needed basis, but long-acting bronchodilators are given if symptom are persistent. Long-acting bronchodilators reduce symptoms, increase exercise tolerance and reduce exacerbation frequency. Regular treatment with a combination of inhaled corticosteroids with long-acting bronchodilator improves symptoms, lung function, quality of life, and reduces exacerbations in patients with moderate to very severe airflow limitation (FEV1 <60% predicted). The addition of a long-acting beta agonist/inhaled corticosteroids to the long-acting anticholinergic, Tiotropium, improves lung function and further reduces severe exacerbations. The oral phosphordiesterase inhibitor, Roflumilast, reduces moderate and severe exacerbations in COPD patients with chronic bronchitis with moderate to severe airflow limitation and a history of exacerbations. Theophylline is less effective and less well tolerated than long-acting bronchodilators, but does provide additional symptom relief when added to long-acting bronchodilators.

Non pharmacologic therapy—pulmonary rehabilitation reduces breathlessness, improves exercise tolerance and health related quality of life, and reduces exacerbation frequency, particularly when applied post exacerbation.

Long-term oxygen therapy (15h per day) given to patients with chronic respiratory failure (PaO2 ≤7.3 kPa) improves survival.

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.

Acute exacerbations of COPD—these are acute events characterized by an increase in respiratory symptoms (cough and sputum production/purulence, breathlessness) that is beyond the normal day to day variation and leads to a change in medication. Exacerbations can be caused by various factors, the commonest being respiratory tract infections viral and bacterial. Most exacerbations 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 there is increased sputum purulence with increase in dyspnoea and/or increase in sputum volume; (4) corticosteroids—prednisolone 30 to 40 mg daily for 7 to 14 days; and (5) ventilatory support—usually noninvasive, if required and if appropriate.

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