C1. Aetiology and natural history

Cigarette smoking is the most important cause of COPD.^8,9 There is a close relationship between the amount of tobacco smoked and the rate of decline in forced expiratory flow in one second (FEV₁ ), although individuals vary greatly in susceptibility.⁸ Around half of all smokers develop some airflow limitation, and 15%–20% will develop clinically significant disability.⁸ Smokers are also at risk of developing lung cancer, and cardiovascular disease such as ischaemic heart disease and peripheral vascular disease.

In susceptible smokers cigarette smoking results in a steady decline in lung function, with a decrease in FEV₁ of 25–100 mL/year.⁸ While smoking cessation may lead to minimal improvements in lung function, more importantly it will slow the rate of decline in lung function and delay the onset of disablement. At all times smoking cessation is important to preserve remaining lung function.⁸

Impairment increases as the disease progresses, but may not be recognised because of the slow pace of the disease. The time course of development of COPD and disability and the influence of smoking cessation are illustrated in Box 3.

In addition to cigarette smoking, there are a number of other recognised risk factors for COPD¹¹ (see Figure 3-1 below adapted from GOLD 2006). COPD almost always arises from a gene environment interaction. The best characterised genetic predisposition is alpha₁ antitrypsin deficiency, but multiple other genes each make a small contribution and further investigation is required. The risk of COPD is related to the total burden of inhaled particles¹¹ and oxidative stress in the lung. Occupational dust exposure might be responsible for 20 – 30% of COPD. This has long been recognised in underground miners, but recently biological dust has also been identified as a risk factor, particularly in women.¹²  Fortunately the air quality in most Australian cities is relatively good and cooking with biomass fuels (wood, dung etc) is uncommon. Failure to achieve maximum lung function increases the risk of COPD in later life. The role of gender is uncertain. Beyond the age of 45-50 years, female smokers appear to experience an accelerated decline in FEV₁ compared with male smokers¹³ [evidence level II]. Nor is it known whether the increased risk among lower socioeconomic groups is due to greater exposure to pollution, poorer nutrition, more respiratory infection or other factors.¹¹

Although FEV₁ has long been accepted as the single best predictor of mortality in population studies in COPD^8,14 recent studies have suggested various other indices, which may also predict mortality. In patients with established COPD, degree of hyperinflation as measured by inspiratory capacity/ total lung capacity (IC/TLC) ratio was independently associated with all cause and COPD mortality.¹⁵ The 6 minute walk distance (6MWD), peak VO₂ during a cardiopulmonary exercise test, body mass index and dyspnoea score (measured with the modified Medical Research Council Scale) have all been shown to predict mortality better than FEV₁ in patients with established disease. Several of these latter indices incorporated together in a single score, the BODE index (BMI, degree of Obstruction as measured by FEV₁, Dyspnoea score and Exercise capacity measured by 6 minute walk) strongly predicted mortality.¹⁶ Nonetheless, FEV₁ continues to have utility as a predictor of all-cause mortality in COPD. In one study that followed patients after acute exacerbations, the five-year survival rate was only about 10% for those with an FEV₁ <20% predicted, 30% for those with FEV₁ of 20%–29% predicted and about 50% for those with an FEV₁ of 30%–39% predicted.¹⁷ Patients with an FEV₁ <20% predicted and either homogeneous emphysema on HRCT or a DLCO <20% predicted are at high risk for death after LVRS and unlikely to benefit from the intervention.¹⁸ 

Continued smoking and airway hyperresponsiveness are associated with accelerated loss of lung function.¹⁹ However, even if substantial airflow limitation is present, cessation of smoking may result in some improvement in lung function and will slow progression of disease.^19,20

The development of hypoxaemic respiratory failure is an independent predictor of mortality, with a three-year survival of about 40%.²¹ Long term administration of oxygen increases survival to about 50% with nocturnal oxygen²¹ and to about 60% with oxygen administration for more than 15 hours a day²² (see also section P).

Admission to hospital with an infective exacerbation of COPD complicated by hypercapnic respiratory failure is associated with a poor prognosis. A mortality of 11% during admission and 49% at two years has been reported in patients with a partial pressure of carbon dioxide (PCO₂) > 50 mmHg.¹⁷ For those with chronic carbon dioxide retention (about 25% of those admitted with hypercapnic exacerbations), the five-year survival was only 11%.¹⁷

Content last updated: April 2009 Page last updated: April 14, 2009