COPD is a chronic inflammatory process in the lower airways and the lung parenchyma caused by many factors that trigger and maintain inflammation. An imbalance between proteases and anti-proteases may be a contributory factor.
The most important and modifiable aetiological factor for COPD is smoking.
Smokers have a higher prevalence of respiratory symptoms and lung function abnormality, a greater annual rate of decline in FEV1 , and higher death rates from COPD than nonsmokers. Women may have more symptoms than men for the same number of pack-years smoked. About 40–50% of lifelong smokers will develop COPD, compared with only 10% of never-smokers. Passive exposure to cigarette smoke may also contribute to respiratory symptoms and impaired lung function in schoolchildren. However, not all smokers develop clinically significant COPD, which suggests that genetic factors may modify individual risk. The proportion of the risk of COPD attributable to smoking has been estimated as 40–60%, depending on how many risk factors have been taken into account.
Although never-smokers are less likely to have COPD and have less severe COPD than ever-smokers, never-smokers nonetheless comprise about one-quarter of those classified with Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage II+ COPD.
Occupational airborne exposure
Several studies show that 30–40% of the general population report having been exposed to airborne pollutants at work (for further information, see chapters 7 and chapter 24). When the exposure is sufficiently intense or prolonged, occupational dust, chemicals and vapours can cause COPD independently of cigarette smoking. Studies of general populations and working groups show that about 15–20% of COPD cases are due to occupational exposure. In never-smokers, the fraction of COPD attributable to occupational exposure is estimated to be 30%. A variety of occupations may represent an increased risk of COPD, such as mining, agriculture, and textile, paper, wood, chemical, and food processing.
Outdoor and indoor pollution
A high level of urban air pollution is harmful to individuals with COPD, as it can result in exacerbations and a poorer quality of life (for further information on air pollution, see chapter 6). The role of outdoor air pollution in Europe in causing COPD is unclear. The relative importance of short-term, high peak exposures compared with long-term, low-level exposures is not known. Heavy indoor air pollution caused by the use of biomass fuel is a risk factor for the development of COPD.
The risk of developing COPD is inversely related to socioeconomic status based on education or income. The effects of various indicators of socioeconomic status may differ between men and women, and socioeconomic status may also reflect factors such as nutrition, overcrowding and air pollution, as well as genetic determinants.
Early life environmental factors
Smoking mothers, frequent respiratory infections and asthma in childhood, and bronchial hyperreactivity are important risk factors for COPD. The proportion of the risk of COPD attributable to these early childhood events may be as great as that attributable to smoking (see also chapter 4).
The best documented genetic risk factor for COPD is hereditary α1-antitrypsin deficiency (see also chapter 3). However, in most populations, homozygous α1-antitrypsin deficiency is found in fewer than five people per 10 000. Polymorphisms of many genes or combinations of genes may increase (or decrease) the risk of an individual developing COPD. Individual genes may be related to specific phenotypes of COPD. Single genes, such as the gene encoding matrix metalloproteinase (MMP)-12, may be related to decline in lung function. Genome-wide studies of gene expression and genetic variation have provided exciting new avenues for future investigation and potentially new approaches to risk prediction and therapy.