Never-smokers make up >25% of the people with COPD in some studies. Who are these people? The BOLD study gathered data from 14 countries (in the U.S., Europe, Turkey, China, South Africa, Philippines and Australia), including spirometry and questionnaires on environmental exposures and symptoms from 10,000 people. Of the 4,291 never-smokers, 4% had ATS-defined COPD (5.6% by GOLD). Impressively, these never-smokers comprised 20% of the moderate-to-severe (GOLD II+) COPD cases, and 81% of them were undiagnosed. More than two-thirds were women.
They had a 72% rate of respiratory symptoms (compared to 44% for never-smokers without COPD), and they were more likely to report 10 years of exposure to indoor fires (22% vs 15%) and/or organic dusts in the workplace (19% vs 10%) than unobstructed never-smokers. COPD rates in never-smokers were highest in Australia (7.5%) and Poland (9%), and lowest in the U.S. (3.5%). A collective of drug companies are funding this ongoing study that could guide public health efforts (and drug marketing). CHEST 2011;139:752-763.
From the Study:
Risk Factors for COPD in Never Smokers
There is evidence that a substantial proportion of COPD, up to 20%, can be attributed to occupational exposures.21 The ATS concluded that occupational exposures account for 10% to 20% of both symptoms and functional impairment consistent with COPD.22 In an analysis of NHANES III data, the fraction of COPD in never smokers that is attributable to work has been estimated to be 31%.23 In our data, never smokers with moderate to severe COPD reported exposure to organic dusts in the workplace more often than did never smokers with unobstructed airways (30.4% vs 23%). There is some evidence that the airway response to organic dust inhalation is primarily mediated by nonallergic inflammatory mechanisms.24,25 Grain dust, for example, can cause recruitment of neutrophils to the proximal and distal airways.26,27 The results of our study suggest an increased risk of COPD in women after occupational exposure to organic dusts for ≥ 10 years. Similar effects were not seen for inorganic dusts and gases, vapors, and fumes; however, the numbers of participants with these exposures was relatively small in this never-smoker population.
Biomass fuels used by women for cooking and heating have been shown to cause COPD in nonsmoking women.28‐32 In our data, exposure to indoor open fire (with coal or coke) for cooking was bivariately associated with COPD in never smokers, for whom clinical characteristics, impairment in quality of life, and increase in mortality are similar to tobacco smokers.33 However, we did not find statistically significant associations of at least 10 years of reported exposure to heating or cooking biomass in the logistic regressions.
There is evidence that exposure to environmental tobacco smoke is associated with COPD34‐36 and affects women more often than men.37,38 In our study, we did not observe an increased risk of GOLD stage II+ COPD associated with exposure to passive smoking. However, the BOLD questionnaire only assessed current exposure to passive smoking at home within the last 2 weeks and did not consider earlier exposures to passive smoking or to passive smoking in the workplace.
Low socioeconomic status,39 low level of education,40 and severe childhood respiratory infections41,42 have been shown to be associated with a higher prevalence of COPD. In our analysis, more years of education was associated with lower odds of spirometrically determined COPD among female never smokers. Likewise, severe childhood respiratory infections or other breathing problems (leading to hospitalization) and COPD were associated in never smokers.
Pulmonary TB is a frequent cause of chronic pulmonary function impairment, particularly airflow obstruction,43,44 and constitutes an important differential diagnosis to COPD in high-prevalence areas, especially in the absence of other typical risk factors for COPD.12 Our data show that a significantly higher prevalence of reported TB was present among never smokers with airway obstruction than never smokers without obstruction. However, it did not appear as a significant independent predictor in the multivariable logistic model, possibly because of the widely differing prevalences of TB in the BOLD study sites.
COPD can be associated with a progressive loss of skeletal muscle mass; low BMI is an independent predictor of the risk of death.45 In our study, increased odds of GOLD stage were seen in ≥ 10 men and women from the never-smoker population with low BMI (< 20 kg/m2). However, the OR estimate for men was about five times higher than for women (13.37 vs 2.57). In contrast, a high BMI (> 35 kg/m2) was associated with increased odds of GOLD stage II+ only in men. Overall, the association between BMI alterations and the presence of COPD was much more pronounced in men than women from the never-smoker group. It has been shown that a diet rich in meat and refined grains may increase the risk of COPD, whereas a diet with higher intakes of vegetables, fruits, and fish may reduce this risk.46,47 Given the cross-sectional nature of our data, we cannot discriminate whether low BMI precedes COPD or is rather a consequence of the disease.