Elsevier

The Lancet

Volume 374, Issue 9691, 29 August–4 September 2009, Pages 733-743
The Lancet

Review
Chronic obstructive pulmonary disease in non-smokers

https://doi.org/10.1016/S0140-6736(09)61303-9Get rights and content

Summary

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Tobacco smoking is established as a major risk factor, but emerging evidence suggests that other risk factors are important, especially in developing countries. An estimated 25–45% of patients with COPD have never smoked; the burden of non-smoking COPD is therefore much higher than previously believed. About 3 billion people, half the worldwide population, are exposed to smoke from biomass fuel compared with 1·01 billion people who smoke tobacco, which suggests that exposure to biomass smoke might be the biggest risk factor for COPD globally. We review the evidence for the association of COPD with biomass fuel, occupational exposure to dusts and gases, history of pulmonary tuberculosis, chronic asthma, respiratory-tract infections during childhood, outdoor air pollution, and poor socioeconomic status.

Introduction

Chronic obstructive pulmonary disease (COPD) is characterised by progressive airflow obstruction and destruction of lung parenchyma, and is caused by chronic exposure of genetically susceptible individuals to environmental factors. Tobacco smoking was associated with risk of COPD as early as the 1950s;1, 2 smoking was established as a causative risk factor by the findings of Fletcher and Peto's3 8-year prospective study of 792 men, and the larger and longer Framingham cohort offspring study confirmed these results.4 Consequently, later research has focused on smoking as the most important risk factor for COPD; several prevalence studies have been done solely in smokers,5, 6 and most clinical trials in COPD recruit only smokers with at least 20 pack-years of cigarette smoking exposure.

However, in the past decade and especially the past 5 years, results from a growing number of published studies have suggested that risk factors other than smoking are strongly associated with COPD. These factors include exposure to indoor and outdoor air pollutants, workplace exposure to dust and fumes, history of repeated lower respiratory-tract infections during childhood, history of pulmonary tuberculosis, chronic asthma, intrauterine growth retardation, poor nourishment, and poor socioeconomic status.

Section snippets

Evidence of COPD in non-smokers

Phillips7 reported that risk factors other than tobacco smoking were associated with COPD in 1963, and previously Fairbairn8 had reported that outdoor air pollution was an important risk factor. Overwhelming interest in smoking as the major risk factor has overshadowed the importance of non-smoking causes. However, Husman and colleagues9 associated occupation with COPD in 1987 in their 6-year study of Finnish farmers and non-farmers, which showed that a higher proportion of farmers (2·7%) than

Use of biomass fuel

Worldwide, about 50% of all households and 90% of rural households use biomass fuel (wood, charcoal, other vegetable matter, and animal dung) and coal as their main source of domestic energy. About 3 billion people worldwide are exposed to smoke from biomass fuel compared with 1·01 billion people who smoke tobacco, suggesting that exposure to biomass smoke might be the most important global risk factor for COPD.34 About 50% of deaths from COPD in developing countries are attributable to biomass

Occupational exposures

Findings from early studies reported that exposure to toxic gases in the workplace,65 grain dust in farms,66 and dust and fumes in factories67 was strongly associated with COPD. In 2003, results of a systematic epidemiological review into occupational factors associated with COPD by the American Thoracic Society showed that about 15% of COPD cases might be attributable to workplace exposure;68 and a subsequent follow-up provided similar estimates.69

In a study of 1258 adults older than 40 years,

Pulmonary tuberculosis

Pulmonary tuberculosis is associated with chronic airflow obstruction, especially the COPD phenotype, at diagnosis,78, 79 during treatment,80 and several years after treatment has ended.81 Such infection is associated with airway fibrosis, and the immune response to mycobacteria can result in airway inflammation, which is characteristic of COPD. The degree of airflow obstruction is correlated with the extent of disease assessed by radiography, sputum production, and length of time after

Chronic asthma

In 1961, Orie and colleagues85 postulated that asthma and COPD share a common background, and differentiation into each disease can be modulated by environmental and host factors. Although this hypothesis is unresolved,86 chronic airway inflammation and airflow obstruction in individuals with asthma and increased airway hyper-responsiveness might cause lung remodelling from thickening and fibrosis of the airway walls.87 This remodelling could result in irreversible and progressive airflow

Outdoor air pollution

The contribution of outdoor air pollution to COPD was investigated in 1958 in UK postmen—the prevalence of COPD was higher in those working in more polluted areas than in those working in areas with less pollution, and the association was independent of smoking.8 Results of a later study showed reduced lung function in postmen who worked in more polluted cities than in those who worked in less polluted areas.94 These findings have been reinforced by studies in the general population in the UK95

Socioeconomic status

Poor socioeconomic status is a risk factor independently associated with COPD, and is likely to be indicative of other factors such as intrauterine growth retardation, poor nutrition (low intake of antioxidants) and housing conditions, childhood respiratory-tract infections, and exposure to tobacco smoke, biomass smoke and other indoor air pollutants, and occupational risks. These factors might collectively contribute to the risk of COPD. Socioeconomic status has been shown to have a

Population-attributable risk factors

Non-smoking causes of COPD were conventionally estimated to contribute to a small proportion—10–15%—of cases in developed countries, but results of later studies suggest that the true contribution is much higher. Findings from the Swedish OLIN103 and US NHANES III104 studies reported that the population-attributable risk of COPD from smoking was 45% and 44%, respectively, indicating that more than half of COPD cases were due to non-smoking causes. In the BOLD study105 of the prevalence of COPD

Does COPD in never-smokers have a different phenotype?

Very few studies have investigated the non-smoking phenotype of COPD or made comparisons with the smoking phenotype. Ramírez-Venegas and colleagues106 reported that Mexican women who had COPD and had been exposed to smoke from biomass fuel, had similar clinical characteristics, quality of life, and mortality to those with COPD due to tobacco smoking. However, Shavelle and co-workers107 showed that in US patients with COPD the reduction in life expectancy was less for those who had never smoked

Future directions

Little research has been done into the interaction of risk factors for COPD. The burden of COPD is increasing, especially in developing countries, because of increased cigarette smoking and passive smoke exposure, and also exposure to non-smoking risk factors. Several questions need to be addressed. What is the true burden of non-smoking COPD in different countries? Does non-smoking COPD have the same prognosis, the same radiographic and physiological features, and manifest with the same

Search strategy and selection criteria

We searched PubMed (January, 1995–July, 2009) using the search terms “COPD and prevalence”, “COPD and risk factors”, “COPD and occupation”, “COPD and air pollution”, “COPD and tuberculosis”, and “COPD and respiratory-tract infection”. We focused on reports published in the past 5 years, but did not exclude frequently referenced and highly regarded reports published more than 5 years ago. We also searched reference lists of reports identified by this search strategy and selected those we

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