Characteristics and outcomes of chronic obstructive pulmonary disease in never smokers in Denmark: a prospective population study

doi:10.1016/S2213-2600(13)70137-1

The Lancet Respiratory Medicine

Volume 1, Issue 7, September 2013, Pages 543-550

https://doi.org/10.1016/S2213-2600(13)70137-1 Get rights and content

Summary

Background

A substantial proportion of patients with chronic obstructive pulmonary disease (COPD) have never smoked. We tested the hypothesis that, in individuals with COPD, never smokers have different characteristics and less severe outcomes of the disease than smokers do.

Methods

We included individuals from the Copenhagen General Population Study, a prospective population study. We identified individuals with COPD spirometrically; that is, as the ratio between forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) under the lower limit of normal (LLN), excluding individuals with self-reported asthma. We examined general characteristics, symptoms, disease severity, and levels of inflammatory biomarkers and α1-antitrypsin at baseline. We assessed risk of lung-related hospital admissions, cardiovascular comorbidities, and all-cause mortality during a median follow-up of 4 years (IQR 2·5–5·6).

Findings

Between Nov 26, 2003, and July 29, 2010, 68 501 participants from the Copenhagen General Population Study had lung function measurements and complete information on smoking habits available. Of those, we identified 6623 with COPD and no asthma. Of these, 1476 (22%) were never smokers, 2696 (41%) former smokers, and 2451 (37%) current smokers. For comparison we included 24 529 never smokers without COPD. Never smokers with COPD had different clinical characteristics, fewer symptoms, milder disease, and lower levels of inflammatory biomarkers than did current and former smokers with COPD. During follow-up, HRs for hospital admission due to COPD were 8·6 (95% CI 5·3–14) in never smokers, 30 (22–41) in former smokers, and 43 (32–59) in current smokers compared with never smokers without COPD. HRs for hospital admission due to pneumonia were 1·9 (1·4–2·6) in never smokers, 2·8 (2·3–3·4) in former smokers, and 3·4 (2·9–4·2) in current smokers. For hospital admission due to lung cancer, HRs were 11 (5·7–23) in former smokers and 18 (9·2–35) in current smokers, whereas no cases were noted in never smokers. Furthermore, risk of cardiovascular comorbidities and all-cause mortality was increased in former and current smokers but not in never smokers with COPD.

Interpretation

Compared with current and former smokers, never smokers with COPD had different characteristics and milder disease, limited to the lungs. However, morbidity due to lung-related hospital admissions was nonetheless substantial in never smokers with COPD.

Funding

Herlev Hospital, Copenhagen University Hospital, Copenhagen County Foundation, and University of Copenhagen.

Introduction

Smoking is the single most important risk factor for chronic obstructive pulmonary disease (COPD). Consequently, previous research has mainly focused on smokers¹ and trials normally exclude participants without a 10 pack-year history. However, a substantial proportion of patients with COPD have never smoked2, 3, 4 indicating that other exposures must be important. Outdoor air pollution, passive smoking, occupational dust, early-life events, and biomass fuel exposure have previously been suggested as additional risk factors for COPD.5, 6, 7, 8, 9 However, concurrent cigarette smoking in most populations studied has precluded accurate characterisation of these potential risk factors. Furthermore, studies examining severity of lung function impairment, prevalence of comorbidities, and mortality in never smokers with COPD compared with former and current smokers are scarce or do not exist.¹ Thus, definitive conclusions regarding characteristics and clinical outcomes of COPD in never smokers have not yet been made.

We tested the hypothesis that in individuals with COPD, never smokers have different characteristics and less severe outcomes of the disease than smokers do. For this purpose, we examined participants from the Copenhagen General Population Study and identified individuals with COPD, excluding those with self-reported asthma. We examined characteristics, symptoms, disease severity, and levels of inflammatory biomarkers and α₁-antitrypsin in never smokers, former smokers, and current smokers with COPD at baseline and estimated risk of lung-related hospital admissions, cardiovascular comorbidities, and all-cause mortality in prospective analyses.

Section snippets

Study design and participants

We included in the study individuals from the Copenhagen General Population Study, an ongoing prospective population study initiated in 2003. Individuals were randomly selected on the basis of the national Danish Civil Registration System, with an age restriction of 20–100 years. We identified individuals with COPD spirometrically; that is, as the ratio between forced expiratory volume in 1 s (FEV₁) and forced vital capacity (FVC) under the lower limit of normal (LLN), excluding individuals

Results

Between Nov 26, 2003, and July 29, 2010, 68 501 participants had lung function measurements and complete information on smoking habits available. After excluding 4154 individuals with self-reported asthma, 6623 participants had COPD defined by spirometry. Of these, 1476 (22%) were never smokers, 2696 (41%) former smokers, and 2451 (37%) current smokers (figure 1). For comparison, we included 24 529 never smokers without COPD.

More never smokers with COPD than never smokers without COPD had a

Discussion

In this study, we noted that never smokers with COPD had different characteristics and milder disease limited to the lungs than did current and former smokers with COPD. However, morbidity due to lung-related hospital admissions was nonetheless substantial in never smokers with COPD. These findings are novel.

The only potential risk factor for COPD identified in never smokers was a familial disposition for asthma, which was also apparent in former and current smokers. This might reflect a common

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ArticlesCharacteristics and outcomes of chronic obstructive pulmonary disease in never smokers in Denmark: a prospective population study

Summary

Background

Methods

Findings

Interpretation

Funding

Introduction

Section snippets

Study design and participants

Results

Discussion

Lancet

Chest

Am J Med

Chest

Lancet

Respir Med

Lancet

Br J Dis Chest

J Clin Epidemiol

Chest

Lancet

Occupational exposures and the risk of COPD: dusty trades revisited

Thorax

Reduced exposure to PM10 and attenuated age-related decline in lung function

N Engl J Med

An official American Thoracic Society public policy statement: Novel risk factors and the global burden of chronic obstructive pulmonary disease

Am J Respir Crit Care Med

Early life origins of chronic obstructive pulmonary disease

Thorax

Articles
Characteristics and outcomes of chronic obstructive pulmonary disease in never smokers in Denmark: a prospective population study