Airflow Limitation Increases Lung Cancer Risk in Smokers: The Lifelines Cohort Study

Our plain-English summary of Airflow Limitation Increases Lung Cancer Risk in Smokers: The Lifelines Cohort Study, by Y. Du, G. Sidorenkov, H.J.M. Groen, et al (Cancer Epidemiology, Biomarkers & Prevention, 2022).

The study

• Authors: Y. Du, G. Sidorenkov, H.J.M. Groen, M.A. Heuvelmans, R. Vliegenthart, M.D. Dorrius, W. Timens, G.H. de Bock
• Journal: Cancer Epidemiology, Biomarkers & Prevention
• Published: 2022;31(7):1442-1449
• Cited by: 8 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Background: The relationship between smoking, airflow limitation, and lung cancer occurrence is unclear. This study aims to evaluate the relationship between airflow limitation and lung cancer, and the effect modification by smoking status.

Methods: We included participants with spirometry data from Lifelines, a population-based cohort study from the Northern Netherlands. Airflow limitation was defined as FEV1/FVC ratio < 0.7. The presence of pathology-confirmed primary lung cancer during a median follow-up of 9.5 years was collected. The Cox regression model was used and hazard ratios (HR) with 95% confidence interval (95% CI) were reported. Adjusted confounders included age, sex, educational level, smoking, passive smoking, asthma status and asbestos exposure. The effect modification by smoking status was investigated by estimating the relative excess risk due to interaction (RERI) and the ratio of HRs with 95% CI.

Results: Out of 98,630 participants, 14,200 (14.4%) had airflow limitation. In participants with and without airflow limitation, lung cancer incidence was 0.8% and 0.2%, respectively. The adjusted HR between airflow limitation and lung cancer risk was 1.7 (1.4-2.3). The association between airflow limitation and lung cancer differed by smoking status [former smokers: 2.1 (1.4-3.2), current smokers: 2.2 (1.5-3.2)] and never smokers [0.9 (0.4-2.1)]. The RERI and ratio of HRs was 2.1 (0.7-3.4) and 2.5 (1.0-6.5) for former smokers, and 4.6 (95% CI, 1.8-7.4) and 2.5 (95% CI, 1.0-6.3) for current smokers, respectively.

Conclusions: Airflow limitation increases lung cancer risk and this association is modified by smoking status.

Impact: Ever smokers with airflow limitation are an important target group for the prevention of lung cancer.

©2022 The Authors; Published by the American Association for Cancer Research.

In plain English

This population-based cohort study used data from Lifelines, a cohort in the Northern Netherlands. It asked whether airflow limitation, a breathing-test result defined as an FEV1/FVC ratio below 0.7, was linked to later lung cancer. It was not mainly a study of asbestos. Asbestos exposure, estimated from self-reported occupation using a job-exposure matrix, was one of several adjusted factors, and no separate lung cancer risk estimate for asbestos exposure was reported. Of 98,630 adults, 14,200 had airflow limitation. Over a median 9.5 years, lung cancer was diagnosed in 0.8% (112/14,200) of those with airflow limitation and 0.2% (159/84,430) of those without. The adjusted hazard ratio was 1.7 (95% CI 1.4–2.3), and it was higher with more severe airflow limitation. The hazard ratio was 2.1 (1.4–3.2) in former smokers and 2.2 (1.5–3.2) in current smokers. In never smokers it was 0.9 (0.4–2.1), not statistically significant, with only six cases among never smokers with airflow limitation. The authors concluded that airflow limitation was associated with increased lung cancer risk, more pronounced in smokers, even former smokers, than in never smokers. They noted that unmeasured confounding could affect the results.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Population-based cohort study (Lifelines), using Cox regression with age as the time scale
• Who was studied: 98,630 adults (18 years and older) with valid spirometry at baseline, recruited 2006 to 2013 in the three northern provinces of the Netherlands. Follow-up was a median of 9.5 years, with pathology registry linkage up to January 26, 2021. Of these, 20,849 were current smokers and 32,351 were former smokers.
• Exposure: The main exposure was airflow limitation at baseline, defined as an FEV1/FVC ratio below 0.7 on pre-bronchodilator spirometry, graded by severity (GOLD criteria). Asbestos exposure was not the exposure studied. It was a covariate assigned from self-reported occupation using the International Job Exposure Matrix for Asbestos. No fiber types were specified.
• Main results:
  • Lung cancer incidence was 0.8% (112/14,200) in participants with airflow limitation and 0.2% (159/84,430) in those without.
  • In the entire cohort, after adjustment for smoking and other covariates (including asbestos exposure), the hazard ratio for airflow limitation and lung cancer was 1.7 (95% CI, 1.4–2.3).
  • By severity, hazard ratios were 1.5 (95% CI, 1.1–2.1) for mild, 2.1 (95% CI, 1.5–2.9) for moderate and 3.7 (95% CI, 1.6–8.5) for severe airflow limitation (p for trend less than 0.001). The severe group had only 6 lung cancer cases among 219 participants.
  • Airflow limitation was associated with adenocarcinoma (HR 1.8; 95% CI, 1.2–2.5) and squamous cell carcinoma (HR 2.3; 95% CI, 1.4–4.0). The hazard ratio for small cell lung carcinoma was 1.0 (95% CI, 0.4–2.3).
  • In the subset meeting lung cancer screening criteria (n = 4,009), the adjusted hazard ratio was 2.0 (95% CI, 1.2–3.3).
  • By smoking status, hazard ratios for airflow limitation were 0.9 (95% CI, 0.4–2.1) in never smokers, 2.1 (95% CI, 1.4–3.2) in former smokers and 2.2 (95% CI, 1.5–3.2) in current smokers.
  • In never smokers the association was not statistically significant. Only six lung cancer cases occurred in never smokers with airflow limitation, compared with 37 in never smokers with normal lung function. The authors said this result should be interpreted with caution.
  • Effect modification by smoking was measured in two ways. On the additive scale, the relative excess risk due to interaction (RERI) was 2.1 (95% CI, 0.7–3.4) for former smokers and 4.6 (95% CI, 1.8–7.4) for current smokers. On the multiplicative scale, the ratio of hazard ratios was 2.5 (95% CI, 1.0–6.5) for former smokers and 2.5 (95% CI, 1.0–6.3) for current smokers.
  • In sensitivity analyses, airflow limitation defined by the lower limit of normal gave an adjusted HR of 1.7 (95% CI, 1.3–2.3). In participants aged 50 and older the adjusted HR was 1.8 (95% CI, 1.3–2.4).
  • Asbestos exposure was classified for 793 (5.6%) of the 14,200 participants with airflow limitation and 4,175 (4.9%) of the 84,430 with normal lung function. Among lung cancer cases, 5 in the airflow limitation group and 6 in the normal lung function group were classified as exposed. The article reports no separate estimate of lung cancer risk associated with asbestos exposure.
• The authors' conclusion: The authors concluded that airflow limitation is associated with an increased risk of lung cancer. They found this more pronounced in smokers, even if they stopped smoking, than in never smokers, and found it for both squamous cell carcinoma and adenocarcinoma. In the abstract the authors put it as airflow limitation 'increases' lung cancer risk.
• Limitations the authors state:
  • As an observational cohort study, other confounding factors that were not taken into account may affect the results.
  • The number of lung cancer cases in never smokers was small, which might give low statistical power.
  • All participants were treated as Caucasian when calculating reference lung function values.
  • Using a fixed cut-off to define airflow limitation may cause misclassification.

Topics

The National Library of Medicine indexes this study under subjects our site covers: Lung cancer.

Medical terms in this study, explained in our Lexicon: Lung Cancer, Cohort Study, Spirometry, FEV1/FVC Ratio, Pathology, Hazard Ratio, confidence interval, Asbestos Exposure.

Related studies

• Asbestos exposure, cigarette smoking, and airflow limitation in long-term Canadian chrysotile miners and millers — R. Bégin, R. Boileau, et al. (1987)
• Asbestos and airflow limitation — Z. Mohsenifar, A.J. Jasper, et al. (1986)
• Methylation-derived Neutrophil-to-Lymphocyte Ratio and Lung Cancer Risk in Heavy Smokers — L. Grieshober, S. Graw, et al. (2018)
• Occupational Exposure to Talc Increases the Risk of Lung Cancer: A Meta-Analysis of Occupational Cohort Studies — C.J. Chang, Y.K. Tu, et al. (2017)
• Chronic obstructive lung diseases and risk of non-small cell lung cancer in women — A.G. Schwartz, M.L. Cote, et al. (2009)
• Occupational risk factors for chronic respiratory disease in a New Zealand population using lifetime occupational history — A. Hansell, R.E. Ghosh, et al. (2014)

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