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Original research
Airflow limitation and mortality during cancer screening in the National Lung Screening Trial: why quantifying airflow limitation matters
  1. Robert P Young1,
  2. Ralph C Ward2,
  3. Raewyn J Scott1,
  4. Greg D Gamble1,
  5. Gerard Silvestri2
  1. 1The University of Auckland Faculty of Medical and Health Sciences, Auckland, New Zealand
  2. 2Medical University of South Carolina, Charleston, South Carolina, USA
  1. Correspondence to Dr Robert P Young, The University of Auckland Faculty of Medical and Health Sciences, Auckland, Auckland, New Zealand; roberty{at}adhb.govt.nz

Abstract

Importance Current eligibility criteria for lung cancer (LC) screening are derived from randomised controlled trials and primarily based on age and smoking history. However, the individual benefits of screening are highly variable and potentially attenuated by co-morbidities such as advanced airflow limitation (AL).

Objective To examine the relationship between the presence and severity of AL and screening outcomes.

Methods This was a secondary analysis of 18 463 high-risk smokers, a substudy from the National Lung Screening Trial, who underwent pre-bronchodilator spirometry at baseline and median follow-up of 6.1 years. We used descriptive statistics and a competing risk proportional hazards model to examine differences in screening outcomes by chronic obstructive pulmonary disease severity group.

Results The risk of developing LC increased with worsening AL (effect size=0.34, p<0.0001), as did the risk of dying of LC (effect size=0.35, p<0.0001). While those with severe AL (Global Initiative for Obstructive Lung Disease, GOLD grade 3–4) had the highest risk of LC and the highest LC mortality, they also had fewer adenocarcinomas (effect size=−0.20, p=0.008) and a lower surgery rate (effect size=−0.16, p=0.014) despite comparable staging, and greater non-LC mortality relative to LC mortality (effect size=0.30, p<0.0001). In participants with no AL, screening with CT was associated with a significant reduction in LC deaths relative to chest X-ray (30.3%, 95% CI 4.5% to 49.2%, p<0.05). The clinically relevant but attenuated reduction in those with AL (18.5%, 95% CI −8.4% to 38.7%, p>0.05) could be attributed to GOLD 3–4, where no appreciable mortality reduction was observed.

Conclusion Despite a greater risk of LC, severe AL was not associated with any apparent reduction in LC mortality following screening.

  • Lung Cancer
  • COPD epidemiology

Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Data availability statement

All data relevant to the study are included in the article or uploaded as online supplemental information.

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Footnotes

  • Contributors RPY and RJS contributed to the conception and design; acquisition, analysis and interpretation; drafting and review for important intellectual content and final approval of the manuscript. GS contributed to the analysis and interpretation; drafting and review for important intellectual content and final approval of the manuscript. RCW and GDG contributed to bio statistical analysis, drafting, review and final approval of the manuscript.

  • Funding The authors have not declared a specific grant for this research from any funding agency in the public, commercial or not-for-profit sectors.

  • Competing interests None declared.

  • Provenance and peer review Not commissioned; externally peer reviewed.

  • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.