Associations of prior lung diseases on risk of lung cancer in populations with no smoking history: A systematic review and meta-analysis.
Authors: Swami Nishwant , Hong Ji Hyung , Kho Sooyeon , Kang Haemin , Lin Laura , Ni Shy , Dee Edward Christopher Christopher , Florez Narjust , Gomez Scarlett L. , Cheng Iona 
Published: June 2024

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Background: Individuals without prior tobacco use account for a growing proportion of lung cancer cases, but the impact of prior lung diseases on lung cancer risk in this population remains unclear. We performed a meta-analysis of studies examining the association of prior lung diseases – tuberculosis (TB), asthma (AS), and chronic bronchitis (CB) – with lung cancer risk among individuals without prior tobacco use. Methods: PubMed and Embase were searched from inception to Jan 20th, 2024 for studies examining the association between TB, AS, and/or CB and lung cancer risk in populations over 18 years old who never smoke. Studies were excluded if (1) “never-smoking” was not defined as having never smoked or smoked less than 100 cigarettes in their lifetime; (2) they were not written in English, Mandarin, or Korean; (2) odds ratios (OR)/hazard ratios (HR) were not reported. Summary effect estimates with 95% CI were calculated for case-control (summary OR) and cohort (summary HR) studies using random effects models with inverse variance weighting. Subgroup meta-analyses and meta-regressions were conducted among case-control studies by continent [Asia vs. non-Asia (North America and Europe)]. There was insufficient information to examine differences across the subgroups of sex and race and ethnicity. Results: 17 case-control studies and five cohort studies were examined. Among case-control studies, history of TB (13 studies), AS (10 studies), and CB (nine studies) were statistically significantly associated with an increased risk of lung cancer in patients without prior tobacco use (TB: summary OR=1.75, 95% CI 1.43-2.15, I2 = 29; AS: summary OR=1.46, 95% CI 1.06-2.02, I2 = 34; CB: summary OR=1.36, 95% CI 1.07-1.72, I2 = 0). Among cohort studies, TB (four studies) was associated with a statistically significant increase in lung cancer risk (summary HR=1.81, 95% CI 1.34-2.44, I2 = 44). There were insufficient number of cohort studies to summarize the associations of CB (no studies) or AS (one study) with lung cancer risk. The summary OR for TB and AS with lung cancer risk was larger in Asian vs. non-Asian populations (TB: Asian populations summary OR=1.79 95% CI 1.40-2.28, I2 = 47 vs. non-Asian populations summary OR=1.47 95% CI 0.88-2.44, I2 = 0; AS: Asian populations summary OR=2.63 95% CI 1.10-6.28, I2 = 40 vs. non-Asian populations summary OR=1.31 95% CI 0.96-1.79, I2 = 20). However, there was no evidence of heterogeneity in summary OR by continent using meta-regression (TB: p=0.58; AS: p=0.16). Conclusions: In this meta-analysis, history of TB, AS, and CB were associated with lung cancer risk among populations who never smoked, informing potential etiologies of the shifting global burden of lung cancer. Future studies examining these associations should analyze more diverse patient populations and disaggregate findings by sex, race and ethnicity, socioeconomic status, and geography.