Association between smoking and prognosis in idiopathic pulmonary fibrosis: A systematic review and meta-analysis

Clinical Snapshot

Key Findings

• P Value: p-for-interaction < 0.001 for regional subgroup analysis of mortality; specific p-values for individual pooled estimates not reported in abstract

• Effect Size: Non-East Asian studies: HR 1.17 (ever vs. never smokers, mortality); East Asian studies: HR 0.75 (ever vs. never smokers, mortality); Lung cancer: HR 1.88 (current vs. non-current smokers)

• Primary Outcome: Overall mortality did not differ significantly by smoking status in the pooled analysis. However, significant regional heterogeneity was identified: ever smokers had higher mortality in non-East Asian populations but paradoxically lower mortality in East Asian populations compared with never smokers.

• Nnt Or Sensitivity: Hazard ratios are the primary effect measure. NNT cannot be calculated from the available data. No sensitivity analyses or prediction intervals reported in the abstract.

• Confidence Interval: Non-East Asian mortality: 95% CI 1.03–1.33; East Asian mortality: 95% CI 0.62–0.91; Lung cancer: 95% CI 1.24–2.87

Clinical Application

Smoking status is routinely documented in IPF clinical assessment. The lung cancer risk finding (HR 1.88 for current smokers) supports existing clinical practice of lung cancer surveillance in IPF patients who continue to smoke. Smoking cessation counselling is already standard of care and is reinforced by these findings. No new diagnostic tests or therapeutic interventions are required to implement the clinical implications of this review. In Australia, IPF is managed according to RACGP and Thoracic Society of Australia and New Zealand (TSANZ) guidelines. Antifibrotic agents pirfenidone and nintedanib are PBS-listed for IPF (PBS items 5619B and 5620C respectively), and their differential use between Australian and East Asian cohorts may contribute to the regional mortality differences observed. The TGA has approved both agents. Australian IPF registries (e.g., the Australian IPF Registry) could provide population-specific data to validate these findings in a local context. The nearly two-fold increased lung cancer risk in current smokers supports low-dose CT lung cancer screening consideration in this high-risk subgroup, consistent with emerging Australian lung cancer screening program discussions. Smoking cessation support through Quitline and NRT (PBS-subsidised) remains a priority intervention for all IPF patients who smoke. Adults with a confirmed diagnosis of IPF, particularly those with a current or prior smoking history. The regional interaction finding is most directly applicable to non-East Asian populations (including Australian, European, and North American patients), where ever-smoking is associated with modestly increased mortality risk (HR 1.17).

Abstract

BACKGROUND: Although smoking is a well-established risk factor for idiopathic pulmonary fibrosis (IPF) development, its impact on clinical outcomes remains unclear. RESEARCH QUESTION: Is smoking associated with clinical outcomes of IPF? METHODS: A systematic search of PubMed, Embase, and the Cochrane Library was conducted to identify studies reporting associations between smoking status and IPF outcomes, including mortality, acute exacerbation (AE), lung cancer development, and baseline lung function. Summary estimates with 95% confidence intervals (CIs) were pooled using random-effects model. Subgroup analyses were conducted by study region. RESULTS: Forty-nine studies comprising 32 974 patients were included. Overall mortality did not differ by smoking status. However, significant regional differences were observed, with ever smokers demonstrating higher mortality in non - East Asian studies (Hazard ratio [HR] 1.17, 95% CI: 1.03-1.33) but lower mortality in East Asian studies (HR 0.75, 95% CI: 0.62-0.91, p-for-interaction < 0.001) compared with never smokers. Current smokers had a higher risk of developing lung cancer compared with non-current smokers (HR 1.88, 95% CI: 1.24-2.87). No significant associations were observed between smoking and the risk of AEs or baseline forced vital capacity. CONCLUSION: Smoking was not associated with overall mortality in IPF, although significant regional differences were observed.

References

1. 1.Kim, K., Seok, J., & Yoon, H.-Y. (2026). Association between smoking and prognosis in idiopathic pulmonary fibrosis: A systematic review and meta-analysis. Pulmonology. https://doi.org/10.1080/25310429.2026.2693393