Early-Life Exposure to Tobacco Smoke and the Risk of Idiopathic Pulmonary Fibrosis: A Population-Based Cohort Study
Bibliographic record
Abstract
Abstract Rationale Tobacco smoking is a well-established risk factor for idiopathic pulmonary fibrosis (IPF), yet the influence of early-life tobacco exposure on future IPF risk remains poorly understood. Objectives We sought to test the hypothesis that early-life tobacco exposure may elevate the risk of developing IPF, with this effect potentially modified by genetic susceptibility to IPF and mediated through accelerated biological aging. Methods Using data from over 430,000 participants in the UK Biobank, we performed a prospective cohort study to examine the associations of maternal smoking around birth and age of smoking initiation with IPF risk. We evaluated the combined effects and interactions between early-life tobacco exposure and genetic susceptibility to IPF, which were quantified using polygenic risk scores. We assessed biological aging, as measured by telomere length and phenotypic age, as potential mediators in the associations between early-life tobacco exposure and IPF risk. Cox proportional hazards models were used to estimate hazard ratios (HRs) and 95% confidence intervals (CIs). Results Maternal smoking around birth was associated with a higher risk of IPF (HR = 1.26; 95% CI = 1.11–1.43). Compared with never-smokers, individuals who initiated smoking in childhood (HR = 3.65; 95% CI = 3.02–4.41), adolescence (HR = 2.64; 95% CI = 2.28–3.05), and adulthood (HR = 2.09; 95% CI = 1.79–2.44) exhibited increased IPF risk (P for trend <0.001). An additive interaction was observed between age of smoking initiation and genetic risk for IPF. Individuals with high genetic risk, maternal smoking exposure, and childhood smoking initiation had a 16-fold greater risk of IPF (HR = 16.47; 95% CI = 9.57–28.32), compared with those with low genetic risk and no tobacco exposure. Telomere length and phenotypic age each mediated approximately 10% of the effect of maternal smoking on IPF, with weaker mediation effects observed for later ages of smoking initiation. Conclusions Early-life tobacco exposure may elevate the risk of IPF, with effects modified by genetic susceptibility and partially mediated through accelerated biological aging.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.002 | 0.002 |
| Meta-epidemiology (narrow) | 0.000 | 0.001 |
| Meta-epidemiology (broad) | 0.000 | 0.001 |
| Bibliometrics | 0.001 | 0.001 |
| Science and technology studies | 0.001 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".