Dietary Pattern, Sputum DNA Methylation, and Lung Health: An Epidemiological Study in People Who Ever Smoked.

Abstract

Background: We previously identified a sputum 12-gene methylation panel that predicts lung aging and risk for lung cancer.

Research question: Can the sputum methylation panel be used as a readout to derive a dietary pattern beneficial for lung health? Is this dietary pattern associated with various subjective and objective lung health phenotypes? Does this relationship vary among people who currently smoke vs previously smoked?

Study design and methods: Using the Lovelace Smoker Cohort (LSC), we employed the least absolute shrinkage and selection operator regularized Poisson regression to define a dietary pattern for sputum. Associations of the dietary pattern with objective and subjective lung health measurements were examined using generalized linear and Cox models in the LSC and the Prostate, Lung, Colorectal, and Ovarian (PLCO) Cancer Screening trial.

Results: The Dietary Pattern for Healthy Lung (DiPHeaL) includes low consumption of processed meat, and high consumption of dark green vegetables, tea, alcohol, and fruit juice. In the LSC, a higher DiPHeaL score (1 SD) was associated with better FEV₁ (by 96.1 mL/s), FEV₁/FVC ratio (by 1.83%), and respiratory quality of life (by 4.9 for activity score), and decreased cardiopulmonary mortality (by 47%) in participants who previously smoked (all P values < .05), but not in participants who currently smoke. Moreover, effect sizes of the DiPHeaL score on respiratory quality of life measures were greater among participants who previously smoked with airway obstruction compared with those without. Associations with cardiovascular and respiratory mortality were replicated in PLCO participants who previously smoked . A higher DiPHeaL score was also associated with lower lung cancer incidence in participants who previously smoked, as well as reduced COPD incidence and lung cancer mortality regardless of smoking status in the PLCO.

Interpretation: We defined a novel dietary pattern for lung epigenetic aging, which linked to lung health measurements. Participants who previously smoked, especially those with airway obstruction, may benefit the most from nutritional modification.