Dietary pattern, sputum DNA methylation, and lung health: an epidemiological study in people who ever smoked.

Background: We previously identified a panel of sputum DNA methylation that predicts lung ageing 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 (current smoker) versus previously smoked (former smoker)?

Study design and methods: Using the Lovelace Smoker Cohort (LSC), we employed the LASSO 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, higher DiPHeaL score (one standard deviation) 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 former smokers (all Ps<0.05), but not in current smokers. Moreover, effect sizes of the DiPHeaL score on respiratory quality of life measures were greater among former smokers with airway obstruction compared to those without. Associations with cardiovascular and respiratory mortality were replicated in PLCO former smokers. Greater DiPHeaL score was also associated with lower lung cancer incidence in former smokers, 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. Former smokers, especially those with airway obstruction, may benefit the most from nutritional modification.