BackgroundOccupational exposure to pesticides has been associated with lung and cognitive function exacerbations. In the present study, we tested the effectiveness of breathing focused yoga intervention on alleviation of adverse respiratory and cognitive effects associated with chronic pesticide exposure in farmers.MethodsWe undertook a parallel, two-armed randomized controlled trial with blinded outcome assessors on a chronically pesticide-exposed farming population. The study was conducted at district Panipat, State Haryana located in the Northern part of India from November 2019 to August 2020. A total of 634 farmers were screened, and 140 farmers were randomized to breathing-focused yoga intervention (BFY, n = 70) and waitlist control arms (n = 65). BFY was delivered weekly in 45-min group sessions over 12 weeks followed by home-based practice. The primary outcome was the change in spirometry-based markers of pulmonary function from baseline expressed as raw values, Global Lung Initiative (GLI) percent predicted (pp), and GLI z-scores after 24 weeks of intervention. Secondary variables were Trail making tests (TMT A and B), Digit symbol substitution (DSST), and WHO Quality of life-BREF (WHOQOL-Bref). Analysis was by intention-to-treat. Mediation analysis was done considering oxidative stress markers as potential mediators.ResultsAt the end of 6 months of intervention, the overall follow-up in the participants was 87.85% (n = 123); 90% (n = 63) in the control group, and 85.71% in the yoga group (n = 60). The mean age of the study cohort (n = 140) was 38.75 (SD = 7.50) years. Compared with the control group, at 24 weeks post-intervention, the BFY group had significantly improved status of the raw sand z scores markers of airway obstruction, after adjusting for confounders, FEV1, FVC, FEF25-75 [z score-adjusted mean differences (95% CI); 1.66 (1.10–2.21) 1.88 (1.21–2.55), and 6.85 (5.12–8.57), respectively. A fraction of FEF25-75 change (mediation percentage 23.95%) was explained by glutathione augmentation. There were also significant improvements in cognitive scores of DSST, TMT-A and TMT-B, and WHOQOL-Bref.ConclusionIn conclusion, regular practice of BFY could improve the exacerbations in the markers of airway obstruction in chronically pesticide-exposed farmers and cognitive variables. A significant mediating effect of glutathione augmentation was also observed concerning the effect of the intervention on FEF25-75. These findings provide an important piece of beneficial evidence of the breathing-based yoga intervention that needs validation across different farming ethnicities.Clinical Trial Registration:www.ClinicalTrials.gov, identifier: CTRI/2019/11/021989.