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Rationale  Gastroesophageal reflux disease (GERD) is a common comorbidity in chronic obstructive pulmonary disease (COPD) and has been associated with increased risk of acute exacerbations, hospitalization, emergency room visits, costs, and quality-of-life impairment. However, it remains unclear whether GERD contributes to the progression of COPD as measured by lung function or computed tomography.    Objective  To determine the impact of GERD on longitudinal changes in lung function and radiographic lung disease in the COPDGene cohort.    Methods  We evaluated 5728 participants in the COPDGene cohort who completed Phase I (baseline) and Phase II (5-year follow-up) visits. GERD status was based on participant-reported physician diagnoses. We evaluated associations between GERD and annualized changes in lung function [forced expired volume in 1 s (FEV 1 ) and forced vital capacity (FVC)] and quantitative computed tomography (QCT) metrics of airway disease and emphysema using multivariable regression models. These associations were further evaluated in the setting of GERD treatment with proton-pump inhibitors (PPI) and/or histamine-receptor 2 blockers (H 2  blockers).    Results  GERD was reported by 2101 (36.7%) participants at either Phase I and/or Phase II. GERD was not associated with significant differences in slopes of FEV 1  (difference of − 2.53 mL/year; 95% confidence interval (CI), − 5.43 to 0.37) or FVC (difference of − 3.05 mL/year; 95% CI, − 7.29 to 1.19), but the odds of rapid FEV 1  decline of ≥40 mL/year was higher in those with GERD (adjusted odds ratio (OR) 1.20; 95%CI, 1.07 to 1.35). Participants with GERD had increased progression of QCT-measured air trapping (0.159%/year; 95% CI, 0.054 to 0.264), but not other QCT metrics such as airway wall area/thickness or emphysema. Among those with GERD, use of PPI and/or H 2  blockers was associated with faster decline in FEV 1  (difference of − 6.61 mL/year; 95% CI, − 11.9 to − 1.36) and FVC (difference of − 9.26 mL/year; 95% CI, − 17.2 to − 1.28).    Conclusions  GERD was associated with faster COPD disease progression as measured by rapid FEV 1  decline and QCT-measured air trapping, but not by slopes of lung function. The magnitude of the differences was clinically small, but given the high prevalence of GERD, further investigation is warranted to understand the potential disease-modifying role of GERD in COPD pathogenesis and progression.    Clinical trials registration   NCT00608764 .

Impact of gastroesophageal reflux on longitudinal lung function and quantitative computed tomography in the COPDGene cohort