Prognostic Significance of Ventilatory Efficiency in Hypersensitivity Pneumonitis

BackgroundVentilatory efficiency, measured by a cardiopulmonary exercise testing, is an important metric for evaluating cardiopulmonary diseases. However, its relationship with clinical outcomes in hypersensitivity pneumonitis remains unclear. ObjectiveTo determine if ventilatory efficiency correlates with various stages of severity and predicts mortality in HP. Study Design and MethodsWe conducted a retrospective cohort study from 2009 to 2019 involving patients with non-fibrotic (nfHP) and fibrotic HP (fHP), and idiopathic pulmonary fibrosis (IPF), which served as the comparison group. CPET variables, including ventilatory efficiency (slope and intercept from the linear regression model of ventilation (VE) vs. carbon dioxide output (VCO2) and the nadir ratio), were assessed across various forced vital capacity (FVC%) and diffusing capacity for carbon monoxide (DLCO%) ranges. We used a multivariate logistic regression model to identify predictors of five-year mortality and Kaplan-Meier plots to assess survival. Results164 patients were analyzed, with a mean age of 65.6{+/-}12.0 years and 54.3% male. Twenty-five (15.2%) had nfHP, 66 (40.2%) fHP, and 73 (44.5%) IPF. Overall, an increase in the VE/VCO2 slope and nadir was observed as the DLCO% decreased, but there was no significant change with a decrease in FVC%, while the intercept remained unchanged. Patients with pulmonary hypertension (35%, 57/164) and fHP or IPF had significantly elevated VE/VCO2 slope and nadir when compared to patients without pulmonary hypertension or nfHP, respectively. A VE/VCO2 slope [≥]42 (AUC 0.67; 95% CI 0.53-0.82) was identified as a predictor for survival (HR 3.65; 95% CI, 1.04-12.80). Restricting the analysis to patients with HP showed similar results (HR 5.49; 95% CI, 1.19 - 33.54). InterpretationIn patients with HP, VE/VCO2 was associated with the presence of pulmonary fibrosis, PH, reduced DLCO, and a higher mortality risk. A VE/VCO2 slope threshold of 42 may be a useful prognostic marker for stratifying patients into low-risk and high-risk groups.