Chumpagern W; University Faculty of Medicine, Khon Kaen, Thailand.
Spagnolo P; Ratanawatkul P; Mohning MP; Fernandez Perez ER

BMJ open respiratory research. 13(1), 2026 Jul 09.

BACKGROUND: Ventilatory efficiency (VE) from cardiopulmonary exercise
testing (CPET) is a valuable prognostic metric for evaluating
cardiopulmonary diseases. However, its relationship with clinical outcomes
in hypersensitivity pneumonitis (HP) remains unclear. We aimed to
determine whether VE correlates with disease severity and predicts
mortality in HP.

RESEARCH QUESTION: In patients with HP, does VE correlate with disease
severity and predict mortality?

METHODS: This retrospective cohort study (2009-2019) included patients
with non-fibrotic (nfHP) and fibrotic HP (fHP) and idiopathic pulmonary
fibrosis (IPF), which served as the comparison group. CPET variables,
including VE/carbon dioxide (VE/VCO2), were assessed across various forced
vital capacity (FVC%) and diffusing capacity for carbon monoxide (DLCO%)
ranges. Multivariate logistic regression identified predictors of 5-year
mortality and survival was assessed with Kaplan-Meier plots.

RESULTS: 164 patients were analysed (mean age of 65.6+/-12.0 years, 54.3%
male). 25 had nfHP, 66 fHP and 73 IPF. Overall, an increase in the VE/VCO2
slope and nadir was observed as the DLCO% decreased, but not with a
decrease in FVC%, while the intercept remained unchanged. Patients with
pulmonary hypertension (35%, 57/164) and fHP or IPF had significantly
higher VE/VCO2 slope and nadir when compared with patients without
pulmonary hypertension or nfHP, respectively. A VE/VCO2 slope >=42
predicted survival (HR 3.65; 95% CI 1.04 to 12.80). Restricting the
analysis to patients with HP showed similar results (HR 5.49; 95% CI 1.19
to 33.54).

INTERPRETATION: In patients with HP, elevated VE/VCO2 is associated with
the presence of pulmonary fibrosis, PH, reduced DLCO and a higher
mortality risk. A VE/VCO2 slope threshold of 42 may serve as a practical
prognostic marker for stratification.