Targeted metabolomic analysis of exhaled breath condensate before and after bronchial provocation by eucapnic voluntary hyperventilation in adolescents with asthma: an exploratory study.

OBJECTIVE

To analyze endogenous metabolites in exhaled breath condensate before and after eucapnic voluntary hyperventilation (EVH) in adolescents with asthma with and without exercise-induced bronchoconstriction (EIB).

METHODS

This was an exploratory study including 44 adolescents with asthma in the 10- to 20-year age bracket. They were divided into two groups: the group of patients with EIB (n = 25) and that of those without (n = 19). EIB was defined as a ≥ 10% reduction in FEV1 after a six-minute EVH challenge using 5% carbon dioxide. Ventilation was maintained at 21 times the baseline FEV1. Exhaled breath condensate was collected before EVH and 15-30 min after EVH by using a validated device. Samples were analyzed by proton nuclear magnetic resonance focusing on the region of d1.60-2.00 parts per million. Data were preprocessed by using sum normalization and autoscaling for orthogonal partial least squares discriminant analysis.

RESULTS

All participants completed the protocol without adverse events. The mean reduction in FEV1 was significantly greater in the group of patients with EIB than in that of those without (-25.13% vs. -4.37%; mean difference, -20.76%; 95% CI, -26.45 to -15.07). In the EIB group, responses were classified as mild (n = 15), moderate (n = 9), or severe (n = 1). Post-EVH orthogonal partial least squares discriminant analysis showed significant separation between pre- and post-EVH metabolic profiles in the group of patients with EIB (p < 0.001) but not in that of those without (p = 0.195). The discriminative response in patients with EIB was associated with a marked increase in acetate signal intensity at 1.76 parts per million.

CONCLUSIONS

Adolescents with EIB show a distinct metabolic fingerprint that is significantly associated with ventilatory stress. Acetate emerged as a key metabolic differentiator, suggesting a specific biochemical pathway associated with the exercise response and supporting its potential role in precision phenotyping of EIB.