Post hoc analysis of a combined cohort from two clinical trials evaluating the relationship between bronchodilator reversibility (BDR) to salbutamol and mannitol airway hyperresponsiveness (AHR, defined as PD10 FEV1 < 635 mg) in 37 adults with severe, uncontrolled asthma prior to starting biologics.
No significant correlation was found between mannitol PD10 and BDR by any measure — FEV1 (absolute r = −0.137, % predicted r = 0.040), small airway indices (FEF25-75, AX, R5-R20), or across T2 biomarker subgroups (FeNO ≥/< 50 ppb; eosinophils ≥/< 500 cells/µL). The lack of correlation was consistent regardless of BDR threshold applied (>5%, >10%, ≥12%).
- Small, single-centre cohort (n=37) limits generalisability. - Retrospective analysis; patients were on high-dose ICS/LABA (mean beclomethasone-equivalent 1720 µg/day), which may have influenced both BDR and AHR despite standardised pre-test withholding. - Only indirect (mannitol) challenge was used; direct challenge (methacholine) would more closely reflect airway smooth muscle function.
In severe, uncontrolled asthma, BDR and mannitol AHR measure distinct physiological processes and cannot substitute for one another — both should be included in a full functional assessment alongside T2 biomarkers and symptom burden.
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