Airway hyperresponsiveness to mannitol improves in both type 2 high and type 2 low asthma after specialist management

Type 2 low (T2-low) asthma is reported to respond less to anti-inflammatory treatment compared with Type 2 high (T2-high) asthma. Airway hyperresponsiveness (AHR) to mannitol, a marker of airway mast cell activation, may be indicative of response to treatment in patients with T2-low disease. We investigated whether AHR to mannitol improves in patients with T2-low asthma after specialist management.

Patients with asthma or suspected asthma, referred to our specialist outpatient clinic, were enrolled consecutively and assessed with FeNO, asthma control, blood eosinophils, mannitol and methacholine tests and induced sputum. T2-low asthma was defined in patients with FeNO < 25ppb and sputum eosinophils < 3% and blood eosinophils < 300µl^-1 at inclusion. Patients with asthma and AHR to mannitol (PD15 ≤ 635 mg) were followed and reassessed after 12 months of specialist management.

Thirty-two patients (Females: 56%, age: 22 years (15-59)) were followed. Fourteen (44%) with T2-high and 18 (56%) with T2-low asthma. Baseline AHR to mannitol was comparable: G_mean PD15: 150 mg (95% CI 61-368) and 214 mg (95% CI 106-432) for T2-high and T2-low asthma respectively (P = 0.51). Both groups improved equally: G_mean PD15: 488 mg (95% CI 311-767) and 507 mg (95% CI 345-746); corresponding to a doubling-dose of: 3.00 (95% CI 1.58-5.74, P = 0.003) and 2.28 (95% CI 1.47-3.53, P = 0.001) respectively. There were no concomitant improvements in AHR to methacholine.

Patients with asthma and AHR to mannitol improve similarly in responsiveness to mannitol after 12 months of specialist management regardless of Type 2 inflammatory biomarker levels. Mechanisms driving AHR in T2-low asthma need to be further elucidated.