Fixed airway obstruction and bronchodilator responsiveness phenotypes in severe asthma population from SANI registry

Background: Data on asthma with fixed airway obstruction (FAO) are heterogeneous due to different and misleading definitions. Describing the FAO phenotype has significant implications for severe asthma (SA) comprehension. Objective: To characterise SA patients with FAO in the Severe Asthma Network in Italy (SANI) registry at baseline, and to compare with those with reversible airway obstruction (bronchodilator responsiveness, BDR). The potential for re-evaluating FAO or BDR in the follow-up was explored. Methods: FAO was defined as a forced expiratory volume in the first second (FEV1)/forced vital capacity ratio < Lower Limit of Normal (LNN) after a bronchodilator test with an increase in FEV1 of <12% or 200 mL, compared with BDR and no airway obstruction (no-AO). Clinical reported outcomes, including asthma control (ACT), quality of life (AQLQ) and exacerbations (AEs) were collected. The effect of demographic, clinical and biohumoral variables on FAO, BDR and no-AO groups at baseline and during the follow-up was estimated. Results: Among 354 patients, 190 (53.7%) reported AO with 116 (60.1%) resulting in FAO. The overall FAO rate at enrolment was 32.8%. Compared with BDR, FAO patients had better asthma control (34.5% vs 20.3%, p=0.004), a higher ACT (17.4 vs 15.2, p=0.005) and AQLQ (4.6 vs 3.8, p=0.001) score. FAO patients were less likely to visit the emergency room or be hospitalised than BDR (p=0.050), with no difference in AEs. The effect of airway calibre on fractional exhaled nitric oxide is more likely to cause its lower level within FAO compared with BDR (29.5 vs 46.0 ppb, p=0.04) than a lower T2 burden. A variation from FAO to BDR or no-AO was associated with the Global Initiative for Asthma classification (step 4 vs 5: HR 3.58 (95% CI 1.16 to 11.03)) and the age of asthma onset (30-39 vs <20 years: HR 3.94 (95% CI 1.09 to 14.30)) CONCLUSION: Stratifying SA patients from the SANI registry reveals an FAO phenotype that expresses different clinical outcomes and biological markers compared to BDR. Over time, FAO may be reversible in late-onset SA with less inhaled corticosteroid treatment.