Collagens and airway function in severe asthma

Rationale: Severe asthmatics may develop fixed airflow obstruction, but its association with extracellular matrix deposition in the airways is not clear. We aimed to investigate collagens I, III and IV content in the airways of severe asthmatics and their relation with airway function. Methods: Sixty-two severe asthmatics received a 2-week 40 mg/day prednisone trial and 800 mcg budesonide + 24 mcg formoterol daily as maintenance therapy and 200 mcg budesonide + 6 mcg formoterol as rescue medication for 12 weeks. All patients were non or ex-smokers ≤ 10 pack-years. Patients were classified based on post-broncodilator (BD) airflow obstruction after the 2-week oral corticosteroid trial into 3 groups: non-persistent obstruction (NPO, FEV1 ≥ 80%pred + FEV1/FVC > 0.70), persistent obstruction (PO, FEV1 > 50% and < 80%pred + FEV1/FVC ≤ 0.70) or fixed obstruction (FO, FEV1 ≤ 50%pred + FEV1/FVC ≤ 0.70). Endobronchial biopsies were performed at the end of 12 weeks. Collagens I, III and IV in the inner layer (IL, submucosal area comprised between the basement membrane and inner border of the airway smooth muscle) and within the airway smooth muscle bundles (ASM) were quantified by immunohistochemistry and digital image analysis and are presented as fractional area (FA) or mean density (MD). This study was approved by the University of São Paulo Clinics Hospital Ethics Committee. Results: Fourteen patients were classified as NPO, 36 as PO and 12 as FO. Greater collagen IV FA was found in the IL of FO patients compared to NPO patients (0.16 ± 0.07 vs. 0.09 ± 0.07, p = 0.045). Collagens I and III airway content was not different among the groups. Among FO asthmatics, collagen IV FA in the IL was inversely correlated with post-BD FEV1 %change (r = - 0.804, p = 0.02), collagen III MD in the IL correlated with pre-BD FEV1 (r = - 0.711, p = 0.048) and collagen III FA in the ASM correlated with post-BD FEV1 (r = -0.886, p = 0.02). Conclusion: Collagen IV deposition in the inner layer is increased in asthmatics with severe airway obstruction and may play a role in their fixed airflow limitation. In addition, collagen III content in the submucosa seems to influence airway function in severe asthmatics.