Clinical and pathological characteristics of severely asthmatic children with persistent airflow limitation

Introduction Severe therapy resistant asthma (STRA) in children is heterogeneous: many have normal lung function, however there is a group with persistent airflow limitation (PAL). Little is known about PAL in children and previous studies are limited by the definitions used. We hypothesised that when PAL is classified according to stringent criteria (post bronchodilator FEV1 z score <−1.96 after a one-month systemic steroid trial (ERM 2011,Ch 5; 51–59) this group would have distinct clinical, inflammatory and pathological characteristics compared to children without PAL. Methods Retrospective analysis of 103 STRA children. Patients were classified as STRA if they had ongoing poor control despite high dose inhaled corticosteroids plus at least one add on therapy having been assessed as part of a systematic protocol when modifiable factors such as poor adherence were identified and corrected. All children underwent bronchoscopy, bronchoalveolar lavage (BAL) and endobronchial biopsy and received intramuscular triamcinolone. Asthma control test score (ACT); inflammation (exhaled nitric oxide (FENO), induced sputum); spirometry (FEV1. FVC) were measured on the day of bronchoscopy and 4 weeks later. The best FEV1 in the year post triamcinolone was recorded. Results 26/103 (25.2%) STRA children were classified with PAL. There were no differences in the demographic characteristics between the groups. Fewer children with PAL had a previous Paediatric Intensive Care Unit admission (21.7% versus 47.1%); there were no other differences in asthma control. Children with PAL had a higher number of submucosal eosinophils (p=0.021) in endobronchial biopsies before triamcinolone, but there were no differences in airway luminal inflammation in BAL. However, there was a trend towards lower sputum eosinophils post, but not pre, triamcinolone in children with PAL (0.65% (0–17) versus 2.5% (0–42.8), p=0.054). There were no differences in blood eosinophils or FENO levels. All children classified as PAL post triamcinolone continued to have reduced FEV1 (post bronchodilator z score <−1.96) in the following 12 months. Conclusion PAL is relatively common in paediatric STRA even when a very stringent definition is used. Mucosal eosinophilic inflammation is associated with PAL and may represent a therapeutic target. Further work is needed to elucidate underlying mechanisms