Airway smooth muscle cells from severe asthma patients with fixed airflow obstruction are responsive to steroid and bronchodilator treatment in vitro

European Respiratory Society
Publication Type:
Journal Article
ERJ Open Research, 2021, 7, (2), pp. 1-4
Issue Date:
Full metadata record
Asthma is characterised by recurrent symptoms associated with variable airflow obstruction and airway hyperresponsiveness, all of which are improved with combination inhaled corticosteroid (ICS)/long-acting β-agonist (LABA) treatment in mild-to-moderate asthma [1]. A proportion of patients however develop fixed airflow obstruction (FAO), despite optimised treatment. FAO is prevalent in up to 60% of patients with severe asthma and is associated with a more rapid decline in lung function and increased symptoms [2]. The underlying mechanisms of FAO in asthma are poorly understood; therefore, development of novel treatment strategies remains a challenge. Airway smooth muscle cells (ASMCs) are the major effector cells of bronchoconstriction in asthma and also contribute to the inflammatory process by secreting pro-inflammatory cytokines and chemokines. Therefore, ASMCs are a major target of both β2-agonist and ICS treatment [3]. Although several studies have suggested that steroid signalling [4] or β2-adrenoceptor (β2AR) signalling may be abnormally regulated in severe asthma [5], it remains unknown whether impaired airway smooth muscle corticosteroid and/or β2-agonist response may contribute to the development of FAO. The aim of this study was to investigate whether primary human ASMCs obtained from severe asthma patients with FAO differ in their response to β2-agonists and corticosteroids compared with asthma patients without FAO and healthy controls. We hypothesised that ASMCs from asthma patients with FAO are less responsive to corticosteroid and β2-agonist treatment than those from patients without FAO
Please use this identifier to cite or link to this item: