Abstract
BackgroundSevere asthma is a heterogeneous disease and the relationship between airway inflammation and airway remodelling is poorly understood. We sought to define sputum mediator profiles in severe asthmatics categorised by CT-determined airway geometry and sputum differential cell counts.MethodsIn a single centre cross-sectional observational study we recruited 59 subjects with severe asthma that underwent sputum induction and thoracic CT. Quantitative CT analysis of the apical segment of the right upper lobe (RB1) was performed. Forty-one mediators in sputum samples were measured of which 21 mediators that were assessable in >50% of samples were included in the analyses.ResultsIndependent of airway geometry, sputum MMP9 and IL-1β were elevated in those groups with a high sputum neutrophil count while sputum ICAM was elevated in those subjects with a low sputum neutrophil count. In contrast, sputum CCL11, IL-1α and fibrinogen were different in groups stratified by both sputum neutrophil count and airway geometry. Sputum CCL11 concentration was elevated in subjects with a low sputum neutrophil count and high luminal and total RB1 area, whereas sputum IL1α was increased in subjects with a high sputum neutrophil count and low total RB1 area. Sputum fibrinogen was elevated in those subjects with RB1 luminal narrowing and in those subjects with neutrophilic inflammation without luminal narrowing.ConclusionsWe have demonstrated that sputum mediator profiling reveals a number of associations with airway geometry. Whether these findings reflect important biological phenotypes that might inform stratified medicine approaches requires further investigation.
Highlights
Asthma affects up to 5% of the adult population and approximately 10% of asthmatics have severe or refractory disease [1,2]
We found that airway wall remodelling defined by CT was most closely associated with neutrophilic inflammation and airflow obstruction but was poorly associated with patient reported outcomes [10]
Subjects with a low total area and luminal area were older with a later age of onset of disease, higher body mass index, more bronchiectasis and more frequent exacerbations (Table 2)
Summary
Asthma affects up to 5% of the adult population and approximately 10% of asthmatics have severe or refractory disease [1,2]. We found that airway wall remodelling defined by CT was most closely associated with neutrophilic inflammation and airflow obstruction but was poorly associated with patient reported outcomes [10]. This association between persistent neutrophilic inflammation and lung function decline is a consistent observation in asthma and COPD [12,13]. We hypothesised that there is differential sputum mediator profiles in severe asthmatics stratified by airway geometry determined by CT analysis. We sought to define sputum mediator profiles in severe asthmatics categorised by CT-determined airway geometry and sputum differential cell counts
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