Sputum mast cells associate with clinical and inflammatory features of asthma

<b>Sputum mast cells associate with clinical and inflammatory features of asthma:</b> Despite their known pathogenic role, the relationship of mast cells (MCs) to inflammatory and clinical features of asthma is poorly understood. We aimed to quantify sputum MCs and examine their relationship to airway and circulatory immune cells and clinical variables in asthma. We conducted flow cytometric analysis of induced sputum to quantify MCs, basophils and other immune cells (n=45 asthma, n=6 non-asthma). Relationship of MCs to sputum and blood (n=19) immune cells in asthma, participant demographics, asthma history, spirometry and dose response slope (DRS) to hypertonic saline was determined. Eosinophilic asthma (EA) was defined by ≥3% sputum eosinophils. Sputum MCs, basophils and eosinophils were significantly intercorrelated and increased in asthma vs non-asthma. MCs and basophils were elevated in EA. MCs and basophils, but not eosinophils, correlated with DRS. Cutoff-based comparison of MC high vs low asthma showed more uncontrolled asthma and reduced FEV1 and FVC in MC high asthma. Similar clinical associations with MC high status were observed in a subpopulation (n = 15) lacking airway eosinophilia or neutrophilia. ROC analysis showed peripheral blood eosinophil (PBE) count predicted elevated sputum eosinophils (AUC=86.7%, P=0.02) or basophils (AUC=82.8%, P=0.016), but not MCs (AUC=52.4%, P=0.87). Sputum MCs are elevated in asthma and they relate to key clinical features of asthma (asthma control, DRS, spirometry). Discord between MCs and PBE suggests MCs are regulated by discrete mechanisms to eosinophils. The clinical significance of elevated MCs in a subset of non-eosinophilic asthma merits further investigation.