Relationship of sputum mast cells with clinical and inflammatory characteristics of asthma

Abstract

Background: Mast cells (MCs) are innate immune cells that regulate atopic and nonatopic inflammation in the airways. MCs play a critical role in the pathogenesis of asthma, yet their relationship to airway and systemic inflammation and clinical characteristics of asthma is poorly understood. Objective: To quantify MCs in induced sputum samples and understand their relationship to airway and circulatory immune cells, and clinical variables in asthma. Methods: We employed flow cytometry of sputum samples to quantify MCs, basophils and other immune cells in 51 participants (45 asthma and 6 non-asthma controls). Relationship of MCs to airway (n = 45) and blood (n = 19) immune cells, participant demographics, asthma history, spirometry and airways hyperresponsiveness (AHR) to hypertonic saline was determined by correlation and comparison of cut-off-based sputum MC high vs low participants. Results: Mast cells, basophils and eosinophils were increased in asthma vs non-asthma control sputum. In asthma sputum, MCs, basophils and eosinophils were significantly intercorrelated, and MCs and basophils were elevated in participants with eosinophilic asthma. MCs and basophils, but not eosinophils, correlated with AHR. Sputum MC high asthma was characterized by an increased proportion of participants with uncontrolled asthma and reduced FEV 1 and FVC. Trends towards similar clinical associations with elevated MCs were observed in a paucigranulocytic subpopulation (n = 15) lacking airway eosinophilia or neutrophilia. Receiver operator characteristic (ROC) analysis showed peripheral blood eosinophil (PBE) count predicted elevated sputum eosinophils and basophils, but not MCs. Conclusions and Clinical Relevance: Sputum MCs are elevated in asthma, and their measurement may be useful as they relate to key clinical features of asthma (spirometry, asthma control, AHR). PBE count did not predict airway MC status, suggesting direct measurement of airway MCs by sensitive methods such as flow cytometry should be further developed. | 697 FRICKER Et al.

Neutrophilic asthma features increased airway classical monocytes

“…When appropriate, studies were registered with the Australian New Zealand Clinical Trials Registry (ACTRN12614001003662, ACTRN12617000395336, ACTRN12617000991314). Key flow cytometry findings were validated in a second independent cohort consisting of 26 individuals with asthma described previously who were not also part of the cohort described above 26 …”

“…asthma, macrophage, mannose receptor, monocyte, neutrophil, severe asthma, sputum with asthma described previously who were not also part of the cohort described above. 26…”

Underestimation of airway luminal eosinophilia by quantitative sputum cytometry

“…Although our analysis was limited to assessment of eosinophilic activity, there might be other aspect of cellular inflammation that are often not taken into consideration leading to inaccurate characterization as a non-T2 endotype. These include lymphocyte [ 20 ] and mast cell numbers [ 21 ] in sputum that can be identified particularly with more advanced microscopy, flow cytometry, and mass cytometry. They could also be markers of corticosteroid responsiveness and it remains to be seen how often these endotypes may occur in the absence of eosinophilia.…”

Underestimation of Luminal Eosinophilia by Quantitative Sputum Cytometry

“…Although our analysis was limited to assessment of eosinophilic activity, there might be other aspect of cellular in ammation that are often not taken into consideration leading to inaccurate characterization as a non-T2 endotype. These include lymphocyte (20) and mast cell numbers (21) in sputum that can be identi ed particularly with more advanced microscopy, ow cytometry, and mass cytometry. They could also be markers of steroid responsiveness and it remains to be seen how often these endotypes may occur in the absence of eosinophilia.…”