Mast cell gene expression in eosinophilic COPD patients

<b>Introduction:</b> Higher sputum mast cell gene expression and tryptase protein levels have been observed in COPD patients with more sputum eosinophils, suggesting a role for mast cells in T2 inflammation in COPD. We have further investigated mast cell numbers and characteristics in COPD, and their associations with T2 inflammation, by studying bronchoscopy and sputum samples. <b>Method:</b> We compared mast cell gene expression using RNAseq data generated from bronchial brushings and sputum samples from COPD patients with higher versus lower blood eosinophil counts (&gt;250 vs &lt;150 cells/µL respectively). We examined associations between mast cell gene expression and T2 biomarkers. We measured mast cell numbers in bronchial biopsies by immunohistochemistry. <b>Results:</b> We observed increased expression of tryptase and carboxypeptidase mRNA, and a mast cell specific 11-gene signature in bronchial brushings and sputum cells of eosinophilhigh compared to eosinophillow COPD patients. The 11-gene signature was associated with airway eosinophil numbers, and IL-13 gene expression in bronchial brushings and sputum, and with IL-5 in sputum only (rho 0.4 – 0.8 p&lt;0.05). There was no difference in the number of tissue mast cells between groups. <b>Discussion:</b> We observed increased mRNA expression of pulmonary mast cell activation markers in eosinophilic COPD patients. Mast cell gene expression was associated with T2 biomarkers, implicating mast cells as components of the T2 inflammation network in eosinophilic COPD.