mRNAseq of human sputum macrophages and alveolar-like monocyte-derived macrophages of healthy controls and aspirin-exacerbated respiratory disease (AERD) patients

Aspirin-exacerbated respiratory disease (AERD) represents a particularly severe endotype of chronic rhinosinusitis with nasal polyps (CRSwNP), which affects around 10-16% of CRSwNP patients. AERD is characterized by severe and refractory nasal polyposis, bronchial asthma and intolerance to non-steroidal anti-inflammatory drugs (NSAIDs), including aspirin. Today, the pathogenesis of AERD remains incompletely understood and curative treatments are lacking. Macrophages are important source and target cells of arachidonic acid metabolites during type 2 inflammation, that have been neglected in AERD pathogenesis despite their presence in the nasal mucosa of AERD patients. Using a global transcriptomic approach, we identified systemic and local changes in macrophages between AERD patients and healthy controls. We isolated macrophages from induced sputum (sMac) and compared them to 7-days in vitro-differentiated, alveolar-like monocyte-derived macrophages (aMDM). Cells were lysed in RLT buffer with 1% beta-mercaptoethanol and stored at -80°C until RNA isolation and RNAseq. Since sMac yield of healthy controls was low, we pooled RNA of three donors (= sample S1) but excluded the data from subsequent analyses. Thus Analysis 1 shows the intra-group comparison of AERD sMac vs. AERD aMDM. In a second analysis (Analysis 2), we compared AERD aMDM vs. healthy control aMDM for transcriptome differences present in monocyte (blood)-derived cells.