Comprehensive Analysis of Nasal Polyps Reveals a More Pronounced Type 2 Transcriptomic Profile of Epithelial Cells and Mast Cells in Aspirin-Exacerbated Respiratory Disease

Abstract

Chronic rhinosinusitis with nasal polyps is affecting up to 3% of Western populations. About 10% of patients with nasal polyps also suffer from asthma and intolerance to aspirin, a syndrome called aspirin-exacerbated respiratory disease. Although eosinophilic inflammation is predominant in polyps of both diseases, phenotypic differences in the tissue-derived microenvironment, elucidating disease-specific characteristics, have not yet been identified. We sought to obtain detailed information about phenotypic and transcriptional differences in epithelial and immune cells in polyps of aspirin-tolerant and intolerant patients. Cytokine profiles in nasal secretions and serum of patients suffering from aspirin-exacerbated respiratory disease (n = 10) or chronic rhinosinusitis with nasal polyps (n = 9) were assessed using a multiplex mesoscale discovery assay. After enrichment for immune cell subsets by flow cytometry, we performed transcriptomic profiling by employing single-cell RNA sequencing. Aspirin-intolerant patients displayed significantly elevated IL-5 and CCL17 levels in nasal secretions corresponding to a more pronounced eosinophilic type 2 inflammation. Transcriptomic profiling revealed that epithelial and mast cells not only complement one another in terms of gene expression associated with the 15-lipoxygenase pathway but also show a clear type 2-associated inflammatory phenotype as identified by the upregulation of POSTN, CCL26, and IL13 in patients with aspirin-exacerbated respiratory disease. Interestingly, we also observed cellular stress responses indicated by an increase of MTRNR2L12, MTRNR2L8, and NEAT1 across all immune cell subsets in this disease entity. In conclusion, our findings support the hypothesis that epithelial and mast cells act in concert as potential drivers of the pathogenesis of the aspirin-exacerbated respiratory disease.

The nasal microbiome in patients suffering from non-steroidal anti-inflammatory drugs-exacerbated respiratory disease in absence of corticosteroids

“…Patients suffering from CRSwNP or N-ERD, and therefore suffering from polyps, showed severely impaired olfactory performance as assessed by the Sniffin' Sticks test and diseasesspecific quality of life as determined by SNOT-22. The associated significantly higher levels of IL-5 and Eotaxin-3 in nasal mucosal lining fluids are characteristic of the pronounced type 2 endotype in these patient groups (14,33). Though a role for the nasal microbiome in olfactory function has been suggested (18, 34), we did not observe any association of the smell performance as assessed by TDI score with nasal microbiome composition.…”

Integrative Analysis and Experimental Validation of Competing Endogenous RNAs in Obstructive Sleep Apnea

“…Experiments showed that upregulation of OIP5-AS1 was closely related to the acceleration of cell apoptosis and the inflammatory response [ 71 , 72 ]. NEAT1 is widely expressed in mammalian cell types, and is overexpressed in several inflammation-related disorders [ 73 , 74 ]. In the acute kidney injury mouse model, KCNQ1OT1 was highly expressed, and knockdown of the KCNQ1OT1 promoted cell proliferation and prevented apoptosis and inflammation [ 75 ].…”

Genomic Insights into Pediatric Intestinal Inflammatory and Eosinophilic Disorders using Single-sell RNA-sequencing

“…Specifically among DEGs detected in EoD compared to controls, within CD4 + T there was an upregulation of genes associated with the chronic rhinosinusitis and nasal polyps ( SCGB3A1 and MTRNR2L8 ) (61, 62), and downregulation of IL27RA , whose decreased expression is associated with allergic airway inflammation (63). Within DC cells, there was also dysregulation of genes associated with chronic obstructive pulmonary disorder (COPD) ( LILRA5, IGLC2 , and IGLC3 ) (64, 65).…”