Journal of Asthma and Allergy (Apr 2021)
Transcriptional Changes in Chronic Rhinosinusitis with Asthma Favor a Type 2 Molecular Endotype Independent of Polyp Status
Abstract
Amarbir S Gill,1 Abigail Pulsipher,1 Jorgen S Sumsion,2 Gretchen M Oakley,1 Laurie W Leclair,3 Heather Howe,3 Richard R Orlandi,1 Jeremiah A Alt1 1Division of Otolaryngology – Head and Neck Surgery, Department of Surgery, University of Utah, Salt Lake City, UT, USA; 2School of Medicine, University of Utah, Salt Lake, USA; 3Department of Pulmonology/Critical Care Medicine, University of Utah, Salt Lake City, UT, USACorrespondence: Jeremiah A AltDivision of Otolaryngology – Head & Neck Surgery, Department of Surgery, University of Utah School of Medicine, 50 North Medical Drive, Room 3C120, Salt Lake City, UT, 84132, USATel +1 801 585-7143Fax +1 801 585-5744Email [email protected]: Data regarding the inflammatory profile of patients with asthma and chronic rhinosinusitis (CRS-A) with (CRSwNP-A) and without (CRSsNP-A) nasal polyposis remain limited.Objective: Define and compare systemic transcriptional changes in patients with CRS-A to those with non-asthma-related CRS with (CRSwNP) and without nasal polyposis (CRSsNP).Methods: Thirty-four patients with CRS-A (n=19) and CRS (n=15) were prospectively enrolled into an observational study. Demographic information and subjective and objective disease severity measures were recorded. Multiplex gene expression analysis of mRNA extracted from peripheral blood was performed. A total of 594 genes associated with innate/adaptive immunity were analyzed using NanoString technology. Gene expression ratios were reported for genes that were differentially expressed among these cohorts. Linear regression analysis was used to compare the mRNA transcript copy numbers for each gene with disease severity.Results: There was no significant difference in age, gender, nasal polyposis, or health-related quality of life measures between the two groups (p> 0.05). HLA class II histocompatibility antigen, DRB3-1 beta chain (HLA-DRB3) was significantly upregulated in the peripheral blood of patients with CRSsNP-A compared to CRSsNP, whereas chemokine (C-C motif) ligands 4 (CCL4) and zinc finger protein helios (IKZF2) were significantly upregulated in CRSwNP-A compared to CRSwNP (p< 0.05).Conclusion: Patients with CRSsNP-A demonstrate a molecular endotype associated with a Th2-dominant inflammatory profile compared to CRSsNP. Patients with CRSwNP-A similarly demonstrate an overrepresentation of genes associated with Th2-driven inflammation compared to patients with CRSwNP.Keywords: chronic rhinosinusitis, asthma, gene transcription, inflammatory markers, nasal polyposis, endotype
