Transcriptional Changes in Chronic Rhinosinusitis with Asthma Favor a Type 2 Molecular Endotype Independent of Polyp Status

Abstract

Background 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.

Identification of key genes and pathways in chronic rhinosinusitis with nasal polyps and asthma comorbidity using bioinformatics approaches

“…Studies report IgE-mediated release of immune mediators and upregulation of type 2 cytokines in the upper and lower airways of patients with CRSwNP and asthma comorbidity ( 28 ). In addition, CRSwNP patients present with upregulation of genes associated with type 2 inflammation in the nasal mucosa which is significantly higher in patients with asthma ( 29 ). The common pathophysiology of the upper and lower airways has important implications for the diagnosis and treatment of respiratory comorbidities.…”

Comorbid asthma may be associated with local inflammatory profile switching among patients with chronic rhinosinusitis without nasal polyposis

“…Tissues were stored, prepared, and analyzed as previously described. 3 Multiplex gene expression analysis of mRNA extracted examined 594 genes associated with innate and Gene expression ratios (GERs) were calculated for genes that were significantly and differentially expressed between patients with CRSsNP-A versus CRSsNP. Student t tests were used to analyze continuous variables, while chi-square/Fisher exact tests were used for categorical variables.…”

“…Peripheral blood (1–3 mL) and sinonasal tissue (4.0 mm 2 anterior ethmoid tissue being discarded) were collected intraoperatively. Tissues were stored, prepared, and analyzed as previously described 3 . Multiplex gene expression analysis of mRNA extracted examined 594 genes associated with innate and adaptive immunity in allergy, autoimmune, and infectious diseases (Human Immunology v2 Panel; NanoString Technologies).…”

“…2 A recent investigation reported that patients with asthma and CRSsNP (CRSsNP-A) manifest with systemic upregulation of genes associated with Th2 inflammation compared with those without asthma (CRSsNP). 3 Whether these systemic transcriptional changes affect gene expression locally within the sinuses, however, remains unknown. Our objective herein was to define and compare the local versus systemic gene transcription pro-files of patients with CRSsNP-A with those of patients with CRSsNP.…”

“…A recent investigation reported that patients with asthma and CRSsNP (CRSsNP‐A) manifest with systemic upregulation of genes associated with Th2 inflammation compared with those without asthma (CRSsNP) 3 . Whether these systemic transcriptional changes affect gene expression locally within the sinuses, however, remains unknown.…”