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. 2023 Dec;13(12):2133-2143.
doi: 10.1002/alr.23207. Epub 2023 Jul 1.

Inflammatory characteristics of central compartment atopic disease

Kolin E Rubel  1 , Rory J Lubner  1 , Andrea A Lopez  1 , Ping Li  1 , Li-Ching Huang  2 , Quanhu Sheng  2 , Jeffanie Wu  1 , Sarah K Wise  3 , John M DelGaudio  3 , Rakesh K Chandra  1 , Naweed Chowdhury  1 , Justin H Turner  1
Affiliations

Inflammatory characteristics of central compartment atopic disease

Kolin E Rubel et al. Int Forum Allergy Rhinol. 2023 Dec.

Abstract

Background: Central compartment atopic disease (CCAD) is an emerging phenotype of chronic rhinosinusitis with nasal polyposis (CRSwNP) characterized by prominent central nasal inflammatory changes. This study compares the inflammatory characteristics of CCAD relative to other phenotypes of CRSwNP.

Methods: A cross-sectional analysis of data from a prospective clinical study was performed on patients with CRSwNP who were undergoing endoscopic sinus surgery (ESS). Patients with CCAD, aspirin-exacerbated respiratory disease (AERD), allergic fungal rhinosinusitis (AFRS), and non-typed CRSwNP (CRSwNP NOS) were included and mucus cytokine levels and demographic data were analyzed for each group. Chi-squared/Mann-Whitney U tests and partial least squares discriminant analysis (PLS-DA) were performed for comparison and classification.

Results: A total of 253 patients were analyzed (CRSwNP, n = 137; AFRS, n = 50; AERD, n = 42; CCAD, n = 24). Patients with CCAD were the least likely to have comorbid asthma (p = 0.0004). The incidence of allergic rhinitis in CCAD patients did not vary significantly compared to patients with AFRS and AERD, but was higher compared to patients with CRSwNP NOS (p = 0.04). On univariate analysis, CCAD was characterized by less inflammatory burden, with reduced levels of interleukin 6 (IL-6), IL-8, interferon gamma (IFN-γ), and eotaxin relative to other groups and significantly lower type 2 cytokines (IL-5, IL-13) relative to both AERD and AFRS. These findings were supported by multivariate PLS-DA, which clustered CCAD patients into a relatively homogenous low-inflammatory cytokine profile.

Conclusions: CCAD has unique endotypic features compared to other patients with CRSwNP. The lower inflammatory burden may be reflective of a less severe variant of CRSwNP.

Keywords: central compartment atopic disease; cytokine; endotype; nasal polyp; phenotype.

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Conflict of interest statement

Disclosure of potential conflicts of interest: R.K. Chandra is a consultant for Regeneron and Optinose. J.H. Turner has received grant support from the NIH/National Institute of Allergy and Infectious Diseases (NIAID) and NIH/National Institute on Aging (NIA) and personal fees from Regeneron. S.K. Wise is on the Consultant/Advisory Board for Chitogel, NeurENT, and OptiNose. The remaining authors declare that they have no relevant conflicts of interest.

Figures

Figure 1.
Figure 1.. Mucus cytokines in patients with CCAD, AERD, AFRS, patients with CRSwNP NOS
Cytokine values are plotted on a log scale for each CRSwNP subgroup. Solid lines indicate medians with interquartile ranges.
Figure 2.
Figure 2.. PLS-DA plot of patients with CCAD, AERD, AFRS, patients with CRSwNP NOS
partial least squares linear discriminant analysis was used to separate classes based on cytokines and investigate differential cytokine patterns between groups. Component 1 is primarily weighted towards type 2 inflammatory markers while component 2 is weighted more towards type 1 and 3 inflammatory markers. Note clustering of CCAD around low values of both components, suggestive of generally low inflammatory burden. Ellipses represent the 95% bounds for each CRSwNP phenotype, with the area of each circle measuring the overall heterogeneity of cluster members.
Figure 3.
Figure 3.. Identification of inflammatory disease clusters in CRSwNP patients. * represents patients with CCAD
Dendogram representing hierarchical cluster analysis of patients with CRSwNP. Analysis was performed by using the Ward method on squared Euclidian distances with seventeen cytokines as biological variables.
See this image and copyright information in PMC

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