Association of cytokine profile with prior treatment failure and revision surgery in chronic rhinosinusitis

Abstract

Background Inflammatory patterns in chronic rhinosinusitis (CRS) may predict disease severity, need for multiple sinus surgeries, and treatment response. This study analyzes nasal mucus inflammatory cytokine patterns in patients with (CRSwNP) and without (CRSsNP) nasal polyposis and their association with revision sinus surgery. Methods A total of 319 CRS patients who underwent sinus surgery were included. Cytokines were quantified in intraoperative mucus specimens using a multiplex flow cytometric bead assay. Cytokine expression patterns in patients with 0, 1, and ≥2 previous surgeries were analyzed using Kruskal‐Wallis and principal component (PC) regression analyses. Results There were 122 (38%) patients with CRSsNP and 197 (62%) with CRSwNP. On univariate analysis, interleukin (IL)‐1β, IL‐6, IL‐8, and IL‐21 were associated with increasing number of sinus surgeries in CRSsNP, as were IL‐2, IL‐4, IL‐5, IL‐6, IL‐9, IL‐17A, and tumor necrosis factor (TNF)‐α in CRSwNP. PC analysis with continuous Poisson regression in CRSwNP demonstrated that high IL‐5 and IL‐13 and low IL‐1β, IL‐12, and IL‐21 were associated with more prior surgeries. In CRSsNP low IL‐13 and high IL‐5 and regulated‐on‐activation, normal T‐cell–expressed and secreted (RANTES) were associated with more prior surgeries. Age remained a significant covariate in the full regression model for CRSsNP, but was nonsignificant in CRSwNP. Conclusion In CRSwNP, elevated IL‐5 and IL‐13 levels were higher at time of surgery in patients with more prior surgeries. Type 2 cytokines in CRSsNP demonstrated mixed associations with revision surgery. For both phenotypes, IL‐10, IL‐12, and IL‐21 were consistently lower as number of prior surgeries increased, suggesting that treatment‐resistant disease may be modulated by impairment in these signaling pathways.

Utilization of Transcriptomic Profiling to Identify Molecular Markers Predicting Successful Recovery Following Endoscopic Sinus Surgery for Chronic Rhinosinusitis

“…Persistence of disease is associated with a Type‐1 high inflammatory profile. While consistent with previous observations, 10 the mechanistic implications were not previously described.…”

Inflammatory characteristics of central compartment atopic disease

“…Our group has previously used unstructured statistical approaches to identify CRS endotypes using mucus cytokine levels 20,21,27–29 . Here we sought to use a similar approach to determine whether patients with CCAD have any unique endotypic features.…”

“…Sparse partial least squares discriminant analysis (sPLS‐DA) is a supervised, multivariate approach that identifies linear cytokine groupings that best differentiate or classify between previously known or specified groups. As such, it can be thought of as a supervised version of principal component analysis, which our group has used previously 20,21 . For the present analysis, sPLS‐DA was implemented using the mixOmics package in R, using inflammatory nasal mucus levels alone to identify potentially different cytokine patterns between AERD, AFRS, CCAD, and non‐typed CRSwNP 22 .…”

“…As such, it can be thought of as a supervised version of principal component analysis, which our group has used previously. 20,21 For the present analysis, sPLS-DA was implemented using the mixOmics package in R, using inflammatory nasal mucus levels alone to identify potentially different cytokine patterns between AERD, AFRS, CCAD, and non-typed CRSwNP. 22 Cytokine component loadings and PLS-DA plots were then used to assess the relative distribution of patients in each group across the three sPLS-DA components.…”

“…Our group has previously used unstructured statistical approaches to identify CRS endotypes using mucus cytokine levels. 20,21,[27][28][29] Here we sought to use a similar approach to determine whether patients with CCAD have any unique endotypic features. We identified six CRSwNP inflammatory disease clusters and validated their stability using bootstrap analysis.…”