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. 2022 Jan 26:8:806911.
doi: 10.3389/fmed.2021.806911. eCollection 2021.

Endotyping Seasonal Allergic Rhinitis in Children: A Cluster Analysis

Velia Malizia  1 , Giuliana Ferrante  2 , Giovanna Cilluffo  1 , Rosalia Gagliardo  1 , Massimo Landi  1   3 , Laura Montalbano  1 , Salvatore Fasola  1 , Mirella Profita  1 , Amelia Licari  4 , Gian Luigi Marseglia  4 , Stefania La Grutta  1
Affiliations

Endotyping Seasonal Allergic Rhinitis in Children: A Cluster Analysis

Velia Malizia et al. Front Med (Lausanne). .

Abstract

Background: Seasonal Allergic Rhinitis (SAR) is a heterogeneous inflammatory disease. We hypothesized that a cluster analysis based on the evaluation of cytokines in nasal lavage (NL) could characterize distinctive SAR endotypes in children.

Methods: This cross-sectional study enrolled 88 children with SAR. Detailed medical history was obtained by well-trained physicians. Quality of life and sleep quality were assessed through standardized questionnaires [Pediatric Rhinoconjunctivitis Quality of Life Questionnaire (PRQLQ) and Pittsburgh Sleep Quality Index (PSQI) respectively]. Children were grouped through K-means clustering using Interleukin (IL)-5, IL-17, IL-23, and Interferon (INF)-γ in NL.

Results: Out of the 88 patients enrolled, 80 were included in the cluster analysis, which revealed three SAR endotypes. Cluster 1 showed lower levels of IL-5 and IL-17 and intermediate levels of IL-23 and IFN-γ; Cluster 2 had higher levels of IL-5 and intermediate levels of IL-17, IL-23, and IFN-γ; Cluster 3 showed higher levels of IL-17, IL-23, and IFN-γ and intermediate levels of IL-5. Cluster 1 showed intermediate values of nasal pH and nasal nitric oxide (nNO), and a lower percentage of neutrophils at nasal cytology than Clusters 2 and 3. Cluster 2 had a lower level of nasal pH, a higher nNO, higher scores in the ocular domain of PRQLQ, and worse sleep quality than Clusters 1 and 3. Cluster 3 showed a higher percentage of neutrophils at nasal cytology than Clusters 1 and 2.

Conclusions: Our study identified three endotypes based on the evaluation of cytokines in NL, highlighting that childhood SAR is characterized by heterogeneous inflammatory cytokines.

Keywords: allergic rhinitis; children; cluster analysis; cytokines; endotypes.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. The reviewer RC declared past collaborations with the authors AL and GLM to the handling editor.

Figures

Figure 1
Figure 1
Optimal number of clusters (A) and cluster plot (B). According to Elbow method, cluster size and interpretability the optimal number of clusters was 3; the clusters identified are reported in the cluster plot in which observations are represented by points, square and triangles using principal components.
Figure 2
Figure 2
IL-5, IL-17, IL-23, and INF-γ by clusters.
Figure 3
Figure 3
Sensitivity analysis: IL-5, IL-17, IL-23, and INF-γ by clusters.
See this image and copyright information in PMC

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