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Personalized Management of Patients with Chronic Rhinosinusitis with Nasal Polyps in Clinical Practice: A Multidisciplinary Consensus Statement.

ABSTRACT: Chronic rhinosinusitis (CRS) is a sino-nasal chronic inflammatory disease, occurring in 5-15% of the general population. CRS with nasal polyps (CRSwNP) is present in up to 30% of the CRS population. One-third of CRSwNP patients suffer from disease that is uncontrolled by current standards of care. Biologics are an emerging treatment option for patients with severe uncontrolled CRSwNP, but their positioning in the treatment algorithm is under discussion. Effective endotyping of CRSwNP patients who could benefit from biologics treatment is required, as suggested by international guidelines. Other issues affecting management include comorbidities, such as allergy, non-steroidal anti-inflammatory drug-exacerbated respiratory disease, and asthma. Therefore, the choice of treatment in CRSwNP patients depends on many factors. A multidisciplinary approach may improve CRSwNP management in patients with comorbidities, but currently there is no shared management model. We summarize the outcomes of a Delphi process involving a multidisciplinary panel of otolaryngologists, pulmonologists, and allergist-immunologists involved in the management of CRSwNP, who attempted to reach consensus on key statements relating to the diagnosis, endotyping, classification and management (including the place of biologics) of CRSwNP patients.

SUBMITTER: De Corso E

PROVIDER: S-EPMC9143504 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Personalized Management of Patients with Chronic Rhinosinusitis with Nasal Polyps in Clinical Practice: A Multidisciplinary Consensus Statement.

De Corso Eugenio E Bilò Maria Beatrice MB Matucci Andrea A Seccia Veronica V Braido Fulvio F Gelardi Matteo M Heffler Enrico E Latorre Manuela M Malvezzi Luca L Pelaia Girolamo G Senna Gianenrico G Castelnuovo Paolo P Canonica Giorgio Walter GW

Journal of personalized medicine 20220523 5

Chronic rhinosinusitis (CRS) is a sino-nasal chronic inflammatory disease, occurring in 5-15% of the general population. CRS with nasal polyps (CRSwNP) is present in up to 30% of the CRS population. One-third of CRSwNP patients suffer from disease that is uncontrolled by current standards of care. Biologics are an emerging treatment option for patients with severe uncontrolled CRSwNP, but their positioning in the treatment algorithm is under discussion. Effective endotyping of CRSwNP patients wh ...[more]

PMID: 35629268

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Project description:BackgroundMolecular signatures of chronic rhinosinusitis with nasal polyps (CRSwNP) related to macrophages remain unclear. This study aimed to develop a macrophage-associated diagnostic signature for CRSwNP.MethodsTranscriptome data from 54 patients with CRSwNP and 37 healthy controls across GSE136825, GSE36830, and GSE72713 were used to identify differentially expressed genes (DEGs) between two groups. Gene Set Enrichment Analysis and Weighted Gene Co-Expression Network Analysis pinpointed crucial pathways and gene clusters. A diagnostic model was created from these analyses and receiver operating characteristic curve (ROC), and further validated in our transcriptome data from 29 samples. Immune cell infiltration analysis was performed and linked those diagnostic genes to macrophages and verified by single-cell RNA sequencing data. Immunofluorescence co-staining of CD163 and HMOX1 was performed in nasal tissues. Mouse bone marrow-derived macrophage (BMDMs) cultures were used in functional experiments. Correlations between the expression of HMOX1 and eotaxin genes were investigated.ResultsDEGs of CRSwNP versus control group were enriched in the INTERLEUKIN_4_AND_13_SIGNALING pathways. A four-gene diagnostic model (HMOX1, ALOX5, F13A1 and ITGB2) was developed and demonstrated high diagnostic precision with an area under ROC curve of 0.980 for training dataset and 0.895 for test dataset. M2 macrophage presence and HMOX1 expression significantly correlated with CRSwNP (p < 0.001). Single-cell RNA sequencing data underscored the altered cellular composition in CRSwNP, with HMOX1 notably expressed in M2 macrophages. Immunofluorescence staining highlighted the increased infiltration of CD163+ M2 macrophages in nasal mucosa samples of eosinophilic CRSwNP, which correlated with HMOX1 protein levels (p < 0.05). The HMOX1 inhibitor zinc protoporphyrin reduced the ratio of CD163 + HMOX1 + M2 macrophages in mouse BMDM cultures (p < 0.05). HMOX1 expression showed a strong positive correlation with the expression of eotaxin genes (CCL11, CCL24, and CCL26; p < 0.05 respectively).ConclusionM2 macrophage-derived HMOX1 can be used as an innovative diagnostic signature for CRSwNP, which might be a potential regulator of eosinophilic inflammation.

Dataset Information

Personalized Management of Patients with Chronic Rhinosinusitis with Nasal Polyps in Clinical Practice: A Multidisciplinary Consensus Statement.

Publications

Personalized Management of Patients with Chronic Rhinosinusitis with Nasal Polyps in Clinical Practice: A Multidisciplinary Consensus Statement.

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