Dupilumab dampens mucosal type 2 response during acetylsalicylic acid challenge in N-ERD patients DOI Creative Commons
Julia Eckl‐Dorna, Christina Morgenstern,

Katharina Poglitsch

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 7, 2024

ABSTRACT Rationale Non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is characterized by the clinical triad of hypersensitivity to NSAIDs, nasal polyposis, and asthma. The cells mediators causing acute symptoms when driving reaction acetylsalicylic acid (ASA) ingestion, remain poorly defined. Objectives To investigate dynamics during ASA provocation in N-ERD patients before twenty-four weeks after therapy with IL-4 receptor alpha-blocking antibody dupilumab. Methods Nasal mucosal lining fluids N-ERD, chronic rhinosinusitis polyp (CRSwNP) healthy controls were collected at selected time points up two hours provocation. Analysis thirty-three different inflammatory as well transcriptomic profiling was performed. In patients, repeated dupilumab therapy. Measurements Main Results Sixty minutes ASA, showed a significant increase type 2 associated cytokines (i.e., TSLP, IL-5, eotaxin-3) compared other patient groups. This effect diminished independent development tolerance. Transcriptomics revealed dampened upregulation pathways genes AREG ) enhanced downregulation lipid ALOX15 peroxisome metabolisms NOS2 Conclusions Treatment leads reduced cytokine secretion distinct changes profile provocation, but show no association tolerance development.

Language: Английский

Endotyping in Chronic Rhinosinusitis—An EAACI Task Force Report DOI Creative Commons
Sanna Toppila‐Salmi, Sietze Reitsma, Valérie Hox

et al.

Allergy, Journal Year: 2024, Volume and Issue: 80(1), P. 132 - 147

Published: Dec. 6, 2024

ABSTRACT Chronic rhinosinusitis (CRS) is a clinical syndrome defined by typical sinonasal symptoms persisting for at least 12 weeks. CRS divided into two distinct phenotypes, with nasal polyps (CRSwNP) and without (CRSsNP). The aim of the review to provide an update on current knowledge in endotypes. prevailing hypothesis regarding pathogenesis suggests that dysfunctional interactions between host environmental stressors mucosal surface drive diverse inflammatory mechanisms. Genetic epigenetic variations immune system are believed play significant role pathomechanisms CRS. Various agents (such as microbes irritants) have been implicated In healthy state, mucosa acts barrier, modulating stimulation mounting appropriate responses against pathogens minimal tissue damage. Different endotypes may exist based specific mechanistic pathways driving chronic inflammation There need understand order better predict, diagnose, treat This literature provides limitations endotyping practice. Understanding optimal management has progressed significantly last decades; however, there still several unmet needs endotype research.

Language: Английский

Citations

4
Immunology of Nasal Polyposis and Allergic Rhinitis DOI
Sven Schneider, Julia Eckl‐Dorna

Elsevier eBooks, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 1, 2025

Language: Английский

Citations

0
Dupilumab dampens mucosal type 2 response during acetylsalicylic acid challenge in N-ERD patients DOI Creative Commons
Julia Eckl‐Dorna, Christina Morgenstern,

Katharina Poglitsch

et al.

medRxiv (Cold Spring Harbor Laboratory), Journal Year: 2024, Volume and Issue: unknown

Published: June 7, 2024

ABSTRACT Rationale Non-steroidal anti-inflammatory drug-exacerbated respiratory disease (N-ERD) is characterized by the clinical triad of hypersensitivity to NSAIDs, nasal polyposis, and asthma. The cells mediators causing acute symptoms when driving reaction acetylsalicylic acid (ASA) ingestion, remain poorly defined. Objectives To investigate dynamics during ASA provocation in N-ERD patients before twenty-four weeks after therapy with IL-4 receptor alpha-blocking antibody dupilumab. Methods Nasal mucosal lining fluids N-ERD, chronic rhinosinusitis polyp (CRSwNP) healthy controls were collected at selected time points up two hours provocation. Analysis thirty-three different inflammatory as well transcriptomic profiling was performed. In patients, repeated dupilumab therapy. Measurements Main Results Sixty minutes ASA, showed a significant increase type 2 associated cytokines (i.e., TSLP, IL-5, eotaxin-3) compared other patient groups. This effect diminished independent development tolerance. Transcriptomics revealed dampened upregulation pathways genes AREG ) enhanced downregulation lipid ALOX15 peroxisome metabolisms NOS2 Conclusions Treatment leads reduced cytokine secretion distinct changes profile provocation, but show no association tolerance development.

Language: Английский

Citations

0