Case Report: Dual monoclonal antibody therapy in chronic rhinosinusitis with nasal polyps and severe eosinophilic asthma-a proteome analysis.

Context: Recent insights into type 2 inflammation have led to the development of monoclonal antibody therapies for severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP). Despite add-on therapy with a monoclonal antibody, some individuals remain uncontrolled in terms of upper and/or lower airway symptoms, prompting an exploration of the efficacy of combining biological therapies and their impact on inflammatory pathways.

Objectives: In this article, we present a distinctive case of a patient with CRSwNP, severe eosinophilic asthma, and uncontrolled upper airway symptoms, who experienced substantial clinical and local inflammatory improvements through dual monoclonal antibody therapy.

The multi-omics single-cell landscape of sinus mucosa in uncontrolled severe chronic rhinosinusitis with nasal polyps.

Uncontrolled severe chronic rhinosinusitis with nasal polyps (CRSwNP) is associated with elevated levels of type 2 inflammatory cytokines and raised immunoglobulin concentrations in nasal polyp tissue. By using single-cell RNA sequencing, transcriptomics, surface proteomics, and T cell and B cell receptor sequencing, we found the predominant cell types in nasal polyps were shifted from epithelial and mesenchymal cells to inflammatory cells compared to nasal mucosa from healthy controls. Broad expansions of CD4 T effector memory cells, CD4 tissue-resident memory T cells, CD8 T effector memory cells and all subtypes of B cells in nasal polyp tissues.

Differential protease content of mast cells and the processing of IL-33 in induced allergic airway inflammation in mice.

Background: Recent studies strongly implicated mast cell-derived proteases as regulators of IL-33 activity by enzymatic cleavage in its central domain. A better understanding of the role of mast cell proteases on IL-33 activity is needed. We aimed to compare the expression of mast cell proteases in C57BL/6 and BALB/c mice, their role in the cleavage of IL-33 cytokine, and their contribution to allergic airway inflammation.

Neutrophils Affect IL-33 Processing in Response to the Respiratory Allergen .

Future precision medicine requires further clarifying the mechanisms of inflammation in the severe endotypes of chronic airway diseases such as asthma and chronic rhinosinusitis (CRS). The presence of neutrophils in the airways is often associated with severe airway inflammation, while their precise contribution to the severe inflammation is largely unknown. We aimed to study the role of neutrophils in BALB/c and C57BL/6 mice exposed to ().

Novel antibody cocktail targeting Bet v 1 rapidly and sustainably treats birch allergy symptoms in a phase 1 study.

Background: The efficacy of an allergen-specific IgG cocktail to treat cat allergy suggests that allergen-specific IgG may be a major protective mechanism elicited by allergen immunotherapy.

Objectives: Extending these findings, we tested a Bet v 1-specific antibody cocktail in birch-allergic subjects.

Methods: This was a phase 1, randomized, double-blind, study with 2 parts.

Unravelling the expression of interleukin-9 in chronic rhinosinusitis: A possible role for Staphylococcus aureus.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a Th2 biased inflammation, associated with nasal colonization of Staphylococcus (S.) aureus. Interleukin (IL)-9 is a pro-inflammatory Th2 cytokine with a pivotal role in asthma, allergy and chronic obstructive pulmonary disease (COPD), but is less studied in CRSwNP.

Mouse Strain-Dependent Difference Toward the Allergen Serine Protease-Like Protein D Reveals a Novel Regulator of IL-33.

( can secrete a broad range of virulence factors, among which staphylococcal serine protease-like proteins (Spls) have been identified as bacterial allergens. The allergen serine protease-like protein D (SplD) induces allergic asthma in C57BL/6J mice through the IL-33/ST2 signaling axis. Analysis of C57BL/6J, C57BL/6N, CBA, DBA/2, and BALB/c mice treated with intratracheal applications of SplD allowed us to identify a frameshift mutation in the serine (or cysteine) peptidase inhibitor, clade A, and member 3I (S) causing a truncated form of SERPINA3I in BALB/c, CBA, and DBA/2 mice.

A substantial neutrophilic inflammation as regular part of severe type 2 chronic rhinosinusitis with nasal polyps.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is generally associated with severe type 2 immune reactions in the white population. However, recent findings suggest an additional role for neutrophils in severe type 2 inflammation.

Objective: This study aimed to characterize the neutrophilic inflammation in CRSwNP and its relation to eosinophilic inflammation in severe type 2 immune reactions.

Chronic rhinosinusitis: assessment of changes in nociceptive neurons.

Background: Pain is a major symptom of chronic rhinosinusitis (CRS). It is mainly associated with CRS without nasal polyps (CRSsNP) and has a major impact in the decision to move on to surgery. Patients with CRS with nasal polyps (CRSwNP) are characterized by trigeminal hypoesthesia and suffer from less pain.

Type 2 inflammation in chronic rhinosinusitis without nasal polyps: Another relevant endotype.

Background: Chronic rhinosinusitis without nasal polyps (CRSsNP) is mainly considered a type 1 mediated disease. The role and clinical significance of type 2 immune responses in CRSsNP have not been addressed sufficiently; a recent cluster analysis for CRS described the existence of a subgroup of patients with CRSsNP with a type 2 inflammation.

Objective: We aimed to characterize the underlying type 2 immune response and its clinical significance in patients with CRSsNP.

Staphylococcus aureus Induces a Mucosal Type 2 Immune Response via Epithelial Cell-derived Cytokines.

Rationale: Chronic rhinosinusitis with nasal polyps is characterized by a T-helper cell type 2-skewed upper airway inflammation. Mucosal Staphylococcus aureus colonization is found in the majority of patients with nasal polyps. S.

IL-21 Is Increased in Nasal Polyposis and after Stimulation with Staphylococcus aureus Enterotoxin B.

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) is an inflammatory disease associated with lymphoid aggregates and local IgE production related to Staphylococcus aureus enterotoxins. T-follicular helper cells and their effector cytokine interleukin (IL)-21 play an important role in germinal center proliferation.

Methods: IL-21 was determined on the mRNA level by qPCR in nasal tissue of 3 groups of patients: control (n = 17), chronic rhinosinusitis without nasal polyposis (CRSsNP; n = 23), and CRSwNP (n = 35).

Extracellular eosinophilic traps in association with Staphylococcus aureus at the site of epithelial barrier defects in patients with severe airway inflammation.

Background: Chronic rhinosinusitis with nasal polyps is characterized by T2-biased eosinophilic inflammation. Eosinophils have been shown to generate so-called extracellular eosinophilic traps (EETs) under similar pathologic conditions.

Objective: Our aim was to investigate a possible link between EET formation and the presence of Staphylococcus aureus, an organism frequently colonizing the upper airways, at the human mucosal site of the disease.

Inflammatory endotypes of chronic rhinosinusitis based on cluster analysis of biomarkers.

Background: Current phenotyping of chronic rhinosinusitis (CRS) into chronic rhinosinusitis with nasal polyps (CRSwNP) and chronic rhinosinusitis without nasal polyps (CRSsNP) might not adequately reflect the pathophysiologic diversity within patients with CRS.

Objective: We sought to identify inflammatory endotypes of CRS. Therefore we aimed to cluster patients with CRS based solely on immune markers in a phenotype-free approach.

Systemic expression of inflammatory mediators in patients with chronic rhinosinusitis and nasal polyps with and without Aspirin Exacerbated Respiratory Disease.

Background: Systemic reactions are related to the pathogenesis of Aspirin Exacerbated Respiratory Disease (AERD). With this work we wanted to study the changes in the systemic levels of inflammatory mediators in both baseline and after oral aspirin challenge in patients with and without AERD.

Methods: Patients with nasal polyposis and asthma with AERD (n=20) and without (n=18) were orally challenged with aspirin in a single-blind placebo controlled study.

The expression of dendritic cell subsets in severe chronic rhinosinusitis with nasal polyps is altered.

Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is characterized as a Th2-driven disease. Activated dendritic cells (DCs) are the main T-cell activators; their role in the chronic inflammatory process of nasal polyposis is still unclear.

Methods: The regulation of DC subsets was analyzed in nasal polyp tissue from CRSwNP patients and compared to inferior turbinate tissue from healthy subjects.

Inflammatory patterns in upper airway disease in the same geographical area may change over time.

Background: Inflammatory patterns of nasal polyps (NPs) may vary. Changes over time have not been investigated so far. This study was designed to evaluate the inflammatory patterns of NPs in Thailand at two time points 12 years apart, explore differences in Staphylococcus aureus (SA) mucosal carriage rates over time, and the latter's relationship with the inflammatory patterns.

Omalizumab is effective in allergic and nonallergic patients with nasal polyps and asthma.

Background: Adult patients with nasal polyps often have comorbid asthma, adding to the serious effect on the quality of life of these patients. Nasal polyps and asthma might represent a therapeutic challenge; inflammation in both diseases shares many features, such as airway eosinophilia, local IgE formation, and a T(H)2 cytokine profile. Omalizumab is a human anti-IgE mAb with proved efficacy in patients with severe allergic asthma.

RAGE processing in chronic airway conditions: involvement of Staphylococcus aureus and ECP.

Background: The receptor for advanced glycation end products (RAGE) is a multiligand receptor that exists as a membrane-bound (mRAGE) form and a soluble (sRAGE) form. RAGE is reported to play a role in diverse pathologies including lower airway conditions, but the exact mechanism of action remains poorly understood. In the upper airways, the involvement of RAGE remains completely unexplored.

Mepolizumab, a humanized anti-IL-5 mAb, as a treatment option for severe nasal polyposis.

Background: Approximately 85% of nasal polyps (NPs) in white subjects are characterized by prominent eosinophilia. IL-5 is the key driver of eosinophilic differentiation and survival.

Objective: We sought to investigate the therapeutic potential of inhibiting IL-5 with a humanized mAb as treatment for severe nasal polyposis.