Neuroimmune signalling pathways in chronic rhinosinusitis with nasal polyps.

Purpose Of Review: To evaluate the role of neuroimmune signalling pathways in the pathogenesis of chronic rhinosinusitis with nasal polyps (CRSwNP).

Recent Findings: The sinonasal mucosa is densely infiltrated by immune cells and neuronal structures that share an intimate spatial relationship within tissue compartments. Together, such neuroimmune units play a critical role in airway defence and homeostatic function.

Chronic rhinosinusitis with nasal polyps: eosinophils versus B lymphocytes in disease pathogenesis.

Purpose Of Review: To highlight the current evidence that supports the view that eosinophils may not drive disease in chronic rhinosinusitis with nasal polyps (CRSwNP) and the emerging evidence for B cells as an important player in this disease.

Recent Findings: Eosinophil depletion studies in CRSwNP do not fully support a critical role for eosinophils in CRSwNP. Almost complete eosinophil depletion with dexpramipexole had no impact on polyp size reduction or clinical improvement.

Breathing pattern disorder in chronic rhinosinusitis with severe asthma: nasal obstruction and polyps do not increase prevalence.

Objectives: Chronic rhinosinusitis (CRS) with severe asthma are associated with breathing pattern disorder (BPD). Mouth breathing is a sign of breathing pattern disorder, and nose breathing a fundamental part of breathing pattern retraining for BPD. The prevalence of BPD in relation to CRS subtypes and the relationship of nasal obstruction to BPD in CRS and associated severe asthma is unknown.

Mepolizumab Reduces Systemic Corticosteroid Use in Chronic Rhinosinusitis With Nasal Polyps.

Background: Systemic corticosteroids (SCSs) are associated with short- and long-term adverse effects.

Objective: To assess mepolizumab efficacy according to prior SCS use and characterize mepolizumab's SCS-sparing capabilities, in patients with severe chronic rhinosinusitis with nasal polyps.

Methods: In the randomized, double-blind, phase III SYNAPSE trial (NCT03085797), adults with severe chronic rhinosinusitis with nasal polyps eligible for repeat sinus surgery despite standard of care treatment received mepolizumab (100 mg subcutaneously) or placebo every 4 weeks for 52 weeks.

B cells and upper airway disease: allergic rhinitis and chronic rhinosinusitis with nasal polyps evaluated.

: The first mucosal site to encounter inhaled allergen, antigen, and microbes is the upper airway. It must perforce have a rapid system of environmental threat recognition and self-defense. B cells play a critical role in such airway host-defense, tissue surveillance, and immune modulation.

Chronic Rhinosinusitis with Nasal Polyps: Targeting IgE with Anti-IgE Omalizumab Therapy.

Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex, clinically heterogeneous and persistent inflammatory disorder of the upper airway. Detailed mechanistic insights into disease pathogenesis are lacking, but it is now accepted that local tissue IgE driven T2-high inflammatory pathways are critical to disease. The recent CRSwNP Phase 3 POLYP1 and POLYP2 replicate studies of blocking IgE with omalizumab confirmed rapid improvements in all clinical parameters of sinonasal disease, confirming a pivotal role for IgE driven inflammatory pathways in CRSwNP.

Chronic rhinosinusitis with nasal polyps: mechanistic insights from targeting IL-4 and IL-13 via IL-4Rα inhibition with dupilumab.

: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex immunological upper airway disease . CRSwNP, particularly in Caucasians, often has a more distinct T2 inflammatory endotype. IL-4 and IL-13 are key upstream cytokines that help establish and sustain T2 inflammation as well as strongly influencing tissue remodeling.

Dupilumab: Clinical Efficacy of Blocking IL-4/IL-13 Signalling in Chronic Rhinosinusitis with Nasal Polyps.

In September 2019, published details of two large Phase III double-blind placebo-controlled studies (LIBERTY NP SINUS-24 and LIBERTY NP SINUS-52) confirming the clinical efficacy of the biologic dupilumab in simultaneously blocking both IL-4/IL-13 signalling in chronic rhinosinusitis with nasal polyps (CRSwNP). The studies demonstrated that dupilumab (Dupixent, Sanofi and Regeneron) 300mg subcutaneously administered was clinically effective when added for patients with moderate to severe CRSwNP already maintained on the standard intranasal steroid mometasone furoate. Duration of treatment ranged from injections either 2 weekly for 24 weeks (SINUS-24) or every 2 weeks for 52 weeks or finally every 2 weeks for 24 weeks stepping down thereafter to every 4 weeks for a further 28 weeks (SINUS-52).

Allergen-induced asthma, chronic rhinosinusitis and transforming growth factor-β superfamily signaling: mechanisms and functional consequences.

: Often co-associated, asthma and chronic rhinosinusitis (CRS) are complex heterogeneous disease syndromes. Severity in both is related to tissue inflammation and abnormal repair (termed remodeling). Understanding signaling factors that can modulate, integrate the activation, and regulation of such key processes together is increasingly important.

Chronic rhinosinusitis with nasal polyps: insights into mechanisms of disease from emerging biological therapies.

: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a complex disease of the upper airway, with long-term morbidity. With detailed mechanistic studies currently lacking, understanding of the immunopathogenesis is still limited. However, outcomes from CRSwNP clinical studies using biologics that block key mediators or cells may provide some insights into how immune signaling pathways potentially integrate and modulate each other and contribute to disease.

Reduced need for surgery in severe nasal polyposis with mepolizumab: Randomized trial.

Background: Patients with eosinophilic nasal polyposis frequently require surgery, and recurrence rates are high.

Objective: We sought to assess the efficacy and safety of mepolizumab versus placebo for severe bilateral nasal polyposis.

Methods: This randomized, double-blind, placebo-controlled trial recruited patients aged 18 to 70 years with recurrent nasal polyposis requiring surgery.

Antibodies and superantibodies in patients with chronic rhinosinusitis with nasal polyps.

Background: Chronic rhinosinusitis with nasal polyps is associated with local immunoglobulin hyperproduction and the presence of IgE antibodies against Staphylococcus aureus enterotoxins (SAEs). Aspirin-exacerbated respiratory disease is a severe form of chronic rhinosinusitis with nasal polyps in which nearly all patients express anti-SAEs.

Objectives: We aimed to understand antibodies reactive to SAEs and determine whether they recognize SAEs through their complementarity-determining regions (CDRs) or framework regions.

Activin-A is overexpressed in severe asthma and is implicated in angiogenic processes.

Activin-A is a pleiotropic cytokine that regulates allergic inflammation. Its role in the regulation of angiogenesis, a key feature of airways remodelling in asthma, remains unexplored. Our objective was to investigate the expression of activin-A in asthma and its effects on angiogenesis in vitro.

IL-25/IL-33-responsive TH2 cells characterize nasal polyps with a default TH17 signature in nasal mucosa.

Background: Chronic rhinosinusitis with nasal polyposis (CRSwNP) in Western countries is characterized by eosinophilia, IgE production, and TH2 cytokine expression. Type 2 innate lymphoid cells from polyps produce IL-5 and IL-13 in response to IL-25 and IL-33, although the relevance of this axis to local mucosal T-cell responses is unknown.

Objective: We sought to investigate the role of the IL-25/IL-33 axis in local mucosal T-cell responses in patients with CRSwNP.

Mepolizumab for eosinophilic severe asthma: recent studies.

Introduction: In September 2014 two large clinical studies of the anti-IL-5 monoclonal antibody mepolizumab in severe asthma were published in the New England Journal of Medicine (MENSA and SIRIUS).

Areas Covered: Eosinophilic inflammation has long been recognised as a feature of asthma. Identification of IL-5 as a key cytokine specific for eosinophil development and survival lead to development of monoclonal antibody therapy targeting this pathway.

Allergic rhinitis, chronic rhinosinusitis and asthma: unravelling a complex relationship.

Purpose Of Review: Allergic rhinitis, chronic rhinosinusitis (CRS) and asthma have a high worldwide prevalence and confer a significant socioeconomic burden. This article reviews the recent advances in allergic rhinitis, CRS and asthma with view to understanding the upper and lower airway as one system.

Recent Findings: Allergic rhinitis, CRS and asthma demonstrate strong epidemiological coassociation, and early life risk factors for upper airway disease are now apparent.

Chronic rhinosinusitis: therapeutic efficacy of anti-inflammatory and antibiotic approaches.

Despite the high prevalence of chronic rhinosinusitis (CRS) worldwide, the exact pathogenesis of the disease remains unknown. Even with therapeutic intervention, treatment response is often only partial and frequently ineffective. The inability to define exact disease phenotypes in relation to specific disease mechanisms has led to a broad based approach with both anti-inflammatory and anti-microbial intervention.

The effects of an anti-IL-13 mAb on cytokine levels and nasal symptoms following nasal allergen challenge.

Background: IL-13 is a key T(H)2 cytokine that is implicated in allergic responses.

Objective: We evaluated the effects of an anti-IL-13-blocking antibody compared with placebo on repeated nasal allergen challenge responses in hay fever patients out of season.

Methods: We performed a parallel group double-blind study of anti-IL-13 (single dose, 6 mg/kg intravenously, n = 16) and placebo (n = 15), with an additional open label group given a topical nasal corticosteroid (n = 5).

Expression of functional receptor activity modifying protein 1 by airway epithelial cells with dysregulation in asthma.

Background: Epithelial cell expression of calcitonin gene-related peptide (CGRP) is a feature of provoked asthma. Receptor activity modifying protein 1 (RAMP1) and the calcitonin receptor-like receptor combine to form the CGRP1 receptor.

Objective: To determine whether functional RAMP1 is expressed by airway epithelial cells and whether there are alterations in asthma.

Seasonal allergic rhinitis: fluticasone propionate and fluticasone furoate therapy evaluated.

Seasonal allergic rhinitis (SAR) is increasing in prevalence such that 1 in 4 persons is affected in the UK. It represents a considerable burden of disease since in a significant proportion of individuals the severity of nasal-ocular symptoms has an important effect on daily activity, performance and quality of life. Intranasal steroids (INS) form the mainstay of treatment, having been shown in meta-analyses to be superior to oral antihistamines, intranasal antihistamines and anti-leukotrienes.