Relationship between longitudinal changes in type‐2 inflammation, immunoglobulin E sensitization, and clinical outcomes in young asthmatics

Biologic agents, monoclonal antibodies that target highly-specific molecular pathways of inflammation, are becoming integrated into care pathways for multiple disorders that are relevant in otolaryngology and allergy. These conditions share common inflammatory mechanisms of so-called Type 2 inflammation with dysregulation of immunoglobulin E production and eosinophil and mast cell degranulation leading to tissue damage. Biologic agents are now available for the treatment of chronic rhinosinusitis with nasal polyps (CRSwNP), asthma, eosinophilic granulomatosis with polyangiitis (EGPA), atopic dermatitis (AD), and chronic spontaneous urticaria (CSU). This paper summarizes the diagnosis and management of these conditions and critically reviews the clinical trial data that has led to regulatory approval of biologic agents for these conditions.

Download Full-text

Moulds and Staphylococcus aureus enterotoxins are relevant allergens to affect Type 2 inflammation and clinical outcomes in chronic rhinosinusitis patients

ERJ Open Research ◽

10.1183/23120541.00265-2020 ◽

2020 ◽

Vol 6 (4) ◽

pp. 00265-2020

Author(s):

Yoshihiro Kanemitsu ◽

Kensuke Fukumitsu ◽

Ryota Kurokawa ◽

Norihisa Takeda ◽

Yoshiyuki Ozawa ◽

...

Keyword(s):

Staphylococcus Aureus ◽

Clinical Outcomes ◽

Chronic Rhinosinusitis ◽

Specific Ige ◽

Sinus Surgery ◽

Tissue Samples ◽

Asthmatic Patients ◽

Staphylococcus Aureus Enterotoxins ◽

Type 2 Inflammation

BackgroundSensitisation to moulds and Staphylococcus aureus enterotoxins (SEs) is associated with the pathophysiology of both asthma and chronic rhinosinusitis (CRS). The purpose of this study was to clarify the contribution of sensitisation to these allergens to Type 2 inflammation in the blood, nose and the lower airways, and clinical outcomes in CRS patients.MethodsWe prospectively enrolled 56 CRS patients who underwent endoscopic sinus surgery (ESS) (20 with comorbid asthma) and 28 healthy controls between October 2015 and December 2017. CRS patients were followed up for 12 months after surgery. Type 2 inflammation-related biomarkers were analysed using blood, resected tissue samples and sputum. 10 allergens including Alternaria, Aspergillus and SEs were measured. Type 2 inflammation-related biomarkers and clinical outcomes were compared in the stratification with the presence or absence of allergen sensitisation.ResultsSensitisation rate to moulds and SEs in asthmatic patients was increased when changing the cut-off value of specific IgE titre from 0.35 UA·mL−1 to 0.10 UA·mL−1 (1.7- and 4.5-fold, respectively). Moulds and SEs affected the prevalence of asthma and eosinophilic CRS by interacting with each other. All Type 2 inflammation-related biomarkers except for eosinophils in sinus tissue were significantly higher in patients with mould or SE (mould/SE) sensitisation (≥0.10 UA·mL−1) (n=19) than in those without (n=37) and healthy subjects (all p<0.05). Meanwhile, mould/SE sensitisation did not affect longitudinal changes in clinical outcomes after ESS. Changes in serum mould/SE-IgE levels after ESS remained unclear.ConclusionMould/SE sensitisation (≥0.10 UA·mL−1) may affect the development of Type 2 inflammation and clinical outcomes in CRS patients.

Download Full-text

ACO (Asthma–COPD Overlap) Is Independent from COPD, a Case in Favor: A Systematic Review

Diagnostics ◽

10.3390/diagnostics11050859 ◽

2021 ◽

Vol 11 (5) ◽

pp. 859

Author(s):

Naoya Fujino ◽

Hisatoshi Sugiura

Keyword(s):

Immunoglobulin E ◽

Rapid Decline ◽

Chronic Obstructive ◽

Obstructive Pulmonary Disease ◽

Diagnostic Biomarkers ◽

Diagnosis Criteria ◽

Molecular Pathophysiology ◽

Over 40 Years ◽

Type 2 Inflammation

Asthma and chronic obstructive pulmonary disease (COPD) are now recognized to be able to co-exist as asthma–COPD overlap (ACO). It is clinically relevant to evaluate whether patients with COPD concurrently have components of asthma in primary care. This is because: (i) ACO is a relatively common condition among asthma (over 40 years of age) or COPD irrespective of its diagnosis criteria; (ii) patients with ACO can have higher frequency of exacerbation and more rapid decline in lung function than those with asthma or COPD; and (iii) asthmatic features such as eosinophilic airway inflammation are promising indicators for prediction of inhaled corticosteroid-responsiveness in COPD. The aim of this review to evaluate diagnostic markers for ACO. We searched PubMed for articles related to ACO published until 2020. Articles associated with diagnostic biomarkers were included. We identified a total of 25 studies, some of which have revealed that a combination of biomarkers such as fractional exhaled nitric oxide and serum immunoglobulin E is useful to discern type 2 inflammation in the airways of COPD. Here, we review the current understanding of the clinical characteristics, biomarkers and molecular pathophysiology of ACO in the context of how ACO can be differentiated from COPD.

Download Full-text

Understanding the key issues in the treatment of uncontrolled persistent asthma with type 2 inflammation

European Respiratory Journal ◽

10.1183/13993003.03393-2020 ◽

2021 ◽

pp. 2003393

Author(s):

William W. Busse ◽

Monica Kraft ◽

Klaus F. Rabe ◽

Yamo Deniz ◽

Paul Rowe ◽

...

Keyword(s):

Immunoglobulin E ◽

Persistent Asthma ◽

Response To Treatment ◽

Immune Mediators ◽

Type 2 Cytokines ◽

Key Issues ◽

Ige Mediated ◽

Sputum Eosinophils ◽

Type 2 Inflammation

Asthma is a complex respiratory disease that varies in severity and response to treatment. Several asthma phenotypes with unique clinical and inflammatory characteristics have been identified. Endotypes, based on distinct molecular profiles, help to further understand the heterogeneity within asthma. Type 2 inflammation, involving both the innate (type 2 innate lymphoid cell) and adaptive (T helper type 2 cells) immune systems, underpins the complex pathophysiology of chronic inflammation in asthma, as well as the presence of comorbid disease (such as chronic rhinosinusitis with nasal polyps, allergic rhinitis, and atopic dermatitis). Type 2 inflammation is characterised by upregulation of type 2 cytokines interleukin (IL)-4, IL-5, and IL-13, immunoglobulin E (IgE)-mediated release of immune mediators, and dysfunction of epithelial or epidermal barriers. Targeting these key proximal type 2 cytokines has shown efficacy in recent studies adopting a personalised approach to treatment using targeted biologics. Elevated levels of biomarkers downstream of type 2 cytokines, including fractional exhaled nitric oxide, serum IgE, and blood and sputum eosinophils, have been linked to mechanisms involved in type 2 inflammation, and have the potential to aid diagnosis, and predict and monitor response to treatment. The objective of this review is to summarise the current understanding of the biology of type 2 inflammation in asthma, examine its influence on type 2 inflammatory comorbidities, and discuss how type 2 inflammatory biomarkers can be harnessed to further personalise treatments in the age of biologic medicines.

Download Full-text

Practical Review of Biologics in Chronic Rhinosinusitis With Nasal Polyps

Journal of Rhinology ◽

10.18787/jr.2021.00382 ◽

2021 ◽

Vol 28 (3) ◽

pp. 131-140

Author(s):

Ki-Il Lee ◽

Gwanghui Ryu ◽

Shin Hyuk Yoo ◽

Yong Min Kim ◽

Ji-Hun Mo ◽

...

Keyword(s):

United States ◽

Monoclonal Antibody ◽

Chronic Rhinosinusitis ◽

Nasal Polyps ◽

Immunoglobulin E ◽

Drug Hypersensitivity ◽

Significant Proportion ◽

The United States ◽

Type 2 Inflammation

Well-characterized in chronic rhinosinusitis, type 2 inflammation is frequently associated with nasal polyps, comorbid asthma, and nonsteroidal anti-inflammatory drug hypersensitivity. Despite medical and surgical treatment, it recurs in a significant proportion of patients. Thus, severe uncontrolled type 2 chronic rhinosinusitis with nasal polyps is the most difficult-to-treat phenotype of chronic rhinosinusitis. Recently, dupilumab, a monoclonal antibody against IL-4 receptor α, and omalizumab, a monoclonal antibody against immunoglobulin E, were approved for patients with chronic rhinosinusitis with nasal polyps in the United States, Europe, and Korea. Therefore, rhinologists should understand novel biologics and their use. Here, we provide a literature review of several biologics with their indications, effectiveness, and safety.

Download Full-text