scholarly journals Exacerbation Risk and Type 2 Inflammation in Placebo Patients During a Phase 2b Study of Dupilumab in Patients With Uncontrolled Persistent Asthma

2018 ◽  
Vol 141 (2) ◽  
pp. AB112
Author(s):  
Mario Castro ◽  
Brian N. Swanson ◽  
Shyamalie Jayawardena ◽  
Jennifer D. Hamilton ◽  
Nikhil Amin ◽  
...  
Keyword(s):  
Persistent Asthma ◽  
Exacerbation Risk ◽  
Type 2 Inflammation

Patient characteristics, biomarkers, and exacerbation risk in severe, uncontrolled asthma

2021 ◽  
pp. 2100413
Author(s):  
Monica Kraft ◽  
Guy Brusselle ◽  
J. Mark FitzGerald ◽  
Ian D. Pavord ◽  
Matthew Keith ◽  
...  
Keyword(s):  
Asthma Exacerbation ◽  
Clinical Characteristics ◽  
Nasal Polyposis ◽  
Blood Eosinophil ◽  
Uncontrolled Asthma ◽  
Asian Race ◽  
Exacerbation Risk ◽  
Type 2 Inflammation ◽  
Eosinophil Counts

BackgroundGreater precision in asthma exacerbation risk prediction may improve outcomes. We sought to identify clinical characteristics and biomarkers associated with elevated exacerbation risk in patients with severe, uncontrolled asthma.MethodsData were pooled from seven similarly designed Phase II and III randomized controlled clinical trials of biologic therapies for the treatment of severe, uncontrolled asthma that enrolled comparable patient populations. Annualized asthma exacerbation rates (AAERs) for patients randomized to placebo were assessed by baseline clinical characteristics and by biomarker concentrations at baseline and over the study duration.ResultsThe AAER for the 2016 patients in the combined placebo group was 0.91 (95% CI 0.84‒0.98). Baseline characteristics associated with greater AAER were frequent or severe exacerbations within the prior 12 months, nasal polyposis, maintenance oral corticosteroid use, Asian race, and Asian or Western European region. AAER increased with baseline blood eosinophil counts and fractional exhaled nitric oxide (FeNO) concentration, with the greatest AAER occurring for patients with eosinophils ≥300 cells·μL−1 and FeNO ≥50 ppb. No relationship was observed between baseline serum immunoglobulin E concentration and AAER. Combining type 2 inflammation criteria for eosinophils and FeNO had greater prognostic value than either biomarker alone. Persistent eosinophil and FeNO elevations throughout the study period were associated with greater AAER.ConclusionsExacerbation history, maintenance corticosteroid use, nasal polyposis, Asian race, geographic region, and elevations in blood eosinophil counts and FeNO concentrations (particularly when combined and/or persistently achieving type 2 inflammation criteria) were associated with increased exacerbation risk in patients with severe, uncontrolled asthma.

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

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.

scholarly journals Pathological Roles and Clinical Usefulness of Periostin in Type 2 Inflammation and Pulmonary Fibrosis

Biomolecules ◽  
2021 ◽  
Vol 11 (8) ◽  
pp. 1084
Author(s):  
Junya Ono ◽  
Masayuki Takai ◽  
Ayami Kamei ◽  
Yoshinori Azuma ◽  
Kenji Izuhara
Keyword(s):  
Pulmonary Fibrosis ◽  
Transforming Growth Factor ◽  
Biological Fluids ◽  
Allergic Inflammation ◽  
Transforming Growth Factor Β ◽  
Serum Levels ◽  
Vital Role ◽  
Interleukin 4 ◽  
Type 2 Inflammation

Periostin is known to be a useful biomarker for various diseases. In this article, we focus on allergic diseases and pulmonary fibrosis, for which we and others are now developing detection systems for periostin as a biomarker. Biomarker-based precision medicine in the management of type 2 inflammation and fibrotic diseases since heterogeneity is of utmost importance. Periostin expression is induced by type 2 cytokines (interleukin-4/-13) or transforming growth factor-β, and plays a vital role in the pathogenesis of allergic inflammation or interstitial lung disease, respectively, andits serum levels are correlated disease severity, prognosis and responsiveness to the treatment. We first summarise the importance of type 2 biomarker and then describe the pathological role of periostin in the development and progression of type 2 allergic inflammation and pulmonary fibrosis. In addition, then, we summarise the recent development of assay methods for periostin detection, and analyse the diseases in which periostin concentration is elevated in serum and local biological fluids and its usefulness as a biomarker. Furthermore, we describe recent findings of periostin as a biomarker in the use of biologics or anti-fibrotic therapy. Finally, we describe the factors that influence the change in periostin concentration under the healthy conditions.

Lung function fluctuation patterns unveil asthma and COPD phenotypes unrelated to type 2 inflammation

2021 ◽  
Author(s):  
Edgar Delgado-Eckert ◽  
Anna James ◽  
Delphine Meier-Girard ◽  
Maciej Kupczyk ◽  
Lars I. Andersson ◽  
...  
Keyword(s):  
Lung Function ◽  
Type 2 Inflammation ◽  
Function Fluctuation

scholarly journals COVID-19, severe asthma and biologicals targeting type 2 inflammation: results in a third-level hospital in Madrid, Spain.

2021 ◽  
Vol 147 (2) ◽  
pp. AB40
Author(s):  
Alicia Domínguez Estirado ◽  
Gabriela Zambrano Ibarra ◽  
Filip Skrabski ◽  
Francisco Javier De Castro Martínez ◽  
Julia De Pedro ◽  
...  
Keyword(s):  
Severe Asthma ◽  
Level Hospital ◽  
Type 2 Inflammation

Chitinase 3-like-1 protects airway function despite promoting type 2 inflammation during fungal-associated allergic airway inflammation

2021 ◽  
Author(s):  
Joseph J. Mackel ◽  
Jaleesa M. Garth ◽  
MaryJane Jones ◽  
Diandra A. Ellis ◽  
Jonathan P. Blackburn ◽  
...  
Keyword(s):  
Airway Inflammation ◽  
Periodic Acid ◽  
Acute Infection ◽  
Allergic Bronchopulmonary Aspergillosis ◽  
Allergic Airway Inflammation ◽  
Lung Edema ◽  
Periodic Acid Schiff ◽  
Wide Range ◽  
Type 2 Inflammation

Exposure to fungi can result in a wide range of comorbidities depending on the immune status of the host. Chronic exposure and reactivity to fungi such as Aspergillus fumigatus can result in conditions such as severe asthma with fungal sensitization (SAFS) or allergic bronchopulmonary aspergillosis (ABPA). However, the pathophysiology of SAFS and ABPA are not well understood. Here, we report that the chitinase-like protein YKL-40 is elevated in lung lavage fluid from human asthmatics that are sensitized to fungi. Initial studies demonstrated that mice deficient in the murine ortholog of YKL-40, breast regression protein-39 (BRP-39, chitinase-3-like 1, Chi3l1), were not more susceptible to acute infection with A. fumigatus. However, in an experimental model of fungal-associated allergic airway inflammation (fungal asthma), Chi3l1-/- mice had significantly increased airway hyperresponsiveness (AHR). Surprisingly, increased AHR in Chi3l1-/- mice occurred in the presence of significantly lower type 2 responses (decreased eosinophil numbers and decreased IL-4, IL-5, IL-33, CCL17 and CCL22 levels), although type 1 and type 17 responses were not different. Increased AHR was not associated with differences in Periodic-acid-Schiff staining of lung tissue, differences in the expression of Muc5ac and Clca3, nor differences in lung edema. Bone marrow chimera studies revealed that the presence of BRP-39 in either the hematopoietic or non-hematopoietic compartment was sufficient for controlling AHR during fungal asthma. Collectively, these results indicate that BRP-39 protects against AHR during fungal asthma despite contributing to type 2 inflammation, thus highlighting an unexpected protective role for BRP-39 in allergic fungal asthma.

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