Beyond Single Cytokines: Targeting Co‐Receptor CD131 in Asthma‐COPD Overlap DOI Open Access
Chantal Donovan

Respirology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

A proportion of patients have lung disease with features both asthma and COPD. Critically, these experience increased severity poorer quality life, there are no curative treatments. These may be referred to as having 'asthma-COPD overlap' (abbreviated ACO) or 'asthma + COPD', generalised descriptions including preceding COPD development, mixed eosinophilic neutrophilic inflammation, airway remodelling/fibrosis, impaired function (post-bronchodilator FEV1/forced vital capacity < 0.70, baseline resistance hyperresponsiveness [AHR]). Treating ACO is also challenging, many exhibiting reduced responses current treatments used for individually. Given the heterogeneity ACO, developing experimental models that replicate different combinations critical understanding underlying mechanisms, identifying evaluating new therapies. The study by Wang colleagues in a recent publication Respirology [1] describes mouse model early life development induced house dust mite (HDM) antigen, emphysema later elastase treatment. This has key COPD, AHR, its phenotypic presentation consistent previous [2] (as comprehensively reviewed [3] [4]). Importantly, this was preclinical testing platform therapy targeting CD131 (human monoclonal antibody against CD131; CSL311), which authors prophylactically administered their exacerbation rhinovirus (RV1b). shared/co-receptor IL-3, IL-5 GM-CSF, moves beyond single-cytokine targeted approaches, provides strategy treating complex heterogeneous diseases such ACO. CSL311 treatment neutrophils eosinophils tissue compartments, monocytes alveolar macrophages tissue. Furthermore, emphysema-like enlargement collagen deposition, but not mucous secreting cell numbers, airways. Reducing resulted AHR improved inspiratory capacity. major strength RNA sequencing analysis conducted on lungs from CSL311-treated mice. analyses revealed ACO-induced type-2 inflammation fibrosis signalling pathways signatures were reversed identified through computational similar previously published combined HDM cigarette smoke exposure [2], suggesting CSL311-treatment could novel option phenotypes An interesting observation did reverse type-1 interferon responses, compound does adversely affect antimicrobial defence mechanisms lungs. Therefore, subsequently explored effects prophylactic inhibition RV1b infection-induced asthma. eosinophils, numbers AHR. Interestingly, unlike had effect neutrophil alter viral levels. As all cytokine-modifying treatments, risk immunosuppression, leading infections more severe infections; thus data promising they suggest remain intact do clearance. viruses produce immune further studies other warranted. Perhaps most logical progression assess whether beneficial bacterial exacerbations an exciting future drug discovery There are, however, few unknowns can addressed studies, affects HDM-specific IgE therapeutic, rather than prophylactic, reverses features. raises possibility earlier prevent COPD/ACO. To some degree, explorations predicated establishing at higher Nevertheless, represents area worth exploring. Despite discussion asthma-COPD overlap over past decade, advances research efforts transcriptomic profiling data, pace progress field been slow. Global Initiative Asthma (GINA) guidelines still highlight need better define [5]. Thus, building study, warranted accelerate options patients. potential reignite enthusiasm discovering offers innovative pipeline facilitates aimed effective author declares conflicts interest. linked related article. view article, visit https://doi.org/10.1111/resp.14877.

Language: Английский

Beyond Single Cytokines: Targeting Co‐Receptor CD131 in Asthma‐COPD Overlap DOI Open Access
Chantal Donovan

Respirology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 2, 2025

A proportion of patients have lung disease with features both asthma and COPD. Critically, these experience increased severity poorer quality life, there are no curative treatments. These may be referred to as having 'asthma-COPD overlap' (abbreviated ACO) or 'asthma + COPD', generalised descriptions including preceding COPD development, mixed eosinophilic neutrophilic inflammation, airway remodelling/fibrosis, impaired function (post-bronchodilator FEV1/forced vital capacity < 0.70, baseline resistance hyperresponsiveness [AHR]). Treating ACO is also challenging, many exhibiting reduced responses current treatments used for individually. Given the heterogeneity ACO, developing experimental models that replicate different combinations critical understanding underlying mechanisms, identifying evaluating new therapies. The study by Wang colleagues in a recent publication Respirology [1] describes mouse model early life development induced house dust mite (HDM) antigen, emphysema later elastase treatment. This has key COPD, AHR, its phenotypic presentation consistent previous [2] (as comprehensively reviewed [3] [4]). Importantly, this was preclinical testing platform therapy targeting CD131 (human monoclonal antibody against CD131; CSL311), which authors prophylactically administered their exacerbation rhinovirus (RV1b). shared/co-receptor IL-3, IL-5 GM-CSF, moves beyond single-cytokine targeted approaches, provides strategy treating complex heterogeneous diseases such ACO. CSL311 treatment neutrophils eosinophils tissue compartments, monocytes alveolar macrophages tissue. Furthermore, emphysema-like enlargement collagen deposition, but not mucous secreting cell numbers, airways. Reducing resulted AHR improved inspiratory capacity. major strength RNA sequencing analysis conducted on lungs from CSL311-treated mice. analyses revealed ACO-induced type-2 inflammation fibrosis signalling pathways signatures were reversed identified through computational similar previously published combined HDM cigarette smoke exposure [2], suggesting CSL311-treatment could novel option phenotypes An interesting observation did reverse type-1 interferon responses, compound does adversely affect antimicrobial defence mechanisms lungs. Therefore, subsequently explored effects prophylactic inhibition RV1b infection-induced asthma. eosinophils, numbers AHR. Interestingly, unlike had effect neutrophil alter viral levels. As all cytokine-modifying treatments, risk immunosuppression, leading infections more severe infections; thus data promising they suggest remain intact do clearance. viruses produce immune further studies other warranted. Perhaps most logical progression assess whether beneficial bacterial exacerbations an exciting future drug discovery There are, however, few unknowns can addressed studies, affects HDM-specific IgE therapeutic, rather than prophylactic, reverses features. raises possibility earlier prevent COPD/ACO. To some degree, explorations predicated establishing at higher Nevertheless, represents area worth exploring. Despite discussion asthma-COPD overlap over past decade, advances research efforts transcriptomic profiling data, pace progress field been slow. Global Initiative Asthma (GINA) guidelines still highlight need better define [5]. Thus, building study, warranted accelerate options patients. potential reignite enthusiasm discovering offers innovative pipeline facilitates aimed effective author declares conflicts interest. linked related article. view article, visit https://doi.org/10.1111/resp.14877.

Language: Английский

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