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Refractory airway type 2 inflammation in a large subgroup of asthmatic patients treated with inhaled corticosteroids.

ABSTRACT: BACKGROUND:Airway type 2 inflammation is usually corticosteroid sensitive, but the role of type 2 inflammation as a mechanism of asthma in patients receiving high-dose inhaled corticosteroids (ICSs) is uncertain. OBJECTIVE:We sought to determine whether airway type 2 inflammation persists in patients treated with ICSs and to evaluate the clinical features of patients with steroid-resistant airway type 2 inflammation. METHODS:We used quantitative PCR to generate a composite metric of type 2 cytokine gene expression (type 2 gene mean [T2GM]) in induced sputum cells from healthy control subjects, patients with severe asthma receiving ICSs (n = 174), and patients with nonsevere asthma receiving ICSs (n = 85). We explored relationships between asthma outcomes and T2GM values and the utility of noninvasive biomarkers of airway T2GM. RESULTS:Sputum cell T2GM values in asthmatic patients were significantly increased and remained high after treatment with intramuscular triamcinolone. We used the median T2GM value as a cutoff to classify steroid-treated type 2-low and steroid-resistant type 2-high (srT2-high) subgroups. Compared with patients with steroid-treated type 2-low asthma, those with srT2-high asthma were older and had more severe asthma. Blood eosinophil cell counts predicted srT2-high asthma when body mass index was less than 40 kg/m2 but not when it was 40 kg/m2 or greater, whereas blood IgE levels strongly predicted srT2-high asthma when age was less than 34 years but not when it was 34 years or greater. CONCLUSION:Despite ICS therapy, many asthmatic patients have persistent airway type 2 inflammation (srT2-high asthma), and these patients are older and have more severe disease. Body weight and age modify the performance of blood-based biomarkers of airway type 2 inflammation.

SUBMITTER: Peters MC

PROVIDER: S-EPMC6128784 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Refractory airway type 2 inflammation in a large subgroup of asthmatic patients treated with inhaled corticosteroids.

Peters Michael C MC Kerr Sheena S Dunican Eleanor M EM Woodruff Prescott G PG Fajt Merritt L ML Levy Bruce D BD Israel Elliot E Phillips Brenda R BR Mauger David T DT Comhair Suzy A SA Erzurum Serpil C SC Johansson Mats W MW Jarjour Nizar N NN Coverstone Andrea M AM Castro Mario M Hastie Annette T AT Bleecker Eugene R ER Wenzel Sally E SE Fahy John V JV

The Journal of allergy and clinical immunology 20180307 1

<h4>Background</h4>Airway type 2 inflammation is usually corticosteroid sensitive, but the role of type 2 inflammation as a mechanism of asthma in patients receiving high-dose inhaled corticosteroids (ICSs) is uncertain.<h4>Objective</h4>We sought to determine whether airway type 2 inflammation persists in patients treated with ICSs and to evaluate the clinical features of patients with steroid-resistant airway type 2 inflammation.<h4>Methods</h4>We used quantitative PCR to generate a composite ...[more]

PMID: 29524537

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Project description:BackgroundViruses are important triggers of asthma exacerbations. They are also detected outside of exacerbation. Alteration of anti-viral response in asthmatic patients has been shown although the mechanisms responsible for this defect remain unclear. The objective of this study was to compare in virus-infected and not-infected allergic asthmatic children, aged 6 to 16 years, admitted to hospital for a severe exacerbation, the innate immune response and especially the expression of pattern recognition receptor (PRR) and their function.MethodsVirus identification was performed both during the exacerbation and at steady state (eight weeks later). Data assessed at both periods included clinical features, anti-viral response and inflammation (in sputum and plasma), and PRR expression/function in blood mononuclear cells.ResultsViruses were identified in 46 out of 72 children (median age 8.9 years) during exacerbation, and among them, in 17 at steady state. IFN-β, IFN-γ and IL-29 levels in sputum and plasma were similar between infected and not infected patients at both times, as well as the expression of TLR3, RIG-I and MDA5 in blood monocytes and dendritic cells. Airway inflammation in infected patients was characterized by significantly higher IL-5 concentration and eosinophil count. Compared to patients only infected at exacerbation, the re-infected children significantly exhibited lower levels of IFN-γ in plasma and sputum at exacerbation associated with modifications in PRR expression and function in blood mononuclear cells. These re-infected patients also presented an airway neutrophilic inflammation at steady state.ConclusionOur results reports in asthmatic children that impaired anti-viral response during virus-induced exacerbation is more pronounced in a subgroup of patients prone to re-infection by virus. This subgroup is characterized by altered PRR function and a different pattern of airway inflammation.Trial registrationThis multicenter prospective study was approved by the regional investigational review board (ref: 08/07).

Dataset Information

Refractory airway type 2 inflammation in a large subgroup of asthmatic patients treated with inhaled corticosteroids.

Publications

Refractory airway type 2 inflammation in a large subgroup of asthmatic patients treated with inhaled corticosteroids.

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