期刊
JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY
卷 143, 期 1, 页码 104-+出版社
MOSBY-ELSEVIER
DOI: 10.1016/j.jaci.2017.12.1009
关键词
Severe asthma; type 2 inflammation; steroid resistance; biomarkers
资金
- National Institutes of Health [PO1 HL107201, R01 HL080414, U19, AI077439, U10 HL109146, U10 HL109164, U10 HL109172, U10 HL109086, U10 HL109250, U10 HL109168, U10HL109257, U10 HL109152, K23 HL138303, K12 HL119997-04]
- Parker B. Francis Foundation
- NATIONAL CENTER FOR ADVANCING TRANSLATIONAL SCIENCES [UL1TR000448, UL1TR002345] Funding Source: NIH RePORTER
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL107202, K12HL119997, U10HL109168, U10HL109086, R01HL080414, K23HL138303, U10HL109146] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF ALLERGY AND INFECTIOUS DISEASES [U19AI077439] Funding Source: NIH RePORTER
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/m(2) but not when it was 40 kg/m(2) 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-highasthma), andthese patients are older and have more severe disease. Body weight and age modify the performance of blood-based biomarkers of airway type 2 inflammation.
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