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

JOURNAL OF ALLERGY AND CLINICAL IMMUNOLOGY

卷:143

Article

Peters, Michael C.^1,2  Kerr, Sheena^1,2  Dunican, Eleanor M.^1,2  Woodruff, Prescott G.^1,2  Fajt, Merritt L.³  Levy, Bruce D.^4,5  Israel, Elliot^4,5  Phillips, Brenda R.⁶  Mauger, David T.⁶  Comhair, Suzy A.⁷  Erzurum, Serpil C.⁷  Johansson, Mats W.⁸  Jarjour, Nizar N.⁹  Coverstone, Andrea M.¹⁰  Castro, Mario^11,12  Hastie, Annette T.¹³  Bleecker, Eugene R.¹³  Wenzel, Sally E.³  Fahy, John V.^1,2 

[1] Univ Calif San Francisco, Dept Med, Div Pulm & Crit Care Med, San Francisco, CA USA

[2] Univ Calif San Francisco, Cardiovasc Res Inst, San Francisco, CA USA

[3] Univ Pittsburgh, Sch Med, Dept Med, Pulm Allergy & Crit Care Med Div, Pittsburgh, PA 15260 USA

[4] Brigham & Womens Hosp, Dept Med, Div Pulm & Crit Care Med, 75 Francis St, Boston, MA 02115 USA

[5] Harvard Med Sch, Boston, MA USA

[6] Penn State Univ, Dept Publ Hlth Sci, Div Stat & Bioinformat, Hershey, PA USA

[7] Cleveland Clin Cleveland, Dept Pathobiol, Cleveland, OH USA

[8] Univ Wisconsin, Sch Med, Dept Biomol Chem, Madison, WI 53706 USA

[9] Univ Wisconsin, Sch Med, Sect Pulm & Crit Care Med, Madison, WI 53706 USA

[10] Washington Univ, Sch Med, Dept Pediat, Div Allergy Immunol & Pulm Med, St Louis, MO 63130 USA

[11] Washington Univ, Dept Med, Div Pulm & Crit Care Med, St Louis, MO 63130 USA

[12] Washington Univ, Dept Med, Dept Pediat, St Louis, MO 63130 USA

[13] Wake Forest Univ, Bowman Gray Sch Med, Ctr Genom & Personalized Med Res, Winston Salem, NC USA

关键词: Severe asthma;    type 2 inflammation;    steroid resistance;    biomarkers;   

DOI  :  10.1016/j.jaci.2017.12.1009

来源: Elsevier

【 摘 要 】

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.

【 授权许可】

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