An airway epithelial IL-17A response signature identifies a steroid-unresponsive COPD patient subgroup

© 2019 American Society for Clinical Investigation. All rights reserved. BACKGROUND. Chronic obstructive pulmonary disease (COPD) is a heterogeneous smoking-related disease characterized by airway obstruction and inflammation. This inflammation may persist even after smoking cessation and responds variably to corticosteroids. Personalizing treatment to biologically similar "molecular phenotypes" may improve therapeutic efficacy in COPD. IL-17A is involved in neutrophilic inflammation and corticosteroid resistance, and thus may be particularly important in a COPD molecular phenotype. METHODS. We generated a gene expression signature of IL-17A response in bronchial airway epithelial brushings from smokers with and without COPD (n = 238), and validated it using data from 2 randomized trials of IL-17 blockade in psoriasis. This IL-17 signature was related to clinical and pathologic characteristics in 2 additional human studies of COPD: (a) SPIROMICS (n = 47), which included former and current smokers with COPD, and (b) GLUCOLD (n = 79), in which COPD participants were randomized to placebo or corticosteroids. RESULTS. The IL-17 signature was associated with an inflammatory profile characteristic of an IL-17 response, including increased airway neutrophils and macrophages. In SPIROMICS the signature was associated with increased airway obstruction and functional small airways disease on quantitative chest CT. In GLUCOLD the signature was associated with decreased response to corticosteroids, irrespective of airway eosinophilic or type 2 inflammation. CONCLUSION. These data suggest that a gene signature of IL-17 airway epithelial response distinguishes a biologically, radiographically, and clinically distinct COPD subgroup that may benefit from personalized therapy

Erratum: Clinical Significance of Bronchodilator Responsiveness Evaluated by Forced Vital Capacity in COPD: SPIROMICS Cohort Analysis [Corrigendum].

[This corrects the article DOI: 10.2147/COPD.S220164.]

Positioning new pharmacotherapies for COPD

Igor Z Barjaktarevic,1 Anthony F Arredondo,1 Christopher B Cooper1,2 1Department of Medicine, 2Department of Physiology, David Geffen School of Medicine, University of California, Los Angeles, Los Angeles, CA, USA Abstract: COPD imposes considerable worldwide burden in terms of morbidity and mortality. In recognition of this, there is now extensive focus on early diagnosis, secondary prevention, and optimizing medical management of the disease. While established guidelines recognize different grades of disease severity and offer a structured basis for disease management based on symptoms and risk, it is becoming increasingly evident that COPD is a condition characterized by many phenotypes and its control in a single patient may require clinicians to have access to a broader spectrum of pharmacotherapies. This review summarizes recent developments in COPD management and compares established pharmacotherapy with new and emerging pharmacotherapies including long-acting muscarinic antagonists, long-acting β-2 sympathomimetic agonists, and fixed-dose combinations of long-acting muscarinic antagonists and long-acting β-2 sympathomimetic agonists as well as inhaled cortiocosteroids, phosphodiesterase inhibitors, and targeted anti-inflammatory drugs. We also review the available oral medications and new agents with novel mechanisms of action in early stages of development. With several new pharmacological agents intended for the management of COPD, it is our goal to familiarize potential prescribers with evidence relating to the efficacy and safety of new medications and to suggest circumstances in which these therapies could be most useful. Keywords: COPD phenotypes, once-daily inhalers, fixed-combination inhalers, long-acting muscarinic antagonist, LAMA, long-acting β-2 sympathomimetic agonist, LAB