To the Editor:
We read with interest the findings of Peters and colleagues in patients with severe asthma who reported that an increase in baseline circulating IL-6 levels of 1 pg/μl was associated with a 10% increased risk of an exacerbation over 3 years and was 14% when excluding patients on oral corticosteroids (1). Elevated levels of IL-6 in induced sputum in patients with asthma are related to impaired lung function (2, 3).
IL-6 is also a key component of the cytokine response in viral illness. For example, in hospitalized patients with severe coronavirus disease (COVID-19), circulating levels of IL-6 are the strongest predictor of the need for mechanical ventilation. In the in vitro murine model of acute lung injury, systemic IL-6 levels are suppressed by both budesonide and formoterol (4). Furthermore, in primary airway epithelial cell cultures, pretreatment with budesonide, formoterol, and glycopyrronium inhibited IL-6 production after infection with the common cold coronavirus (HCoV-229E) (5). Single-inhaler therapy comprising beclomethasone, formoterol, and glycopyrronium reduces exacerbations in patients with uncontrolled asthma with persistent airflow limitation (6). Hence, we would be interested to know whether such patients who have higher levels of circulating IL-6 might benefit more from such triple therapy in terms of protection from viral-induced exacerbations including severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2).
Supplementary Material
Footnotes
Originally Published in Press as DOI: 10.1164/rccm.202006-2354LE on July 20, 2020
Author disclosures are available with the text of this letter at www.atsjournals.org.
References
- 1.Peters MC, Mauger D, Ross KR, Phillips B, Gaston B, Cardet JC, et al. NHLBI Severe Asthma Research Program Evidence for exacerbation-prone asthma and predictive biomarkers of exacerbation frequency Am J Respir Crit Care Med 2020202973–982 [DOI] [PMC free article] [PubMed] [Google Scholar]
- 2.Dixon AE, Raymond DM, Suratt BT, Bourassa LM, Irvin CG. Lower airway disease in asthmatics with and without rhinitis. Lung. 2008;186:361–368. doi: 10.1007/s00408-008-9119-1. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 3.Neveu WA, Allard JL, Raymond DM, Bourassa LM, Burns SM, Bunn JY, et al. Elevation of IL-6 in the allergic asthmatic airway is independent of inflammation but associates with loss of central airway function. Respir Res. 2010;11:28. doi: 10.1186/1465-9921-11-28. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 4.Suda K, Tsuruta M, Eom J, Or C, Mui T, Jaw JE, et al. Acute lung injury induces cardiovascular dysfunction: effects of IL-6 and budesonide/formoterol. Am J Respir Cell Mol Biol. 2011;45:510–516. doi: 10.1165/rcmb.2010-0169OC. [DOI] [PubMed] [Google Scholar]
- 5.Yamaya M, Nishimura H, Deng X, Sugawara M, Watanabe O, Nomura K, et al. Inhibitory effects of glycopyrronium, formoterol, and budesonide on coronavirus HCoV-229E replication and cytokine production by primary cultures of human nasal and tracheal epithelial cells. Respir Investig. 2020;58:155–168. doi: 10.1016/j.resinv.2019.12.005. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 6.Singh D, Virchow JC, Canonica GW, Vele A, Kots M, Georges G, et al. Extrafine triple therapy in patients with asthma and persistent airflow limitation Eur Respir J[online ahead of print] 19 May 2020 [DOI] [PubMed] [Google Scholar]
Associated Data
This section collects any data citations, data availability statements, or supplementary materials included in this article.