Systemic IL-6 and Severe Asthma.

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).