Inhaled Glucocorticoids in Patients with Mild Asthma with Low Sputum Eosinophil Levels

From the Greek meaning short of breath, asthma affects 25 million people living in the United States. Within this heterogenous group is a subset of patients with mild persistent asthma, defined as symptoms occurring >2 times per week with minor limitations in activities of daily living. Current guidelines recommend treatment with inhaled glucocorticoids to reduce inflammation in these individuals. However, questions remain about the effect of inhaled glucocorticoids in individuals with mild persistent asthma without inflammation based on low levels of sputum eosinophilia.

In the randomized, double-blind crossover Steroids in Eosinophil Negative Asthma (SEINA) Trial, Lazarus and colleagues compared the efficacy of an inhaled glucocorticoid (mometasone), a long-acting muscarinic antagonist (tiotropium), or placebo in 295 patients with mild, persistent asthma and low eosinophil counts (<2%). After 42 weeks, the response to either mometasone or tiotropium as compared with placebo did not differ significantly.

The following NEJM Journal Watch summary explains the study in further detail.

David J. Amrol, MD reviewing Lazarus SC et al. N Engl J Med 2019 May 19 Wong GWK. N Engl J Med 2019 May 19

Inhaled steroids (ICS) are first-line agents for patients with mild asthma, but whether they are effective in the roughly 50% of patients with noneosinophilic asthma is unclear. Researchers compared the effectiveness of daily ICS versus long-acting antimuscarinic agents (LAMAs) in patients with mild asthma and <2% sputum eosinophil counts.

In a double-blinded crossover trial, 295 adolescent and adult patients with mild asthma (73% had no eosinophilia) were treated with daily mometasone (an ICS), tiotropium (Spiriva; a LAMA), or placebo for 12 weeks each. A composite asthma score (which encompassed lung function and symptoms), was similar in all three groups among patients without eosinophilia. As expected, patients with sputum eosinophilia of ≥2% improved while using mometasone but not while using tiotropium or placebo.

Comment: I routinely check the peripheral absolute eosinophil count in patients with severe asthma to determine if inflammation amenable to a biologic agent (e.g., anti-IgE or anti-interleukin therapy) is present. Soon, we might be checking eosinophil counts in our mild asthmatic patients to see if they will be responsive to ICS. Unfortunately, we have no effective alternative maintenance treatment available for patients with mild noneosinophilic asthma, as evidenced by tiotropium's failure to improve outcomes in this study. We currently have no information about as-needed use of ICS plus long-acting β-agonists (LABAs) in patients with mild noneosinophilic asthma.

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Amanda Fernandes is a 2018-2019 NEJM editorial fellow.