Relationship Between Eosinophils and Exacerbation Risk in Asthma Varies by Therapy

In adults with mild asthma, the relationship between blood eosinophil counts and disease exacerbations differs according to the inhaler therapy being used — that is, as needed salbutamol, as-needed budesonide-formoterol, or maintenance budesonide plus as-needed salbutamol. Results of the analysis were published in The Lancet Respiratory Medicine.

A prespecified subgroup analysis of a previously published 52-week, multicenter, open-label, parallel-group, randomized controlled trial was conducted in 16 clinical trial units based in primary and secondary care centers in Australia, New Zealand, Italy, and the United Kingdom. Investigators sought to evaluate the associations between blood eosinophil counts and exhaled nitric oxide (FeNO) with outcomes and response to therapy in adults with mild asthma.

Eligible study participants included those who self-reported an asthma diagnosis from a physician and were between aged 18 and 75. Other inclusion criteria were use of short-acting β agonist (SABA) therapy as the only type of asthma treatment during the 3 months before study recruitment. Self-reported SABA use consisted of the use of the agent on ≥2 occasions in the past 4 weeks, but on average on ≤2 occasions per day in that time period for patients who had not experienced any severe exacerbations in the previous 12 months.

In this subanalysis, the primary outcome was the annual rate of asthma exacerbations per patient. An exacerbation was defined as “worsening asthma resulting in an urgent medical care consultation (primary care visit, emergency department visit, or hospital admission), a prescription of systemic glucocorticoids for any duration, or an episode of high β agonist use (>16 uses of salbutamol or >8 uses of budesonide-formoterol within 24 h), or all three.”

All eligible participants were randomly assigned in a 1:1:1 ratio, stratified by country, to 1 of the following 3 treatments: as-needed salbutamol (i2 inhalations of 100 µg in a pressurized metered dose inhaler); maintenance budesonide (200 µg twice daily by inhaler) plus as-needed salbutamol (2 inhalations of 100 µg); or, as-needed budesonide-formoterol (1 inhalation of budesonide 200 µg and formoterol 6 µg by inhaler). Between March 17, 2016, and August 29, 2017, a total of 675 participants were enrolled in the study; \ 656 of whom had results available for blood eosinophil analysis and 668 had results for FeNO levels.

Results of the study showed that in those participants who received as-needed salbutamol, the proportion of individuals who experienced a severe exacerbation increased progressively and significantly with increasing blood eosinophil counts (P =.014). No significant interactions were detected between blood eosinophil counts and FeNO levels. Furthermore, no difference was observed between the effect of as-needed salbutamol compared with as-needed salbutamol with respect to either exacerbations or severe exacerbations.

Significant interactions were reported, however, between blood eosinophil count subgroups and the effect of maintenance budesonide plus as-needed salbutamol, compared with as-needed salbutamol, both regarding exacerbations (P =.0006) and severe exacerbations

(P =.0007). Moreover, the use of maintenance budesonide plus as-needed salbutamol was more effective than the use of as-needed salbutamol in patients with blood eosinophil counts of ≥0.3 x 10⁹/L, both with respect to exacerbations (rate ratio, 0.13; 95% CI, 0.05-0.33) and severe exacerbations (risk odds ratio, 0.11; 95% CI, 0.03-0.45).

The investigators concluded that the results of this study are in line with consistent evidence demonstrating that in patients with more severe asthma, blood eosinophil counts are an independent prognostic marker of risk for disease exacerbations and a predictive biomarker of a patient’s response to inhaled corticosteroids.

Disclosure: This study was in part supported by AstraZeneca. Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Pavord ID, Holliday M, Reddel HK, et al; on behalf of the Novel START Study Team. Predictive value of blood eosinophils and exhaled nitric oxide in adults with mild asthma: a prespecified subgroup analysis of an open-label, parallel-group, randomised controlled trial [published online March 11, 2020]. Lancet Respir Med. doi:10.1016/S2213-2600(20)30053-9