Research in context
Evidence before this study
In patients with more severe asthma and chronic obstructive pulmonary disease (COPD), sputum and blood eosinophil counts are associated with increased risk of exacerbations and a beneficial effect of inhaled corticosteroids (ICS). Exhaled nitric oxide (FeNO) is also associated with risk of adverse asthma outcomes, and a composite score including FeNO and blood eosinophil count might improve the prediction of future risk in response to treatment in patients with severe asthma. Whether these biomarkers have prognostic value or predict the effect of regular or as-needed ICS on exacerbations in patients with mild asthma is not certain. The identification of a prognostic and predictive biomarker in this group would be a substantial advance because although ICS are effective at a population level, many patients have a low burden of symptoms and exacerbations and struggle to commit to treatment with regular ICS.
Added value of the study
This study is a prespecified subgroup analysis of a 52-week, open-label, parallel-group randomised controlled trial in patients with mild asthma, which compared as-needed salbutamol with maintenance budesonide plus as-needed salbutamol and with as-needed budesonide–formoterol. Compared with patients with baseline blood eosinophil counts of less than 0·15 × 109/L, patients with blood eosinophil counts of 0·3 × 109/L or more had similar baseline Asthma Control Questionnaire scores and FEV1 % predicted, but they were three times as likely to have ever had an asthma exacerbation requiring hospital admission. In patients with blood eosinophil counts of 0·3 × 109/L or more, maintenance budesonide plus as-needed salbutamol was more effective than only as-needed salbutamol for exacerbations and severe exacerbations. By contrast, in patients with blood eosinophil counts of less than 0·15 × 109/L, exacerbations and severe exacerbations tended to be higher for maintenance budesonide plus as-needed salbutamol than for only as-needed salbutamol. There was no consistent interaction between treatment response and FeNO or the composite score. The beneficial effects of as-needed budesonide–formoterol compared with as-needed salbutamol were independent of biomarker profile.
Implications of all the available evidence
These findings are in keeping with consistent evidence in patients with more severe asthma and COPD that the blood eosinophil count is an independent prognostic marker of risk for exacerbations and a predictive biomarker of the response to maintenance ICS. The study supports the view that the measurement of blood eosinophils is an important component of risk assessment and treatment selection across the spectrum of obstructive lung diseases. Our findings show that the effects of as-needed budesonide–formoterol are independent of biomarker status.