Abstract: Three new studies were added in this update, resulting in a total of six included studies (five in adults and one involving children/adolescents). These six studies were clinically and methodologically heterogeneous (use of medications, cut-off for percentage of sputum eosinophils and definition of asthma exacerbation). Of 374 participants randomised, 333 completed the trials. In the meta-analysis, there was a significant reduction in the occurrence of any exacerbations when treatment was based on sputum eosinophil counts, compared to that based on clinical symptoms with or without lung function; pooled odds ratio (OR) was 0.57 (95% confidence interval (CI) 0.38 to 0.86). The risk of having one or more exacerbations over 16 months was 82% in the control arm and 62% (95% CI 49% to 74%) in the sputum strategy arm, resulting in a number needed to treat to benefit (NNTB) of 6 (95% CI 4 to 13). There were also differences between the groups in the rate of exacerbation (any exacerbation per year) and severity of exacerbations defined by requirement for use of oral corticosteroids and hospitalisations: the risk of one or more hospitalisations over 16 months was 24% in controls compared to 8% (95% CI 3% to 21%) in the sputum arm. Data for clinical symptoms, quality of life and spirometry were not significantly different between groups. The mean dose of inhaled corticosteroids per day was also similar in both groups. However sputum induction was not always possible. The included studies did not record any adverse events. One study was not blinded and thus was considered to have a high risk of bias. However, when this study was removed in a sensitivity analysis, the difference between the groups for the primary outcome (exacerbations) remained statistically significant between groups. The GRADE quality of the evidence ranged from moderate (for the outcomes 'Occurrence of any exacerbation' and 'Hospitalisation' ) to low (for the outcome 'Mean dose of inhaled corticosteroids per person per day') due to the inconsistency in defining exacerbations and the small number of hospital admissions. In this updated review, tailoring asthma interventions based on sputum eosinophils is beneficial in reducing the frequency of asthma exacerbations in adults with asthma. Adults with frequent exacerbations and severe asthma may derive the greatest benefit from this additional monitoring test, although we were unable to confirm this through subgroup analysis. There is insufficient data available to assess tailoring asthma medications based on sputum eosinophilia in children. Further robust RCTs need to be undertaken and these should include participants with different underlying asthma severities and endotypes.

Plain-language summary: We included studies that compared adjustment of asthma medicines by counting sputum eosinophils versus usual care. To be included, the studies has to decide who would be in which group by chance. The participants all had asthma, diagnosed according to asthma guidelines. The most recent search for studies was undertaken in February 2017. This updated review includes six studies involving 382 people with asthma (55 children/adolescents, 327 adults). The studies varied in several ways including study duration and follow-up, sputum eosinophil counts used for adjusting medication and the way the asthma attacks were defined. Studies were between 6 and 24 months long. The age spread of participants in the studies was 12 to 48 years. We found that guiding asthma medicines based on sputum eosinophil counts (compared to a control group) reduced the number and severity of asthma attacks in adults. In the control group where treatment was guided according to clinical symptoms, 82 participants out of 100 had at least one attack. This was reduced to 62 out of 100 in participants who had their medications guided by sputum eosinophil count. We are not certain about the effect on other measures, such as quality of life or dose of inhaled steroids needed. There is not enough data in children to assess whether using sputum eosinophil is useful. We are moderately confident in the evidence for any asthma attack and hospital admissions. We were concerned about the different ways the studies defined asthma attacks and the small number of hospital admissions overall, which makes it harder to detect a difference. We are less confident in the evidence about the dose of inhaled steroids. This is because the studies used very different doses. Also, we cannot tell if the eosinophil-guided treatment reduced or increased the steroid dose overall.