Tailored interventions based on sputum eosinophils versus clinical symptoms for asthma in children and adults

Background

Drug treatment for asthma is usually guided by various measures, such as asthma symptoms and lung function tests. In this review we wanted to find out if it was more beneficial to guide treatment according to sputum eosinophils. Eosinophils are a type of white blood cell that is increased in some forms of inflammation. The number of eosinophils in the sputum can tell us about levels of one type of inflammation in the lungs. We looked for evidence about whether measuring eosinophils in the sputum to guide asthma treatment improves asthma outcomes in children and adults.

Study characteristics

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.

Key results

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.

Quality of the evidence

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.

Authors' conclusions: 

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.

Read the full abstract...
Background: 

Asthma severity and control can be measured both subjectively and objectively. Sputum analysis for evaluation of percentage of sputum eosinophilia directly measures airway inflammation, and is one method of objectively monitoring asthma. Using sputum analysis to adjust or tailor asthma medications is potentially superior to traditional methods based on symptoms and spirometry.

Objectives: 

To evaluate the efficacy of tailoring asthma interventions based on sputum analysis in comparison to traditional methods (usually symptom-based with or without spirometry/peak flow) for asthma-related outcomes in children and adults.

Search strategy: 

We searched the Cochrane Airways Group Specialised Register of Trials, the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, trials' registries, and reference lists of articles. The last search was conducted in February 2017.

Selection criteria: 

All randomised controlled comparisons of adjustment of asthma therapy based on sputum eosinophils compared to traditional methods (primarily clinical symptoms and spirometry/peak flow).

Data collection and analysis: 

Results of searches were reviewed against pre-determined criteria for inclusion. In this update, two reviewers selected relevant studies, independently assessed trial quality and extracted the data. We contacted authors for further information when relevant. We analysed data as 'treatment received' and performed sensitivity analyses.

Main results: 

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.

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