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

Helen L. Petsky, Albert Li, Anne B. Chang

    Research output: Contribution to journalReview articleResearchpeer-review

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    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 methods: 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 ofmedications, 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.
    Author's 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.

    Original languageEnglish
    Article numberCD005603
    Pages (from-to)1-51
    Number of pages51
    JournalCochrane Database of Systematic Reviews
    Volume2017
    Issue number8
    DOIs
    Publication statusPublished - 24 Aug 2017

    Fingerprint

    Sputum
    Eosinophils
    Asthma
    Spirometry
    Confidence Intervals
    Adrenal Cortex Hormones
    Hospitalization
    Eosinophilia
    Numbers Needed To Treat
    MEDLINE
    Patient Selection
    Registries
    Meta-Analysis
    Therapeutics
    Odds Ratio
    Quality of Life
    Inflammation

    Cite this

    @article{4ef0cc79cfd24c989a7e05dad7f83a05,
    title = "Tailored interventions based on sputum eosinophils versus clinical symptoms for asthma in children and adults",
    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 methods: 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 analyseddata 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 ofmedications, 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 spirometrywere 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.Author's 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.",
    author = "Petsky, {Helen L.} and Albert Li and Chang, {Anne B.}",
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    doi = "10.1002/14651858.CD005603.pub3",
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    Tailored interventions based on sputum eosinophils versus clinical symptoms for asthma in children and adults. / Petsky, Helen L.; Li, Albert; Chang, Anne B.

    In: Cochrane Database of Systematic Reviews, Vol. 2017, No. 8, CD005603, 24.08.2017, p. 1-51.

    Research output: Contribution to journalReview articleResearchpeer-review

    TY - JOUR

    T1 - Tailored interventions based on sputum eosinophils versus clinical symptoms for asthma in children and adults

    AU - Petsky, Helen L.

    AU - Li, Albert

    AU - Chang, Anne B.

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    N2 - 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 methods: 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 analyseddata 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 ofmedications, 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 spirometrywere 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.Author's 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.

    AB - 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 methods: 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 analyseddata 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 ofmedications, 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 spirometrywere 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.Author's 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.

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