Corticosteroids as adjunctive therapy in the treatment of influenza

Background: Specific treatments for influenza are limited to neuraminidase inhibitors and adamantanes. Corticosteroids show evidence of benefit in sepsis and related conditions, most likely due to their anti-inflammatory and immunomodulatory properties. Although commonly prescribed for severe influe...

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Main Authors: Rodrigo, Chamira, Leonardi-Bee, Jo, Nguyen-Van-Tam, Jonathan, Lim, Wei Shen
Format: Article
Published: Wiley 2016
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Online Access:https://eprints.nottingham.ac.uk/37689/
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author Rodrigo, Chamira
Leonardi-Bee, Jo
Nguyen-Van-Tam, Jonathan
Lim, Wei Shen
author_facet Rodrigo, Chamira
Leonardi-Bee, Jo
Nguyen-Van-Tam, Jonathan
Lim, Wei Shen
author_sort Rodrigo, Chamira
building Nottingham Research Data Repository
collection Online Access
description Background: Specific treatments for influenza are limited to neuraminidase inhibitors and adamantanes. Corticosteroids show evidence of benefit in sepsis and related conditions, most likely due to their anti-inflammatory and immunomodulatory properties. Although commonly prescribed for severe influenza, there is uncertainty over their potential benefit or harm. Objectives: To systematically assess the effectiveness and potential adverse effects of corticosteroids as adjunctive therapy in the treatment of influenza, taking into account differences in timing and doses of corticosteroids. Search methods: We searched CENTRAL (2015, Issue 5), MEDLINE (1946 to June week 1, 2015), EMBASE (1974 to June 2015), CINAHL (1981 to June 2015), LILACS (1982 to June 2015), Web of Science (1985 to June 2015), abstracts from the last three years of major infectious disease and microbiology conferences, and references of included articles. Selection criteria: We included randomised controlled trials (RCTs), quasi-RCTs and observational studies that compared corticosteroid treatment with no corticosteroid treatment for influenza or influenza-like illness. We did not restrict studies by language of publication, influenza subtypes, clinical setting or age of participants. We selected eligible studies in two stages: sequential examination of title and abstract, followed by full text. Data collection and analysis: Two pairs of review authors independently extracted data and assessed risk of bias. We pooled estimates of effect using random-effects meta-analysis models, where appropriate. We assessed heterogeneity using the I2 statistic and assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Main results: We identified 19 eligible studies (3459 individuals), all observational; 13 studies (1917 individuals) were suitable for inclusion in the meta-analysis of mortality. Of these, 12 studied patients infected with 2009 influenza A H1N1 virus (H1N1pdm09). Risk of bias was greatest in the 'comparability domain' of the Newcastle-Ottawa scale, consistent with potential confounding by indication. Data specific to mortality were of very low quality. Reported doses of corticosteroids used were high and indications for their use were not well reported. On meta-analysis, corticosteroid therapy was associated with increased mortality (odds ratio (OR) 3.06, 95% confidence interval (CI) 1.58 to 5.92). Pooled subgroup analysis of adjusted estimates of mortality from four studies found a similar association (OR 2.82, 95% CI 1.61 to 4.92). Three studies reported greater odds of hospital-acquired infection related to corticosteroid therapy; all were unadjusted estimates and we graded the data as very low quality. Authors' conclusions: We did not identify any completed RCTs of adjunctive corticosteroid therapy for treating influenza. The available evidence from observational studies is of very low quality with confounding by indication a major potential concern. Although we found that adjunctive corticosteroid therapy was associated with increased mortality, this result should be interpreted with caution. In the context of clinical trials of adjunctive corticosteroid therapy in sepsis and pneumonia that report improved outcomes, including decreased mortality, more high-quality research is needed (both RCTs and observational studies). Currently, we do not have sufficient evidence in this review to determine the effectiveness of corticosteroids for patients with influenza.
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spelling nottingham-376892020-05-04T17:42:40Z https://eprints.nottingham.ac.uk/37689/ Corticosteroids as adjunctive therapy in the treatment of influenza Rodrigo, Chamira Leonardi-Bee, Jo Nguyen-Van-Tam, Jonathan Lim, Wei Shen Background: Specific treatments for influenza are limited to neuraminidase inhibitors and adamantanes. Corticosteroids show evidence of benefit in sepsis and related conditions, most likely due to their anti-inflammatory and immunomodulatory properties. Although commonly prescribed for severe influenza, there is uncertainty over their potential benefit or harm. Objectives: To systematically assess the effectiveness and potential adverse effects of corticosteroids as adjunctive therapy in the treatment of influenza, taking into account differences in timing and doses of corticosteroids. Search methods: We searched CENTRAL (2015, Issue 5), MEDLINE (1946 to June week 1, 2015), EMBASE (1974 to June 2015), CINAHL (1981 to June 2015), LILACS (1982 to June 2015), Web of Science (1985 to June 2015), abstracts from the last three years of major infectious disease and microbiology conferences, and references of included articles. Selection criteria: We included randomised controlled trials (RCTs), quasi-RCTs and observational studies that compared corticosteroid treatment with no corticosteroid treatment for influenza or influenza-like illness. We did not restrict studies by language of publication, influenza subtypes, clinical setting or age of participants. We selected eligible studies in two stages: sequential examination of title and abstract, followed by full text. Data collection and analysis: Two pairs of review authors independently extracted data and assessed risk of bias. We pooled estimates of effect using random-effects meta-analysis models, where appropriate. We assessed heterogeneity using the I2 statistic and assessed the quality of the evidence using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) framework. Main results: We identified 19 eligible studies (3459 individuals), all observational; 13 studies (1917 individuals) were suitable for inclusion in the meta-analysis of mortality. Of these, 12 studied patients infected with 2009 influenza A H1N1 virus (H1N1pdm09). Risk of bias was greatest in the 'comparability domain' of the Newcastle-Ottawa scale, consistent with potential confounding by indication. Data specific to mortality were of very low quality. Reported doses of corticosteroids used were high and indications for their use were not well reported. On meta-analysis, corticosteroid therapy was associated with increased mortality (odds ratio (OR) 3.06, 95% confidence interval (CI) 1.58 to 5.92). Pooled subgroup analysis of adjusted estimates of mortality from four studies found a similar association (OR 2.82, 95% CI 1.61 to 4.92). Three studies reported greater odds of hospital-acquired infection related to corticosteroid therapy; all were unadjusted estimates and we graded the data as very low quality. Authors' conclusions: We did not identify any completed RCTs of adjunctive corticosteroid therapy for treating influenza. The available evidence from observational studies is of very low quality with confounding by indication a major potential concern. Although we found that adjunctive corticosteroid therapy was associated with increased mortality, this result should be interpreted with caution. In the context of clinical trials of adjunctive corticosteroid therapy in sepsis and pneumonia that report improved outcomes, including decreased mortality, more high-quality research is needed (both RCTs and observational studies). Currently, we do not have sufficient evidence in this review to determine the effectiveness of corticosteroids for patients with influenza. Wiley 2016-03-07 Article PeerReviewed Rodrigo, Chamira, Leonardi-Bee, Jo, Nguyen-Van-Tam, Jonathan and Lim, Wei Shen (2016) Corticosteroids as adjunctive therapy in the treatment of influenza. Cochrane Database of Systematic Reviews (3). CD010406. ISSN 1469-493X Humans Adrenal Cortex Hormones [adverse effects] [therapeutic use] Chemotherapy Adjuvant [adverse effects] Cross Infection [etiology] Influenza A Virus H1N1 Subtype Influenza Human [drug therapy] [mortality] Intensive Care Units [statistics & numerical data] Observational Studies as Topic http://onlinelibrary.wiley.com/doi/10.1002/14651858.CD010406.pub2/abstract;jsessionid=8D52364CBBDDD8C4B38DD7C01B67C18A.f02t01 doi:10.1002/14651858.CD010406.pub2 doi:10.1002/14651858.CD010406.pub2
spellingShingle Humans
Adrenal Cortex Hormones [adverse effects] [therapeutic use] Chemotherapy
Adjuvant [adverse effects] Cross Infection [etiology] Influenza A Virus
H1N1 Subtype Influenza
Human [drug therapy] [mortality] Intensive Care Units [statistics & numerical data] Observational Studies as Topic
Rodrigo, Chamira
Leonardi-Bee, Jo
Nguyen-Van-Tam, Jonathan
Lim, Wei Shen
Corticosteroids as adjunctive therapy in the treatment of influenza
title Corticosteroids as adjunctive therapy in the treatment of influenza
title_full Corticosteroids as adjunctive therapy in the treatment of influenza
title_fullStr Corticosteroids as adjunctive therapy in the treatment of influenza
title_full_unstemmed Corticosteroids as adjunctive therapy in the treatment of influenza
title_short Corticosteroids as adjunctive therapy in the treatment of influenza
title_sort corticosteroids as adjunctive therapy in the treatment of influenza
topic Humans
Adrenal Cortex Hormones [adverse effects] [therapeutic use] Chemotherapy
Adjuvant [adverse effects] Cross Infection [etiology] Influenza A Virus
H1N1 Subtype Influenza
Human [drug therapy] [mortality] Intensive Care Units [statistics & numerical data] Observational Studies as Topic
url https://eprints.nottingham.ac.uk/37689/
https://eprints.nottingham.ac.uk/37689/
https://eprints.nottingham.ac.uk/37689/