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A real-life comparative effectiveness study into the addition of antibiotics to the management of asthma exacerbations in primary care

Clare S. Murray, Sarah J. Lucas, John Blakey, Alan Kaplan, Alberto Papi, James Paton, Wanda Phipatanakul, David Price, Oon Hoe Teoh, Mike Thomas, Steve Turner, Nikolaos G. Papadopoulos
European Respiratory Journal 2021; DOI: 10.1183/13993003.03599-2020
Clare S. Murray
1Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
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Sarah J. Lucas
2Respiratory Effectiveness Group, Ely, UK
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John Blakey
3Respiratory Medicine, Sir Charles Gairdner Hospital, Perth, Australia
4Australia and Medical School, Curtin University, Perth, Australia
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Alan Kaplan
5Family Physician Airways Group of Canada, University of Toronto, Thornhill, ON, Canada
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Alberto Papi
6Respiratory Medicine, Dept of Medical Sciences, University of Ferrara, Ferrara, Italy
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James Paton
7School of Medicine, University of Glasgow, Glasgow, UK
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Wanda Phipatanakul
8Department of Pediatrics, Boston Children's Hospital, Boston, MA, United States
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David Price
9Observational and Pragmatic Research Institute, Singapore, Singapore
10Centre of Academic Primary Care, Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK
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Oon Hoe Teoh
11Department of Paediatrics, KK Women's and Children's Hospital, Singapore, Singapore
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Mike Thomas
12Primary Care and Population Sciences, Faculty of Medicine, University of Southampton, Southampton, UK
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Steve Turner
13Child Health, University of Aberdeen, Aberdeen, UK
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Nikolaos G. Papadopoulos
1Division of Infection, Immunity and Respiratory Medicine, School of Biological Sciences, Faculty of Biology, Medicine and Health, University of Manchester, NIHR Manchester Biomedical Research Centre, Manchester University Hospitals NHS Foundation Trust, Manchester Academic Health Science Centre, Manchester, UK
14Allergy Department, 2nd Pediatric Clinic, National and Kapodistrian University of Athens, Athens, Greece
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  • For correspondence: nikolaos.papadopoulos@manchester.ac.uk
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Abstract

Background Asthma exacerbations are major contributors to asthma morbidity and mortality. They are usually managed with bronchodilators and oral corticosteroids (OCS), but clinical trial evidence suggests antibiotics could be beneficial. We aimed to assess whether treatment of asthma exacerbations with antibiotics in addition to OCS improved outcomes in larger more representative routine care populations.

Method A retrospective comparative effectiveness study into managing asthma exacerbations with OCS alone versus OCS plus antibiotics was conducted using the Optimum Patient Care Research Database. The dataset included 28 637 patients, following propensity score matching 20 024 adults and 4184 children were analysed.

Results Antibiotics in addition to OCS were prescribed for the treatment of asthma exacerbations in 45% of adults and 32% of children.

Compared to OCS alone, OCS plus antibiotics was associated with reduced risk of having an asthma/wheeze consultation in the following 2 weeks (children HR 0.84 (95% CI 0.73–0.96), p=0.012; adults HR 0.86 (95% CI 0.81–0.91), p<0.001), but an increase in risk of a further OCS prescription for a new/ongoing exacerbation within 6 weeks in adults (HR 1.11 (95% CI 1.01–1.21), p=0.030), but not children.

Penicillins, but not macrolides, were associated with a reduction in the odds of a subsequent asthma/wheeze consultation compared to OCS alone, in both adults and children.

Conclusion Antibiotics were frequently prescribed in relation to asthma exacerbations, contrary to guideline recommendations. Overall, the routine addition of antibiotics to OCS in the management of asthma exacerbations appeared to confer little clinical benefit, especially when considering the risks of antibiotic overuse.

Footnotes

This manuscript has recently been accepted for publication in the European Respiratory Journal. It is published here in its accepted form prior to copyediting and typesetting by our production team. After these production processes are complete and the authors have approved the resulting proofs, the article will move to the latest issue of the ERJ online. Please open or download the PDF to view this article.

Conflict of interest: Dr. Murray reports personal fees from AstraZeneca, personal fees from Thermo Fisher, personal fees from Boehringer Ingelheim, personal fees from GSK, personal fees from Novartis, outside the submitted work.

Conflict of interest: Dr. Lucas has nothing to disclose.

Conflict of interest: Dr. Blakey reports personal fees and non-financial support from AstraZeneca, personal fees from TEVA, personal fees and non-financial support from Boehringer Ingelheim, non-financial support from GSK, grants from Novartis, outside the submitted work.

Conflict of interest: Dr. Kaplan reports personal fees from AstraZeneca, personal fees from Behring, personal fees from Boehringer Ingelheim, personal fees from GSK, personal fees from Novartis, personal fees from Reva, personal fees from Covis, personal fees from Merck, personal fees from Trudell, personal fees from Pfizer, personal fees from Purdue, personal fees from NovoNordisk, personal fees from Griffols, outside the submitted work.

Conflict of interest: Dr. Papi reports grants, personal fees, non-financial support and other from GlaxoSmithKline, grants, personal fees and non-financial support from AstraZeneca, grants, personal fees, non-financial support and other from Boehringer Ingelheim, grants, personal fees, non-financial support and other from Chiesi Farmaceutici, grants, personal fees, non-financial support and other from TEVA, personal fees, non-financial support and other from Mundipharma, personal fees, non-financial support and other from Zambon, personal fees, non-financial support and other from Novartis, grants, personal fees and non-financial support from Menarini, personal fees, non-financial support and other from Sanofi/Regeneron, personal fees from Roche, grants from Fondazione Maugeri, grants from Fondazione Chiesi, personal fees from Edmondpharma, outside the submitted work.

Conflict of interest: Dr. Paton has nothing to disclose.

Conflict of interest: Dr. Phipatanakul reports grants and personal fees from Genentech/Novartis, grants and personal fees from Regeneron/Sanofi, other from thermo fisher, other from gsk, other from kaleo, other from lincoln diagnostics, other from monaghen, during the conduct of the study.

Conflict of interest: Dr. Price reports grants and personal fees from AstraZeneca, grants and personal fees from Chiesi, grants and personal fees from Boehringer Ingelheim, grants and personal fees from Teva Pharmaceuticals, grants, personal fees and other from Novartis, grants and personal fees from Circassia, grants and personal fees from Mylan, grants and personal fees from Regeneron Pharmaceuticals, grants and personal fees from Mundipharma, grants and personal fees from Pfizer, grants from Respiratory Effectiveness Group, grants and personal fees from Sanofi Genzyme, grants and personal fees from Theravance, grants from UK National Health Service, personal fees from Amgen, personal fees from GSK, personal fees from Cipla, personal fees from Kyorin, personal fees from Thermofisher, outside the submitted work; and Stock/stock options from AKL Research and Development Ltd which produces phytopharmaceuticals; owns 74% of the social enterprise Optimum Patient Care Ltd (Australia and UK) and 74% of Observational and Pragmatic Research Institute Pte Ltd (Singapore); is peer reviewer for grant committees of the Efficacy and Mechanism Evaluation programme, and Health Technology Assessment; and was an expert witness for GlaxoSmithKline.

Conflict of interest: Dr. Teoh has nothing to disclose.

Conflict of interest: Dr. Thomas reports personal fees from GSK, personal fees from Novartis, personal fees from Boehringer Ingelheim, outside the submitted work.

Conflict of interest: Dr. Turner has nothing to disclose.

Conflict of interest: Dr. Papadopoulos reports personal fees from Novartis, personal fees from Nutricia, personal fees from HAL, personal fees from MENARINI/FAES FARMA, personal fees from SANOFI, personal fees from MYLAN/MEDA, personal fees from BIOMAY, personal fees from AstraZeneca, personal fees from GSK, personal fees from MSD, personal fees from ASIT BIOTECH, personal fees from Boehringer Ingelheim, grants from Gerolymatos International SA, grants from Capricare, outside the submitted work.

This is a PDF-only article. Please click on the PDF link above to read it.

  • Received May 22, 2020.
  • Accepted December 7, 2020.
  • Copyright ©ERS 2021
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A real-life comparative effectiveness study into the addition of antibiotics to the management of asthma exacerbations in primary care
Clare S. Murray, Sarah J. Lucas, John Blakey, Alan Kaplan, Alberto Papi, James Paton, Wanda Phipatanakul, David Price, Oon Hoe Teoh, Mike Thomas, Steve Turner, Nikolaos G. Papadopoulos
European Respiratory Journal Jan 2021, 2003599; DOI: 10.1183/13993003.03599-2020

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A real-life comparative effectiveness study into the addition of antibiotics to the management of asthma exacerbations in primary care
Clare S. Murray, Sarah J. Lucas, John Blakey, Alan Kaplan, Alberto Papi, James Paton, Wanda Phipatanakul, David Price, Oon Hoe Teoh, Mike Thomas, Steve Turner, Nikolaos G. Papadopoulos
European Respiratory Journal Jan 2021, 2003599; DOI: 10.1183/13993003.03599-2020
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