TY - JOUR
T1 - Hormone Replacement Therapy and Risk of Severe Asthma Exacerbation in Perimenopausal and Postmenopausal Women
T2 - 17-Year National Cohort Study
AU - Nwaru, Bright I.
AU - Shah, Syed A.
AU - Tibble, Holly
AU - Pillinger, Rebecca
AU - Mclean, Susannah
AU - Ryan, Dermot
AU - Critchley, Hilary
AU - Hawrylowicz, Catherine M.
AU - Simpson, Colin R.
AU - Soyiri, Ireneous N.
AU - Appiagyei, Francis
AU - Price, David
AU - Sheikh, Aziz
N1 - Funding Information:
This work was supported by Asthma UK, grant number: AUK-IG-2016-346 and Health Data Research UK. We thank Optimum Patient Care (OPC) and Observational and Pragmatic Research Institute Pte Ltd (OPRI) for making the OPCRD database (www.opcrd.co.uk) available free of charge. B. I. Nwaru acknowledges the support of Knut and Alice Wallenberg Foundation, the Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg, Sweden, and the VBG Group Herman Krefting Foundation on Asthma and Allergy. A. Sheikh acknowledges support of Health Data Research UK (BREATHE).Conflicts of interest: C. R. Simpson, A. Sheikh, and C. M. Hawrylowicz currently receive funding from Asthma UK, and A. Sheikh also received funding from Health Data Research UK. S. McLean was funded by Asthma UK and the University of Edinburgh for her contribution. H. Critchley has clinical research support for laboratory consumables and staff from Bayer AG; and provides consultancy advice (but with no personal remuneration) for Bayer AG, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc, and Myovant Sciences GmbH; and receives royalties from UpToDate for an article on abnormal uterine bleeding. D. Price has board membership with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals, and Thermo Fisher; consultancy agreements with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Mundipharma, Novartis, Pfizer, Teva Pharmaceuticals, and Theravance; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Teva Pharmaceuticals, Theravance, and UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, and Teva Pharmaceuticals; payment for the development of educational materials from Mundipharma and Novartis; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartism, and Thermo Fisher; funding for patient enrolment or completion of research from Novartis; 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); and is a peer reviewer for grant committees of the Efficacy and Mechanism Evaluation Programme and Health Technology Assessment Programme. The rest of the authors declare that they have no relevant conflicts of interest.
Funding Information:
This work was supported by Asthma UK , grant number: AUK-IG-2016-346 and Health Data Research UK . We thank Optimum Patient Care (OPC) and Observational and Pragmatic Research Institute Pte Ltd (OPRI) for making the OPCRD database (www.opcrd.co.uk) available free of charge. B. I. Nwaru acknowledges the support of Knut and Alice Wallenberg Foundation , the Wallenberg Centre for Molecular and Translational Medicine, University of Gothenburg , Sweden, and the VBG Group Herman Krefting Foundation on Asthma and Allergy . A. Sheikh acknowledges support of Health Data Research UK (BREATHE).
Funding Information:
Conflicts of interest: C. R. Simpson, A. Sheikh, and C. M. Hawrylowicz currently receive funding from Asthma UK , and A. Sheikh also received funding from Health Data Research UK . S. McLean was funded by Asthma UK and the University of Edinburgh for her contribution. H. Critchley has clinical research support for laboratory consumables and staff from Bayer AG ; and provides consultancy advice (but with no personal remuneration) for Bayer AG, PregLem SA, Gedeon Richter, Vifor Pharma UK Ltd, AbbVie Inc, and Myovant Sciences GmbH; and receives royalties from UpToDate for an article on abnormal uterine bleeding. D. Price has board membership with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals, and Thermo Fisher; consultancy agreements with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Mundipharma, Novartis, Pfizer, Teva Pharmaceuticals, and Theravance; grants and unrestricted funding for investigator-initiated studies (conducted through Observational and Pragmatic Research Institute Pte Ltd) from AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Pfizer, Regeneron Pharmaceuticals, Respiratory Effectiveness Group, Sanofi Genzyme, Teva Pharmaceuticals, Theravance, and UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, and Teva Pharmaceuticals; payment for the development of educational materials from Mundipharma and Novartis; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartism, and Thermo Fisher; funding for patient enrolment or completion of research from Novartis; 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); and is a peer reviewer for grant committees of the Efficacy and Mechanism Evaluation Programme and Health Technology Assessment Programme . The rest of the authors declare that they have no relevant conflicts of interest.
Publisher Copyright:
© 2021 The Authors
PY - 2021/7
Y1 - 2021/7
N2 - Background: The impact of hormone replacement therapy (HRT) on clinical outcomes in menopausal women is uncertain. Objective: To investigate the association between use of HRT and severe asthma exacerbation in perimenopausal and postmenopausal women with asthma. Methods: We used the Optimum Patient Care Research Database, a population-based longitudinal primary care database in the United Kingdom, to construct a 17-year (January 1, 2000, to December 31, 2016) cohort of perimenopausal and postmenopausal (46-70 years, N = 31,656) women. We defined use of HRT, its subtypes, and duration of HRT use. Severe asthma exacerbation was defined as an asthma-related hospitalization, emergency department visits due to asthma, and/or prescription of oral corticosteroids. Analyses were undertaken using multilevel mixed-effects Poisson regression. Results: At baseline, 22% of women were using any HRT, 11% combined HRT, and 11% estrogen-only HRT. Previous, but not current, use of any (incidence rate ratio [IRR]: 1.24, 95% confidence interval [CI]: 1.22-1.26), combined (IRR: 1.28, 95% CI: 1.25-1.31), and estrogen-only HRT (IRR: 1.18, 95% CI: 1.14-1.21), and longer duration (1-2 years: IRR: 1.16, 95% CI: 1.13-1.19; 3-4 years: IRR: 1.43, 95% CI: 1.38-1.48; 5+ years: IRR: 1.32, 95% CI: 1.28-1.36) of HRT use were associated with increased risk of severe asthma exacerbation compared with nonuse. The risk estimates were greater among lean women (body mass index [BMI] <25 kg/m2) than among heavier women (BMI 25-29.9 kg/m2 and ≥30 kg/m2) and higher among smokers than nonsmokers. Conclusion: Use of HRT and subtypes, particularly previous, but not current, use and use for more than 2 years, is associated with an increased risk of severe asthma exacerbation in perimenopausal/postmenopausal women with established asthma. Lean women and smokers are at greater risk than heavier women and nonsmokers, respectively.
AB - Background: The impact of hormone replacement therapy (HRT) on clinical outcomes in menopausal women is uncertain. Objective: To investigate the association between use of HRT and severe asthma exacerbation in perimenopausal and postmenopausal women with asthma. Methods: We used the Optimum Patient Care Research Database, a population-based longitudinal primary care database in the United Kingdom, to construct a 17-year (January 1, 2000, to December 31, 2016) cohort of perimenopausal and postmenopausal (46-70 years, N = 31,656) women. We defined use of HRT, its subtypes, and duration of HRT use. Severe asthma exacerbation was defined as an asthma-related hospitalization, emergency department visits due to asthma, and/or prescription of oral corticosteroids. Analyses were undertaken using multilevel mixed-effects Poisson regression. Results: At baseline, 22% of women were using any HRT, 11% combined HRT, and 11% estrogen-only HRT. Previous, but not current, use of any (incidence rate ratio [IRR]: 1.24, 95% confidence interval [CI]: 1.22-1.26), combined (IRR: 1.28, 95% CI: 1.25-1.31), and estrogen-only HRT (IRR: 1.18, 95% CI: 1.14-1.21), and longer duration (1-2 years: IRR: 1.16, 95% CI: 1.13-1.19; 3-4 years: IRR: 1.43, 95% CI: 1.38-1.48; 5+ years: IRR: 1.32, 95% CI: 1.28-1.36) of HRT use were associated with increased risk of severe asthma exacerbation compared with nonuse. The risk estimates were greater among lean women (body mass index [BMI] <25 kg/m2) than among heavier women (BMI 25-29.9 kg/m2 and ≥30 kg/m2) and higher among smokers than nonsmokers. Conclusion: Use of HRT and subtypes, particularly previous, but not current, use and use for more than 2 years, is associated with an increased risk of severe asthma exacerbation in perimenopausal/postmenopausal women with established asthma. Lean women and smokers are at greater risk than heavier women and nonsmokers, respectively.
KW - Asthma exacerbation
KW - Cohort study
KW - Combined hormone therapy
KW - Estrogen-only therapy
KW - Hormone replacement therapy
KW - Menopause
KW - Women
UR - http://www.scopus.com/inward/record.url?scp=85106222049&partnerID=8YFLogxK
U2 - 10.1016/j.jaip.2021.02.052
DO - 10.1016/j.jaip.2021.02.052
M3 - Article
C2 - 33705997
VL - 9
SP - 2751-2760.e1
JO - The Journal of Allergy and Clinical Immunology: In Practice
JF - The Journal of Allergy and Clinical Immunology: In Practice
SN - 2213-2198
IS - 7
ER -