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Asthma
Original research
Asthma exacerbations are associated with a decline in lung function: a longitudinal population-based study
  1. Seyi Soremekun1,
  2. Liam G Heaney2,
  3. Derek Skinner3,4,
  4. Lakmini Bulathsinhala3,4,
  5. Victoria Carter3,4,
  6. Isha Chaudhry3,4,
  7. Naeimeh Hosseini3,4,
  8. Neva Eleangovan3,4,
  9. Ruth Murray3,4,
  10. Trung N Tran5,
  11. Benjamin Emmanuel5,
  12. Esther Garcia Gil6,
  13. Andrew Menzies-Gow7,
  14. Matthew Peters8,
  15. Njira Lugogo9,
  16. Rupert Jones4,10,
  17. David B Price4,11,12
  1. 1 London School of Hygiene and Tropical Medicine, London, UK, UK
  2. 2 UK Severe Asthma Network and National Registry, Queen’s University Belfast, Belfast, UK
  3. 3 Optimum Patient Care, Cambridge, UK
  4. 4 Observational and Pragmatic Research Institute, Singapore
  5. 5 AstraZeneca, Gaithersburg, Maryland, USA
  6. 6 AstraZeneca, Barcelona, Spain
  7. 7 UK Severe Asthma Network and National Registry, Royal Brompton & Harefield NHS Foundation Trust, London, UK
  8. 8 Department of Thoracic Medicine, Concord Hospital, Sydney, New South Wales, Australia
  9. 9 Department of Medicine, Division of Pulmonary and Critical Care Medicine, University of Michigan, Ann Arbor, Michigan, USA
  10. 10 Faculty of Medicine & Dentistry, University of Plymouth, Plymouth, UK
  11. 11 Optimum Patient Care UK, Cambridge, England, UK
  12. 12 Division of Applied Health Sciences, University of Aberdeen, Aberdeen, UK
  1. Correspondence to Professor David B Price, Optimum Patient Care UK, Cambridge, England, UK; dprice{at}opri.sg

Abstract

Rationale Progressive lung function (LF) decline in patients with asthma contributes to worse outcomes. Asthma exacerbations are thought to contribute to this decline; however, evidence is limited with mixed results.

Methods This historical cohort study of a broad asthma patient population in the Optimum Patient Care Research Database, examined asthma patients with 3+eligible post-18th birthday peak expiratory flow rate (PEF) records (primary analysis) or records of forced expiratory flow in 1 s (FEV1) (sensitivity analysis). Adjusted linear growth models tested the association between mean annual exacerbation rate (AER) and LF trajectory.

Results We studied 1 09 182 patients with follow-up ranging from 5 to 50 years, of which 75 280 had data for all variables included in the adjusted analyses. For each additional exacerbation, an estimated additional −1.34 L/min PEF per year (95% CI −1.23 to –1.50) were lost. Patients with AERs >2/year and aged 18–24 years at baseline lost an additional −5.95 L/min PEF/year (95% CI −8.63 to –3.28) compared with those with AER 0. These differences in the rate of LF decline between AER groups became progressively smaller as age at baseline increased. The results using FEV1 were consistent with the above.

Conclusion To our knowledge, this study is the largest nationwide cohort of its kind and demonstrates that asthma exacerbations are associated with faster LF decline. This was more prominent in younger patients but was evident in older patients when it was related to lower starting LF, suggesting a persistent deteriorating phenotype that develops in adulthood over time. Earlier intervention with appropriate management in younger patients with asthma could be of value to prevent excessive LF decline.

  • asthma

Data availability statement

Data are available upon reasonable request. The dataset supporting the conclusions of this article was derived from the Optimum Patient Care Research Database (www.opcrd.co.uk). The OPCRD has ethical approval from the National Health Service (NHS) Research Authority to hold and process anonymised research data (Research Ethics Committee reference: 15/EM/0150). This study was approved by the Anonymised Data Ethics Protocols and Transparency (ADEPT) committee – the independent scientific advisory committee for the OPCRD. The authors do not have permission to give public access to the study dataset; researchers may request access to OPCRD data for their own purposes. Access to OCPRD can be made via the OCPRD website (https://opcrd.co.uk/our-database/data-requests/) or via the enquiries email info@opcrd.co.uk.

http://creativecommons.org/licenses/by-nc/4.0/

This is an open access article distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited, appropriate credit is given, any changes made indicated, and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/.

https://doi.org/10.1136/thorax-2021-217032

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    Data availability statement

    Data are available upon reasonable request. The dataset supporting the conclusions of this article was derived from the Optimum Patient Care Research Database (www.opcrd.co.uk). The OPCRD has ethical approval from the National Health Service (NHS) Research Authority to hold and process anonymised research data (Research Ethics Committee reference: 15/EM/0150). This study was approved by the Anonymised Data Ethics Protocols and Transparency (ADEPT) committee – the independent scientific advisory committee for the OPCRD. The authors do not have permission to give public access to the study dataset; researchers may request access to OPCRD data for their own purposes. Access to OCPRD can be made via the OCPRD website (https://opcrd.co.uk/our-database/data-requests/) or via the enquiries email info@opcrd.co.uk.

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    Footnotes

    • Twitter @OPRI_SG

    • Correction notice This article has been corrected since it was published Online First. Some errors in the text have been fixed.

    • Contributors SS, DBP, LGH and TNT conceived the study analysis which was developed with input from all authors from inception. DBP acts as the guarantor. Data preparation and analysis was performed by SS and DS. SS and RM produced the first draft of the manuscript to which all authors contributed. The final version of the manuscript has been fully reviewed and approved by all authors.

    • Funding This study was conducted by the Observational and Pragmatic Research Institute (OPRI) Pte Ltd and was partially funded by Optimum Patient Care Global and AstraZeneca Ltd.

    • Competing interests DS, VC and NE are employees of Optimum Patient Care, and SS, LB, IC and NH were employees of Optimum Patient Care. Optimum Patient Care is a co-funder of the International Severe Asthma Registry. LGH declares he has received grant funding, participated in advisory boards and given lectures at meetings supported by Amgen, AstraZeneca, Boehringer Ingelheim, Circassia, Hoffmann la Roche, GlaxoSmithKline, Novartis, and Teva; he has taken part in asthma clinical trials sponsored by Boehringer Ingelheim, Hoffmann la Roche, and GlaxoSmithKline for which his institution received remuneration; he is the Academic Lead for the Medical Research Council Stratified Medicine UK Consortium in Severe Asthma which involves industrial partnerships with a number of pharmaceutical companies including Amgen, AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Hoffmann la Roche, and Janssen. TNT and BE are employees of AstraZeneca, and EGG was an employee of AstraZeneca. AstraZeneca is a co-funder of the International Severe Asthma Registry. AM-G has attended advisory boards for AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline, Novartis, Sanofi and Teva, and has received speaker fees from AstraZeneca, Boehringer Ingelheim, Novartis, Roche, Teva and Vectura. He has participated in research with AstraZeneca for which his institution has been remunerated and has attended international conferences with Teva. He has had consultancy agreements with AstraZeneca, Sanofi, and Vectura. MP declares personal fees and non-financial support from AstraZeneca and GlaxoSmithKline. NL consulted for AstraZeneca and GSK; served on protocol committee with AstraZeneca; and served on advisory board with AstraZeneca, GSK, Sanofi, Novartis, Genentech and Teva. RJ reports grants, personal fees, and non-financial support from AstraZeneca and OPRI, personal fees and non-financial support from Boehringer Ingelheim, grants, personal fees, and non-financial support from GSK, grants and non-financial support from Novartis, non-financial support from Nutricia, and personal fees from Pfizer outside the submitted work. DBP has advisory board membership with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, Circassia, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals, Thermofisher; consultancy agreements with Amgen, AstraZeneca, Boehringer Ingelheim, Chiesi, GlaxoSmithKline, Mylan, Mundipharma, Novartis, Pfizer, Teva Pharmaceuticals, 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, UK National Health Service; payment for lectures/speaking engagements from AstraZeneca, Boehringer Ingelheim, Chiesi, Cipla, GlaxoSmithKline, Kyorin, Mylan, Mundipharma, Novartis, Regeneron Pharmaceuticals, Sanofi Genzyme, Teva Pharmaceuticals; payment for the development of educational materials from Mundipharma, Novartis; payment for travel/accommodation/meeting expenses from AstraZeneca, Boehringer Ingelheim, Mundipharma, Mylan, Novartis, Thermofisher; 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); 5% shareholding in Timestamp which develops adherence monitoring technology; is peer reviewer for grant committees of the Efficacy and Mechanism Evaluation programme, and Health Technology Assessment; and was an expert witness for GlaxoSmithKline.

    • Provenance and peer review Not commissioned; externally peer reviewed.

    • Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.