https://orcid.org/0000-0003-0313-7080
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Abstract
Introduction
Although β2-adrenoceptor (β2AR) agonists have been associated with a lower risk of Parkinson’s disease (PD), the findings are inconclusive and may reflect confounding by indication. We studied the association between inhaled β2AR agonists and risk of PD in persons with asthma or chronic obstructive pulmonary disease (COPD).
Methods
The nested case-control study was conducted within a register-based Finnish Parkinson’s disease study (FINPARK) and included 1406 clinically verified PD cases diagnosed during 1999–2015, who also had asthma/COPD >3 years before PD. PD cases were matched with up to seven controls by age, sex, duration of asthma/COPD, pulmonary diagnosis, and region (N = 8630). Cumulative and average annual exposure to short- and long-acting β2AR agonists before a 3-year lag period was assessed with quartiles of defined daily doses (DDDs). Adjusted odds ratios (aORs) were calculated with 95% confidence intervals (CIs) using conditional logistic regression.
Results
Cumulative exposure to either short- or long-acting β2AR agonists was not associated with a risk of PD. With average annual exposure, a decreased risk was observed only for the highest quartile of long-acting β2AR agonists (aOR 0.75; 95% CI 0.58–0.97). In the stratified analysis the lowest risk estimates were observed among those with both asthma and COPD diagnoses. The suggestion of an inverse association was seen for the highest quartile of long-acting β2AR agonists in asthma.
Discussion
Higher levels of exposure to β2AR agonists were not consistently associated with a reduced risk of PD. The inverse association in the highest category of average annual exposure to long-acting β2AR agonists may be explained by unmeasured confounding, such as disease severity or smoking.
Data Sharing Statement
The datasets generated and/or analysed during the current study are not publicly available due to restrictions by the register maintainers and Finnish legislation but are available from the corresponding author upon reasonable request and with permission of the register maintainers.
Ethics Approval and Informed Consent
Register maintainers have approved the FINPARK study plan. Data were pseudonymized before submission to the research team and study participants were not contacted. Therefore, according to Finnish legislation (including Personal Data Act 23/1999, Act on the Openness of Government Activities 621/1999 and Act on the Secondary Use of Health and Social Data 552/2019, and previous Act on the National Healthcare registers [no official English translation as this is not available] 556/1989), the study has been granted an exemption from requiring ethics approval or informed consent.
Acknowledgments
This paper was presented at the 18th Congress of the European Geriatric Medicine Society as online poster with interim findings. The poster’s abstract was published in Abstracts of the 18th Congress of the European Geriatric Medicine Society. Eur Geriatr Med 13 (Suppl 1), 1–439 (2022). https://doi.org/10.1007/s41999-022-00711-8. An oral presentation of this paper with interim findings was given at the 38th International Conference on Pharmacoepidemiology & Therapeutic Risk Management and at the 14th annual Nordic Pharmacoepidemiological Network meeting in 2022.
Author Contributions
All authors made a significant contribution to the work reported, whether that is in the conception, study design, execution, acquisition of data, analysis and interpretation, or in all these areas; took part in drafting, revising or critically reviewing the article; gave final approval of the version to be published; have agreed on the journal to which the article has been submitted; and agree to be accountable for all aspects of the work.
Disclosure
AP reports grant from the Finnish Parkinson Foundation and The Michael J. Fox Foundation for Parkinson’s Research. HK reports grants from Kuopio Area Respiratory Foundation and The Research Foundation of the Pulmonary Diseases and payment for lectures from Boehringer Ingelheim Ltd and MSD Ltd and Stock ownership of Orion Ltd, all outside the submitted work. JT reports grant from Janssen-Cilag paid to his employing institution, Karolinska Institutet. JT is also a consultant to HLS Therapeutics and WebMed Global and has received lecture fees from Janssen-Cilag and Otsuka; all outside of the submitted work. AMT reports grant from the Michael J Fox Foundation for Parkinson’s research (grant MJFF-008834 which paid salary for AP) related to this manuscript. AMT also reports research grant from Amgen, paid through the institution she is employed at, outside of the submitted manuscript. SH has got lecture fees from Eisai Ltd. MT and MK have no conflicts of interest to declare for this work.