Clinical Epidemiology (Jun 2023)
β2-Adrenoceptor Agonists in Asthma or Chronic Obstructive Pulmonary Disease and Risk of Parkinson’s Disease: Nested Case-Control Study
Abstract
Anne Paakinaho,1 Miia Tiihonen,1 Heikki Koskela,2,3 Marjaana Koponen,1,4 Jari Tiihonen,5,6 Sirpa Hartikainen,1 Anna-Maija Tolppanen1 1School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland; 2Unit for Medicine and Clinical Research, Pulmonary Division, Kuopio University Hospital, Kuopio, Finland; 3School of Medicine, Faculty of Health Sciences, University of Eastern Finland, Kuopio, Finland; 4Centre for Medicine Use and Safety, Faculty of Pharmacy and Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia; 5Department of Forensic Psychiatry, University of Eastern Finland, Niuvanniemi Hospital, Kuopio, Finland; 6Department of Clinical Neuroscience, Karolinska Institutet, and Center for Psychiatry Research, Stockholm City Council, Stockholm, SwedenCorrespondence: Anne Paakinaho, School of Pharmacy, Faculty of Health Sciences, University of Eastern Finland, P.O. Box 1627, Kuopio, FI-70211, Finland, Tel +358 405408490, Email [email protected]: Although β 2-adrenoceptor (β 2AR) 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 β 2AR 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 β 2AR 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 β 2AR 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 β 2AR 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 β 2AR agonists in asthma.Discussion: Higher levels of exposure to β 2AR 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 β 2AR agonists may be explained by unmeasured confounding, such as disease severity or smoking.Keywords: Parkinson disease, adrenergic beta-2 receptor agonists, asthma, chronic obstructive pulmonary disease, risk factors
