β2-adrenoceptor Agonists and Risk of Parkinson's Disease: Nested Case-control Study of People with Asthma or Chronic Obstructive Pulmonary Disease

Background: β2-adrenoceptor (β2AR) agonists have been associated with a decreased risk of Parkinson's disease (PD), but there are only two previous studies that are restricted to persons with asthma or chronic obstructive pulmonary disease (COPD), a typical user population for these drugs.

Objectives: To study the association between use of β2AR agonists and risk of PD in persons with asthma or COPD.

Methods: The study was conducted within the register-based Finnish Parkinson's disease (FINPARK) study, a case-control study nested within population of Finland. This study included 1,406 cases with clinically verified PD diagnosed during 1999-2015, who also had asthma/COPD >3 years before PD. On the date of diagnosis (index date), PD cases were matched with up to seven control persons by age, sex, duration of asthma/COPD, pulmonary diagnosis, and region (N=8,630). Exposure to short- and long-acting β2AR agonists was extracted from the Prescription Register since 1995 until beginning of a 3-year lag period. Cumulative and average annual exposure was assessed among users with quartiles of defined daily doses (DDDs) and the lowest quartile was used as reference. Adjusted odds ratios (aORs) were calculated with 95% confidence intervals (CIs) using conditional logistic regression adjusted for confounders.


Results: Cumulative exposure to β2AR agonists in DDDs was not associated with risk of PD aOR; 95% CI for highest quartile of short-acting β2AR agonists 0.84; 0.69-1.02, and for long-acting β2AR agonists 0.88; 0.67-1.16. For 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) and when stratified according pulmonary diagnosis the lowest point estimates for relative risk (aOR 0.48) were observed among those with both asthma and COPD diagnoses. Suggestion of inverse association was seen for highest quartile of long-acting β2AR agonists in asthma (aOR 0.74; 95% CI 0.55-1.01).


Conclusions: Higher levels of exposure to β2AR agonists were not consistently associated with reduced risk of PD among persons with asthma/COPD. The protective association in highest category of annual exposure to long-acting β2AR agonists may be explained by unmeasured confounding such as disease severity or smoking.