β2-Adrenoceptor Agonists in Asthma or Chronic Obstructive Pulmonary Disease and Risk of Parkinson's Disease: Nested Case-Control Study.

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.