Patients with asthma or allergic rhinitis had modestly higher Parkinson disease incidence in a nationwide Korean cohort study, although the observational findings did not establish causality.
Researchers analyzed Korean National Health Insurance Service data from more than 5 million adults aged 40 years or older who underwent national health screening in 2009. Patients with prior Parkinson disease diagnoses between 2006 and 2009 were excluded, and incident Parkinson disease was identified from 2010 to 2019 using insurance claims data.
Allergic diseases were defined using ICD-10 diagnostic codes in combination with health care utilization criteria, including at least 2 outpatient visits per year for the same condition or at least 1 hospitalization between 2006 and 2009.
Following adjustment for demographic, lifestyle, and clinical factors, asthma was associated with a 16% higher hazard of Parkinson disease, and allergic rhinitis was associated with an 18% higher hazard. Atopic dermatitis was not significantly associated with Parkinson disease incidence.
Researchers also observed a dose-response relationship between allergic disease burden and Parkinson disease risk. Patients with more frequent outpatient visits for allergic disease had progressively higher Parkinson disease incidence, and patients with both asthma and allergic rhinitis had a 28% higher hazard of Parkinson disease compared with patients without either condition.
Age-stratified analyses showed that the association between asthma and Parkinson disease was stronger among patients younger than 65 years, whereas allergic rhinitis and overall allergic disease burden showed stronger associations among older patients. No statistically significant interactions were observed for sex, smoking status, alcohol use, or physical activity.
The findings may support hypotheses linking chronic airway inflammation with neuroinflammatory pathways involved in Parkinson disease. In their discussion, the researchers noted that allergic airway diseases affect the nasal mucosa and respiratory tract, which are connected to the olfactory system — a proposed early site of alpha-synuclein accumulation in Parkinson disease pathogenesis. The lack of association with atopic dermatitis may further support the possibility that airway-specific inflammatory mechanisms contribute to the observed relationship.
In a separate hospital-based analysis, researchers compared peripheral blood counts from 234 patients with Parkinson disease and 468 age- and sex-matched controls. Patients with Parkinson disease had higher eosinophil and neutrophil counts, higher eosinophil-to-neutrophil ratios, and a greater proportion with eosinophil counts of 200 cells/µL or higher.
Medication subgroup analyses were exploratory and susceptible to confounding by disease severity and treatment indication. Researchers reported lower Parkinson disease risk among patients using oral beta-2 agonists, whereas systemic corticosteroid use was associated with higher Parkinson disease risk among patients with asthma and allergic rhinitis — an association the researchers suggested likely reflected greater underlying allergic disease severity rather than a direct pharmacologic effect. Antihistamine findings differed by disease subtype, with higher Parkinson disease risk observed among antihistamine users with asthma but among nonusers with allergic rhinitis.
The investigators acknowledged several limitations, including the observational design, reliance on claims-based diagnoses, and the possibility of surveillance bias because patients with allergic disease may have more frequent health care encounters. They also noted that prodromal Parkinson disease could not be fully excluded despite the washout period, raising the possibility of reverse causation. Additionally, the hospital-based blood analysis was cross-sectional and could not establish temporal relationships between eosinophilia and Parkinson disease.
The cohort consisted entirely of patients in South Korea, which may limit generalizability to other populations.
“Despite these limitations, our findings consistently demonstrate that individuals with allergic diseases, particularly those with greater severity or multimorbidity, are at higher risk for developing PD,” wrote first study author Hee Jin Chang, MD, of Chungnam National University Hospital and Chungnam National University College of Medicine, Daejeon, South Korea, and colleagues.
Disclosures: The researchers reported no competing financial or nonfinancial interests. No funding was received.
Source: npj Parkinson’s Disease