Year: 2021
Type: conference-abstract
Abstract: Background.We have discovered that androgen receptors (ARs) are expressed in human airways.Androgens may benefit asthma, and asthma prevalence is lower in men than in women.Indeed, AR deficient mice have increased severity of antigen-induced airway inflammation and bronchoconstriction.We therefore hypothesized that in humans, as in the mice, AR deficiency is associated with increased asthma risk.Methods.Patients with complete androgen insensitivity syndrome (AIS; ICD10 E34.51) or incomplete AIS (E34.52) have an inherited loss of AR function.The risk of asthma in human AR deficiency has not been studied.We analyzed the prevalence of asthma in AIS among 76,200,860 unique patients in IBM® Explorys, using ICD-10-CM codes for asthma (J45*) and for complete and incomplete AIS.Risk was adjusted for age category, obesity and nicotine addiction using a logistic regression model.We excluded COPD (J44*).In a validation study, we compared all AIS to age-matched controls among ∼18 million unique subjects in the Indiana Network for Patient Care Oracle database at the Regenstrief Institute.IRB approvals were from the Cleveland Clinic (Explorys analysis) and Indiana University (Regenstrief analysis).Results.In Explorys, 310 patients had complete, and 670 incomplete, AIS.Asthma prevalence was higher in AIS (both complete and incomplete) than in controls (18.4% vs 6.8%, p<0.001).The odds ratio (OR) for having asthma was higher in complete than incomplete AIS (vs.controls, with 95% CI: 4.01 [3.07-5.24] vs. 2.65 [2.16 -3.26].Asthma risk was increased after adjustment for age, obesity and nicotine dependence (adjusted OR [95% CI]: 2.01 [1.77 -2.29]).Adjusted risk was also higher in nonsmokers with complete ; n=220) than incomplete AIS 2.28 [1.76 -2.99]; n=530).In the validation cohort, there were 65 AIS or incomplete AIS patients and 130 age-matched controls.The OR for having asthma was 2. 26 [1.2-4.28].Conclusion.AIS is strongly associated with increased asthma risk; and this risk is higher in complete than in partial AIS.This work suggests for the first time that large, EMR-based dataset may be useful for studying genetic deletions in human diseases in general; and in sexually dimorphic diseases in particular.We demonstrate that AR can have a protective effect against human asthma.This information will be of immediate importance to a variety medical and surgical practitioners.Further, it suggests the possibility that androgen signaling might be exploited to therapeutic benefit in asthma.
Language: English
Subfield: Physiology
Field: Medicine
Domain: Health Sciences
Open Access status: gold
OpenAlex ID: W4247090948