Sex-specific age-related worsening of pathological endotypic traits in patients with obstructive sleep apnea

Study Objectives Obstructive sleep apnea (OSA) is more prevalent in men and older adults. Few studies have explored variations in pathological endotypic traits by age and sex using a large patient sample, offering insights into the development of the disease. Our study aims to examine how endotype characteristics of OSA vary across ages in different sex.Methods A cross-sectional study was conducted, enrolling 2296 adult patients referred for in-laboratory diagnostic polysomnography at a single sleep center in Taiwan. Among them, 1374 had an apnea-hypopnea index >= 5. Using the "Phenotyping Using Polysomnography" method, we estimated four endotypic traits-arousal threshold, upper airway collapsibility, loop gain, and upper airway muscle compensation. Demographic and polysomnographic characteristics were compared between sexes and age groups. Generalized linear regression and generalized additive models were employed to explore the associations of sex and age with endotypic traits.Results Men with OSA exhibited higher collapsibility and lower compensation than women (difference: 4.32 %eupnea and 4.49 %eupnea, respectively). Younger patients with OSA had a higher prevalence of obesity, more snoring symptoms, and lower loop gain compared to older patients. For men, age was correlated with increased collapsibility, increased loop gain, and decreased arousal threshold after 37 years old. Whereas in women, endotypic traits were not associated with age, except for an increase in loop gain with advancing age.Conclusions Personalized treatment options for OSA should take into consideration age and sex. Reducing loop gain could be a treatment objective for older patients with OSA. Graphical Abstract