The Korean Obstructive Sleep Apnea Morbidity Study (KOSMOS) Protocol

Article information

Chronobiol Med. 2025;7(2):102-109

Publication date (electronic) : 2025 June 27

doi : https://doi.org/10.33069/cim.2025.0004

Sei Won Kim¹, Hyeon Hui Kang¹, Kyu Yean Kim², Jin Woo Kim², Hong Jun Jeon³, Doo-Heum Park³, Jae Won Choi⁴, Eui Joong Kim⁴, Dong-Hyun Joo⁵, Young Jae Cho⁵, Sei Won Lee⁶, So-Jin Lee⁷, Wan Seok Seo⁸, So-Hyun Ahn⁹, Seok-Jin Hong¹⁰, Jin Oh Na¹¹, Sang Haak Lee^,1, Korean Academy of Sleep Medicine

¹Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea

²Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Uijeongbu, Korea

³Department of Psychiatry, Konkuk University Medical Center, Konkuk University School of Medicine, Seoul, Korea

⁴Department of Psychiatry, Nowon Eulji Medical Center, Eulji University, Seoul, Korea

⁵Division of Pulmonary and Critical Care Medicine, Department of Internal Medicine, Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seongnam, Korea

⁶Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Korea

⁷Department of Psychiatry, Gyeongsang National University School of Medicine, Jinju, Korea

⁸Department of Psychiatry, Yeungnam University College of Medicine, Daegu, Korea

⁹Department of Psychiatry, Chungnam National University Hospital, Daejeon, Korea

¹⁰Department of Otorhinolaryngology-Head & Neck Surgery, Kangbuk Samsung Hospital, Sungkyunkwan University School of Medicine, Seoul, Korea

¹¹Division of Cardiology, Department of Internal Medicine, Korea University Guro Hospital, Seoul, Korea

Corresponding author: Sang Haak Lee, MD, PhD, Division of Pulmonary, Critical Care and Sleep Medicine, Department of Internal Medicine, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, 1021 Tongil-ro, Eunpyeong-gu, Seoul 03312, Korea. Tel: 82-2-2030-4640, E-mail: mdlee@catholic.ac.kr

Received 2025 January 27; Revised 2025 February 13; Accepted 2025 February 20.

Abstract

INTRODUCTION

Obstructive sleep apnea (OSA) is characterized by repetitive upper airway narrowing or collapse during sleep, which causes intermittent hypoxia and sleep fragmentation [1,2]. The estimated prevalence of OSA in the general population is 9%–38% [3]. Moreover, the prevalence of OSA is 20%–50% among the population aged ≥65 years [4,5] and >40% among the obese [6,7]. However, up to 80% of moderate-to-severe OSA cases are undiagnosed despite adequate access to medical services [8,9]. OSA is associated with hypertension, diabetes mellitus, atrial fibrillation, heart failure, coronary heart disease, stroke, and death [10-13]. Intermittent hypoxemia, sympathetic activation, oxidative stress, and inflammation have been proposed as the underlying mechanisms [14-16].

Currently, diagnosis and treatment of OSA relies primarily on the apnea-hypopnea index (AHI). However, OSA is a heterogeneous syndrome, with various predisposing factors, pathophysiological mechanisms, clinical presentations, and consequences of respiratory events [17,18]. As a result, treatment compliance and outcomes vary among the clinical subtypes of OSA [17]. The best OSA treatment approach involves accurate clinical subtype diagnosis and long-term follow-up. A large-scale cohort study of OSA patients is needed.

In Korea, the number of sleep studies has increased sharply since national health insurance coverage started in 2018 [19]. Korean patients with OSA are approached and treated differently by specialists in internal medicine, otolaryngology, neurology, and psychiatry. Therefore, multicenter, multidisciplinary research is essential for determining the clinical characteristics of Korean OSA patients, who have different anatomical structures from those of Westerners, to allow for treatment tailored to Koreans. For this purpose, the Korean Obstructive Sleep apnea Morbidity Study (KOSMOS), a prospective large multicenter cohort, was designed.

METHODS

Measurements

Baseline characteristics

Demographic characteristics determined at visit 0 or 1 included sex, age, clinical department enrolled from, employment, shift work, menopause, bed partner, and pets (Table 1). Health-related behaviors such as smoking, alcohol, and caffeine use were examined at visit 1 (V1) and every 12 months thereafter. Smoking history was assessed in terms of current smoking status, amount smoked, and age of smoking initiation/cessation. Smoking status was classified as never-smoker, ex-smoker, current smoker, and unknown. Never-smoker was defined as lifetime smoking of less than five packs (100 cigarettes). Ex-smoker and current smoker were defined as lifetime smoking of more than five packs (100 cigarettes), and participants were classified according to whether they had smoked within the last 30 days. Alcohol history was investigated in terms of the frequency and amount of drinking, and the frequency of excessive drinking. Caffeine intake per day was investigated according to the content of each beverage. Medical and medication history, presence of snoring, allergy, and survival were checked at V1 and every 12 months thereafter. Family medical history was checked at V1 and every 12 months thereafter.

Table 1.

Summary of the Korean Obstructive Sleep apnea Morbidity Study (KOSMOS) data collection

Anthropometric measurements

Anthropometric measurements and blood pressure were taken by trained researchers or nurses in the hospital, with the subjects wearing light clothing with no shoes. Height and neck/waist/hip circumference were measured to the nearest 0.1 cm and body weight to the nearest 0.1 g. Neck, waist, and hip circumference were measured using standardized procedures at the levels of the cricothyroid membrane, midpoint between lowest palpable rib and iliac crest, and greater trochanter, respectively. Circumferences were measured with the patients in a standing position using a flexible anthropometric tape. Circumference measurements are taken while ensuring even breathing and during a gentle exhalation, ensuring that the tape does not compress the skin. Except for height, the anthropometric measurements were checked at V1 and every 12 months thereafter. Height was measured only once, at V1. Body mass index (BMI) was calculated as body weight in kilograms divided by height in meters squared. Blood pressure measured before and after sleep for PSG was recorded at V1 and every 12 months thereafter; the blood pressure was measured once during a clinical visit using an automatic device with the correct cuff size after resting in a stable position for 5 minutes.

Questionnaires

The Fatigue Severity Scale (FSS) [21], Korean Translation of Composite Scale (KtCS) [22], Korean version of the Pittsburgh Sleep Quality Index (PSQI-K) [23], Korean version of the Epworth Sleepiness Scale (KESS) [24], International Prostate Symptom Score (IPSS) [25], Hospital Anxiety and Depression Scale (HADS) [26], Korean version of the Berlin Questionnaire (K-BQ) [27], Snoring, Tiredness, Observed apnea and high blood Pressure–Body mass index, Age, Neck circumference, Gender (STOPBANG) questionnaire [28], Insomnia Severity Index (ISI) [29], and Quality of Life Scale-abbreviated version (QOL BREF) [30] were administered at enrollment. The presence or absence of the four symptoms listed in the diagnostic criteria for restless leg syndrome (RLS) published by the International Restless Legs Syndrome Study Group (IRLSSG) was also checked at enrollment [31]. Except for IRLSSG-based RLS diagnostic criteria and KtCS, all questionnaires are administered at 12-month intervals.

Polysomnography

All PSG raw data were scored by experienced sleep technicians according to the American Academy of Sleep Medicine (AASM) manual for the scoring of sleep and associated events. All reports were reviewed and interpreted by sleep physicians at each sleep center. Total sleep time, sleep efficiency, sleep latency, rapid eye movement (REM) latency, sleep stages, awakenings, arousals, apnea and hypopnea, limb movements, snores, oxygen desaturation, average/minimum/maximum oxygen saturation during desaturation, obstructive/mixed/central/total apnea, obstructive/mixed/central/total hypopnea, AHI, respiratory effort-related arousal, respiratory disturbance index (RDI), and respiratory event duration were recorded at V1. After PSG at V1, treatment options (PAP therapy, non-PAP therapy, or observation without treatment) were assessed. For patients who underwent PAP titration, PAP type, pressure, periodic limb movements, and supplemental oxygen use were also checked at V1.

PAP therapy and compliance

Patients receiving PAP treatment were surveyed at V2 and every 12 months thereafter regarding the method of and compliance to PAP treatment. Interface, PAP type, pressure, usage (average use time [all days] and percentage of days with use ≥4 h), average AHI, supplemental oxygen, leak, and the manufacturer and model of PAP device were recorded.

Data collection and management

Study data are collected by sites and entered into a central e-clinical trial platform (Korea University Medical Center [KUMC] MEBICA System, http://kumc.mebica.net). Data validation and the assessment of missing data are carried out by the KOSMOS cohort’s quality control committee, comprised of statistical cohort experts, in collaboration with the Clinical Trial Center of Korea University Anam Hospital. Regular data reports and reviews are conducted on a quarterly basis. Periodic audits are conducted independent of the site investigators.

FINDINGS TO DATE

From April 2020 to January 2025, 529 OSA patients (386 males, 143 females) were enrolled. Due to the impact of COVID-19, patient enrollment encountered challenges in the early stages of the research; however, the rate of registration recovered following the pandemic. The median age, BMI, and neck circumference were 60.0 (range: 45.0–68.0) years, 27.4 (range: 24.7–30.5) kg/m², and 38.0 (range: 36.0–41.0) cm, respectively (Table 2). The most common comorbidities were dyslipidemia (43.5%), hypertension (28.2%), diabetes (21.7%), rhinitis (18.7%), asthma (15.3%), and fatty liver (15.3%). The respective prevalences of arrhythmia, coronary artery disease, other heart diseases, and cerebrovascular disease were 7.4%, 6.8%, 10.4%, and 4.0%, respectively. Comparing men and women, there were significant differences in age (p<0.001), neck circumference (p<0.001), waist circumference (p<0.001), and smoking status (p<0.001). The main reasons for visiting a sleep clinic were snoring, apnea, choking, daytime sleepiness, and fatigue (Table 3). Snoring was the most common reason for a hospital visit in both men and women. Apnea and choking were significantly more frequent reasons for a hospital visit in men than women (p<0.001). By contrast, insomnia and lower extremity tremor or discomfort were more frequent reasons for a hospital visit in women (p=0.015 and p=0.022, respectively). The median AHI, RDI, and oxygen desaturation index (ODI) were 34.2 (range: 20.1–55.6), 37.8 (range: 20.7–59.5), and 26.6 (range: 13.9–46.7), respectively (Table 4). Men had significantly higher AHI, RDI, and ODI values than women (p=0.002, p=0.006, and p=0.003, respectively). The minimum oxygen saturation during non-REM (NREM) and REM sleep was 83.0% (range: 78.0–87.0) and 83.0% (range: 76.0–87.0), respectively. Of the enrolled OSA patients, 47.8% received PAP prescriptions. APAP was the most frequently used device, followed by fixed CPAP. The median pressure for the fixed CPAP user was 8.0 (range: 6.0–10.0) cm H₂O.

Table 2.

Summary of the baseline characteristics of the cohort participants (visit 0 or 1)

Table 3.

Reasons for visiting a sleep clinic

Table 4.

Polysomnography and PAP titration results

STRENGTHS AND LIMITATIONS

The KOSMOS cohort is the first and only prospective multicenter multidisciplinary OSA cohort study in Korea. The KOSMOS cohort is designed to accord with the interests of various departments related to sleep medicine, and collaboration among departments is also feasible. The follow-up period for the cohort is 30 years, which is sufficient for detailed analysis of the patients’ progress and prognosis.

An association between OSA and cardiovascular diseases has frequently been reported [16,32,33]. CPAP, a first-line treatment for OSA, is beneficial with respect to the prevention and prognosis of cardiovascular disease [34-37], although some recent randomized controlled trials found that the use of CPAP did not prevent the occurrence or progression of cardiovascular events [38-40]. However, most of the studies were conducted in Western populations, and few analyses of Korean data have been performed. Multicenter research is necessary for assessing the clinical characteristics of Korean OSA patients, who have different anatomical structures and lifestyles from Westerners; this will allow for Korean-specific treatments.

This study had some limitations. The participating sleep centers are mainly large university hospitals, so patients in small hospitals were not enrolled. Therefore, there is a possibility of patient selection bias. In addition, the study includes many questionnaires, which may be difficult to complete if the patient cannot read or does not have enough time. There is also a possibility of bias if less compliant participants drop out. Finally, no biological samples were collected.

CONCLUSION

The KOSMOS cohort is the first and only prospective multicenter multidisciplinary OSA cohort study in Korea. Through this long-term planned cohort study, we will be able to gain a detailed understanding of the characteristics of OSA in Koreans and also conduct a thorough analysis of the disease’s progression and prognosis.

Article information Continued