Obstructive sleep apnea in patients with interstitial lung disease: Prevalence and predictive factors

PLOS ONE RESEARCH ARTICLE Obstructive sleep apnea in patients with interstitial lung disease: Prevalence and predictive factors Jae Ha Lee ID1, Chan Sun Park2, Jin Woo Song ID3* 1 Division of Pulmonology, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea, 2 Division of Allergy, Department of Internal Medicine, Inje University Haeundae Paik Hospital, Inje University College of Medicine, Busan, Republic of Korea, 3 Department of Pulmonary and Critical Care Medicine, Asan Medical Center, University of Ulsan College of Medicine, Seoul, Republic of Korea a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 OPEN ACCESS Citation: Lee JH, Park CS, Song JW (2020) Obstructive sleep apnea in patients with interstitial lung disease: Prevalence and predictive factors. PLoS ONE 15(10): e0239963. https://doi.org/ 10.1371/journal.pone.0239963 Editor: Muhammad Adrish, BronxCare Health System, Affiliated with Icahn School of Medicine at Mount Sinai, NY, USA, UNITED STATES Received: June 2, 2020 Accepted: September 16, 2020 Published: October 5, 2020 Copyright: © 2020 Lee et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This study was supported by the Basic Science Research Program, through the National Research Foundation of Korea (NRF) funded by the Ministry of Science and Technology, Republic of Korea, in the form of grants awarded to JWS (NRF2016R1A2B4016318, NRF-2019R1A2C2008541). The funders had no role in study design, data * Abstract Interstitial lung diseases (ILDs) are chronic, progressive, parenchymal lung diseases with high morbidity and mortality. In recent studies, the prevalence of obstructive sleep apnea (OSA) in patients with ILD has been reported to be high. However, the prevalence and predictive factors of OSA in Korean ILD patients are not well defined. Therefore, the aim of this study was to evaluate the prevalence and predictive factors of OSA in Korean patients with ILD. Clinical data from 86 patients with ILD enrolled from December 2017 to April 2019 at Haeundae-Paik Hospital, Busan, South Korea, were retrospectively analyzed. OSA was monitored with a level 4 portable device and defined as an apnea-hypopnea index of more than 5 per hour of sleep. The median follow-up period was 7 months. The mean age was 69.8 years, and 64% of participants were men. Among the ILDs, idiopathic pulmonary fibrosis (IPF) was the most common (66.3%), followed by connective tissue disease–associated ILD (16.3%) and cryptogenic organizing pneumonia (5.8%). Forty-six ILD patients (53.5%) were diagnosed with OSA, and IPF patients had OSA more frequently (64.9% vs. 31.0%, p = 0.003) than those with other ILDs. Older age (odds ratio [OR], 1.11, 95% CI 1.04–1.19, p = 0.002), higher body weight (OR 1.05, 95% CI 1.01–1.10, p = 0.012), and diabetes mellitus (OR 4.03, 95% CI 1.26–12.91, p = 0.019) were independent risk factors for OSA in the multivariable logistic regression analysis. In the multivariable Cox analysis, an IPF diagnosis was a significant risk factor for one-year mortality (hazard ratio [HR] 7.92, 95% CI: 1.01– 61.83, p = 0.048) in ILD patients; however, OSA was not. In conclusion, half of Korean patients with ILD had OSA. Older age, higher body weight, and diabetes mellitus were risk factors for OSA in patients with ILD. Introduction Interstitial lung diseases (ILD) are a heterogeneous group of diffuse parenchymal lung disorders with highly variable clinical courses and outcomes [1]. Among the ILDs, idiopathic PLOS ONE | https://doi.org/10.1371/journal.pone.0239963 October 5, 2020 1 / 12 PLOS ONE collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. Prevalence and predictive factors of OSA in Korean patients with ILD pulmonary fibrosis (IPF) is the most common type of idiopathic interstitial pneumonia and has a median survival time of 3–4 years [2, 3]. ILD patients often have comorbidities that significantly affect their clinical outcomes. Several comorbidities, including gastroesophageal reflux disease, pulmonary hypertension, depression, and obstructive sleep apnea (OSA), are known to be frequently associated with ILDs [4]. Especially among IPF patients, international guidelines from the American Thoracic Society, European Respiratory Society, Japanese Respiratory Society, and Latin American Thoracic Association have acknowledged the importance of comorbidities [5]. Among those comorbidities, an increasing number of studies is describing the importance of OSA in patients with ILD. The prevalence of OSA in ILD has been reported to range from 17–88%, compared with 2–4% in healthy adults [6–8]. OSA is characterized by repetitive episodes of upper airway collapse leading to apnea, hypopnea, intrathoracic pressure swings, intermittent hypoxia, and arousal from sleep due to consecutive activation of the sympathetic nervous system [9]. Recent studies have demonstrated that OSA in ILD patients is related to excessive daytime sleepiness, poor quality of life, morbidity, and premature mortality [10, 11]. In a previous study including middle-aged Koreans (40–69 years old), the prevalence of OSA was reported 27.1% in men and 16.8% in women [12]. However, the prevalence and predictive factors for OSA in Korean patients with ILD are not well defined. Therefore, our aim in this study was to evaluate the prevalence and predictive factors for OSA in Korean patients with ILD and to evaluate clinical differences between ILD patients with and without OSA. Materials and methods Study subjects Eighty-six patients with ILD who underwent respiratory polygraphy (RP) at Haeundae-Paik Hospital, Busan, Republic of Korea, using a portable device (SOMNOcheck micro, level 4, Weinmann Medical Technology, Hamburg, Germany) from December 2017 to April 2019 were included in this study. All patients met diagnostic criteria in international guidelines by the American Thoracic Society (ATS) and European Respiratory Society (ERS) [2, 5]. OSA was defined as an apnea hypopnea index (AHI) of more than 5 events per hour, and the respiratory polygraphy findings were scored following the recommendations in the American Academy of Sleep Medicine (AASM) guideline [13, 14]. This study was approved by the Institutional Review Board of Haeundae-Paik Hospital (approval number: 2019-08-012), and the requirement for written informed consent was waived due to the retrospective nature of this study. Clinical information Clinical and survival data were retrospectively obtained from medical records. Sleep data were sco (...truncated)