Prognostic Significance of Obstructive Sleep Apnea in a Population of Subjects with Interstitial Lung Diseases

Pulm Ther https://doi.org/10.1007/s41030-023-00215-1 ORIGINAL RESEARCH Prognostic Significance of Obstructive Sleep Apnea in a Population of Subjects with Interstitial Lung Diseases Debora Valecchi . Elena Bargagli . Maria Grazia Pieroni . Metella Rosa Refini . Piersante Sestini . Paola Rottoli . Andrea S. Melani Received: October 21, 2022 / Accepted: January 16, 2023 Ó The Author(s) 2023 ABSTRACT Introduction: Obstructive sleep apnea (OSA) is often observed in subjects with interstitial lung disease (ILD). It may have a negative impact on the course of ILD, but its prognostic significance in relation to other known indicators of poor outcome is unclear. Methods: After a detailed work-up, including overnight unattended type III polygraphy, all subjects newly diagnosed with ILDs referred to our clinics were followed-up for at least 1.5 years or until death or progression of disease [[ 10% decline in forced vital capacity (FVC) below baseline]. We analyzed relationships between some prespecified variables of interest, D. Valecchi
E. Bargagli
M. G. Pieroni
M. R. Refini
P. Sestini
P. Rottoli Department of Medical Science, Surgery and Neuroscience, Respiratory Diseases and Lung Transplant Unit, University of Siena, Siena, Italy D. Valecchi e-mail: E. Bargagli e-mail: M. G. Pieroni e-mail: M. R. Refini e-mail: including sleeping results, to establish parameters predictive of progressive course. Results: Our population consisted of 46 subjects (mean age 59.6 years; males 61%); 23.9% and 41% had idiopathic pulmonary fibrosis and ILD associated with systemic diseases, respectively. Mean baseline forced vital capacity and diffusion capacity of carbon monoxide were 83% and 57% of predicted, respectively. Mean (± SE) Apnea–Hypopnea Index (AHI) was 17 (± 3) events/h. AHI in the ranges 5–14.9, 15–29.9, and C 30 was recorded in 14 (31%), 6 (13%), and 9 (20%) subjects, respectively. Mean distance covered in the 6-MWG walk test (6MWT) was 302 (± 19) m and 26 subjects (57%) showed exertional oxyhemoglobin desaturation. The median follow-up was about P. Sestini e-mail: P. Rottoli e-mail: A. S. Melani (&) Dipartimento di Scienze Mediche, Laboratorio per lo Studio dei Disturbi Respiratori Sonno-Correlati, Respiratory Diseases and Lung Transplant Unit, Policlinico Le Scotte, CMR, Azienda Ospedaliera Universitaria Senese, Viale Bracci, 53100 Siena, Italy e-mail: Pulm Ther 18 months. Multivariate logistic regression analysis showed that exertional desaturation (HR 8.2; 1.8–36.5 95% CI; p = 0.006) and AHI C 30, namely the threshold of severe OSA (HR 7.5; 1.8–30.6; p = 0.005), were the only independent variables related to progressive disease course. Conclusion: We conclude that exertional desaturation and elevated AHI had independent negative prognostic significance in our ILD population. Keywords: Idiopathic pulmonary fibrosis; Interstitial lung disease; Obstructive sleep apnea; Sleep breathing disordered, survival Key Summary Points Why carry out the study? In accordance with previous literature data we found that that OSA was common in our population with mixed interstitial lung disease (ILD). It is unclear whether and how much Obstructive sleep apnea (OSA) is predictive of poor outcome with respect to other known negative prognostic indicators. What was learned from the study? We showed prospectively that exertional oxyhemoglobin desaturation during the 6-minute walk test and a high ApneaHypopnea Index (C events/hour), the parameter commonly used to define severe OSA, were independently associated with progressive disease course in our mixed ILD population. INTRODUCTION Interstitial lung diseases (ILDs) are a heterogeneous family of pulmonary disorders with diffuse parenchymal fibrosing lesions classified on the basis of etiological, clinical, radiological, and histopathological findings. Idiopathic pulmonary fibrosis (IPF), the most common ILD, has a rapidly progressive course associated with increasing exertional dyspnea, reduced exercise tolerance, deteriorating quality of life, and poor prognosis [1]. Although the natural history of ILDs other than IPF varies, a significant percentage of subjects with these diseases, approximately one-third, also show rapid evolution with loss of lung function and progression of disease [2, 3]. It is important to know all the factors that can have a negative influence on outcome of subjects with IPF and ILD. The factors so far associated with poor prognosis in IPF and ILD include age [2–4], baseline predicted forced vital capacity (FVC) [2–5], diffusion capacity of the lung for carbon monoxide (DLco) [3, 4] and their decline over time [3–5], as well as distance walked in the 6-minute walk test (6MWT) [6] and exertional oxyhemoglobin desaturation during 6MWT [7]. Obstructive sleep apnea (OSA) is a highly prevalent sleep-related breathing disorder characterized by repeated episodes of partial (hypopnea) and/or complete (apnea) closure of the upper airways despite ongoing respiratory effort during sleep. Sleep poligraphy is the key examination for diagnosing OSA and grading its severity in terms of the number of apneas and hypopneas per hour of sleep [Apnea–Hypopnea Index (AHI)]. Males and older persons are prevalent among those with OSA, which is often associated with sleeping hypoxemia and poor sleep quality and quantity. If not treated, it is associated with increased morbidity. Although OSA and sleep-related hypoxemia were widely believed to be relatively uncommon and to have little clinical impact in subjects with ILD [8, 9], recent studies have found that they are common among subjects with ILD [10–37]. OSA is now identified as a comorbidity in the IPF guidelines [1]. It is suggested that OSA may have a unfavorable impact on the course of IPF and ILD [25], but its role with respect to other known indicators of poor outcome is unclear. The aim of this prospective observational study was to investigate the frequency of OSA and, above all, its prognostic significance in a group of subjects with ILD. Pulm Ther METHODS All adults consecutively diagnosed with ILD at our regional referral Center for Sarcoidosis and other Interstitial Lung Diseases at the Respiratory Diseases and Lung Transplant Unit, Siena, Italy, from May 2016 to May 2017 were considered as eligible for this study. ILD was diagnosed by multidisciplinary evaluation according to international guidelines [1]. Subjects were enrolled if they were clinically stable for at least 1 month prior to the scheduled appointment for the sleep study, which was scheduled within 2 (± 2) weeks of their first referral to our chest clinics, and prior to any change in baseline drug treatment, which also had to be stable for at least a month. Other exclusion criteria were: estimated life expectancy less than 6 months, recent (\ 12 months) chest or upper airway surgery, concomitant congestive heart failure, severe psychiatric disorder, drug or alcohol abuse, thoracic or neuromuscu (...truncated)