Obstructive Sleep Apnoea in Sarcoidosis (OSASA)

Obstructive Sleep Apnoea in Sarcoidosis: A Cross-sectional Observational Study

Sarcoidosis is a multisystemic granulomatous disease of unknown origin. Fatigue is a common problem in sarcoidosis affecting between 50% and 80% of patients, and thus represents a major impairment of their quality of life.

The findings of recent studies suggest a high prevalence of obstructive sleep apnoea (OSA) in patients with sarcoidosis, estimating a range from 17% to 67%. Pathomechanisms leading to this increased OSA prevalence are still unclear, yet likely to be multifactorial including sarcoid myopathy and neuropathy leading to impaired integrity of the upper airways as well as corticosteroid induced obesity.

While both diseases, Sarcoidosis and OSA, could lead to fatigue and excessive daytime sleepiness (EDS) the current managing strategies differ significantly. OSA patients are mostly treated with continuous positive airway pressure (CPAP) whereas sarcoidosis associated fatigue may require increased immunosuppressive therapy. Little is known about treatment of fatigue and sleepiness in patients suffering from both conditions.This study aims to close this knowledge gap and define prevalence of OSA in a swiss cohort with sarcoidosis patients.

Therefore, we plan a prospective, observational, controlled study to investigate the prevalence of sleepiness, fatigue, life quality and obstructive sleep apnoea in patients with Sarcoidosis.

Patients treated in the University Hospital Zurich due to sarcoidosis will be invited by letter to take part in this study. After confirmed consent and baseline assessments at the University Hospital Zurich, these patients will undergo a single night, in-home sleep study to assess possible OSA.

Sleepiness and fatigue specific questionnaires and in-home respiratory polygraphy (oRP) are obtained in all subjects. To assess inflammation status and other conditions connected to sleepiness like hypothyroidism and anaemia, sarcoidosis patients will undergo blood sampling.

Study Overview

• Status: Completed
• Conditions: Fatigue; Obstructive Sleep Apnea; Sarcoidosis; Sleepiness
• Intervention / Treatment: Diagnostic test: Home sleep apnea testing

• Study Type: Observational
• Enrollment (Actual): 149

Contacts and Locations

Study Locations

• Switzerland
  • Zürich, Switzerland, 8091
    • University Hospital Zurich

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Probability Sample

Study Population

Sarcoidosis group: Subjects with a definite diagnosis of sarcoidosis according to international ATS and WASOG guideline

vs

Control group: matched control subjects without sarcoidosis

Description

Inclusion Criteria:

• Sarcoidosis group: Subjects with a definite diagnosis of sarcoidosis according to international ATS and WASOG guideline.
• Informed consent
• 18 years or above
• Control group: No sarcoidosis, no OSA

Exclusion Criteria:

• Moribund or severe disease prohibiting protocol adherence
• Continuous positive airway pressure treatment for OSA at baseline
• Use of oxygen therapy or home ventilation
• Physical or intellectual impairment precluding informed consent or protocol adherence
• Pregnant patients

Study Plan

How is the study designed?

Design Details

• Observational Models: Other
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Sarcoidosis group; Subjects with a definite diagnosis of sarcoidosis according to international ATS and WASOG guideline	Diagnostic test: Home sleep apnea testing; Sarcoidosis patients and control subjects will undergo one night of home sleep apnea testing using ApnoeaLinkTM Plus device (ResMed Corporation, Poway, Calif). The device records the patient's nasal respiratory pressure signal as a surrogate of nasal flow, respiratory movements by a thoracic impedance belt, and finger pulse oximetry. The results of the sleep study will be scored automatically with dedicated software (ResMed Corporation, Poway, Calif), and manually reviewed to ensure data accuracy.
Control group; Control subjects have no sarcoidosis and will be sex, age (± 3 years), height (± 20 cm), and weight (± 15 kg) matched to sarcoidosis patients.	Diagnostic test: Home sleep apnea testing; Sarcoidosis patients and control subjects will undergo one night of home sleep apnea testing using ApnoeaLinkTM Plus device (ResMed Corporation, Poway, Calif). The device records the patient's nasal respiratory pressure signal as a surrogate of nasal flow, respiratory movements by a thoracic impedance belt, and finger pulse oximetry. The results of the sleep study will be scored automatically with dedicated software (ResMed Corporation, Poway, Calif), and manually reviewed to ensure data accuracy.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Prevalence of OSA in sarcoidosis patients compared to matched controls	Conventional thresholds according to the American Academy of Sleep Medicine Task Force of AHI ≥5, ≥15 and ≥30 will be used to define mild, moderate and severe OSA respectively. OSA prevalence will be compared between both groups.	through one sleep study night

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Apnoea-Hypopnea Index (AHI)	AHI will be compared between both groups.	through one sleep study night
Fatigue Severity Scale (FAS)	FAS will be compared between both groups. Score ranges from 10 to 50 points with 50 points presenting the most severe form of fatigue.	one day
Blood pressure	Blood pressure will be compared between both groups.	one day
Lung function test	Lung function tests will be compared between both groups.	one day
Puls wave analysis	Applanation-derived augmentation index (AIx) will be compared between both groups.	one day
Interleukin-2 blood levels	Association between Interleukin-2 blood levels and OSA severity (AHI) and excessive daytime sleepiness (ESS) in sarcoidosis will be assessed.	one day
Oxygen-Desaturation Index (ODI)	ODI will be compared between both groups.	through one sleep study night
Epworth Sleepiness Scale (ESS)	ESS will be compared between both groups. The test measures subjective sleepiness. The scale ranges from 0 to 24 points. More points indicate higher sleepiness.	one day
Functional outcomes of sleep questionnaire (FOSQ)	FOSQ will be compared between both groups. The score ranges from 5 to 20 points. Higher scores indicate better functional status.	one day
Short-form-36 (SF-36)	SF-36 will be compared between both groups. The SF-36 consists of eight scaled scores, which are the weighted sums of the questions in their section. Each scale is directly transformed into a 0-100 scale on the assumption that each question carries equal weight. The lower the score the more disability.	one day
Patient Health Questionnaire (PHQ) Module 9	PHQ 9 will be compared between both groups. The test results range between 0 and 27 points. Higher scores indicate severe forms of depression.	one day
NoSAS-Score	NoSAS-Score will be compared between both groups. The score ranges from 0-17 points. The patient has a high probability of sleep disordered breathing if he has a NoSAS-Score of 8 or higher.	one day
Heart rate	Heart rate will be compared between both groups	one day
Neopterin blood level	Association between Neopterin blood levels and OSA severity (AHI) and excessive daytime sleepiness (ESS) in sarcoidosis will be assessed.	one day
C-reactive protein (CRP) blood levels	Association between CRP blood levels and OSA severity (AHI) and excessive daytime sleepiness (ESS) in sarcoidosis will be assessed.	one day

Collaborators and Investigators

• Sponsor: Malcolm Kohler
• Investigators: Principal Investigator: Malcolm Kohler, Prof, University of Zurich

Publications and helpful links

General Publications

• Roeder M, Sievi NA, Schneider A, Osswald M, Malesevic S, Kolios A, Nilsson J, Kohler M, Franzen D. The prevalence of obstructive sleep apnea in sarcoidosis and its impact on sleepiness, fatigue, and sleep-associated quality of life: a cross-sectional study with matched controls (the OSASA study). J Clin Sleep Med. 2022 Oct 1;18(10):2415-2422. doi: 10.5664/jcsm.10140.

Study record dates

Study Major Dates

• Study Start (Actual): October 28, 2019
• Primary Completion (Actual): August 31, 2021
• Study Completion (Actual): October 31, 2021

Study Registration Dates

• First Submitted: October 30, 2019
• First Submitted That Met QC Criteria: November 5, 2019
• First Posted (Actual): November 8, 2019

Study Record Updates

• Last Update Posted (Actual): January 14, 2022
• Last Update Submitted That Met QC Criteria: January 13, 2022
• Last Verified: January 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Nervous System Diseases; Respiratory Tract Diseases; Lymphoproliferative Disorders; Lymphatic Diseases; Respiration Disorders; Sleep Disorders, Intrinsic; Dyssomnias; Sleep Wake Disorders; Signs and Symptoms, Respiratory; Sleep Apnea Syndromes; Sleep Apnea, Obstructive; Apnea; Sarcoidosis; Sleepiness
• Other Study ID Numbers: 2019-01604

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No