Obstructive Sleep Apnoea in Sarcoidosis

Study Overview
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Brief Summary
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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.

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

Conditions
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Sarcoidosis, Obstructive Sleep Apnea, Fatigue, Sleepiness

Intervention / Treatment
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* Diagnostic Test: Home sleep apnea testing


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sarcoidosis group<br>Subjects with a definite diagnosis of sarcoidosis according to international ATS and WASOG guideline | Diagnostic Test: Home sleep apnea testing<br>* 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.<br>|
| Control group<br>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<br>* 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.<br>|

What is the study measuring?
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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 |