Assessment of Continuous Positive Airway Pressure Therapy in OSA and ILD

Columbia University

Status: Terminated

Conditions: Obstructive Sleep Apnea; Interstitial Lung Disease

Treatments: Device: Continuous positive airway pressure (CPAP) therapy; Device: Nox A1 Recorder

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT03901534

1R01HL137234-01 (U.S. NIH Grant/Contract)

AAAR6902

Details and patient eligibility

About

The purpose of this study is to evaluate whether biomarkers of lung epithelial and endothelial injury are associated with obstructive sleep apnea (OSA) and interstitial lung disease (ILD).

Full description

This study is comprised of 3 aims:

Aim 1: Determine whether the greater OSA severity is associated with higher levels of serum biomarkers of AEC and endothelial injury and ECM remodeling in community-dwelling adults. This is a retrospective study that will analyze biospecimens from those who participated in the MESA sleep study [Chen et al].

Aim 2: Determine whether CPAP use is associated with reductions in alveolar epithelial cell (AEC) injury and endothelial injury, and extracellular matrix (ECM) remodeling biomarkers in adults with moderate-to-severe OSA. This is a retrospective study that will analyze biospecimens from those who participated in either the HeartBEAT [Gottlieb et al] and BestAIR [Bakker et al] studies.

Revised Aim 3: a) Determine whether untreated OSA promotes AEC and endothelial injury and ECM remodeling biomarkers in adults with ILD and OSA compared with those without OSA; b) Determine prospectively whether clinically-initiated 4-week PAP therapy increases markers of alveolar endothelial lung injury in OSA. Participants will be recruited at Columbia University and be assigned CPAP therapy as an intervention.

Enrollment: 2,021 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion Criteria for Patients with ILD:

1. Ability to provide informed consent.

2. Age 18 years or greater

3. Diagnosis of any of the following fibrotic interstitial lung diseases as defined by ATS/ERS/JRS/ALAT guidelines and research statements and Delphi surveys:

   • Idiopathic pulmonary fibrosis
   • Idiopathic non-specific interstitial pneumonia (NSIP) with fibrosis
   • Chronic hypersensitivity pneumonitis with fibrosis
   • Connective tissue disease related interstitial lung disease (CTD-ILD)
   • Unclassifiable idiopathic interstitial pneumonia with fibrosis

Exclusion criteria for Patients with ILD:

1. Clinically significant lung disease other than fibrotic interstitial lung disease
2. Planned change to the IPF treatment during the study period
3. Current cigarette smoking (past 4 weeks)
4. Lower respiratory tract infection in past 60 days. (Upper respiratory tract infection is not a contraindication)
5. History of life-threatening cardiac arrhythmias
6. Known chronic heart failure (LVEF < 45% or echo evidence of RV dysfunction or PH)
7. Chronic opiate analgesic use
8. History of sleepiness-related automobile accident within past year of enrollment
9. Expected survival time in the opinion of the investigator of less than 6 months
10. History of stroke or spinal cord injury

Inclusion criteria for OSA patients:

1. Age 18 years or greater
2. Clinical diagnosis of untreated OSA documented by nocturnal polysomnography

Exclusion criteria for OSA patients:

1. Current treatment with CPAP or oral appliance
2. Identical exclusion criteria as for ILD patients

Trial design

Primary purpose: Treatment

Allocation: Non-Randomized

Interventional model: Sequential Assignment

Masking: None (Open label)

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2,021 participants in 4 patient groups

Community based Multi-Ethnic Study of Atherosclerosis (MESA)

No Intervention group

Description:

This cohort includes biospecimens collected from 1852 participants in the MESA sleep study \[Chen et al\]. Serum biomarkers were measured by immunoassay in the Laboratory for Clinical Biochemistry Research at the University of Vermont. All participants in this cohort will be analyzed for only the Aim 1 outcome measures.

HeartBEAT and BestAir

No Intervention group

Description:

The cohort includes 62 men and 20 women with newly diagnosed moderate-to-severe OSA and without known severe lung disease, who had participated in either of two randomized trials of PAP therapy, the HeartBEAT \[Gottlieb et al\] and BestAIR \[Bakker et al\] studies. Participants were selected for this analysis based on mean PAP adherence of ≥4 hours daily over a follow-up period of 3 months in the HeartBEAT study and 6 months in the BestAIR study. Morning serum samples drawn at baseline and at the end of the PAP treatment period were assayed using commercially available ELISA for each biomarker in the Laboratory for Clinical Biochemistry Research at the University of Vermont Larner College of Medicine. All participants in this cohort will be analyzed for only the Aim 2 outcome measures.

CPAP treatment of OSA

Experimental group

Description:

Participants with obstructive sleep apnea (OSA) will be treated with continuous positive airway pressure therapy (CPAP). All participants in this cohort will be analyzed for only the Aim 3a outcome measures.

Treatment:

Device: Continuous positive airway pressure (CPAP) therapy

ILD screening for OSA

Experimental group

Description:

Participants with interstitial lung disease (ILD) will be screened for OSA by polysomnography. All participants in this cohort will be analyzed for only the Aim 3b outcome measures.

Treatment:

Device: Nox A1 Recorder