Assessment of Continuous Positive Airway Pressure Therapy in OSA and ILD
Phase: NA
Conditions: Interstitial Lung Disease, Obstructive Sleep Apnea
Sponsor: Columbia University

 
 
 
 
 
 
 
 
Assessment of Continuous Positive Airway Pressure 
Therapy in OSA and ILD 
 
ClinicalTrials.gov ID: NCT03901534 
Date of IRB approval: June 3, 2024 
 
 

BACKGROUND 
 
Study Purpose and Rationale 
Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease of the peripheral lung 
parenchyma that affects 0.5% of older adults in the U.S. and confers a median survival of only 
3.8 years.1-3 While pirfenidone and nintedanib slow disease progression, neither drug reverses 
fibrosis nor prevents ongoing subclinical alveolar epithelial cell (AEC) injury, the antecedent 
cause of fibrosis in IPF.4,5 We and others have shown that subclinical AEC injury as well as 
extracellular matrix (ECM) remodeling are also detectable using serum biomarkers, including 
increases in surfactant protein-D (SP-D), Krebs von den Lungen-6 (KL-6), and MMP-7 (a 
marker of AEC injury and ECM remodeling). Each of these biomarkers is also elevated in IPF 
and other fibrotic ILDs.6-11 We and others have found that obstructive sleep apnea (OSA), a 
condition that is highly prevalent in adults with fibrotic interstitial lung diseases, including IPF, 
is also associated with increases in serum KL-6, SP-A and MMP-7, and with angiopoietin-2 
(Ang-2; an endothelial marker), and that OSA is associated with subclinical ILD on CT.12-15 
These data support (1) the use of serum biomarkers to detect subclinical AEC injury and ECM 
remodeling, and (2) the hypothesis that OSA may contribute to subclinical AEC injury. Based on 
these data, our central hypothesis is that moderate-to-severe obstructive sleep apnea causes 
subclinical AEC injury and, in susceptible individuals, peripheral lung fibrosis and fibrotic 
ILD.16 OSA might lead to AEC injury and ECM remodeling by exerting peripheral stretch of the 
lung, which has been hypothesized to be an underlying cause of IPF and other fibrotic ILDs.12,13 
Obstructive apneas and hypopneas are characterized by repetitive forceful inspiratory efforts 
against a completely or partially closed airway.17 This causes wide swings in pleural pressure 
exerting peripheral tractional stress on the lung, potentially causing stretch and injury to AECs 
analogous to that which occurs during positive pressure ventilation.18-20 Other mechanisms 
linking OSA and subclinical AEC injury are possible, including promotion of oxidative injury by 
intermittent hypoxia and microaspiration from gastroesophageal reflux disease (GERD).21,22 We 
propose to leverage the Multi-Ethnic Study of Atherosclerosis (MESA) Sleep Study, a 
community-based cross-sectional study, the HeartBEAT and BestAIR randomized clinical trials 
of CPAP for OSA, and an inception cohort of ILD patients diagnosed with OSA. We propose to 
establish OSA as a modifiable contributor to AEC and endothelial injury and thereby provide 

sufficient evidence to support a large-scale clinical trial testing whether CPAP improves clinical 
outcomes in IPF. This will be achieved through three Specific Aims: 
 
Specific Aim 1: Determine whether greater OSA severity is associated with higher levels of 
serum biomarkers of AEC and endothelial injury and ECM remodeling in community dwelling 
adults.  
 
Specific Aim 2: Determine whether CPAP use is associated with reductions in AEC and 
endothelial injury and ECM remodeling biomarkers in adults with moderate-to-severe OSA. 
Using stored serum samples from the HeartBEAT and BestAIR trials, we will assess serum 
MMP-7, SP-D, SP-A, and Ang-2 levels in adults with moderate-to-severe OSA after randomly 
allocated CPAP or no-CPAP. We hypothesized that CPAP use will be associated with reductions 
in these biomarkers. This hypothesis has been proven incorrect. Contrary to our hypothesis, the 
levels of four biomarkers of lung inflammation and extracellular remodeling were not reduced by 
CPAP in patients with OSA. Indeed, CPAP therapy was associated with an increased circulating 
level of Ang-2, an endothelial growth factor that is released from pulmonary endothelial cells in 
the setting of acute lung injury. This finding raises the possibility that CPAP, by increasing 
alveolar distension, may exacerbate processes that contribute to lung inflammation in OSA.  
 
Original Specific Aim 3: 1) Determine whether untreated OSA promotes AEC and endothelial 
injury and ECM remodeling biomarkers in adults with ILD and OSA compared with those 
without OSA; 2) Determine prospectively whether clinically-initiated 4-week PAP therapy 
increases markers of alveolar endothelial lung injury in OSA.  
 
The results of Aim 2 analysis indicating potential harm associated with CPAP therapy in OSA 
necessitated revision of the original aim 3. The revised Aim 3 is: a) to determine prospectively 
whether clinically-initiated 4-week PAP therapy increases markers of alveolar endothelial lung 
injury in OSA; b) to determine whether untreated OSA promotes AEC and endothelial injury and 
ECM remodeling biomarkers in adults with ILD and OSA compared with those without OSA. 
Rationale behind revision of Aim 3: Considering that CPAP unexpectedly increased a marker of 
alveolar endothelial injury in OSA patients without known ILD, we think it is essential to 

validate these findings in a prospective cohort and to document prospectively whether untreated 
OSA worsens existing lung injury in patients with concomitant ILD. We will use a two-pronged 
approach to address this question: 1) We plan to recruit prospectively additional 78 patients with 
untreated moderate-to-severe OSA and assess the above biomarkers of alveolar endothelial 
injury before and after 4 weeks of clinically-initiated PAP therapy (not randomly allocated 
owing to the well-recognized societal hazard posed by untreated OSA patients with daytime 
somnolence). Using the effect size and SD estimates from the HeartBEAT and BestAir samples, 
a sample of 78 patients will provide 80% power to detect an effect of the size that we observed in 
Aim 2 with a(2) = 0.05; 2) We will recruit all participants as planned for Aim 3 (anticipated 100 
patients with ILD and concomitant OSA and 65 patients with ILD who do not have OSA) and 
compare their baseline levels of alveolar epithelial and endothelial injury biomarkers. This 
approach is crucial to establish whether patients with concomitant ILD and OSA have a greater 
degree of alveolar endothelial injury compared with ILD patients without OSA. If OSA turns out 
not to contribute independently to alveolar endothelial injury, this information would also be 
valuable considering that PAP may worsen existing alveolar endothelial injury in ILD patients, 
which suggest that alternative treatments for OSA that do not increase alveolar distension (for 
example, oral appliances) may be particularly suitable for patients with concomitant ILD and 
OSA. After validating our findings from Aim 2 as described above, we will explore in future 
studies whether oral appliances lower markers of AEC and endothelial injury in ILD patients 
with OSA. 
 
Study Design 
 
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. We will perform cross-sectional analyses in this Aim. 
Sampling frame and participants: We will sample participants from the MESA Sleep 
Study. We will sample the 1,830 MESA Sleep study participants who have available 
polysomnography data and no self-reported lung disease. We realize that a small proportion of 
participants will have missing or low-quality samples. 

Measurement of exposures: The primary exposure of interest will be the obstructive AHI, 
defined as the number of all obstructive apneas and hypopneas with >4% desaturation during 
sleep divided by the # of hours of sleep. We will also examine the number of obstructive apneas 
and hypopneas regardless of desaturation observed per hour of sleep, the proportion of sleep time 
with obstructive apneas and hypopneas, nadir and average oxyhemoglobin saturation (SpO2), the 
percentage of sleep time with an SpO2 3% desaturation or arousal. We also will explore indices 
specific to sleep state (REM/NREM), and oxygen desaturation events occurring without prior 
apneas/hypopneas. 
Measurement of outcomes: Our outcomes of interest are 4 serum protein biomarkers. 
Laboratory analyses using MESA Exam 5 morning fasting serum will be performed using 
quantitative sandwich ELISA assays from R&D Systems (MMP-7, SP-D, Ang-2) and Biovendor 
(SP-A) at the MESA Core Laboratory at the University of Vermont where these samples are 
stored. 
Aim 2: Determine whether CPAP use is associated with reductions in AEC and 
endothelial injury and ECM remodeling biomarkers in adults with moderate-to-severe OSA. 
Study Design: Retrospective cohort study using data and biosamples from two previously 
performed studies. 
Sampling frames and participants: Participants will be sampled from two completed 
clinical trials: the HeartBEAT and BestAIR trials. Each trial shares common design features and 
study eligibility criteria with a few exceptions, notably the timing of the measurement of the 
primary endpoint. Both were designed to test the hypothesis that active CPAP compared to a 
control intervention improves 24-hour blood pressure in patients with moderate-to-severe OSA 
and cardiovascular risk factors. The results of the HeartBEAT trial have been reported in the 
New England Journal of Medicine23. It was a four-site, three-arm, parallel group, randomized 
trial of 12 weeks of CPAP, oxygen supplementation, or healthy lifestyle and sleep education for 
adults aged 45 to 75 years with moderate-to-severe OSA (AHI > 15/hr) and either23 coronary 
artery disease or24 three or more cardiovascular risk factors23. Those with heart failure, a resting 
SpO2 < 90%, any current use of supplemental oxygen, or current smoking were excluded. All 
HeartBEAT participants with available serum who were randomized to the CPAP arm or the 
healthy lifestyle and sleep education arm (n = 200) will be included in this Aim (those 
randomized to oxygen will not be included in this Aim). The BestAIR trial is a two-site, 

randomized trial comparing active CPAP (with or without behavioral support for CPAP use) to 
control interventions (education with or without sham CPAP) over 6 to 12 months of follow-
up24. For the purpose of this analysis, all individuals receiving active CPAP will be compared to 
all individuals in the control arms. Inclusion criteria were similar to the HeartBEAT trial: age 45 
to 75 years with moderate-to-severe OSA (AHI > 15/hr) with clinical heart disease, diabetes or 
>3 cardiovascular risk factors. All BestAIR participants will be included (n = 169). 
Exposure measurement: We will use the original randomized allocation assigned in the 
two trials as our primary exposure. In both trials, participants were randomly assigned with equal 
probability to treatment arms using a stratified permuted block design with stratification by 
recruitment site and presence of coronary artery disease. 
Outcomes: We will measure MMP-7, SP-D, SP-A, and Ang-2 in baseline and follow-up 
(3 months in HeartBEAT; 6 months in BestAIR) morning fasting sera using commercially 
available ELISA kits as described in Aim 1. These samples are already stored at the University 
of Vermont. 
This Aim 2 has been completed. We focused on BestAIR and HeartBEAT trials 
participants with moderate to severe OSA (AHI 15) who adhered with CPAP for 4 h daily. As 
this adherence level is averaged over all days, it is higher than the conventional clinical target of 
4 hours/night for at least 5 nights/week, and was chosen because we expected the effect to be 
most pronounced in these patients. In addition, this planned “per protocol” analysis, restricting to 
individuals randomized to CPAP who used it for at least 4 hours/night based on objective 
monitoring, corresponds with our current Aim 3 study design. However, contrary to our 
hypothesis, the levels of four biomarkers of lung inflammation and extracellular remodeling 
were not reduced by effective PAP therapy in OSA patients. In fact, effective PAP therapy was 
associated with an increased circulating level of Ang-2, an endothelial growth factor considered 
a marker of acute lung injury. 
Given the limited biospecimen resource, we re-evaluated the markers planned for 
analysis and decided to substitute osteopontin for SP-A, as a putative marker of fibrogenesis and 
ECM remodeling, and therefore likely to provide more valuable information than SP-A. SP-A 
had been identified as a marker of AEC injury; however, it was felt that SP-D is a better marker 
of the same domain, and the redundancy was not needed, especially considering limited 
biospecimen resources. 

Revised Specific Aim 3: a) to determine prospectively whether clinically-initiated 4-week 
PAP therapy increases markers of alveolar endothelial lung injury in OSA. b) to determine 
whether untreated OSA promotes AEC and endothelial injury and ECM remodeling biomarkers 
in adults with ILD and OSA compared with those without OSA. 
 
Study Design & Sampling Frame: We will perform a prospective study. We will sample 
participants from the New York Presbyterian/Columbia Pulmonary Fibrosis Foundation Care 
Center and from The Columbia University Center for Sleep Medicine. 
Selection Criteria, Expected Enrollment, and Screening: This study plans to enroll 
approximately 165 subjects with interstitial lung disease. We anticipate that 100 of those will 
have concomitant OSA and 65 will not have concomitant OSA. We will enroll 78 OSA patients 
from The Columbia University Center for Sleep Medicine and assess the above biomarkers of 
alveolar endothelial injury before and after 4 weeks of clinically-initiated PAP therapy (not 
randomly allocated owing to the well-recognized societal hazard posed by untreated OSA 
patients with daytime somnolence). 
 
Inclusion Criteria for Patients with ILD: 
1. 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 surveys3, 4, 5: 
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 
Study Overview: After informed consent and review of inclusion/exclusion criteria, study 
participants will undergo full-night polysomnography at their baseline visit (see below). 
Phlebotomy, spirometry, 6-minute walk test, diffusing capacity, and questionnaires completed at 
the research visit. 
 
Inclusion criteria for OSA patients: 
1. Age >18 years 
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 
 
STATISTICAL PROCEDURES 
 
Polysomnography: Participants with ILD will undergo home polysomnography (PSG) 
after they have consented to the study. We will use the Nox A1 sleep recorder manufactured by 
Nox Medical (Reykavik, Iceland) for the home PSG recordings. This will strictly be a research 
study and not meant for clinical purposes. PSG devices will be returned to Columbia and 
recordings uploaded by the research team. PSG exams will be transferred to and scored by the 
Brigham and Women’s Sleep Reading Center (Boston, MA, USA) in accordance with the 
American Academy of Sleep Medicine Manual28. Patients without ILD will be recruited from 
The Columbia University Center for Sleep Medicine after clinically indicated polysomnography. 

Supplemental oxygen: If participants use supplemental oxygen while sleeping at baseline, 
they will use their supplemental oxygen as prescribed by their healthcare provider during the 
home PSG. 
Phlebotomy and urine will be performed using methods previously used in MESA. 
Morning fasting blood with tourniquet time < 2 min. will be drawn. Mid-stream urine will be 
collected. The samples will be processed within 30 minutes and stored at -80°C. 
Spirometry and DLCO will be performed by trained technicians in accordance with 
ATS/ERS guidelines in the MESA PFT lab in the CTSA and PFT lab in Herbert Irving Pavilion 
3rd Floor.30, 31 
Questionnaires will be completed by participants. Questionnaires include Epworth 
Sleepiness Scale (ESS).32,37 
Demographic and clinical data (age, gender, race/ethnicity, smoking status, cigarette 
packyears, and medical history) will be ascertained using standardized questionnaires. Height 
and weight will be measured using a calibrated stadiometer scale. A board-certified 
pulmonologist will perform a standardized physical exam and record her or his findings in a pre-
formatted form. 
Clinical Data & Events: We will record clinical data, including, hospitalizations, 
exacerbations, and deaths. 
Outcome measures: 1) Determine whether untreated OSA promotes AEC and endothelial 
injury and ECM remodeling biomarkers serum (MMP-7, SP-D, osteopontin and Ang-2) in adults 
with ILD and OSA compared with those without OSA; 2) Determine prospectively whether 
clinically-initiated 4-week PAP therapy increases markers of alveolar endothelial lung injury 
(MMP-7, SP-D, osteopontin and Ang-2) in OSA. All assays will be performed in Dr. Tracy’s lab 
as described in Aim 1. Secondary outcomes will include changes in FVC, DLCO, 6-minute walk 
distance, dyspnea, and HRQOL. 
Data Management: We will use a REDCap database for data entry and management as 
we have previously done in the Lung Transplant Body Composition Study. 
 
STUDY PROCEDURES 
 

For patients with ILD, after informed consent and review of inclusion/exclusion criteria, 
study participants will undergo home polysomnography (see below). Phlebotomy, spirometry, 
diffusing capacity and questionnaires will be measured at the research visit. 
Participants with ILD will undergo home polysomnography (PSG) after they have 
consented to the study. We will use the Nox A1 sleep recorder manufactured by Nox Medical 
(Reykavik, Iceland) for the home PSG recordings. This will strictly be a research study and not 
meant for clinical purposes. PSG devices will be returned to Columbia and recordings uploaded 
by the research team. After being uploaded, studies will be exported in standardized format 
(European Data file; edf) and transferred by secure FTP to the Sleep Reading Center at Brigham 
& Women’s Hospital for scoring by a single research sleep technologist according to well-
established protocols. Brigham Sleep Reading Center will perform interpretation using standard 
AASM scoring criteria. 
For patients with OSA only (without ILD), they will undergo clinically indicated 
polysomnography in the Center for Sleep Medicine. The investigators have no role in 
determining the need for polysomnography or CPAP therapy in this OSA only cohort. CPAP 
will be prescribed by their clinician provider and not by the study investigators. Therefore, 
polysomnography and CPAP are not considered study procedures for OSA only cohort. 
Supplemental oxygen: If participants use supplemental oxygen while sleeping at baseline, 
they will use their supplemental oxygen as prescribed by their healthcare provider during the 
home PSG. 
Phlebotomy will be performed via venipuncture. Morning fasting blood with tourniquet 
time < 2 min. will be drawn. Samples will be processed within 30 minutes and stored at --80°C. 
Mid-stream urine will be collected. 
Six-minute Walk Test (6MWT), Spirometry, and DLCO will be performed by trained 
staff in accordance with ATS/ERS guidelines. 
Participants will complete Epworth Sleepiness Scale (ESS). These questionnaires will be 
administered according to the instructions provided in the attached documents.  
 
RECRUITMENT AND CONSENT 
 

Patients with ILD will be recruited from the ILD center. Patients who express interest in 
the study will be referred to the study team, and study team members will approach interested 
patients to provide additional information about the study. HIPAA form D is required for study 
investigators and research team to pre-screen and identify patients from the clinical practice who 
have met the inclusion criteria. These participants will be approached during their regularly 
scheduled clinic visits and given information about the study. For “OSA only” cohort, they will 
be recruited from the Center for Sleep Medicine after their OSA diagnosis had been confirmed 
clinically by polysomnography. All patients in the Center for Sleep Medicine will be screened 
for eligibility, and those that are eligible based on inclusion and exclusion criteria will be 
approached by phone call. Enrollment and consent will occur during the research visit. 
 
RESEARCH AIMS & ABSTRACTS 
 
Research Questions/Hypotheses: 
Specific Aim 1: Determine whether greater OSA severity is associated with higher 
levels of serum biomarkers of AEC and endothelial injury and ECM remodeling in 
community dwelling adults. We hypothesize that a higher obstructive AHI is associated with 
greater serum MMP-7, SP-D, SP-A, and Ang-2 levels in 1,830 MESA Sleep Study participants 
after controlling for potential confounders. 
Specific Aim 2: Determine whether CPAP use is associated with reductions in AEC 
and endothelial injury and ECM remodeling biomarkers in adults with moderate-to-severe 
OSA. Using stored serum samples from the HeartBEAT and BestAIR trials, we will perform 
randomized comparisons of serum MMP-7, SP-D, osteopontin, and Ang-2 levels in 369 adults 
with moderate-to-severe OSA who received CPAP or control interventions. We hypothesize that 
CPAP use will be associated with reductions in these biomarkers. 
Revised Specific Aim 3: a) to determine prospectively whether clinically-initiated 4-
week PAP therapy increases markers of alveolar endothelial lung injury in OSA. b) to determine 
whether untreated OSA promotes AEC and endothelial injury and ECM remodeling biomarkers 
in adults with ILD and OSA compared with those without OSA.. 
 
Scientific Abstract: 

Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic disease of the peripheral lung 
parenchyma that affects ~0.5% of older adults in the US and carries a median survival time of 
only 3.8 years. While pirfenidone and nintedanib slow the decline of lung function in IPF, 
neither drug reverses fibrosis or prevents the ongoing alveolar epithelial cell (AEC) injury that 
leads to fibrosis in IPF. The identification of interventions that prevent AEC injury in IPF would 
have a paradigmshifting impact. A recent novel hypothesis suggests that “tractional” injury in the 
periphery of the lung may be responsible for the development of IPF. Our central hypothesis is 
that obstructive sleep apnea (OSA), which affects 59-88% of adults with IPF, is a prevalent 
cause of recurrent peripheral tractional stress in the lung that leads to AEC injury and, in 
susceptible individuals, lung fibrosis. We believe that Müeller maneuvers occurring during 
obstructive apneas and hypopneas likely stretch and injury alveolar epithelial cells, contributing 
to fibrosis in susceptible adults over the course of 10-20 years. In mice, inspiratory resistive 
loading (analogous to an obstructive hypopnea) induces AEC injury and results in increased 
alveolar-capillary membrane permeability. In humans, we and others have shown that adults with 
OSA have elevated circulating levels of surfactant protein-A (SP-A) and Krebs von den Lungen-
6 (KL-6), markers of AEC injury, and elevated matrix metalloproteinase-7 (MMP-7) levels, a 
marker of extracellular matrix remodeling, suggesting that subclinical AEC injury and ECM 
remodeling occurs in OSA in otherwise healthy adults. Alveolar epithelial and endothelial injury 
is also detectable by measurement of serum surfactant protein-D (SP-D) and angiopoetin-2 (Ang-
2), respectively. In IPF, AEC injury is detectable by elevations in some of these markers, and 
MMP-7 levels are a key diagnostic and prognostic biomarker in IPF. We propose to establish 
OSA as a contributor to AEC injury in those with and without IPF, and to obtain data that will 
inform and justify a phase 2 clinical trial of continuous positive airway pressure (CPAP) to 
improve outcomes in adults with IPF and OSA. We will investigate associations between OSA 
and evidence of AEC and endothelial injury and ECM remodeling in the MESA Sleep Study, a 
population-based cohort of adults who underwent home polysomnography in 2010-2012. We 
will also investigate whether treatment with CPAP is associated with a change in serum markers 
of AEC and endothelial injury and ECM remodeling in adults with OSA without IPF. Our study 
will provide strong evidence for or against a pathogenic role of OSA in IPF, and is likely to 
provide critical data that we will use to design a phase 2 trial asking whether oral appliances 
lower markers of alveolar epithelial and endothelial injury in ILD patients with OSA. 

 
Lay Abstract: 
Interstitial lung diseases are a family of lung diseases characterized by inflammation and 
scarring of the walls of the air sacs of the lungs. These diseases are not due to infection; nor are 
they a form of cancer. In most cases, scar tissue builds up over the course of a few years and 
leads to lung failure and death. Most patients die within 3 to 5 years. Few treatments are 
available. Some can undergo a lung transplant, but most people are unable to receive one due to 
contraindications to transplantation and/or due to a shortage of donors. We have developed a 
research program that investigates the causes of IPF and other interstitial lung diseases, since 
most cases occur for unknown reasons. Our research has identified sleep apnea as a possible 
contributor to interstitial lung disease. 
We now propose to perform three studies: 
1) Perform research blood tests for markers of lung injury and inflammation in people 
with and without sleep apnea using an existing large study called “MESA.” This part of the study 
will use existing data and existing blood samples that are stored at the University of Vermont. 
This Aim will not include enrollment of any new study participants. We will test whether these 
markers are elevated in people with sleep apnea compared to those without sleep apnea. 
2) Perform research blood tests for markers of lung injury and inflammation in people 
with sleep apnea and determine whether treating sleep apnea lowers the levels of these markers 
in the blood. We will use existing data and existing blood samples from two prior studies. The 
blood samples are stored in the University of Vermont. The University of Vermont Laboratory 
will measure these markers and provide the data to us. This Aim will not include enrollment of 
any new study participants. 
3) Perform sleep studies on adults with obstructive sleep apnea and interstitial lung 
diseases who we prospectively enroll at our center. They will undergo non-invasive studies, 
including sleep study, breathing tests, blood tests, walking test, and questionnaires. We will also 
perform blood tests before and after CPAP therapy prescribed clinically in patients with 
obstructive sleep apnea without known lung disease. 
We hope that all of these studies will help us understand whether sleep apnea damages 
the lungs and whether people with and without ILD, and whether treatment of sleep apnea affects 
the lungs. 

 
 
 

 
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