Assessment of Continuous Positive Airway Pressure Therapy in IPF (ACT-IPF)

The purpose of this study is to evaluate whether biomarkers of lung injury and remodeling are responsive to effective continuous positive airway pressure (CPAP) treatment in adults with idiopathic pulmonary fibrosis (IPF) and moderate-to-severe obstructive sleep apnea (OSA).

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 very poor median survival. Repetitive injury to the lung with abnormal healing likely results in fibrosis as treatment of those risk factors that cause these injuries may improve outcomes. Obstructive sleep apnea (OSA), a form of sleep disordered breathing, is highly prevalent in adults with IPF and may be a risk factor in IPF by exerting peripheral tractional stress on the lung and promoting oxidative injury by intermittent hypoxia. Effective treatment of OSA with continuous positive airway pressure (CPAP) reduces the number of obstructive events in OSA and therefore may reduce repetitive injury to the lung in adults with IPF. Participants in this study will undergo polysomnography to determine whether they have OSA, and if so, its severity based on the apnea-hypopnea index (AHI, events/ hour). Those participants with moderate-to-severe OSA will undergo CPAP treatment for up to 48 weeks with an interim period of withdrawal of CPAP. The primary aim of this study will examine the effect of CPAP treatment and its withdrawal and re-initiation on biomarkers of lung injury and remodeling in adults with IPF and moderate-to-severe OSA who are adherent to CPAP (expected sample size for this group is 30). The study will stop enrollment after 30 participants in this group are enrolled.

Interstitial Lung Disease (ILD), Idiopathic Pulmonary Fibrosis (IPF), Obstructive Sleep Apnea (OSA), CPAP

Participants with moderate-to-severe OSA will be treated for 12 weeks with Auto-CPAP followed by withdrawal of auto-CPAP

Forced vital capacity, or FVC, is defined as the amount of air which can be forcibly exhaled from the lungs after taking the deepest breath possible.

Diffusing capacity of the lungs for carbon monoxide (DLCO) is a medical test that determines how much oxygen travels from the alveoli of the lungs to the blood stream.

The SGRQ is a 50-item questionnaire developed to measure health status (quality of life) in patients with diseases of airways obstruction. Scores range from 0 to 100, with higher scores indicating more limitations.

The SOBQ is a a 24-item questionnaire that assesses self-reported shortness of breath while performing a variety of activities of daily living. Items are assessed on a 6-point scale (0 = "not at all" to 5 = "maximal or unable to do because of breathlessness") for a total score ranging from 0 to 120.

The ESS is a self-administered questionnaire with 8 questions. Respondents are asked to rate, on a 4-point scale (0-3), their usual chances of dozing off or falling asleep while engaged in eight different activities. The ESS score (the sum of 8 item scores, 0-3) can range from 0 to 24. The higher the ESS score, the higher that person's average sleep propensity in daily life (ASP), or their 'daytime sleepiness'.

The SAQLI is a 35-item questionnaire is used to assess obstructive sleep apnea-related quality of life (QOL). Items are assessed on a 7-point scale with 0 indicating "all the time" to 7 indicating "not at all".

ATAQ-IPF is a 74-item questionnaire used to assess quality of life among adults with idiopathic pulmonary fibrosis.

Cough visual analog scale, a standardized scale ranging from 0 (no cough) to 100 (severe cough) on a continuous scale.

We will examine primary and secondary outcomes in participants with 1. Moderate-to-severe OSA who are not adherent to CPAP 2. No or Mild OSA

Inclusion Criteria: Informed consent Age equal to or greater than 50 years Diagnosis of IPF as defined by the 2018 ATS/ERS/JRS/ALAT guidelines Exclusion Criteria: Clinically significant lung disease other than IPF Planned change to the IPF treatment during the study period Known contraindication to CPAP Current use of CPAP, an oral appliance, or hypoglossal nerve stimulation for treatment of OSA Current cigarette smoking (past 4 weeks) Lower respiratory tract infection in the past 60 days. (Upper respiratory tract infection is not a contraindication) History of life-threatening cardiac arrhythmias Known chronic heart failure (Left ventricle ejection fraction < 45% or echo evidence of right ventricle dysfunction or pulmonary hypertension) Chronic opiate analgesic use History of stroke or spinal cord injury History of sleepiness-related automobile accident within past year of enrollment Expected survival time in the opinion of the investigator of less than 6 months Commercial driver's license or occupation

Researchers will be required to submit a written request to the Study Principal Investigator (PI) describing the use of the specimens. The researcher must also document institutional review board (IRB) approval and sign a material transfer agreement. The Study PI will make all decisions about use of the specimens. No identifiable information will be released, only coded anonymized samples and non-identifiable clinical/demographic information. For genomic data generated from whole-exome sequencing, the genotype and relevant phenotype data for participants who consented to share data will be registered and shared through the database of Genotypes and Phenotypes (dbGaP), a controlled access database, once the sequencing data have been cleaned and quality control procedures are completed.

Researchers will be required to submit a written request to the Study PI describing the use of the specimens. The researcher must also document IRB approval and sign a material transfer agreement. The Study PI will make all decisions about use of the specimens. No identifiable information will be released, only coded samples and non-identifiable clinical/demographic information.