Ambulatory Oxygen Therapy for Individuals With Mild-to-moderate Interstitial Lung Disease

Study Overview
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Brief Summary
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The investigators plan to conduct a study to find out if giving portable oxygen therapy (during physical activity) to patients with interstitial lung disease will improve quality of life, exercise tolerance, shortness of breath, and blood vessel function. Oxygen will be provided for a period of 8 weeks. Additionally, the investigators plan to investigate if it is helpful to deliver individualized support when providing oxygen therapy, through check-in phone calls with a respiratory therapist and by providing additional educational material.

Detailed Description
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Brief Summary: The investigators plan to conduct a study to find out if giving portable oxygen therapy (during physical activity) to patients with interstitial lung disease will improve quality of life, exercise tolerance, shortness of breath, and blood vessel function. Oxygen will be provided for a period of 8 weeks. Additionally, the investigators plan to investigate if it is helpful to deliver individualized support when providing oxygen therapy, through check-in phone calls with a respiratory therapist and by providing additional educational material. Detailed Description: BACKGROUND Interstitial lung disease (ILD) is comprised of a group of pulmonary diseases that are characterized by inflammation and/or lung parenchymal fibrosis. Individuals with ILD may be normoxic at rest; however, underlying impairments in gas exchange can contribute to a reduction in oxygen saturation (SpO2) during exertion. Hypoxemia can cause inflammation and cardiovascular dysfunction, which could lead to cardiac events. A recent study found that 78% of ILD patients had cardiovascular comorbidity, which was predictive of death within this ILD cohort. Oxygen therapy is used in patients with advanced lung disease with resting hypoxemia; however, there is limited evidence regarding its clinical efficacy. Furthermore, there is little support to describe the benefit of ambulatory oxygen therapy in individuals with lung disease who are normoxemic at rest but become hypoxemic with exertion. Accordingly, thresholds for the prescription of oxygen therapy vary between (and within) health districts and geographical regions, and individuals who might benefit from supplemental oxygen typically do not qualify for funding of oxygen therapy under unclear guidelines. Furthermore, data from studies in patients with chronic obstructive pulmonary disease (COPD) are often extrapolated for use in guiding oxygen therapy in patients with ILD, which is likely inappropriate considering recent research demonstrated that individuals with fibrotic ILD experience greater hypoxemia than those with COPD during the 6-minute walk test (6MWT). Oxygen therapy may be beneficial in reducing inflammation, oxidative stress, and pulmonary artery pressure, all of which are elevated in ILD. Furthermore, a reduction in dyspnea during exercise with exertional oxygen therapy might increase daily physical activity, exercise tolerance, and reduce overall sedentary time, which would have a positive effect on vascular function. These postulated outcomes, however, are confounded by various practical, psychological, and social challenges associated with use of an oxygen concentrator, as well as challenges with proper titration of oxygen levels (accurately targeting appropriate SpO2) in relation to exertional intensity. Paradoxically, if the flow of oxygen is too high, activation of inflammatory and oxidative pathways may inhibit the benefits related to the alleviation of hypoxemia. Thus, integration of patient-specific disease support tools is essential when initiating oxygen therapy to ensure appropriate oxygenation during exertion. OBJECTIVE To assess the feasibility of oxygen therapy, education, and support for individuals with fibrotic interstitial lung disease and exertional hypoxemia. As a secondary objective, the effects of exertional oxygen therapy and support on physical activity, vascular function, and health-related quality of life in individuals with fibrotic interstitial lung disease will be investigated. PRIMARY AND SECONDARY ENDPOINTS Health related quality of life as assessed by the EQ-5D-5L and the K-BILD Exercise tolerance, assessed by 6MWD while breathing room air Daily physical activity and sedentary time as assessed by a remote monitor. Dyspnea, as measured by the Dyspnea 12 questionnaire Cough using the visual analog scale (VAS) and cough score (measured by Leicester Cough Questionnaire; LCQ) Vascular function, measured by flow mediated dilation (FMD) of the brachial artery Pulmonary artery systolic pressure (PASP) measured by cardiac echocardiography Cardiac systolic and diastolic function assessed by cardiac echocardiography Systemic inflammation STUDY DESIGN Single-blind (assessment team) open-label randomized control TRIAL TREATMENT Participants will be randomized into one of three arms: Control: (Arm 1) 8 Weeks of usual care (n=20) Treatment: (Arm 2) 8 Weeks of supplemental oxygen(n=20) (Arm 3) 8 Weeks of supplemental oxygen plus educational materials and scheduled support (n=20) All: 2-week baseline prior to intervention and 2-week washout post-intervention to document carry-over effect of intervention. DURATION Seven sessions will be completed over a 13-week period. TIMELINE Visit 1) Participant enrollment, medical history, standard pulmonary function test (PFT) and 6-minute walk test (6MWT); followed by 1-week for collection of baseline physical activity and SpO2. During this visit, participants will be provided a wrist-worn activity monitor and a finger-worn pulse oximeter. This visit will take approximately 3 hours. Visit 2) Doppler measurements of systemic vascular function (flow mediated dilation) will be measured at rest while breathing room air. A small sample of venous blood will be taken to analyze inflammatory levels and reactive oxygen species. Participants will fill out questionnaires relating to health-related quality of life, dyspnea, and cough. Finally, participants will perform tests of lung diffusing capacity for carbon monoxide (DLCO) under three different conditions: seated, supine, and during exercise at 40W on a cycle ergometer. Visit 3) One to three days after Visit 2, participants will return for the second day of pre-intervention baseline testing. An echocardiographic exam will be completed to determine pulmonary artery systolic pressure as well as systolic and diastolic function in the left and right ventricles of the heart. To enhance the Doppler signal during the cardiac ultrasound, agitated saline contrast will be used. Two 6-minute walk tests will then be completed, separated by half an hour. This visit will take approximately 2 hours. Following this day, participants will be randomized into one of three arms for an 8-week intervention. Eight-week intervention, randomized into one of: No oxygen Exertional oxygen Exertional oxygen + additional support Visit 4) Repeat Day 2 protocol. Visit 5) Repeat Day 3 protocol. Two-week washout period Visit 6) Repeat Day 2 protocol. Visit 7) Repeat Day 3 protocol. The total duration of time spent for each participant will be approximately 12 hours.

Official Title
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Ambulatory Oxygen Therapy for Individuals With Mild-to-moderate Interstitial Lung Disease

Conditions
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Fibrotic Interstitial Lung Disease

Intervention / Treatment
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* Drug: Exertional Oxygen
* Behavioral: Education and Support


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Individuals with fibrotic ILD (all sub-groups of ILD) who have normal oxygen saturation at rest (SpO2 > 90%) but develop exertional hypoxemia as demonstrated by a SpO2 = 80-89% with activity (measured during 6MWT). Exclusion Criteria: Use of home oxygen therapy within the previous year for the management of ILD, co-morbid conditions that may require oxygen therapy (such as COPD, cardiovascular disease, or other illnesses), or individuals that require the use of non-invasive ventilation. Additionally, individuals with significant cardiovascular, metabolic, neuromuscular or any other disease that could contribute to dyspnea or abnormal cardiopulmonary responses to exercise will be excluded. Individuals with musculoskeletal injuries that prevent them from completing cycle ergometry exercise trials and ambulation will also be excluded. Individuals with peripheral vascular disease will be excluded from measurement of vascular function (flow mediated dilation).

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 85 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Single-blind open-label randomized control
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Arm 1 - Usual Care<br>8 weeks of usual care with no supplemental oxygen provided | |
| Experimental: Arm 2 - Exertional Oxygen<br>8 weeks of portable oxygen use (from a concentrator) during exertion | Drug: Exertional Oxygen<br>* Use of a portable oxygen concentrator for exertional activities lasting >2 minutes<br>* Other names: Supplemental oxygen, ambulatory oxygen;|
| Experimental: Arm 3 - Exertional Oxygen + Support<br>8 weeks of portable oxygen use (from a concentrator) during exertion, plus additional phone calls with a respiratory educator and educational material | Drug: Exertional Oxygen<br>* Use of a portable oxygen concentrator for exertional activities lasting >2 minutes<br>* Other names: Supplemental oxygen, ambulatory oxygen;Behavioral: Education and Support<br>* Participants will receive disease-specific educational material (Living Well with Pulmonary Fibrosis: Oxygen), and will have scheduled phone appointments with a certified respiratory educator after 1, 3, and 5 weeks of oxygen therapy in order to address individual barriers to oxygen use and facilitate the optimal use of portable oxygen.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Feasibility of investigation | Number of patients recruited and completing the protocol in each arm | 2 years | 
| Exercise tolerance | 6 minute walk distance | Before and immediately after the intervention | 
| Health Related Quality of Life, (EuroQol-5 Dimension-5 Level; EQ-5D-5L) | Questionnaire for Health-Related Quality of Life. Possible Range = 5-25; 5 = 11111 (no problems on any dimension); 25 = 55555 (extreme problems on all dimensions) | Before and immediately after the intervention | 
| Health Related Quality of Life, (King's Brief Interstitial Lung Disease Questionnaire; KBILD) | Health status questionnaire. Domain and total score ranges are 0-100; 100 represents best health status | Before and immediately after the intervention | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Dyspnea (Dyspnea-12 Questionnaire) | Range from 0-36, 0 represents no breathlessness and 36 represents maximal severity | Before and immediately after the intervention | 
| Vascular function | Flow-mediated dilation | Before and immediately after the intervention | 
| Cough (Leicester cough questionnaire; LCQ) | Quality of life measure of chronic cough. Range from 3-21, lower score indicating greater impairment of health status due to chronic cough | Before and immediately after the intervention | 
| Pulmonary Artery Pressure | Echocardiography-derived pulmonary artery systolic pressure | Before and immediately after the intervention | 
| Cardiac Output | Assessed by echocardiography (L/min) | Before and immediately after the intervention | 
| Systemic Inflammation | C-Reactive Protein (CRP, venous blood, mg/L) | Before and immediately after the intervention | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Exertional Oxygen, Ambulatory Oxygen, Interstitial Lung Disease