Hyperbaric Oxygen Therapy for Lung Transplantation

Study Overview
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Brief Summary
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The objective of this study is to evaluate the effect of hyperbaric oxygen therapy (HBOT) on airway complications in post-lung transplant recipients with evidence of restricted levels of blood and oxygen in the airway tissue. Study subjects with extensive airway tissue damage in the early post-transplant period will be randomized to HBOT or usual care and followed clinically for 12 months following randomization. The investigators hypothesize that HBOT will decrease the number of airway complications in the treated subjects.

Detailed Description
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Hyperbaric oxygen therapy (HBOT) will be performed with the standard HBOT protocol used at Duke for the treatment of compromised grafts and flaps. This is 2 hours of breathing >99% medical grade oxygen inside an air-pressurized chamber at atmospheric pressure of 2 once a day for 20 sessions. These sessions will be scheduled 3-5 times per week, depending on the availability of the patient and the hyperbaric medicine physician. The HBOT procedure used for this study will be identical to that used for clinical practice in the Duke University Health System Center for Hyperbaric Medicine and Environmental Physiology, including the oxygen that is used in the chamber. Patients will receive treatment through the regular clinical hyperbaric service. These are routine, not special, treatment sessions and they will receive them alongside other Duke University Medical Center patients being treated for other reasons. The medical grade oxygen used is a part of the Duke University Health System Center for Hyperbaric Medicine and Environmental Physiology hyperbaric chamber system. While the patients randomized to receive usual care will not undergo HBOT, both study groups will receive standard serial bronchoscopies for airway clearance and for the collection of bronchoalveolar lavage fluid for culture data, due to the high rate of infection in lung transplant patients. All subjects will undergo the standard surveillance bronchoscopies every 3 to 4 weeks (x3) for clearance of the exudate from the airway, as well as monitoring progression of the airway abnormalities. As participants in this study, an, endobronchial biopsy of the airway epithelium will be performed at the main carina to collect a sample of recipient epithelium as well as at the first subcarina for each donor lung. Three samples will be collected from each of the biopsy sites. These samples are small (1 to 2 mm) and are thought to have a minimal clinical risk of minor bleeding associated with the procedure. Biopsy will add roughly 3 minutes total to each procedure.

Official Title
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Hyperbaric Oxygen Therapy for Lung Transplantation-Associated Pseudomembranes and Central Airway Stenosis

Conditions
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Disorder Related to Lung Transplantation, Central Airway Stenosis, Airway Exudative Plaques, Airway Complications Post-Lung Transplantation

Intervention / Treatment
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* Drug: Hyperbaric Oxygen Therapy
* Procedure: Endobronchial Biopsy of Airway Epithelium


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Post-lung transplant patient Extensive exudative plaques at 1 month bronchoscopy No sign of airway improvement, or showing worsening of plaques at follow-up bronchoscopy 2-3 weeks after 1 month bronchoscopy. Exclusion Criteria: Use of mechanical ventilation with fraction of inspired oxygen(FiO2) greater than 40% Use of extracorporeal membrane oxygenation Use of inhaled nitric oxide Presence of pneumothorax Pregnancy Inability to provide informed consent

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 90 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Hyperbaric Oxygen, Airway Biopsy<br>The hyperbaric oxygen therapy (HBOT) will be performed with the standard HBOT protocol used at Duke for the treatment of compromised grafts and flaps. This is 2 hours of breathing >99% medical grade oxygen inside an air-pressurized chamber at atmospheric pressure of 2 (2 ATA) once a day for 20 sessions. These sessions will be scheduled 3-5 times per week, depending on the availability of the patient and the hyperbaric medicine physician. During standard bronchoscopies, an endobronchial biopsy of the airway epithelium will be performed. Biopsy will add roughly 3 minutes total to each procedure. | Drug: Hyperbaric Oxygen Therapy<br>* 2 hours of breathing >99% medical grade oxygen inside an air-pressurized chamber at 2 ATA once a day for 20 sessions. These sessions will be scheduled 3-5 times per week, depending on the availability of the patient and the hyperbaric medicine physician.<br>* Other names: Hyperbaric Oxygen;Procedure: Endobronchial Biopsy of Airway Epithelium<br>* During standard post-transplantation bronchoscopies, participants in this study will undergo an endobronchial biopsy of the airway epithelium for each donor lung.<br>* Other names: Airway Biopsy;|
| Other: No Hyperbaric Oxygen, Airway Biopsy<br>No hyperbaric oxygen therapy administered, but lung biopsy still completed during standard post-lung transplant bronchoscopies. An endobronchial biopsy of the airway epithelium will be performed. Biopsy will add roughly 3 minutes total to each procedure. | Procedure: Endobronchial Biopsy of Airway Epithelium<br>* During standard post-transplantation bronchoscopies, participants in this study will undergo an endobronchial biopsy of the airway epithelium for each donor lung.<br>* Other names: Airway Biopsy;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Subjects Needing Airway Stent Placement as Determined by Transbronchial Lung Biopsy. | Airways with stenosis refractory to serial balloon dilation x 3, or at risk for acute obstruction due to stenosis were treated with airway stents. | 12 months | 
| Number of Subjects Experiencing Acute Cellular Rejection as Determined by Transbronchial Lung Biopsy | Pathologic specimens will be examined for the presence of acute cellular rejection. | 12 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Number of Subjects With Development of Clinically Significant Airway Stenosis |  | 12 months | 
| Number of Subjects Receiving Balloon Bronchoplasty for Management of Stenosis |  | 12 months | 
| Number of Subjects With Development of Clinically Significant Lung Infection | As defined by initiation of antimicrobials to treat the suspected organism. | 12 months | 
| Number of Subjects With Development of Bronchitis Obliterans Syndrome |  | 12 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Hyperbaric Oxygen, Lung Transplantation, Central Airway Stenosis, Airway Exudative Plaques, Hyperbaric Oxygen Therapy, Post-Lung Transplantation, Airway Ischemia, Endobronchial Biopsy, Bronchoscopy