Acute Intermittent Hypoxia and Respiratory Strength Training to Improve Breathing Function After SCI
Abstract
The fundamental goal of this proposed research is to determine if repeated exposure to brief periods of low oxygen levels (called acute intermittent hypoxia or AIH) coupled with respiratory strength training will improve breathing function in individuals with breathing impairment due to spinal cord injury. Breathing impairment greatly reduces quality of life and is a leading cause of illness, re-hospitalization, and death in people with SCI. Thus, it is critical to devise new strategies that restore breathing function. Our research group developed novel methods using AIH to strengthen spared respiratory neural pathways after SCI, increasing breathing ability. In both rodent models and humans with SCI, repeated AIH restores lost breathing ability. This approach has also translated to humans with SCI, since even a single day of AIH, or daily AIH for 5 consecutive days, induces recovery of non-respiratory functions, improving both walking and hand function after SCI. One important finding in the studies of non-respiratory function is that AIH-induced benefits are greatly enhanced by combining AIH with task-specific training. For example, walking recovery is greatly amplified when daily AIH is followed 30 minutes later by walking practice, and the functional benefits from combined therapy lasted days to weeks longer. Based on these findings, it may also be that a combination of daily AIH with an established form of task-specific rehabilitation, respiratory strength training, may elicit greater improvements in respiratory function in people with chronic SCI. Unfortunately, combined daily AIH and respiratory strength training has not been studied. Here, we hypothesize that exposure to daily AIH combined with respiratory strength training will improve breathing ability more than either treatment alone, and that the duration of functional benefits will be longer. AIH will be delivered on 5 consecutive days, each consisting of fifteen 1.5 minute episodes of low oxygen with 1 minute intervals breathing room air. Respiratory strength training will involve 4 sets of 6 to 10 forceful breaths through a small, hand-held device that resists air flow in or out of the mouth. The resistance will be set for each individual based on their maximal ability. Our first aim is to test the hypothesis that inspiratory and expiratory strength 1 day after the 5-day intervention will be greater when AIH is combined with respiratory strength training (30 minutes later) than with either treatment alone. Second, we hypothesize that improvements in inspiratory and expiratory strength from combined daily AIH and respiratory strength training will persist longer than the functional benefits from either intervention alone as assessed 1 week post-intervention. In this 4-year study, we will enroll 53 adults (~14 per year) with chronic, incomplete SCI and >20% impairment in standard tests of respiratory function. Each participant will complete four 5-day intervention protocols in a randomized order, with 3 weeks between the protocols. Respiratory strength training is the current "standard of care" for those suffering from impaired breathing ability after SCI. Our AIH protocol is based on decades of research in animal models which has been adapted for use in humans. We have taken great care to develop a safe, easily-tolerated AIH protocol for humans. Using the "low dose" AIH protocol to be utilized in this study, functional benefits have been reported without any reports of adverse responses or unwanted side effects in all six published studies in humans with SCI. Participants in all studies are unable to distinguish AIH versus normal oxygen levels, demonstrating that there is minimal stress with this procedure. Since AIH is non-invasive and can be delivered using relatively simple and low-cost "hypoxicators," there is considerable potential to translate combined daily AIH and respiratory strength training into clinical settings, thereby reducing breathing impai
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Oct 29, 2018
- Source ID
- W81XWH1810718
Entities
People
- Emily J Fox
Organizations
- United States Army
- University of Florida