Breathing Less Oxygen May Help SCI Survivors Breathe Better
Back to physical health resource hub
For spinal cord injury survivors, being able to breathe effectively is a significant problem affecting their quality of life. Now, Brooks Rehabilitation and University of Florida (UF) researchers believe that breathing air with less oxygen, for short periods, might be a solution to help them breathe better.
Numerous studies have shown that breathing impairments are consistently a leading cause of illness or rehospitalization for people living in the community with spinal cord injuries.
Though there has been a significant amount of data demonstrating that respiratory issues affect the length and quality of life of spinal cord injury survivors, there hasn’t been significant advancement in the development of rehabilitative therapies that improve respiratory health and outcomes.
Over the past five years, researchers from Brooks Clinical Research Center and the UF Center for Breathing Research and Therapeutics (BREATHE) have been focused on providing solutions for the respiratory issues SCI survivors face.
Changing the narrative on respiratory therapy for SCI patients
Over two decades of breathing research eventually led to a 2018 research collaboration with Emily Fox, PhD, director of neuromuscular research at Brooks Rehabilitation and of the Brooks-UF PHHP Research Collaboration, and Gordon Mitchell, PhD, director of UF Center for Breathing Research and Therapeutics (BREATHE), for the study Fluctuating Oxygen for Recovery after SCI (FLO2).
Over the years, Dr. Mitchell’s breathing research using rats had found something unexpected: breathing air with less oxygen for short periods might help people with spinal cord injuries.
Dr. Fox and Dr. Mitchell decided to collaborate on this further by translating his findings from rats to humans who have chronic spinal cord injuries. By taking knowledge and evidence already established and applying it in a new way, they began conducting what is known as clinical translation research.
The key to the collaboration was Dr. Fox’s experience as a clinical researcher with expertise in spinal cord injury and Dr. Mitchell’s experience as a basic scientist. Basic science is a type of research that aims to improve scientific theories to better understand the laws of nature, while clinical research is the study of the safety and effectiveness of medical interventions on humans.
The approach they used to test this theory is called acute intermittent hypoxia (AIH). The FLO2 study specifically tested the idea that combining breathing low oxygen with respiratory rehabilitation training is better than either intervention alone. Study outcomes were focused on the effects of combining these two treatments.
Another important part of these two researchers working together was establishing bidirectional translation within the research. This is where the researchers ensured that what was learned in the basic science lab could be safely applied or tested with humans, and, in turn, what they learned about human spinal cord injury was applied back in the basic science research.
What is therapeutic acute intermittent hypoxia?
Study participants would come to the clinical research center at Brooks and participate in a series of breathing treatments:
- The person breathes air with lower oxygen, 9% instead of the normal 21%, for just one minute.
- Then they breathe normal air for 1.5 minutes
- This pattern repeats about 15 times in a session.
“For the FLO2 study, it is very mild,” said Dr. Fox. “We ask our participants, ‘Do you think you got room air or low oxygen?’ And it was about a fifty-fifty chance that they even knew they had received AIH.”
When taken to the extreme, hypoxia can be unhealthy or dangerous, such as in people who suffer from sleep apnea. However, in a mild application, such as with AIH, it is proving to have rehabilitative benefits for people with chronic incomplete spinal cord injury, including those with quadriplegia or paralysis from the neck down.
Why AIH works
The lack of oxygen boosts the body’s ability to better accept rehabilitative treatments. This brief exposure to lower oxygen triggers changes in the brain and spinal cord that make nerve cells work better. According to Dr. Fox, it is “turning up the volume” on the signals that control breathing and movement.
When oxygen levels drop briefly, it causes special sensors in a person’s neck to detect the change. These sensors then alert the brain, and the brain releases a chemical called serotonin. The serotonin release triggers neuroplasticity, which are changes that help nerve cells work better. This makes muscle contraction stronger, including breathing muscles.
“It helps create stronger connections between the neurons, so when we rehab, activating those neurons, they fire more and fire in a more connected fashion,” said Dr. Fox.
The benefits of this treatment expand beyond respiratory rehabilitation. AIH could help improve arm movements like grasping or standing and walking in SCI survivors. And this treatment could even expand to other conditions such as ALS, multiple sclerosis, stroke and brain injury.
The impact of respiratory weakness on the SCI community
Globally, 15.4 million people are living with spinal cord injuries. In the U.S., that number is estimated to be over 300,000 annually, with about 18,000 new spinal cord injuries occurring each year.
Respiratory issues and breathing impairments are common in the SCI community because a spinal cord injury causes weakness or paralysis of the muscles that help a person breathe in and out or cough.
Muscles used to breathe or cough include the diaphragm, intercostal muscles, abdominal muscles, neck muscles and upper airway dilator muscles. When these muscles are weakened, it makes it hard for SCI patients to breathe well or properly cough. This increases the chances of secretions and the development of infections in the lungs, often leading to complications such as pneumonia and respiratory failure. Many SCI survivors need lifelong ventilator support.
FLO2 study outcomes launch further research
The FLO2 study was conducted over five years and involved over 30 participants with SCI. Analysis of the data set is currently under way and study results are promising. However, clinical trials are rarely one-size-fits-all. The researchers have already determined that some participants showed little to no benefit from the treatment while others demonstrated a positive response. The results are now a central focus of a new clinical trial with Dr. Fox and Dr. Mitchell named BioFLO or Genetic Biomarkers of Fluctuating Oxygen.
The study will focus on improving the effectiveness of AIH and better understanding the diversity of response to AIH treatment in the FLO2 study.
BioFLO will test whether combining therapeutic AIH with a slight increase in carbon dioxide will enhance outcomes for patients with a spinal cord injury versus AIH alone. In addition, they are seeking to identify genetic biomarkers that will help predict which individuals will benefit the most or the least from this type of treatment.
Initial investigations with uninjured individuals have shown that when there is a slight elevation of carbon dioxide in the breathing mixture, it indicates a higher activation of the diaphragm (primary breathing muscle) and neuroplasticity, which are the changes that help nerve cells work better.
BioFLO kicked off in January 2024 with its first spinal cord injury patient. The study is looking to evaluate 62 participants with a spinal cord injury. It is supported by a $3.6 million grant from the Department of Defense.
The significance of biomarker research in physical rehabilitation
The focus on biomarker genetic research in rehabilitation therapy has become an important factor for the researchers at Brooks and UF, as well as the larger physical rehabilitation community, as medicine moves away from a “one size fits all approach.”
However, challenges exist in the use of biomarkers and genetics in physical rehabilitation research around standardizing data, development of comprehensive databases, and data that unifies “interindividual heterogeneity,” which is the different characteristics or responses people exhibit to stimuli due to multiple factors: genetics, environment and life experiences. This can make it difficult for research departments to prioritize and identify genetic biomarkers.
“This study is a critical step in our research programs (at Brooks and UF) to develop therapeutic approaches that amplify the effects of rehabilitation and advance recovery for people with spinal cord injury and other neurologic conditions,” said Dr. Fox. “This study will not only advance the understanding and use of therapeutic intermittent hypoxia but also help ensure future trials and use in the clinic target those most likely to benefit.”
Integrating science into practice
For Brooks’ clinical research team, the work doesn’t stop there. More testing needs to be done before AIH can be integrated into clinical practice; however, the research team is working towards that goal.
A full-scale clinical trial at multiple sites will need to be conducted to gather more data on the efficacy of therapeutic acute intermittent hypoxia as a treatment.
Currently, the research team is working with clinicians across Brooks to bring the infrastructure into place to conduct clinical trials for this study at Brooks hospitals. They are also working with key stakeholders towards developing methods and steps needed to bring research breakthroughs such as this into practice at a system level to empower Brooks clinicians to help patients go beyond what is currently possible.
“The FLO2 study is giving us a better foundation of understanding what our patients do and how they change under our care,” said Dr. Fox. “This will then allow us to bring these new therapies we are researching into clinical practice.”
SCI Data Sources
References:
-
- Spinalcord.com. (2023). 2023 United States Spinal Cord Injury Statistics
- World Health Organization. (2023). Spinal cord injury
- Rabadi, M. H., Mayanna, S. K., & Vincent, A. S. (2017). Predictors of mortality in veterans with traumatic spinal cord injury. Spinal Cord, 55, 489-493.
