title: Daily intermittent hypoxia enhances walking after chronic spinal cord injury: a randomized trial.
abstract: OBJECTIVE
  To test the hypothesis that daily acute intermittent hypoxia (dAIH) and dAIH combined with overground walking improve walking speed and endurance in persons with chronic incomplete spinal cord injury (iSCI).
  
  
  METHODS
  Nineteen subjects completed the randomized, double-blind, placebo-controlled, crossover study. Participants received 15, 90-second hypoxic exposures (dAIH, fraction of inspired oxygen [Fio2] = 0.09) or daily normoxia (dSHAM, Fio2 = 0.21) at 60-second normoxic intervals on 5 consecutive days; dAIH was given alone or combined with 30 minutes of overground walking 1 hour later. Walking speed and endurance were quantified using 10-Meter and 6-Minute Walk Tests. The trial is registered at ClinicalTrials.gov (NCT01272349).
  
  
  RESULTS
  dAIH improved walking speed and endurance. Ten-Meter Walk time improved with dAIH vs dSHAM after 1 day (mean difference [MD] 3.8 seconds, 95% confidence interval [CI] 1.1-6.5 seconds, p = 0.006) and 2 weeks (MD 3.8 seconds, 95% CI 0.9-6.7 seconds, p = 0.010). Six-Minute Walk distance increased with combined dAIH + walking vs dSHAM + walking after 5 days (MD 94.4 m, 95% CI 17.5-171.3 m, p = 0.017) and 1-week follow-up (MD 97.0 m, 95% CI 20.1-173.9 m, p = 0.014). dAIH + walking increased walking distance more than dAIH after 1 day (MD 67.7 m, 95% CI 1.3-134.1 m, p = 0.046), 5 days (MD 107.0 m, 95% CI 40.6-173.4 m, p = 0.002), and 1-week follow-up (MD 136.0 m, 95% CI 65.3-206.6 m, p < 0.001).
  
  
  CONCLUSIONS
  dAIH ± walking improved walking speed and distance in persons with chronic iSCI. The impact of dAIH is enhanced by combination with walking, demonstrating that combinatorial therapies may promote greater functional benefits in persons with iSCI.
  
  
  METHODS
  This study provides Class I evidence that transient hypoxia (through measured breathing treatments), along with overground walking training, improves walking speed and endurance after iSCI.
authors.affiliation: From the Department of Rehabilitation Medicine (H.B.H., R.D.T.), Emory University, Atlanta, GA; Department of Physical Medicine and Rehabilitation (A.J., M.H., W.Z.R.), Northwestern University, Chicago; Sensory Motor Performance Program (A.J., W.Z.R.), Rehabilitation Institute of Chicago, IL; Department of Comparative Biosciences (G.S.M.), University of Wisconsin, Madison; Department of Biomedical Engineering (R.D.T.), Georgia Institute of Technology, Atlanta; and The Shepherd Center (R.D.T.), Atlanta, GA.
authors.forename: Heather B
authors.initials: HB
authors.lastname: Hayes
authors.forename: Arun
authors.initials: A
authors.lastname: Jayaraman
authors.forename: Megan
authors.initials: M
authors.lastname: Herrmann
authors.forename: Gordon S
authors.initials: GS
authors.lastname: Mitchell
authors.forename: William Z
authors.initials: WZ
authors.lastname: Rymer
authors.forename: Randy D
authors.initials: RD
authors.lastname: Trumbower
mesh_terms: D000328:Adult; D000368:Aged; D002908:Chronic Disease; D018592:Cross-Over Studies; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D005081:Exercise Therapy; D005260:Female; D006801:Humans; D000860:Hypoxia; D008297:Male; D008875:Middle Aged; D061214:Patient Safety; D020127:Recovery of Function; D013119:Spinal Cord Injuries / Q000534:rehabilitation*; D016896:Treatment Outcome; D016138:Walking / Q000502:physiology*; D055815:Young Adult