Impact of respiratory muscle training on sleep disordered breathing in people with tetraplegia: A sub-analysis of a randomised controlled trial

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Chaminda Lewis, Rachel McBain, Nirupama Wijesuriya, and 4 more This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-7522267/v1 This work is licensed under a CC BY 4.0 License Status: Under Revision Version 1 posted 9 You are reading this latest preprint version Abstract Study Design: Sub-analysis of a randomised controlled trial. Objectives: Respiratory muscle training (RMT) in people with tetraplegia yields marked improvements in inspiratory muscle strength. The present study investigated whether RMT also modifies sleep disordered breathing (SDB) and daytime sleepiness. Setting: Independent research institute in Sydney, Australia. Methods: Sixty-two adults with tetraplegia underwent six weeks of supervised RMT. The active-RMT group trained the respiratory muscles through progressive threshold loading to a mean intensity of 50% maximal inspiratory pressure whereas the sham-RMT group experienced the same training protocol, but their device had no progressive threshold load. Primary measures of SDB were obtained using level II ambulatory polysomnograms and daytime sleepiness was assessed using the Epworth Sleepiness Score (ESS). Results: Forty-eight participants completed two home-based polysomnograms. Maximal inspiratory pressure (primary outcome) increased more after active intervention than sham, between-group difference 11.8cmH2O (95%CI, 5.2 to 18.4, p=0.001). There were no between group differences for any SDB parameter from baseline to 6-weeks (p=0.173 to p=0.935; e.g. mean apnoea-hypopnea index (±SD): active 46 ± 21 vs. 45 ± 22 events/h; sham 44 ± 25 vs. 40 ± 25 events/h; p=0.553) and ESS: active 9.5 ± 5.7 vs. 9.2 ± 6.7; sham 10.8 ± 6.2 vs. 10.1 ± 5.8; p=0.952. Conclusions: Despite significant increases in inspiratory muscle strength, 6 weeks of supervised respiratory muscle training at a mean intensity of 50% maximal inspiratory pressure does not reduce SDB or daytime sleepiness in people with tetraplegia and severe SDB. Health sciences/Signs and symptoms/Respiratory signs and symptoms Biological sciences/Neuroscience/Circadian rhythms and sleep/Sleep Health sciences/Neurology/Neurological disorders/Spinal cord diseases Figures Figure 1 Figure 2 Figure 3 INTRODUCTION Sleep disordered breathing (SDB) is a common sequelae of spinal cord injury (SCI) with SDB risk factors such as obesity and male sex being more common in this population compared to people without a SCI. [ 1 ] SDB includes obstructive sleep apnoea (OSA), central sleep apnoea (CSA) and sleep-related hypoventilation disorders, and is prevalent after tetraplegia. [ 2 , 3 ] In tetraplegia, SDB prevalence peaks at 83% at 3 months post injury with a subsequent reduction in severity after 6 months. [ 2 ] However, the prevalence is still much greater than the non-SCI population and varies between 27 to 81%. [ 2 , 3 ] SDB is associated with an increase in adverse cardiovascular outcomes. [ 4 ] Obesity, diabetes and cardiovascular morbidity is common after SCI. [ 5 ] Cardiovascular and respiratory disease are the leading causes of death 12 months after SCI. [ 6 ] While little is known about the long-term consequences of nocturnal hypoventilation and hypercapnia in SCI, it is possible that SDB contributes to increased cardiovascular mortality in chronic tetraplegia and therefore, represents a modifiable cardiovascular risk factor. However, there are no data on long-term outcomes or the impact of treating SDB in this population. Additionally, excessive daytime sleepiness, disturbed and poor sleep quality are common problems in people with tetraplegia. [ 1 , 7 ] The reasons behind the high prevalence of SDB in tetraplegia are likely multifactorial. While the motor and sensory innervation of pharyngeal muscles that maintain upper airway patency remain intact in tetraplegia, upper airway dilator muscle reflex responses are altered in many people with tetraplegia and sleep apnoea. [ 8 ] Other factors that affect upper airway collapsibility are also altered after SCI. Increased collapsibility of the upper airway during sleep is a driver of SDB pathogenesis both non-SCI [ 9 ] as well as in tetraplegia, where the upper airway critical closing pressure of the pharynx is higher (less negative/more collapsible). [ 10 ] Decreased lung volume and accompanying reductions in tracheal traction can increase airway collapsibility. [ 11 ] In people with tetraplegia lung volume in supine may be reduced further in the presence of high BMI or large abdominal girth. [ 5 ] Disruption of the sympathetic control of airway mucosa and high nasal resistance may also play a role in the high prevalence of SDB in people with SCI. [ 12 ] Upper airway muscles, including genioglossus, maintain upper airway patency. People with OSA have significantly higher basal genioglossal activity that is believed to compensate for a more collapsible upper airway. [ 13 ] Activity of the genioglossus is reduced at sleep onset [ 14 ] with a greater reduction in people with OSA. [ 15 ] Genioglossus activity is modulated by afferents of upper airway mechanoreceptors, [ 16 ] lung and chest wall stretch receptors. [ 8 ] SDB treatment indications in SCI are similar to the general population. The gold standard of treatment is positive airway pressure (PAP) with either continuous or bi-level nocturnal non-invasive ventilation. [ 17 ] However, adherence with PAP therapy is low in the SCI population with compliance between 23% and 50%. [ 17 ] Thus, a well-tolerated, self-administered, home-based alternative therapeutic modality such as respiratory muscle training (RMT), which would also train the upper airway muscles, has merit, yet has shown mixed results. In people without a SCI threshold inspiratory muscle training (IMT) over 12-weeks improves the Functional Outcomes of Sleep Questionnaire score and snoring (n = 27), [ 18 ] and a reduction in the apnoea-hypopnea index (AHI) and Epworth Sleepiness Scale (ESS) of people with moderately severe OSA (n = 22) [ 19 ] but not in people with mild to moderate OSA after 5-weeks IMT (n = 9). [ 20 ] Pilot studies in tetraplegia suggest RMT increased inspiratory muscle strength, reduced AHI and improved nocturnal oxygen saturation. [ 21 , 22 ] The aim of the current study was to investigate, as part of a larger randomised controlled trial, the effect of RMT on SDB severity and daytime sleepiness in people with tetraplegia. We hypothesised that AHI would reduce after RMT due to increased inspiratory muscle strength. If the severity of SDB can be reduced with RMT, it would offer a low-cost alternative form of treatment, that may be better tolerated than PAP. METHODS Study design A planned sub-analysis of a double-blind, randomised controlled trial to compare the effect of RMT on SDB severity and daytime sleepiness. The trial was pre-registered at Australian New Zealand Clinical Trials Registry (ACTRN 12612000929808) and conducted at a single site between November 2013 and December 2016. All procedures were approved by the South-Eastern Sydney Local Health District Human Research Ethics Committee (Reference No. 12/192) and the University of New South Wales Human Research Ethics Committee (Reference No. HC13388) and complied with the Declaration of Helsinki 2013. Participants Participants aged over 18 years with C3-C8 neurological level of SCI and American Spinal Injury Association Impairment Scale grades A-C were recruited from Prince of Wales Hospital, Sydney or the community as part of a larger RMT trial. [ 23 ] Sixty-two people with tetraplegia participated. Those with significant chest trauma, pneumothorax, significant co-existing respiratory or neurological condition, cognitive impairment or mechanically ventilated were excluded. Prior to enrolment, informed written consent was obtained from participants or with the aid of a family member or an independent third party if unable to sign independently. Randomisation and blinding A computer-generated random allocation schedule was used to minimise differences between treatment groups (sham and active; see Boswell-Ruys et al [ 23 ] for details). Stratification was based on, time since injury (acute ( 1 year)); motor complete versus motor incomplete SCI; and a baseline AHI (above or below 15 events/h). Participants, treating therapists, sleep technicians, polysomnography scorer and assessors were blind to allocated treatment throughout the trial. Intervention Participants performed supervised RMT twice daily for six-weeks using a portable threshold-RMT device (Threshold IMT, Philips Respironics, New Jersey, USA). Five days a week, 3–5 sets of 12 inspiratory breaths, sets separated by two minutes of resting breathing, were completed. Expiratory breaths followed the same protocol. The training procedure employed a nonlinear exercise regime that was tailored to increase training intensity as strength improved. Participants commenced training at 30% baseline maximal inspiratory pressure (PImax) or maximal expiratory pressure (PEmax) which thereafter increased weekly by 10% (capped at 80% PImax or PEmax). Further details about device modifications for sham or active and RMT can be found in Boswell-Ruys et al. [ 23 ] Outcome measures The primary outcome was total AHI. All sleep parameters were assessed in participants’ homes using portable level II polysomnography (Alice PDx, Philips Respironics, Murrysville, Pennsylvania, USA). The parameters recorded included apnoea and hypopnoea events per hour of sleep (AHI), central sleep apnoea events (CSA), and AHI events during rapid- and non-rapid eye movement (REM and NREM) sleep and sleep duration. The minimum and mean blood oxygen desaturation (SpO2) during sleep, and the percentage of time that saturation was < 90% were calculated. Daytime somnolence was assessed using the Epworth Sleepiness Scale (ESS). The primary outcome in the parent trial was inspiratory muscle strength measured as PImax, with secondary outcomes of lung function; inspiratory capacity (IC), vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow during a cough (PEFc), and maximal expiratory pressure (PEmax) all measured with a portable lung function machine (Hyp’air, Belgium) following the American Thoracic Society (ATS) guidelines. Statistical analysis Data were analysed using analysis of covariance (ANCOVA) adjusted for the baseline measures. The treatment effect size was estimated by the between-group mean difference and corresponding 95% confidence intervals. The relationship between baseline or change in PImax and change in AHI and change in ESS were analysed with Pearson’s correlations. Missing data were deleted on a case-wise basis. An alpha level < 0.05 was considered significant. All statistical analyses were performed with IBM SPSS Statistics (v25, IBM Corp., Armonk, NY, USA). RESULTS Sixty-two people with cervical SCI were recruited; 48 participants had complete and analysable diagnostic polysomnography at baseline and after 6-weeks of supervised training, and 57 participants had complete ESS data (see Fig. 1 ). The RMT protocol was adhered to by all participants. Baseline characteristics (Table 1 ) were well matched between groups. However, no female participants were allocated to the active training group. Table 1 Participant characteristics at baseline for sleep disordered breathing analysis Sham RMT Active RMT Number of participants Total 26 22 Acute ( 1-year post injury) 16 12 Motor Complete Injury (AIS A-B) 18 16 Motor Incomplete Injury (AIS C) 8 6 AHI 31 events/h 20 16 Age (years) a 53.9 ± 14.9 48.4 ± 14.5 Sex (m:f) 22:4 22:0 Body-mass index (kg/m 2 ) a 24.4 ± 5.5 24.9 ± 5.3 Lung function measures a PImax (cmH 2 O) 50.0 ± 19.2 50.6 ± 24.0 PEmax (cmH 2 O) 32.0 ± 15.1 33.0 ± 18.4 FEV 1 (l) 1.90 ± 0.73 1.93 ± 0.79 FVC (l) 2.50 ± 0.94 2.55 ± 1.00 Vital Capacity (l) 2.59 ± 0.94 2.57 ± 0.89 Inspiratory Capacity (l) 2.06 ± 0.64 2.13 ± 0.63 PEFc (l/s) 4.74 ± 1.71 4.88 ± 1.34 Sleep disordered breathing parameters a Total AHI (events/h) 43.7 ± 24.5 46.1 ± 21.3 CSA (events/h) 0.5 ± 1.5 0.4 ± 0.9 Total REM AHI (events/h) 45.8 ± 19.2 51.6 ± 30.8 Total NREM AHI (events/h) 39.4 ± 24.7 40.9 ± 21.1 Min SpO 2 (%) 73.8 ± 15.0 75.7 ± 12.2 Time SpO 2 < 90% (%) 8.5 ± 12.8 10.5 ± 12.5 Mean SpO 2 (%) 93.5 ± 2.2 93.3 ± 2.1 Sleep duration (minutes) 286 ± 100 285 ± 84 Epworth Sleepiness Scale (ESS) b Total (number of participants) 31 26 ESS 11 (number of participants) 12 10 ESS (score/24) a 10.8 ± 6.2 9.5 ± 5.7 RMT, respiratory muscle training; AIS, American Spinal Injury Association (ASIA) Impairment Scale; AHI, Apnoea Hypopnoea Index; PImax, Maximal Inspiratory Pressure; PEmax, Maximal Expiratory Pressure; FEV 1 , Forced Expiratory Volume in 1 second; FVC, Forced Vital Capacity; PEFc, Peak expiratory Cough Flow; CSA, Central Sleep Apnoea; REM, Rapid eye movement; NREM, Non-rapid eye movement; Min SpO 2, Minimum oxygen saturation; Time SpO 2 < 90%, Percentage of time with oxygen saturation < 90%; Mean SpO 2 , Mean oxygen saturation; ESS, Epworth Sleepiness Scale. a means ± SD ; b ESS questionnaires completed by more participants and analysed with increased sample size, however ESS comparisons to other data were performed on complete datasets only. Following 6 weeks of supervised RMT, PImax was significantly higher in the active group when compared with the sham group (Table 2 ). The mean difference between the two groups (active-sham) was 11.8 cmH2O (95% CI: 5.2 to 18.4, p = 0.001). Based on severity classifications, 88% had moderate or severe SDB, and 8% had mild SDB. Ten percent of participants had mild daytime sleepiness while 31% reported moderate or excessive daytime sleepiness (Fig. 2 ). Table 2 Outcome measures at baseline, after 6-weeks of respiratory muscle training. Sham RMT group Active RMT group Baseline n = 26 6-Weeks n = 26 Baseline n = 22 6-Weeks n = 22 P-value 6-weeks Respiratory muscle strength measures PImax (cmH 2 O) 50.0 ± 19.2 55.5 ± 21.4 50.6 ± 24.0 67.8 ± 23.5 0.001 PEmax (cm H 2 O) 32.0 ± 15.1 37.6 ± 19.2 33.0 ± 18.4 39.7 ± 23.6 0.775 Lung function measures FEV 1 (l) 1.90 ± 0.73 1.89 ± 0.81 1.93 ± 0.79 2.00 ± 0.88 0.385 FVC (l) 2.50 ± 0.94 2.54 ± 1.04 2.55 ± 1.00 2.65 ± 1.11 0.349 Inspiratory Capacity (l) 2.06 ± 0.64 2.1 ± 0.8 2.13 ± 0.63 2.2 ± 0.7 0.546 Vital Capacity (l) 2.59 ± 0.94 2.7 ± 0.9 2.57 ± 0.89 2.8 ± 1.0 0.269 PEFc (l/s) 4.74 ± 1.71 4.87 ± 1.81 4.88 ± 1.34 5.01 ± 1.53 1.000 Sleep disordered breathing parameters AHI (events/h) 44 ± 25 40 ± 25 46 ± 21 45 ± 22 0.553 CSA (events/h) 1 ± 2 0 ± 1 0 ± 1 1 ± 3 0.173 REM AHI (events/h) 46 ± 19 39 ± 25 52 ± 31 45 ± 22 0.882 NREM AHI (events/h) 39 ± 25 36 ± 22 41 ± 21 42 ± 22 0.286 Min SpO 2 (%) 74 ± 15 76 ± 10 76 ± 12 78 ± 10 0.756 Time SpO 2 < 90% (%) 9 ± 13 12 ± 14 11 ± 13 11 ± 14 0.935 Mean SpO 2 (%) 94 ± 2 93 ± 2 93 ± 2 94 ± 2 0.381 Sleep duration (mins) 286 ± 100 281 ± 97 285 ± 84 325 ± 84 0.079 Epworth Sleepiness Scale (ESS) Baseline n = 32 6-Weeks n = 31 Baseline n = 30 6-Weeks n = 26 P-value 6-weeks ESS total score (/24) 10.8 ± 6.2 10.1 ± 5.8 9.5 ± 5.7 9.2 ± 6.7 0.952 Respiratory muscle strength measures a PImax (cmH 2 O) 51.5 ± 19.7 54.9 ± 21.3 48.4 ± 22.6 63.7 ± 24.0 < 0.001 PEmax (cm H 2 O) 33.2 ± 14.0 37.4 ± 17.8 33.2 ± 14.0 37.4 ± 17.8 0.799 Lung function measures a FEV 1 (l) 1.90 ± 0.72 1.89 ± 0.78 1.76 ± 0.76 1.84 ± 0.85 0.385 FVC (l) 2.56 ± 0.93 2.55 ± 1.00 2.29 ± 1.00 2.46 ± 1.08 0.349 Inspiratory Capacity (l) 2.10 ± 0.69 2.11 ± 0.81 1.97 ± 0.72 1.99 ± 0.79 0.979 Vital Capacity (l) 2.58 ± 0.91 2.67 ± 1.07 2.3 ± 0.80 2.50 ± 0.99 0.126 PEFc (l/s) 4.66 ± 1.61 4.75 ± 1.76 4.56 ± 1.46 4.70 ± 1.55 0.893 Data shown as mean ± SD; p < 0.05 was considered significant for analysis of covariance adjusted for the baseline measures. RMT, respiratory muscle training; PImax, Maximal Inspiratory Pressure; PEmax, Maximal Expiratory Pressure; FEV 1 , Forced Expiratory Volume in 1 second; FVC, Forced Vital Capacity; PEFc, Peak expiratory Cough Flow; AHI, Apnoea Hypopnoea Index; CSA, Central Sleep Apnoea; REM, Rapid eye movement; NREM, Non-rapid eye movement; Min SpO 2, Minimum oxygen saturation; Time SpO 2 < 90%, Percentage of time with oxygen saturation < 90%; Mean SpO 2 , Mean oxygen saturation; ESS, Epworth Sleepiness Scale. a values for comparisons to ESS data were performed on complete datasets. After 6 weeks of RMT there was no significant reduction in the AHI between the groups (active-sham), with a mean difference of 3 events/h (95% CI: -8 to 14, p = 0.553), nor was there a difference in ESS scores between groups (-0.06, 95% CI: -2.0 to 1.9, p = 0.952). Figure 3 shows individual AHI and ESS values (panel A and B, respectively) pre- and post- RMT for each participant, along with group means (± SD). There was no significant change in the remaining sleep or lung function parameters post training (Table 2 ). For people with acute tetraplegia, after 6 weeks of RMT there was no significant reduction in the AHI between the groups (active-sham), with a mean difference of 2 events/h (95% CI: -16 to 19, p = 0.845), nor was there a difference in ESS scores between groups (1.6, 95% CI: -3.3 to 6.4, p = 0.507). For people with chronic tetraplegia, after 6 weeks of RMT there was no significant reduction in the AHI between the groups (active-sham), with a mean difference of 3 events/h (95% CI: -13 to 18, p = 0.729), nor was there a difference in ESS scores between groups (-1.4, 95% CI: -3.6 to 0.9, p = 0.225). There was no correlation between baseline PImaxor change in PImax and change in AHI (p = 0.397 and p = 0.847, respectively) or change in ESS (p = 0.219 and p = 0.199, respectively). DISCUSSION This study indicates that 6-weeks of intensive of RMT does not alter the severity of SDB nor reduce daytime sleepiness for people with tetraplegia. No between-group differences were observed between Sham-RMT and Active-RMT groups, despite a 23% greater increase in inspiratory muscle strength (PImax) in the Active-RMT group. The prevalence of SDB in our cohort was 96%, yet no between-group differences in SDB were found after RMT in the newly injured population nor in people with chronic tetraplegia. Our results are similar to a 3-month RMT feasibility program in people with motor-incomplete SCI with no significant improvements in any outcome except PImax, for people with severe OSA. [ 24 ] Both studies are in contrast to a 12-week threshold-IMT program in people without SCI where the AHI and ESS were reduced by 6% and 20% for people with moderately severe OSA, with AHI scores < 30 events/h being a predictor of responders. [ 19 ] However, our group predominantly had severe SDB, making direct comparisons difficult. Potentially our 6-week program in people with tetraplegia was not long enough to induce the changes seen in people without SCI. However, training occurred twice daily with improvements in PImax, similar to Sankari et al (2024), who did not see improvements in SDB measures or tongue strength. [ 24 ] While it is possible to measure the strength of some upper airway muscles, it was not the primary outcome of the parent study. Future studies would benefit with measures of genioglossus protrusion strength after RMT to determine if this could be a mechanism for improvement in SDB, or the investigation of strategies to improve respiratory muscle endurance as a therapeutic target. Similar to other studies, [ 23 , 24 ] and not unexpected in this analysis, was finding no change in lung function or expiratory muscle strength after 6-weeks of RMT. This could underlie the lack of change in SDB seen in this study. The RMT intensity at average ~ 50% PImax over 6-weeks was comparable to previous RMT studies in SCI, [ 21 , 22 , 24 ] yet the absolute PImax of the cohort was relatively low (mean 50 cmH2O, ~ 40% predicted non-SCI). Thus, the absolute pressure at which the participants are training may be too low to effectively improve the strength of the upper airway muscles. This may be a limitation in this cohort because they are training their available intact respiratory muscles with a breathing effort that they perceived as severe (a modified Borg score of 5). [ 23 ] With the same rationale, the RMT intensity may not be sufficient to overcome other physiological factors such as high nasal resistance. In people with tetraplegia and OSA, nasal resistance and resulting upper airway collapsibility during sleep is higher compared to non-SCI individuals with OSA [ 12 ] most likely due to sympathetic dysfunction and unopposed parasympathetic outflow. Nasal decongestants such as phenylephrine reduce nasal resistance but have no impact on the severity of SDB. [ 25 ] Although higher airway surface tension of the liquid/secretions of the upper airway mucosa in OSA results in increased airway collapsibility, [ 26 ] surface tension in people with tetraplegia is not significantly different from non-SCI individuals. [ 27 ] While decreased lung volume may be a contributor to increased airway collapsibility due to decreased tracheal traction, [ 11 ] we saw no changes in lung volume in sitting after RMT. Lung volumes were not measured supine during our study thus, it cannot be determined if RMT affected supine lung volumes. Additionally, neither airway collapsibility, neck circumference nor abdominal girth were measured directly before and after RMT which are potential limitations of this study. Other studies that investigate the impact of muscle training on OSA in people without SCI have provided mixed results with the physiological mechanisms not clearly understood. In people without SCI, didgeridoo playing reduced the AHI and daytime sleepiness; [ 28 ] singing exercises reduced sleepiness and snoring; [ 29 ] and oropharyngeal exercises decreased neck circumference, snoring, daytime sleepiness and some people had reduced AHI. [ 30 ] The majority of our cohort had severe SDB, on average greater than 40 events/h with a large variance. To demonstrate a reduction of AHI by 15 events/h to change SDB severity category such that AHI is reduced to below 30 events/h, a sample of 46 participants per group would be required. Thus, in retrospect our study was underpowered to detect a clinically meaningful reduction in AHI, if present. However, this would appear unlikely given that the between group point estimates and 95%CIs were near identical in the current study. The lack of change in our study may also be related to the relatively short duration of RMT compared to the non-SCI population, where changes in SDB were observed after 12-weeks of RMT. [ 18 , 19 ] Improvements seen in the case report and pilot studies are difficult to explain given our findings, but may be related to the individual participant characteristics i.e. PImax, as some people were strong, or time since injury, as some people were still in the acute phase of SCI recovery. [ 21 , 22 ] Additionally, in our sub-group analysis, the numbers of people in each group (acute/chronic and mild/moderate-severe) were small and not sufficient to demonstrate similar changes as seen in the non-SCI population. RMT is a low-cost intervention that has been increasingly integrated into clinical care to increase inspiratory muscle strength after SCI. However, our study suggests that RMT at ~ 50% PImax does not reduce SDB or its consequences in people with acute or chronic tetraplegia over a short duration. Declarations Data availability: Data are available from the corresponding author on reasonable request. Acknowledgements: The authors would like to acknowledge the assistance of Erlinda Bolange and Melanie Madronio for their technical assistance with polysomnography. Author contributions: CBR, RHCL, DJE, BBL, SG, JB were responsible for the design of the trial; CBR, RHCL coordinated the trial; RHCL, CBR, JB were responsible for statistical design and analysis; CBR, RHCL, RAM, NSW trained all participants and set up the sleep studies; RHCL, CBR cleaned, collated and prepared data for analysis and drafted the manuscript. All authors have read and approved the final manuscript. Funding: This study was completed with support from the National Health and Medical Research Council (NHMRC) of Australia and the Prince of Wales Hospital Foundation. DJE is supported by a NHMRC Leadership Fellowship (1196261). Competing Interests: Outside the current work, DJE reports grants from Bayer, Apnimed, Eli Lilly, Restera (formally Invicta Medical), Restora, Withings and Takeda and serves on Scientific Advisory Boards or as a consultant for Restera, Mosanna, Restora, ResSleep, Takeda and Apnimed. The other authors have no conflicts of interest to report. References Biering-Sorensen, F, Jennum, P, Laub, M. Sleep disordered breathing following spinal cord injury. Respir Physiol Neurobiol. 2009; 169:165-70. Berlowitz, DJ, Brown, DJ, Campbell, DA, Pierce, RJ. A longitudinal evaluation of sleep and breathing in the first year after cervical spinal cord injury. Arch Phys Med Rehabil. 2005; 86:1193-9. Graco, M, McDonald, L, Green, S, Jackson, M, Berlowitz, D. 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Kirkness, JP, Madronio, M, Stavrinou, R, Wheatley, JR, Amis, TC. Surface tension of upper airway mucosal lining liquid in obstructive sleep apnea/hypopnea syndrome. Sleep. 2005; 28:457-63. Verma, M, Seto-Poon, M, Wheatley, JR, Amis, TC, Kirkness, JP. Influence of breathing route on upper airway lining liquid surface tension in humans. J Physiol. 2006; 574:859-66. Puhan, MA, Suarez, A, Lo Cascio, C, Zahn, A, Heitz, M, Braendli, O. Didgeridoo playing as alternative treatment for obstructive sleep apnoea syndrome: randomised controlled trial. BMJ. 2006; 332:266-70. Hilton, MP, Savage, JO, Hunter, B, McDonald, S, Repanos, C, Powell, R. Singing exercises improve sleepiness and frequency of snoring among snorers: A randomised controlled trial. Int J Otolaryngology Head Neck Surgery. 2013; 2:97-102. Guimaraes, KC, Drager, LF, Genta, PR, Marcondes, BF, Lorenzi-Filho, G. Effects of oropharyngeal exercises on patients with moderate obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2009; 179:962-6. Additional Declarations There is a duality of interest Supplementary Files CONSORT2010Checklist.doc Consort checklist Cite Share Download PDF Status: Under Revision Version 1 posted Editorial decision: revise 03 Nov, 2025 Review # 2 received at journal 06 Oct, 2025 Reviewer # 2 agreed at journal 06 Oct, 2025 Review # 1 received at journal 04 Oct, 2025 Reviewer # 1 agreed at journal 18 Sep, 2025 Reviewers invited by journal 17 Sep, 2025 Editor assigned by journal 16 Sep, 2025 Submission checks completed at journal 04 Sep, 2025 First submitted to journal 02 Sep, 2025 You are reading this latest preprint version Research Square lets you share your work early, gain feedback from the community, and start making changes to your manuscript prior to peer review in a journal. As a division of Research Square Company, we’re committed to making research communication faster, fairer, and more useful. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-7522267","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Article","associatedPublications":[],"authors":[{"id":516755005,"identity":"afb3f6cc-e80d-4642-8bdc-23b4892c2563","order_by":0,"name":"Claire Boswell-Ruys","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAABFElEQVRIiWNgGAWjYFACHjApwwfh2cCEmQlq4WGD8NJI13KYsBb+Bt6DD3+22QC18D6T5vlzPo9fIvfhB4YK68QG9jMG2LRIHOBLNuZtSwNqYTeT5m27XSw5I91YguFMemIDTw5WLQYMPGbSjNsO87DJP2OT5m24nbjhRhqDBGPb4cQGBtxaJH9u+w+0hY0N6LBziftvpDH/YPwH1ML/BqcWCd5tB6Ba2A4kbpBIY5NgbABqkcBui8RhkF/+JYO0MFvObUtOnHHmGZtFwrF04zaJZwVYQ6y99+DDH2fs5PgZ2BhvvPljl9jfnsZ840ONtWw/f/IGrKGMHP5MPDBWAhCzYVWPBhh/EKNqFIyCUTAKRhwAABpNT/bhjz9EAAAAAElFTkSuQmCC","orcid":"https://orcid.org/0000-0003-4922-5262","institution":"[email protected]","correspondingAuthor":true,"prefix":"","firstName":"Claire","middleName":"","lastName":"Boswell-Ruys","suffix":""},{"id":516755006,"identity":"c7fea141-5cae-4711-988b-3240766552d2","order_by":1,"name":"R.H. 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1","display":"","copyAsset":false,"role":"figure","size":59056,"visible":true,"origin":"","legend":"\u003cp\u003eParticipant flow diagram for the number (n) of participants enrolled, allocated to Sham- and Active- RMT (respiratory muscle training) groups, and included in the analyses. IMT, inspiratory muscle training; SDB, sleep disordered breathing; ESS, Epworth sleepiness scale; PSG, polysomnography.\u003c/p\u003e","description":"","filename":"Figure1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7522267/v1/d97ff69338d83b847c00fb10.jpg"},{"id":92472986,"identity":"0206b461-045a-431b-b289-5f4098453018","added_by":"auto","created_at":"2025-09-30 06:57:09","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":38462,"visible":true,"origin":"","legend":"\u003cp\u003ePercentage of participants with sleep disordered breathing (SDB) severity classifications (panel A) and daytime sleepiness classification levels based on Epworth Sleepiness Scale (ESS) score (panel B).\u003c/p\u003e","description":"","filename":"Figure2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7522267/v1/ffe084d394bd1423781ccba5.jpg"},{"id":92472995,"identity":"7ad3b6f6-29ad-41fc-9d9e-6c893ea3617e","added_by":"auto","created_at":"2025-09-30 06:57:10","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":93398,"visible":true,"origin":"","legend":"\u003cp\u003eThe Apnoea-Hypoxia Index (AHI) and Epworth Sleepiness Scale (ESS) score data (panel A and B, respectively), pre- and post- 6-weeks of respiratory muscle training (RMT), individual participants are connected by a line. Participants in the Sham RMT group are represented by squares (left panels) and those in the Active RMT group by circles (right panels). Group means are represented by individual symbols and corresponding SD as a vertical line.\u003c/p\u003e","description":"","filename":"Figure3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7522267/v1/b78b686fe57418567c3db1ad.jpg"},{"id":92476423,"identity":"2e683fde-8cac-440b-8da3-fa4a439569fb","added_by":"auto","created_at":"2025-09-30 07:21:14","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":1067885,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7522267/v1/48c8fd29-49ec-4bb1-8dc7-34ba7b71e36a.pdf"},{"id":92472989,"identity":"4d7c2d50-7a45-48ad-acbe-e42fbbce1c8f","added_by":"auto","created_at":"2025-09-30 06:57:09","extension":"doc","order_by":2,"title":"","display":"","copyAsset":false,"role":"supplement","size":223744,"visible":true,"origin":"","legend":"Consort checklist","description":"","filename":"CONSORT2010Checklist.doc","url":"https://assets-eu.researchsquare.com/files/rs-7522267/v1/04a78f51e588e7be6050417d.doc"}],"financialInterests":"There is a duality of interest","formattedTitle":"Impact of respiratory muscle training on sleep disordered breathing in people with tetraplegia: A sub-analysis of a randomised controlled trial","fulltext":[{"header":"INTRODUCTION","content":"\u003cp\u003eSleep disordered breathing (SDB) is a common sequelae of spinal cord injury (SCI) with SDB risk factors such as obesity and male sex being more common in this population compared to people without a SCI. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e] SDB includes obstructive sleep apnoea (OSA), central sleep apnoea (CSA) and sleep-related hypoventilation disorders, and is prevalent after tetraplegia. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e] In tetraplegia, SDB prevalence peaks at 83% at 3 months post injury with a subsequent reduction in severity after 6 months. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e] However, the prevalence is still much greater than the non-SCI population and varies between 27 to 81%. [\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e, \u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eSDB is associated with an increase in adverse cardiovascular outcomes. [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e] Obesity, diabetes and cardiovascular morbidity is common after SCI. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Cardiovascular and respiratory disease are the leading causes of death 12 months after SCI. [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e] While little is known about the long-term consequences of nocturnal hypoventilation and hypercapnia in SCI, it is possible that SDB contributes to increased cardiovascular mortality in chronic tetraplegia and therefore, represents a modifiable cardiovascular risk factor. However, there are no data on long-term outcomes or the impact of treating SDB in this population. Additionally, excessive daytime sleepiness, disturbed and poor sleep quality are common problems in people with tetraplegia. [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThe reasons behind the high prevalence of SDB in tetraplegia are likely multifactorial. While the motor and sensory innervation of pharyngeal muscles that maintain upper airway patency remain intact in tetraplegia, upper airway dilator muscle reflex responses are altered in many people with tetraplegia and sleep apnoea. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] Other factors that affect upper airway collapsibility are also altered after SCI. Increased collapsibility of the upper airway during sleep is a driver of SDB pathogenesis both non-SCI [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e] as well as in tetraplegia, where the upper airway critical closing pressure of the pharynx is higher (less negative/more collapsible). [\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e] Decreased lung volume and accompanying reductions in tracheal traction can increase airway collapsibility. [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] In people with tetraplegia lung volume in supine may be reduced further in the presence of high BMI or large abdominal girth. [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e] Disruption of the sympathetic control of airway mucosa and high nasal resistance may also play a role in the high prevalence of SDB in people with SCI. [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eUpper airway muscles, including genioglossus, maintain upper airway patency. People with OSA have significantly higher basal genioglossal activity that is believed to compensate for a more collapsible upper airway. [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e] Activity of the genioglossus is reduced at sleep onset [\u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e] with a greater reduction in people with OSA. [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e] Genioglossus activity is modulated by afferents of upper airway mechanoreceptors, [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] lung and chest wall stretch receptors. [\u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eSDB treatment indications in SCI are similar to the general population. The gold standard of treatment is positive airway pressure (PAP) with either continuous or bi-level nocturnal non-invasive ventilation. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] However, adherence with PAP therapy is low in the SCI population with compliance between 23% and 50%. [\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e] Thus, a well-tolerated, self-administered, home-based alternative therapeutic modality such as respiratory muscle training (RMT), which would also train the upper airway muscles, has merit, yet has shown mixed results. In people without a SCI threshold inspiratory muscle training (IMT) over 12-weeks improves the Functional Outcomes of Sleep Questionnaire score and snoring (n\u0026thinsp;=\u0026thinsp;27), [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e] and a reduction in the apnoea-hypopnea index (AHI) and Epworth Sleepiness Scale (ESS) of people with moderately severe OSA (n\u0026thinsp;=\u0026thinsp;22) [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] but not in people with mild to moderate OSA after 5-weeks IMT (n\u0026thinsp;=\u0026thinsp;9). [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e] Pilot studies in tetraplegia suggest RMT increased inspiratory muscle strength, reduced AHI and improved nocturnal oxygen saturation. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] The aim of the current study was to investigate, as part of a larger randomised controlled trial, the effect of RMT on SDB severity and daytime sleepiness in people with tetraplegia. We hypothesised that AHI would reduce after RMT due to increased inspiratory muscle strength. If the severity of SDB can be reduced with RMT, it would offer a low-cost alternative form of treatment, that may be better tolerated than PAP.\u003c/p\u003e"},{"header":"METHODS","content":"\u003cdiv id=\"Sec3\" class=\"Section2\"\u003e\u003ch2\u003eStudy design\u003c/h2\u003e\u003cp\u003eA planned sub-analysis of a double-blind, randomised controlled trial to compare the effect of RMT on SDB severity and daytime sleepiness. The trial was pre-registered at Australian New Zealand Clinical Trials Registry (ACTRN 12612000929808) and conducted at a single site between November 2013 and December 2016. All procedures were approved by the South-Eastern Sydney Local Health District Human Research Ethics Committee (Reference No. 12/192) and the University of New South Wales Human Research Ethics Committee (Reference No. HC13388) and complied with the Declaration of Helsinki 2013.\u003c/p\u003e\u003c/div\u003e\n\u003ch3\u003eParticipants\u003c/h3\u003e\n\u003cp\u003eParticipants aged over 18 years with C3-C8 neurological level of SCI and American Spinal Injury Association Impairment Scale grades A-C were recruited from Prince of Wales Hospital, Sydney or the community as part of a larger RMT trial. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] Sixty-two people with tetraplegia participated. Those with significant chest trauma, pneumothorax, significant co-existing respiratory or neurological condition, cognitive impairment or mechanically ventilated were excluded. Prior to enrolment, informed written consent was obtained from participants or with the aid of a family member or an independent third party if unable to sign independently.\u003c/p\u003e\n\u003ch3\u003eRandomisation and blinding\u003c/h3\u003e\n\u003cp\u003eA computer-generated random allocation schedule was used to minimise differences between treatment groups (sham and active; see Boswell-Ruys et al [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] for details). Stratification was based on, time since injury (acute (\u0026lt;\u0026thinsp;6 months) versus chronic (\u0026gt;\u0026thinsp;1 year)); motor complete versus motor incomplete SCI; and a baseline AHI (above or below 15 events/h). Participants, treating therapists, sleep technicians, polysomnography scorer and assessors were blind to allocated treatment throughout the trial.\u003c/p\u003e\n\u003ch3\u003eIntervention\u003c/h3\u003e\n\u003cp\u003eParticipants performed supervised RMT twice daily for six-weeks using a portable threshold-RMT device (Threshold IMT, Philips Respironics, New Jersey, USA). Five days a week, 3\u0026ndash;5 sets of 12 inspiratory breaths, sets separated by two minutes of resting breathing, were completed. Expiratory breaths followed the same protocol. The training procedure employed a nonlinear exercise regime that was tailored to increase training intensity as strength improved. Participants commenced training at 30% baseline maximal inspiratory pressure (PImax) or maximal expiratory pressure (PEmax) which thereafter increased weekly by 10% (capped at 80% PImax or PEmax). Further details about device modifications for sham or active and RMT can be found in Boswell-Ruys et al. [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]\u003c/p\u003e\n\u003ch3\u003eOutcome measures\u003c/h3\u003e\n\u003cp\u003eThe primary outcome was total AHI. All sleep parameters were assessed in participants\u0026rsquo; homes using portable level II polysomnography (Alice PDx, Philips Respironics, Murrysville, Pennsylvania, USA). The parameters recorded included apnoea and hypopnoea events per hour of sleep (AHI), central sleep apnoea events (CSA), and AHI events during rapid- and non-rapid eye movement (REM and NREM) sleep and sleep duration. The minimum and mean blood oxygen desaturation (SpO2) during sleep, and the percentage of time that saturation was \u0026lt;\u0026thinsp;90% were calculated. Daytime somnolence was assessed using the Epworth Sleepiness Scale (ESS). The primary outcome in the parent trial was inspiratory muscle strength measured as PImax, with secondary outcomes of lung function; inspiratory capacity (IC), vital capacity (VC), forced vital capacity (FVC), forced expiratory volume in one second (FEV1), peak expiratory flow during a cough (PEFc), and maximal expiratory pressure (PEmax) all measured with a portable lung function machine (Hyp\u0026rsquo;air, Belgium) following the American Thoracic Society (ATS) guidelines.\u003c/p\u003e\u003cdiv id=\"Sec8\" class=\"Section2\"\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eData were analysed using analysis of covariance (ANCOVA) adjusted for the baseline measures. The treatment effect size was estimated by the between-group mean difference and corresponding 95% confidence intervals. The relationship between baseline or change in PImax and change in AHI and change in ESS were analysed with Pearson\u0026rsquo;s correlations. Missing data were deleted on a case-wise basis. An alpha level\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant. All statistical analyses were performed with IBM SPSS Statistics (v25, IBM Corp., Armonk, NY, USA).\u003c/p\u003e\u003c/div\u003e"},{"header":"RESULTS","content":"\u003cp\u003eSixty-two people with cervical SCI were recruited; 48 participants had complete and analysable diagnostic polysomnography at baseline and after 6-weeks of supervised training, and 57 participants had complete ESS data (see Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e). The RMT protocol was adhered to by all participants. Baseline characteristics (Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e) were well matched between groups. However, no female participants were allocated to the active training group.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eParticipant characteristics at baseline for sleep disordered breathing analysis\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"3\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eSham RMT\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eActive RMT\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003ctr\u003e\u003cth align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003eNumber of participants\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAcute (\u0026lt;\u0026thinsp;6 months post injury)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChronic (\u0026gt;\u0026thinsp;1-year post injury)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMotor Complete Injury (AIS A-B)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e18\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMotor Incomplete Injury (AIS C)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAHI\u0026thinsp;\u0026lt;\u0026thinsp;5 events/h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAHI 5\u0026ndash;15 events/h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAHI 16\u0026ndash;30 events/h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAHI\u0026thinsp;\u0026gt;\u0026thinsp;31 events/h\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e20\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eAge\u003c/b\u003e (years) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e53.9\u0026thinsp;\u0026plusmn;\u0026thinsp;14.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e48.4\u0026thinsp;\u0026plusmn;\u0026thinsp;14.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSex\u003c/b\u003e (m:f)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e22:4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e22:0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003e\u003cb\u003eBody-mass index\u003c/b\u003e (kg/m\u003csup\u003e2\u003c/sup\u003e) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e24.4\u0026thinsp;\u0026plusmn;\u0026thinsp;5.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e24.9\u0026thinsp;\u0026plusmn;\u0026thinsp;5.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLung function measures\u003c/b\u003e \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePImax (cmH\u003csub\u003e2\u003c/sub\u003eO)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50.0\u0026thinsp;\u0026plusmn;\u0026thinsp;19.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e50.6\u0026thinsp;\u0026plusmn;\u0026thinsp;24.0\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePEmax (cmH\u003csub\u003e2\u003c/sub\u003eO)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32.0\u0026thinsp;\u0026plusmn;\u0026thinsp;15.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e33.0\u0026thinsp;\u0026plusmn;\u0026thinsp;18.4\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFEV\u003csub\u003e1\u003c/sub\u003e (l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFVC (l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.55\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVital Capacity (l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.89\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInspiratory Capacity (l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePEFc (l/s)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.74\u0026thinsp;\u0026plusmn;\u0026thinsp;1.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.88\u0026thinsp;\u0026plusmn;\u0026thinsp;1.34\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSleep disordered breathing parameters\u003c/b\u003e \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal AHI (events/h)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e43.7\u0026thinsp;\u0026plusmn;\u0026thinsp;24.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e46.1\u0026thinsp;\u0026plusmn;\u0026thinsp;21.3\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSA (events/h)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e0.5\u0026thinsp;\u0026plusmn;\u0026thinsp;1.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0.4\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal REM AHI (events/h)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e45.8\u0026thinsp;\u0026plusmn;\u0026thinsp;19.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e51.6\u0026thinsp;\u0026plusmn;\u0026thinsp;30.8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal NREM AHI (events/h)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39.4\u0026thinsp;\u0026plusmn;\u0026thinsp;24.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40.9\u0026thinsp;\u0026plusmn;\u0026thinsp;21.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMin SpO\u003csub\u003e2\u003c/sub\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e73.8\u0026thinsp;\u0026plusmn;\u0026thinsp;15.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e75.7\u0026thinsp;\u0026plusmn;\u0026thinsp;12.2\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime SpO\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;\u0026lt;\u0026thinsp;90% (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e8.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.5\u0026thinsp;\u0026plusmn;\u0026thinsp;12.5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean SpO\u003csub\u003e2\u003c/sub\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e93.5\u0026thinsp;\u0026plusmn;\u0026thinsp;2.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e93.3\u0026thinsp;\u0026plusmn;\u0026thinsp;2.1\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSleep duration (minutes)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e286\u0026thinsp;\u0026plusmn;\u0026thinsp;100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e285\u0026thinsp;\u0026plusmn;\u0026thinsp;84\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEpworth Sleepiness Scale (ESS)\u003c/b\u003e \u003csup\u003eb\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTotal (number of participants)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e26\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eESS\u0026thinsp;\u0026lt;\u0026thinsp;11 (number of participants)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e16\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eESS\u0026thinsp;\u0026gt;\u0026thinsp;11 (number of participants)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eESS (score/24) \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e9.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003eRMT, respiratory muscle training; AIS, American Spinal Injury Association (ASIA) Impairment Scale; AHI, Apnoea Hypopnoea Index; PImax, Maximal Inspiratory Pressure; PEmax, Maximal Expiratory Pressure; FEV\u003csub\u003e1\u003c/sub\u003e, Forced Expiratory Volume in 1 second; FVC, Forced Vital Capacity; PEFc, Peak expiratory Cough Flow; CSA, Central Sleep Apnoea; REM, Rapid eye movement; NREM, Non-rapid eye movement; Min SpO\u003csub\u003e2,\u003c/sub\u003e Minimum oxygen saturation; Time SpO\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;\u0026lt;\u0026thinsp;90%, Percentage of time with oxygen saturation\u0026thinsp;\u0026lt;\u0026thinsp;90%; Mean SpO\u003csub\u003e2\u003c/sub\u003e, Mean oxygen saturation; ESS, Epworth Sleepiness Scale.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"3\"\u003e\u003csup\u003ea\u003c/sup\u003e \u003cem\u003emeans\u003c/em\u003e\u0026thinsp;\u0026plusmn;\u0026thinsp;\u003cem\u003eSD\u003c/em\u003e; \u003csup\u003eb\u003c/sup\u003e \u003cem\u003eESS questionnaires completed by more participants and analysed with increased sample size, however ESS comparisons to other data were performed on complete datasets only.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003eFollowing 6 weeks of supervised RMT, PImax was significantly higher in the active group when compared with the sham group (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The mean difference between the two groups (active-sham) was 11.8 cmH2O (95% CI: 5.2 to 18.4, p\u0026thinsp;=\u0026thinsp;0.001). Based on severity classifications, 88% had moderate or severe SDB, and 8% had mild SDB. Ten percent of participants had mild daytime sleepiness while 31% reported moderate or excessive daytime sleepiness (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab2\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 2\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003eOutcome measures at baseline, after 6-weeks of respiratory muscle training.\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"6\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c3\" namest=\"c2\"\u003e\u003cp\u003eSham RMT group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colspan=\"2\" nameend=\"c5\" namest=\"c4\"\u003e\u003cp\u003eActive RMT group\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u0026nbsp;\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6-Weeks\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6-Weeks\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003cp\u003e6-weeks\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRespiratory muscle strength measures\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePImax (cmH\u003csub\u003e2\u003c/sub\u003eO)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e50.0\u0026thinsp;\u0026plusmn;\u0026thinsp;19.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e55.5\u0026thinsp;\u0026plusmn;\u0026thinsp;21.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e50.6\u0026thinsp;\u0026plusmn;\u0026thinsp;24.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e67.8\u0026thinsp;\u0026plusmn;\u0026thinsp;23.5\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePEmax (cm H\u003csub\u003e2\u003c/sub\u003eO)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e32.0\u0026thinsp;\u0026plusmn;\u0026thinsp;15.1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37.6\u0026thinsp;\u0026plusmn;\u0026thinsp;19.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e33.0\u0026thinsp;\u0026plusmn;\u0026thinsp;18.4\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e39.7\u0026thinsp;\u0026plusmn;\u0026thinsp;23.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.775\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c3\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLung function measures\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colspan=\"3\" nameend=\"c6\" namest=\"c4\"\u003e\u0026nbsp;\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFEV\u003csub\u003e1\u003c/sub\u003e (l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.73\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.93\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.00\u0026thinsp;\u0026plusmn;\u0026thinsp;0.88\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.385\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFVC (l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.54\u0026thinsp;\u0026plusmn;\u0026thinsp;1.04\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.55\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.65\u0026thinsp;\u0026plusmn;\u0026thinsp;1.11\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.349\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInspiratory Capacity (l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.06\u0026thinsp;\u0026plusmn;\u0026thinsp;0.64\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.1\u0026thinsp;\u0026plusmn;\u0026thinsp;0.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.13\u0026thinsp;\u0026plusmn;\u0026thinsp;0.63\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.2\u0026thinsp;\u0026plusmn;\u0026thinsp;0.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.546\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVital Capacity (l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.59\u0026thinsp;\u0026plusmn;\u0026thinsp;0.94\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.7\u0026thinsp;\u0026plusmn;\u0026thinsp;0.9\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.57\u0026thinsp;\u0026plusmn;\u0026thinsp;0.89\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.8\u0026thinsp;\u0026plusmn;\u0026thinsp;1.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.269\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePEFc (l/s)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.74\u0026thinsp;\u0026plusmn;\u0026thinsp;1.71\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.87\u0026thinsp;\u0026plusmn;\u0026thinsp;1.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.88\u0026thinsp;\u0026plusmn;\u0026thinsp;1.34\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e5.01\u0026thinsp;\u0026plusmn;\u0026thinsp;1.53\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1.000\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eSleep disordered breathing parameters\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAHI (events/h)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e44\u0026thinsp;\u0026plusmn;\u0026thinsp;25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e40\u0026thinsp;\u0026plusmn;\u0026thinsp;25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e46\u0026thinsp;\u0026plusmn;\u0026thinsp;21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e45\u0026thinsp;\u0026plusmn;\u0026thinsp;22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.553\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eCSA (events/h)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e0\u0026thinsp;\u0026plusmn;\u0026thinsp;1\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1\u0026thinsp;\u0026plusmn;\u0026thinsp;3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.173\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eREM AHI (events/h)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e46\u0026thinsp;\u0026plusmn;\u0026thinsp;19\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e39\u0026thinsp;\u0026plusmn;\u0026thinsp;25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e52\u0026thinsp;\u0026plusmn;\u0026thinsp;31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e45\u0026thinsp;\u0026plusmn;\u0026thinsp;22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.882\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eNREM AHI (events/h)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e39\u0026thinsp;\u0026plusmn;\u0026thinsp;25\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e36\u0026thinsp;\u0026plusmn;\u0026thinsp;22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e41\u0026thinsp;\u0026plusmn;\u0026thinsp;21\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e42\u0026thinsp;\u0026plusmn;\u0026thinsp;22\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.286\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMin SpO\u003csub\u003e2\u003c/sub\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e74\u0026thinsp;\u0026plusmn;\u0026thinsp;15\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e76\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e76\u0026thinsp;\u0026plusmn;\u0026thinsp;12\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e78\u0026thinsp;\u0026plusmn;\u0026thinsp;10\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.756\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eTime SpO\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;\u0026lt;\u0026thinsp;90% (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e9\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e12\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e11\u0026thinsp;\u0026plusmn;\u0026thinsp;13\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e11\u0026thinsp;\u0026plusmn;\u0026thinsp;14\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.935\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eMean SpO\u003csub\u003e2\u003c/sub\u003e (%)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e94\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e93\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e93\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e94\u0026thinsp;\u0026plusmn;\u0026thinsp;2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.381\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSleep duration (mins)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e286\u0026thinsp;\u0026plusmn;\u0026thinsp;100\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e281\u0026thinsp;\u0026plusmn;\u0026thinsp;97\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e285\u0026thinsp;\u0026plusmn;\u0026thinsp;84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e325\u0026thinsp;\u0026plusmn;\u0026thinsp;84\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.079\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eEpworth Sleepiness Scale (ESS)\u003c/b\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u0026nbsp;\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;32\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e6-Weeks\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;31\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eBaseline\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;30\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e6-Weeks\u003c/p\u003e\u003cp\u003en\u0026thinsp;=\u0026thinsp;26\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003eP-value\u003c/p\u003e\u003cp\u003e6-weeks\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eESS total score (/24)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e10.8\u0026thinsp;\u0026plusmn;\u0026thinsp;6.2\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e10.1\u0026thinsp;\u0026plusmn;\u0026thinsp;5.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e9.5\u0026thinsp;\u0026plusmn;\u0026thinsp;5.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e9.2\u0026thinsp;\u0026plusmn;\u0026thinsp;6.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.952\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eRespiratory muscle strength measures\u003c/b\u003e \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePImax (cmH\u003csub\u003e2\u003c/sub\u003eO)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e51.5\u0026thinsp;\u0026plusmn;\u0026thinsp;19.7\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e54.9\u0026thinsp;\u0026plusmn;\u0026thinsp;21.3\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e48.4\u0026thinsp;\u0026plusmn;\u0026thinsp;22.6\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e63.7\u0026thinsp;\u0026plusmn;\u0026thinsp;24.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e\u0026lt;\u0026thinsp;0.001\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePEmax (cm H\u003csub\u003e2\u003c/sub\u003eO)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e33.2\u0026thinsp;\u0026plusmn;\u0026thinsp;14.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e37.4\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e33.2\u0026thinsp;\u0026plusmn;\u0026thinsp;14.0\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e37.4\u0026thinsp;\u0026plusmn;\u0026thinsp;17.8\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.799\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colspan=\"6\" nameend=\"c6\" namest=\"c1\"\u003e\u003cp\u003e\u003cb\u003eLung function measures\u003c/b\u003e \u003csup\u003ea\u003c/sup\u003e\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFEV\u003csub\u003e1\u003c/sub\u003e (l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e1.90\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1.89\u0026thinsp;\u0026plusmn;\u0026thinsp;0.78\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.76\u0026thinsp;\u0026plusmn;\u0026thinsp;0.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.84\u0026thinsp;\u0026plusmn;\u0026thinsp;0.85\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.385\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eFVC (l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.56\u0026thinsp;\u0026plusmn;\u0026thinsp;0.93\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.55\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.29\u0026thinsp;\u0026plusmn;\u0026thinsp;1.00\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.46\u0026thinsp;\u0026plusmn;\u0026thinsp;1.08\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.349\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eInspiratory Capacity (l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.10\u0026thinsp;\u0026plusmn;\u0026thinsp;0.69\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.11\u0026thinsp;\u0026plusmn;\u0026thinsp;0.81\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e1.97\u0026thinsp;\u0026plusmn;\u0026thinsp;0.72\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e1.99\u0026thinsp;\u0026plusmn;\u0026thinsp;0.79\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.979\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eVital Capacity (l)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e2.58\u0026thinsp;\u0026plusmn;\u0026thinsp;0.91\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2.67\u0026thinsp;\u0026plusmn;\u0026thinsp;1.07\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e2.3\u0026thinsp;\u0026plusmn;\u0026thinsp;0.80\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e2.50\u0026thinsp;\u0026plusmn;\u0026thinsp;0.99\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.126\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003ePEFc (l/s)\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c2\"\u003e\u003cp\u003e4.66\u0026thinsp;\u0026plusmn;\u0026thinsp;1.61\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e4.75\u0026thinsp;\u0026plusmn;\u0026thinsp;1.76\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003e4.56\u0026thinsp;\u0026plusmn;\u0026thinsp;1.46\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003e4.70\u0026thinsp;\u0026plusmn;\u0026thinsp;1.55\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e0.893\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003eData shown as mean\u0026thinsp;\u0026plusmn;\u0026thinsp;SD; p\u0026thinsp;\u0026lt;\u0026thinsp;0.05 was considered significant for analysis of covariance adjusted for the baseline measures. RMT, respiratory muscle training; PImax, Maximal Inspiratory Pressure; PEmax, Maximal Expiratory Pressure; FEV\u003csub\u003e1\u003c/sub\u003e, Forced Expiratory Volume in 1 second; FVC, Forced Vital Capacity; PEFc, Peak expiratory Cough Flow; AHI, Apnoea Hypopnoea Index; CSA, Central Sleep Apnoea; REM, Rapid eye movement; NREM, Non-rapid eye movement; Min SpO\u003csub\u003e2,\u003c/sub\u003e Minimum oxygen saturation; Time SpO\u003csub\u003e2\u003c/sub\u003e\u0026thinsp;\u0026lt;\u0026thinsp;90%, Percentage of time with oxygen saturation\u0026thinsp;\u0026lt;\u0026thinsp;90%; Mean SpO\u003csub\u003e2\u003c/sub\u003e, Mean oxygen saturation; ESS, Epworth Sleepiness Scale.\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd colspan=\"6\"\u003e\u003csup\u003ea\u003c/sup\u003e \u003cem\u003evalues for comparisons to ESS data were performed on complete datasets.\u003c/em\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eAfter 6 weeks of RMT there was no significant reduction in the AHI between the groups (active-sham), with a mean difference of 3 events/h (95% CI: -8 to 14, p\u0026thinsp;=\u0026thinsp;0.553), nor was there a difference in ESS scores between groups (-0.06, 95% CI: -2.0 to 1.9, p\u0026thinsp;=\u0026thinsp;0.952). Figure\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e shows individual AHI and ESS values (panel A and B, respectively) pre- and post- RMT for each participant, along with group means (\u0026plusmn;\u0026thinsp;SD). There was no significant change in the remaining sleep or lung function parameters post training (Table\u0026nbsp;\u003cspan refid=\"Tab2\" class=\"InternalRef\"\u003e2\u003c/span\u003e).\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003eFor people with acute tetraplegia, after 6 weeks of RMT there was no significant reduction in the AHI between the groups (active-sham), with a mean difference of 2 events/h (95% CI: -16 to 19, p\u0026thinsp;=\u0026thinsp;0.845), nor was there a difference in ESS scores between groups (1.6, 95% CI: -3.3 to 6.4, p\u0026thinsp;=\u0026thinsp;0.507).\u003c/p\u003e\u003cp\u003eFor people with chronic tetraplegia, after 6 weeks of RMT there was no significant reduction in the AHI between the groups (active-sham), with a mean difference of 3 events/h (95% CI: -13 to 18, p\u0026thinsp;=\u0026thinsp;0.729), nor was there a difference in ESS scores between groups (-1.4, 95% CI: -3.6 to 0.9, p\u0026thinsp;=\u0026thinsp;0.225).\u003c/p\u003e\u003cp\u003eThere was no correlation between baseline PImaxor change in PImax and change in AHI (p\u0026thinsp;=\u0026thinsp;0.397 and p\u0026thinsp;=\u0026thinsp;0.847, respectively) or change in ESS (p\u0026thinsp;=\u0026thinsp;0.219 and p\u0026thinsp;=\u0026thinsp;0.199, respectively).\u003c/p\u003e"},{"header":"DISCUSSION","content":"\u003cp\u003eThis study indicates that 6-weeks of intensive of RMT does not alter the severity of SDB nor reduce daytime sleepiness for people with tetraplegia. No between-group differences were observed between Sham-RMT and Active-RMT groups, despite a 23% greater increase in inspiratory muscle strength (PImax) in the Active-RMT group. The prevalence of SDB in our cohort was 96%, yet no between-group differences in SDB were found after RMT in the newly injured population nor in people with chronic tetraplegia.\u003c/p\u003e\u003cp\u003eOur results are similar to a 3-month RMT feasibility program in people with motor-incomplete SCI with no significant improvements in any outcome except PImax, for people with severe OSA. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] Both studies are in contrast to a 12-week threshold-IMT program in people without SCI where the AHI and ESS were reduced by 6% and 20% for people with moderately severe OSA, with AHI scores\u0026thinsp;\u0026lt;\u0026thinsp;30 events/h being a predictor of responders. [\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] However, our group predominantly had severe SDB, making direct comparisons difficult. Potentially our 6-week program in people with tetraplegia was not long enough to induce the changes seen in people without SCI. However, training occurred twice daily with improvements in PImax, similar to Sankari et al (2024), who did not see improvements in SDB measures or tongue strength. [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] While it is possible to measure the strength of some upper airway muscles, it was not the primary outcome of the parent study. Future studies would benefit with measures of genioglossus protrusion strength after RMT to determine if this could be a mechanism for improvement in SDB, or the investigation of strategies to improve respiratory muscle endurance as a therapeutic target.\u003c/p\u003e\u003cp\u003eSimilar to other studies, [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] and not unexpected in this analysis, was finding no change in lung function or expiratory muscle strength after 6-weeks of RMT. This could underlie the lack of change in SDB seen in this study. The RMT intensity at average\u0026thinsp;~\u0026thinsp;50% PImax over 6-weeks was comparable to previous RMT studies in SCI, [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e, \u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] yet the absolute PImax of the cohort was relatively low (mean 50 cmH2O, ~\u0026thinsp;40% predicted non-SCI). Thus, the absolute pressure at which the participants are training may be too low to effectively improve the strength of the upper airway muscles. This may be a limitation in this cohort because they are training their available intact respiratory muscles with a breathing effort that they perceived as severe (a modified Borg score of 5). [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e] With the same rationale, the RMT intensity may not be sufficient to overcome other physiological factors such as high nasal resistance. In people with tetraplegia and OSA, nasal resistance and resulting upper airway collapsibility during sleep is higher compared to non-SCI individuals with OSA [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e] most likely due to sympathetic dysfunction and unopposed parasympathetic outflow. Nasal decongestants such as phenylephrine reduce nasal resistance but have no impact on the severity of SDB. [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] Although higher airway surface tension of the liquid/secretions of the upper airway mucosa in OSA results in increased airway collapsibility, [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e] surface tension in people with tetraplegia is not significantly different from non-SCI individuals. [\u003cspan citationid=\"CR27\" class=\"CitationRef\"\u003e27\u003c/span\u003e] While decreased lung volume may be a contributor to increased airway collapsibility due to decreased tracheal traction, [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e] we saw no changes in lung volume in sitting after RMT. Lung volumes were not measured supine during our study thus, it cannot be determined if RMT affected supine lung volumes. Additionally, neither airway collapsibility, neck circumference nor abdominal girth were measured directly before and after RMT which are potential limitations of this study.\u003c/p\u003e\u003cp\u003eOther studies that investigate the impact of muscle training on OSA in people without SCI have provided mixed results with the physiological mechanisms not clearly understood. In people without SCI, didgeridoo playing reduced the AHI and daytime sleepiness; [\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e] singing exercises reduced sleepiness and snoring; [\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e] and oropharyngeal exercises decreased neck circumference, snoring, daytime sleepiness and some people had reduced AHI. [\u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/p\u003e\u003cp\u003eThe majority of our cohort had severe SDB, on average greater than 40 events/h with a large variance. To demonstrate a reduction of AHI by 15 events/h to change SDB severity category such that AHI is reduced to below 30 events/h, a sample of 46 participants per group would be required. Thus, in retrospect our study was underpowered to detect a clinically meaningful reduction in AHI, if present. However, this would appear unlikely given that the between group point estimates and 95%CIs were near identical in the current study. The lack of change in our study may also be related to the relatively short duration of RMT compared to the non-SCI population, where changes in SDB were observed after 12-weeks of RMT. [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e] Improvements seen in the case report and pilot studies are difficult to explain given our findings, but may be related to the individual participant characteristics i.e. PImax, as some people were strong, or time since injury, as some people were still in the acute phase of SCI recovery. [\u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e, \u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e] Additionally, in our sub-group analysis, the numbers of people in each group (acute/chronic and mild/moderate-severe) were small and not sufficient to demonstrate similar changes as seen in the non-SCI population.\u003c/p\u003e\u003cp\u003eRMT is a low-cost intervention that has been increasingly integrated into clinical care to increase inspiratory muscle strength after SCI. However, our study suggests that RMT at ~\u0026thinsp;50% PImax does not reduce SDB or its consequences in people with acute or chronic tetraplegia over a short duration.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability:\u003c/strong\u003e Data are available from the corresponding author on reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u003c/strong\u003e The authors would like to acknowledge the assistance of Erlinda Bolange and Melanie Madronio for their technical assistance with polysomnography.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthor contributions:\u003c/strong\u003e CBR, RHCL, DJE, BBL, SG, JB were responsible for the design of the trial; CBR, RHCL coordinated the trial; RHCL, CBR, JB were responsible for statistical design and analysis; CBR, RHCL, RAM, NSW trained all participants and set up the sleep studies; RHCL, CBR cleaned, collated and prepared data for analysis and drafted the manuscript. All authors have read and approved the final manuscript.\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u003c/strong\u003e This study was completed with support from the National Health and Medical Research Council (NHMRC) of Australia and the Prince of Wales Hospital Foundation. DJE is supported by a NHMRC Leadership Fellowship (1196261).\u0026nbsp;\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting Interests:\u003c/strong\u003e Outside the current work, DJE reports grants from Bayer, Apnimed, Eli Lilly, Restera (formally Invicta Medical), Restora, Withings and Takeda and serves on Scientific Advisory Boards or as a consultant for Restera, Mosanna, Restora, ResSleep, Takeda and Apnimed. The other authors have no conflicts of interest to report.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eBiering-Sorensen, F, Jennum, P, Laub, M. Sleep disordered breathing following spinal cord injury. Respir Physiol Neurobiol. 2009; 169:165-70.\u003c/li\u003e\n\u003cli\u003eBerlowitz, DJ, Brown, DJ, Campbell, DA, Pierce, RJ. A longitudinal evaluation of sleep and breathing in the first year after cervical spinal cord injury. Arch Phys Med Rehabil. 2005; 86:1193-9.\u003c/li\u003e\n\u003cli\u003eGraco, M, McDonald, L, Green, S, Jackson, M, Berlowitz, D. Prevalence of sleep-disordered breathing in people with tetraplegia - a systematic review and meta-analysis. Spinal Cord. 2021; 59:474-84.\u003c/li\u003e\n\u003cli\u003eMarin, JM, Carrizo, SJ, Vicente, E, Agusti, AG. Long-term cardiovascular outcomes in men with obstructive sleep apnoea-hypopnoea with or without treatment with continuous positive airway pressure: an observational study. Lancet. 200; 365:1046-53.\u003c/li\u003e\n\u003cli\u003eRajan, S, McNeely, MJ, Hammond, M, Goldstein, B, Weaver, F. Association between obesity and diabetes mellitus in veterans with spinal cord injuries and disorders. Am J Phys Med Rehabil. 2010; 89:353-61.\u003c/li\u003e\n\u003cli\u003eMiddleton, JW, Dayton, A, Walsh, J, Rutkowski, SB, Leong, G, Duong, S. Life expectancy after spinal cord injury: a 50-year study. Spinal Cord. 2012; 50:803-11.\u003c/li\u003e\n\u003cli\u003eFogelberg, DJ, Hughes, AJ, Vitiello, MV, Hoffman, JM, Amtmann, D. Comparison of sleep problems in individuals with spinal cord injury and multiple sclerosis. J Clin Sleep Med. 2016; 12:695-701.\u003c/li\u003e\n\u003cli\u003eWijesuriya, NS, Gainche, L, Jordan, AS, Berlowitz, DJ, LeGuen, M, Rochford, PD, et al. Genioglossus reflex responses to negative upper airway pressure are altered in people with tetraplegia and obstructive sleep apnoea. J Physiol. 2018; 596:2853-64.\u003c/li\u003e\n\u003cli\u003eEckert, DJ, White, DP, Jordan, AS, Malhotra, A, Wellman, A. Defining phenotypic causes of obstructive sleep apnea. Identification of novel therapeutic targets. Am J Respir Crit Care Med. 2013; 188:996-1004.\u003c/li\u003e\n\u003cli\u003eSankari, A, Bascom, AT, Badr, MS. Upper airway mechanics in chronic spinal cord injury during sleep. J Appl Physiol (1985). 2014; 116:1390-5.\u003c/li\u003e\n\u003cli\u003eIsono, S. Obesity and obstructive sleep apnoea: mechanisms for increased collapsibility of the passive pharyngeal airway. Respirology. 2012; 17:32-42.\u003c/li\u003e\n\u003cli\u003eGainche, L, Berlowitz, DJ, LeGuen, M, Ruehland, WR, O\u0026apos;Donoghue, FJ, Trinder, J, et al. Nasal resistance is elevated in people with tetraplegia and is reduced by topical sympathomimetic administration. J Clin Sleep Med. 2016; 12:1487-92.\u003c/li\u003e\n\u003cli\u003eMezzanotte, WS, Tangel, DJ, White, DP. Waking genioglossal electromyogram in sleep apnea patients versus normal controls (a neuromuscular compensatory mechanism). J Clin Invest. 1992; 89:1571-9.\u003c/li\u003e\n\u003cli\u003eWorsnop, C, Kay, A, Kim, Y, Trinder, J, Pierce, R. Effect of age on sleep onset-related changes in respiratory pump and upper airway muscle function. J Appl Physiol (1985). 2000; 88:1831-9.\u003c/li\u003e\n\u003cli\u003eFogel, RB, Trinder, J, White, DP, Malhotra, A, Raneri, J, Schory, K, et al. The effect of sleep onset on upper airway muscle activity in patients with sleep apnoea versus controls. J Physiol. 2005; 564:549-62.\u003c/li\u003e\n\u003cli\u003eHorner, RL, Innes, JA, Holden, HB, Guz, A. Afferent pathway(s) for pharyngeal dilator reflex to negative pressure in man: a study using upper airway anaesthesia. J Physiol. 1991; 436:31-44.\u003c/li\u003e\n\u003cli\u003eBerlowitz, DJ, Spong, J, Pierce, RJ, Ross, J, Barnes, M, Brown, DJ. The feasibility of using auto-titrating continuous positive airway pressure to treat obstructive sleep apnoea after acute tetraplegia. Spinal Cord. 2009; 47:868-73.\u003c/li\u003e\n\u003cli\u003eErturk, N, Calik-Kutukcu, E, Arikan, H, Savci, S, Inal-Ince, D, Caliskan, H, et al. The effectiveness of oropharyngeal exercises compared to inspiratory muscle training in obstructive sleep apnea: A randomized controlled trial. Heart Lung. 2020; 49:940-948.\u003c/li\u003e\n\u003cli\u003eLin, HC, Chiang, LL, Ong, JH, Tsai, KL, Hung, CH, Lin, CY. The effects of threshold inspiratory muscle training in patients with obstructive sleep apnea: a randomized experimental study. Sleep Breath. 2020; 24:201-9. \u003c/li\u003e\n\u003cli\u003eHerkenrath, SD, Treml, M, Priegnitz, C, Galetke, W, Randerath, WJ. Effects of respiratory muscle training (RMT) in patients with mild to moderate obstructive sleep apnea (OSA). Sleep Breath. 2018; 22:323-8.\u003c/li\u003e\n\u003cli\u003eWang, TG, Wang, YH, Tang, FT, Lin, KH, Lien, IN. Resistive inspiratory muscle training in sleep disordered breathing of traumatic tetraplegia. Arch Phys Med Rehab. 2002; 82:491-6.\u003c/li\u003e\n\u003cli\u003eBoswell-Ruys, CL, Lewis, RHC, Gandevia, SC, Butler, JE. Respiratory muscle training may improve respiratory function and obstructive sleep apnoea in people with cervical spinal cord injury. Spinal Cord Ser Cases. 2015; 1:15010.\u003c/li\u003e\n\u003cli\u003eBoswell-Ruys, CL, Lewis, RHC, Wijeysuriya, NS, McBain, RA, Lee, BB, McKenzie, DK, et al. Impact of respiratory muscle training on respiratory muscle strength, respiratory function and quality of life in individuals with tetraplegia: a randomised clinical trial. Thorax. 2020; 75:279-88.\u003c/li\u003e\n\u003cli\u003eSankari, A, Najjar, AA, Maresh, SA, Prowting, JL, Fung, CH, Knack, A, et al. Feasibility of oropharyngeal and respiratory muscle training in individuals with OSA and spinal cord injury or disease: A pilot study. Physiological Reports. 2024; 12:e15930.\u003c/li\u003e\n\u003cli\u003eWijesuriya, NS, Eckert, DJ, Jordan, AS, Schembri, R, Lewis, RHC, Meaklim, H, et al. A randomised controlled trial of nasal decongestant to treat obstructive sleep apnoea in people with cervical spinal cord injury. Spinal Cord. 2019; 57:579-85.\u003c/li\u003e\n\u003cli\u003eKirkness, JP, Madronio, M, Stavrinou, R, Wheatley, JR, Amis, TC. Surface tension of upper airway mucosal lining liquid in obstructive sleep apnea/hypopnea syndrome. Sleep. 2005; 28:457-63.\u003c/li\u003e\n\u003cli\u003eVerma, M, Seto-Poon, M, Wheatley, JR, Amis, TC, Kirkness, JP. Influence of breathing route on upper airway lining liquid surface tension in humans. J Physiol. 2006; 574:859-66.\u003c/li\u003e\n\u003cli\u003ePuhan, MA, Suarez, A, Lo Cascio, C, Zahn, A, Heitz, M, Braendli, O. Didgeridoo playing as alternative treatment for obstructive sleep apnoea syndrome: randomised controlled trial. BMJ. 2006; 332:266-70.\u003c/li\u003e\n\u003cli\u003eHilton, MP, Savage, JO, Hunter, B, McDonald, S, Repanos, C, Powell, R. Singing exercises improve sleepiness and frequency of snoring among snorers: A randomised controlled trial. Int J Otolaryngology Head Neck Surgery. 2013; 2:97-102.\u003c/li\u003e\n\u003cli\u003eGuimaraes, KC, Drager, LF, Genta, PR, Marcondes, BF, Lorenzi-Filho, G. Effects of oropharyngeal exercises on patients with moderate obstructive sleep apnea syndrome. Am J Respir Crit Care Med. 2009; 179:962-6.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"spinal-cord","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"sc","sideBox":"Learn more about [Spinal Cord](http://www.nature.com/sc/)","snPcode":"41393","submissionUrl":"https://mts-sc.nature.com/cgi-bin/main.plex","title":"Spinal Cord","twitterHandle":"@journalsci","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false},"keywords":"","lastPublishedDoi":"10.21203/rs.3.rs-7522267/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7522267/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eStudy Design:\u003c/strong\u003eSub-analysis of a randomised controlled trial.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eObjectives:\u003c/strong\u003eRespiratory muscle training (RMT) in people with tetraplegia yields marked improvements in inspiratory muscle strength. The present study investigated whether RMT also modifies sleep disordered breathing (SDB) and daytime sleepiness.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eSetting:\u003c/strong\u003e Independent research institute in Sydney, Australia.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eMethods:\u003c/strong\u003e Sixty-two adults with tetraplegia underwent six weeks of supervised RMT. The active-RMT group trained the respiratory muscles through progressive threshold loading to a mean intensity of 50% maximal inspiratory pressure whereas the sham-RMT group experienced the same training protocol, but their device had no progressive threshold load. Primary measures of SDB were obtained using level II ambulatory polysomnograms and daytime sleepiness was assessed using the Epworth Sleepiness Score (ESS).\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eResults:\u003c/strong\u003e Forty-eight participants completed two home-based polysomnograms. Maximal inspiratory pressure (primary outcome) increased more after active intervention than sham, between-group difference 11.8cmH2O (95%CI, 5.2 to 18.4, p=0.001). There were no between group differences for any SDB parameter from baseline to 6-weeks (p=0.173 to p=0.935; e.g. mean apnoea-hypopnea index (±SD): active 46 ± 21 vs. 45 ± 22 events/h; sham 44 ± 25 vs. 40 ± 25 events/h; p=0.553) and ESS: active 9.5 ± 5.7 vs. 9.2 ± 6.7; sham 10.8 ± 6.2 vs. 10.1 ± 5.8; p=0.952.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions:\u003c/strong\u003eDespite significant increases in inspiratory muscle strength, 6 weeks of supervised respiratory muscle training at a mean intensity of 50% maximal inspiratory pressure does not reduce SDB or daytime sleepiness in people with tetraplegia and severe SDB.\u003c/p\u003e","manuscriptTitle":"Impact of respiratory muscle training on sleep disordered breathing in people with tetraplegia: A sub-analysis of a randomised controlled trial","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-09-30 06:57:05","doi":"10.21203/rs.3.rs-7522267/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"revise","date":"2025-11-03T15:04:47+00:00","index":"","fulltext":""},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-10-06T18:40:50+00:00","index":2,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-10-06T17:26:11+00:00","index":2,"fulltext":"This content is not available."},{"type":"editorInvitedReview","content":"This content is not available.","date":"2025-10-04T17:49:48+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewerAgreed","content":"This content is not available.","date":"2025-09-18T11:43:30+00:00","index":1,"fulltext":"This content is not available."},{"type":"reviewersInvited","content":"","date":"2025-09-17T23:20:01+00:00","index":"","fulltext":""},{"type":"editorAssigned","content":"","date":"2025-09-16T17:06:46+00:00","index":"","fulltext":""},{"type":"checksComplete","content":"","date":"2025-09-04T16:00:42+00:00","index":"","fulltext":""},{"type":"submitted","content":"Spinal Cord","date":"2025-09-03T03:25:49+00:00","index":"","fulltext":""}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"spinal-cord","isNatureJournal":false,"hasQc":false,"allowDirectSubmit":false,"externalIdentity":"sc","sideBox":"Learn more about [Spinal Cord](http://www.nature.com/sc/)","snPcode":"41393","submissionUrl":"https://mts-sc.nature.com/cgi-bin/main.plex","title":"Spinal Cord","twitterHandle":"@journalsci","acdcEnabled":true,"dfaEnabled":true,"editorialSystem":"ejp","reportingPortfolio":"Nature AJ","inReviewEnabled":true,"inReviewRevisionsEnabled":false}}],"origin":"","ownerIdentity":"9c0957cd-92f6-4ff6-811c-cde27c7b001c","owner":[],"postedDate":"September 30th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"in-revision","subjectAreas":[{"id":55411588,"name":"Health sciences/Signs and symptoms/Respiratory signs and symptoms"},{"id":55411589,"name":"Biological sciences/Neuroscience/Circadian rhythms and sleep/Sleep"},{"id":55411590,"name":"Health sciences/Neurology/Neurological disorders/Spinal cord diseases"}],"tags":[],"updatedAt":"2025-11-03T15:09:09+00:00","versionOfRecord":[],"versionCreatedAt":"2025-09-30 06:57:05","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7522267","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7522267","identity":"rs-7522267","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}