Routine lung volume recruitment in boys with Duchenne muscular dystrophy: a randomised clinical trial

Sherri L Katz, Jean K Mah, Hugh J McMillan, Craig Campbell, Vid Bijelić, Nick Barrowman, Franco Momoli, Henrietta Blinder, Shawn D Aaron, Laura C McAdam, The Thanh Diem Nguyen, Mark Tarnopolsky, David F Wensley, David Zielinski, Louise Rose, Nicole Sheers, David J Berlowitz, Lisa Wolfe, Doug McKim, Sherri L Katz, Jean K Mah, Hugh J McMillan, Craig Campbell, Vid Bijelić, Nick Barrowman, Franco Momoli, Henrietta Blinder, Shawn D Aaron, Laura C McAdam, The Thanh Diem Nguyen, Mark Tarnopolsky, David F Wensley, David Zielinski, Louise Rose, Nicole Sheers, David J Berlowitz, Lisa Wolfe, Doug McKim

Abstract

Background: Impaired cough results in airway secretion retention, atelectasis and pneumonia in individuals with Duchenne muscular dystrophy (DMD). Lung volume recruitment (LVR) stacks breaths to inflate the lungs to greater volumes than spontaneous effort. LVR is recommended in DMD clinical care guidelines but is not well studied. We aimed to determine whether twice-daily LVR, compared with standard of care alone, attenuates the decline in FVC at 2 years in boys with DMD.

Methods: In this multicentre, assessor-blinded, randomised controlled trial, boys with DMD, aged 6-16 years with FVC >30% predicted, were randomised to receive conventional treatment or conventional treatment plus manual LVR twice daily for 2 years. The primary outcome was FVC % predicted at 2 years, adjusted for baseline FVC % predicted, age and ambulatory status. Secondary outcomes included change in chest wall distensibility (maximal insufflation capacity minus FVC) and peak cough flow.

Results: Sixty-six boys (36 in LVR group, 30 in control) were evaluated (median age (IQR): 11.5 years (9.5-13.5), median baseline FVC (IQR): 85% predicted (73-96)). Adjusted mean difference in FVC between groups at 2 years was 1.9% predicted (95% CI -6.9% to 10.7%; p=0.68) in the direction of treatment benefit. We found no differences in secondary outcomes.

Conclusion: There was no difference in decline in FVC % predicted with use of twice-daily LVR for boys with DMD and relatively normal lung function. The burden associated with routine LVR may outweigh the benefit. Benefits of LVR to maintain lung health in boys with worse baseline lung function still need to be clarified.

Trial registration number: NCT01999075.

Keywords: Duchenne muscular dystrophy; child; lung volume recruitment; randomized controlled trial; respiratory therapy.

Conflict of interest statement

Competing interests: None declared.

© Author(s) (or their employer(s)) 2022. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.

Figures

Figure 1
Figure 1
CONSORT flow diagram. CONSORT, Consolidated Standards of Reporting Trials; LVR, lung volume recruitment; PFT, pulmonary function test.
Figure 2
Figure 2
Secondary analysis of FVC % predicted over time. Marginal means by group with 95% CI from mixed effect model of FVC % predicted, adjusted for age and ambulatory status, at 6-month intervals. LVR, lung volume recruitment.
Figure 3
Figure 3
Kaplan-Meier curve for a single missing data imputation. LVR, lung volume recruitment.
Figure 4
Figure 4
Change in secondary outcomes (MIC−VC (L), PCF-assisted – PCF-unassisted (L/min), MIP (cm H2O), MEP (cm H2O) and TLC (L) over time. Marginal means by group with 95% CI from mixed effect model of secondary outcomes, adjusted for age and ambulatory status, at 6-month intervals. MEP, maximal expiratory pressure; MIC, maximum insufflation capacity; MIP, maximal inspiratory pressure; PCF, peak cough flow; TLC, total lung capacity.

References

    1. Birnkrant DJ, Bushby K, Bann CM, et al. . Diagnosis and management of Duchenne muscular dystrophy, part 1: diagnosis, and neuromuscular, rehabilitation, endocrine, and gastrointestinal and nutritional management. Lancet Neurol 2018;17:251–67. 10.1016/S1474-4422(18)30024-3
    1. Panitch HB. The pathophysiology of respiratory impairment in pediatric neuromuscular diseases. Pediatrics 2009;123 Suppl 4:S215–8. 10.1542/peds.2008-2952C
    1. Hull J. British thoracic Society guideline for respiratory management of children with neuromuscular weakness: commentary. Thorax 2012;67:654–5. 10.1136/thoraxjnl-2012-202043
    1. Amin R, MacLusky I, Zielinski D, et al. . Pediatric home mechanical ventilation: a Canadian thoracic Society clinical practice guideline executive summary. Can J Respir Crit Care Sleep Med 2017;1:7–36. 10.1080/24745332.2017.1300463
    1. Bushby K, Finkel R, Birnkrant DJ. Diagnosis and management of Duchenne muscular dystrophy, part 2: implementation of multidisciplinary care.[Erratum appears in Lancet Neurol. 2010 Mar;9(3):237]. Lancet Neurol 2010;9:177–89.
    1. McKim DA, Road J, Avendano M, et al. . Home mechanical ventilation: a Canadian thoracic Society clinical practice guideline. Can Respir J 2011;18:197–215. 10.1155/2011/139769
    1. Lynne Katz S, On behalf of the CTS Pediatric Home Ventilation Guidelines Panel . Section 5: airway clearance. Can J Respir Crit Care Sleep Med 2018;2:32–40. 10.1080/24745332.2018.1494979
    1. Chatwin M, Toussaint M, Gonçalves MR, et al. . Airway clearance techniques in neuromuscular disorders: a state of the art review. Respir Med 2018;136:98–110. 10.1016/j.rmed.2018.01.012
    1. Sheers N, Howard ME, Berlowitz DJ. Respiratory adjuncts to NIV in neuromuscular disease. Respirology 2019;24:512–20. 10.1111/resp.13431
    1. Bach JR, Mahajan K, Lipa B, et al. . Lung insufflation capacity in neuromuscular disease. Am J Phys Med Rehabil 2008;87:720–5. 10.1097/PHM.0b013e31817fb26f
    1. Katz SL, Barrowman N, Monsour A, et al. . Long-term effects of lung volume recruitment on maximal inspiratory capacity and vital capacity in Duchenne muscular dystrophy. Ann Am Thorac Soc 2016;13:217–22. 10.1513/AnnalsATS.201507-475BC
    1. McKim DA, Katz SL, Barrowman N, et al. . Lung volume recruitment slows pulmonary function decline in Duchenne muscular dystrophy. Arch Phys Med Rehabil 2012;93:1117–22. 10.1016/j.apmr.2012.02.024
    1. Chiou M, Bach JR, Jethani L, et al. . Active lung volume recruitment to preserve vital capacity in Duchenne muscular dystrophy. J Rehabil Med 2017;49:49–53. 10.2340/16501977-2144
    1. Kang SW, Bach JR. Maximum insufflation capacity. Chest 2000;118:61–5. 10.1378/chest.118.1.61
    1. Fauroux B, Guillemot N, Aubertin G, et al. . Physiologic benefits of mechanical insufflation-exsufflation in children with neuromuscular diseases. Chest 2008;133:161–8. 10.1378/chest.07-1615
    1. Molgat-Seon Y, Hannan LM, Dominelli PB, et al. . Lung volume recruitment acutely increases respiratory system compliance in individuals with severe respiratory muscle weakness. ERJ Open Res 2017;3. 10.1183/23120541.00135-2016. [Epub ahead of print: 14 03 2017].
    1. Kang SW, Bach JR. Maximum insufflation capacity: vital capacity and cough flows in neuromuscular disease. Am J Phys Med Rehabil 2000;79:222–7. 10.1097/00002060-200005000-00002
    1. Rafiq MK, Bradburn M, Proctor AR, et al. . A preliminary randomized trial of the mechanical insufflator-exsufflator versus breath-stacking technique in patients with amyotrophic lateral sclerosis. Amyotroph Lateral Scler Frontotemporal Degener 2015;16:448–55. 10.3109/21678421.2015.1051992
    1. Birnkrant DJ, Bushby KMD, Amin RS, et al. . The respiratory management of patients with Duchenne muscular dystrophy: a DMD care considerations Working group specialty article. Pediatr Pulmonol 2010;45:739–48. 10.1002/ppul.21254
    1. Taves DR. Minimization: a new method of assigning patients to treatment and control groups. Clin Pharmacol Ther 1974;15:443–53. 10.1002/cpt1974155443
    1. Biggar WD, Harris VA, Eliasoph L, et al. . Long-Term benefits of deflazacort treatment for boys with Duchenne muscular dystrophy in their second decade. Neuromuscul Disord 2006;16:249–55. 10.1016/j.nmd.2006.01.010
    1. Rideau Y, Jankowski LW, Grellet J. Respiratory function in the muscular dystrophies. Muscle Nerve 1981;4:155–64. 10.1002/mus.880040213
    1. Birnkrant DJ, Bushby K, Bann CM, et al. . Diagnosis and management of Duchenne muscular dystrophy, part 2: respiratory, cardiac, bone health, and orthopaedic management. Lancet Neurol 2018;17:347–61. 10.1016/S1474-4422(18)30025-5
    1. Boitano LJ. Equipment options for cough augmentation, ventilation, and noninvasive interfaces in neuromuscular respiratory management. Pediatrics 2009;123 Suppl 4:S226–30. 10.1542/peds.2008-2952F
    1. American Thoracic S . Standardization of spirometry, 1994 update. AJRCCM 1994;1995:1107–36.
    1. Mayer OH, Finkel RS, Rummey C, et al. . Characterization of pulmonary function in Duchenne muscular dystrophy. Pediatr Pulmonol 2015;50:487–94. 10.1002/ppul.23172
    1. Wanger J, Clausen JL, Coates A, et al. . Standardisation of the measurement of lung volumes. Eur Respir J 2005;26:511–22. 10.1183/09031936.05.00035005
    1. Stanojevic S, Wade A, Stocks J, et al. . Reference ranges for spirometry across all ages: a new approach. Am J Respir Crit Care Med 2008;177:253–60. 10.1164/rccm.200708-1248OC
    1. Kang S-W, Kang Y-S, Sohn H-S, et al. . Respiratory muscle strength and cough capacity in patients with Duchenne muscular dystrophy. Yonsei Med J 2006;47:184–90. 10.3349/ymj.2006.47.2.184
    1. Kang SW, Shin JC, Park CI, et al. . Relationship between inspiratory muscle strength and cough capacity in cervical spinal cord injured patients. Spinal Cord 2006;44:242–8. 10.1038/sj.sc.3101835
    1. Sancho J, Servera E, Díaz J, et al. . Predictors of ineffective cough during a chest infection in patients with stable amyotrophic lateral sclerosis. Am J Respir Crit Care Med 2007;175:1266–71. 10.1164/rccm.200612-1841OC
    1. Suárez AA, Pessolano FA, Monteiro SG, et al. . Peak flow and peak cough flow in the evaluation of expiratory muscle weakness and bulbar impairment in patients with neuromuscular disease. Am J Phys Med Rehabil 2002;81:506–11. 10.1097/00002060-200207000-00007
    1. Katz SL, McKim D, Hoey L, et al. . Respiratory management strategies for Duchenne muscular dystrophy: practice variation amongst Canadian sub-specialists. Pediatr Pulmonol 2013;48:59–66. 10.1002/ppul.22548
    1. Phillips MF, Quinlivan RC, Edwards RH, et al. . Changes in spirometry over time as a prognostic marker in patients with Duchenne muscular dystrophy. Am J Respir Crit Care Med 2001;164:2191–4. 10.1164/ajrccm.164.12.2103052
    1. Velasco MV, Colin AA, Zurakowski D, et al. . Posterior spinal fusion for scoliosis in Duchenne muscular dystrophy diminishes the rate of respiratory decline. Spine 2007;32:459–65. 10.1097/01.brs.0000255062.94744.52
    1. R Core Team . R: a language and environment for statistical computing. Vienna, Austria: R foundation for statistical computing, 2020. Available:
    1. van Buuren S, Groothius-Oudshoorn K. Multivariate imputation by chained equations in R. J Stat Softw 2011;45:1–67.
    1. Herbert RD, Kasza J, Bo K. Analysis of randomised trials with long-term follow-up. BMC Med Res Methodol 2018;18:48. 10.1186/s12874-018-0499-5
    1. Blinder H, Momoli F, Bokhaut J, et al. . Predictors of adherence to positive airway pressure therapy in children: a systematic review and meta-analysis. Sleep Med 2020;69:19–33. 10.1016/j.sleep.2019.12.015
    1. Kravitz RM. Airway clearance in Duchenne muscular dystrophy. Pediatrics 2009;123 Suppl 4:Suppl-5–235. 10.1542/peds.2008-2952G
    1. Proulx F, Blinder H, Barrowman N, et al. . Current practice and evolution of pediatric respiratory management of Duchenne muscular dystrophy in Canada. Can J Respir Crit Care Sleep Med 2021;13:1–15. 10.1080/24745332.2020.1867486

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