, Volume 197, Issue 1, pp 1–8 | Cite as

Cough Effectiveness and Pulmonary Hygiene Practices in Patients with Pompe Disease

  • Teresa Pitts
  • Rachel Bordelon
  • Alyssa Huff
  • Barry J. Byrne
  • Barbara K. SmithEmail author



While factors leading to hypoventilation have been well studied in Pompe disease, cough effectiveness and airway clearance practices are less understood. We aimed to identify significant factors that influence peak cough flow (PCF) in Pompe, and to detect whether pulmonary hygiene practices were reflective of reduced PCF.


This is a prospective observational study of 20 subjects with Pompe disease (infantile-onset: 7, juvenile-onset: 6, adult-onset: 14). Subjects performed spirometry, maximal respiratory pressures, and cough (voluntary: n = 24, spontaneous: n = 3). Subjects or their parents reported airway clearance and secretion management practices. Relationships between disease variables, pulmonary function, and cough parameters as well as group differences in cough parameters were evaluated.


Subjects with infantile-onset disease had significantly lower PCF (p < 0.05) and tended to require more external ventilatory support (p = 0.07). In juvenile- and adult-onset disease, PCF differed according to external ventilatory requirement [daytime: 83.6 L/min (95% CI 41.2–126.0); nighttime: 224.6 L/min (95% CI 139.1–310.2); none: 340.2 L/min (95% CI 193.3–487.6), p < 0.005]. Cough inspiratory volume also differed significantly by ventilatory requirement [daytime: 5.5 mL/kg (95% CI 3.0–8.0); nighttime: 16.0 mL/kg (95% CI 11.8–20.2); none: 26.8 mL/kg (95% CI 11.9–41.7), p < 0.001]. However, routine airway clearance or secretion management practices were only consistently reported among patients with infantile-onset disease (infantile: 86%, juvenile: 0%, adult: 14%, p < 0.005).


Cough weakness was detected in the majority of patients with Pompe disease and was influenced by both inspiratory and expiratory muscle function. Patients at risk for problems or with ineffective PCF should be urged to complete routine pulmonary hygiene.


Cough Pulmonary hygiene Pompe disease Respiratory muscles 



Forced vital capacity


Acid alpha-glucosidase


Interquartile range


Maximal inspiratory pressure


Maximal expiratory pressure


Mechanical ventilation


Peak cough flow



Some data were collected as part of NCT02354651, supported by R21-HD090752 to BKS, through the National Institute of Child Health and Human Development.

Compliance with Ethical Standards

Conflict of interest

No conflicts exist for any of the authors.


  1. 1.
    Wens SC, Ciet P, Perez-Rovira A et al (2015) Lung MRI and impairment of diaphragmatic function in Pompe disease. BMC Pulm Med 15:54CrossRefGoogle Scholar
  2. 2.
    American Association of Neuromuscular & Electrodiagnostic Medicine (2009) Diagnostic criteria for late-onset (childhood and adult) Pompe disease. Muscle Nerve 40:149–160CrossRefGoogle Scholar
  3. 3.
    Boentert M, Prigent H, Vardi K et al (2016) Practical recommendations for diagnosis and management of respiratory muscle weakness in late-onset Pompe disease. Int J Mol Sci 17Google Scholar
  4. 4.
    Gungor D, de Vries JM, Hop WC et al (2011) Survival and associated factors in 268 adults with Pompe disease prior to treatment with enzyme replacement therapy. Orphanet J Rare Dis 6:34CrossRefGoogle Scholar
  5. 5.
    Schoser B, Fong E, Geberhiwot T et al (2017) Maximum inspiratory pressure as a clinically meaningful trial endpoint for neuromuscular diseases: a comprehensive review of the literature. Orphanet J Rare Dis 12:52CrossRefGoogle Scholar
  6. 6.
    Bach JR, Saporito LR (1996) Criteria for extubation and tracheostomy tube removal for patients with ventilatory failure. A different approach to weaning. Chest 110:1566–1571CrossRefGoogle Scholar
  7. 7.
    Bach JR, Goncalves MR, Hamdani I, Winck JC (2010) Extubation of patients with neuromuscular weakness: a new management paradigm. Chest 137:1033–1039CrossRefGoogle Scholar
  8. 8.
    Bach JR, Ishikawa Y, Kim H (1997) Prevention of pulmonary morbidity for patients with Duchenne muscular dystrophy. Chest 112:1024–1028CrossRefGoogle Scholar
  9. 9.
    Jones HN, Crisp KD, Robey RR, Case LE, Kravitz RM, Kishnani PS (2015) Respiratory muscle training (RMT) in late-onset Pompe disease (LOPD): effects of training and detraining. Mol Genet Metab 117:120–128CrossRefGoogle Scholar
  10. 10.
    Miller MR, Hankinson J, Brusasco V et al (2005) Standardisation of spirometry. Eur Respir J 26:319–338CrossRefGoogle Scholar
  11. 11.
    European, Respiratory Society, American Thoracic Society (2002) ATS/ERS statement on respiratory muscle testing. Am J Respir Crit Care Med 166:518–624CrossRefGoogle Scholar
  12. 12.
    Chatwin M, Toussaint M, Goncalves MR et al (2018) Airway clearance techniques in neuromuscular disorders: a state of the art review. Respir Med 136:98–110CrossRefGoogle Scholar
  13. 13.
    Kroos M, Hoogeveen-Westerveld M, van der Ploeg A, Reuser AJ (2012) The genotype-phenotype correlation in Pompe disease. Am J Med Genet C 160:59–68CrossRefGoogle Scholar
  14. 14.
    Morrow B, Zampoli M, van Aswegen H, Argent A (2013) Mechanical insufflation-exsufflation for people with neuromuscular disorders. Cochrane Database Syst Rev 2013:CD010044Google Scholar
  15. 15.
    Mahede T, Davis G, Rutkay A et al (2015) Use of mechanical airway clearance devices in the home by people with neuromuscular disorders: effects on health service use and lifestyle benefits. Orphanet J Rare Dis 10:54CrossRefGoogle Scholar
  16. 16.
    Arora NS, Gal TJ (1981) Cough dynamics during progressive expiratory muscle weakness in healthy curarized subjects. J Appl Physiol 51:494–498CrossRefGoogle Scholar
  17. 17.
    Prigent H, Orlikowski D, Laforet P et al (2012) Supine volume drop and diaphragmatic function in adults with Pompe disease. Eur Respir J 39:1545–1546CrossRefGoogle Scholar
  18. 18.
    Smith BK, Corti M, Martin AD, Fuller DD, Byrne BJ (2016) Altered activation of the diaphragm in late-onset Pompe disease. Respir Physiol Neurobiol 222:11–15CrossRefGoogle Scholar
  19. 19.
    LoMauro A, D’Angelo MG, Aliverti A (2015) Assessment and management of respiratory function in patients with Duchenne muscular dystrophy: current and emerging options. Ther Clin Risk Manage 11:1475–1488Google Scholar
  20. 20.
    Sarmento A, de Andrade AF, Lima IN, Aliverti A, de Freitas Fregonezi GA, Resqueti VR (2017) Air stacking: a detailed look into physiological acute effects on cough peak flow and chest wall volumes of healthy subjects. Respir Care 62:432–443CrossRefGoogle Scholar
  21. 21.
    Trebbia G, Lacombe M, Fermanian C et al (2005) Cough determinants in patients with neuromuscular disease. Respir Physiol Neurobiol 146:291–300CrossRefGoogle Scholar
  22. 22.
    Fuller DD, ElMallah MK, Smith BK et al (2013) The respiratory neuromuscular system in Pompe disease. Respir Physiol Neurobiol 189:241–249CrossRefGoogle Scholar
  23. 23.
    McCool FD (2006) Global physiology and pathophysiology of cough: ACCP evidence-based clinical practice guidelines. Chest 129:48S–53SCrossRefGoogle Scholar
  24. 24.
    Laghi F, Maddipati V, Schnell T, Langbein WE, Tobin MJ (2017) Determinants of cough effectiveness in patients with respiratory muscle weakness. Respir Physiol Neurobiol 240:17–25CrossRefGoogle Scholar
  25. 25.
    McKim DA, Hendin A, LeBlanc C, King J, Brown CR, Woolnough A (2012) Tracheostomy decannulation and cough peak flows in patients with neuromuscular weakness. Am J Phys Med Rehabil 91:666–670CrossRefGoogle Scholar
  26. 26.
    Gaeta M, Barca E, Ruggeri P et al (2013) Late-onset Pompe disease (LOPD): correlations between respiratory muscles CT and MRI features and pulmonary function. Mol Genet Metab 110:290–296CrossRefGoogle Scholar
  27. 27.
    Yasuda T, Wu C, Nakagawa N, Nagamura K (2013) Studies on an automobile muffler with the acoustic characteristic of low-pass filter and Helmholtz resonator. Appl Acoust 74:49–57CrossRefGoogle Scholar
  28. 28.
    Chatwin M, Ross E, Hart N, Nickol AH, Polkey MI, Simonds AK (2003) Cough augmentation with mechanical insufflation/exsufflation in patients with neuromuscular weakness. Eur Respir J 21:502–508CrossRefGoogle Scholar
  29. 29.
    Bianchi C, Baiardi P (2008) Cough peak flows: standard values for children and adolescents. Am J Phys Med Rehabil 87:461–467CrossRefGoogle Scholar
  30. 30.
    Dohna-Schwake C, Ragette R, Teschler H, Voit T, Mellies U (2006) Predictors of severe chest infections in pediatric neuromuscular disorders. Neuromuscul Disord 16:325–328CrossRefGoogle Scholar
  31. 31.
    Hull J, Aniapravan R, Chan E et al (2012) British Thoracic Society guideline for respiratory management of children with neuromuscular weakness. Thorax 67(Suppl 1):i1–i40CrossRefGoogle Scholar
  32. 32.
    Lee KK, Ward K, Rafferty GF, Moxham J, Birring SS (2015) The intensity of voluntary, induced, and spontaneous cough. Chest 148:1259–1267CrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Kentucky Spinal Cord Injury Research CenterUniversity of LouisvilleLouisvilleUSA
  2. 2.Department of Osteopathic MedicineA.T. Still UniversityKirksvilleUSA
  3. 3.Department of Physiology and BiophysicsUniversity of LouisvilleLouisvilleUSA
  4. 4.Department of PediatricsUniversity of FloridaGainesvilleUSA
  5. 5.Departments of Physical Therapy and PediatricsUniversity of FloridaGainesvilleUSA

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