, Volume 192, Issue 2, pp 321–328 | Cite as

The Combination of Exercise and Respiratory Training Improves Respiratory Muscle Function in Pulmonary Hypertension

  • Hans-Joachim KabitzEmail author
  • Hinrich-Cordt Bremer
  • Anja Schwoerer
  • Florian Sonntag
  • Stephan Walterspacher
  • David Johannes Walker
  • Nicola Ehlken
  • Gerd Staehler
  • Wolfram Windisch
  • Ekkehard Grünig



Increased dyspnea and reduced exercise capacity in pulmonary arterial hypertension (PAH) can be partly attributed to impaired respiratory muscle function. This prospective study was designed to assess the impact of exercise and respiratory training on respiratory muscle strength and 6-min walking distance (6MWD) in PAH patients.


Patients with invasively confirmed PAH underwent 3 weeks of in-hospital exercise and respiratory training, which was continued at home for another 12 weeks. Medication remained constant during the study period. Blinded observers assessed efficacy parameters at baseline (I) and after 3 (II) and 15 weeks (III). Respiratory muscle function was assessed by twitch mouth pressure (TwPmo) during nonvolitional supramaximal magnetic phrenic nerve stimulation.


Seven PAH patients (4 women; mean pulmonary artery pressure 45 ± 11 mmHg, median WHO functional class 3.1 ± 0.4, idiopathic/associated PAH n = 5/2) were included. The training program was feasible and well tolerated by all patients with excellent compliance. TwPmo was I: 0.86 ± 0.37 kPa, II: 1.04 ± 0.29 kPa, and III: 1.27 ± 0.44 kPa, respectively. 6MWD was I: 417 ± 51 m, II: 509 ± 39 m, and III: 498 ± 39 m, respectively. Both TwPmo (+0.41 ± 0.34 kPa, +56 ± 39 %) and 6MWD (+81 ± 30 m, +20 ± 9 %) increased significantly in the period between baseline and the final assessment (pairwise comparison: p = 0.012/<0.001; RM-ANOVA considering I, II, III: p = 0.037/<0.001).


Exercise and respiratory training as an adjunct to medical therapy may be effective in patients with PAH to improve respiratory muscle strength and exercise capacity. Future, randomized, controlled trials should be carried out to further investigate these findings.


Breathing exercises Diaphragm Respiratory muscle weakness Twitch pressure Inspiratory muscle training 



The authors thank all patients who participated in this demanding study. We are grateful to nSpire Health GmbH (Oberthulba, Germany) for technical support, Dr. Claudia Schmoor (Biometry and Data Management, Center of Clinical Trials, University Medical Center Freiburg, Germany) for biometric consulting, and Dr. Sandra Dieni for writing assistance. This work was supported by a research grant from the German Research Society DFG (Deutsche Forschungsgemeinschaft), Bonn, Germany [KA 2992/2-1]. Further support was provided by the German Pulmonary Hypertension self-help group (Pulmonale Hypertonie e.v.), Rheinstetten, Germany. The study was registered at the WHO Primary Register of Germany (German Clinical Trials Register DRKS00003567).

Conflict of interest

The authors declare that they have no conflict of interest.

Ethical Standards

The Institutional Review Board for human studies at the Universities of Freiburg and Heidelberg, Germany approved the study protocol. All experiments comply with the current laws of Germany and the study was performed in agreement with the ethical standards laid down in the current version of the Declaration of Helsinki (59th World Medical Association General Assembly, Seoul, Korea, October 2008). Written informed consent was obtained from all patients.


  1. 1.
    ATS (2002) ATS statement: guidelines for the six-minute walk test. Am J Respir Crit Care Med 166:111–117CrossRefGoogle Scholar
  2. 2.
    ATS/ERS (2002) ATS/ERS statement on respiratory muscle testing. Am J Respir Crit Care Med 166:518–624CrossRefGoogle Scholar
  3. 3.
    Dall’Ago P, Chiappa GRS, Guths H, Stein R, Ribeiro JP (2006) Inspiratory muscle training in patients with heart failure and inspiratory muscle weakness: a randomized trial. J Am Coll Cardiol 47:757–763CrossRefPubMedGoogle Scholar
  4. 4.
    D’Alonzo GE, Gianotti LA, Pohil RL, Reagle RR, DuRee SL, Fuentes F, Dantzker DR (1987) Comparison of progressive exercise performance of normal subjects and patients with primary pulmonary hypertension. Chest 92:57–62CrossRefPubMedGoogle Scholar
  5. 5.
    de Man FS, van Hees HWH, Handoko ML, Niessen HW, Schalij I, Humbert M, Dorfmuller P, Mercier O, Bogaard H, Postmus PE, Westerhof N, Stienen GJM, van der Laarse WJ (2011) Diaphragm muscle fiber weakness in pulmonary hypertension. Am J Respir Crit Care Med 183:1411–1418CrossRefPubMedGoogle Scholar
  6. 6.
    Dorfmuller P, Perros F, Balabanian K, Humbert M (2003) Inflammation in pulmonary arterial hypertension. Eur Respir J 22:358–363CrossRefPubMedGoogle Scholar
  7. 7.
    Fernandez R, Cabrera J, Calaf N, Benito S (1990) P 0.1/PIMax: an index for assessing respiratory capacity in acute respiratory failure. Intensive Care Med 16:175–179CrossRefPubMedGoogle Scholar
  8. 8.
    Galie N, Hoeper MM, Humbert M, Torbicki A, Vachiery J, Barbera JA, Beghetti M, Corris P, Gaine S, Gibbs JS, Gomez-Sanchez MA, Jondeau G, Klepetko W, Opitz C, Peacock A, Rubin L, Zellweger M, Simonneau G (2009) Guidelines for the diagnosis and treatment of pulmonary hypertension. Eur Respir J 34:1219–1263CrossRefPubMedGoogle Scholar
  9. 9.
    Grunig E, Ehlken N, Ghofrani A, Staehler G, Meyer FJ, Juenger J, Opitz CF, Klose H, Wilkens H, Rosenkranz S, Olschewski H, Halank M (2011) Effect of exercise and respiratory training on clinical progression and survival in patients with severe chronic pulmonary hypertension. Respiration 81:394–401CrossRefPubMedGoogle Scholar
  10. 10.
    Grunig E, Lichtblau M, Ehlken N, Ghofrani HA, Reichenberger F, Staehler G, Halank M, Fischer C, Seyfarth HJ, Klose H, Meyer A, Sorichter S, Wilkens H, Rosenkranz S, Opitz C, Leuchte H, Karger G, Speich R, Nagel C (2012) Safety and efficacy of exercise training in various forms of pulmonary hypertension. Eur Respir J 40:84–92CrossRefPubMedGoogle Scholar
  11. 11.
    Hassoun PM, Mouthon L, Barbera JA, Eddahibi S, Flores SC, Grimminger F, Jones PL, Maitland ML, Michelakis ED, Morrell NW, Newman JH, Rabinovitch M, Schermuly R (2009) Inflammation, growth factors, and pulmonary vascular remodeling. J Am Coll Cardiol 54:S10–S19CrossRefPubMedGoogle Scholar
  12. 12.
    Heritier F, Rahm F, Pasche P, Fitting JW (1994) Sniff nasal inspiratory pressure. A noninvasive assessment of inspiratory muscle strength. Am J Respir Crit Care Med 150:1678–1683CrossRefPubMedGoogle Scholar
  13. 13.
    Humbert M, Monti G, Brenot F, Sitbon O, Portier A, Grangeot-Keros L, Duroux P, Galanaud P, Simonneau G, Emilie D (1995) Increased interleukin-1 and interleukin-6 serum concentrations in severe primary pulmonary hypertension. Am J Respir Crit Care Med 151:1628–1631CrossRefPubMedGoogle Scholar
  14. 14.
    Jaenisch RB, Hentschke VS, Quagliotto E, Cavinato PR, Schmeing LA, Xavier LL, Dal Lago P (2011) Respiratory muscle training improves hemodynamics, autonomic function, baroreceptor sensitivity, and respiratory mechanics in rats with heart failure. J Appl Physiol 111:1664–1670CrossRefPubMedGoogle Scholar
  15. 15.
    Joppa P, Petrasova D, Stancak B, Tkacova R (2006) Systemic inflammation in patients with COPD and pulmonary hypertension. Chest 130:326–333CrossRefPubMedGoogle Scholar
  16. 16.
    Kabitz HJ, Walker D, Walterspacher S, Windisch W (2007) Controlled twitch mouth pressure reliably predicts twitch esophageal pressure. Respir Physiol Neurobiol 156:276–282CrossRefPubMedGoogle Scholar
  17. 17.
    Kabitz H, Schwoerer A, Bremer H, Sonntag F, Walterspacher S, Walker D, Schaefer V, Ehlken N, Staehler G, Halank M, Klose H, Ghofrani HA, Hoeper MM, Gruenig E (2008) Impairment of respiratory muscle function in pulmonary hypertension. Clin Sci (Lond) 114:165–171CrossRefGoogle Scholar
  18. 18.
    Mainguy V, Maltais F, Saey D, Gagnon P, Martel S, Simon M, Provencher S (2010) Peripheral muscle dysfunction in idiopathic pulmonary arterial hypertension. Thorax 65:113–117CrossRefPubMedGoogle Scholar
  19. 19.
    Mancini DM, Henson D, La Manca J, Donchez L, Levine S (1995) Benefit of selective respiratory muscle training on exercise capacity in patients with chronic congestive heart failure. Circulation 91:320–329CrossRefPubMedGoogle Scholar
  20. 20.
    McGoon M, Gutterman D, Steen V, Barst R, McCrory DC, Fortin TA, Loyd JE (2004) Screening, early detection, and diagnosis of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 126:14S–34SCrossRefPubMedGoogle Scholar
  21. 21.
    Mereles D, Ehlken N, Kreuscher S, Ghofrani S, Hoeper MM, Halank M, Meyer FJ, Karger G, Buss J, Juenger J, Holzapfel N, Opitz C, Winkler J, Herth FFJ, Wilkens H (2006) Exercise and respiratory training improve exercise capacity and quality of life in patients with severe chronic pulmonary hypertension. Circulation 114:1482–1489CrossRefPubMedGoogle Scholar
  22. 22.
    Meyer FJ, Lossnitzer D, Kristen AV, Schoene AM, Kubler W, Katus HA, Borst MM (2005) Respiratory muscle dysfunction in idiopathic pulmonary arterial hypertension. Eur Respir J 25:125–130CrossRefPubMedGoogle Scholar
  23. 23.
    Miller MR, Crapo R, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Enright P, van der Grinten CPM, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R (2005) General considerations for lung function testing. Eur Respir J 26:153–161CrossRefPubMedGoogle Scholar
  24. 24.
    Miller MR, Hankinson J, Brusasco V, Burgos F, Casaburi R, Coates A, Crapo R, Enright P, van der Grinten CPM, Gustafsson P, Jensen R, Johnson DC, MacIntyre N, McKay R, Navajas D, Pedersen OF, Pellegrino R (2005) Standardisation of spirometry. Eur Respir J 26:319–338CrossRefPubMedGoogle Scholar
  25. 25.
    Mills GH, Kyroussis D, Hamnegard CH, Polkey MI, Green M, Moxham J (1996) Bilateral magnetic stimulation of the phrenic nerves from an anterolateral approach. Am J Respir Crit Care Med 154:1099–1105CrossRefPubMedGoogle Scholar
  26. 26.
    Miyamoto S, Nagaya N, Satoh T, Kyotani S, Sakamaki F, Fujita M, Nakanishi N, Miyatake K (2000) Clinical correlates and prognostic significance of six-min walk test in patients with primary pulmonary hypertension. Comparison with cardiopulmonary exercise testing. Am J Respir Crit Care Med 161:487–492CrossRefPubMedGoogle Scholar
  27. 27.
    Naeije R (2005) Breathing more with weaker respiratory muscles in pulmonary arterial hypertension. Eur Respir J 25:6–8CrossRefPubMedGoogle Scholar
  28. 28.
    Polkey MI, Moxham J (2001) Clinical aspects of respiratory muscle dysfunction in the critically ill. Chest 119:926–939CrossRefPubMedGoogle Scholar
  29. 29.
    Polkey MI, Green M, Moxham J (1995) Measurement of respiratory muscle strength. Thorax 50:1131–1135PubMedCentralCrossRefPubMedGoogle Scholar
  30. 30.
    Rhodes J, Barst RJ, Garofano RP, Thoele DG, Gersony WM (1991) Hemodynamic correlates of exercise function in patients with primary pulmonary hypertension. J Am Coll Cardiol 18:1738–1744CrossRefPubMedGoogle Scholar
  31. 31.
    Rubin LJ (1997) Primary pulmonary hypertension. N Engl J Med 336:111–117CrossRefPubMedGoogle Scholar
  32. 32.
    Rubin LJ (2004) Diagnosis and management of pulmonary arterial hypertension: ACCP evidence-based clinical practice guidelines. Chest 126:7S–10SCrossRefPubMedGoogle Scholar
  33. 33.
    Simonneau G, Robbins IM, Beghetti M, Channick RN, Delcroix M, Denton CP, Elliott CG, Gaine SP, Gladwin MT, Jing Z, Krowka MJ, Langleben D, Nakanishi N (2009) Updated clinical classification of pulmonary hypertension. J Am Coll Cardiol 54:S43–S54CrossRefPubMedGoogle Scholar
  34. 34.
    Sun XG, Hansen JE, Oudiz RJ, Wasserman K (2001) Exercise pathophysiology in patients with primary pulmonary hypertension. Circulation 104:429–435CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Hans-Joachim Kabitz
    • 1
    Email author
  • Hinrich-Cordt Bremer
    • 2
  • Anja Schwoerer
    • 1
  • Florian Sonntag
    • 1
  • Stephan Walterspacher
    • 1
  • David Johannes Walker
    • 1
  • Nicola Ehlken
    • 3
  • Gerd Staehler
    • 4
  • Wolfram Windisch
    • 5
  • Ekkehard Grünig
    • 3
  1. 1.Department of PneumologyUniversity Hospital FreiburgFreiburgGermany
  2. 2.Department of PneumologySchwarzwald-Baar Klinikum DonaueschingenDonaueschingenGermany
  3. 3.Department of Cardiology and PneumologyUniversity Hospital HeidelbergHeidelbergGermany
  4. 4.Department of Pneumology and CardiologyLoewenstein Hospital LoewensteinLoewensteinGermany
  5. 5.Department of PneumologyLungenklinik Merheim - Kliniken der Stadt Köln gGmbHCologneGermany

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