Journal of Applied Physiology AJP: Endocrinology and Metabolism
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J Appl Physiol 105: 763, 2008; doi:10.1152/japplphysiol.90745.2008
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LETTER TO THE EDITOR

Last Word on Point:Counterpoint: The major limitation to exercise performance in COPD is 1) inadequate energy supply to the respiratory and locomotor muscles, 2) lower limb muscle dysfunction, 3) dynamic hyperinflation

TO THE EDITOR: It is good news that there is a consensus: all correspondents agree that exercise limitation is multifactorial in COPD, a point we made at the outset of both our Point:Counterpoint article and our subsequent rebuttal. We are also pleased that West and Wagner (5) agree with our Point:Counterpoint figure showing that the initiating event in exercise limitation is expiratory flow limitation; this sets in motion a train of events that severely impairs ventilatory pump function (2), including a reduction in cardiac output and energy supplies to working muscles (1). Scano (5), an author on this paper, asks "how does...respiratory pressure influence cardiac output in exercising humans?": he himself has already provided the answer. However Zakynthinos' and Vogiatzis' (5) thoughtful letter makes us question whether expiratory flow-limitation is always the initiating event. They point out that in early COPD exercise performance is impaired by leg fatigue whereas most patients are not flow limited. In our rebuttal we claim that dynamic hyperinflation, although occurring in stage 1 patients, did not limit exercise performance, and that skeletal myopathy was unlikely. Then why was exercise impaired?

As Gosker and Schols (5) state, we need much better knowledge about the natural history of exercise intolerance in COPD. We agree that longitudinal studies, particularly in GOLD stages 1 and 2, should be done. Ofir et al. (4) show that in these patients the anaerobic threshold is abnormally low. We hold it to be axiomatic that if there is abnormal oxygen demand somewhere in the body the locomotor muscles will reach a lactate threshold at a lower than normal exercise workload. In COPD it is certain that respiratory muscles demand abnormally large oxygen supplies. Increased airway resistance, frequency dependence of compliance, energetically wasteful rapid shallow breathing, the dynamic hyperinflation threshold load, and any expiratory flow-limitation present will increase the oxygen cost of breathing. We do not claim as Norman Jones (5) suggests that the respiratory muscles "steal" 55% of total oxygen uptake; that is what they demand. Whether or not they get it depends on the competition between respiratory and locomotor muscles for the available energy supplies. This will start prematurely because of the high oxygen cost of breathing and will lead to exercise limitation. Jones states that in COPD the oxygen consumption is 150 ml/min greater than normal at all exercise workloads. Does he really believe that the oxygen cost of breathing is independent of workload!? Levison (misspelled in PubMed as "Evison") and Cherniack (3) showed 40 years ago that the oxygen cost of breathing in COPD is excessive, that it increases rapidly as ventilation increases, and that it is an important cause of exercise limitation. The idea that inadequate energy supplies limits exercise in COPD is not new. Levison's and Cherniack's classic studies have been steadfastly ignored by most of the experts in the field of exercise physiology. It is time to give them the credit that is their due.

REFERENCES

  1. Aliverti A, Dellacà RL, Lotti P, Bertini S, Duranti R, Scano G, Heyman J, Lo Mauro A, Pedotti A, Macklem PT. Influence of expiratory flow-limitation during exercise on systemic oxygen delivery in humans. Eur J Appl Physiol 95: 229–242, 2005.[CrossRef][Web of Science][Medline]
  2. Aliverti A, Kayser B, Macklem PT. A human model of the pathophysiology of chronic obstructive pulmonary disease. Respirology 12: 478–485, 2007.[CrossRef][Web of Science][Medline]
  3. Levison H, Cherniack RM. Ventilatory cost of exercise in chronic obstructive pulmonary disease. J Appl Physiol 25: 21–27, 1968.[Free Full Text]
  4. Ofir D, Laveneziana P, Webb KA, Lam YM, O'Donnell DE. Mechanisms of dyspnea during cycle exercise in symptomatic patients with GOLD stage I chronic obstructive pulmonary disease. Am J Respir Crit Care Med 177: 622–629, 2008.[Abstract/Free Full Text]
  5. West JB, Wagner PD, Neder JA, Scano GL, Jones NL, Zakynthinos SG, Vogiatzis I, Nici L, Calverley PM, Gosker HR, Schols AM, Palange P, Marciniuk DD, Butcher SJ. Comments on Point:Counterpoint: The major limitation to exercise performance in COPD is 1) inadequate energy supply to the respiratory and locomotor muscles, 2) lower limb muscle dysfunction, 3) dynamic hyperinflation. J Appl Physiol; doi:10.1152/japplphysiol.zdg-8100.pcpcomm.2008.[Free Full Text]

Andrea Aliverti1
Peter T. Macklem2
 1TBM-Lab, Dipartimento di Bioingegneria, Politecnico di Milano, Italy; 2Meakins-Christie Laboratories, McGill University Health Centre, Research Institute, Montreal, Canada




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