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Point-Counterpoint: Andrea Aliverti, PhD, Peter T Macklem, Richard Debigare, Francois Maltais, Denis E O'Donnell, and Katherine A Webb, M.Sc. Point: Counterpoint - The major limitations to exercise performance in COPD J Appl Physiol 2008; 0: 90336.2008v1 [Abstract] [PDF]

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To the Editor:

John B. West   (4 April 2008)

MEASUREMENTS, ESTIMATES,INTERPRETATIONS, MYTHS

Norman L. Jones   (21 April 2008)

COPD Point: Counterpoint commentary

Linda Nici, MD   (28 April 2008)

To the Editor: 4 April 2008
John B. West, Distinguished Professor of Medicine and Physiology School of Medicine, University of California, San Diego Send letter to journal: Re: To the Editor: jwest{at}ucsd.edu John B. West	Two comments. 1. It is extremely unlikely that all patients with COPD have the same major limitation (1, 2, 4). 2. As regards the three choices, I would choose none of the above. I do not understand the term dynamic hyperinflation. Hyperinflation refers to a large lung volume which is a static not dynamic measurement. A major limitation to exercise performance in COPD is the inability of the patient to increase his ventilation. The basic mechanism for this is dynamic compression of the airways. This may lead to hyperinflation but the fundamental problem is that any increase in expiratory flow rate is impossible because the flow is independent of effort (3). Incidentally this year is the 50th anniversary of this landmark paper. References 1. Aliverti A, Macklem P. The major limitation to exercise performance in COPD is inadequate energy supply to the respiratory and locomotor muscles. J Appl Physiol, in press 2008. 2. Debigare R, Maltais F. The major limitation to exercise performance in COPD is lower limb muscle dysfunction. J Appl Physiol, in press 2008. 3. Hyatt RE, Schilder DP, Fry DL. Relationship between maximum expiratory flow and degree of lung inflation. J Appl Physiol 13: 331-336, 1958. 4. ODonnell D, Webb K. The major limitation to exercise performance in COPD is dynamic hyperinflation. J Appl Physiol, in press 2008.
MEASUREMENTS, ESTIMATES,INTERPRETATIONS, MYTHS 21 April 2008
Norman L. Jones McMaster University Send letter to journal: Re: MEASUREMENTS, ESTIMATES,INTERPRETATIONS, MYTHS jonesn{at}univmail.cis.mcmaster.ca Norman L. Jones	MEASUREMENTS, ESTIMATES,INTERPRETATIONS, MYTHS   The three papers each present a different view of the main factors limiting exercise in COPD- expiratory muscle work with excess respiratoryVO2 (1), leg muscle dysfunction (2) and inspiratory muscle effort due to hyperinflation (3). All three accept that there are many factors that contribute to limitation, which probably accounts for them all remaining standing at the end of round 2.  Spectators look on, matching their own biases with those of the protagonists.  From my perspective, the calculations presented by Aliverti and Mcklem are unconvincing, in according a primary role to respiratory muscle oxygen consumption.   No one doubts that some patients do (but most don’t) develop high intrathoracic expiratory pressures (4, 5), in excess of the pressure needed to achieve maximum expired flow/volume. We do not know the validity of respiratory muscle work estimated from pressure/volume measurements, nor the calculations of respiratory muscle VO2. The stealing of 55% of oxygen uptake by the respiratory muscles seems an overestimate. In contrast to the respiratory muscles, the increase in oxygen uptake by skeletal muscles during cycling may be accurately estimated from power output (W). In a large study of COPD patients (6), the VO2/W relationship was parallel to that of healthy subjects but higher by 150 ml/min, similar to the excess VO2 that accompanies maximum respiratory loading during exercise (7), but less than their estimates. Many factors, acting in a combination that is unique to the individual, contribute to symptom intensity, which is what stops all of us exercising.   Norman L Jones McMaster University Canada   jonesn{at}mcmaster.ca   REFERENCES.   Aliverti, A., Macklem, P.T. The major limitation to exercise performance in COPD is inadequate energy supply to the respiratory and locomotor muscles. Debigaré, R., Maltais, F. major limitation to exercise performance in COPD islower limb muscle dysfunction. O’Donnell, D.E., Webb, K.A. major limitation to exercise performance in COPD is dynamic hyperinflation. Potter, W.A., Olafsson, S., Hyatt, R.E. Ventilatory mechanics and expiratory flow limitation during exercise in patients with obstructive lung disease. J Clin Invest 50: 901-919; 1971. Stubbing, D.G., Pengelly, L.D., Morse, J.L.C., Jones, N.L. Pulmonary mechanics during exercise in subjects with chronic airflow obstruction. J Appl Physiol 49: 511-515; 1980. Jones,N.L., Jones,G., Edwards, R.H.T. Exercise tolerance in chronic airway obstruction. Amer Rev Resp Dis 103: 477-491; 1971. El-Manshawi, E., Killian, K.J., Summers, E., Jones, N.L. Breathlessness during exercise with and without resistive loading. J Appl Physiol 61: 896-905; 1986.
COPD Point: Counterpoint commentary 28 April 2008
Linda Nici, MD, Associate Chief, Pulmonary & Critical Care Section; Providence Veterans Affairs Medical Center Associate Professor of Medicine; Brown University School of Medicine Send letter to journal: Re: COPD Point: Counterpoint commentary Linda_Nici{at}brown.edu Linda Nici, MD	“You jest about what you suppose to be a triviality, in asking whether the hen came first from an egg or the egg from a hen, but the point should be regarded as one of importance, one worthy of discussion, and careful discussion at that." (Macrobius, 400 AD) This debate illustrates the difficulties in determining the primary physiologic abnormality that limits exercise performance in COPD. It is apparent from the arguments put forth that there is compelling evidence to support the presence of dynamic hyperinflation (DH) resulting from expiratory flow limitation (1) and intrinsic peripheral muscle dysfunction in patients with COPD (2). While the hypothesis put forth by Drs. Alverti and Macklem of inadequate energy supplies and learned response to exercise is interesting (3), there is little evidence that DH is caused by a de- recruitment of expiratory muscles. In fact, it has been observed even in mild COPD (4). Furthermore, dyspnea does not correlate with expiratory effort (5). As pointed out by Drs Debigare and Maltais, it is also unlikely that low oxygen availability to the lower limb in COPD is a main factor for most patients (6, 7) in that both structural and functional muscle abnormalities persist despite lung transplantation and optimal bronchodilation (2). Most importantly, however, a key concept that must be recognized in this debate is the heterogeneity of the COPD population and the likelihood that, for the individual, one or more of these pathophysiologic mechanisms may be major contributors to exercise limitation, and therefore be the appropriate target(s) for intervention. References: 1. Aliverti A, Macklem P. The major limitation to exercise performance in COPD is inadequate energy supply to the respiratory and locomotor muscles. J Appl Physiol, in press 2008. 2. Debigare R, Maltais F. The major limitation to exercise performance in COPD is lower limb muscle dysfunction. J Appl Physiol, in press 2008. 3. O'Donnell D, Webb K. The major limitation to exercise performance in COPD is dynamic hyperinflation. J Appl Physiol, in press 2008. 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 COPD. Am J Respir Crit Care Med. 2208; 117:622-629. 5. O’Donnell DE, Hamilton AL, Webb KA. Sensory-mechanical relationships during high intensity, constant work rate exercise in COPD. J Appl Physiol 2006; 101:1025-1035. 6. Maltais F, Jobin J, Sullivan MJ, Bernard S, Whittom F, Killian KJ, Desmeules M, Belanger M, LeBlanc P. Metabolic and hemodynamic responses of the lower limb during exercise in patients with COPD. J Appl Physiol 1998; 84:1573-1580. 7. Sala E, Roca J, Marrades RM, Alonso J, Gonzalez de Suso JM, Moreno A, Barbera JA, Nadal J, de Jover L, Rodriguiz-Roison R, Wagner PD. Effects of endurance training on skeletal muscle biogenetics in COPD. Am J Respir Crit Care Med 1999; 159: 1726-1734.