J Appl Physiol 105: 756-a-757-a, 2008;
doi:10.1152/japplphysiol.90336.2008e
8750-7587/08 $8.00
POINT-COUNTERPOINT
Rebuttal from Drs. O'Donnell and Webb
Aliverti and Macklem propose a novel hypothesis of exercise limitation in COPD that highlights excessive expiratory muscle activity as the primary component. They propose that as the disease advances, dynamic lung hyperinflation (DH) and "derecruitment" of abdominal muscles evolve as "learned" responses to exercise. The dramatic consequences of excessive expiratory muscle pressure generation are seen when healthy individuals breathe via a Starling resistor to the point of hypercapnia. From the published literature in moderate to severe COPD we can conclude that: 1) inspiratory muscle loading/functional weakness and the associated respiratory difficulty are primary limiting factors (7); 2) expiratory muscle activity is variable (but not dichotomous) and in the majority of studies peak tidal expiratory pressure rises smoothly to 
20–25% of maximal expiratory pressure at end-exercise (2); 3) expiratory muscle recruitment is not protective of DH, which was present in 84% of 463 patients (4, 6); 4) dyspnea intensity does not correlate with indexes of expiratory effort in COPD and expiratory difficulty is rarely reported (7); 5) significant DH (>0.5 liters) occurs during exercise in early COPD (9); 6) expiratory muscles are recruited in the most advanced COPD: unloading of the inspiratory muscles [via lung volume reduction surgery (5) or pressure support ventilation (3)] consistently reduced expiratory pressures. There is no convincing evidence that DH is actively induced during exercise in COPD; it likely arises passively. Excessive expiratory muscle activity at higher ventilations is counterproductive in COPD and is likely maladaptive; its contribution to dyspnea and exercise intolerance is unknown.
Debigaré and Maltais highlight the primary role of peripheral muscle dysfunction in exercise limitation. This view must be tempered by evidence to the contrary. 1) In multinational trials using cycle exercise (4, 6), dyspnea was the primary or coprimary exercise-limiting symptom in the majority (70%), which likely underestimates its prevalence during weight-bearing exercise. 2) Resting and dynamic inspiratory capacity correlates strongly with peak 
O2 (8). 3) Wagner (10) persuasively argued that many of the morphologic and biochemical abnormalities of skeletal muscle in COPD are related to deconditioning (likely secondary to dyspnea-induced activity avoidance). 4) Respiratory impairment may directly cause leg muscle dysfunction through ventilatory/locomotor muscle competition, arterial hypoxemia, or increased sympathetic nervous system activation and attendant vasoconstriction. 5) A primary respiratory component is suggested by a shift in the locus of sensory limitation during exercise from "the lungs to the legs" after bronchodilators (4) and by the suboptimal response to exercise training when bronchodilation is inadequate (1). We conclude that effective dyspnea alleviation is an absolute prerequisite to achieve and sustain improvements of peripheral muscle function in COPD.
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Copyright © 2008 by the American Physiological Society.
