Mechanisms of non-pharmacologic adjunct therapies used during exercise in COPD.

Individuals with chronic obstructive pulmonary disease (COPD) are often limited in their ability to perform exercise due to a heightened sense of dyspnea and/or the occurrence of leg fatigue associated with a reduced ventilatory capacity and peripheral skeletal muscle dysfunction, respectively. Pulmonary rehabilitation programs have been shown to improve exercise tolerance and health related quality of life. Additional therapeutic approaches such as non-invasive ventilatory support (NIVS), heliox (He-O(2)) and supplemental oxygen have been used as non-pharmacologic adjuncts to exercise to enhance the ability of patients with COPD to exercise at a higher exercise-intensity and thus improve the physiological benefits of exercise. The purpose of the current review is to examine the pathophysiology of exercise limitation in COPD and to explore the physiological mechanisms underlying the effect of the adjunct therapies on exercise in patients with COPD. This review indicates that strategies that aim to unload the respiratory muscles and enhance oxygen saturation during exercise alleviate exercise limiting factors and improve exercise performance in patients with COPD. However, available data shows significant variability in the effectiveness across patients. Further research is needed to identify the most appropriate candidates for these forms of therapies.

Diaphragm activation during exercise in chronic obstructive pulmonary disease.

Although it has been postulated that central inhibition of respiratory drive may prevent development of diaphragm fatigue in patients with chronic obstructive pulmonary disease (COPD) during exercise, this premise has not been validated. We evaluated diaphragm electrical activation (EAdi) relative to maximum in 10 patients with moderately severe COPD at rest and during incremental exhaustive bicycle exercise. Flow was measured with a pneumotachograph and volume by integration of flow. EAdi and transdiaphragmatic pressures (Pdi) were measured using an esophageal catheter. End-expiratory lung volume (EELV) was assessed by inspiratory capacity (IC) maneuvers, and maximal voluntary EAdi was obtained during these maneuvers. Minute ventilation (V E) was 12.2 +/- 1.9 L/min (mean +/- SD) at rest, and increased progressively (p < 0.001) to 31.0 +/- 7.8 L/min at end-exercise. EELV increased during exercise (p < 0.001) causing end-inspiratory lung volume to attain 97 +/- 3% of TLC at end-exercise. Pdi at rest was 9.4 +/- 3.2 cm H(2)O and increased during the first two thirds of exercise (p < 0.001) to plateau at about 13 cm H(2)O. EAdi was 24 +/- 6% of voluntary maximal at rest and increased progressively during exercise (p < 0.001) to reach 81 +/- 7% at end-exercise. In conclusion, dynamic hyperinflation during exhaustive exercise in patients with COPD reduces diaphragm pressure-generating capacity, promoting high levels of diaphragm activation.

Changes in respiratory effort sensation over time are linked to the frequency content of diaphragm electrical activity.

This study evaluated whether respiratory effort sensation (RES) changes over time when breathing is performed with constant contraction pattern, fixed diaphragm activation, and maintained pressure generation. Another aim was to assess whether there was any association between RES and the power spectrum center frequency of the diaphragm (CFdi) electrical activity. Six healthy subjects performed two 10-min periods targeting diaphragm electrical activation (EAdi) to 40% of maximum using (1) expulsive or Mueller maneuvers at FRC generating a mean transdiaphragmatic (Pdi) pressure of 55.0 +/- 22.7 cm H(2)O (+/- SD) and (2) inspiration to 71.2 +/- 14.1% of inspiratory capacity (IC) generating a Pdi of 21.4 +/- 5.2 cm H(2)O. The Pdi did not decrease over time during either maneuver. During both periods RES increased (p < 0.001) and CFdi decreased (p < 0.001) over time with higher Pdi levels producing larger decreases in CFdi (p = 0.003) and greater increases in RES (p = 0.008). Changes in CFdi and RES were related, and identical slopes were obtained during the two maneuvers. In conclusion, while breathing with a fixed pattern, constant diaphragm activation, and maintained pressure generation, RES increases over time and is associated with CFdi independent of the level of diaphragm pressure generated.

Voluntary activation of the human diaphragm in health and disease.

Intersubject comparison of the crural diaphragm electromyogram, as measured by an esophageal electrode, requires a reliable means for normalizing the signal. The present study set out 1) to evaluate which voluntary respiratory maneuvers provide high and reproducible diaphragm electromyogram root-mean-square (RMS) values and 2) to determine the relative diaphragm activation and mechanical and ventilatory outputs during breathing at rest in healthy subjects (n = 5), in patients with severe chronic obstructive pulmonary disease (COPD, n = 5), and in restrictive patients with prior polio infection (PPI, n = 6). In all groups, mean voluntary maximal RMS values were higher during inspiration to total lung capacity than during sniff inhalation through the nose (P = 0.035, ANOVA). The RMS (percentage of voluntary maximal RMS) during quiet breathing was 8% in healthy subjects, 43% in COPD patients, and 45% in PPI patients. Despite the large difference in relative RMS (P = 0.012), there were no differences in mean transdiaphragmatic pressure (P = 0.977) and tidal volumes (P = 0.426). We conclude that voluntary maximal RMS is reliably obtained during an inspiration to total lung capacity but a sniff inhalation could be a useful complementary maneuver. Severe COPD and PPI patients breathing at rest are characterized by increased diaphragm activation with no change in diaphragm pressure generation.

Effects of pursed-lips breathing and expiratory resistive loading in healthy subjects.

To examine the effect of pursed-lips breathing (PLB) on breathing pattern and respiratory mechanics, we studied 11 healthy subjects breathing with and without PLB at rest and during steady-state bicycle exercise. Six of these subjects took part in a second study, which compared the effects of PLB to expiratory resistive loading (ERL). PLB was found to prolong expiratory and total breath durations and to promote a slower and deeper breathing pattern. During exercise, the compensatory increase that occurred in tidal volume was not sufficient to counter the reduction in breathing frequency, causing minute ventilation to be reduced. Although ERL similarly caused minute ventilation and breathing frequency to be decreased, unlike PLB, it produced no change in tidal volume and prolonged expiratory and total breath durations to a lesser extent. PLB and ERL increased the expiratory resistance to a comparable degree, also increasing the expiratory resistive work of breathing and promoting greater expiratory rib cage and abdominal muscle recruitment in response to the expiratory loads. End-expiratory lung volume, which was determined from inspiratory capacity maneuvers, was not altered by PLB; however, with ERL it was increased by 0.20 and 0.24 liter during rest and exercise, respectively. Inspiratory muscle recruitment patterns were not altered by PLB at rest, although small increases in the relative contribution of the rib cage/accessory muscles in conjunction with abdominal muscle relaxation occurred during exercise. Similar trends were observed with ERL. We conclude that, although ERL and PLB induce comparable respiratory muscle recruitment responses, they are not equivalent with respect to breathing pattern changes and effect on end-expiratory lung volume.