Factors Limiting Exercise Performance in Lung Disease

Factors Limiting Exercise Performance In Lung Disease· Ventilatory Insufficiency Michael]. Belman, M.D., F.C.C.lt

Because of the additive effects of impaired ventilatory muscle function on the one band and the increased ventilatory load on the other, increasing attention is now directed at therapies to improve ventilatory muscle function. Three main approaches are being used: (i) reduction in load; (2) increase' in intrinsic ventilatory muscle function; and (3) reduction in dyspnea perception. While promising results have been achieved, additional investigative work is required to resolve outstanding questions.

S·

everal investigators have emphasized the importance of expiratory flow limitation during increasing levels of ventilation in patients with chronic obstructive pulmonary ·disease'(eOPD}.l.i More recent emphasis has shifted to the respiratory muscles and the signmcance of the increased inspiratory load.1.3 VENnLATORyFuNcnON

Dynamic hyperinflation (DH), an inevitable consequence of the tachypnea during increasing ventilatory levels in COPO patients, directly affects performance of the ventilatory pump.· Because of the DR, tidal breathing occurs on a less compliant portion of th~ pressure volume c~rve resulting in an increase in elastic load. 3 Secondl~ as inspiration begins before passive FRC is reached, the inspiratory muscles must generate additiOnal. pressure to overcome the elastic recoil. This positive end-expiratory pressure (intrinsic PEEP) constitutes a threshold load. In addition, these patients demonstrate exaggerated frequency dependence of compliance. Thus, even if the DH is discounted, the functional compliance would be reduced at higher breathing frequencies. Because of the greater elastic and threshold loads described above, there is·a signmcant restrictive inspiratory load in COPD,althougb the major mechanical defect is resistive in expiration.• The effect of the inspiratory load is further aggravated by the fact that inspiratory muscle function is impaired in these patients: 5 The adverse effects include changes in the geometry of the diaphragm and chest wall, including changes in diaphragm length. In addition, there may be intrinsic changes in inspiratory muscle function, including atrophy secondary to malnutrition, and impaired function secondary to hypoxemia and hypercapnia. These factors singly or iIi combination signmcantly i"lpair diaphragmatic contractility. An additional aggravating factor is the increased velocity of inspiratory muscle contraction required during increased *From the UCLA School of Medicine and Cedars-Sinai Medical Center,· Los Angeles. t Associate Director, Pulmonary Division. tDirector, Pulmonary Physiology Laboratory. t Associate Professor of Medicine.

ventilatory levels. Because maximal force is inversely related to increasing velocity of contraction (inspiratory flow rate), there is a reduction in maximal respiratory muscle force. THERAPEUTIC ,ApPROACHES

The pathogenetic role of the impaired ventilatory mechanics has led many investigators to explore widely different approaches to improve overall function. Three main approaches have been used: (1) a reduction in the ventilatory load; (2) an increase in the intrinsic capacity ofthe ventilatory muscles; and (3) an alteration in the relations~p between load and dyspnea without directly affecting ventilatory level, ie, demand and capacity are unchanged, but dyspnea perception relative to ventilatory level is reduced. s .7 REDUcnON IN VENTILATORY DEMAND

During exercise, VE increases in proportion to Veol , and PaCOI is regulated near restiDg levels. The relationship between these variables is expressed in the following equation: VE = kVco/PaCOI (1- VDNT) The reduction in Vco~ can be achieved. through changing metaboiic substrate by dietary modification, a reduction in VDNT through bronchodilation or changing the COl set point by inducing metabolic alkalosis. 8 These approaches have had limited success. In normal individuals, signmcant reductions in exercise ventilation have been achieved after training regimens. The major benefit of these is a reduction in lactate acidosis, the buffering of which generates excess COl in addition to the aerobic COl production. Recent work by Casaburi et al8 in mildly impaired COPD patients showed a similar response to that of normal subjects, namely a reduction in exercise lactate and minu~e ventilation. That this approach will be helpful in severely impaired COPD patients remairis speculative as it is in this group that peak ~xercise capacity is greatly reduced and previous work suggests that such patients are incapable of training at exercise intensities capable of producing reductions in exercise lactic acid. 9 Reductions in demand can also be achieved by improving efficiency of movement. This may be particularly important in the performance of activities of daily living. Oxygen therapy and opiates have also been used to reduce ventilatory demand. 10 INCREASING VENTILATORY CAPACITI

Increased strength and endurance of the ventilatory muscles could theoretically improve maximal ventilatory capacity and thus, exercise performance. I~proved nutrition, ventilatory muscle training, and pharmacotherapy have been used to improve ventilatory muscle function. These CHEST I 101 I 5 I MA"1, 1992 I Supplement

253S

methods have been reviewed extensivel~s,l1 While each of these techniques has produced some benefit, there is as yet no broad consensus of their efficacy in clinical practice. Unloading of the ventilatory muscles through intermittent ventilatory support as a method of reversing chronic ventilatory muscle fatigue has also been evaluated. A large randomized study has recently been completed and preliminary results indicate that negative pressure ventilation did not signi6cantly improve dyspnea or exercise function. 12 There is still interest in exploring the value of positive pressure ventilation applied noninvasively, but to our knowledge, large-scale randomized studies of this modality have not yet been done. VENTILATION-DYSPNEA RELATIONSHIPS

Improvements in functional capacity ~ave been achieved without directly altering ventilatory demand or maximal ventilatory capacity: As Altose6 has stated, ~'The ideal intervention would blunt perceptual responses and decrease the conscious awareness of respiratory muscle contraction . . . even at the same degree of respiratory efferent output and muscle tension." Some pharmacologic agents, especially codeine, have been evaluated as dyspnea-reducing agents with partial success. 10 More recently, Supinski and co-workers 13 have suggested that the reduction in breathlessness was probably related to a decrease in ventilation rather than a direct effect on breathlessness per se. In some cases, the side effects of the opiates have limited their continued use. Several previous investigators have also emphasized the role of psychotherapy or dyspnea desensitization as the result of exercise training as a positive factor affecting exercise tolerance. 14 In this regard, a recent study that shows progressive reduction in dyspnea perception with repetitive testing only; in the absence of a true training response, emphasizes the importance of this mechanism. IS Agle and coinvestigators14 have suggested that the dyspneic COPD patient may become desensitized to dyspnea after exercising in a supportive medical environment. This mechanism was also stressed by Levine et al 16 who noted a comparable improvement in dyspnea in a sham-treated group as compared with that achieved in the patients who received the active treatment. POSITIVE AIRWAY PRESSURE

Recently; attention has been directed to unloading the respiratory muscles through the application of continuous positive airway pressure. This has been done in COPO patients on ventilators and in ambulatory patients. As noted, the elastic and threshold loads in COPO require high pressures for the initiation and maintenance of inspiration. Through the application of positive pressure at the mouth, which incidently has also been achieved in ambulatory patients by means ofa simple portable device, improvements in exercise capacity and reductions in dyspnea have been noted. 17,18 The ventilatory limitation in COPO has generated a multipronged attack, the goal of which is to improve functional capacity despite the impaired ventilatory mechanics. Several of the approaches Iescribed above have shown promise, but there is little consensus regarding the best 254S

method and the appropriate target group to which the different methods should be applied. It is hoped that future investigative work will resolve the many outstanding questions. The enormity of the problem of impaired and disabled COPO patients throughout the world demands nothing less. REFERENCES

1 Potter WA, Olafsson S, Hyatt RE. Ventilatory mechanics and expiratory Bow limitation during exercise in patients with obstructive lung disease. J Clin Invest 1971; 50:910-19 2 Stubbing DG, Pengelly LD, Morse J1£, Jones NL. Pulmonary mechanics· during exercise in subjects with chronic airBow obstruction. J Appl Physioll980; 49:511-15 3 Sharp J. The chest wall and respiratory muscles in air8.ow limitation. In: Roussos C, Macklem eds. The thorax. New York: Marcel Dekker, 1985; 29:1155-1202 4 Younes M. Determinants of thoracic excursions during exercise. In: Whipp BJ, Wasserman K, eds. Pulmonary physiology and pathophysiology of exercise: lung biology in health and disease. New York: Marcel Dekker, 1990:1-65 5 Rochester DF. Effect of COPD on the respiratory muscles in chi-onic obstructive pulmonary disease. Chemiack NS, ed. Philadelphia: WB Saunders, 1991:134-56 6 Altose MD. Assessment and management of breathlessness. Chest 1985; 88:77-83 7 Casaburi R, Wasserman K. Exercise training in pulmonary rehabilitation [editorial]. N Engl J Moo 1986; 314:1509-11 8 Casaburi R, Patessio A, Ioli F, Zanaboni S, Donner CF, Wasserman K. Reductions in exercise lactic acidosis and ventilation as a result of exercise training in patients with obstructive lung disease. Am Rev Respir Dis 1991; 143:9-18 9 Belman MJ, Kendregan BA. Exercise training fails to increase skeletal muscle enzymes in patients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1981; 123:256-61 10 Woodcock AA, Gross ER, Gellert A, Shah S, Johnson M, Geddes DM. Effects of dihydrocodeine, alcohol, and caffeine on breathlessness and exercise tolerance in patients with chronic obstructive lung disease and normal blood gases. N Engl J Med 1981; 305:1611-16 11 Belman MJ, ed. Respiratory muscle function in health and disease. Coo Chest Med 1988; 9:175-358 12 Martin JG. Clinical intervention in chronic respiratory failure. Chest 1989; 97: I05S-OSS 13 Supinski G, Dimarco A, Bark H, Chapman K, Clary S, Altose M. Effect of codeine on the sensations elicited by loaded breathing. Am Rev Respir Dis 1990; 141:1516-21 14 Agle D~ Baum GL, Chester EH, Wendt M. Multidiscipline treatment of chronic pulmonary insufficiency, I: psychologic aspects of rehabilitation. Psychosom Moo 1991; 345:41-9 15 Belman MJ, Brooks LR, Ross DJ, Mohsenifar Z. Variability of breathlessness measurement in patients with chronic obstructive lung disease. Chest 1991; 99:566-71 16 Levine S, Weiser ~ Gillen J. Evaluation of a ventilatory muscle endurance training program in the rehabilitation ofpatients with chronic obstructive pulmonary disease. Am Rev Respir Dis 1986; 133:400-06 17 O'Donnell DE, Sanii R, Younes M. Improvement in exer<..ojse endurance in patients with chronic airflow limitation using continuous positive airway pressure. Am Rev Respir Dis 1988; 138:1510-14 18 Petrof B, Legare M, Goldberg ~ Milic-Emili J, Gottfired S. Effect of continuous positive airway pressure on respiratory muscle function during weaning from mechanical ventilation in COPD. Am Rev Respir Dis 1988; 137:A65

n:

Factors Umiting Exercise Performance in Lung Disease (Michael J. Belman)