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Exercise Training Programs for Pediatric Patients with Chronic Lung Disease
Symposium on The Chest
Exercise Training Programs for Pediatric Patients with Chronic Lung Disease Thomas G. Keens, M.D.*
Present therapy for chronic lung disease in pediatrics is directed primarily toward preventing pulmonary infection and lung damage. Less emphasis is placed on the ventilatory muscles, which, in some cases, must cope with the significantly increased work of breathing. Respiratory failure can be viewed as inadequate power of ventilatory muscles to overcome increased respiratory loads. Often, lung damage as a result of chronic lung disease cannot be reversed, thus the respiratory load cannot be significantly reduced. However, the strength and endurance of ventilatory muscles can be altered. 5, 7, 36, 37 Intuitively, the pediatric physician dealing with pulmonary disease has known that exercise is good for patients with lung disease, but has attributed its benefits to nonspecific effects such as improved morale, efficiency, and better neuromuscular coordination. 4 , 8, 12, 13, 16, 29, 41, 42, 44, 46, 48, 51, 52, 54 Ventilatory muscles, like other skeletal muscles, may become fatigued, and this may result in respiratory failure. 40, 49 Aerobic exercise programs improve the endurance of ventilatory muscles, thus decreasing their susceptibility to fatigue. 36 This paper will describe the effects of physical conditioning in general and in patients with chronic lung disease. It will discuss the mechanism of these effects, and outline the types of exercise programs which might be effective in pediatric patients with lung disease. Effects of Training with Aerobic Exercise Aerobic exercise requires a prolonged continuous output of muscular work. Running, swimming, cross country skiing, and hiking are examples of aerobic exercise. Aerobic exercise depends on muscle endurance or resistance to fatigue. A muscle is fatigued when it can no longer generate the tension required to perform work. Because performance of muscular work requires energy, fatigue occurs when a mus*Neonatal-Respiratory Disease Division, Children's Hospital of Los Angeles; Assistant Professor of Pediatrics, University of Southern California School of Medicine, Los Angeles, California
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cle has no energy available for contraction. Although muscles store some energy as glycogen, this alone cannot support muscular work for very long. Thus the muscle must be able to produce energy. It can do this either by anaerobic or aerobic metabolism. Anaerobic metabolism of glucose to lactate is a relatively inefficient way to produce energy, and this cannot continue for a very long period of time. Muscles or muscle fibers which depend primarily on anaerobic metabolism fatigue relatively rapidly. 10, 20 Aerobic metabolism of glucose or fatty acids through pyruvate via the Krebs cycle is a relatively efficient way to produce energy. Muscles or muscle fibers which depend primarily on aerobic metabolism are relatively fatigue resistant. 10, 20 Maximal oxygen consumption, or aerobic capacity, is the measure of the capacity of a muscle, or an individual, to do aerobic work. . Training with aerobic exercise increases the aerobic capacity of the muscles that are specifically stressed by the exercise. 3(}-32 In a running program, for example, the leg muscles would improve their aerobic capacity with an increased training stress. 17, 25, 30, 32 The increased aerobic capacity means the muscle can produce more energy as a result of an increase in oxidative enzymes, to, 20, 25, 30·32 and thus can perform a higher level of work before fatiguing. Increased oxygen consumption requires an increased oxygen delivery to the tissues. Thus the heart must increase cardiac output, and this serves as an aerobic training stress for the heart. 17,31 However, only those muscles which participate in the training stress will show an improved aerobic capacity, or training effect. The arm muscles, for example, would not significantly improve in a running program. It requires a minimum of about 20 to 30 minutes per day, four to five days per week, to improve aerobic capacity by aerobic exercise in the average person. 2 ,17 More training will result in a greater response. Conversely, if exercise is stopped, the aerobic capacity will decrease again to the baseline, and the gains of exercise will be lost. Exercise must be continued to maintain increased aerobic capacity.
Limitation of Exercise in Chronic Lung Disease In normal subjects, exercise is probably limited by the aerobic capacity of the working muscles and the heartY Neither the lungs nor the ventilatory muscles are thought to limit exercise in normal persons. However, in patients with chronic lung disease, limitation of exercise is due primarily to lung mechanics. 11, 14,21·23,27,33,34,38 The volume of minute ventilation during exercise may nearly equal the patient's maximal breathing capacity, suggesting that the limits of ventilation are being achieved. 14, 21-23,33,34 Further, the mechanical properties of the diseased lung are such that work of breathing is markedly increased. During exercise, when ventilation requirements are high, the work of breathing is increased to such an extent that oxygen consumption required for the ventilatory muscles alone forms a major fraction of the consumption of oxygen in the total body. 11, 38 At these high workloads, fatigue of the ventilatory muscles during exercise may further contribute to the limitation of exercise. 4o ,49 Once optimal pulmonary
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therapy has been instituted in chronic lung diseases, pulmonary mechanics cannot usually be further improved. However, improvement in the endurance of ventilatory muscles may improve tolerance for exercise in these patients. 5 Training of Ventilatory Muscles Ventilatory muscles, like other skeletal muscles, adapt to increased aerobic training by increasing aerobic capacity.35, 39 Increases in oxidative enzymes have been documented in the ventilatory muscles of rats exposed to chronically increased respiratory loads, indicating increased endurance. 35 A further change in contractile properties toward slow-twitch characteristics also occurred. 35 This represents improved biochemical efficiency of the utilization of energy by these ventilatory muscles, again resulting in improved endurance. 24 Leith and Bradley demonstrated that strength or endurance of ventilatory muscles could be improved by specific exercise programs in man. 7,37 The technique of endurance training for ventilatory muscles involves isocapneic hyperventilation at increasing volumes of minute ventilation at least 20 to 30 minutes per day. This exercise is a specific aerobic training stress for the ventilatory muscles and is accompanied by an increased oxygen consumption of those muscles as training progresses. 5,7 Belman and Mittman have shown that specific endurance training for ventilatory muscles also improves general endurance during exercise in patients with chronic lung disease. 5 The maximal ventilation that can be sustained is increased, thus allowing an increase in the volume of minute ventilation potentially usable during exercise. 5, 36, 37 This technique produces similar changes in children with cystic fibrosis. 36 However, specific endurance training for ventilatory muscles is a tedious therapeutic regimen, requiring a fair amount of equipment, and is not well adapted for use in pediatric patients with chronic lung disease. Gross and coworkers used an inspiratory resistance to train both strength and endurance of the ventilatory muscles in quadriplegic patients. 28 These patients breathed against an inspiratory resistance for 30 minutes per day. Both strength and endurance of the ventilatory muscles improved. There was also an increased resistance to fatigue of these muscles. Effects of Aerobic Exercise Training in Chronic Lung Disease Numerous studies have been performed on the effects of general exercise training in chronic lung disease. 1, 3, 4, 8, 9, 12, 13, 16,29,41, 42, 44, 4648,51,52,54 Uniformly, these studies show no changes in tests of pulmonary function. Thus, exercise programs do not significantly alter pulmonary mechanics. It is the anecdotal experience of many exercise programs that the production of cough and sputum is enhanced during exercise, giving much the same benefits as vigorous pulmonary physiotherapy. These claims have not been investigated. However, it is reasonable to assume that deeper breathing associated with exercise may stimulate more cough. Many studies of exercise programs in chronic lung disease suggest an increased tolerance for
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the specific training exercise, usually walking the treadmill. 3,4, 8, 12, 13, 29, 42, 44, 46. 48, 51, 52 However, only a few studies document an increased aerobic capacity'3, 16,41,44,52 Most studies attribute the improved tolerance for exercise to improved efficiency of movement and better neuromuscular coordination. " 3, 4. 8, 9, 12, 29, 42, 4&-48, 51, 54 Some studies also indicate subjective improvements and changes on personality tests. 3, 8. 13,29,44,46 Thus in patients with chronic lung disease following exercise training, most studies attribute improved tolerance for exercise to nonspecific training effects. All of the above studies were done with adult patients, but results of pediatric studies are similar. Orenstein studied 13 patients with cystic fibrosis before and after a three month program of running. 45 Five improved their tolerance for exercise, and another four performed the same work at a lower heart rate. There were no changes in tests of pulmonary function. A few studies of training through exercise in asthmatic children demonstrate increased tolerance for exercise. 19,43,50 Two of the studies show symptomatic improvement and decreased wheezing. 19, 50 In one study, asthmatic children were trained by running and demonstrated a decrease in exercise-induced asthma. 43 In another in which swimming was used for training, the children showed increased endurance while swimming, but no change in exercise-induced asthma following running. 19 Only one study measured endurance of the ventilatory muscles before and after a general exercise program in patients with chronic lung disease. 36 Seven patients with cystic fibrosis participating in an intensive swimming and canoeing program for four weeks at a summer camp improved endurance of ventilatory muscles 57 per cent. 35 Thus general exercise training in pediatric patients with chronic lung disease results in a substantial increase in endurance of ventilatory muscles. Although the specific exercise used in this study involved the upper body, any aerobic exercise of sufficient intensity will probably also improve endurance of ventilatory muscles. 35, 39 In retrospect, improvement in endurance of ventilatory muscles probably occurred in all studies of patients with chronic lung disease undergoing exercise trianing, although it was not measured, and this was probably partly responsible for the improved tolerance for exercise in all these patients. Once specific training of the ventilatory muscles is stopped, half the training gains are lost after six weeks of inactivity.36 Presumably, the same is true of gains in endurance of ventilatory muscles following training with general aerobic exercise. Thus, training must be continued to maintain the benefits derived. This is an important point which has not been generally applied. Prolonged effects of exercise training programs have not been rigorously studied in patients with lung disease. There are no data on whether exercise training affects ultimate survival in pediatric patients with chronic lung disease.
Exercise Programs for Pediatric Patients with Lung Disease The goals of exercise training programs in chronic lung disease are usually to improve tolerance for exercise. 3, 4, 8, 12, 13,29,42,44,46,48,51,52
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Endurance of ventilatory muscles can also be improved by aerobic exercise training, and is another goal of exercise programs. 36 Specific training of ventilatory muscles is not required to achieve improved endurance of ventilatory muscles in pediatric patients,36 and need not be used. Pediatric patients with lung disease who are still active can be encouraged to participate in aerobic exercise to the extent they are able. Team sports emphasizing sustained activity, such as soccer or basketball, may be used. Similarly, tennis, squash, raquetball, cycling, hiking, or cross country skiing provide sufficient exercise for endurance in an enjoyable setting. The latter are especially good since the patient can continue these activities into later life. Running or swimming programs are excellent, but the discipline required may be difficult to impose on the average pediatric patient. The exercise should be performed at least 20 to 30 Ininutes per day, four or five days per week, at an intensity sufficient to elevate the heart rate. This is well tolerated by patients. Weight lifting in usual practice is not aerobic exercise, and will not improve endurance. It is the practice of the author to encourage aerobic physical activity in all pediatric patients with lung disease. In more debilitated patients, exercise programs may be desirable to improve tolerance for exercise so that daily activities are more easily performed. The exercise program can be structured around the specific activity which is most useful to the individual patient. In most cases, this is walking. Thus treadmill exercise is commonly used. Tolerance for exercise is difficult to predict from tests of pulmonary function at rest. Thus, it is helpful to measure the patient's maximal tolerance for exercise using a graded exercise stress test. 33 It should be noted that maximal heart rates may not be achieved if exercise is primarily liInited by lung disease. Direct measurement of maximal oxygen consumption is the measure of a patient's endurance. In severely debilitated patients, the length of time a patient can exercise at a low workload may be a more meaningful index of progress. Since arterial desaturation may occur near maximal exercise in patients with severe abnormalities of gas exchange, exercise testing should be performed with continuous oxygen monitoring using an ear oximeter or transcutaneous oxygen electrode. For training, a workload which can be tolerated for 20 minutes should be chosen. Initially, some patients may not be able to exercise at any workload for that period of time However, the length of time may improve with training. Once the patient can tolerate 20 Ininutes of exercise at a given workload, the stress can be gradually increased. When the patient has achieved a level of fitness which allows him to perform daily activities, the exercise program should be adapted for continued use at home to maintain fitness. Failure to encourage continued exercise outside the hospital may result in a loss of the fitness gained by the exercise program. Breathing exercises emphasizing breathing techniques, such as diaphragmatic breathing, are not replacements for training programs using aerobic exercise. These exercises attempt to train the patient to use ventilatory muscles more efficiently, but do not alter the strength or endurance of ventilatory muscles. These techniques are controversial, and it is beyond the scope of this article to discuss them. 26 Singing
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and playing wind instruments have also been advocated. 18 These may affect patterns of use of ventilatory muscles but there is no evidence that they alter tolerance for exercise or the strength or endurance of ventilatory muscles. Oxygen-Assisted Exercise Some hypoxic patients with chronic lung disease can improve tolerance for exercise by breathing supplemental oxygen. 3 • 6. 15.42.47.53 Supplemental oxygen is especially useful when the patient's tolerance for exercise is so low that daily activities are performed with difficulty or not at all. Oxygen can be given by nasal cannula or mask from a portable oxygen supply.3. 6. 15. 42. 47.53 It is important to measure oxygen requirements during exercise since they cannot be extrapolated from resting values. Arterial blood gases, arterialized blood gases, measurements by ear oximeter, or transcutaneous oxygen electrode during exercise may all be effective. Arterial oxygen tensions well above 100 mm of mercury at rest may be required to prevent arterial desaturation during even light exercise in severely affected patients. Further, the activity level of the pediatric patient cannot always be accurately predicted in advance, so that a margin of safety is recommended. This is especially true of the rare patient requiring supplemental oxygen even at rest. For example, on adequate supplemental oxygen to maintain a Pa02 of 100 at rest, a patient of the author becomes cyanotic and disoriented from hypoxia while fighting with his brother. Sibling rivalry cannot usually be predicted in advance. An exercise program while the patient is receiving supplemental oxygen may further increase tolerance for exercise. 3.46.4 7 As tolerance for exercise improves with training, oxygen requirements may need to be reassessed. In some cases, a given patient might be more active if his supplemental oxygen were increased. Summary Training programs employing aerobic exercise improve tolerance for exercise of patients with chronic lung disease. Parameters of pulmonary function are not changed following exercise training. However, endurance of ventilatory muscles and resistance to fatigue do improve with aerobic training. The improved endurance of ventilatory muscles may be a reason for the improved tolerance for exercise in patients with chronic lung disease following training with exercise. Children with chronic lung disease can probably achieve the same benefits by participating in aerobic sports activities (tennis, squash, raquetball, cycling, hiking, swimming, cross country skiing, or running). More debilitated patients may require a more structured program of exercise. Some hypoxic patients may also require supplemental oxygen to improve tolerance for exercise to the point where daily activities can be easily performed. The effects of physical training are not maintained if exercise is stopped. Thus, exercise programs should be designed in such a way that patients will continue to exercise on their own outside the hospital or clinic. Improvement of tolerance for exercise by a training program of aerobic exercise may significantly
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improve the rehabilitative potential and quality of life for some pediatric patients with chronic lung disease. Whether exercise training improves survival in pediatric patients with lung disease is not known.
REFERENCES 1. Alpert, J. S., Bass, H., Szucs, M. S., et al.: Effects of phYSical training on hemodynamics and pulmonary function at rest and during exercise in patients with chronic obstructive pulmonary disease. Chest, 66:647, 1974. 2. American College of Sports Medicine: Position statement on the recommended quantity and quality of exercise for developing and maintaining fitness in healthy adults. Med. Sci. Sports, 1O(3):vii, 1978. 3. Barach, A. L.: Oxygen supported exercise and rehabilitation of patients with chronic obstructive lung disease. Ann. Allergy, 24:51, 1966. 4. Bass, H., Whitcomb, J. F., and Forman, R.: Exercise training: therapy for patients with chronic obstructive pulmonary disease. Chest, 57:116,1970. 5. Belman, M. J., and Mittman, C.: Ventilatory muscle training improves exercise endurance in chronic obstructive pulmonary disease patients (abstract). Clin. Res., 27:54, 1979. 6. Bradley, B. L., Garner, A. E., Billiu, D., et aI.: Oxygen-assisted exercise in chronic obstructive lung disease. Am. Rev. Resp. Dis., 118 :239, 1978. 7. Bradley, M. E., and Leith, D. E.: Ventilatory muscle training and oxygen cost of sustained hyperpnea. J. AppI. Physiol.: Respirat. Environ. Exercise PhysioI., 45:885, 1978. 8. Brundin, A.: Physical training in severe chronic obstructive lung disease. I. Clinical course, physical working capacity, and ventilation. Scand. J. Resp. Dis., 55:25, 1974. 9. Brundin, A.: Physical training in severe chronic obstructive lung disease. II. Observations on gas exchange. Scand. J. Resp. Dis., 55:37, 1974. 10. Burke, R. E., Levine, D. N., Tsairis, P., et al.: Physiological types and histochemical profiles in motor units of the cat gastrocnemius. J. PhysioI., 234:723, 1973. 11. Cherniack, R. M.: Oxygen cost of breathing as a limiting factor in physical performance. Proc. Int. Symp. Cardiovasc. Respir. Effects. Hypoxia. Kingston, Ontario, 1965, pp. 346-359. 12. Chester, E. H., Belman, M. J., Bahler, R. C., et al.: Multidisciplinary treatment of chronic pulmonary insufficiency. III. The effect of physical training on cardiopulmonary performance in patients with chronic obstructive pulmonary disease. Chest, 72:695,1977. 13. Christie, D.: Physical training in chronic obstructive lung disease. Br. Med. J., 2:150, 1968. 14. Clark, T. J. H., Freedman, S., Campbell, E. J. M., et al.: The ventilatory capacity of patients with chronic airways obstruction. Clin. Sci., 36:307, 1969. 15. Cotes, J. E., and Gilson, J. C.: Effect of oxygen on exercise ability in chronic respiratory insufficiency. Lancet, 1 :872, 1956. 16. Degre, S., Sergysels, R., Messin, R., et aI.: Hemodynamic responses to physical training in patients with chronic lung disease. Am. Rev. Resp. Dis., 110:395, 1974. 17. Faulkner, J. A.: New perspectives in training for maximal performance. J.A.M.A., 205:741, 1968.
18. Finney, G.: Vocal exercise and nineteenth-century hygiene in France. Clio Med. 12:147,1977. 19. Fitch, K. D., Morton, A. R., and Blanksby, B. A.: Effects of swimming training on children with asthma. Arch. Dis. Child., 51 :190, 1976. 20. Fitts, R. H., Booth, F. W., Winder, W. W., et al.: Skeletal muscle respiratory capacity, endurance, and glycogen utilization. Am. J. Physiol., 228:1029,1975. 21. Gabriel, S.: The physical working capacity in patients with chronic obstructive and restrictive lung disease. Scand. J. Resp. Dis. (Suppl.), 77: 130, 1971. 22. Geubelle, F., and Jovanovic, M.: Specific factors limiting exercise in children with respiratory disease. Scand. J. Resp. Dis. (SuppI.), 77: 112, 1971. 23. Godfrey, S., and Mearns, M.: Pulmonary function and response to exercise in cystic fibrosis. Arch. Dis. Child., 46:144, 1971. 24. Goldspink, G., Larson, R. F., and Davies, R. E.: The immediate energy supply and the cost of maintenance of isometric tension for different muscles in the hamster. Z. Vergleich PhysioI., 66:389, 1970. 25. Gollnick, P. D., Armstrong, R. G., Saltin, R., et al.: Effect of training on enzyme activity and fiber composition of human skeletal muscle. J. Appl. Physiol., 34:107,1973. 26. Grimby, G.: Aspects of lung expansion in relation to pulmonary physiotherapy. Am. Rev. Resp. Dis. (SuppI.), 110:145,1974.
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27. Grimby, G.: Peripheral limiting factors during exercise in chronic lung diseases. Bull. Europ. Physiopath. Resp., 13 :381, 1977. 28. Gross, D., Riley, E., Grassino, A., et al.: Influence of resistive training on respiratory muscle strength and endurance in quadriplegia (abstract). Am. Rev. Resp. Dis., 117:343, 1978. 29. Guthrie, A. G., and Petty, T. L.: Improved exercise tolerance in patients with chronic airway obstruction. Phys. Therap., 50:1333, 1970. 30. Hickson, R. C., Bomze, H. A., and Holloszy, J. 0.: Linear increase in aerobic power induced by a strenuous program of endurance exercise. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol., 42:372, 1977. 31. Hickson, R. C., Bomze, H. A., and Holloszy, J. 0.: Faster adjustment of O2 uptake to the energy requirement of exercise in the trained state. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol., 44:877, 1978. 32. Holloszy, J. 0.: Biochemical adaptations in muscle. J. BioI. Chern., 242:2278, 1967. 33. Jones, N. L., Jones, G., and Edwards, R. H. T.: Exercise tolerance in chronic airway obstruction. Am. Rev. Resp. Dis., 103 :477, 1971. 34. Jonson, B.: Pulmonary mechanics as a factor limiting the capacity for work in disease. Scand. J. Resp. Dis. (Suppl.), 77:94, 1971. 35. Keens, T. G., Chen, V., Patel, P., et al.: Cellular adaptations of the ventilatory muscles to a chronic increased respiratory load. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol.,44:905, 1978. 36. Keens, T. G., Krastins, 1. R. B., Wannamaker, E. M., et al.: Ventilatory muscle endurance training in normal subjects and patients with cystic fibrosis. Am. Rev. Resp. Dis., 116:853, 1977. 37. Leith, D. E., and Bradley, M.: Ventilatory muscle strength and endurance training. J. Appl. Physiol., 44 :508, 1976. 38. Levison, H., and Cherniack, R. M.: Ventilatory cost of exercise in chronic obstructive pulmonary disease. J. Appl. Physiol., 25:21, 1968. 39. Lieberman, D. A., Maxwell, L. C., and Faulkner, J. A.: Adaptation of guinea pig diaphragm muscle to aging and endurance training. Am. J. Physiol., 222:556, 1972. 40. Macklem, P. T., and Roussos, C. S.: Respiratory muscle fatigue: a cause of respiratory failure? Clin. Sci. Mol. Med., 53:419,1977. 41. Mertens, D. J., Shephard, R. J., and Kavanagh, T.: Long-term exercise therapy for chronic obstructive lung disease. Respiration, 35:96,1978. 42. Miller, W. F., Taylor, H. F., and Jasper, L.: Exercise training in the rehabilitation of patients with severe respiratory insufficiency due to pulmonary emphysema: the role of oxygen breathing. South. Med. J., 55: 1216, 1962. 43. Miller, W. W., Schneider, M., Miller, L. C., et al.: Physical training effects on exerciseinduced asthma (abstract). Med. Sci. Sports, 10:48, 1978. 44. Nicholas, J. J., Gilbert, R., Gabe, R., et al.: Evaluation of an exercise therapy program for patients with chronic obstructive pulmonary disease. Am. Rev. Resp. Dis., 102:1, 1970. 45. Orenstein, D., Franklin, B., Germann, K., et al.: Exercise studies in cystic fibrosis patients (abstract). Med Sci. Sports, 11 :(in press, 1979). 46. Paez, P. N., Phillipson, E. A., Masangkay, M., et al.: The physiologic basis of training patients with emphysema. Am. Rev. Resp. Dis., 95:944, 1967. 47. Pierce, A. K., Paez, P. N., and Miller, W. F.: Exercise training with the aid of a portable oxygen supply in patients with emphysema. Am. Rev. Resp. Dis., 91 :653, 1965. 48. Pierce, A. K., Taylor, H. F., Archer, R. K., et al.: Responses to exercise training in patients with emphysema. Arch. Intern. Med., 113:28, 1964. 49. Roussos, C. S., and Macklem, P. T.: Diaphragmatic fatigue in man. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol., 43:189, 1977. 50. Sly, R. M., Harper, R. T., and Rosselot, 1.: The effect of physical conditioning upon asthmatic children. Ann. Allergy, 30:86, 1972. 51. Smodlaka, V. N., and Adamovich, D. R.: Reconditioning of emphysema patients using interval training. N. Y. State J. Med., 74:951,1974. 52. Vyas, M. N., Banister, E. W., Morton, J. W., et al.: Response to exercise in patients with chronic airway obstruction. I. Effects of exercise training. Am. Rev. Resp. Dis., 103:390,1971. 53. Vyas, M. N., Banister, E. W., Morton, J. W., et al.: Response to exercise in patients with chronic airway obstruction. II. Effects of breathing 40 per cent oxygen. Am. Rev. Resp. Dis., 103:401,1971. 54. Woolf, C. R., and Suero, J. T.: Alterations in lung mechanics and gas exchange following training in chronic obstructive lung disease. Dis. Chest, 55:37,1969. Neonatal Respiratory Disease Division Children's Hospital of Los Angeles 4650 Sunset Boulevard Los Angeles, California 90027
Exercise Training Programs for Pediatric Patients with Chronic Lung Disease Thomas G. Keens, M.D.*
Present therapy for chronic lung disease in pediatrics is directed primarily toward preventing pulmonary infection and lung damage. Less emphasis is placed on the ventilatory muscles, which, in some cases, must cope with the significantly increased work of breathing. Respiratory failure can be viewed as inadequate power of ventilatory muscles to overcome increased respiratory loads. Often, lung damage as a result of chronic lung disease cannot be reversed, thus the respiratory load cannot be significantly reduced. However, the strength and endurance of ventilatory muscles can be altered. 5, 7, 36, 37 Intuitively, the pediatric physician dealing with pulmonary disease has known that exercise is good for patients with lung disease, but has attributed its benefits to nonspecific effects such as improved morale, efficiency, and better neuromuscular coordination. 4 , 8, 12, 13, 16, 29, 41, 42, 44, 46, 48, 51, 52, 54 Ventilatory muscles, like other skeletal muscles, may become fatigued, and this may result in respiratory failure. 40, 49 Aerobic exercise programs improve the endurance of ventilatory muscles, thus decreasing their susceptibility to fatigue. 36 This paper will describe the effects of physical conditioning in general and in patients with chronic lung disease. It will discuss the mechanism of these effects, and outline the types of exercise programs which might be effective in pediatric patients with lung disease. Effects of Training with Aerobic Exercise Aerobic exercise requires a prolonged continuous output of muscular work. Running, swimming, cross country skiing, and hiking are examples of aerobic exercise. Aerobic exercise depends on muscle endurance or resistance to fatigue. A muscle is fatigued when it can no longer generate the tension required to perform work. Because performance of muscular work requires energy, fatigue occurs when a mus*Neonatal-Respiratory Disease Division, Children's Hospital of Los Angeles; Assistant Professor of Pediatrics, University of Southern California School of Medicine, Los Angeles, California
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cle has no energy available for contraction. Although muscles store some energy as glycogen, this alone cannot support muscular work for very long. Thus the muscle must be able to produce energy. It can do this either by anaerobic or aerobic metabolism. Anaerobic metabolism of glucose to lactate is a relatively inefficient way to produce energy, and this cannot continue for a very long period of time. Muscles or muscle fibers which depend primarily on anaerobic metabolism fatigue relatively rapidly. 10, 20 Aerobic metabolism of glucose or fatty acids through pyruvate via the Krebs cycle is a relatively efficient way to produce energy. Muscles or muscle fibers which depend primarily on aerobic metabolism are relatively fatigue resistant. 10, 20 Maximal oxygen consumption, or aerobic capacity, is the measure of the capacity of a muscle, or an individual, to do aerobic work. . Training with aerobic exercise increases the aerobic capacity of the muscles that are specifically stressed by the exercise. 3(}-32 In a running program, for example, the leg muscles would improve their aerobic capacity with an increased training stress. 17, 25, 30, 32 The increased aerobic capacity means the muscle can produce more energy as a result of an increase in oxidative enzymes, to, 20, 25, 30·32 and thus can perform a higher level of work before fatiguing. Increased oxygen consumption requires an increased oxygen delivery to the tissues. Thus the heart must increase cardiac output, and this serves as an aerobic training stress for the heart. 17,31 However, only those muscles which participate in the training stress will show an improved aerobic capacity, or training effect. The arm muscles, for example, would not significantly improve in a running program. It requires a minimum of about 20 to 30 minutes per day, four to five days per week, to improve aerobic capacity by aerobic exercise in the average person. 2 ,17 More training will result in a greater response. Conversely, if exercise is stopped, the aerobic capacity will decrease again to the baseline, and the gains of exercise will be lost. Exercise must be continued to maintain increased aerobic capacity.
Limitation of Exercise in Chronic Lung Disease In normal subjects, exercise is probably limited by the aerobic capacity of the working muscles and the heartY Neither the lungs nor the ventilatory muscles are thought to limit exercise in normal persons. However, in patients with chronic lung disease, limitation of exercise is due primarily to lung mechanics. 11, 14,21·23,27,33,34,38 The volume of minute ventilation during exercise may nearly equal the patient's maximal breathing capacity, suggesting that the limits of ventilation are being achieved. 14, 21-23,33,34 Further, the mechanical properties of the diseased lung are such that work of breathing is markedly increased. During exercise, when ventilation requirements are high, the work of breathing is increased to such an extent that oxygen consumption required for the ventilatory muscles alone forms a major fraction of the consumption of oxygen in the total body. 11, 38 At these high workloads, fatigue of the ventilatory muscles during exercise may further contribute to the limitation of exercise. 4o ,49 Once optimal pulmonary
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therapy has been instituted in chronic lung diseases, pulmonary mechanics cannot usually be further improved. However, improvement in the endurance of ventilatory muscles may improve tolerance for exercise in these patients. 5 Training of Ventilatory Muscles Ventilatory muscles, like other skeletal muscles, adapt to increased aerobic training by increasing aerobic capacity.35, 39 Increases in oxidative enzymes have been documented in the ventilatory muscles of rats exposed to chronically increased respiratory loads, indicating increased endurance. 35 A further change in contractile properties toward slow-twitch characteristics also occurred. 35 This represents improved biochemical efficiency of the utilization of energy by these ventilatory muscles, again resulting in improved endurance. 24 Leith and Bradley demonstrated that strength or endurance of ventilatory muscles could be improved by specific exercise programs in man. 7,37 The technique of endurance training for ventilatory muscles involves isocapneic hyperventilation at increasing volumes of minute ventilation at least 20 to 30 minutes per day. This exercise is a specific aerobic training stress for the ventilatory muscles and is accompanied by an increased oxygen consumption of those muscles as training progresses. 5,7 Belman and Mittman have shown that specific endurance training for ventilatory muscles also improves general endurance during exercise in patients with chronic lung disease. 5 The maximal ventilation that can be sustained is increased, thus allowing an increase in the volume of minute ventilation potentially usable during exercise. 5, 36, 37 This technique produces similar changes in children with cystic fibrosis. 36 However, specific endurance training for ventilatory muscles is a tedious therapeutic regimen, requiring a fair amount of equipment, and is not well adapted for use in pediatric patients with chronic lung disease. Gross and coworkers used an inspiratory resistance to train both strength and endurance of the ventilatory muscles in quadriplegic patients. 28 These patients breathed against an inspiratory resistance for 30 minutes per day. Both strength and endurance of the ventilatory muscles improved. There was also an increased resistance to fatigue of these muscles. Effects of Aerobic Exercise Training in Chronic Lung Disease Numerous studies have been performed on the effects of general exercise training in chronic lung disease. 1, 3, 4, 8, 9, 12, 13, 16,29,41, 42, 44, 4648,51,52,54 Uniformly, these studies show no changes in tests of pulmonary function. Thus, exercise programs do not significantly alter pulmonary mechanics. It is the anecdotal experience of many exercise programs that the production of cough and sputum is enhanced during exercise, giving much the same benefits as vigorous pulmonary physiotherapy. These claims have not been investigated. However, it is reasonable to assume that deeper breathing associated with exercise may stimulate more cough. Many studies of exercise programs in chronic lung disease suggest an increased tolerance for
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the specific training exercise, usually walking the treadmill. 3,4, 8, 12, 13, 29, 42, 44, 46. 48, 51, 52 However, only a few studies document an increased aerobic capacity'3, 16,41,44,52 Most studies attribute the improved tolerance for exercise to improved efficiency of movement and better neuromuscular coordination. " 3, 4. 8, 9, 12, 29, 42, 4&-48, 51, 54 Some studies also indicate subjective improvements and changes on personality tests. 3, 8. 13,29,44,46 Thus in patients with chronic lung disease following exercise training, most studies attribute improved tolerance for exercise to nonspecific training effects. All of the above studies were done with adult patients, but results of pediatric studies are similar. Orenstein studied 13 patients with cystic fibrosis before and after a three month program of running. 45 Five improved their tolerance for exercise, and another four performed the same work at a lower heart rate. There were no changes in tests of pulmonary function. A few studies of training through exercise in asthmatic children demonstrate increased tolerance for exercise. 19,43,50 Two of the studies show symptomatic improvement and decreased wheezing. 19, 50 In one study, asthmatic children were trained by running and demonstrated a decrease in exercise-induced asthma. 43 In another in which swimming was used for training, the children showed increased endurance while swimming, but no change in exercise-induced asthma following running. 19 Only one study measured endurance of the ventilatory muscles before and after a general exercise program in patients with chronic lung disease. 36 Seven patients with cystic fibrosis participating in an intensive swimming and canoeing program for four weeks at a summer camp improved endurance of ventilatory muscles 57 per cent. 35 Thus general exercise training in pediatric patients with chronic lung disease results in a substantial increase in endurance of ventilatory muscles. Although the specific exercise used in this study involved the upper body, any aerobic exercise of sufficient intensity will probably also improve endurance of ventilatory muscles. 35, 39 In retrospect, improvement in endurance of ventilatory muscles probably occurred in all studies of patients with chronic lung disease undergoing exercise trianing, although it was not measured, and this was probably partly responsible for the improved tolerance for exercise in all these patients. Once specific training of the ventilatory muscles is stopped, half the training gains are lost after six weeks of inactivity.36 Presumably, the same is true of gains in endurance of ventilatory muscles following training with general aerobic exercise. Thus, training must be continued to maintain the benefits derived. This is an important point which has not been generally applied. Prolonged effects of exercise training programs have not been rigorously studied in patients with lung disease. There are no data on whether exercise training affects ultimate survival in pediatric patients with chronic lung disease.
Exercise Programs for Pediatric Patients with Lung Disease The goals of exercise training programs in chronic lung disease are usually to improve tolerance for exercise. 3, 4, 8, 12, 13,29,42,44,46,48,51,52
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Endurance of ventilatory muscles can also be improved by aerobic exercise training, and is another goal of exercise programs. 36 Specific training of ventilatory muscles is not required to achieve improved endurance of ventilatory muscles in pediatric patients,36 and need not be used. Pediatric patients with lung disease who are still active can be encouraged to participate in aerobic exercise to the extent they are able. Team sports emphasizing sustained activity, such as soccer or basketball, may be used. Similarly, tennis, squash, raquetball, cycling, hiking, or cross country skiing provide sufficient exercise for endurance in an enjoyable setting. The latter are especially good since the patient can continue these activities into later life. Running or swimming programs are excellent, but the discipline required may be difficult to impose on the average pediatric patient. The exercise should be performed at least 20 to 30 Ininutes per day, four or five days per week, at an intensity sufficient to elevate the heart rate. This is well tolerated by patients. Weight lifting in usual practice is not aerobic exercise, and will not improve endurance. It is the practice of the author to encourage aerobic physical activity in all pediatric patients with lung disease. In more debilitated patients, exercise programs may be desirable to improve tolerance for exercise so that daily activities are more easily performed. The exercise program can be structured around the specific activity which is most useful to the individual patient. In most cases, this is walking. Thus treadmill exercise is commonly used. Tolerance for exercise is difficult to predict from tests of pulmonary function at rest. Thus, it is helpful to measure the patient's maximal tolerance for exercise using a graded exercise stress test. 33 It should be noted that maximal heart rates may not be achieved if exercise is primarily liInited by lung disease. Direct measurement of maximal oxygen consumption is the measure of a patient's endurance. In severely debilitated patients, the length of time a patient can exercise at a low workload may be a more meaningful index of progress. Since arterial desaturation may occur near maximal exercise in patients with severe abnormalities of gas exchange, exercise testing should be performed with continuous oxygen monitoring using an ear oximeter or transcutaneous oxygen electrode. For training, a workload which can be tolerated for 20 minutes should be chosen. Initially, some patients may not be able to exercise at any workload for that period of time However, the length of time may improve with training. Once the patient can tolerate 20 Ininutes of exercise at a given workload, the stress can be gradually increased. When the patient has achieved a level of fitness which allows him to perform daily activities, the exercise program should be adapted for continued use at home to maintain fitness. Failure to encourage continued exercise outside the hospital may result in a loss of the fitness gained by the exercise program. Breathing exercises emphasizing breathing techniques, such as diaphragmatic breathing, are not replacements for training programs using aerobic exercise. These exercises attempt to train the patient to use ventilatory muscles more efficiently, but do not alter the strength or endurance of ventilatory muscles. These techniques are controversial, and it is beyond the scope of this article to discuss them. 26 Singing
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and playing wind instruments have also been advocated. 18 These may affect patterns of use of ventilatory muscles but there is no evidence that they alter tolerance for exercise or the strength or endurance of ventilatory muscles. Oxygen-Assisted Exercise Some hypoxic patients with chronic lung disease can improve tolerance for exercise by breathing supplemental oxygen. 3 • 6. 15.42.47.53 Supplemental oxygen is especially useful when the patient's tolerance for exercise is so low that daily activities are performed with difficulty or not at all. Oxygen can be given by nasal cannula or mask from a portable oxygen supply.3. 6. 15. 42. 47.53 It is important to measure oxygen requirements during exercise since they cannot be extrapolated from resting values. Arterial blood gases, arterialized blood gases, measurements by ear oximeter, or transcutaneous oxygen electrode during exercise may all be effective. Arterial oxygen tensions well above 100 mm of mercury at rest may be required to prevent arterial desaturation during even light exercise in severely affected patients. Further, the activity level of the pediatric patient cannot always be accurately predicted in advance, so that a margin of safety is recommended. This is especially true of the rare patient requiring supplemental oxygen even at rest. For example, on adequate supplemental oxygen to maintain a Pa02 of 100 at rest, a patient of the author becomes cyanotic and disoriented from hypoxia while fighting with his brother. Sibling rivalry cannot usually be predicted in advance. An exercise program while the patient is receiving supplemental oxygen may further increase tolerance for exercise. 3.46.4 7 As tolerance for exercise improves with training, oxygen requirements may need to be reassessed. In some cases, a given patient might be more active if his supplemental oxygen were increased. Summary Training programs employing aerobic exercise improve tolerance for exercise of patients with chronic lung disease. Parameters of pulmonary function are not changed following exercise training. However, endurance of ventilatory muscles and resistance to fatigue do improve with aerobic training. The improved endurance of ventilatory muscles may be a reason for the improved tolerance for exercise in patients with chronic lung disease following training with exercise. Children with chronic lung disease can probably achieve the same benefits by participating in aerobic sports activities (tennis, squash, raquetball, cycling, hiking, swimming, cross country skiing, or running). More debilitated patients may require a more structured program of exercise. Some hypoxic patients may also require supplemental oxygen to improve tolerance for exercise to the point where daily activities can be easily performed. The effects of physical training are not maintained if exercise is stopped. Thus, exercise programs should be designed in such a way that patients will continue to exercise on their own outside the hospital or clinic. Improvement of tolerance for exercise by a training program of aerobic exercise may significantly
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improve the rehabilitative potential and quality of life for some pediatric patients with chronic lung disease. Whether exercise training improves survival in pediatric patients with lung disease is not known.
REFERENCES 1. Alpert, J. S., Bass, H., Szucs, M. S., et al.: Effects of phYSical training on hemodynamics and pulmonary function at rest and during exercise in patients with chronic obstructive pulmonary disease. Chest, 66:647, 1974. 2. American College of Sports Medicine: Position statement on the recommended quantity and quality of exercise for developing and maintaining fitness in healthy adults. Med. Sci. Sports, 1O(3):vii, 1978. 3. Barach, A. L.: Oxygen supported exercise and rehabilitation of patients with chronic obstructive lung disease. Ann. Allergy, 24:51, 1966. 4. Bass, H., Whitcomb, J. F., and Forman, R.: Exercise training: therapy for patients with chronic obstructive pulmonary disease. Chest, 57:116,1970. 5. Belman, M. J., and Mittman, C.: Ventilatory muscle training improves exercise endurance in chronic obstructive pulmonary disease patients (abstract). Clin. Res., 27:54, 1979. 6. Bradley, B. L., Garner, A. E., Billiu, D., et aI.: Oxygen-assisted exercise in chronic obstructive lung disease. Am. Rev. Resp. Dis., 118 :239, 1978. 7. Bradley, M. E., and Leith, D. E.: Ventilatory muscle training and oxygen cost of sustained hyperpnea. J. AppI. Physiol.: Respirat. Environ. Exercise PhysioI., 45:885, 1978. 8. Brundin, A.: Physical training in severe chronic obstructive lung disease. I. Clinical course, physical working capacity, and ventilation. Scand. J. Resp. Dis., 55:25, 1974. 9. Brundin, A.: Physical training in severe chronic obstructive lung disease. II. Observations on gas exchange. Scand. J. Resp. Dis., 55:37, 1974. 10. Burke, R. E., Levine, D. N., Tsairis, P., et al.: Physiological types and histochemical profiles in motor units of the cat gastrocnemius. J. PhysioI., 234:723, 1973. 11. Cherniack, R. M.: Oxygen cost of breathing as a limiting factor in physical performance. Proc. Int. Symp. Cardiovasc. Respir. Effects. Hypoxia. Kingston, Ontario, 1965, pp. 346-359. 12. Chester, E. H., Belman, M. J., Bahler, R. C., et al.: Multidisciplinary treatment of chronic pulmonary insufficiency. III. The effect of physical training on cardiopulmonary performance in patients with chronic obstructive pulmonary disease. Chest, 72:695,1977. 13. Christie, D.: Physical training in chronic obstructive lung disease. Br. Med. J., 2:150, 1968. 14. Clark, T. J. H., Freedman, S., Campbell, E. J. M., et al.: The ventilatory capacity of patients with chronic airways obstruction. Clin. Sci., 36:307, 1969. 15. Cotes, J. E., and Gilson, J. C.: Effect of oxygen on exercise ability in chronic respiratory insufficiency. Lancet, 1 :872, 1956. 16. Degre, S., Sergysels, R., Messin, R., et aI.: Hemodynamic responses to physical training in patients with chronic lung disease. Am. Rev. Resp. Dis., 110:395, 1974. 17. Faulkner, J. A.: New perspectives in training for maximal performance. J.A.M.A., 205:741, 1968.
18. Finney, G.: Vocal exercise and nineteenth-century hygiene in France. Clio Med. 12:147,1977. 19. Fitch, K. D., Morton, A. R., and Blanksby, B. A.: Effects of swimming training on children with asthma. Arch. Dis. Child., 51 :190, 1976. 20. Fitts, R. H., Booth, F. W., Winder, W. W., et al.: Skeletal muscle respiratory capacity, endurance, and glycogen utilization. Am. J. Physiol., 228:1029,1975. 21. Gabriel, S.: The physical working capacity in patients with chronic obstructive and restrictive lung disease. Scand. J. Resp. Dis. (Suppl.), 77: 130, 1971. 22. Geubelle, F., and Jovanovic, M.: Specific factors limiting exercise in children with respiratory disease. Scand. J. Resp. Dis. (SuppI.), 77: 112, 1971. 23. Godfrey, S., and Mearns, M.: Pulmonary function and response to exercise in cystic fibrosis. Arch. Dis. Child., 46:144, 1971. 24. Goldspink, G., Larson, R. F., and Davies, R. E.: The immediate energy supply and the cost of maintenance of isometric tension for different muscles in the hamster. Z. Vergleich PhysioI., 66:389, 1970. 25. Gollnick, P. D., Armstrong, R. G., Saltin, R., et al.: Effect of training on enzyme activity and fiber composition of human skeletal muscle. J. Appl. Physiol., 34:107,1973. 26. Grimby, G.: Aspects of lung expansion in relation to pulmonary physiotherapy. Am. Rev. Resp. Dis. (SuppI.), 110:145,1974.
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27. Grimby, G.: Peripheral limiting factors during exercise in chronic lung diseases. Bull. Europ. Physiopath. Resp., 13 :381, 1977. 28. Gross, D., Riley, E., Grassino, A., et al.: Influence of resistive training on respiratory muscle strength and endurance in quadriplegia (abstract). Am. Rev. Resp. Dis., 117:343, 1978. 29. Guthrie, A. G., and Petty, T. L.: Improved exercise tolerance in patients with chronic airway obstruction. Phys. Therap., 50:1333, 1970. 30. Hickson, R. C., Bomze, H. A., and Holloszy, J. 0.: Linear increase in aerobic power induced by a strenuous program of endurance exercise. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol., 42:372, 1977. 31. Hickson, R. C., Bomze, H. A., and Holloszy, J. 0.: Faster adjustment of O2 uptake to the energy requirement of exercise in the trained state. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol., 44:877, 1978. 32. Holloszy, J. 0.: Biochemical adaptations in muscle. J. BioI. Chern., 242:2278, 1967. 33. Jones, N. L., Jones, G., and Edwards, R. H. T.: Exercise tolerance in chronic airway obstruction. Am. Rev. Resp. Dis., 103 :477, 1971. 34. Jonson, B.: Pulmonary mechanics as a factor limiting the capacity for work in disease. Scand. J. Resp. Dis. (Suppl.), 77:94, 1971. 35. Keens, T. G., Chen, V., Patel, P., et al.: Cellular adaptations of the ventilatory muscles to a chronic increased respiratory load. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol.,44:905, 1978. 36. Keens, T. G., Krastins, 1. R. B., Wannamaker, E. M., et al.: Ventilatory muscle endurance training in normal subjects and patients with cystic fibrosis. Am. Rev. Resp. Dis., 116:853, 1977. 37. Leith, D. E., and Bradley, M.: Ventilatory muscle strength and endurance training. J. Appl. Physiol., 44 :508, 1976. 38. Levison, H., and Cherniack, R. M.: Ventilatory cost of exercise in chronic obstructive pulmonary disease. J. Appl. Physiol., 25:21, 1968. 39. Lieberman, D. A., Maxwell, L. C., and Faulkner, J. A.: Adaptation of guinea pig diaphragm muscle to aging and endurance training. Am. J. Physiol., 222:556, 1972. 40. Macklem, P. T., and Roussos, C. S.: Respiratory muscle fatigue: a cause of respiratory failure? Clin. Sci. Mol. Med., 53:419,1977. 41. Mertens, D. J., Shephard, R. J., and Kavanagh, T.: Long-term exercise therapy for chronic obstructive lung disease. Respiration, 35:96,1978. 42. Miller, W. F., Taylor, H. F., and Jasper, L.: Exercise training in the rehabilitation of patients with severe respiratory insufficiency due to pulmonary emphysema: the role of oxygen breathing. South. Med. J., 55: 1216, 1962. 43. Miller, W. W., Schneider, M., Miller, L. C., et al.: Physical training effects on exerciseinduced asthma (abstract). Med. Sci. Sports, 10:48, 1978. 44. Nicholas, J. J., Gilbert, R., Gabe, R., et al.: Evaluation of an exercise therapy program for patients with chronic obstructive pulmonary disease. Am. Rev. Resp. Dis., 102:1, 1970. 45. Orenstein, D., Franklin, B., Germann, K., et al.: Exercise studies in cystic fibrosis patients (abstract). Med Sci. Sports, 11 :(in press, 1979). 46. Paez, P. N., Phillipson, E. A., Masangkay, M., et al.: The physiologic basis of training patients with emphysema. Am. Rev. Resp. Dis., 95:944, 1967. 47. Pierce, A. K., Paez, P. N., and Miller, W. F.: Exercise training with the aid of a portable oxygen supply in patients with emphysema. Am. Rev. Resp. Dis., 91 :653, 1965. 48. Pierce, A. K., Taylor, H. F., Archer, R. K., et al.: Responses to exercise training in patients with emphysema. Arch. Intern. Med., 113:28, 1964. 49. Roussos, C. S., and Macklem, P. T.: Diaphragmatic fatigue in man. J. Appl. Physiol.: Respirat. Environ. Exercise Physiol., 43:189, 1977. 50. Sly, R. M., Harper, R. T., and Rosselot, 1.: The effect of physical conditioning upon asthmatic children. Ann. Allergy, 30:86, 1972. 51. Smodlaka, V. N., and Adamovich, D. R.: Reconditioning of emphysema patients using interval training. N. Y. State J. Med., 74:951,1974. 52. Vyas, M. N., Banister, E. W., Morton, J. W., et al.: Response to exercise in patients with chronic airway obstruction. I. Effects of exercise training. Am. Rev. Resp. Dis., 103:390,1971. 53. Vyas, M. N., Banister, E. W., Morton, J. W., et al.: Response to exercise in patients with chronic airway obstruction. II. Effects of breathing 40 per cent oxygen. Am. Rev. Resp. Dis., 103:401,1971. 54. Woolf, C. R., and Suero, J. T.: Alterations in lung mechanics and gas exchange following training in chronic obstructive lung disease. Dis. Chest, 55:37,1969. Neonatal Respiratory Disease Division Children's Hospital of Los Angeles 4650 Sunset Boulevard Los Angeles, California 90027