Exercise tolerance and exercise conditioning in children with chronic lung disease

Exercise tolerance and exercise conditioning in children with chronic lung disease D a v i d M, O r e n s t e i n , MD From the Department of Pediatrics, University of Pittsburgh School of Medicine

In this article I will discuss recent work that sheds light on the responses tO exercise in children with chronic pulmonary disorders, especially cystic fibrosis and asthma. I will discuss both the acute responses to a single bout of exercise (exercise tolerance) and the longer-term responses to repeated bouts of exercise (exercise conditioning). The studies should make it clear that with proper management, these children can safely participate in exercise programs, and can gain at least the same benefits as normal children. BACKGROUND EXERCISE PHYSIOLOGY Aerobic or endurance exercise is exercise for which the energy requirements can be met entirely or nearly entirely through aerobic (oxygen-dependent) pathways. This type of exercise lasts longer than 30 seconds and is of low or moderate intensity. Exercise of higher intensity exceeds the oxygen delivery and utilization capacity of the organism and therefore must depend on non-oxygen-dependent (anaerobic) metabolism. Similarly, exercise of very short duration, or stop-and-go exercise, takes place before the cardiovascular system has redistributed blood flow to newly exercising muscle and therefore is anaerobic exercise. Aerobic exercise tolerance is dependent on the various links in the oxygen intake-delivery-utilization chain, and aerobic fitness is most often defined in terms of maximum oxygen uptake, or consumption.1 Aerobic exercise tolerance, depending as it does on the oxygen delivery chain, can be limited by the weakest link in that chain. This consideration is often overlooked when the weak link is the respiratory system. During exercise testing with progressively increasing loads to exhaustion, normal children are usually limited by

Reprint requests: David M. Orenstein, MD, Children's Hospital of Pittsburgh, One Children's Place, 3705 Fifth Ave. at DeSoto St., Pittsburgh, PA 15213.

their cardiovascular systems. At the point of exhaustion, heart rate has usually reached an age-determined maximum value (about 200 _+ 10 beats/rain in most children and adolescents; roughly 220 minus age in years in adults). 2 The exercising muscle itself may also contribute to limiting exercise if it cannot process any more oxygen (this, in turn, is dependent on the density of mitochondria, filled with oxidative enzymes). Even at exhaustion, the DLco EIA FEVI MVV PFT VC Vo2max

Diffusing capacity for carbon monoxide Exercise-induced asthma Forced expired volume in one second Maximum voluntary ventilation Pulmonary function test Vital capacity Minute ventilation Maximum oxygen consumption

pulmonary system almost never is a limiting factor in normal children and adolescents. An indication of the tremendous ventilatory reserve is the low minute ventilation employed even at a heart rate of >--200 beats/rain. VE seldom exceeds 70% of the resting maximum voluntary ventilation? Aerobic fitness is often defined in terms of "~o2; increased aerobic fitness resulting from exercise conditioning is seen as an increase in Vo2max. The increase in oxygen consumption comes from increases in both oxygen delivery to exercising muscle (cardiovascular system) and oxygen use by the muscles. Although both the cardiovascular system and muscles can increase their capacity with aerobic exercise conditioning, the respiratory system probably cannot.4 Conditioning most likely does not alter the maximum heart rate, but it brings about a tremendous potential for increased cardiac output by increasing cardiac stroke volume. Therefore the same number of heartbeats produces a much greater total output. Conversely, a similar oxygen requirement can be met with a much lower

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The Journal of Pediatrics June 1988

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Fig. 4. Selected initial exercise data on all patients in study, including maximum heart rate (HRm,,~), at maximum peak oxygen consumption (ml/kg/min), and proportion of maximum breathing capacity used during maximum exercise. Broken lines indicate group means; boxed areas indicate norm~.lranges. (From Orenstein DM, Franklin BA, Doershuk CF, et al. Chest 1981;80:392-8.)

heart rate. In fact, a decreased heart rate for a similar submaximum work load--termed a training bradycardia--is a hallmark of increased aerobic fitness. Muscle mitochondrial density also increases with conditioning, resulting in an increase in oxidative enzyme capacity. More oxygenated blood can therefore be delivered to the exercising muscle, and more of that delivered oxygen can be used in the production of energy for muscle contraction. CYSTIC FIBROSIS Exercise tolerance. Studies from our laboratory and others have confirmed Godfrey and Mearns's~observations from the early 1970s that patients with cystic fibrosis reach exhaustion in a progressive exercise test before they have reached an age-predicted maximum heart rate. Nevertheless, many have had to employ much, if not all, of their ventilatory capacity, with "~E even exceeding their MVV. This combination of a relatively low maximum heart rate and a high ~'E/MVV ratio demonstrates that in these patients it is ventilatory factors that limit exercise tolerance, and they do so before the cardiovascular system has been pushed to its limit. Fig. 1 illustrates the results of progressive exercise tests to exhaustion in a typical group of patients with cystic fibrosis with a wide range of disease severity. There is a tremendous range of fitness and exercise

tolerance among patients with cystic fibrosis, from the nearly bedridden to the very athletic. With a large group of patients, there is a very high correlation between resting pulmonary function and exercise tolerance. However, there is great individual variation, making the resting pulmonary function test result a poor predictor of exercise tolerance in the individual patient. This is not to imply that pulmonary function does not influence exercise tolerance in the individual but, rather, that the exact relationship between PFT results and exercise tolerance differs from patient to patient. Cerny et al. 6 demonstrated what most patients with cystic fibrosis report, namely, that changing pulmonary function changes exercise tolerance in individual patients. They studied 17 patients with cystic fibrosis at the beginning and end of a 2-week hospitalization for intensive treatment Of pulmonary exacerbations. The patients achieved much higher workloads, markedly improved Vozmax, and a lower perception of exertion when their pulmonary function had improved. Gas exchange. There has been some controversy concerning gas exchange during exercise in patients with cystic fibrosis. Godfrey and Mearns 5 first indicated an improvement, with decreased venous admixture. Cerny et al. 7 found, to the contrary, that patients with severe lung disease had predictable desaturation during exercise. We then studied a larger group of patients and found a different pattern (Fig. 2): of our 91 patients, none had

Volume 112 Number 6

Exercise tolerance and conditioning in chronic lung disease

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desaturation during exercise if they had resting forced expired volume in I second greater than 50% of the forced vital capacity. 8 Even those whose FEV~/VC ratio was less than 50% were just as likely to maintain their oxyhemoglobin saturation at preexercise levels or even to increase them as they were to have desaturation. However, some of the patients in this severely obstructed group did have marked desaturation. Lebecque et al? found the diffusing capacity for carbon monoxide to serve a similar predictive role: patients with DLco >80% of the predicted value could be predicted not to be at risk for desaturation during exercise; yet those whose diffusing caPacity was <65% of the predicted value all had desaturation. Unfortunately, not all pulmonary function laboratories are equipped to measure DLco in children (and some children may be too sick or too small to perform the test even if the laboratory is suitably equipped). We therefore advise exercis e testing with oxyhemoglobin saturation monitoring in patients with an FEV1/VC ratio <50% to identify patients with desaturation, so that they can be counseled to exercise at an intensity below that which causes desaturation. The role of supplemental oxygen to prevent exercise desaturation or

improve exercise tolerance or both has not yet been adequately studied in patients with cystic fibrosis. Exercise in the heat. Cystic fibrosis patients have been known, since the mid-1950s, to have greater than normal concentrations of sodium and chloride in their sweat) ~ but only relatively recently has the performance of cystic fibrosis patients' sweat glands during exercise and heat stress been studied.".lZ Not surprisingly, CF patients lost more than normal amounts of sodium and chloride when they exercised for 90 minutes in the heat (100 ~ F, 38 ~ C), so much so that they showed decreased serum sodium and chloride concentrations. However, patients have superb homeostatic control: within 24 hours after the 90-minute exercise and heat stress, body weight and serum electrolytes were back to baseline when patients were given a free choice of fluid and food. Repeated bouts of exercise and heat stress bring about considerable heat acclimation in patients with cystic fibrosis, so that they are able to perform the same task with lower body temperatures and lower heart rates, but patients with cystic fibrosis are not able to decrease the sodium and chloride concentrations of their sweat as normal subjects can. lz

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ASTHMA Exercise-induced asthma. The phenomenon of shortness of breath after vigorous exercise has been recognized for centuries, and for decades it has been recognized that bronchoconstriction after exercise runs a typical course. It occurs after exercise, is most likely to occur after running, is less likely after walking or cycling, and is least likely after swimming; it is more likely to occur after 6 to 8 minutes of fairly intense exercise (heart rate around 170 beats/min), and less likely to occur after shorter or longer bouts or after less intense exercise~3; and it is much more likely to occur in cold air. ~4 Only relatively recently has some of the pathophysiology of this phenomenon become clear. Deal et al., ~5-~7in a series of studies, showed that inhalation of cold dry air resulted in the delivery of relatively cold dry air to the carina. This finding refutes the common belief that the upper airway is always 100% efficient in its role as an organ of heat exchange, delivering only fully humidified, 37 ~ C air to the bronchi. Deal et al. next showed (1) that the degree of postexercise bronchoconstriction produced by a given intensity of exercise could be reproduced precisely at rest by the inhalation of cold dry air at the same VE employed during exercise and (2) that it could be abolished (after both resting hyperpnea and exercise) with the inhalation of air that was humidified and warmed to body temperature. Thus it appears that EIA has more to do with the temperature and/or humidity of tlle air that reaches the bronchi than with exercise itself. Almost certainly, the "protective" effect of swimming must relate to the high humidity of the inspired air. Prevention of exercise-induced asthma. Prevention of EIA can be accomplished in the large majority of young patients through several different routes. Pharmacologic means are the most effective and practical. Inhaled betaadrenergic agonists (e.g., albuterol, metaproterenol) administered just before activity are extremely effective for most. ~3Inhaled cromolyn sodium before activity is also effective in many, although not all, patients with EIA~3; it is especially helpful now that it is available in solution and in metered-dose inhalers, and not just the powder (the physical irriation of this form offset the pharmacologic advantages of this drug for many children). Nonpharmacologic approaches may also be useful in preventing EIA in the susceptible individual. Altering life-style is effective, and often employed, but it is not always to be encouraged. If there is no exercise, there will be no EIA, but there will, of course, be none of the benefits of exercise. Many children with asthma have chosen, or have had their parents or teachers choose for them, to omit physical education classes and other opportunities for exercise and are consequently considerably less fit than

The Journal o f Pediatrics June 1988

their peers? 8 Behavior can be altered without limiting physical activity. Swimming or bicycling can be chosen as one's sport, rather than running. Among running events, long slow distance running or short sprints can be chosen in preference to 1-mile and 2-mile races. Cold-air effects can be modified by wrapping a scarf around the nose and mouth, thereby warming the inspired air. The benefits of exercise are so important for children and adults, and prevention of EIA is so easy for the majority of patients, that physicians should encourage their patients with asthma to be active and should not allow themselves to be enlisted in a conspiracy to avoid physical education classes or other activity. E X E R C I S E P R O G R A M S FOR C H I L D R E N WITH PULMONARY DISEASE Cystic fibrosis. Exercise programs have now been shown in several different studies to be of benefit to patients with cystic fibrosis. 19-2~Keens et al. 19 first showed that a program of daily heavy breathing exercises resulted in increased endurance of the ventilatory muscles. Specific upper body exercise (swimming, canoeing) produced similar results. We then showed that a 3-month running program consisting of three 30-minute sessions each week resulted in improved work tolerance, increased fitness (increased 9"ozmax; training bradycardia), improved ventilatory muscle endurance, but no change in resting pulmonary function,z~ Zach et al. z1'22 used different exercise programs, one an intensive swim-training program and the other a camp program of almost constant hiking, swimming, jogging, etc., for 17 days. They demonstrated improved expiratory flow rates, a benefit that was shortlived after cessation of the exercise programs. Edlund et al. z3 also used a swimming program and showed improved exercise tolerance but no improvement in resting pulmonary function. The final answer is not yet in on whether exercise programs can improve pulmonary function or longevity in patients with cystic fibrosis, or whether exercise can substitute for the time-honored but tedious chest physical therapy and postural drainage treatments. There is, however, no doubt that exercise programs can increase physical working capacity in these patients and thus can be expected to improve their quality of life. Asthma. Despite the fact that patients with asthma have often excluded themselves (or have been excluded by others) from many of the normal activities of childhood, it has long been thought that activity was likely to benefit them. However, only within the past few years have the effects of aerobic exercise programs been examined carefully in children/8,24 Like patients with cystic fibrosis, children with asthma can increase their work caPacity.18.24

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Exercise tolerance and conditioning in chronic lung disease

If they are treated with a bronchodilator before each exercise session, they can also increase their aerobic fitness (~'o2max). TMThey probably do not change their susceptibility to EIA, although improved fitness should m e a n a lower "~E for high-ifitensity exercise. This, i n turn, should decrease the stimulus for E I A at a given level of exercise while not altering the reactivity of the airways. T h e 1984 Olympics saw 67 of 597 athletes on the United States team with EIA. They b r o u g h t back 15 gold, 21 silver, and 5 bronze medals, in events as diverse as swimming, shooting, basketball, and track and field? 5 In t h a t same year, three Norwegian teenagers with cystic fibrosis completed the N e w York City m a r a t h o n . 26 N o t every youngster with cystic fibrosis or a s t h m a can achieve these levels of competitive success, but these examples should remind patients, families, and physicians alike t h a t the diagnosis of a s t h m a or cystic fibrosis should not deprive a youngster of the pleasure and physical benefits of exercise.

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1. Shephard RJ. Endurance fitness. Toronto: University of Toronto Press, 1977. 2. Astrand PO, Rodahl K. Textbook of work physiology. New York: McGraw-Hilt, 1977:322-5. 3. Godfrey S. Exercise testing in children. Philadelphia: WB Saunders, t974:68. 4. Astrand PO, Rodahl K. Textbook of work physiology. New York: McGraw-Hill, 1977:395-6. 5. Godfrey S, Mearns M. Pulmonary function and response to exercise in cystic fibrosis. Arch Dis Child 1971;46:144-51. 6. Cerny F J, Cropp GJA, Bye MR. Hospital therapy improves exercise tolerance and lung function in cystic fibrosis. Am J Dis Child 1984;138:26t-5. 7. Cerny F J, Pullano TP, Cropp GJA. Cardiorespiratory adaptations to exercise in cystic fibrosis. Am Rev Respir Dis 1982;126:217-20. 8. Henke KG, Orenstein DM. Oxygen saturation during exercise in cystic fibrosis. Am Rev Respir Dis 1984;129:708-11. 9. Lebecque P, Lapierre JG, Lamarre A, Coates AL. Diffusion capacity and oxygen desaturation effects on exercise in patients with cystic fibrosis. Chest 1987;91:693-7. 10. di Sant'Agnese PA, Darling RC, Perera GA, et al. Abnormal electrolyte composition of sweat in cystic fibrosis of the pancreas. Pediatrics 1953;12:549-63. I 1. Orenstein DM, Henke KG, Costill DL, Doershuk CF, Lemon

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PJ, Stern RC. Exercise and heat stress in cystic fibrosis patients. Pediatr Res 1983;17:267-9. Orenstein DM, Henke KG, Green CG. Heat acclimation in cystic fibrosis. J Appl Physiol: Respir Envrion Exercise Physiol 1984;57:408-12. Fitch KD, Godfrey S. Asthma and athletic performance. JAMA 1976;236:152-7. Strauss RH, McFadden ER, Ingram RH, Jaeger JJ. Enhancement of exercise-induced asthma by cold air. N Engl J Med 1977;297:743-7. Deal EC, McFadden ER, Ingram RH, Strauss RH, Jaeger JJ. Role of respiratory exchange in production of exerciseinduced asthma. J Appl Physiol: Respir Environ Exercise Physiol 1979;46:467-75. Deal EC, McFadden ER, Ingram RH, Jaeger JJ. Hypernea and heat flux: initial reaction sequence in exercise-induced asthma. J Appl Physiol: Respir Environ Exercise Physiol 1979;46:476-83. Deal EC, McFadden ER, Ingram RH, Jaeger JJ. Esophageal temperature during exercise in asthmatic and nonasthmatir subjects. J Appl Physiol: Respir Environ Exercise Physiol 1979;46:484-90. Orenstein DM, Reed ME, Grogan FT, Crawford LV. Exercise conditioning in children with asthma. J PEDIATR 1985; 106:556-60. Keens TG, Krastins IR, Wannamaker EM, et al. Ventilatory muscle endurance training in normal subjects and patients with cystic fibrosis. Am Rev Respir Dis 1977;116:853-60. Orenstein DM, Franklin BA, Doershuk CF, et al. Exercise conditioning and cardiopulmonary fitness in cystic fibrosis: the effects of a three-month supervised running program. Chest 1981 ;80:392-8. Zach MS, Purrer B, Oberwaldner B. Effect of swimming on forced expiration and sputum clearance in cystic fibrosis. Lancet 1981;2:1201-3. Zach M, Oberwaldner B, Hausler F. Cystic fibrosis: physical exercise versus chest physiotherapy. Arch Dis Child 1982; 57:587-9. Edlund LD, French RW, Herbst J J, et al. Effects of a swimming program on children with cystic fibrosis. Am J Dis Child 1986;140:80-3. Nickerson BG, Bautista DB, Namey MA, et al. Distance running improves fitness in asthmatic children without pulmonary complications or changes in exercise-induced bronchospasm. Pediatrics 1983:71 : 147. Monahan T. Sidelined asthmatics get back in the game. Physician Sports Med 1986; 14(5):61-6. Lawson D, ed. CF: Horizons. Proceedings of 9th International Cystic Fibrosis Congress, Brighton, England, June 1984.