Sports medicine pioneers, such as Oded Bar-Or, recognized the need to study exercise risks and benefits in children with chronic disease.1 The Canadian Paediatric Society (CPS) and Canadian Academy of Sport Medicine (CASM) endorse the present statement regarding issues in children with juvenile idiopathic arthritis, hemophilia, asthma, and cystic fibrosis.
JUVENILE IDIOPATHIC ARTHRITIS
Juvenile idiopathic arthritis (JIA) (previously known as juvenile rheumatoid arthritis) has a prevalence of 1 in 10002 children. There are 7 subtypes of JIA, likely representing different pathogenic mechanisms.3 Chronic arthritis is defined by the presence of joint swelling or by 2 or more of the following: joint pain, warmth, and limited range of motion for at least 6 weeks. Constitutional signs or symptoms include anorexia, weight loss, growth failure, and fatigue. Extra-articular manifestations include ocular, cardiac, pulmonary, and hematopoetic involvement. Juvenile idiopathic arthritis persists into adulthood in up to 55% of patients, which may have a major impact on physical or psychosocial function. Children with JIA have reduced vigorous physical activity levels, sports participation, and decreased fitness.4
Muscle atrophy, weakness, and anemia contribute to reduced fitness, but deconditioning from reduced physical activity is likely the greatest cause. Reduced participation because of disease symptom severity, treatment-related side effects, or worries that exercise may aggravate disease are problematic.
Potential Benefits of Exercise
Physical activity should be encouraged in all children. The psychosocial benefits of group participation cannot be understated. Exercise can have positive biological effects by reducing loss of proteoglycans and cartilage damage, and optimizing bone mineral density. Active children have lower obesity risks, which can worsen joint load.
Research suggests children with JIA can participate in aquatic or land-based weight-bearing exercise programs without disease exacerbation.4 Aquatic exercise encourages range of motion, strength and fitness, with less stress on joints. Weight-bearing activity helps promote bone health.
Most published studies are small, not randomized, have great variation in study design and use different exercise modalities. The exercise intensity, frequency, and duration also vary. Despite these differences, the results are generally consistent, suggesting an exercise program (a minimum 6 weeks) improves aerobic fitness; allows better muscle strength and function; decreases disease activity; improves self-efficacy, energy level, and quality of life; and reduces pain and medication use, with no clear effect on function during activities.4-8 Importantly, sports participation does not appear to exacerbate disease.9 The 2002 Exercise and Physical Activity Conference Arthritis Working Group guidelines recommend moderate fitness and strengthening exercises for children with JIA.8
Potential Risks of Exercise
Conventionally, affected children were advised to limit strain on arthritic joints for fear it may aggravate joint pain or swelling, increasing risk of injury. Muscle atrophy surrounding active joints and periarticular osteopenia may increase the risk of fracture. The effect of tissue loading during exercise on joint surfaces and growth plates in children with arthritis is unknown, and requires further study.
Young children with JIA may have gross motor delays, affecting sport readiness. Children with cervical spine arthritis are at greater risk of spinal cord injury (especially during contact sports), and those with temporomandibular joint disease may sustain dental injury. Complications of JIA, such as uveitis and its sequelae (visual impairment), may increase the risk of eye injury. Myocarditis and pericarditis in systemic arthritis, and aortic valve insufficiency or aortic root anomalies in HLA-B27-associated arthritis, may increase the risk of cardiovascular complications with exercise.10
Children with long-standing JIA may have difficulties with endurance sports. Greater submaximal energy expenditures are reported, suggesting increased metabolic demands for routine physical activity.11 A meta-analysis of 5 JIA studies found that aerobic fitness in children with JIA was 22% lower than their healthy peers.12 Most research suggests aerobic fitness is not related to disease severity or activity but rather to disease duration.12-14
Recommendations: Children with Juvenile Idiopathic Arthritis (JIA)
* Can safely participate in sports without disease exacerbation.
* Should participate in moderate fitness, flexibility, and strengthening exercises.
* Can participate in impact activities and competitive contact sports if their disease is well controlled and they have adequate physical capacity.
* Should be encouraged to be physically active as tolerated. Those with moderate to severe impairment or actively inflamed joints should limit activities within pain limits.
* Should gradually return to full activity following a disease flare.
* Should take individualized training (especially for children with severe joint disease) within a group exercise format for physical/social benefit. Physiotherapists on pediatric rheumatology health care teams should coordinate individual exercise programs.
* Should have radiographic screening for C1-C2 instability before participation in collision/contact sports if they have neck arthritis. If present, further evaluation is required.
* Should wear appropriately fitted mouth guards during activities with jaw and dental injury risk (per general population), especially if they have jaw involvement.
* Should wear appropriate eye protection (per general population) during activities with ocular injury risk.
Hemophilia is an X-linked recessive inherited bleeding disorder caused by the absence, deficiency, or dysfunction of plasma coagulation factor VIII or IX. Hemophilia has an incidence of 1 per 5000 newborns. Clinical phenotype and risk of hemorrhage varies from mild to severe, and is related to functional plasma factor levels.15
Children with severe hemophilia (< 1%-2% of normal factor levels) have spontaneous bleeding even without trauma. Joint or muscle hemorrhage, easy bruising, and prolonged bleeding after trauma are common, and severe bleeding (intracranial, vital organs, airway) may occur. Repeated joint hemorrhage causes synovitis, leading to joint degeneration and arthropathy. Hemophilia is characterized by joint contractures, limited range of motion, and chronic pain. The knees, ankles, and elbows are most commonly affected. Prophylactic treatment with the deficient factor reduces spontaneous bleeding and the risk for hemophilic arthropathy.
Potential Benefits of Exercise
Regularly active children at hemophilia camps have fewer bleeding episodes than their sedentary peers.16 Greater muscle strength around affected joints may help to protect joints from hemarthrosis, increase joint stability, and reduce injury risk.17 Prophylactic physical therapy improving periarticular muscle strength was demonstrated to reduce the frequency of hemorrhage.17,18 Proprioceptive training may decrease joint damage and improve athletic performance.19 Weight-bearing exercise can improve bone health in children with severe hemophilia who have reduced bone mineral density.20 Aerobic exercise may have a beneficial effect on coagulation. Vigorous exercise increases factor VIII levels transiently in healthy individuals, and submaximal exercise can modify coagulation parameters in those with mild to moderate hemophilia.21
Potential Risks of Exercise
Fitness, anaerobic power, and muscle strength is lower in children with hemophilia.19,21 Affected children may restrict activity due to parental concern, musculoskeletal pain, or deconditioning. Although hemophilia itself does not negatively affect fitness or athletic performance, chronic hemophilic arthropathy may lead to impaired neuromuscular function, diminished muscle strength, and endurance. Participation in collision or contact sports can result in a life-threatening bleeding event. The actual risk of muscular, articular, and intracranial hemorrhage depends on the individual child's hemorrhagic tendency, history of bleeds, prophylactic treatment, and sport participation.
Recommendations: Children with Hemophilia
* Should receive appropriate factor prophylaxis to reduce the risk of bleeding in sport.
* Should undergo vigilant assessment of joint and muscle function before sport selection. If restrictions are required, physicians should counsel children and their families about safe alternatives.
* Should be carefully assessed before allowing participation in contact or collision sports such as martial arts, hockey, or football. Consultation with a sport medicine physician and/or pediatric hematologist may help.
* Require written strategies (coach, parent, or school) before sport participation to prevent or treat bleeds.
* Should wear protective equipment, undergo physical therapy, or take prophylactic factor replacement therapy.
* Require factor replacement, ice, splinting, and rest to manage acute bleeds. Physical activity should be avoided until joint pain or swelling has resolved. Return to sport requires individualized assessment and appropriate rehabilitation.
Asthma is the most common pediatric chronic disease, with over 300 000 Canadian children affected.22 Higher rates appear to be associated with poor socioeconomic status, obesity, and low physical activity levels. Asthma is a chronic inflammatory disorder of the airways, characterized by airway hyperresponsiveness and reversible airflow limitation. Typical presenting symptoms include shortness of breath, cough, and wheezing. Asthma is associated with greater bronchial hyper-reactivity to viral infections, cigarette smoke, inhaled allergens, emotional stress, environmental factors, and exercise. Exercise and emotions trigger bronchospasm but minimal inflammation. Rarely is exercising the only trigger, making ‘exercise induced bronchospasm’ (EIB) better terminology.
Almost 90% of asthmatics and 40% of individuals with allergic rhinitis experience EIB. In children, EIB may be the first presentation of asthma. Overall prevalence in high school, college, and Olympic athletes is 12%,23 although this is probably underestimated.24 Exercise-related dyspnea is often mistakenly diagnosed as EIB; however, bronchial hyperresponsiveness is not associated with exercise-related dyspnea.25
In patients with EIB, bronchoconstriction typically occurs after 8 to 15 minutes of physical activity and resolves within 60 minutes. Running and other land-based cardiovascular exercise (rarely swimming) are common triggers. One popular hypothesis regarding EIB pathogenesis is the evaporation of water lining the airways secondary to higher ventilatory rates during and after exercise.26 Alternatively, cold, dry air may cause an osmotic gradient across mast cells, resulting in mediator release. Fifty percent of asthmatic children without EIB symptoms can be diagnosed using an exercise challenge pulmonary function test (PFT).26,27 A drop of 10% to 15% in forced expiratory volume (FEV1) in 1 second from baseline, following vigorous exercise for approximately 6 to 8 minutes, is diagnostic of EIB. The sensitivity and specificity of exercise PFT in children are up to 63% and 94%, respectively.28 Eucapnic voluntary hyperventilation testing is the preferred challenge test for EIB in athletes, because pharmacological challenge tests have low sensitivity in this setting.29
Asthma management should include identification of disease severity and known triggers, and the creation of a written action plan. Those with persistent symptoms and/or abnormal baseline PFT require ongoing anti-inflammatory treatment with inhaled corticosteroids and/or leukotriene antagonists. Beta2-agonists are used as rescue medication or before exercise to prevent EIB. Children with mild intermittent disease triggered by exercise may benefit from non-pharmacologic interventions (nose breathing and warm-up exercises) as well as pre-event inhaled beta2-agonists. Those in prolonged activities may benefit from a long-acting beta2-agonist (formoterol) with rapid onset. Athletes should take these agents 15 to 30 minutes before exercise.30 Those who compete nationally and internationally require a therapeutic use exemption form, with documentation of asthma or EIB to use certain medications.27,30 Athletes are strongly advised to consult the Canadian Centre for Ethics in Sport (www.cces.ca), the World Anti-Doping Agency (www.wada-ama.org), and their international sport federation to determine the current required documentation.
Children with asthma exhibit similar activity levels as unaffected peers.31 Both have similar self-perceptions or physical self-concept. Disease severity and parental concerns present possible barriers.
Potential Benefits of Exercise
Physical and/or psychosocial benefits of exercise are evident. Bronchial hyperresponsiveness increases with decreasing hours of exercise per week.32 Swimming can increase aerobic fitness and decrease asthma morbidity.33 Exercise training can improve aerobic capacity; however, PFTs do not change significantly.34
Exercise may decrease EIB severity by increasing the threshold for triggering bronchospasm. Almost 50% of affected individuals can experience this ‘refractory period’ up to 4 hours after initial exercise, resulting in decreased bronchoconstriction during subsequent exercise.35 In some cases, athletes can warm-up with exercise 45 to 60 minutes before scheduled activities to reduce their subsequent asthmatic symptoms, and to improve exercise capacity and quality of life.
Potential Risks of Exercise
High-intensity exercise can trigger EIB by increasing minute ventilation and respiratory heat/water losses leading to a greater drop in forced expiratory volume FEV1.36 Permanent bronchial changes may occur in endurance athletes, who seem to have higher rates of bronchial hyperresponsiveness.37 Certain sports expose individuals to dry, cool air,38 environmental allergens, and pollutants, which may trigger flares. Athletes in running and winter sports have more reported symptoms.39 Breathing humid air during swimming may be protective,40 but potential risks from exaggerated parasympathetic tone (‘diving reflex’), and chlorine-related airway irritation that triggers bronchoconstriction may occur.33 It is controversial whether asthma patients are at higher risk of scuba diving injury. They should have normal spirometry (especially residual volume) at rest and in response to exercise before being certified to dive.
Asthma-related deaths of individuals younger than 20 years of age, although rare, have been reported in both competitive and recreational sports (eg, basketball and track).41
Recommendations: Children with Asthma
* Are able to participate in any physical activity if symptoms are well controlled. Swimming is less likely to trigger EIB than running.
* Should keep an accurate history of symptoms, trigger exposures, treatments, and course of recovery from episodes of bronchospasm.
* Should be diagnosed with EIB by a drop in FEV1 (10%-15%) after a 6 to 8 minute exercise challenge and a positive response to beta2-agonist medication. Eucapnic voluntary hyperventilation testing is recommended in athletes.
* Should use leukotriene inhibitors, inhaled corticosteroids, and/or long acting beta2-agonists for optimal long-term disease control, and avoid overuse of short-acting beta2-agonists.
* Should take inhaled beta2-agonists 15 to 30 minutes before exercise.
* Should not scuba dive if they have asthma symptoms or abnormal PFTs.
* Who compete nationally or internationally require a therapeutic use exemption with confirmation of asthma and/or EIB to use certain medications. Consultation with a sport medicine physician is suggested.
Cystic fibrosis (CF) is the most common lethal autosomal recessive disease in Canada, affecting 1 in 3600 Caucasian live births.42 Men and women are equally affected, although men have a longer life expectancy.43 Cystic Fibrosis is caused by mutations in the CF transmembrane conductance regulator protein, a complex chloride channel located in all exocrine tissues.44 Abnormal chloride transport leads to viscous secretions in the pulmonary, gastrointestinal, endocrine, and reproductive systems, and greater salt loss in sweat. Diagnostic sweat chloride testing remains the gold standard. Sixty percent are diagnosed by 1 year of age and 90% by 10 years of age.42 Rapid diagnosis using genetic and newborn sweat chloride show promise.42 Pulmonary disease causes most morbidity and mortality, but early diagnosis and improvements in therapy have increased mean survival rates to 33 years of age.45
Physicians emphasizing exercise, in addition to routine CF treatment, help CF children develop positive attitudes toward exercise. Some may become triathletes or marathon runners.46 Disease severity is variable among children with CF, affecting individual exercise tolerance.
Potential Benefits of Exercise
Cystic fibrosis children with high aerobic fitness experience slower deterioration in lung function and greater survival rates.47-49 Training programs can improve exercise tolerance, particularly those with low fitness levels.50 Enhanced lung mucous clearance can occur during intense exercise.51 Swimming, walking, and jogging can improve strength and endurance of respiratory muscles.52 Strength training may improve fat-free mass, weight gain, muscle strength, and FEV1 in affected patients.53
Potential Risks of Exercise
Children with CF may cough with exercise, causing brief oxygen desaturation. However, there is no evidence this effect causes significant injury.46,54 Some children cough because of underlying asthma. Major limitations to exercise are degrees of lung disease and subnormal ventilatory capacity. These limitations may be a consequence of bronchial narrowing (edema), bronchospasm, mucous plugging, and reduced alveolar ventilation.55 Lung parenchyma destruction results in decreased diffusing capacity leading to oxygen desaturation, CO2 retention, and cyanosis.55,56 Desaturation of arterial oxygen from significant ventilation-perfusion mismatching, intrapulmonary right-to-left shunting or cor pulmonale with congestive right heart failure57 occurs. Cardiac dysfunction is noted in patients with advanced CF (resting FEV1 lower than 50% predicted) who have lower stroke volumes or cardiac output, and in mild CF patients during submaximal exercise testing. Maximal heart rate during testing is often lower than healthy peers.58 All CF patients can develop localized air trapping, increasing the risk of air embolus or pneumothorax during scuba diving.
Resting energy expenditure is 5% to 25% higher in CF youth,59-62 limiting exercise tolerance. Chronic malnutrition may cause lower muscle mass or strength (respiratory or skeletal), impairing sport performance.63 These working muscles have poor oxidative efficiency, contributing to early fatigability.63
Affected children have greater sweat-related salt losses, making exercise in hot or humid environments challenging.64 Prolonged exercise (1.5-3 hours), can lead to hyponatremic dehydration.65 Prevention by ingesting flavored sodium chloride-containing drinks (50 mmol/L) above thirst levels is recommended.65 Cystic fibrosis-related diabetes mellitus make hypoglycemia and dehydration (polyuria) potential concerns with prolonged exercise; hence, additional carbohydrate supplementation is required.66 Multilobular biliary cirrhosis and portal hypertension are frequent complications of CF liver disease, leading to esophageal varices and splenomegaly. Those with splenomegaly or liver dysfunction have a higher risk of organ damage during contact or collision sports.
Recommendations: Children with CF
* Should be encouraged to participate in any physical activity. Consultation with a sport medicine physician or pediatric respirologist is suggested.
* Should have individualized exercise programs that include strength training.
* Require supervised or unsupervised home exercises that elevate heart rate 70% to 80% of maximum to increase aerobic exercise tolerance.
* Who cough during exercise should not necessarily stop activity.
* Those with severe CF should undergo exercise testing to identify maximal heart rate, levels at which oxygen desaturation and ventilation limits occur, exercise-related bronchospasm, and response to therapy.
* Should absolutely avoid scuba diving.
* Should drink flavored sodium chloride-containing fluids above thirst to prevent hyponatremic dehydration. Those with diabetes mellitus require additional carbohydrates during prolonged exercise.
* With an enlarged spleen or diseased liver should avoid contact or collision sports.
Physical activity and sport are primary means of exercise and social activity in childhood. Through participation, children can develop fitness, social skills, and relationships. Despite chronic disease, each individual has a unique exercise tolerance and physical capacity.
This position statement was jointly prepared by members of the Canadian Paediatric Society's Healthy Active Living and Sport Medicine Committee, and the Canadian Academy of Sport Medicine's Paediatric Sport and Exercise Medicine Committee. It was also reviewed by the following groups of the Canadian Paediatric Society: Community Paediatrics Committee, Psychosocial Paediatrics Committee, Respiratory Health Section, and Paediatric Rheumatology Section.
1. Bar-Or O. Clinical implications of pediatric exercise physiology. Ann Clin Res
. 1982;14(suppl 34):97-106.
2. Manners PJ, Bower C. Worldwide prevalence of juvenile arthritis why does it vary so much? J Rheumatol
3. Petty RE, Southwood TR, Manners P, et al. International League of Associations for Rheumatology classification of juvenile idiopathic arthritis: second revision, Edmonton, 2001. J Rheumatol
4. Klepper SE. Exercise and fitness in children with arthritis: evidence of benefits for exercise and physical activity. Arthritis Rheum
5. Klepper SE. Effects of an eight-week physical conditioning program on disease signs and symptoms in children with chronic arthritis. Arthritis Care Res
6. Takken T, Van Der Net J, et al. Aquatic fitness training for children with juvenile idiopathic arthritis. Rheumatology (Oxford)
7. Singh-Grewal D, Wright V, Bar-Or O, et al. Pilot study of fitness training and exercise testing in polyarticular childhood arthritis. Arthritis Rheum
8. Work group recommendations: 2002 Exercise and Physical Activity Conference, St. Louis, Missouri. Session V: evidence of benefit of exercise and physical activity in arthritis. Arthritis Rheum
9. Kirchheimer JC, Wanivenhaus A, Engel A. Does sport negatively influence joint scores in patients with juvenile rheumatoid arthritis. An 8-year prospective study. Rheumatol Int
10. Rice SG. Medical conditions affecting sports participation. Pediatrics
11. Giannini MJ, Protas EJ. Aerobic capacity in juvenile rheumatoid arthritis patients and healthy children. Arthritis Care & Research
12. Takken T, Hemel A, van der Net J, et al. Aerobic fitness in children with juvenile idiopathic arthritis: a systematic review. J Rheumatol
13. Giannini MJ, Protas EJ. Exercise response in children with and without juvenile rheumatoid arthritis: a case-comparison study. Phys Ther
14. Takken T, van der Net J, Helders PJ. Relationship between functional ability and physical fitness in juvenile idiopathic arthritis patients. Scand J Rheumatol
15. Journeycake JM, Buchanan GR. Coagulation disorders. Pediatr Rev
16. National Hemophilia Foundation. Playing It Safe: Bleeding Disorders, Sports and Exercise. New York, NY: National Hemophilia Foundation; 2005.
17. Buzzard BM. Physiotherapy for prevention and treatment of chronic hemophilic synovitis. Clin Orthop
18. Brettler DB, Forsberg AD, O'Connell FD, et al. A long-term study of hemophilic arthropathy of the knee joint on a program of Factor VIII replacement given at time of each hemarthrosis. Am J Hematol
19. Hilberg T, Herbsleb M, Puta C, et al. Physical training increases isometric muscular strength and proprioceptive performance in haemophilic subjects. Haemophilia
20. Barnes C, Wong P, Egan B, et al. Reduced bone density among children with severe hemophilia. Pediatrics
21. Koch B, Galioto FM Jr, Kelleher J, et al. Physical fitness in children with hemophilia. Arch Phys Med Rehabil
23. Rupp NT, Brudno DS, Guill MF. The value of screening for risk of exercise-induced asthma in high school athletes. Ann Allergy
24. Wilber RL, Rundell KW, Szmedra L, et al. Incidence of exercise-induced bronchospasm in Olympic winter sport athletes. Med Sci Sports Exerc
25. Seear M, Wensley D, West N. How accurate is the diagnosis of exercise induced asthma among Vancouver schoolchildren? Arch Dis Child
26. Kattan M, Keens TG, Mellis CM, et al. The response to exercise in normal and asthmatic children. J Pediatr
27. Anderson SD, Sue-Chu M, Perry CP, et al. Bronchial challenges in athletes applying to inhale a beta2
-agonists at the 2004 Summer Olympics. J Allergy Clin Immunol
28. Godfrey S, Springer C, Bar-Yishay E, et al. Cut-off points defining normal and asthmatic bronchial reactivity to exercise and inhalation challenges in children and young adults. Eur Respir J
29. Holzer K, Douglass JA. Exercise induced bronchoconstriction in elite athletes: measuring the fall. Thorax
30. Cardona I, D'Alonzo GE Jr, Becker J. A pilot survey of beta2
-agonists inhaler availability for children with asthma during organized sporting events. Ann Allergy Asthma Immunol
31. Nystad W. The physical activity level in children with asthma based on a survey among 7-16 year old school children. Scand J Med Sci Sports
32. Nystad W, Stigum H, Carlsen KH. Increased level of bronchial responsiveness in inactive children with asthma. Respir Med
33. Bar-Or O, Inbar O. Swimming and asthma. Benefits and deleterious effects. Sports Med
34. Counil FP, Varray A, Matecki S, et al. Training of aerobic and anaerobic fitness in children with asthma. J Pediatr
35. Edmunds AT, Tooley M, Godfrey S. The refractory period after exercise-induced asthma: its duration and relation to the severity of exercise. Am Rev Respir Dis
36. Noviski N, Bar-Yishay E, Gur I, et al. Respiratory heat/water loss alone does not determine the severity of exercise-induced asthma. Eur Respir J
37. Verges S, Flore P, Blanchi MP, et al. A 10-year follow-up study of pulmonary function in symptomatic elite cross-country skiers-athletes and bronchial dysfunctions. Scand J Med Sci Sports
38. Zeitoun M, Wilk B, Matsuzaka A, et al. Facial cooling enhances exercise-induced bronchoconstriction in asthmatic children. Med Sci Sports Exerc
39. Bar-Yishay E, Gur I, Inbar O, et al. Differences between swimming and running as stimuli for exercise-induced asthma. Eur J Appl Physiol Occup Physiol
40. Inbar O, Dotan R, Dlin RA, et al. Breathing dry or humid air and exercise-induced asthma during swimming. Eur J Appl Physiol Occup Physiol
41. Becker JM, Rogers J, Rossini G, et al. Asthma deaths during sports: report of a 7-year experience. J Allergy Clin Immunol
43. Rosenfeld M, Davis R, FitzSimmons S, et al. Gender gap in cystic fibrosis mortality. Am J Epidemiol
44. Orenstein DM, Higgins LW. Update on the role of exercise in cystic fibrosis. Curr Opin Pulm Med
45. Salcedo Posadas A, Girón Moreno R, Beltrán Bengoechea B. Complementary therapies in cystic fibrosis: evidence of therapeutic benefits and treatment recommendations. Ann Pediatr (Barc)
46. Orenstein DM. Cystic fibrosis. In: Goldberg B, ed. Sports and Exercise for Children with Chronic Health Conditions. Champaign, IL: Human Kinetics; 1995:167-186.
47. Schneiderman-Walker J, Pollock SL, Corey M, et al. A randomized controlled trial of a 3-year home exercise program in cystic fibrosis. J Pediatr
48. Nixon PA, Orenstein DM, Kelsey SF, et al. The prognostic value of exercise testing in patients with cystic fibrosis. N Engl J Med
49. Zinman R, Corey M, Coates AL, et al. Nocturnal home oxygen in the treatment of hypoxemic cystic fibrosis patients. J Pediatr
50. Andreasson B, Jonson B, Kornfalt R, et al. Long-term effects of physical exercise on working capacity and pulmonary function in cystic fibrosis. Acta Paediatr Scand
51. Zach M, Oberwaldner B, Hausler F. Cystic fibrosis: physical exercise versus chest physiotherapy. Arch Dis Child
52. Asher MI, Pardy RL, Coates AL, et al. The effects of inspiratory muscle training in patients with cystic fibrosis. Am Rev Respir Dis
53. Selvadurai HC, Blimkie CJ, Meyers N, et al. Randomized controlled study of in-hospital exercise training programs in children with cystic fibrosis. Pediatr Pulmonol
54. Coates AL. Oxygen therapy, exercise, and cystic fibrosis. Chest
55. Godfrey S, Mearns M. Pulmonary function and response to exercise in cystic fibrosis. Arch Dis Child
56. Marcus CL, Bader D, Stabile MW, et al. Supplemental oxygen and exercise performance in patients with cystic fibrosis with severe pulmonary disease. Chest
57. Stern RC, Borkat G, Hirschfeld SS, et al. Heart failure in cystic fibrosis. Treatment and prognosis of cor pulmonale with failure of the right side of the heart. Am J Dis Child
58. Perrault H, Coughlan M, Marcotte JE, et al. Comparison of cardiac output determinants in response to upright and supine exercise in patients with cystic fibrosis. Chest
59. Amin N, Dozor AJ. Effects of administration of aerosolized recombinant human deoxyribonuclease on resting energy expenditure in patients with cystic fibrosis. Pediatr Pulmonol
60. Bronstein MN, Davies PS, Hambidge KM, et al. Normal energy expenditure in the infant with presymptomatic cystic fibrosis. J Pediatr
61. Shepherd RW, Holt TL, Vasques-Velasquez L, et al. Increased energy expenditure in young children with cystic fibrosis. Lancet
62. Vaisman N, Pencharz PB, Corey M, et al. Energy expenditure of patients with cystic fibrosis. J Pediatr
63. de Meer K, Gulmans VA, van Der Laag J. Peripheral muscle weakness and exercise capacity in children with cystic fibrosis. Am J Respir Crit Care Med
64. Orenstein DM, Henke KG, Costill DL, et al. Exercise and heat stress in cystic fibrosis patients. Pediatr Res
65. Kriemler S, Wilk B, Schurer W, et al. Preventing dehydration in children with cystic fibrosis who exercise in the heat. Med Sci Sports Exerc
66. Temple MY, Bar-Or O, Riddell MC. The reliability and repeatability of the blood glucose response to prolonged exercise in adolescent boys with IDDM. Diabetes Care