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Physical activity and exercise in asthma: Relevance to etiology and treatment

2005; Elsevier BV; Volume: 115; Issue: 5 Linguagem: Inglês

10.1016/j.jaci.2005.01.033

1097-6825

Sue Lucas, Thomas A.E. Platts‐Mills,

Inhalation and Respiratory Drug Delivery

There is little doubt that the cause of the increased prevalence and severity of asthma is multifactorial. Although the factors of allergen exposure and hygiene are almost certainly necessary for its development, there is a growing body of literature that implicates lifestyle change, specifically decreased physical activity, as a contributor to the increase in asthma prevalence and severity. Several literature reviews of exercise conditioning in patients with asthma have been published. These reviews and recent controlled trials emphasize that although many of the studies of exercise conditioning in asthmatic patients involved different methods and outcome measures, the overwhelming majority of studies demonstrated the capacity for asthmatic subjects to exercise safely and significantly improve their cardiovascular fitness and quality of life. There are several proposed pathophysiologic mechanisms responsible for the effects of decreased activity on the lung function of patients with asthma. A prescription for exercise has been endorsed for all asthmatic subjects by the American College of Sports Medicine and the American Thoracic Society. The allergy community has placed emphasis on medical therapy and allergen avoidance; in addition, exercise avoidance has not been formally incorporated into the National Asthma Education and Prevention Program guidelines. It is our belief that an exercise prescription should be part of the treatment for all cases of asthma. The real question is whether prolonged physical activity and, in particular, outdoor play of children plays a role in prophylaxis against persistent wheezing. If so, the decrease in physical activity might have played a major role in recent increases in asthma prevalence and severity. There is little doubt that the cause of the increased prevalence and severity of asthma is multifactorial. Although the factors of allergen exposure and hygiene are almost certainly necessary for its development, there is a growing body of literature that implicates lifestyle change, specifically decreased physical activity, as a contributor to the increase in asthma prevalence and severity. Several literature reviews of exercise conditioning in patients with asthma have been published. These reviews and recent controlled trials emphasize that although many of the studies of exercise conditioning in asthmatic patients involved different methods and outcome measures, the overwhelming majority of studies demonstrated the capacity for asthmatic subjects to exercise safely and significantly improve their cardiovascular fitness and quality of life. There are several proposed pathophysiologic mechanisms responsible for the effects of decreased activity on the lung function of patients with asthma. A prescription for exercise has been endorsed for all asthmatic subjects by the American College of Sports Medicine and the American Thoracic Society. The allergy community has placed emphasis on medical therapy and allergen avoidance; in addition, exercise avoidance has not been formally incorporated into the National Asthma Education and Prevention Program guidelines. It is our belief that an exercise prescription should be part of the treatment for all cases of asthma. The real question is whether prolonged physical activity and, in particular, outdoor play of children plays a role in prophylaxis against persistent wheezing. If so, the decrease in physical activity might have played a major role in recent increases in asthma prevalence and severity. Asthma prevalence, severity, and hospitalization have increased over the last 4 decades. Although there seems to have been a slight plateau in asthma incidence in recent years, the prevalence remains very high, and true causes of the epidemic remain an enigma. The increase has affected many different populations, but the increase has disproportionately affected African Americans and Latinos living in poverty in the United States. By contrast, rural areas that have maintained a traditional lifestyle remain unaffected: good examples have been studied in Africa, Australia, and Papua New Guinea. Many explanations for the increase have been postulated, but none of them are sufficient to explain the scale or consistency of the change. Indeed, it is becoming increasingly evident that the cause of the changes in asthma must be multifactorial, including contributions from allergen exposure, hygiene, and lifestyle. This article will briefly review the 2 former factors and more thoroughly elaborate on lifestyle change, with a specific emphasis on the relevance of changes in physical activity. The pulmonary physiology underlying the effects of activity will be discussed as well. A prescription for exercise has been endorsed for all asthmatic subjects by the American College of Sports Medicine (ACSM)1American College of Sports Medicine ACSM's guidelines for exercise testing and prescription.6th ed. Lippencott Williams & Wilkins, Philadelphia2000Google Scholar and the American Thoracic Society (ATS)2American Thoracic Society Pulmonary rehabilitation.Am J Respir Crit Care Med. 1999; 159: 1666-1682Crossref PubMed Scopus (454) Google Scholar. Currently, the National Asthma Education and Prevention Program Guidelines for the Diagnosis and Management of Asthma3National Asthma Education and Prevention Program Expert panel report: guidelines for the diagnosis and management of asthma: update on selected topics, 2002.J Allergy Clin Immunol. 2002; 110: S141-S219PubMed Google Scholar do not include recommendations for exercise as part of the treatment for patients with asthma. There have been strong and consistent associations between aeroallergen sensitization, especially to dust mites, and asthma. Supported by bronchial challenge and avoidance studies, these are strongly suggestive of a causal relationship between sensitization and asthma.4Sporik R. Chapman M.D. Platts-Mills T.A. House dust mite exposure as a cause of asthma.Clin Exp Allergy. 1992; 22: 897-906Crossref PubMed Scopus (260) Google Scholar Subsequently, many different perennial allergens from other parts of the world have been implicated as determinants of inflammation and bronchial hyperreactivity (BHR). The hygiene hypothesis proposes that decreased exposure to infections and farm animals–endotoxin or increased antibiotic use has decreased the activation of control mechanisms based on T regulator cells. The dominance of TH2 responses in atopic individuals has been consistently demonstrated. Although there is good evidence for a change of this kind with the move from traditional lifestyle, the major changes in hygiene occurred in the United States or United Kingdom long before the increase in asthma. Furthermore, there are good reasons to believe that hay fever was epidemic in London and New York before the start of the increase of asthma. If we assume that the real increase in asthma has occurred between 1960 and 2000, what are the lifestyle changes that match this increase? The obvious candidates are diet and physical activity. Obesity, however, is the product of these changes that is easiest to measure. Obviously, these three are strongly interrelated, but there are good arguments for a primary role of either obesity itself, changes in diet, or decreased physical activity in the increase in asthma. Adult and pediatric obesity has become an epidemic in industrialized nations over the past 2 decades. The prevalence of childhood obesity in the United States increased 100% between 1980 and 1994.5National Center for Health Statistics. Health, United States, 2000. With adolescent health chartbook. Table 69, updated on 07/27/00. Available at: http://www.cdc/gov/nchs/products/pubs/pubd/hus/tables/2000/updated/00hus69.pdf. Accessed July 24, 2004.Google Scholar In the 1990s, obesity came under scrutiny for its potential contribution to the increase in asthma. Obesity has been associated with reduction in deep breathing, contributing to airway narrowing through smooth muscle latching,6Tantisira K.G. Weiss S.T. Complex interactions in complex traits: obesity and asthma.Thorax. 2001; 56: II64-II74PubMed Google Scholar decreased forced expiratory flow at 25% to 75% of forced vital capacity,7Biring M.S. Lewis M.I. Liu J.T. Mohsenifar Z. Pulmonary physiologic changes of morbid obesity.Am J Med Sci. 1999; 318: 293-297Crossref PubMed Google Scholar reflux-induced bronchoconstriction,8Ricciardolo F.L. Mechanisms of citric acid-induced bronchoconstriction.Am J Med. 2001; 111: 18S-24SAbstract Full Text Full Text PDF PubMed Google Scholar shortness of breath, increased wheezing,9Figueroa-Munoz J.I. Chinn S. Rona R.J. Association between obesity and asthma in 4-11 year old children in the UK.Thorax. 2001; 56: 133-137Crossref PubMed Scopus (264) Google Scholar, 10Schachter L.M. Salome C.M. Peat J.K. Woolcock A.J. Obesity is a risk factor for asthma and wheeze but not airway hyperresponsiveness.Thorax. 2001; 56: 4-8Crossref PubMed Scopus (334) Google Scholar and increased release of inflammatory mediators.11Visser M. Bouter L.M. McQuillan G.M. Wenner M.H. Harris T.B. Elevated C-reactive protein levels in overweight and obese adults.JAMA. 1999; 282: 2131-2135Crossref PubMed Scopus (1963) Google Scholar, 12Visser M. Bouter L.M. McQuillan G.M. Wenner M.H. Harris T.B. Low-grade systemic inflammation in overweight children.Pediatrics. 2001; 107: E13Crossref PubMed Scopus (329) Google Scholar Perzanowski and colleagues13Perzanowski M.S. Ng'ang'a L.W. Carter M.C. Odhiambo J. Ngari P. Vaughan J.W. et al.Atopy, asthma, and antibodies to Ascaris among rural and urban children in Kenya.J Pediatr. 2002; 140: 582-588Abstract Full Text Full Text PDF PubMed Scopus (101) Google Scholar evaluated the relationship between body mass index (BMI) and asthma among rural and urban children in Kenya and the United States. They found that urban American children had significantly higher BMIs and increased prevalence of asthma (Table I). They also found that despite having larger lung volumes and being taller and heavier than the African children, the children in Atlanta had an FEV1 as a percentage of predicted value that was significantly lower (Table I). One randomized controlled trial demonstrated improved lung function in asthmatic subjects with dietary weight loss.14Stenius-Aarniala B. Poussa T. Kvarnstrom J. Gronlund E.L. Ylikahri M. Mustajuki P. Immediate and longterm effects of weight reduction in obese people with asthma: randomized controlled study.BMJ. 2000; 320: 827-832Crossref PubMed Scopus (463) Google Scholar Although there is an abundance of literature demonstrating the association of asthma and obesity, there is only one study that has established that obesity precedes asthma independent of activity level.15Camargo C.A. Weiss S.T. Zhang S. Willett W.C. Speizer F.E. Prospective study of Body Mass Index, weight change, and risk of adult-onset asthma in women.Arch Intern Med. 1999; 159: 2582-2588Crossref PubMed Scopus (680) Google Scholar Could it be that increased sedentary lifestyle has more influence on asthma prevalence and severity than obesity and diet? Certainly the association between obesity and asthma is not comparable with the association between obesity and diseases, such as type II diabetes. It is our view that there is a more logical case related to changes in physical activity and also a more convincing explanation for the effects of exercise on asthma than the effect of obesity on increased asthma.Table IAnthropometric and spirometric measurements on children in rural and urban Kenya and Atlanta, GeorgiaKabiti (rural)Thika (urban)AtlantaNo. enrolled136129112Age (y)11.5 (9-15)10.0 (8-13)10.8 (10-12)Height (cm)†P < .01 between children from Kenya and Atlanta.137 (120-159)135 (123-154)150 (112-168)Weight (kg)†P < .01 between children from Kenya and Atlanta.31 (20-51)30 (20-45)46 (22-112)Body fat (%)∗P < .01 between all locations (Mann-Whitney U test).15.5 (6-23)17.4 (12-31)19.8 (14-32)Initial LFTs FVC (L)†P < .01 between children from Kenya and Atlanta.1.99 (1.27-3.08)1.93 (1.06-2.58)2.49 (1.41-5.92) FEV1 (L)†P < .01 between children from Kenya and Atlanta.1.66 (0.97-2.53)1.6 (0.92-2.19)2 (1.19-4.16) % Predicted†P < .01 between children from Kenya and Atlanta.‡Percent predicted FEV1 values were race adjusted.95.696.489.2 PEF (L/m)†P < .01 between children from Kenya and Atlanta.242 (91-426)228 (102-358)292 (174-692)Values are presented as means (ranges).LFT, Lung function test; FVC, forced vital capacity; PEF, peak expiratory flow.∗ P < .01 between all locations (Mann-Whitney U test).† P < .01 between children from Kenya and Atlanta.‡ Percent predicted FEV1 values were race adjusted. Open table in a new tab Values are presented as means (ranges). LFT, Lung function test; FVC, forced vital capacity; PEF, peak expiratory flow. There has been a steady decrease in the levels of physical activity of adults and children in America over the last 3 decades. This decrease corresponds in time course to the increased prevalence of asthma. Rasmussen et al,16Rasmussen F. Lambrechtsen J. Siersted H.C. Hansen H.S. Hansen N.C. Low physical fitness in childhood is associated with the development of asthma in young adulthood: the Odense schoolchild study.Eur Respir J. 2000; 16: 866-870Crossref PubMed Scopus (154) Google Scholar in their 10.5-year prospective study of 757 children, concluded that decreased physical fitness in childhood was significantly (P < .01) correlated with the development of adolescent asthma. Huovinen et al,17Huovinen E. Kaprio J. Laitinen L.A. Koskenvuo Social predictor of adult asthma: a co-twin case-control study.Thorax. 2001; 56: 234-236Crossref PubMed Scopus (50) Google Scholar in their 17-year study of 262 twin pairs, showed that the twin who participated in exercise conditioning had a decreased risk of asthma. Unlike BMI, levels of physical activity are difficult to measure. Recently, when compared with healthy peers, statistically significantly lower levels of activity have been documented in low-income preschool children with a history of asthma and wheezing by using Actiwatches (Mini Mitter Company, Inc, Bend, Ore).18Firrincieli V. Keller A. Ehrensberger R. Platts-Mills J. Shuffleberger C. Geldmaker B. et al.Decreased physical activity among Head Start children with a history of wheezing: use of an accelerometer to measure activity.Pediatr Pulmonol. 2004; (In press)Google Scholar The Actiwatches that measure movement were worn on the wrist for 6 to 7 days, and children with a history of wheezing or a recent emergency department visit for wheezing demonstrated lower levels of vigorous and prolonged activity. There were no significant correlations between BMI and physical activity or wheezing, suggesting that activity level could have played a role in the development or persistence of wheezing independent of obesity. Most studies have shown that asthmatic subjects have a lower aerobic fitness level than their nonasthmatic peers. However, this limited fitness level in asthmatic subjects seems not to be related to their degree of obstruction but rather to their decreased levels of habitual activity.19Clark C.J. The role of physical training in asthma.in: Casaburi R. Petty T.L. Principles and practice of pulmonary rehabilitation. WB Saunders Co, Philadelphia1993: 424-438Google Scholar Although seemingly counterintuitive given the potential for exercise-induced bronchospasm (EIB), exercise has long been recognized as a possible method of improving subjective and objective asthma indices. The possibility that exercise could be a treatment for asthma was recognized in 1882 by Henry Hide Salter.20Salter H.H. On asthma: its' pathology and treatment.1st ed. William Wood & Company, New York1882Google Scholar However, the regimens he proposed were slightly "unrealistic" (see Box 1).Box 1Salter (1882) on exercise as a treatment for asthmaExercise—I have seen several cases in which prolonged bodily exertion has been of great benefit, indeed, some in which it has been the best remedy to which the asthmatic could resort.This treatment is, of course, rather prophylactic than curative—it must be taken in the intervals of the attacks: but when so taken it seems to have a marvelous efficacy in keeping them off, and in giving to the asthmatic a lightness and freedom of respiration to which at other times he is a stranger.The following cases are good examples illustrative of this point:Case I.—"Of all remedies," writes a confirmed asthmatic to me, "there is none for me so complete and lasting as a day of severe walking exercise—five-and-twenty miles over hilly ground, or across heaths. The strain must never be great. I begin slowly, almost saunteringly, and only increase my pace when it is pleasanter to do so than not.Case II—The following extract from an interesting case sent me by a medical friend: "For the last twenty years, in fact ever since I can recollect, my father has been running the gauntlet of medical men in England and Scotland, without any sort of benefit, so much so that about eight years ago he gave this plan up, and took the treatment into his own hands—I ought to say legs, perhaps, for his only curative measure consisted in walking exercise; about twenty miles a day was, he considered, an average dose, and the result is that he is now comparatively free from attacks. Exercise—I have seen several cases in which prolonged bodily exertion has been of great benefit, indeed, some in which it has been the best remedy to which the asthmatic could resort. This treatment is, of course, rather prophylactic than curative—it must be taken in the intervals of the attacks: but when so taken it seems to have a marvelous efficacy in keeping them off, and in giving to the asthmatic a lightness and freedom of respiration to which at other times he is a stranger. The following cases are good examples illustrative of this point: Case I.—"Of all remedies," writes a confirmed asthmatic to me, "there is none for me so complete and lasting as a day of severe walking exercise—five-and-twenty miles over hilly ground, or across heaths. The strain must never be great. I begin slowly, almost saunteringly, and only increase my pace when it is pleasanter to do so than not. Case II—The following extract from an interesting case sent me by a medical friend: "For the last twenty years, in fact ever since I can recollect, my father has been running the gauntlet of medical men in England and Scotland, without any sort of benefit, so much so that about eight years ago he gave this plan up, and took the treatment into his own hands—I ought to say legs, perhaps, for his only curative measure consisted in walking exercise; about twenty miles a day was, he considered, an average dose, and the result is that he is now comparatively free from attacks. It is well documented that the incidence of EIB after proper medical prophylaxis is extremely low.21Orenstein D.M. Pulmonary problems and management concerns in youth sports.Pediatr Clin North Am. 2002; 49: 709-721Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar Several recent literature reviews have supported the benefits and safety of exercise in asthmatic subjects.19Clark C.J. The role of physical training in asthma.in: Casaburi R. Petty T.L. Principles and practice of pulmonary rehabilitation. WB Saunders Co, Philadelphia1993: 424-438Google Scholar, 21Orenstein D.M. Pulmonary problems and management concerns in youth sports.Pediatr Clin North Am. 2002; 49: 709-721Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar, 22Orenstein D.M. Asthma and sports.in: Bar-Or O. The child and adolescent athlete. Vol V. The encyclopedia of sports medicine of the International Olympic Committee. Blackwell Scientific Publications, Oxford1996: 433-454Google Scholar, 23Satta A. Exercise training in asthma.J Sports Med Phys Fitness. 2000; 40: 277-283PubMed Google Scholar Although studies vary in terms of design, outcome measures, exercise mode, duration, intensity, and outcome variables, the majority of studies on pediatric and adult asthmatic subjects have demonstrated improved objective and subjective markers of disease. Orenstein's 2002 literature review of exercising patients with pulmonary disease concluded that asthmatic subjects can improve cardiopulmonary fitness with exercise conditioning.21Orenstein D.M. Pulmonary problems and management concerns in youth sports.Pediatr Clin North Am. 2002; 49: 709-721Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar In addition to decreased risk of cardiovascular disease and diabetes, the benefits of conditioning on asthma are both subjective (increased participation in activities, improved emotional status, and decreased intensity of wheezing attacks) and objective (improved running performance and increased aerobic fitness). He, however, also points out it is unclear whether improved fitness influences the severity of underlying asthma. Several studies have reported that exercise conditioning does not influence inflammation as judged on the basis of preconditioning and postconditioning methacholine challenges.24Robinson D.M. Egglestone D.M. Hill P.M. Rea H.H. Richards G.N. Robinson S.M. The effects of a physical conditioning programme on asthmatic patients.N Z Med J. 1992; 105: 253-256PubMed Google Scholar, 25Cochrane L.M. Clark C.J. Benefits and problems of a physical training program for asthmatic patients.Thorax. 1990; 45: 345-351Crossref PubMed Scopus (118) Google Scholar Orenstein21Orenstein D.M. Pulmonary problems and management concerns in youth sports.Pediatr Clin North Am. 2002; 49: 709-721Abstract Full Text Full Text PDF PubMed Scopus (24) Google Scholar suggested that some older studies erroneously concluded that underlying asthma was less severe after exercise conditioning because when challenged with the same preconditioning workload in the fit state, asthmatic patient's minute ventilation was lower, making the stimulus for EIB less intense. Regardless, it seems to us, any measure that makes doing the same workload less asthmogenic seems prudent, irrespective of the mechanism. He concluded that "exercise conditioning is good for patients with asthma, but probably does not lead to decreased underlying airway reactivity." In Satta's 2000 review of 48 articles on exercise training for patients with asthma,23Satta A. Exercise training in asthma.J Sports Med Phys Fitness. 2000; 40: 277-283PubMed Google Scholar he draws attention to the fact that "much of the research suffers from methodological problems such as small sample size, the lack of adequate control groups, incomplete outcome measures, lack of prospective data collection." However, his literature review highlighted the health benefits of exercise conditioning on asthmatic subjects, including improved fitness level and quality of life. He also highlighted positive outcomes, including reductions in the need for medications, fewer visits to the emergency department, decreased exercise-related fear and anxiety, and less absenteeism from school. Some studies have documented improvement in spirometry (decreased peak flow variability and increased FEV1), whereas others did not. He also cited several studies that failed to demonstrate an improvement in nonspecific BHR. Another thorough literature review of 90 articles on exercise conditioning for asthma by Clark19Clark C.J. The role of physical training in asthma.in: Casaburi R. Petty T.L. Principles and practice of pulmonary rehabilitation. WB Saunders Co, Philadelphia1993: 424-438Google Scholar identified that the categories of patients chosen, the control groups, the disease severity, and the type of physiologic measurements of the studies varied greatly. Furthermore, there were few studies on adult asthmatic patients before 1993. The training programs varied with respect to mode, frequency, duration, and intensity, and the use of prophylactic β-agonists for EIB was often not specified. He concluded that despite these methodological differences, "almost universally the clinical studies have shown major improvement in exercise performance in patients after participation in rehabilitation programs." There are several more recent controlled trials that provide sound data to support incorporating exercise into asthma management (Table II).24Robinson D.M. Egglestone D.M. Hill P.M. Rea H.H. Richards G.N. Robinson S.M. The effects of a physical conditioning programme on asthmatic patients.N Z Med J. 1992; 105: 253-256PubMed Google Scholar, 25Cochrane L.M. Clark C.J. Benefits and problems of a physical training program for asthmatic patients.Thorax. 1990; 45: 345-351Crossref PubMed Scopus (118) Google Scholar, 26Hallstrand T.S. Bates P.W. Schoene R.B. Aerobic conditioning in mild asthma decreases the hyperpnea of exercise and improves exercise and ventilatory capacity.Chest. 2000; 118: 1460-1469Crossref PubMed Scopus (94) Google Scholar, 27Cambach W. Chadwick-Straver R.V.M. Wagenaar R.C. van Keimpema A.R.J. Kemper H.C.G. The effects of a community-based pulmonary rehabilitation programme on exercise tolerance and quality of life: a randomized controlled trial.Eur Respir J. 1997; 10: 104-113Crossref PubMed Scopus (239) Google Scholar, 28Varray A.L. Mercier J.G. Terral C.M. Prefaut C.G. Individualized aerobic and high intensity training for asthmatic children in an exercise readaptation program—Is training always helpful for better adaptation to exercise?.Chest. 1991; 99: 579-586Crossref PubMed Scopus (100) Google Scholar In these studies and the remainder of the studies reviewed above there were no major adverse reactions to conditioning programs. There are, however, some recent studies that have reported increased asthma symptoms among children involved in vigorous sports.29McConnell R. Berhane K. Gilliland F. Islam T. Gauderman W.J. Avol E. et al.Asthma in exercising children exposed to ozone: a cohort study.Lancet. 2002; 359: 386-391Abstract Full Text Full Text PDF PubMed Scopus (618) Google Scholar, 30Nystad W. Nafstad P. Harris J.R. Physical activity affects the prevalence of reported wheeze.Eur J Epidemiol. 2001; 17: 209-212Crossref PubMed Scopus (23) Google Scholar Although the literature is replete with studies demonstrating the benefits of conditioning asthmatic subjects, there is a relative dearth of physiologic explanations for these positive outcomes.Table IIReview of controlled trials after 1990 on the benefits of exercise conditioning in asthmatic patientsReferenceAsthmatic patientsControl subjectsFitness measuresFitness trendTime (wk)OtherHallstrand et al26Hallstrand T.S. Bates P.W. Schoene R.B. Aerobic conditioning in mild asthma decreases the hyperpnea of exercise and improves exercise and ventilatory capacity.Chest. 2000; 118: 1460-1469Crossref PubMed Scopus (94) Google Scholar5 A5 A, H↑ VO2max∗P < .05., ↓ AT∗P < .05., ↓ VE∗P < .05.↑10↑ Fitness = in H and asthmatic subjectsCambach et al27Cambach W. Chadwick-Straver R.V.M. Wagenaar R.C. van Keimpema A.R.J. Kemper H.C.G. The effects of a community-based pulmonary rehabilitation programme on exercise tolerance and quality of life: a randomized controlled trial.Eur Respir J. 1997; 10: 104-113Crossref PubMed Scopus (239) Google Scholar§Randomized controlled trial.43 A23 COPD↑ ET‡P < .001., ↓ ƒc‡P < .001., ↑ WD‡P < .001.,↑12↑ QOL‡P < .001. Multidisciplinary rehab programRobinson et al24Robinson D.M. Egglestone D.M. Hill P.M. Rea H.H. Richards G.N. Robinson S.M. The effects of a physical conditioning programme on asthmatic patients.N Z Med J. 1992; 105: 253-256PubMed Google Scholar8 A8 A, H↑ VO2max∗P < .05.,↓ VE↑12↑ QOL†P < .01.Varray et al28Varray A.L. Mercier J.G. Terral C.M. Prefaut C.G. Individualized aerobic and high intensity training for asthmatic children in an exercise readaptation program—Is training always helpful for better adaptation to exercise?.Chest. 1991; 99: 579-586Crossref PubMed Scopus (100) Google Scholar7 C7 C Asthma↑ VO2max‡P < .001.,↑ Vth‡P < .001.↑12↓ Intensity of wheezeCochrane and Clark25Cochrane L.M. Clark C.J. Benefits and problems of a physical training program for asthmatic patients.Thorax. 1990; 45: 345-351Crossref PubMed Scopus (118) Google Scholar§Randomized controlled trial.18 A18 A Asthma↑ VO2max‡P < .001.,↓ VE‡P < .001., O2pulse‡P < .001., AT‡P < .001., ↓ VCO2‡P < .001.↑12↓ Lactate∗P < .05., ↓breathlessnessA, Adult; H, healthy; VO2max, maximal oxygen consumption; AT, anaerobic threshold; VE, minute ventilation; COPD, chronic obstructive pulmonary disease; ET, endurance time; ƒc, cardiac frequency; WD, walking distance; QOL, quality of life; C, children; Vth, ventilatory threshold; VCO2, CO2 output.∗ P < .05.† P < .01.‡ P < .001.§ Randomized controlled trial. Open table in a new tab A, Adult; H, healthy; VO2max, maximal oxygen consumption; AT, anaerobic threshold; VE, minute ventilation; COPD, chronic obstructive pulmonary disease; ET, endurance time; ƒc, cardiac frequency; WD, walking distance; QOL, quality of life; C, children; Vth, ventilatory threshold; VCO2, CO2 output. There are many factors influencing the patency of bronchioles (Fig 1). There has been a lot of speculation that collagen deposition or airway remodeling plays a significant role in decreased airway patency or compliance. Some authors have speculated that increased smooth muscle is the cause of excessive bronchoconstriction or changed compliance. Thomson and colleagues,31Thomson R.J. Bramley A.M. Schellenberg R.R. Airway muscle stereology: implications for increased shortening in asthma.Am J Respir Crit Care Med. 1996; 154: 749-757Crossref PubMed Scopus (101) Google Scholar however, evaluated cross-sectional airway muscle in axial airway sections at high resolution and found no evidence of incre