The evaluation of a 13-month maintenance program (MP) for 39 severe COPD patients with FEV(1)%pred 44(7)% who, as result of two different 8-week leg exercise training (LET) programs, one supervised at the hospital (group S; n = 20) and the other self-monitored (SM; n = 19), had achieved different levels of exercise tolerance. After LET, patients in group S had a higher maximal oxygen uptake and endurance time than patients in the SM group [ O(2)max 1.43(0.30) l. min(-1)] vs l.25(0.27) l. min(-1) and endurance-time 16(4) min vs 12 (5) min, respectively). During the MP patients were advised to walk vigorously at least 4 km/day, 4 times/wk. After the MP, while endurance time remained higher than at baseline, it had decreased ( p < 0.01) immediately after LET in both groups and no differences were evident between groups (11(4) min and 10(4), respectively). In contrast, Chronic Respiratory Diseases Questionnaire scores, which had improved significantly after LET in both groups, remained high. Long-term effects of MP were independent of the training strategy or whether physiological improvements had been obtained with the initial LET. SM exercise programs do not seem capable of maintaining physiological improvements in exercise tolerance, though "quality of life" can be maintained.

Exercise Therapy↗

PubMed2003

Endocrinological disturbances in chronic obstructive pulmonary disease.

In this overview, the available literature on endocrinological disturbances in chronic obstructive pulmonary disease (COPD) is reviewed, with stress on growth hormone/insulin-like growth factor I (IGF-I), thyroid hormone and the anabolic steroids. In COPD, little is known about circulating growth hormone or IGF-I concentrations. Some authors find a decrease in growth hormone or IGF-I, others an increase. An increase of growth hormone might reflect a nonspecific response of the body to stress (for instance, hypoxaemia). Until now, only one controlled study on growth hormone supplementation has been published, which however did not reveal any functional benefits. Before growth hormone supplementation can be advised as part of the treatment in COPD, further controlled studies must be performed to investigate its functional efficacy. The prevalence of thyroid dysfunction in COPD and its role in pulmonary cachexia has not been extensively studied. So far, there is no evidence that thyroid function is consistently altered in COPD, except perhaps in a subgroup of patients with severe hypoxaemia. Further research is required to more extensively study the underlying mechanisms and consequences of disturbed thyroid function in this subgroup of COPD patients. A few studies have reported the results of anabolic steroid supplementation in chronic obstructive pulmonary disease. Although some studies have discerned that low circulating levels of testosterone are common in males with chronic obstructive pulmonary disease, little is known about the prevalence, the underlying causes or functional consequences of hypogonadism in these patients. The use of systemic glucocorticosteroids and an influence of the systemic inflammatory response have been suggested as contributing to low testosterone levels. It can be hypothesised that low anabolic hormones will reduce muscle mass and eventually result in a diminished muscle function. Further evidence is required before testosterone replacement can be recommended for males with chronic obstructive pulmonary disease.

Anabolic Agents↗

PubMed2002

A long-term evaluation of once-daily inhaled tiotropium in chronic obstructive pulmonary disease.

Currently available inhaled bronchodilators used as therapy for chronic obstructive pulmonary disease (COPD) necessitate multiple daily dosing. The present study evaluates the long-term safety and efficacy of tiotropium, a new once-daily anticholinergic in COPD. Patients with stable COPD (age 65.2+/-8.7 yrs (mean+/-SD), n=921) were enrolled in two identical randomized double-blind placebo-controlled 1-yr studies. Patients inhaled tiotropium 18 microg or placebo (mean screening forced expiratory volume in one second (FEV1) 1.01 versus 0.99 L, 39.1 and 38.1% of the predicted value) once daily as a dry powder. The primary spirometric outcome was trough FEV1 (i.e. FEV1 prior to dosing). Changes in dyspnoea were measured using the Transition Dyspnea Index, and health status with the disease-specific St. George's Respiratory Questionnaire and the generic Short Form 36. Medication use and adverse events were recorded. Tiotropium provided significantly superior bronchodilation relative to placebo for trough FEV1 response (approximately 12% over baseline) (p<0.01) and mean response during the 3 h following dosing (approximately 22% over baseline) (p<0.001) over the 12-month period. Tiotropium recipients showed less dyspnoea (p<0.001), superior health status scores, and fewer COPD exacerbations and hospitalizations (p<0.05). Adverse events were comparable with placebo, except for dry mouth incidence (tiotropium 16.0% versus placebo 2.7%, p<0.05). Tiotropium is an effective, once-daily bronchodilator that reduces dyspnoea and chronic obstructive pulmonary disease exacerbation frequency and improves health status. This suggests that tiotropium will make an important contribution to chronic obstructive pulmonary disease therapy.

Administration, Inhalation↗

PubMed2002

[Peripheral muscle dysfunction in chronic obstructive pulmonary disease].

Patients with chronic obstructive pulmonary disease (COPD) often develop systemic complications of their disease. Peripheral muscle dysfunction is one such complication and is characterised by atrophy, weakness, and low oxidative capacity. These muscle changes influence exercise tolerance and quality of life independent of the impairment in lung function. In the following article, the evidence for peripheral muscle dysfunction in patients with COPD and the possible clinical implications of this problem will be discussed. Lastly, the available therapeutic options to improve peripheral muscle function in COPD will be reviewed.

Activities of Daily Living↗

PubMed2001

Skeletal muscle dysfunction in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a major health care problem. Formerly mainly a disease of men, women are increasingly frequently afflicted. In many of these patients, exercise intolerance is the chief complaint. Few effective therapies are available. In recent years, dysfunction of the muscles of ambulation has been identified as a source of a portion of the exercise intolerance these patients experience, and this dysfunction has been shown to be, at least in part, remediable. Mechanisms inducing muscle dysfunction include disuse atrophy, malnutrition, low levels of anabolic steroids, and myopathy from corticosteroid use. Endurance exercise training has been conclusively demonstrated to improve exercise tolerance in COPD. Recent studies suggest that strength training is beneficial as well. A new frontier of therapy for muscle dysfunction in COPD is the use of anabolic hormones. Testosterone supplementation has been shown to increase muscle mass and strength in both hypogonadal and eugonadal healthy men. Low-dose testosterone supplementation is being considered for use in postmenopausal women. Though short-term administration of testosterone in moderate doses seems to be well tolerated in both men and women, further studies are required before safety and effectiveness can be established for routine use in COPD patients.

Androgens↗

PubMed2001

Testosterone dose-response relationships in healthy young men.

Testosterone increases muscle mass and strength and regulates other physiological processes, but we do not know whether testosterone effects are dose dependent and whether dose requirements for maintaining various androgen-dependent processes are similar. To determine the effects of graded doses of testosterone on body composition, muscle size, strength, power, sexual and cognitive functions, prostate-specific antigen (PSA), plasma lipids, hemoglobin, and insulin-like growth factor I (IGF-I) levels, 61 eugonadal men, 18-35 yr, were randomized to one of five groups to receive monthly injections of a long-acting gonadotropin-releasing hormone (GnRH) agonist, to suppress endogenous testosterone secretion, and weekly injections of 25, 50, 125, 300, or 600 mg of testosterone enanthate for 20 wk. Energy and protein intakes were standardized. The administration of the GnRH agonist plus graded doses of testosterone resulted in mean nadir testosterone concentrations of 253, 306, 542, 1,345, and 2,370 ng/dl at the 25-, 50-, 125-, 300-, and 600-mg doses, respectively. Fat-free mass increased dose dependently in men receiving 125, 300, or 600 mg of testosterone weekly (change +3.4, 5.2, and 7.9 kg, respectively). The changes in fat-free mass were highly dependent on testosterone dose (P = 0.0001) and correlated with log testosterone concentrations (r = 0.73, P = 0.0001). Changes in leg press strength, leg power, thigh and quadriceps muscle volumes, hemoglobin, and IGF-I were positively correlated with testosterone concentrations, whereas changes in fat mass and plasma high-density lipoprotein (HDL) cholesterol were negatively correlated. Sexual function, visual-spatial cognition and mood, and PSA levels did not change significantly at any dose. We conclude that changes in circulating testosterone concentrations, induced by GnRH agonist and testosterone administration, are associated with testosterone dose- and concentration-dependent changes in fat-free mass, muscle size, strength and power, fat mass, hemoglobin, HDL cholesterol, and IGF-I levels, in conformity with a single linear dose-response relationship. However, different androgen-dependent processes have different testosterone dose-response relationships.

Adult↗

PubMed2001

21st century perspective on chronic obstructive pulmonary disease.

The prediction that chronic obstructive pulmonary disease (COPD) will be the third leading cause of death worldwide by 2020 has enormous economic repercussions. Yet many issues and questions remain unresolved. For example, how can population studies of morbidity and mortality be viewed as comparable, without a worldwide consensus on the definition of COPD? How can the early diagnosis of COPD be improved? Why is it that only a minority of smokers develop COPD, despite tobacco smoking being the primary risk factor for chronic bronchitis and emphysema? How can the efficacy of smoking cessation interventions be improved? To what extent are the pathologic changes in the lungs reversible - and, if so, at what stage? And to what degree is it appropriate to emphasize the similar features of COPD and asthma? It is to be hoped that the emerging post-genomic and proteomic climate will facilitate the unlocking of the genetic substrate for COPD, and thus promote greater therapeutic specificity and efficacy.

Exercise Tolerance↗

PubMed2001

Dose-response effect of oxygen on hyperinflation and exercise endurance in nonhypoxaemic COPD patients.

Dynamic hyperinflation contributes to exertional breathlessness and reduced exercise tolerance in chronic obstructive pulmonary disease (COPD) patients. This study examined whether oxygen supplementation results in a dose-dependent decrease in hyperinflation associated with functional and symptomatic improvement. Ten severe COPD patients without clinically significant oxygen (O2) desaturation during exercise, and seven healthy subjects, performed five exercise tests at 75% of maximally tolerated work rate. Inspired oxygen fraction (FI,O2) was varied (0.21, 0.3, 0.5, 0.75 and 1.0) among tests in a randomized order. Ventilation (V'E) was measured, and end-inspiratory (EILV) and end-expiratory (EELV) lung volume changes were assessed from inspiratory capacity manoeuvres. In the patients, compared to room air, endurance time increased with FI,O2=0.3 (mean+/-SEM 92+/-20%) and increased further with FI,O2=0.5 (157+/-30%). At isotime, compared to room air, there were significant reductions in dyspnoea score, EELV, EILV, V'E and respiratory frequency (fR) with FI,O2=0.3. Improved endurance time negatively correlated with change in EELV (r=0.48, p=0.002) and EILV (r=0.43, p=0.005). The dyspnoea rating decrease correlated with fR decrease. In healthy subjects, smaller V'E and fR decreases were observed at FI,O2=0.5, accompanied by more modestly increased endurance. Oxygen supplementation during exercise induced dose-dependent improvement in endurance and symptom perception in nonhypoxaemic chronic obstructive pulmonary disease patients, which may be partly related to decreased hyperinflation and slower breathing pattern. This effect is maximized at an inspired oxygen fraction of 0.5.

Aged↗

PubMed2000

Peripheral muscle dysfunction in chronic obstructive pulmonary disease.

Peripheral muscle dysfunction is a common systemic complication of moderate to severe COPD and may contribute to disability, handicap, and premature mortality. In contrast to the lung impairment, which is largely irreversible, peripheral muscle dysfunction is potentially remediable with exercise training, nutritional intervention, oxygen, and anabolic drugs. Therapeutic success is often incomplete, however, and a better understanding of the mechanisms involved in the development of peripheral muscle dysfunction in COPD is needed to help develop innovative and more effective therapeutic strategies.

Aging↗

PubMed2000

Comparison of effects of supervised versus self-monitored training programmes in patients with chronic obstructive pulmonary disease.

The effects of two 8 week programmes of reconditioning in chronic obstructive pulmonary disease (COPD) patients were studied. Forty one subjects (mean+/-SD) 644.5) yrs; forced expiratory volume in one second (FEV1) 1.09+/-0.16 L; 40.6+/-6.2% predicted were randomly assigned either to supervised training on a treadmill, 4 days x week(-1) (group S; n=21) or walking 3 or 4 km in 1 h 4 days x week(-1), self-monitored with a pedometer, with weekly visits to encourage adherence (group SM; n=20). Patients were evaluated with the chronic respiratory diseases questionnaire (CRQ) and two exercise tests on a treadmill: incremental (IT) and constant (CT), above lactic threshold or 70% of maximal oxygen uptake (VO2, max) with arterial blood lactate determinations. Estimated mean work rate of training was 69+/-27 W and 25+/-5 W respectively for groups S and SM. Both types of training produced similar changes in the four dimensions of the CRQ. In group S reconditioning yielded significant (p<0.05) increases in VO2, max and increases in duration, with decreased lactate accumulation, ventilation, CO2 output (VCO2), heart rate (HR) and diastolic blood pressure (DBP) at the end of CT. They also adopted a deeper slower pattern of breathing during exercise. The SM group showed significant (p<0.05) increases in duration, lower HR and DBP at the end of CT. Significantly (p<0.05) different effects between S and SM programmes were changes in VO2, max 100+/-101 mL x min(-1) versus 5+/-101 mL x min(-1)), duration of the CT (8.1+/-4.4 min versus 3.9+/-4.7 min), VCO2 (-94+/-153 mL x min(-1) versus 48+/-252 mL x min(-1)), lactate accumulation (-1.3+/-2.2 mmol x L(-1) versus 0+/-1.2 mmol x L(-1) and respiratory rate at the end of CT (4.3+/-3.4 min(-1) versus -1+/-4.2 min(-1)). Supervised, intense training yields physiological improvements in severe chronic obstructive pulmonary disease patients not induced by self-monitored training. The self-monitored, less intense training, increases submaximal exercise endurance, although to a lesser degree.

Aged↗

PubMed2000

Influence of work rate incremental rate on the exercise responses in patients with COPD.

PURPOSE: The peak work rate (Wpeak) measured during a progressive stepwise exercise test is commonly used to select the target training intensity for an exercise training program. In healthy subjects, a greater Wpeak is achieved when a faster rate of increase in work rate is used, whereas VO2 peak is independent of the rate of increase in work rate. This effect might be even more pronounced in chronic obstructive pulmonary disease (COPD) patients, in whom the VO2 kinetics during exercise are slower compared with healthy subjects. METHODS: To investigate this, we studied 10 COPD patients (9 M/1 F, age: 65+/-5 yr [mean +/- SD], FEV1: 33+/-8%). They underwent, on separate days, three stepwise exercise tests on an ergocycle. For each test, increments of 5, 10, or 20 W x min(-1) were used in random order; the investigator was blinded as to which increment was used. VO2, VCO2, heart rate (HR), minute ventilation (VE), breathlessness and leg fatigue at rest, at each work rate, and at maximal capacity were obtained. RESULTS: Wpeak averaged 40+/-13, 53+/-14, and 66+/-19 W for the 5-, 10-, and 20-W protocol, respectively (P < 0.001), whereas VO2 peak was comparable at 0.96+/-0.16, 1.02+/-0.18, and 1.03+/-0.20 L x min(-1). As the rate of increase in work rate became faster, the VO2/work rate relationship shifted to the right. This is exemplified by the VO2 at 40 W, which averaged 0.98+/-0.06, 0.90+/-0.09, and 0.83+/-0.10 L x min(-1) for the 5-, 10-, and 20-W protocol, respectively (P < 0.05). Similar observations were made for the relationship between HR, VE, and symptom scores, and work rate. There was no significant differences in peak values for HR and VE, and symptoms scores. CONCLUSIONS: We conclude that the work rate incremental rate influences the Wpeak achieved, whereas the peak values for VO2, HR, VE, and symptom scores remain comparable. These findings have practical implications for the exercise evaluation of patients with COPD.

Adaptation, Physiological↗