Sex differences and determinants of anxiety symptoms in patients with COPD initiating pulmonary rehabilitation.

BACKGROUND: Anxiety is common in patients with chronic obstructive pulmonary disease (COPD). However, there is little evidence available regarding gender differences, and severity of dyspnea in relation to anxiety in patients with COPD. AIMS: We examined gender differences and the association of dyspnea with anxiety in a cohort of patients with COPD prior to entering a pulmonary rehabilitation (PR) program. METHOD: We analyzed data from a prospective cohort of COPD patients who attended PR from 2013 to 2019 in Lytham, Lancashire, UK. Patients were aged 40 years or older with a post-bronchodilation forced expiratory volume in 1 s (FEV1) less than 80 % of the predicted normal value and FEV1/FVC (forced vital capacity) ratio less than 0.7. We assessed quality of life (QoL) using the Saint George's Respiratory Questionnaire (SGRQ), anxiety using the Anxiety Inventory for Respiratory disease (AIR), dyspnea using the modified Medical Research Council (mMRC) scale, and exercise capacity using the Incremental Shuttle Walk Test (ISWT). RESULTS: Nine hundred ninety-three patients with COPD (mean age = 71 years, FEV1/FVC = 58 % predicted, 51 % male) entered the PR program. Of these, 348 (35 %) had anxiety symptoms (AIR ≥8); of these 165 (47 %) were male and 183 (53 %) female, (χ2 = 3.33, p = 0.06). On logistic multivariate analysis, the following variables were independently associated with elevated anxiety: younger age (p < 0.001), female sex (p = 0.03), higher SGRQ-total score (p < 0.001) and high FEV1/FVC (p < 0.002). Dyspnea was associated with anxiety r = 0.25, p < 0.001. CONCLUSION: Over a third of COPD patients had clinically relevant anxiety symptoms with a higher prevalence in women than men. Anxiety was associated with younger age, female gender, and impaired QoL. Early recognition and treatment of anxiety in patients with COPD is worthy of consideration for those attending PR, especially women.

Instantaneous quantification of skeletal muscle activation, power production, and fatigue during cycle ergometry.

A rapid switch from hyperbolic to isokinetic cycling allows the velocity-specific decline in maximal power to be measured, i.e., fatigue. We reasoned that, should the baseline relationship between isokinetic power (Piso) and electromyography (EMG) be reproducible, then contributions to fatigue may be isolated from 1) the decline in muscle activation (muscle activation fatigue); and 2) the decline in Piso at a given activation (muscle fatigue). We hypothesized that the EMG-Piso relationship is linear, velocity dependent, and reliable for instantaneous fatigue assessment at intolerance during and following whole body exercise. Healthy participants (n = 13) completed short (5 s) variable-effort isokinetic bouts at 50, 70, and 100 rpm to characterize baseline EMG-Piso. Repeated ramp incremental exercise tests were terminated with maximal isokinetic cycling (5 s) at 70 rpm. Individual baseline EMG-Piso relationships were linear (r(2) = 0.95 ± 0.04) and velocity dependent (analysis of covariance). Piso at intolerance (two legs, 335 ± 88 W) was ∼45% less than baseline [630 ± 156 W, confidence interval of the difference (CIDifference) 211, 380 W, P < 0.05]. Following intolerance, Piso recovered rapidly (F = 44.1; P < 0.05; η(2) = 0.79): power was reduced (P < 0.05) vs. baseline only at 0-min (CIDifference 80, 201 W) and 1-min recovery (CIDifference 13, 80 W). Activation fatigue and muscle fatigue (one leg) were 97 ± 55 and 60 ± 50 W, respectively. Mean bias ± limits of agreement for reproducibility were as follows: baseline Piso 1 ± 30 W; Piso at 0-min recovery 3 ± 35 W; and EMG at Piso 3 ± 14%. EMG power is linear, velocity dependent, and reproducible. Deviation from this relationship at the limit of tolerance can quantify the "activation" and "muscle" related components of fatigue during cycling.

Physiological responses to linear treadmill and cycle ergometer exercise in COPD.

Incremental cardiopulmonary exercise testing work rate ideally increases linearly to the subject's tolerance within approximately 10 min. Widely used treadmill protocols often yield shorter exercise times in debilitated patients. We compared a recently described treadmill protocol featuring linear work rate increase, weight adjustments and a priori exercise tolerance estimates with standard cycle and treadmill protocols. We also compared treadmill and cycle responses to examine mechanisms of oxyhaemoglobin desaturation differences. In total, 16 subjects with chronic obstructive pulmonary disease (COPD; mean+/-sd forced expiratory volume in 1 s of 36.5+/-10.9% predicted) performed incremental exercise using cycle, linear treadmill and modified Bruce protocols. Initial linear treadmill speed and grade yielded oxygen uptake (V'(O(2))) similar to cycle unloaded pedalling; Bruce protocol first stage elicited much higher V'(O(2)). Exercise duration was much shorter in Bruce than in cycle or linear treadmill protocols. At peak exercise, greater desaturation was noted in linear treadmill and Bruce protocols compared with cycle (-8.9+/-4.9 versus -8.5+/-4.7 versus -3.7+/-3.3%; p<0.001); at iso-V'(O(2)) values this difference widened as exercise proceeded. Iso-V'(O(2)) desaturation differences were largely related to higher ventilatory response to cycle than to treadmill exercise. The linear incremental treadmill protocol generates responses similar to cycle ergometry in severe COPD. However, cycle ergometry elicits less desaturation than does ambulation, making the linear treadmill protocol advantageous when evaluating COPD patients.

Developing concepts in the pulmonary rehabilitation of COPD.

Randomised trials have demonstrated that pulmonary rehabilitation (PR) can improve dyspnoea, exercise tolerance and health related quality of life. Rehabilitation has traditionally been provided in secondary care to patients with moderate to severe disease. Current concepts are however recommending that it should be delivered in a primary and community care setting for patients with milder disease. There are several opportunities for spreading the word for PR in primary care. One of these is to improve access to PR for all those disabled by their disease by the increase of community schemes and one such scheme being utilised in Canada is reviewed. The essential components of PR include behavior change, patient self-management and prescriptive exercise. In the last decade new strategies have been developed to enhance the effects of exercise training. An overview of these new approaches being an adjunct to exercise training is reviewed. Although the role of exercise training is well established, we are only just beginning to appreciate the importance of behavior change and patient self-management in contributing to improved health and diminished healthcare resource utilisation.

Recommendations on the use of exercise testing in clinical practice.

Evidence-based recommendations on the clinical use of cardiopulmonary exercise testing (CPET) in lung and heart disease are presented, with reference to the assessment of exercise intolerance, prognostic assessment and the evaluation of therapeutic interventions (e.g. drugs, supplemental oxygen, exercise training). A commonly used grading system for recommendations in evidence-based guidelines was applied, with the grade of recommendation ranging from A, the highest, to D, the lowest. For symptom-limited incremental exercise, CPET indices, such as peak O(2) uptake (V'O(2)), V'O(2) at lactate threshold, the slope of the ventilation-CO(2) output relationship and the presence of arterial O(2) desaturation, have all been shown to have power in prognostic evaluation. In addition, for assessment of interventions, the tolerable duration of symptom-limited high-intensity constant-load exercise often provides greater sensitivity to discriminate change than the classical incremental test. Field-testing paradigms (e.g. timed and shuttle walking tests) also prove valuable. In turn, these considerations allow the resolution of practical questions that often confront the clinician, such as: 1) "When should an evaluation of exercise intolerance be sought?"; 2) "Which particular form of test should be asked for?"; and 3) "What cluster of variables should be selected when evaluating prognosis for a particular disease or the effect of a particular intervention?"

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.

Long-term effects of a maintenance program after supervised or self-monitored training programs in patients with COPD.

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.

[Peripheral muscle dysfunction in chronic obstructive pulmonary disease]. / Dysfonction musculaire périphérique dans la bronchopneumopathie chronique obstructive.

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.

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.

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.