The Resistance Exercise in Already Active Diabetic Individuals (READI) Randomized Clinical Trial.

CONTEXT: Resistance exercise training (strength training) and aerobic exercise training are both recommended for people with type 1 diabetes, but it is unknown whether adding resistance exercise provides incremental benefits in people with this condition who already perform aerobic exercise regularly. OBJECTIVE: This work aimed to evaluate the incremental effect of resistance training on glycated hemoglobin A1c (HbA1c), fitness, body composition, and cardiometabolic risk factors in aerobically active people with type 1 diabetes. METHODS: The Resistance Exercise in Already-active Diabetic Individuals (READI) trial (NCT00410436) was a 4-center, randomized, parallel-group trial. After a 5-week run-in period with diabetes management optimization, 131 aerobically active individuals with type 1 diabetes were randomly assigned to resistance exercise (n = 71, intervention-INT) or control (n = 60, CON) for 22 additional weeks. Both groups maintained their aerobic activities and were provided dietary counseling throughout. Exercise training was 3 times per week at community-based facilities. The primary outcome was HbA1c, and secondary outcomes included fitness (peak oxygen consumption, muscle strength), body composition (anthropometrics, dual-energy x-ray absorptiometry, computed tomography), and cardiometabolic risk markers (lipids, apolipoproteins). Assessors were blinded to group allocation. RESULTS: There were no significant differences in HbA1c change between INT and CON. Declines in HbA1c (INT: 7.75 ± 0.10% [61.2 ± 1.1 mmol/mol] to 7.55 ± 0.10% [59 ± 1.1 mmol/mol]; CON: 7.70 ± 0.11% [60.7 ± 1.2 mmol/mol] to 7.57 ± 0.11% [59.6 ± 1.3 mmol/mol]; intergroup difference in change -0.07 [95% CI, -0.31 to 0.18]). Waist circumference decreased more in INT than CON after 6 months (P = .02). Muscular strength increased more in INT than in CON (P < .001). There were no intergroup differences in hypoglycemia or any other variables. CONCLUSION: Adding resistance training did not affect glycemia, but it increased strength and reduced waist circumference, in aerobically active individuals with type 1 diabetes.

Effect of incremental exercise on airway and systemic inflammation in patients with COPD.

Airway and systemic inflammation are features of chronic obstructive pulmonary disease (COPD), and there is growing interest in clarifying the inflammatory processes. Strenuous exercise induces an intensified systemic inflammatory response in patients with COPD, but no study has investigated the airway inflammatory and anti-inflammatory responses to exercise. Twenty steroid-naïve, ex-smokers with diagnosed COPD (forced expired volume in 1 s = 66 ± 12%) underwent baseline collection of venous blood and induced sputum followed by an incremental exercise test to symptom limitation 48 h later. Additional venous blood samples were collected following exercise at 0, 2, and 24 h, while induced sputum was collected 2 and 24 h after exercise. Sputum and blood samples were analyzed for differential cell count, CD4(+) and CD8(+) T lymphocytes (serum only), interleukin (IL)-6, IL-8, IL-10, chemokine (C-C motif) ligand 5 (CCL5), and high sensitivity C-reactive protein (serum only). There was an increase in the number of sputum eosinophils (cells/gram, P = 0.012) and a reduction in sputum IL-6 (P = 0.01) 24 h postexercise. Sputum IL-8 and CCL5 were also persistently decreased after exercise (P = 0.0098 and P = 0.0012, respectively), but sputum IL-10 did not change. There was a decrease in serum eosinophils 2 h after exercise (P = 0.0014) and a reduction in serum CCL5 immediately following and 2 h postexercise (P < 0.0001). Both serum eosinophils and CCL5 returned to baseline levels within 24 h. An acute bout of exercise resulted in a significant increase in the number of sputum eosinophils, which may be mediated by serum CCL5. However, there was also a reduction in sputum proinflammatory cytokines, suggesting some anti-inflammatory effect of exercise in the lungs of steroid-naïve patients with COPD.

CPAP increases exercise tolerance in obese subjects with obstructive sleep apnea.

Obese subjects commonly suffer from exertional dyspnea and exercise intolerance. Preliminary evidence suggests that treatment with nocturnal continuous positive airway pressure (nCPAP) may improve dyspnea in obese patients with obstructive sleep apnea (OSA), but the effect on exercise tolerance is unknown. This study sought to investigate whether nCPAP improves exercise tolerance and exertional dyspnea in obese patients with OSA. Obese patients prescribed nCPAP for moderate/severe OSA and without cardiopulmonary disease were recruited. Patients completed a constant-load exercise test and Baseline and Transitional Dyspnea Index questionnaires (BDI/TDI) at baseline and after one and three months of nCPAP. Primary outcome was change in constant-load exercise time from baseline to one and three months. Secondary outcomes included changes in isotime dyspnea, isotime leg fatigue and BDI/TDI score at one and three months. Fifteen subjects (body mass index = 43 kg m(-2), apnea-hypopnea index = 49(.)hr(-1)) were studied. Constant-load exercise time increased by 2.0 min (40%, p = 0.02) at one month and 1.8 min (36%, p = 0.04) at three months. At one and three months, isotime dyspnea decreased by 1.4 (p = 0.17) and 2 units (p = 0.04), and leg fatigue decreased by 1.2 (p = 0.18) and 2 units (p = 0.02), respectively. BDI/TDI scores were 2.7 (p = 0.001) and 4.5 points (p < 0.001) at one and three months. Peak oxygen consumption and static pulmonary function were unchanged. Nocturnal CPAP improves exercise tolerance and dyspnea in obese patients with OSA. Effects on exercise time and chronic dyspnea were seen after one and three months of nCPAP, while exertional dyspnea was only improved at three months.

Helium-hyperoxia: a novel intervention to improve the benefits of pulmonary rehabilitation for patients with COPD.

BACKGROUND: Helium-hyperoxia (HH) reduces dyspnea and increases exercise tolerance in patients with COPD. We investigated whether breathing HH would allow patients to perform a greater intensity of exercise and improve the benefits of a pulmonary rehabilitation program. METHODS: Thirty-eight nonhypoxemic patients with COPD (FEV(1)=47 +/- 17%(pred)) were randomized to rehabilitation breathing HH (60:40 He:O(2); n = 19) or air (n = 19). Patients cycled for 30 min, 3 days/week for 6 weeks breathing the assigned gas. Exercise intensity was prescribed from baseline, gas-specific, incremental exercise tests and was advanced as tolerated. The primary outcome was exercise tolerance assessed as a change in constant-load exercise time (CLT) following rehabilitation. Secondary outcomes were changes in exertional symptoms, health related quality of life (as assessed by the Short-form 36 and St George respiratory questionnaires), and peak oxygen consumption during an incremental exercise test. RESULTS: The HH group had a greater change in CLT following rehabilitation compared to the air group (9.5 +/- 9.1 vs 4.3 +/- 6.3 min, p < 0.05). At an exercise isotime, dyspnea was significantly reduced in both groups, while leg discomfort only decreased in the HH group. The changes in exertional symptoms and peak oxygen consumption were not different between groups. Health-related quality of life significantly improved in both groups; however, the change in St. George respiratory questionnaire total score was greater with HH (-7.6 +/- 6.4 vs -3.6 +/- 5.6, p < 0.05). During rehabilitation, the HH group achieved a higher exercise intensity and training duration throughout the program (p < 0.05). CONCLUSIONS: Breathing HH during pulmonary rehabilitation increases the intensity and duration of exercise training that can be performed and results in greater improvements in CLT for patients with COPD.

A randomized controlled trial to assess the efficacy of tiotropium in Canadian patients with chronic obstructive pulmonary disease.

BACKGROUND: Patients with chronic obstructive pulmonary disease (COPD) who smoke have a greater annual rate of decline in forced expiratory volume in 1 s (FEV(1)) than those patients who have stopped smoking. OBJECTIVES: To assess the effect of tiotropium on pre-dose (trough) FEV(1) in patients with COPD followed in Canada. METHODS: A total of 913 patients were randomly assigned to receive either tiotropium 18 mug once daily (n=608) or placebo (usual care minus inhaled anticholinergics) (n=305) for 48 weeks in the present randomized, double-blind, parallel-group study. The effect of tiotropium on measurements of lung function (FEV(1), FEV(6) and forced vital capacity), symptoms, health-related quality of life (St George's Respiratory Questionnaire) and exacerbations were examined. RESULTS: Tiotropium improved trough FEV(1) in both current and ex-smokers compared with placebo. Baseline FEV(1) in smokers and ex-smokers was 1.03 L and 0.93 L, respectively (P<0.001). At week 48, the mean difference between the tiotropium and placebo groups was 0.14+/-0.04 L (P<0.001) in the smoker group and 0.08+/-0.02 L (P<0.0001) in the ex-smoker group. Tiotropium also significantly improved trough forced vital capacity and FEV(6) compared with placebo throughout the treatment period (P<0.05, for all). Furthermore, tiotropium significantly improved the St George's Respiratory Questionnaire total score compared with placebo at week 48 (40.9 versus 43.7 units, P<0.005). CONCLUSIONS: Compared with the placebo group, tiotropium provides sustained improvements in lung function in patients with COPD, with improvements for smokers and ex-smokers.

Resource use study in COPD (RUSIC): a prospective study to quantify the effects of COPD exacerbations on health care resource use among COPD patients.

BACKGROUND: There is increasing interest in health care resource use (HRU) in Canada, particularly in resources associated with acute exacerbations of chronic obstructive pulmonary disease (COPD). OBJECTIVE: To identify HRU due to exacerbations of COPD. METHODS: A 52-week, multicentre, prospective, observational study of HRU due to exacerbations in patients with moderate to severe COPD was performed. Patients were recruited from primary care physicians and respirologists in urban and rural centres in Canada. RESULTS: In total, 524 subjects (59% men) completed the study. Their mean age was 68.2+/-9.4 years, with a forced expiratory volume in 1 s of 1.01+/-0.4 L. Patients had significant comorbidities. There were 691 acute exacerbations of COPD, which occurred in 53% of patients: 119 patients (23%) experienced one acute exacerbation, 70 patients (13%) had two acute exacerbations and 89 patients (17%) had three or more acute exacerbations. Seventy-five patients were admitted to hospital, with an average length of stay of 13.2 days. Fourteen of the patients spent time in an intensive care unit (average length of stay 5.6 days). Factors associated with acute exacerbations of COPD included lower forced expiratory volume in 1 s (P<0.001), high number of respiratory medications prescribed (P=0.037), regular use of oral corticosteroids (OCSs) (P=0.008) and presence of depression (P<0.001). Of the 75 patients hospitalized, only 53 received OCSs, four received referral for rehabilitation and 15 were referred for home care. CONCLUSIONS: The present study showed a high prevalence of COPD exacerbations, which likely impacted on HRU. There was evidence of a lack of appropriate management of exacerbations, especially with respect to use of OCSs, and referral for pulmonary rehabilitation and home care.

Emphysema in alpha1-antitrypsin deficiency: does replacement therapy affect outcome?

Severe alpha(1)-antitrypsin (AAT) deficiency is an inherited disorder that leads to the development of emphysema in smokers at a relatively young age; most are disabled in their forties. Emphysema is caused by the protease-antiprotease imbalance when smoking-induced release of neutrophil elastase in the lung is inadequately inhibited by the deficient levels of AAT, the major inhibitor of neutrophil elastase. This protease-antiprotease imbalance leads to proteolytic damage to lung connective tissue (primarily elastic fibers), and the development of panacinar emphysema. AAT replacement therapy, most often applied by weekly intravenous infusions of AAT purified from human plasma, has been used to partially correct the biochemical defect and raise the serum AAT level above a theoretically protective threshold level of 0.8 g/L. A randomized controlled clinical trial was not considered feasible when purified antitrypsin was released for clinical use. However, AAT replacement therapy has not yet been proven to be clinically effective in reducing the progression of disease in AAT-deficient patients. There was a suggestion of a slower progression of emphysema by computed tomography (CT) scan in a small randomized trial. Two nonrandomized studies comparing AAT-deficient patients already receiving replacement therapy with those not receiving it, and a retrospective study evaluating a decline in FEV(1) before and after replacement therapy, suggested a possible benefit for selected patients. Because of the lack of definitive proof of the clinical effectiveness of AAT replacement therapy and its cost, we recommend reserving AAT replacement therapy for deficient patients with impaired FEV(1) (35-65% of predicted value), who have quit smoking and are on optimal medical therapy but continue to show a rapid decline in FEV(1) after a period of observation of at least 18 months. A randomized placebo-controlled trial using CT scan as the primary outcome measure is required. Screening for AAT deficiency is recommended in patients with chronic irreversible airflow obstruction with atypical features such as early onset of disease or disability in their forties or fifties, or positive family history, and in immediate family members of patients with AAT deficiency.

Asthma in adolescents: a randomized, controlled trial of an asthma program for adolescents and young adults with severe asthma.

BACKGROUND: Asthma is common and is often poorly controlled in adolescent subjects. OBJECTIVE: To determine the impact of an age-specific asthma program on asthma control, particularly on exacerbations of asthma requiring emergency department treatment, and on the quality of life of adolescents with asthma. METHODS: The present randomized, controlled trial included patients who were 15 to 20 years of age and had visited emergency departments for management of their asthma. The interventional group attended an age-specific asthma program that included assessment, education and management by a team of asthma educators, respiratory therapists and respiratory physicians. In the control group, spirometry was performed, and the patients continued to receive usual care from their regular physicians. The outcomes were assessed by a questionnaire six months after entry into the study. RESULTS: Ninety-three subjects entered the study and were randomly assigned to the intervention or control group. Of these, only 62 patients were available for review after six months. Subjects in both the control and the intervention groups showed a marked improvement in their level of asthma control, reflected primarily by a 73% reduction in the rate of emergency department attendance for asthma. Other indexes of disease control, including disease-specific quality of life, as assessed by questionnaires, were improved. There was, however, no discernible difference between the subjects in the two groups, with the exception of an improvement in favour of the intervention group in the symptom (actual difference 0.7, P=0.048) and emotional (actual difference 0.8, P=0.028) domains of the asthma quality of life questionnaire. The overall quality of life score favoured the intervention group by a clinically relevant difference of 0.6, but this difference did not reach statistical significance (P=0.06). CONCLUSIONS: Although all subjects demonstrated a significant improvement in asthma control and quality of life, the improvement attributable to this intervention was limited to two domains in disease-specific quality of life.

Hypoxemia and low Crs in vagally denervated lambs result from reduced lung volume and not pulmonary edema.

Vagal denervation performed in the intrathoracic region in newborn lambs leads to hypoxemia and decreased respiratory system compliance (Crs), which could result from atelectasis and/or pulmonary edema. The objective of the present study was to quantify the relative roles of alveolar derecruitment and pulmonary edema as underlying cause(s) of respiratory failure. Vagal denervation was performed in the intrathoracic region and below the recurrent laryngeal nerves in six newborn lambs within 24 h of birth, whereas six were sham operated. Pre- and postinflation Crs was measured to investigate the presence of alveolar derecruitment. Pulmonary edema was assessed with lung wet-dry-to-wet and lung tissue wet-to-dry ratios, total protein, and FITC-BSA recovery in lung tissue and bronchoalveolar lavage. Compared with that in the sham-operated animals, Crs was significantly lower in vagally denervated animals. However, postinflation, pulmonary system compliance obtained by quasi-static lung inflation and deflation to 30 cmH2O showed no significant difference between the sham-operated and denervated lambs. The lung wet-dry-to-wet and lung tissue wet-to-dry ratios, total protein, and FITC-BSA recovery in lung tissue and bronchoalveolar lavage were similar in denervated and sham-operated groups. We provide evidence that reduced lung volume and not pulmonary edema is associated with intrathoracic vagal denervation and is the likely underlying mechanism for hypoxemia and low Crs.