Randomized Trial of Nocturnal Oxygen in Chronic Obstructive Pulmonary Disease.

BACKGROUND: Long-term oxygen therapy improves survival in patients with chronic obstructive pulmonary disease (COPD) and chronic severe daytime hypoxemia. However, the efficacy of oxygen therapy for the management of isolated nocturnal hypoxemia is uncertain. METHODS: We designed this double-blind, placebo-controlled, randomized trial to determine, in patients with COPD who have nocturnal arterial oxygen desaturation without qualifying for long-term oxygen therapy, whether nocturnal oxygen provided for a period of 3 to 4 years would decrease mortality or the worsening of disease such that patients meet current specifications for long-term oxygen therapy. Patients with an oxygen saturation of less than 90% for at least 30% of the recording time on nocturnal oximetry were assigned, in a 1:1 ratio, to receive either nocturnal oxygen or ambient air from a sham concentrator (placebo). The primary outcome was a composite of death from any cause or a requirement for long-term oxygen therapy as defined by the Nocturnal Oxygen Therapy Trial (NOTT) criteria in the intention-to-treat population. RESULTS: Recruitment was stopped prematurely because of recruitment and retention difficulties after 243 patients, of a projected 600, had undergone randomization at 28 centers. At 3 years of follow-up, 39.0% of the patients assigned to nocturnal oxygen (48 of 123) and 42.0% of those assigned to placebo (50 of 119) met the NOTT-defined criteria for long-term oxygen therapy or had died (difference, -3.0 percentage points; 95% confidence interval, -15.1 to 9.1). CONCLUSIONS: Our underpowered trial provides no indication that nocturnal oxygen has a positive or negative effect on survival or progression to long-term oxygen therapy in patients with COPD. (Funded by the Canadian Institutes of Health Research; INOX ClinicalTrials.gov number, NCT01044628.).

Short-Term Oxygen Therapy Outcomes in COPD.

Rationale: Short-term oxygen therapy (STOT) is often prescribed to allow patients with chronic obstructive pulmonary disease (COPD) to be discharged safely from hospital following an acute illness. This practice is widely accepted without being based on evidence. Purpose: Our objective was to describe the characteristics and outcomes of patients with COPD who received STOT. Patients and Methods: The study was a secondary analysis of the INOX trial, a 4-year randomised trial of nocturnal oxygen in COPD. The trial indicated that nocturnal oxygen has no significant effect on survival or progression to LTOT, allowing our merging of patients who received nocturnal oxygen and those who received placebo into a single cohort to study the predictors and outcomes of STOT regardless of the treatment received during the trial. Results: Among the 243 participants in the trial, 60 required STOT on at least one occasion during follow-up. Patients requiring STOT had more severe dyspnoea and lung function impairment, and lower PaO2 at baseline than those who did not. STOT was associated with subsequent LTOT requirement (hazard ratio [HR]: 4.59; 95% confidence interval [CI]: 2.98-7.07) and mortality (HR: 1.93; 95% CI: 1.15-3.24). The association between STOT and mortality was confounded by age, disease severity and comorbidities. Periods of STOT of more than one month and/or repeated prescriptions of STOT increased the probability of progression to LTOT (OR: 5.07; 95% CI: 1.48-18.8). Conclusion: Following an acute respiratory illness in COPD, persistent hypoxaemia requiring STOT is a marker of disease progression towards the requirement for LTOT.

Effects of home-based pulmonary rehabilitation in patients with chronic obstructive pulmonary disease: a randomized trial.

BACKGROUND: Home-based rehabilitation is a promising approach to improve access to pulmonary rehabilitation. OBJECTIVE: To assess whether self-monitored, home-based rehabilitation is as effective as outpatient, hospital-based rehabilitation in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Randomized, multicenter, noninferiority trial. SETTING: 10 academic and community medical centers in Canada. PATIENTS: 252 patients with moderate to severe COPD. INTERVENTION: After a 4-week education program, patients took part in home-based rehabilitation or outpatient, hospital-based rehabilitation for 8 weeks. They were followed for 40 weeks to complete the 1-year study. MEASUREMENTS: The primary outcome was the change in Chronic Respiratory Questionnaire dyspnea subscale score at 1 year. The primary analysis took a modified intention-to-treat approach by using all patients who provided data at the specified follow-up time, regardless of their level of adherence. The analysis used regression modeling that adjusted for the effects of center, sex, and baseline level. All differences were computed as home intervention minus outpatient intervention. RESULTS: Both interventions produced similar improvements in the Chronic Respiratory Questionnaire dyspnea subscale at 1 year: improvement in dyspnea of 0.62 (95% CI, 0.43 to 0.80) units in the home intervention (n = 107) and 0.46 (CI, 0.28 to 0.64) units in the outpatient intervention (n = 109). The difference between the 2 treatments at 1 year was small and clinically unimportant. The 95% CI of the difference did not exceed the prespecified noninferiority margin of 0.5: difference in dyspnea score of 0.16 (CI, -0.08 to 0.40). Most adverse events were related to COPD exacerbations. No serious adverse event was considered to be related to the study intervention. LIMITATION: The contribution of the educational program to the improvement in health status and exercise tolerance cannot be ascertained. CONCLUSION: Home rehabilitation is a useful, equivalent alternative to outpatient rehabilitation in patients with COPD.

A Canadian, multicentre, randomized clinical trial of home-based pulmonary rehabilitation in chronic obstructive pulmonary disease: rationale and methods.

BACKGROUND: Pulmonary rehabilitation remains largely underused. Self-monitored, home-based rehabilitation is a promising approach to improving the availability of pulmonary rehabilitation. OBJECTIVE: To report the rationale and methods of a trial comparing the effectiveness of self-monitored, home-based rehabilitation with hospital-based, outpatient rehabilitation in patients with chronic obstructive pulmonary disease (COPD). STUDY DESIGN: A parallel-group, randomized, noninferiority, multicentre trial will be performed with 240 patients with moderate to severe COPD. INTERVENTION: Patients will be randomly assigned to conventional, supervised, hospital-based outpatient rehabilitation or self-monitored, home-based rehabilitation. Both interventions will include a standardized, comprehensive self-management program, in addition to the hospital-based outpatient or home-based exercise program. After the three-month intervention, patients in both groups will be encouraged to continue exercising at home. Patients will be assessed monthly with telephone interviews and in person at enrollment, three months and 12 months. OUTCOMES: The dyspnea domain of the Chronic Respiratory Questionnaire (CRQ) at 12 months is the primary outcome variable. Secondary outcome variables include total and domain-specific CRQ scores; exercise tolerance and activity of daily living; health service use over the one-year study period; and direct and indirect costs of COPD treatment. ANALYSIS: An intent-to-treat approach will be used as the primary analysis. The primary analysis will focus on the change in the CRQ dyspnea score using a two-sided t distribution based on 95% CIs. The same approach will be used for secondary continuous outcome variables. CONCLUSION: The present trial will address two unresolved issues in pulmonary rehabilitation for patients with COPD: the short-term and long-term effectiveness of home-based pulmonary rehabilitation strategies. The authors will also determine if home-based pulmonary rehabilitation can reduce health service use (eg, hospitalizations and emergency visits) and if it can be done at a lower cost than the traditional hospital-based outpatient pulmonary rehabilitation.

Safety, pharmacodynamics and pharmacokinetics of TPI 1020 in smokers with asthma.

BACKGROUND: TPI 1020 is a novel compound with potential for anti-neutrophil effects. TPI 1020 exerts its effects by a dual mechanism of action involving corticosteroid activity and controlled donation of nitric oxide. OBJECTIVES: We assessed the safety, pharmacodynamic and pharmacokinetic activity of ascending doses of TPI 1020 compared to budesonide in asthma. METHODS: Smokers with mild asthma (n=27) were randomized to receive either 600mcg of TPI 1020 (n=13) or 400mcg of budesonide (n=14) bid for 2weeks followed by 1200 and 800mcg bid, respectively, for an additional week. RESULT: There was no serious adverse event and all but one adverse event were mild or moderate (severe headache with budesonide). Patients receiving TPI 1020 reported three-fold fewer treatment-emergent AEs (n=13) than those receiving budesonide (n=39). TPI 1020 had similar effects as budesonide on FEV(1), PEF, rescue medication, asthma scoring system, methacholine response, sputum eosinophils and exhaled NO. Sputum neutrophils (%) tended to decrease more with TPI 1020 (32.6% decrease versus 3.7% increase for budesonide); the decrease occurring only in patients with high neutrophils at baseline. A significant difference favoring TPI 1020 was noted for CRP. Budesonide caused a statistically significant decrease in 24h urinary free cortisol over 22days (median of 4.4-2.8mcg/ml, p=0.01) whereas TPI 1020 had no such effect (4.4-5.8mcg/ml), suggesting lower systemic corticosteroid exposure following TPI 1020 treatment. CONCLUSION: TPI 1020 appears safe in asthmatic smokers and warrants further investigation in respiratory conditions.

Validity and reliability of the modified shuttle walk test in patients with chronic obstructive pulmonary disease.

OBJECTIVES: (1) To examine the concurrent criterion validity of the modified shuttle walk test (MSWT) by using the 6- (6MWT) and 12-minute walk test (12MWT), (2) to examine the concurrent criterion validity of the estimated maximum oxygen uptake (Vo2max) of the MSWT with actual Vo2max, and (3) to determine test-retest reliability of the MSWT in patients with chronic obstructive pulmonary disease (COPD). DESIGN: Validation study. SETTING: Outpatient pulmonary rehabilitation program. PARTICIPANTS: Thirty clinically stable adults with COPD. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Subjects were randomly assigned to receive either the 6MWT and 12MWT or the MSWT first. The MSWT was repeated 1 week later (N = 30). Estimated Vo2max was calculated, and actual Vo2max was conducted by using the Jones test. Validity of the MSWT was assessed by comparing endurance scores and Vo2max with results from the 6MWT and 12MWT and Jones test, respectively. RESULTS: There was a moderately high correlation between the MSWT and the 6MWT and 12MWT at initial testing (.82 and .74, respectively). Correlation between estimated and actual Vo2max was r equal to .68. Test-retest reliability for the entire sample was high (intraclass correlation coefficient, .88). Results remained quite stable across severity, age, and sex subgroups. CONCLUSIONS: The MSWT is a standardized externally paced submaximal endurance walking test. The results indicate that the MSWT has high concurrent validity and test-retest reliability for patients with COPD.