Oral nitrate supplementation to enhance pulmonary rehabilitation in COPD: ON-EPIC a multicentre, double-blind, placebo-controlled, randomised parallel group study.

RATIONALE: Dietary nitrate supplementation has been proposed as a strategy to improve exercise performance, both in healthy individuals and in people with COPD. We aimed to assess whether it could enhance the effect of pulmonary rehabilitation (PR) in COPD. METHODS: This double-blind, placebo-controlled, parallel group, randomised controlled study performed at four UK centres, enrolled adults with Global Initiative for Chronic Obstructive Lung Disease grade II-IV COPD and Medical Research Council dyspnoea score 3-5 or functional limitation to undertake a twice weekly 8-week PR programme. They were randomly assigned (1:1) to either 140 mL of nitrate-rich beetroot juice (BRJ) (12.9 mmol nitrate), or placebo nitrate-deplete BRJ, consumed 3 hours prior to undertaking each PR session. Allocation used computer-generated block randomisation. MEASUREMENTS: The primary outcome was change in incremental shuttle walk test (ISWT) distance. Secondary outcomes included quality of life, physical activity level, endothelial function via flow-mediated dilatation, fat-free mass index and blood pressure parameters. RESULTS: 165 participants were recruited, 78 randomised to nitrate-rich BRJ and 87 randomised to placebo. Exercise capacity increased more with active treatment (n=57) than placebo (n=65); median (IQR) change in ISWT distance +60 m (10, 85) vs +30 m (0, 70), estimated treatment effect 30 m (95% CI 10 to 40); p=0.027. Active treatment also impacted on systolic blood pressure: treatment group -5.0 mm Hg (-5.0, -3.0) versus control +6.0 mm Hg (-1.0, 15.5), estimated treatment effect -7 mm Hg (95% CI 7 to -20) (p<0.0005). No significant serious adverse events or side effects were reported. CONCLUSIONS: Dietary nitrate supplementation appears to be a well-tolerated and effective strategy to augment the benefits of PR in COPD. TRIAL REGISTRATION NUMBER: ISRCTN27860457.

An evaluation of factors associated with completion and benefit from pulmonary rehabilitation in COPD.

BACKGROUND: Pulmonary Rehabilitation (PR) is an important treatment for patients with chronic obstructive pulmonary disease (COPD) but it is not established whether any baseline parameter can predict response or compliance. AIM: To identify whether baseline measures can predict who will complete the programme and who will achieve a clinically significant benefit from a Minimum Clinical Important Difference (MCID) in terms of exercise capacity and health-related quality of life (HRQoL). METHODS: Data were collected prospectively from patients with COPD at their baseline assessment for an outpatient PR programme in one of eight centres across London. 'Completion' was defined as attending at least 75% of the designated PR visits and return for the follow-up evaluation. The MCID for outcome measures was based on published data. RESULTS: 787 outpatients with COPD (68.1±10.5 years old; 49.6% males) were included. Patients who completed PR (n=449, 57.1%) were significantly older with less severe airflow obstruction, lower anxiety and depression scores, less dyspnoea and better HRQoL. Only baseline CAT score (OR=0.925; 95% CI 0.879 to 0.974; p=0.003) was retained in multivariate analysis. Patients with the lowest baseline walking distance were most likely to achieve the MCID for exercise capacity. No baseline variable could independently predict achievement of an MCID in HRQoL. CONCLUSIONS: Patients with better HRQoL are more likely to complete PR while worse baseline exercise performance makes the achievement of a positive MCID in exercise capacity more likely. However, no baseline parameter could predict who would benefit the most in terms of HRQoL.

The COPD assessment test (CAT): response to pulmonary rehabilitation. A multicentre, prospective study.

BACKGROUND: The COPD (chronic obstructive pulmonary disease) assessment test (CAT) is a recently introduced, simple to use patient-completed quality of life instrument that contains eight questions covering the impact of symptoms in COPD. It is not known how the CAT score performs in the context of clinical pulmonary rehabilitation (PR) programmes or what the minimum clinically important difference is. METHODS: The introduction of the CAT score as an outcome measure was prospectively studied by PR programmes across London. It was used alongside other measures including the St George's Respiratory Questionnaire, the Chronic Respiratory Disease Questionnaire, the Clinical COPD Questionnaire, the Hospital Anxiety and Depression score, the Medical Research Council (MRC) dyspnoea score and a range of different walking tests. Patients completed a 5-point anchor question used to assess overall response to PR from 'I feel much better' to 'I feel much worse'. RESULTS: Data were available for 261 patients with COPD participating in seven programmes: mean (SD) age 69.0 (9.0) years, forced expiratory volume in 1 s (FEV(1)) 51.1 (18.7) % predicted, MRC score 3.2 (1.0). Mean change in CAT score after PR was 2.9 (5.6) points, improving by 3.8 (6.1) points in those scoring 'much better' (n=162), and by 1.3(4.5) in those who felt 'a little better' (n=88) (p=0.002). Only eight individuals reported no difference after PR and three reported feeling 'a little worse', so comparison with these smaller groups was not possible. CONCLUSION: The CAT score is simple to implement as an outcome measure, it improves in response to PR and can distinguish categories of response.