Claire M. Nolan

Minimum clinically important difference for the COPD Assessment Test: a prospective analysis

BACKGROUND The COPD Assessment Test (CAT) is responsive to change in patients with chronic obstructive pulmonary disease (COPD). However, the minimum clinically important difference (MCID) has not been established. We aimed to identify the MCID for the CAT using anchor-based and distribution-based methods. METHODS We did three studies at two centres in London (UK) between April 1, 2010, and Dec 31, 2012. Study 1 assessed CAT score before and after 8 weeks of outpatient pulmonary rehabilitation in patients with COPD who were able to walk 5 m, and had no contraindication to exercise. Study 2 assessed change in CAT score at discharge and after 3 months in patients admitted to hospital for more than 24 h for acute exacerbation of COPD. Study 3 assessed change in CAT score at baseline and at 12 months in stable outpatients with COPD. We focused on identifying the minimum clinically important improvement in CAT score. The St Georges Respiratory Questionnaire (SGRQ) and Chronic Respiratory Questionnaire (CRQ) were measured concurrently as anchors. We used receiver operating characteristic curves, linear regression, and distribution-based methods (half SD, SE of measurement) to estimate the MCID for the CAT; we included only patients with paired CAT scores in the analysis. FINDINGS In Study 1, 565 of 675 (84%) patients had paired CAT scores. The mean change in CAT score with pulmonary rehabilitation was -2·5 (95% CI -3·0 to -1·9), which correlated significantly with change in SGRQ score (r=0·32; p<0·0001) and CRQ score (r=-0·46; p<0·0001). In Study 2, of 200 patients recruited, 147 (74%) had paired CAT scores. Mean change in CAT score from hospital discharge to 3 months after discharge was -3·0 (95% CI -4·4 to -1·6), which correlated with change in SGRQ score (r=0·47; p<0·0001). In Study 3, of 200 patients recruited, 164 (82%) had paired CAT scores. Although no significant change in CAT score was identified after 12 months (mean 0·6, 95% CI -0·4 to 1·5), change in CAT score correlated significantly with change in SGRQ score (r=0·36; p<0·0001). Linear regression estimated the minimum clinically important improvement for the CAT to range between -1·2 and -2·8 with receiver operating characteristic curves consistently identifying -2 as the MCID. Distribution-based estimates for the MCID ranged from -3·3 to -3·8. INTERPRETATION The most reliable estimate of the minimum important difference of the CAT is 2 points. This estimate could be useful in the clinical interpretation of CAT data, particularly in response to intervention studies. FUNDING Medical Research Council and UK National Institute of Health Research.

The five-repetition sit-to-stand test as a functional outcome measure in COPD

Background Moving from sitting to standing is a common activity of daily living. The five-repetition sit-to-stand test (5STS) is a test of lower limb function that measures the fastest time taken to stand five times from a chair with arms folded. The 5STS has been validated in healthy community-dwelling adults, but data in chronic obstructive pulmonary disease (COPD) populations are lacking. Aims To determine the reliability, validity and responsiveness of the 5STS in patients with COPD. Methods Test-retest and interobserver reliability of the 5STS was measured in 50 patients with COPD. To address construct validity we collected data on the 5STS, exercise capacity (incremental shuttle walk (ISW)), lower limb strength (quadriceps maximum voluntary contraction (QMVC)), health status (St Georges Respiratory Questionnaire (SGRQ)) and composite mortality indices (Age Dyspnoea Obstruction index (ADO), BODE index (iBODE)). Responsiveness was determined by measuring 5STS before and after outpatient pulmonary rehabilitation (PR) in 239 patients. Minimum clinically important difference (MCID) was estimated using anchor-based methods. Results Test-retest and interobserver intraclass correlation coefficients were 0.97 and 0.99, respectively. 5STS time correlated significantly with ISW, QMVC, SGRQ, ADO and iBODE (r=−0.59, −0.38, 0.35, 0.42 and 0.46, respectively; all p<0.001). Median (25th, 75th centiles) 5STS time decreased with PR (Pre: 14.1 (11.5, 21.3) vs Post: 12.4 (10.2, 16.3) s; p<0.001). Using different anchors, a conservative estimate for the MCID was 1.7 s. Conclusions The 5STS is reliable, valid and responsive in patients with COPD with an estimated MCID of 1.7 s. It is a practical functional outcome measure suitable for use in most healthcare settings.

Sarcopenia in COPD: prevalence, clinical correlates and response to pulmonary rehabilitation

Background Age-related loss of muscle, sarcopenia, is recognised as a clinical syndrome with multiple contributing factors. International European Working Group on Sarcopenia in Older People (EWGSOP) criteria require generalised loss of muscle mass and reduced function to diagnose sarcopenia. Both are common in COPD but are usually studied in isolation and in the lower limbs. Objectives To determine the prevalence of sarcopenia in COPD, its impact on function and health status, its relationship with quadriceps strength and its response to pulmonary rehabilitation (PR). Methods EWGSOP criteria were applied to 622 outpatients with stable COPD. Body composition, exercise capacity, functional performance, physical activity and health status were assessed. Using a case–control design, response to PR was determined in 43 patients with sarcopenia and a propensity score-matched non-sarcopenic group. Results Prevalence of sarcopenia was 14.5% (95% CI 11.8% to 17.4%), which increased with age and Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) stage, but did not differ by gender or the presence of quadriceps weakness (14.9 vs 13.8%, p=0.40). Patients with sarcopenia had reduced exercise capacity, functional performance, physical activity and health status compared with patients without sarcopenia (p<0.001), but responded similarly following PR; 12/43 patients were no longer classified as sarcopenic following PR. Conclusions Sarcopenia affects 15% of patients with stable COPD and impairs function and health status. Sarcopenia does not impact on response to PR, which can lead to a reversal of the syndrome in select patients.

Reliability and validity of 4-metre gait speed in COPD

In community-dwelling older adults, usual gait speed over 4 m (4MGS) consistently predicts greater risk of adverse health outcomes. The aims of the present study were to assess the reliability of the 4MGS and the relationship with established health outcome measures in chronic obstructive pulmonary disease (COPD). Test-retest and interobserver reliability of the 4MGS were measured in 80 and 58 COPD patients, respectively. In 586 COPD patients, the 4MGS, as well as forced expiratory volume in 1 s (FEV1), the incremental shuttle walk (ISW), Medical Research Council (MRC) dyspnoea scale and St George’s Respiratory Questionnaire (SGRQ) were measured. Participants were stratified according to “slow” (<0.8 m·s−1) or “normal” 4MGS (≥0.8 m·s−1). Intra-class correlation coefficients for test-retest and interobserver reliability were 0.97 and 0.99, respectively. There was a significant positive correlation between 4MGS with ISW (&rgr; = 0.78; p<0.001) and a negative correlation with MRC dyspnoea scale and SGRQ (&rgr; = -0.55 and -0.44; p<0.001 for both). COPD patients with slow 4MGS had significantly reduced ISW and higher MRC dyspnoea scale and SGRQ than those with preserved walking speed, despite similar FEV1 % predicted. The 4MGS is reliable in COPD, correlates with exercise capacity, dyspnoea and health-related quality of life, and has potential as a simple assessment tool in COPD.

Physical frailty and pulmonary rehabilitation in COPD: a prospective cohort study

Background Frailty is an important clinical syndrome that is consistently associated with adverse outcomes in older people. The relevance of frailty to chronic respiratory disease and its management is unknown. Objectives To determine the prevalence of frailty among patients with stable COPD and examine whether frailty affects completion and outcomes of pulmonary rehabilitation. Methods 816 outpatients with COPD (mean (SD) age 70 (10) years, FEV1% predicted 48.9 (21.0)) were recruited between November 2011 and January 2015. Frailty was assessed using the Fried criteria (weight loss, exhaustion, low physical activity, slowness and weakness) before and after pulmonary rehabilitation. Predictors of programme non-completion were identified using multivariate logistic regression, and outcomes were compared using analysis of covariance, adjusting for age and sex. Results 209/816 patients (25.6%, 95% CI 22.7 to 28.7) were frail. Prevalence of frailty increased with age, Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage, Medical Research Council (MRC) score and age-adjusted comorbidity burden (all p≤0.01). Patients who were frail had double the odds of programme non-completion (adjusted OR 2.20, 95% CI 1.39 to 3.46, p=0.001), often due to exacerbation and/or hospital admission. However, rehabilitation outcomes favoured frail completers, with consistently better responses in MRC score, exercise performance, physical activity level and health status (all p<0.001). After rehabilitation, 71/115 (61.3%) previously frail patients no longer met case criteria for frailty. Conclusions Frailty affects one in four patients with COPD referred for pulmonary rehabilitation and is an independent predictor of programme non-completion. However, patients who are frail respond favourably to rehabilitation and their frailty can be reversed in the short term.

The 4-metre gait speed in COPD: responsiveness and minimal clinically important difference

Usual gait speed is a consistent predictor of adverse outcomes in community-dwelling elderly people. The reliability and validity of the 4-m gait speed (4MGS) has recently been demonstrated in patients with chronic obstructive pulmonary disease (COPD). The aims of this study were to assess the responsiveness of the 4MGS and to estimate the minimal clinically important difference (MCID). In 301 COPD patients, 4MGS and incremental shuttle walk (ISW) were measured before and after pulmonary rehabilitation. 4MGS and ISW were also measured at baseline and 1 year later in a separate cohort of 162 COPD patients. The MCID of 4MGS was estimated using distribution and anchor-based methods. 4MGS improved significantly with pulmonary rehabilitation (mean change 0.08 m·s−1, p<0.001). The minimal detectable change at 95% confidence was 0.11 m·s−1. The MCID was estimated at 0.11 m·s−1 (anchored against ISW) and 0.08 m·s−1 (anchored against self-reported improvement). The effect size for 4MGS was greatest in frail individuals. After 12 months, mean 4MGS declined by 0.04 m·s−1. When anchored against a decline of more than the MCID for ISW, change in 4MGS was −0.11 m·s−1. The 4MGS is responsive to pulmonary rehabilitation and longitudinal change in COPD, and has potential as a simple functional assessment tool in COPD. The 4MGS may be particularly useful in frail individuals with COPD. 4-m gait speed is responsive to pulmonary rehabilitation and longitudinal change with an estimated MCID of 0.11 m/s http://ow.ly/pXdmQ

Neuromuscular electrical stimulation to improve exercise capacity in patients with severe COPD: a randomised double-blind, placebo-controlled trial.

BACKGROUND Skeletal muscle dysfunction and exercise intolerance are common in severe chronic obstructive pulmonary disease (COPD). We assessed the effectiveness of neuromuscular electrical stimulation (NMES) as a home-based exercise therapy. METHODS In this double-blind, placebo-controlled trial, undertaken across three UK National Health Service sites, we randomly assigned (1:1) adults with COPD, a forced expiratory volume in 1 s (FEV1) less than 50% predicted, and incapacitating breathlessness (Medical Research Council dyspnoea scale ≥4) to receive active or placebo NMES, daily over a 6-week period. Randomisation was by an independent system using minimisation to balance age, GOLD stage, and quadriceps strength. Participants and outcome assessors were masked to group allocation. The primary endpoint was change in 6-min walk test (6MWT) distance at 6 weeks. Analysis was by intention to treat. The trial was registered as ISRCTN15985261 and is now closed. FINDINGS Between June 29, 2012, and July 4, 2014, we enrolled 73 participants, of whom 52 participants were randomly assigned; 25 to receive active NMES and 27 to placebo NMES. Change in 6MWT distance was greater in the active NMES group (mean 29·9 [95% CI 8·9 to 51·0]) compared with in the placebo group (-5·7 [-19·9 to 8·4]; mean difference at 6 weeks 35·7 m [95% CI 10·5 to 60·9]; p=0·005). Sensitivity analyses for complete-cases and adjustment for baseline values showed similar results. 6 weeks after stopping the intervention the effect waned (7·3 m [95% CI -32·5 to 47·0]; p=0·50). The proportion of participants who had adverse events was similar between groups (five [20%] in the active NMES group and nine [33%] in the placebo group). Two participants, one from each group, reported persistent erythema, which was considered to be possibly related to NMES and the use of adhesive electrodes. INTERPRETATION NMES improves functional exercise capacity in patients with severe COPD by enhancing quadriceps muscle mass and function. These data support the use of NMES in the management of patients unable to engage with conventional pulmonary rehabilitation. More work is needed to study how to maintain the effect. FUNDING National Institute for Health Research.

The Clinical COPD Questionnaire: response to pulmonary rehabilitation and minimal clinically important difference

Background The Clinical COPD Questionnaire (CCQ) is a simple 10-item, health-related quality of life questionnaire (HRQoL) with good psychometric properties. However, little data exists regarding the responsiveness of the CCQ to pulmonary rehabilitation (PR) or the minimal clinically important difference (MCID). The study aims were to assess the responsiveness of the CCQ to PR, to compare the responsiveness of the CCQ to other HRQoL questionnaires and to provide estimates for the MCID. Methods The CCQ, St Georges Respiratory Questionnaire (SGRQ), Chronic Respiratory Questionnaire (CRQ) and COPD Assessment Test (CAT) were measured in 261 patients with COPD before and after outpatient PR. Pre to post PR changes and Cohens effect size were calculated. Changes in CCQ were compared with changes in other HRQoL questionnaires. Using an anchor-based approach and receiver operating characteristic (ROC) curves, the CCQ change cutoffs that identified patients achieving the known MCID for other health status questionnaires with PR were identified. Results The CCQ, SGRQ, CRQ and CAT all significantly improved with PR with an effect size of −0.39, −0.33, 0.62 and −0.25, respectively. CCQ change correlated significantly with change in SGRQ, CRQ and CAT (r=0.48, −0.56, 0.54, respectively; all p<0.001). ROC curves consistently identified a CCQ change cutoff of −0.4 as the best discriminating value to identify the MCID for the SGRQ, CRQ and CAT (area under curve: 0.71, 0.75 and 0.77, respectively; all p<0.001). Conclusions The CCQ is responsive to PR with an estimated clinically important improvement of −0.4 points. The CCQ is a practical alternative to more time-consuming measures of HRQoL.

Gait speed and readmission following hospitalisation for acute exacerbations of COPD: a prospective study

Background Hospitalisation for acute exacerbations of COPD is associated with high risk of readmission. However, no tool has been validated to stratify patients at discharge for risk of readmission. Aim To evaluate the ability of the 4 m gait speed (4MGS), a surrogate marker of frailty, to predict risk of future readmission in hospitalised patients with an acute exacerbation of COPD (AECOPD). Methods 213 patients hospitalised with an AECOPD were recruited prospectively. 4MGS was measured on day of discharge. Logistic regression models were used to assess the association between 4MGS and readmission at 90 days after discharge. Results Baseline characteristics of the cohort: 52% men; mean age 72 years; median FEV1 35%predicted. Mean (SD) 4MGS at hospital discharge was 0.61 (0.26) ms−1. Significant increased rates of all-cause readmission at 90 days were seen across quartiles of decreasing 4MGS (Q4 fastest: 11.5%; Q3: 20.4%; Q2: 30.2%; Q1 slowest: 48.2%; ptrend<0.001). Compared with Q4, those in the slowest 4MGS quartile had unadjusted ORs (95% CIs) for 90-day readmission of 7.12 (2.61 to 19.44) for the whole cohort and 11.56 (3.08 to 43.35) in those aged 65 or over. A multivariate model incorporating 4MGS, Charlson Index, hospital admission in past year, FEV1%predicted and number of exacerbations in past year in those aged 65 or over predicted 90-day readmission with a C-statistic of 0.86. Conclusions The 4MGS, a surrogate marker of physical frailty, independently predicts the risk of readmission in older patients hospitalised for acute exacerbation of COPD. Trial registration number NCT01507415.

The EQ-5D-5L health status questionnaire in COPD: validity, responsiveness and minimum important difference

Background The EQ-5D, a generic health status questionnaire that is widely used in health economic evaluation, was recently expanded to the EQ-5D-5L to address criticisms of unresponsiveness and ceiling effect. Aims To describe the validity, responsiveness and minimum important difference of the EQ-5D-5L in COPD. Methods Study 1: The validity of the EQ-5D-5L utility index and visual analogue scale (EQ-VAS) was compared with four established disease-specific health status questionnaires and other measures of disease severity in 616 stable outpatients with COPD. Study 2: The EQ-5D-5L utility index and EQ-VAS were measured in 324 patients with COPD before and after 8 weeks of pulmonary rehabilitation. Distribution and anchor-based approaches were used to estimate the minimum important difference. Results There were moderate-to-strong correlations between utility index and EQ-VAS with disease-specific questionnaires (Pearsons r=0.47–0.72). A ceiling effect was seen in 7% and 2.6% of utility index and EQ-VAS. Utility index decreased (worsening health status) with indices of worsening disease severity. With rehabilitation, mean (95% CI) changes in utility index and EQ-VAS were 0.065 (0.047 to 0.083) and 8.6 (6.5 to 10.7), respectively, with standardised response means of 0.39 and 0.44. The mean (range) anchor estimates of the minimum important difference for utility index and EQ-VAS were 0.051 (0.037 to 0.063) and 6.9 (6.5 to 8.0), respectively. Conclusions The EQ-5D-5L is a valid and responsive measure of health status in COPD and may provide useful additional cost-effectiveness data in clinical trials.