William D.-C. Man

Community pulmonary rehabilitation after hospitalisation for acute exacerbations of chronic obstructive pulmonary disease: randomised controlled study.

Abstract Objective To evaluate the effects of an early community based pulmonary rehabilitation programme after hospitalisation for acute exacerbations of chronic obstructive pulmonary disease (COPD). Design A single centre, randomised controlled trial. Setting An inner city, secondary and tertiary care hospital in London. Participants 42 patients admitted with an acute exacerbation of COPD. Intervention An eight week, pulmonary rehabilitation programme for outpatients, started within 10 days of hospital discharge, or usual care. Main outcome measures Incremental shuttle walk distance, disease specific health status (St Georges respiratory questionnaire, SGRQ; chronic respiratory questionnaire, CRQ) and generic health status (medical outcomes short form 36 questionnaire, SF-36) at three months after hospital discharge. Results Early pulmonary rehabilitation, compared with usual care, led to significant improvements in median incremental shuttle walk distance (60 metres, 95% confidence interval 26.6 metres to 93.4 metres, P = 0.0002), mean SGRQ total score (−12.7, −5.0 to −20.3, P = 0.002), all four domains of the CRQ (dyspnoea 5.5, 2.0 to 9.0, P = 0.003; fatigue 5.3, 1.9 to 8.8, P = 0.004; emotion 8.7, 2.4 to 15.0, P = 0.008; and mastery 7.5, 4.2 to 10.7, P < 0.001) and the mental component score of the SF-36 (20.1, 3.3 to 36.8, P = 0.02). Improvements in the physical component score of the SF-36 did not reach significance (10.6, −0.3 to 21.6, P = 0.057). Conclusion Early pulmonary rehabilitation after admission to hospital for acute exacerbations of COPD is safe and leads to statistically and clinically significant improvements in exercise capacity and health status at three months.

British Thoracic Society guideline on pulmonary rehabilitation in adults: accredited by NICE

### The role of pulmonary rehabilitation ### Referral and assessment of patients for pulmonary rehabilitation #### Specific situations at assessment ##### Smoking

Outpatient pulmonary rehabilitation following acute exacerbations of COPD

Background Exacerbations of chronic obstructive pulmonary disease (COPD) are characterised by increased dyspnoea, reduced quality of life and muscle weakness. Re-exacerbation and hospital admission are common. Pulmonary rehabilitation (PR) administered after hospital admission for an exacerbation can improve quality of life and exercise capacity. Objective To determine whether outpatient post-exacerbation PR (PEPR) could reduce subsequent hospital admission episodes. Methods Patients admitted to hospital for an exacerbation of COPD were randomised to receive either usual follow-up care (UC) or PEPR after discharge. Hospital admission and emergency department attendances for COPD exacerbations were recorded over a 3-month period and analysed on an intention-to-treat basis. Secondary outcomes included exercise capacity and quadriceps strength. Results 60 patients underwent concealed randomisation at the time of their hospital discharge (UC: n=30, mean (SD) age 65 (10) years, forced expiratory volume in 1 s (FEV1) 52 (22)% predicted; PEPR: n=30, 67(10) years, 52 (20)% predicted). The proportion of patients re-admitted to hospital with an exacerbation was 33% in the UC group compared with 7% in those receiving PEPR (OR 0.15, 95% CI 0.03 to 0.72, p=0.02). The proportion of patients that experienced an exacerbation resulting in an unplanned hospital attendance (either admission or review and discharge from the emergency department) was 57% in the UC group and 27% in those receiving PEPR (OR 0.28, 95% CI 0.10 to 0.82, p=0.02). Conclusions Post-exacerbation rehabilitation in COPD can reduce re-exacerbation events that require admission or hospital attendance over a 3-month period. Clinical Trials Registration Number NCT00557115.

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 Georges 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 (FEV1) 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.

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.

Downregulation of the serum response factor/miR-1 axis in the quadriceps of patients with COPD

Rationale Muscle atrophy confers a poor prognosis in patients with chronic obstructive pulmonary disease (COPD), yet the molecular pathways responsible are poorly characterised. Muscle-specific microRNAs and serum response factor (SRF) are important regulators of muscle phenotype that contribute to a feedback system to regulate muscle gene expression. The role of these factors in the skeletal muscle dysfunction that accompanies COPD is unknown. Methods 31 patients with COPD and 14 healthy age-matched controls underwent lung and quadriceps function assessments, measurement of daily activity and a percutaneous quadriceps muscle biopsy. The expression of muscle-specific microRNAs, myosin heavy chains and components of the serum response factor signalling pathway were determined by qPCR. Results A reduction in expression of miR-1 (2.5-fold, p=0.01) and the myocardin-related transcription factors (MRTFs) A and B was observed in patients compared with controls (MRTF-A mRNA: twofold, p=0.028; MRTF-B mRNA: fourfold, p=0.011). miR-1 expression was associated with smoking history, lung function, fat-free mass index, 6 min walk distance and percentage of type 1 fibres. miR-133 and miR-206 were negatively correlated with daily physical activity. Insulin-like growth factor 1 mRNA was increased in the patients and miR-1 was negatively correlated with phosphorylation of the kinase Akt. Furthermore, the protein levels of histone deacetylase 4, another miR-1 target, were increased in the patients. Conclusions Downregulation of the activity of the MRTF-SRF axis and the expression of muscle-specific microRNAs, particularly miR-1, may contribute to COPD-associated skeletal muscle dysfunction.

Effect of salmeterol on respiratory muscle activity during exercise in poorly reversible COPD

Background: Some patients with irreversible chronic obstructive pulmonary disease (COPD) experience subjective benefit from long acting bronchodilators without change in forced expiratory volume in 1 second (FEV1). Dynamic hyperinflation is an important determinant of exercise induced dyspnoea in COPD. We hypothesised that long acting bronchodilators improve symptoms by reducing dynamic hyperinflation and work of breathing, as measured by respiratory muscle pressure-time products. Methods: Sixteen patients with “irreversible” COPD (<10% improvement in FEV1 following a bronchodilator challenge; mean FEV1 31.1% predicted) were recruited into a randomised, double blind, placebo controlled, crossover study of salmeterol (50 μg twice a day). Treatment periods were of 2 weeks duration with a 2 week washout period. Primary outcome measures were end exercise isotime transdiaphragmatic pressure-time product and dynamic hyperinflation as measured by inspiratory capacity. Results: Salmeterol significantly reduced the transdiaphragmatic pressure-time product (294.5 v 348.6 cm H2O/s/min; p = 0.03), dynamic hyperinflation (0.22 v 0.33 litres; p = 0.002), and Borg scores during endurance treadmill walk (3.78 v 4.62; p = 0.02). There was no significant change in exercise endurance time. Improvements in isotime Borg score were significantly correlated to changes in tidal volume/oesophageal pressure swings, end expiratory lung volume, and inspiratory capacity, but not pressure-time products. Conclusions: Despite apparent “non-reversibility” in spirometric parameters, long acting bronchodilators can cause both symptomatic and physiological improvement during exercise in severe COPD.

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.

Pulmonary rehabilitation following hospitalisation for acute exacerbation of COPD: referrals, uptake and adherence

Abstract Rationale Several randomised controlled trials support the provision of early pulmonary rehabilitation (PR) following hospitalisation for acute exacerbation of chronic obstructive pulmonary disease (AECOPD). However, there is little real-world data regarding uptake, adherence and completion rates. Methods An audit was conducted to prospectively document referral, uptake, adherence and completion rates for early post-hospitalisation outpatient PR in Northwest London over a 12-month period. Results Out of 448 hospital discharges for AECOPD, 90 referrals for post-hospitalisation PR were received. Only 43 patients received and completed PR (9.6% of all hospital discharges) despite a fully commissioned PR service. Conclusions Despite the strong evidence base, there are poor referral and uptake rates for early outpatient PR following hospitalisation for AECOPD, with only a small proportion of the intended target population receiving this intervention.