Neil Greening

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

An early rehabilitation intervention to enhance recovery during hospital admission for an exacerbation of chronic respiratory disease: randomised controlled trial

Objective To investigate whether an early rehabilitation intervention initiated during acute admission for exacerbations of chronic respiratory disease reduces the risk of readmission over 12 months and ameliorates the negative effects of the episode on physical performance and health status. Design Prospective, randomised controlled trial. Setting An acute cardiorespiratory unit in a teaching hospital and an acute medical unit in an affiliated teaching district general hospital, United Kingdom. Participants 389 patients aged between 45 and 93 who within 48 hours of admission to hospital with an exacerbation of chronic respiratory disease were randomised to an early rehabilitation intervention (n=196) or to usual care (n=193). Main outcome measures The primary outcome was readmission rate at 12 months. Secondary outcomes included number of hospital days, mortality, physical performance, and health status. The primary analysis was by intention to treat, with prespecified per protocol analysis as a secondary outcome. Interventions Participants in the early rehabilitation group received a six week intervention, started within 48 hours of admission. The intervention comprised prescribed, progressive aerobic, resistance, and neuromuscular electrical stimulation training. Patients also received a self management and education package. Results Of the 389 participants, 320 (82%) had a primary diagnosis of chronic obstructive pulmonary disease. 233 (60%) were readmitted at least once in the following year (62% in the intervention group and 58% in the control group). No significant difference between groups was found (hazard ratio 1.1, 95% confidence interval 0.86 to 1.43, P=0.4). An increase in mortality was seen in the intervention group at one year (odds ratio 1.74, 95% confidence interval 1.05 to 2.88, P=0.03). Significant recovery in physical performance and health status was seen after discharge in both groups, with no significant difference between groups at one year. Conclusion Early rehabilitation during hospital admission for chronic respiratory disease did not reduce the risk of subsequent readmission or enhance recovery of physical function following the event over 12 months. Mortality at 12 months was higher in the intervention group. The results suggest that beyond current standard physiotherapy practice, progressive exercise rehabilitation should not be started during the early stages of the acute illness. Trial registration Current Controlled Trials ISRCTN05557928.

Bedside assessment of quadriceps muscle by ultrasound after admission for acute exacerbations of chronic respiratory disease

RATIONALE Hospitalization represents a major event for the patient with chronic respiratory disease. There is a high risk of readmission, which over the longer term may be related more closely to the underlying condition of the patient, such as skeletal muscle dysfunction. OBJECTIVES We assessed the risk of hospital readmission at 1 year, including measures of lower limb muscle as part of a larger clinical trial. METHODS Patients hospitalized with an exacerbation of chronic respiratory disease underwent measures of muscle function including quadriceps ultrasound. Independent factors influencing time to hospital readmission or death were identified. Patients were classified into four quartiles based on quadriceps size and compared. MEASUREMENTS AND MAIN RESULTS One hundred and ninety-one patients (mean age, 71.6 [SD, 9.1] yr) were recruited. One hundred and thirty (68%) were either readmitted or died. Factors associated with readmission or death were age (odds ratio [OR], 1.05; 95% confidence interval [CI], 1.01-1.08; P = 0.015), Medical Research Council (MRC) dyspnea grade (OR, 4.57; 95% CI, 2.62-7.95; P < 0.001), home oxygen use (OR, 12.4; 95% CI, 4.53-33.77; P < 0.001), quadriceps (rectus femoris) cross-sectional area (Qcsa) (OR, 0.34; 95% CI, 0.17-0.65; P = 0.001), and hospitalization in the previous year (OR, 4.82; 95% CI, 2.42-9.58; P < 0.001). In the multivariate analyses, home oxygen use (OR, 4.80; 95% CI, 1.68-13.69; P = 0.003), MRC dyspnea grade (OR, 2.57; 95% CI, 1.44-4.59; P = 0.001), Qcsa (OR, 0.46; 95% CI, 0.22-0.95; P = 0.035), and previous hospitalization (OR, 3.04; 95% CI, 1.47-6.29; P = 0.003) were independently associated with readmission or death. Patients with the smallest muscle spent more days in hospital than those with largest muscle (28.1 [SD, 33.9] vs. 12.2 [SD, 23.5] d; P = 0.007). CONCLUSIONS Smaller quadriceps muscle size, as measured by ultrasound in the acute care setting, is an independent risk factor for unscheduled readmission or death, which may have value both in clinical practice and for risk stratification.

Progressive Resistance Exercise Training in CKD: A Feasibility Study

BACKGROUND Skeletal muscle wasting in chronic kidney disease (CKD) is associated with morbidity and mortality. Resistance exercise results in muscle hypertrophy in the healthy population, but is underinvestigated in CKD. We aimed to determine the feasibility of delivering a supervised progressive resistance exercise program in CKD, with secondary aims to investigate effects on muscle size, strength, and physical functioning. STUDY DESIGN Parallel randomized controlled feasibility study. SETTING & PARTICIPANTS Patients with CKD stages 3b to 4 were randomly assigned to the exercise (n=20; 11 men; median age, 63 [IQR, 57-65] years; median estimated glomerular filtration rate, 28.5 [IQR, 19.0-32.0] mL/min/1.73 m(2)) or nonexercise control (n=18; 14 men; median age, 66 [IQR, 45-79] years; estimated glomerular filtration rate, 20.5 [IQR, 16.0-26.0] mL/min/1.73 m(2)) group. INTERVENTION Patients in the exercise group undertook an 8-week progressive resistance exercise program consisting of 3 sets of 10 to 12 leg extensions at 70% of estimated 1-repetition maximum thrice weekly. Patients in the control group continued with usual physical activity. OUTCOMES Primary outcomes were related to study feasibility: eligibility, recruitment, retention, and adherence rates. Secondary outcomes were muscle anatomical cross-sectional area, muscle volume, pennation angle, knee extensor strength, and exercise capacity. MEASUREMENTS Two- and 3-dimensional ultrasonography of skeletal muscle, dynamometry, and shuttle walk tests at baseline and 8 weeks. RESULTS Of 2,349 patients screened, 403 were identified as eligible and 38 enrolled in the study. 33 (87%) completed the study, and those in the exercise group attended 92% of training sessions. No changes were seen in controls for any parameter. Progressive resistance exercise increased muscle anatomical cross-sectional area, muscle volume, knee extensor strength, and exercise capacity. LIMITATIONS No blinded assessors, magnetic resonance imaging not used to assess muscle mass, lack of a healthy control group. CONCLUSIONS This type of exercise is well tolerated by patients with CKD and confers important clinical benefits; however, low recruitment rates suggest that a supervised outpatient-based program is not the most practical implementation strategy.

Age-specific normal values for the incremental shuttle walk test in a healthy British population.

PURPOSE: The Incremental Shuttle Walk Test (ISWT) is an important functional and prognostic marker in chronic disease. Aging has a detrimental effect on exercise performance. The objective of this study was to produce normal age-specific values for the ISWT in a healthy British population and to explore whether additional variables improve the accuracy of a predictive equation. METHODS: Healthy subjects (N = 152), aged 40 to 90 years, were recruited. Data collection occurred over 2 study visits. Anthropometric and demographic data were collected, and lung function and quadriceps maximal voluntary contraction were measured. An accelerometer was worn for 2 consecutive days at home. The Duke Activity Status Index was completed, and the greatest distance from 2 ISWTs was recorded. RESULTS: One hundred forty subjects (56 men) with mean age (SD) of 59.4 (11.0) years completed 2 ISWTs. Forced expiratory volume in 1 second (FEV1) was 109.1% (14.56%) predicted and ISWT distance was 737 m (183 m). Age-specific normal values for the ISWT were observed: mean (lower limit of normal)—40 to 49 years, 824 m (765 m); 50 to 59 years, 788 m (730 m); 60 to 69 years, 699 m (649 m); and 70 years and older, 633 m (562 m). A predictive equation was developed from 114 subjects. Age, body mass index, FEV1, quadriceps maximal voluntary contraction, and Duke Activity Status Index contributed to ISWT distance predicting 50.4% of the variation in performance. CONCLUSION: We have developed age-specific normal values for performance on the ISWT in a healthy British population. However, even using practical, clinically relevant variables, it is not possible to accurately predict exercise capacity from a regression equation.

Does body mass index influence the outcomes of a Waking-based pulmonary rehabilitation programme in COPD?

Body mass index (BMI) is an important prognostic measure in chronic obstructive pulmonary disease (COPD). However, its effects on pulmonary rehabilitation (PR) are unknown. This study aimed to evaluate the effectiveness of a walking-based PR programme across the BMI range and the impact of BMI on exercise performance and health status. A total of 601 patients with COPD completed a PR programme. The effects of BMI on exercise capacity (incremental and endurance shuttle walk tests (ISWT and ESWT)) and health status (chronic respiratory questionnaire (CRQ)) before and after PR were evaluated. 16% of patients were underweight, with 53% overweight or obese. At baseline, the obese had worse ISWT (−54 m ± 14 m; p = 0.001) despite a higher predicted forced expiratory volume in 1 s (7.4m ± 1.6%; p < 0.001). Patients in all BMI categories made clinically important improvements in ISWT distance: BMI <21, 62 m; 21–25, 59 m; 25–30, 59 m; >30, 65 m (p = < 0.001). All four domains of the CRQ increased above the level of clinical significance for all BMI categories (all p < 0.001). The majority of patients with COPD were overweight associated with a lower walking capacity. A walking-based PR programme was comparably effective across the BMI spectrum. Patients with COPD should be referred for standard PR, independent of BMI.

Individualised risk in patients undergoing lung volume reduction surgery (LVRS): The Glenfield BFG Score

Lung volume reduction surgery (LVRS) has been shown to be beneficial in patients with chronic obstructive pulmonary disease, but there is low uptake, partly due to perceived concerns of high operative mortality. We aimed to develop an individualised risk score following LVRS. This was a cohort study of patients undergoing LVRS. Factors independently predicting 90-day mortality and a risk prediction score were identified. Reliability of the score was tested using area under the receiver operating characteristic curve (AUROC). 237 LVRS procedures were performed. The multivariate analysis factors associated independently with death were: body mass index (BMI)<18.5 kg·m−2 (OR 2.83, p=0.059), forced expiratory volume in 1 s (FEV1)<0.71 L (OR 5.47, p=0.011) and transfer factor of the lung for carbon monoxide (TLCO) <20% (OR 5.56, p=0.031). A risk score was calculated and total score assigned. AUROC for the risk score was 0.80 and a better predictor than individual components (p<0.01). The score was stratified into three risk groups. Of the total patients, 46% were classified as low risk. Similar improvements in lung function and health status were seen in all groups. The score was introduced and tested in a further 71 patients. AUROC for 90-day mortality in this cohort was 0.84. It is possible to provide an individualised predictive risk score for LVRS, which may aid decision making for both clinicians and patients. An individualised risk score for lung volume reduction surgery may aid decision making around surgery http://ow.ly/4lxm30b3n05

Comprehensive respiratory assessment in advanced COPD: a ‘campus to clinic’ translational framework

COPD is a clinical syndrome representing a spectrum of lung pathologies associated with systemic comorbidities and exacerbations, which contribute substantial morbidity and mortality. The ‘umbrella’ nature of the syndrome has resulted in the detailed investigation and description of multiple disease phenotypes relating to the heterogeneity of lung pathophysiology but also to other clinical features such as symptom burden, exacerbations, comorbidities, nutritional status and respiratory failure.1–5 Phenotype-specific therapies already exist, for example, lung volume reduction therapies, nutritional support and home non-invasive ventilation. Moreover, this may extend to other features such as increased cardiovascular risk and inflammometry-directed exacerbation management.6 ,7 These advances provide an opportunity to make a significant change in the care of patients with COPD both by personalising the management of patient symptoms and future health risk (as embodied in the updated Global Initiative for Chronic Obstructive Lung Disease (GOLD) staging schema8) and by the proactive identification and treatment of systemic comorbidities that are known to impact on health outcomes. For these scientific developments to translate to patient care, a more detailed, systematic framework for clinical assessment is needed in routine clinical practice. Such an approach is also required to stratify care across the range of disease severity/complexity so that care can be individualised and services organised accordingly. In keeping with this, the UK National Health Service (NHS) National Outcomes Strategy for COPD recommends that the assessment of disease severity should be based on a ‘comprehensive assessment’ of clinical characteristics and that services should be integrated to ensure specialist care focuses on more ‘complex or unstable’ disease.9 Currently, however, in the UK and many other healthcare systems, proactive identification and management of complex medical, psychological and social care needs in COPD occurs infrequently and is poorly coordinated.10 By contrast, a structured approach to managing …

Pulmonary rehabilitation for patients with COPD during and after an exacerbation-related hospitalisation: back to the future?

The European Respiratory Society (ERS) and American Thoracic Society (ATS) guideline on management of chronic obstructive pulmonary disease (COPD) exacerbations was published in the March 2017 issue of the European Respiratory Journal [1]. Based on evidence syntheses, including meta-analyses, relevant evidence up to September 2015 was summarised and clinical recommendations for treatment of COPD exacerbations were formulated. These guidelines were endorsed by the ERS Executive Committee and approved by the ATS Board of Directors in December 2016. Healthcare professionals should educate COPD patients and recommend rehabilitation in the peri-exacerbation period http://ow.ly/gaiC30eQlVE

The Effect of Resistance Exercise on Inflammatory and Myogenic Markers in Patients with Chronic Kidney Disease

Background: Muscle wasting is a common complication of Chronic Kidney Disease (CKD) and is clinically important given its strong association with morbidity and mortality in many other chronic conditions. Exercise provides physiological benefits for CKD patients, however the molecular response to exercise remains to be fully determined. We investigated the inflammatory and molecular response to resistance exercise before and after training in these patients. Methods: This is a secondary analysis of a randomized trial that investigated the effect of 8 week progressive resistance training on muscle mass and strength compared to non-exercising controls. A sub-set of the cohort consented to vastus lateralis skeletal muscle biopsies (n = 10 exercise, n = 7 control) in which the inflammatory response (IL-6, IL-15, MCP-1 TNF-α), myogenic (MyoD, myogenin, myostatin), anabolic (P-Akt, P-eEf2) and catabolic events (MuRF-1, MAFbx, 14 kDa, ubiquitin conjugates) and overall levels of oxidative stress have been studied. Results: A large inflammatory response to unaccustomed exercise was seen with IL-6, MCP-1, and TNF-α all significantly elevated from baseline by 53-fold (P < 0.001), 25-fold (P < 0.001), and 4-fold (P < 0.001), respectively. This response was reduced following training with IL-6, MCP-1, and TNF-α elevated non-significantly by 2-fold (P = 0.46), 2.4-fold (P = 0.19), and 2.5-fold (P = 0.06), respectively. In the untrained condition, an acute bout of resistance exercise did not result in increased phosphorylation of Akt (P = 0.84), but this was restored following training (P = 0.01). Neither unaccustomed nor accustomed exercise resulted in a change in myogenin or MyoD mRNA expression (P = 0.88, P = 0.90, respectively). There was no evidence that resistance exercise training created a prolonged oxidative stress response within the muscle, or increased catabolism. Conclusions: Unaccustomed exercise creates a large inflammatory response within the muscle, which is no longer present following a period of training. This indicates that resistance exercise does not provoke a detrimental on-going inflammatory response within the muscle.