Charlotte E. Bolton

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

Aortic Calcification Is Associated With Aortic Stiffness and Isolated Systolic Hypertension in Healthy Individuals

Arterial stiffening is an independent predictor of mortality and underlies the development of isolated systolic hypertension (ISH). A number of factors regulate stiffness, but arterial calcification is also likely to be important. We tested the hypotheses that aortic calcification is associated with aortic stiffness in healthy individuals and that patients with ISH exhibit exaggerated aortic calcification compared with controls. A total of 193 healthy, medication-free subjects (mean age±SD: 66±8 years) were recruited from the community, together with 15 patients with resistant ISH. Aortic pulse wave velocity (PWV) was measured noninvasively, and aortic calcium content was quantified from high-resolution, thoraco-lumbar computed tomography images using a volume scoring method. In healthy volunteers, calcification was positively and significantly associated with aortic PWV (r=0.6; P<0.0001) but was not related to augmentation index or brachial PWV. Calcification was significantly higher in treatment-resistant and healthy subjects with ISH compared with controls (mean [interquartile range]: 1.92 [1.14 to 3.66], 0.84 [0.35 to 1.75], and 0.19 [0.1 to 0.78] cm3, respectively; P<0.0001 for both). In a multiple regression model, aortic calcium was independently associated with aortic PWV along with age, mean arterial pressure, heart rate, and estimated glomerular filtration rate (R2=0.51; P<0.0001). Only age, calcium phosphate product, and aortic PWV were independently associated with calcification. These data suggest that calcification may be important in the process of aortic stiffening and the development of ISH. Calcification may underlie treatment resistance in ISH, and anticalcification strategies may present a novel therapy.

Insufficient evidence of benefit: a systematic review of home telemonitoring for COPD

RATIONALE, AIMS AND OBJECTIVES The evidence to support the effectiveness of home telemonitoring interventions for patients with chronic obstructive pulmonary disease (COPD) is limited, yet there are many efforts made to implement these technologies across health care services. METHODS A comprehensive search strategy was designed and implemented across 9 electronic databases and 11 European, Australasian and North American telemedicine websites. Included studies had to examine the effectiveness of telemonitoring interventions, clearly defined for the study purposes, for adult patients with COPD. Two researchers independently screened each study prior to inclusion. RESULTS Two randomized trials and four other evaluations of telemonitoring were included. The studies are typically underpowered, had heterogeneous patient populations and had a lack of detailed intervention descriptions and of the care processes that accompanied telemonitoring. In addition, there were diverse outcome measures and no economic evaluations. The telemonitoring interventions in each study differed widely. Some had an educational element that could itself account for the differences between groups. CONCLUSIONS Despite these caveats, the study reports are themselves positive about their results. However, given the risk of bias in the design and scale of the evaluations we conclude that the benefit of telemonitoring for COPD is not yet proven and that further work is required before wide-scale implementation be supported.

Insulin Resistance and inflammation — A Further Systemic Complication of COPD

Chronic obstructive pulmonary disease (COPD) is associated with a continuous systemic inflammatory response. Furthermore, COPD is associated with an excess risk for cardiovascular disease and type II diabetes. Systemic inflammation in other populations is a factor in atherogenesis and has been associated with insulin resistance. We assessed the association between systemic inflammation and insulin resistance in non-hypoxaemic patients with COPD. Fasting plasma glucose, insulin and inflammatory mediators were measured in 56 patients and 29 healthy subjects. Body mass index (BMI) and height squared fat- and fat-free-mass index were similar between subject groups. Using homeostatic modelling techniques, mean (SD) insulin resistance was greater in the patients, 1.68 (2.58) and 1.13 (2.02) in healthy subjects, p = 0.032. Fasting plasma insulin was increased in patients while glucose was similar to that in healthy subjects. Patients had increased circulating inflammatory mediators. Insulin resistance was related to interleukin-6 (IL-6), r = 0.276, p = 0.039, and tumour necrosis factor α soluble receptor I, r = 0.351, p = 0.008. Both IL-6 and BMI were predictive variables of insulin resistance r2 = 0.288, p < 0.05. We demonstrated greater insulin resistance in non-hypoxaemic patients with COPD compared with healthy subjects, which was related to systemic inflammation. This relationship may indicate a contributory factor in the excess risk of cardiovascular disease and type II diabetes in COPD.

Predictors of poor attendance at an outpatient pulmonary rehabilitation programme

BACKGROUND Pulmonary rehabilitation (PR) is recommended for patients with respiratory disease who feel limited by breathlessness. Poor attendance wastes finite resources, increases waiting times and is probably associated with poorer clinical outcomes. We investigated what factors, identifiable from routine hospital data, predict poor attendance once enrolled in a pulmonary rehabilitation programme (PRP). METHODS Retrospective case note study of 239 patients (60% male) of mean (S.D.) age of 66.6 (8.7) years, mean FEV(1) 39.6 (14.6)% predicted, who attended a 6 (short) or 18 (long) week, 18 session, outpatient PRP. Attendance data was analysed using linear multiple regression analysis with the log transformed odds ratio of attendance as the dependant variable. RESULTS Overall median attendance was 16 out of 18 sessions. Being a current smoker (p<0.05), attending a long PRP (p<0.05), more previous hospital admissions (p<0.01), higher Medical Research Council (MRC) dyspnoea score (p<0.01) or enduring a long journey (p<0.001) were independent risk factors for low attendance. Lower body mass index (BMI) and distance from PR centre were of borderline importance (p<0.1) but age, gender, co-morbidity, respiratory diagnosis, FEV(1) and St. Georges Respiratory Questionnaire Score at baseline did not predict later attendance (p>0.2). CONCLUSIONS Attendance at PRPs is independently influenced by smoking status, the degree of breathlessness, frequency of hospital admissions, length of the programme and journey time.

Sub-clinical left and right ventricular dysfunction in patients with COPD

BACKGROUND Cardiovascular manifestations in COPD include increased arterial stiffness, ischaemic heart disease, chronic heart failure and cor pulmonale. We hypothesised that sub-clinical right (RV) and left ventricular (LV) dysfunction occurs in patients with COPD, related to the severity of airflow obstruction, arterial stiffness and systemic inflammation. METHODS Thirty six patients and 14 controls, all free of overt cardiovascular disease underwent tissue Doppler echocardiography, spirometry, measurement of aortic pulse wave velocity (PWV) and venous sampling for inflammatory markers. RESULTS Mean LV myocardial strain and strain rate were less in patients than controls, p<0.05. LV isovolumic relaxation time (IVRT) was prolonged in patients (125+/-15.2ms) compared with controls (98.2+/-21.1ms), p<0.01, indicating LV diastolic dysfunction. The RV free wall strain and strain rate were less in patients than controls, both p<0.05, indicating RV systolic dysfunction. Patients had sub-clinical pulmonary arterial hypertension with a greater RV myocardial relaxation time and Tei index, both p<0.01. Patients with mild airways obstruction had LV and RV dysfunction and evidence of increased RV afterload compared with controls. In multivariate analyses aortic PWV predicted LV IVRT, p<0.01, while FEV(1) predicted RV Tei index and myocardial relaxation time, both p<0.01. CONCLUSIONS Patients with COPD have sub-clinical left ventricular dysfunction related to arterial stiffness, and right ventricular dysfunction related to airways obstruction. Both right and left ventricular dysfunction are present in patients with mild airways obstruction suggesting that cardiac co-morbidities commence early in the development of COPD.

Cellular protein breakdown and systemic inflammation are unaffected by pulmonary rehabilitation in COPD.

Background: Pulmonary rehabilitation can improve the functional capacity, but has a variable effect on the low fat-free mass (FFM) in patients with chronic obstructive pulmonary disease. Hypothesis: Pulmonary rehabilitation would not affect catabolic drives such as systemic inflammation and also protein breakdown. Methods: Patients (n = 40) were studied at the start of an 8-week in-patient pulmonary rehabilitation programme, at the end of the programme and 4 weeks later. FFM and functional capacity (quadriceps strength, handgrip strength and peak workload) were assessed. Pseudouridine (PSU) urinary excretion (cellular protein breakdown) and inflammatory status were determined. Healthy participants had a single baseline assessment (n = 18). Results: PSU, (IL)-6 and soluble tumour necrosis factor (sTNF)α R75 were increased in patients compared with healthy participants, whereas FFM and functional capacity were reduced (all p<0.01). PSU was inversely related to both FFM and skeletal muscle function. FFM and functional parameters increased with rehabilitation, but PSU and inflammatory status were unaffected. The gain in FFM was lost 4 weeks after the completion of rehabilitation (p<0.01). Conclusion: The anabolic effect of pulmonary rehabilitation improved FFM, but it did not reverse the increased protein breakdown or systemic inflammation. Thus, on cessation of pulmonary rehabilitation the FFM gains were lost owing to a loss of anabolic drive.

Lung function in mid-life compared with later life is a stronger predictor of arterial stiffness in men: The Caerphilly Prospective Study

BACKGROUND Increased arterial stiffness predicts future cardiovascular disease and in some cross-sectional studies it is related to worse lung function and obstructive pulmonary disease. We assessed the predictive value of lung function measured in mid-life as compared with later life on arterial stiffness in the Caerphilly Prospective Study (CaPS). METHODS Men aged 47-67 years had lung function measured between 1984 and 1988 and repeated between 2002 and 2004 (n = 827) as well as having carotid-femoral pulse wave velocity (PWV) measured. RESULTS Both forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC) in mid-life and later life were inversely associated with PWV (P < 0.0001) but mid-life measures were stronger predictors. Only mid-life measures remained predictors after mutual adjustment (FEV(1) mid-life beta coeff. -0.65, 95% CI -1.04, -0.26, P < 0.0001; FVC mid-life beta coeff. -0.52, 95% CI -0.82, -0.23, P < 0.0001). Adjustment for smoking status, early life, inflammatory and metabolic factors in sub-groups did not markedly change the associations. CONCLUSIONS Mid-life lung function is a stronger risk factor than in later life for arterial stiffness in men. It is possible that developmental factors influence both lung function and arterial stiffness. Lung function assessment in mid-life may identify individuals at greater risk of their future cardiovascular disease.

Excessive Aortic Inflammation in Chronic Obstructive Pulmonary Disease: An 18F-FDG PET Pilot Study

Chronic obstructive pulmonary disease (COPD) patients exhibit increased cardiovascular risk, even after controlling for smoking. Inflammation may underlie this observation. Methods: We measured vascular inflammation in both COPD patients and controls using 18F-FDG PET/CT. Aortic inflammation was expressed as the target-to-background ratio (TBR) of the standardized uptake value in 7 COPD patients, 5 metabolic syndrome patients, and 7 ex-smokers. Results: Abdominal aortic mean TBR (±SD) was greater in COPD patients than in ex-smoker controls (1.60 ± 0.13 vs. 1.34 ± 0.15, P = 0.0001). Aortic arch and abdominal aorta mean TBRs were higher in metabolic syndrome patients than in COPD patients (aortic arch, 1.80 ± 0.18 vs. 1.53 ± 0.18, P = 0.001, and abdominal aorta, 1.71 ± 0.14 vs. 1.60 ± 0.13, P = 0.001). Conclusion: COPD patients exhibited aortic inflammation that fell between the aortic inflammation exhibited by ex-smokers and that by metabolic syndrome patients. This may in part explain the increased risk of cardiovascular disease in COPD patients.

Does pulmonary rehabilitation address cardiovascular risk factors in patients with COPD

BackgroundPatients with COPD have an increased risk of cardiovascular disease. Whilst pulmonary rehabilitation has proven benefit for exercise tolerance and quality of life, any effect on cardiovascular risk has not been fully investigated. We hypothesised that pulmonary rehabilitation, through the exercise and nutritional intervention, would address these factors.MethodsThirty-two stable patients with COPD commenced rehabilitation, and were compared with 20 age and gender matched controls at baseline assessment. In all subjects, aortic pulse wave velocity (PWV) an independent non-invasive predictor of cardiovascular risk, blood pressure (BP), interleukin-6 (IL-6) and fasting glucose and lipids were determined. These measures, and the incremental shuttle walk test (ISWT) were repeated in the patients who completed pulmonary rehabilitation.ResultsOn commencement of rehabilitation aortic PWV was increased in patients compared with controls (p < 0.05), despite mean BP, age and gender being similar. The IL-6 was also increased (p < 0.05). Twenty-two patients completed study assessments. In these subjects, rehabilitation reduced mean (SD) aortic PWV (9.8 (3.0) to 9.3 (2.7) m/s (p < 0.05)), and systolic and diastolic BP by 10 mmHg and 5 mmHg respectively (p < 0.01). Total cholesterol and ISWT also improved (p < 0.05). On linear regression analysis, the reduction in aortic PWV was attributed to reducing the BP.ConclusionCardiovascular risk factors including blood pressure and thereby aortic stiffness were improved following a course of standard multidisciplinary pulmonary rehabilitation in patients with COPD.