N S Hopkinson

The prevalence of quadriceps weakness in COPD and the relationship with disease severity

Quadriceps strength relates to exercise capacity and prognosis in chronic obstructive pulmonary disease (COPD). We wanted to quantify the prevalence of quadriceps weakness in COPD and hypothesised that it would not be restricted to patients with severe airflow obstruction or dyspnoea. Predicted quadriceps strength was calculated using a regression equation (incorporating age, sex, height and fat-free mass), based on measurements from 212 healthy subjects. The prevalence of weakness (defined as observed values 1.645 standardised residuals below predicted) was related to Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage and Medical Research Council (MRC) dyspnoea score in two cohorts of stable COPD outpatients recruited from the UK (n = 240) and the Netherlands (n = 351). 32% and 33% of UK and Dutch COPD patients had quadriceps weakness. A significant proportion of patients in GOLD stages 1 and 2, or with an MRC dyspnoea score of 1 or 2, had quadriceps weakness (28 and 26%, respectively). These values rose to 38% in GOLD stage 4, and 43% in patients with an MRC Score of 4 or 5. Quadriceps weakness was demonstrable in one-third of COPD patients attending hospital respiratory outpatient services. Quadriceps weakness exists in the absence of severe airflow obstruction or breathlessness.

Abdominal muscle and quadriceps strength in chronic obstructive pulmonary disease

Background: Quadriceps muscle weakness is common in chronic obstructive pulmonary disease (COPD) but is not observed in a small hand muscle (adductor pollicis). Although this could be explained by reduced activity in the quadriceps, the observation could also be explained by anatomical location of the muscle or fibre type composition. However, the abdominal muscles are of a similar anatomical and fibre type distribution to the quadriceps, although they remain active in COPD. Cough gastric pressure is a recently described technique that assesses abdominal muscle (and hence expiratory muscle) strength more accurately than traditional techniques. A study was undertaken to test the hypothesis that more severe weakness exists in the quadriceps than in the abdominal muscles of patients with COPD compared with healthy elderly controls. Methods: Maximum cough gastric pressure and quadriceps isometric strength were measured in 43 patients with stable COPD and 25 healthy elderly volunteers matched for anthropometric variables. Results: Despite a significant reduction in mean quadriceps strength (29.9 kg v 41.2 kg; 95% CI −17.9 to −4.6; p = 0.001), cough gastric pressure was preserved in patients with COPD (227.3 cm H2O v 204.8 cm H2O; 95% CI −5.4 to 50.6; p = 0.11). Conclusions: Abdominal muscle strength is preserved in stable COPD outpatients in the presence of quadriceps weakness. This suggests that anatomical location and fibre type cannot explain quadriceps weakness in COPD. By inference, we conclude that disuse and consequent deconditioning are important factors in the development of quadriceps muscle weakness in COPD patients, or that activity protects the abdominal muscles from possible systemic myopathic processes.

Quadriceps muscle strength in scoliosis.

Quadriceps muscle weakness is an important component of chronic obstructive pulmonary disease (COPD). We hypothesised that quadriceps weakness would also be a feature of restrictive lung disease due to scoliosis. We studied 10 patients with severe scoliosis (median (interquartile range (IQR)) forced expiratory volume in 1 s (FEV1) 35.3 (11)% predicted), 10 patients with severe COPD (FEV1 26.5 (9.0)% pred) and 10 healthy age-matched adults. We measured quadriceps strength, exercise capacity and analysed quadriceps muscle biopsies for myosin heavy-chain (MyHC) isoform expression and the presence of oxidative stress. Both groups exhibited quadriceps weakness with median (IQR) maximal voluntary contraction force being 46.0 (17.0) kg, 21.5 (21.0) kg and 31.5 (11.0) kg, respectively (p = 0.02 and 0.04, respectively, for each patient group against controls). Oxidative stress was significantly greater in the quadriceps of both restrictive and COPD patients. The scoliosis patients exhibited a decrease in the proportion of MyHC type I compared with controls; median (IQR) 35.3 (18.5)% compared with 47.7 (9.3)%, p = 0.028. The scoliosis patients also showed an increase in MyHC IIx (26.3 (15.5)% compared with 11.3 (13.0)%, p = 0.01. Quadriceps weakness is a feature of severe scoliosis; the similarities between patients with scoliosis and patients with COPD suggest a common aetiology to quadriceps weakness in both conditions.

S94 Ultrasound measurement of quadriceps wasting in early chronic obstructive pulmonary disease and its relationship with daily physical activity

Introduction Quadriceps weakness is recognised as an important complication of COPD but few data exist about loss of muscle bulk in early disease. We hypothesised that quadriceps wasting, measured by ultrasound rectus femoris cross-sectional (USRFCSA), would be observed in patients with mild COPD compared to healthy age-matched subjects and that this would correlate with daily physical activity levels. Methods Rectus femoris cross-sectional area was measured using ultrasound (USRFCSA) and daily physical activity (step count and physical activity level—PAL) recorded using a multisensor biaxial armband accelerometer. Fat free mass index (FFMI) and the impedance ratio (Z200/Z5) were determined by bioelectrical impedance analysis. Quadriceps maximum voluntary contraction (QMVC) was used as a measure of strength. Results 150 patients with stable COPD, GOLD stage I (n=38), II (n=38), III (n=37) and IV (n=37), mean (SD) age 66 (9) years, 54% male and 40 age-matched healthy subjects participated in the study. USRFCSA was significantly reduced in stage I COPD patients compared to controls (530 mm2 vs 640 mm2; p=0.0002) (Abstract S94 figure 1); USRFCSA was also reduced in stages II (526 mm2), III (503 mm2) and IV (509 mm2) disease (p=0.0001). Daily physical activity was reduced in stage I patients (steps; p<0.0001, PAL; p=0.002) and stage II–IV COPD (steps and PAL; p<0.0001) compared to healthy subjects. Using multivariate linear regression, USRFCSA (p=0.0003), FFMI (p=0.0003) and the impedance ratio (p=0.001) were all independent predictors of quadriceps strength in COPD. In stage I patients, only USRFCSA was shown to be independently associated with daily physical activity (steps, p=0.03; PAL, p=0.003), while in stage II–IV disease, FEV1% predicted was retained as the only independent correlate with daily physical activity (steps and PAL, p<0.0001).Abstract S94 Figure 1 Ultrasound rectus femoris cross-sectional area vs GOLD stage in COPD patients and healthy controls (ANOVA analysis—no significant difference between I and IV). Conclusions Quadriceps wasting identified by USRFCSA exists in patients with early, as well as advanced, COPD when compared to healthy age-matched controls. Quadriceps bulk is associated with daily physical activity independent of airflow obstruction, in early but not advanced disease. Our data suggest that, rather than being an end-stage phenomenon, quadriceps wasting is present in a substantial minority of COPD patients and is related to physical inactivity in the absence of severe airflow limitation.

P220 Transfer factor and arterial oxygen partial pressure are predictors of survival in hospital outpatients with COPD

Introduction COPD is a disorder characterised by high morbidity and mortality. Although several parameters have been used to predict survival among COPD patients, most of the information on the prognostic value of pulmonary function comes from studies, either conducted in selected COPD populations or where only simple spirometry was measured. Few studies have comprehensively assessed lung function parameters and investigated their impact on survival; a prior smaller study from our group suggested carbon monoxide gas transfer may have prognostic value.1 Objective The study aimed to identify potential predictors of survival in a cohort of stable COPD outpatients. Methods Data from patients, who had their first full lung function tests including blood gas analysis between February 1996 and May 2010 were extracted from the hospitals clinical COPD database. Patients with major co morbidities, such as malignancy, chronic renal failure and chronic heart failure were excluded. Survival data were available for all patients, until May 2011. Demographic data, PaO2 and PaCO2, transfer factor, and plethysmographic lung volumes were initially entered in a univariate regression model. Age, Body Mass Index (BMI), FEV1% predicted, FEV1/FVC, TLC% predicted, TLCOc% predicted, KCOc% predicted, RV% predicted, IC/TLC, PaCO2 and PaO2, were found to be univariately associated with survival and then entered in a stepwise Cox regression analysis model. Corresponding HRs and 95% CI were calculated for each independent predictor. Results Data were available for 641 patients (62.2% male); mean age 61.9±10.2 years, FEV1 38.4±19.7% and BMI 24.3±5.3 kg/m2. Median survival was 92.9 months. Survival rates at 3 and 5 years (all cause mortality) were 0.88 and 0.62. In the total population, age (HR 1.05, 95% CI 1.03 to 1.07), PaO2 (HR 0.843, 95% CI 0.76 to 0.934) and TLCOc% (HR 0.975, 95%CI to 0.965 to 0.986) independently predicted survival. Abstract P220 Figure 1 presents the Kaplan–Meier survival curves, adjusted for age and PO2, for the two population groups, separated using the TLCOc% median value as a cut-off point (>38.0 and =38.0% predicted).Abstract P220 Figure 1 Survival curves adjusted for PO2 and age for the two patient groups, separated according to TLCOc% predicted value. Conclusions Gas transfer measurement provides additional prognostic information compared to spirometry.

P139 Atelectasis following bronchoscopic lung volume reduction (BLVR) is associated with improved survival in COPD

Background A range of bronchoscopic therapies are being developed to reduce lung volumes in COPD patients, either in order to avoid the morbidity and mortality associated with lung volume reduction surgery, or to extend therapy to patient groups in whom LVRS is not appropriate because of disease pattern or severity. Aims Bronchoscopic lung volume reduction (BLVR), using endobronchial valves to target unilateral lobar occlusion in patients with heterogeneous emphysema has been shown to improve lung function and exercise capacity in patients with emphysema. Benefit was most pronounced in, though not confined to, patients where lobar atelectasis occurred. Little data exists on the long-term outcome following BLVR. Study population 19 patients (16 males) FEV1 28.4 (11.9) underwent BLVR between July 2002 and February 2004. Radiological atelectasis was observed in five patients. Survival data to February 2010 was available for all patients. The age dyspnoea obstruction (ADO) score was used to calculate predicted mortality. Results None of the patients in whom atelectasis occurred died during follow up whereas eight out of 14 in the non-atelectasis group died (χ2 p=0.026) (Abstract P139 Figure 1). There was no significant difference between the groups at baseline in lung function, quality of life, exacerbation rate, exercise capacity (shuttle walk test or cycle ergometry) or CT appearances, although BMI was significantly higher in the atelectasis group 21.6(2.9) vs 28.4 (2.9) kg.m−2 (p<0.001). Pre treatment CT appearances did not differ significantly between the atelectasis and non-atelectasis groups in terms of degree of emphysema at either the upper or lower parts of the lungs or in heterogeneity (slope) in either the treated or non-treated lung prior to treatment. ADO score, predicted 3 year mortality was 31.1 (10.0)% in the non-atelectasis group and 32.2 (15.1)% in the atelectasis group (p=0.8). Four of the eight deaths occurred within 3 years of the procedure, representing a 29% mortality rate for the non-atelectasis group (ie, close to that predicted).Abstract P139 Figure 1 Conclusions These data suggest that atelectasis following BLVR is associated with a survival benefit which is not explained by differences at baseline.