Background: Quadriceps weakness and loss of muscle mass predict mortality in chronic obstructive pulmonary disease (COPD). It was hypothesised that a reduced quadriceps cross-sectional area could be detected by ultrasound in patients with COPD compared with healthy subjects, and that measurements relate to strength and fat-free mass (FFM). Methods: Rectus femoris muscle cross-sectional area (RF CSA ) was measured by ultrasound and whole-body FFM estimated using electrical bioimpedance. Quadriceps strength was measured by maximum voluntary contraction and twitch tension (TwQ) following magnetic femoral nerve stimulation. Results: 26 healthy volunteers of mean (SD) age 63 (9) years and 30 patients with COPD of mean (SD) age 67 (9) years and percentage predicted forced expiratory volume in 1 s (FEV 1 ) 48.0 (20.8)% with a similar FFM (46.9 (9.3) kg vs 46.1 (7.3) kg, p = 0.193) participated in the study. Mean RF CSA was reduced in patients with COPD by 25% of the mean value in healthy subjects(2115 mm 2 ; 95% CI 2177 to 254, p = 0.001) and was related to MRC dyspnoea scale score, independent of FFM or sex. Maximum voluntary contraction strength was linearly related to RF CSA in patients with COPD (r = 0.78, p,0.001). TwQ force per unit of RF CSA was similar in both healthy individuals and those with COPD (mean (SD) 17 (4) g/mm 2 vs 18 (3) g/mm 2 , p = 0.657). Voluntary contraction strength per unit of RF CSA was dependent on central quadriceps activation and peripheral oxygen saturation in COPD. Conclusion: Ultrasound measurement of RF CSA is an effort-independent and radiation-free method of measuring quadriceps muscle cross-sectional area in patients with COPD that relates to strength.Even in non-cachectic patients with chronic obstructive pulmonary disease (COPD), quadriceps strength is typically reduced by up to 30% compared with healthy elderly subjects. 1 Quadriceps strength has been shown independently to predict increased healthcare utilisation and mortality in COPD. 2 3 In our cohort of patients with moderate to severe COPD, quadriceps strength together with age provided more powerful prognostic information than whole body fat-free mass (FFM) or forced expiratory volume in 1 s (FEV 1 ). 3 A related measure, mid-thigh cross-sectional area measured by computed tomography (CT), has also been shown to predict mortality. 4 Quadriceps strength may be assessed by maximum voluntary contraction force, but maximum effort cannot be guaranteed and formal testing equipment is cumbersome. 5 6 Effort-independent methods of assessing strength such as femoral nerve stimulation are expensive, not widely available and require specific expertise. 7 Bedside tests are attractive for their simplicity and accessibility but measurement of thigh circumference, for example, may not accurately reflect the muscle compartment. Ionising radiation exposure makes serial measurements with CT 4 or dual energy x ray absorptiometry scanning 8 9 undesirable in large populations. MRI avoids this concern, but accessibility and long scann...

The aim of the present study was to use the diaphragm electromyogram (EMGdi) to compare levels of neural respiratory drive (NRD) in a cohort of healthy subjects and chronic obstructive pulmonary disease (COPD) patients, and to investigate the relationship between NRD and pulmonary function in COPD.EMGdi was recorded at rest and normalised to peak EMGdi recorded during maximum inspiratory manoeuvres (EMGdi % max) in 100 healthy subjects and 30 patients with COPD, using a multipair oesophageal electrode. EMGdi was normalised to the amplitude of the diaphragm compound muscle action potential (CMAPdi,MS) in 64 healthy subjects.The mean¡SD EMGdi % max was 9.0¡3.4% in healthy subjects and 27.9¡9.9% in COPD patients, and correlated with percentage predicted forced expiratory volume in one second, vital capacity and inspiratory capacity in patients. EMGdi % max was higher in healthy subjects aged 51-80 yrs than in those aged 18-50 yrs (11.4¡3.4 versus 8.2¡2.9%, respectively). Observations in the healthy group were similar when peak EMGdi or CMAPdi,MS were used to normalise EMGdi.Levels of neural respiratory drive were higher in chronic obstructive pulmonary disease patients than healthy subjects, and related to disease severity. Diaphragm compound muscle action potential could be used to normalise diaphragm electromyogram if volitional inspiratory manoeuvres could not be performed, allowing translation of the technique to critically ill and ventilated patients.KEYWORDS: Chronic obstructive pulmonary disease, electromyography, respiratory diaphragm O bjective markers of disease severity that reflect the physiological load on the respiratory system in chronic obstructive pulmonary disease (COPD) are currently lacking. Although COPD severity is categorised in terms of forced expiratory volume in one second (FEV1) in management guidelines [1], correlations between FEV1 and breathlessness [2] or quality of life are modest [3], and reported relationships between FEV1 and prognosis are inconsistent [4][5][6]. Two small studies confirm that neural respiratory drive (NRD) is increased in COPD [7] and relates to symptoms [8], but the use of measurements of NRD to assess disease severity in COPD has not been fully investigated, in part because there are no data to define ranges of NRD within the healthy population.In COPD, mechanical abnormalities including airflow obstruction, static and dynamic hyperinflation and intrinsic positive end-expiratory pressure increase the load on the respiratory muscles. The translation of inspiratory muscle contraction into negative intrathoracic pressure, and of pressure changes to ventilation, is impaired as a consequence of muscle shortening, increased velocity of contraction, alteration in geometry and reduced compliance of the respiratory system. This results in high NRD in COPD, and disproportionate increases whenever airways obstruction worsens (and hyperinflation increases) or ventilatory requirements increase. The neural output of the brainstem respiratory centre cannot easily be...

Background: Respiratory muscle weakness is an important clinical problem. Tests of varying complexity and invasiveness are available to assess respiratory muscle strength. The relative precision of different tests in the detection of weakness is less clear, as is the value of multiple tests. Methods: The respiratory muscle function tests of clinical referrals who had multiple tests assessed in our laboratories over a 6-year period were analysed. Thresholds for weakness for each test were determined from published and in-house laboratory data. The patients were divided into three groups: those who had all relevant measurements of global inspiratory muscle strength (group A, n = 182), those with full assessment of diaphragm strength (group B, n = 264) and those for whom expiratory muscle strength was fully evaluated (group C, n = 60). The diagnostic outcome of each inspiratory, diaphragm and expiratory muscle test, both singly and in combination, was studied and the impact of using more than one test to detect weakness was calculated. Results: The clinical referrals were primarily for the evaluation of neuromuscular diseases and dyspnoea of unknown cause. A low maximal inspiratory mouth pressure (PImax) was recorded in 40.1% of referrals in group A, while a low sniff nasal pressure (Sniff Pnasal) was recorded in 41.8% and a low sniff oesophageal pressure (Sniff Poes) in 37.9%. When assessing inspiratory strength with the combination of all three tests, 29.6% of patients had weakness. Using the two non-invasive tests (PImax and Sniff Pnasal) in combination, a similar result was obtained (low in 32.4%). Combining Sniff Pdi (low in 68.2%) and Twitch Pdi (low in 67.4%) reduced the diagnoses of patients with diaphragm weakness to 55.3% in group B. 38.3% of the patients in group C had expiratory muscle weakness as measured by maximum expiratory pressure (PEmax) compared with 36.7% when weakness was diagnosed by cough gastric pressure (Pgas), and 28.3% when assessed by Twitch T10. Combining all three expiratory muscle tests reduced the number of patients diagnosed as having expiratory muscle weakness to 16.7%. Conclusion: The use of single tests such as PImax, PEmax and other available individual tests of inspiratory, diaphragm and expiratory muscle strength tends to overdiagnose weakness. Combinations of tests increase diagnostic precision and, in the population studied, they reduced the diagnosis of inspiratory, specific diaphragm and expiratory muscle weakness by 19-56%. Measuring both PImax and Sniff Pnasal resulted in a relative reduction of 19.2% of patients falsely diagnosed with inspiratory muscle weakness. The addition of Twitch Pdi to Sniff Pdi increased diagnostic precision by a smaller amount (18.9%). Having multiple tests of respiratory muscle function available both increases diagnostic precision and makes assessment possible in a range of clinical circumstances.

Background Neural respiratory drive (NRD) measured from the diaphragm electromyogram (EMGdi) reflects the load/capacity balance of the respiratory muscle pump and is a marker of lung disease severity. EMGdi measurement is invasive, but recording the EMG from the parasternal intercostal muscles using surface electrodes (sEMGpara) could provide a non-invasive method of assessing NRD and disease severity. Objectives To test the hypothesis that NRD measured by sEMGpara correlates with EMGdi, to provide an index of disease severity in cystic fibrosis (CF) and to relate to exercise-induced breathlessness. Methods 15 patients with CF (mean forced expiratory volume in 1 s (FEV 1 ) 53.5% predicted) and 15 age-matched healthy controls were studied. sEMGpara and EMGdi were recorded at rest and during exercise. sEMGpara was recorded using surface electrodes and EMGdi using a multipair oesophageal electrode catheter. Signals were normalised using the peak EMG recorded during maximum respiratory manoeuvres and expressed as EMG%max. The respiratory pattern, metabolic data, oesophageal and gastric pressures and Borg scores were also recorded. Results Mean (SD) resting sEMGpara%max and EMGdi %max were higher in patients with CF than in controls (13.1 (7)% and 18.5 (7.5)% vs 5.8 (3)% and 7.5 (2)%, respectively, p<0.001). In the patients with CF, resting sEMGpara%max and EMGdi%max were related to the degree of airways obstruction (FEV 1 ) (r¼À0.91 and r¼À0.82, both p<0.001), hyperinflation (r¼0.63 and r¼0.56, both p<0.001) and dynamic lung compliance (r¼À0.53 and r¼À0.59, both p<0.001). During exercise, sEMGpara%max and EMGdi%max were strongly correlated with breathlessness in the patients with CF before (r¼0.906, p<0.001) and after (r¼0.975, p<0.001) the onset of neuromechanical dissociation. Conclusion sEMGpara%max provides a non-invasive marker of neural drive, which reflects disease severity and exercise-induced breathlessness in CF.

Patients with chronic obstructive pulmonary disease (COPD) may stop cycling due to leg effort rather than breathlessness. However, cycling is not relevant to many patients, although walking may be more familiar. A total of 84 patients with COPD were asked to name the predominant symptom limiting incremental shuttle walking, endurance shuttle walking, incremental cycle ergometry, and endurance cycle ergometry, performed to exhaustion on four separate days. Furthermore, quadriceps fatigability was evaluated in 12 patients by measuring unpotentiated and potentiated twitch quadriceps tensions before and 30 minutes after incremental walking and cycling. Breathlessness alone was a more commonly cited limiting symptom after incremental walking compared with incremental cycling (81 vs. 34%; p < 0.001) and after endurance walking compared with endurance cycling (75 vs. 29%; p < 0.001). In addition, there was no significant change in mean pre- and postwalking twitch quadriceps tensions. However, cycling produced a significant reduction (unpotentiated 7.42 +/- 2.22 vs. 6.48 +/- 2.09 kg [p < 0.001]; potentiated 10.19 +/- 3.99 vs. 8.45 +/- 3.18 kg [p < 0.001]). Pre- to postexercise changes were significantly greater during cycling compared with walking (unpotentiated p = 0.01; potentiated p = 0.003). Leg effort is an infrequent symptom after walking in COPD, and low frequency fatigue of the quadriceps is an infrequent feature of incremental walking.

Background: Although quadriceps weakness is well recognised in chronic obstructive pulmonary disease (COPD), the aetiology remains unknown. In disabled patients the quadriceps is a particularly underused muscle and may not reflect skeletal muscle function as a whole. Loss of muscle function is likely to be equally distributed if the underlying pathology is a systemic abnormality. Conversely, if deconditioning and disuse are the principal aetiological factors, weakness would be most marked in the lower limb muscles. Methods: The non-volitional technique of supramaximal magnetic stimulation was used to assess twitch tensions of the adductor pollicis, quadriceps, and diaphragm muscles (TwAP, TwQ, and TwPdi) in 22 stable non-weight losing COPD patients and 18 elderly controls. Results: Mean (SD) TwQ tension was reduced in the COPD patients (7.1 (2.2) kg v 10.0 (2.7) kg; 95% confidence intervals (CI) -4.4 to -1.4; p<0.001). Neither TwAP nor TwPdi (when corrected for lung volume) differed significantly between patients and controls (mean (SD) TwAP 6.52 (1.90) N for COPD patients and 6.80 (1.99) N for controls (95% CI -1.5 to 0.97, p=0.65; TwPdi 23.0 (5.6) cm H 2 O for COPD patients and 23.5 (5.2) cm H 2 O for controls (95% CI -4.5 to 3.5, p=0.81). Conclusions: The strength of the adductor pollicis muscle (and the diaphragm) is normal in patients with stable COPD whereas quadriceps strength is substantially reduced. Disuse may be the principal factor in the development of skeletal muscle weakness in COPD, but a systemic process preferentially affecting the proximal muscles cannot be excluded.

Maximal expiratory mouth pressure is a well established test that is used to assess expiratory muscle strength. However, low values are difficult to interpret, as they may result from technical difficulties in performing the test, particularly in patients with facial muscle weakness or bulbar dysfunction. We hypothesized that measuring the gastric pressure during a cough, a natural maneuver recruiting the expiratory muscles, might prove to be a useful additional test in the assessment of expiratory muscle function. Mouth expiratory and cough gastric pressures were measured in 99 healthy volunteers to obtain normal values and in 293 patients referred for respiratory muscle assessment to compare the two measurements. Between-occasion within-subject coefficient of variation, assessed in 24 healthy volunteers, was 10.3% for mouth pressure and 6.9% for cough. Mean +/- SD cough gastric pressure for normal males was 214.4 +/- 42.2 and 165.1 +/- 34.8 cm H2O for females. In 171 patients deemed weak by a low mouth expiratory pressure, 42% had a normal cough gastric pressure. In 105 patients deemed weak by a low cough gastric pressure, 5.7% had a normal expiratory mouth pressure. Low maximal expiratory mouth pressures do not always indicate expiratory muscle weakness. Cough gastric pressure provides a useful complementary test for the assessment of expiratory muscle strength.

The study was a single-blind randomized controlled trial with 3 study groups; reporting followed Consolidated Standards of Reporting Trials (CONSORT) guidelines.9 Subjects were allocated using aBackground and Purpose-Cough protects the lungs from aspiration. We investigated whether respiratory muscle training may improve respiratory muscle and cough function, and potentially reduce pneumonia risk in acute stroke. Methods-We conducted a single-blind randomized placebo-controlled trial in 82 patients with stroke (mean age, 64±14 years; 49 men) within 2 weeks of stroke onset. Participants were masked to treatment allocation and randomized to 4 weeks of daily expiratory (n=27), inspiratory (n=26), or sham training (n=25), using threshold resistance devices. Primary outcome was the change in peak expiratory cough flow of maximal voluntary cough. Intention-to-treat analyses were conducted using ANCOVA, adjusting for baseline prognostic covariates. Results-There were significant improvements in the mean maximal inspiratory (14 cmH 2 O; P<0.0001) and expiratory (15 cmH 2 O; P<0.0001) mouth pressure and peak expiratory cough flow of voluntary cough (74 L/min; P=0.0002) between baseline and 28 days in all groups. Peak expiratory cough flow of capsaicin-induced reflex cough was unchanged. There were no between-group differences that could be attributed to respiratory muscle training. There were also no differences in the 90-day incidence of pneumonia between the groups (P=0.65). Conclusions-Respiratory muscle function and cough flow improve with time after acute stroke. Additional inspiratory or expiratory respiratory muscle training does not augment or expedite this improvement. Clinical Trial Registration-URL: http://www.controlled-trials.com. Unique identifier: ISRCTN40298220.