John Seymour

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.

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.

Quadriceps wasting and physical inactivity in patients with COPD

Quadriceps weakness is an important complication of advanced chronic obstructive pulmonary disease (COPD) but few data exist concerning muscle bulk in early disease. We hypothesised that quadriceps bulk, measured by ultrasound rectus femoris cross-sectional area (USRFCSA), would be reduced in mild, as well as advanced, COPD compared with controls, and would correlate with physical activity. 161 patients with stable COPD and 40 healthy subjects had a measurement of USRFCSA and wore a multisensor armband to record physical activity. USRFCSA was reduced in Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I patients compared with healthy subjects (p=0.0002). Stage II–IV patients had reduced USRFCSA (p<0.0001) compared with controls but were not significantly different from those with stage I disease. Physical activity level was reduced in stage I (p=0.002) and stage II–IV disease compared with controls. Using regression analysis, physical activity level was independently associated with USRFCSA in stage I (p=0.01) but not stage II–IV disease, where residual volume to total lung capacity ratio was the only independent predictor of physical activity level. Quadriceps wasting exists in patients with mild, as well as advanced, COPD, and is independently associated with physical inactivity in GOLD stage I disease. The identification of these patients may guide early lifestyle and therapeutic interventions.

Ultrasound measurement of rectus femoris cross-sectional area and the relationship with quadriceps strength in COPD

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 (RFCSA) 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 (FEV1) 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 RFCSA was reduced in patients with COPD by 25% of the mean value in healthy subjects(−115 mm2; 95% CI −177 to −54, p = 0.001) and was related to MRC dyspnoea scale score, independent of FFM or sex. Maximum voluntary contraction strength was linearly related to RFCSA in patients with COPD (r = 0.78, p<0.001). TwQ force per unit of RFCSA was similar in both healthy individuals and those with COPD (mean (SD) 17 (4) g/mm2 vs 18 (3) g/mm2, p = 0.657). Voluntary contraction strength per unit of RFCSA was dependent on central quadriceps activation and peripheral oxygen saturation in COPD. Conclusion: Ultrasound measurement of RFCSA is an effort-independent and radiation-free method of measuring quadriceps muscle cross-sectional area in patients with COPD that relates to strength.

The value of multiple tests of respiratory muscle strength

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.

Neural Respiratory Drive in Obesity

Background: The load imposed on ventilation by increased body mass contributes to the respiratory symptoms caused by obesity. A study was conducted to quantify ventilatory load and respiratory drive in obesity in both the upright and supine postures. Methods: Resting breathing when seated and supine was studied in 30 obese subjects (mean (SD) body mass index (BMI) 42.8 (8.6) kg/m2) and 30 normal subjects (mean (SD) BMI 23.6 (3.7) kg/m2), recording the electromyogram of the diaphragm (EMGdi, transoesophageal multipair electrode), gastric and oesophageal pressures. Results: Ventilatory load and neural drive were higher in the obese group as judged by the EMGdi (21.9 (9.0) vs 8.4 (4.0)%max, p<0.001) and oesophageal pressure swings (9.6 (2.9) vs 5.3 (2.2) cm H2O, p<0.001). The supine posture caused an increase in oesophageal pressure swings to 16.0 (5.0) cm H2O in obese subjects (p<0.001) and to 6.9 (2.0) cm H2O in non-obese subjects (p<0.001). The EMGdi increased in the obese group to 24.7 (8.2)%max (p<0.001) but remained the same in non-obese subjects (7.0 (3.4)%max, p = NS). Obese subjects developed intrinsic positive end-expiratory pressure (PEEPi) of 5.3 (3.6) cm H2O when supine. Applying continuous positive airway pressure (CPAP) in a subgroup of obese subjects when supine reduced the EMGdi by 40%, inspiratory pressure swings by 25% and largely abolished PEEPi (4.1 (2.7) vs 0.8 (0.4) cm H2O, p = 0.009). Conclusion: Obese patients have substantially increased neural drive related to BMI and develop PEEPi when supine. CPAP abolishes PEEPi and reduces neural respiratory drive in these patients. These findings highlight the adverse respiratory consequences of obesity and have implications for the clinical management of patients, particularly where the supine posture is required.

Neural respiratory drive in healthy subjects and in COPD

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.

Acute ischaemic hemispheric stroke is associated with impairment of reflex in addition to voluntary cough

Cough function is impaired after stroke; this may be important for protection against chest infection. Reflex cough (RC) intensity indices have not been described after stroke. RC, voluntary cough (VC) and respiratory muscle strength were studied in patients within 2 weeks of hemispheric infarct. The null hypotheses were that patients with cortical hemisphere stroke would show the same results as healthy controls on: 1) objective indices of RC and VC intensity; and 2) respiratory muscle strength tests. Peak cough flow rate (PCFR) and gastric pressure (Pga) were measured during maximum VC and RC. Participants also underwent volitional and nonvolitional respiratory muscle testing. Nonvolitional expiratory muscle strength was assessed by measuring Pga increase after magnetic stimulation over the T10 nerve roots (twitch T10 Pga). Stroke severity was scored using the National Institutes of Health Stroke Scale (NIHSS; maximum = 31). 18 patients (mean±sd age 62±15 yrs and NIHSS score 14±8) and 20 controls (56±16 yrs) participated. VC intensity was impaired in patients (PCFR 287±171 versus 497±122 L·min−1) as was VC Pga (98.5±61.6 versus 208.5±61.3 cmH2O; p<0.001 for both). RC PCFR was reduced in patients (204±111 versus 379±110 L·min−1; p<0.001), but RC Pga was not significantly different from that of controls (179.0±78.0 versus 208.0±77.4 cmH2O; p = 0.266). Patients exhibited impaired volitional respiratory muscle tests, but twitch T10 Pga was normal. VC and RC are both impaired in hemispheric stroke patients, despite preserved expiratory muscle strength. Cough coordination is probably cortically modulated and affected by hemispheric stroke.

Sleep-disordered breathing in unilateral diaphragm paralysis or severe weakness

Few data exist concerning sleep in patients with hemidiaphragm paralysis or weakness. Traditionally, such patients are considered to sustain normal ventilation in sleep. In the present study, diaphragm strength was measured in order to identify patients with unilateral paralysis or severe weakness. Patients underwent polysomnography with additional recordings of the transoesophageal electromyogram (EMG) of the diaphragm and surface EMG of extra-diaphragmatic respiratory muscles. These data were compared with 11 normal, healthy subjects matched for sex, age and body mass index (BMI). In total, 11 patients (six males, mean±sd age 56.5±10.0 yrs, BMI 28.7±2.8 kg·m−2) with hemidiaphragm paralysis or severe weakness (unilateral twitch transdiaphragmatic pressure 3.3±1.7 cmH2O (0.33±0.17 kPa) were studied. They had a mean±sd respiratory disturbance index of 8.1±10.1 events·h−1 during non-rapid eye movement (NREM) sleep and 26.0±17.8 events·h−1 during rapid eye movement (REM) sleep (control groups 0.4±0.4 and 0.7±0.9 events·h−1, respectively). The diaphragm EMG, as a percentage of maximum, was double that of the control group in NREM sleep (15.3±5.3 versus 8.9±4.9% max, respectively) and increased in REM sleep (20.0±6.9% max), while normal subjects sustained the same level of activation (6.2±3.1% max). Patients with unilateral diaphragm dysfunction are at risk of developing sleep-disordered breathing during rapid eye movement sleep. The diaphragm electromyogram, reflecting neural respiratory drive, is doubled in patients compared with normal subjects, and increases further in rapid eye movement sleep.

Continuous Transcutaneous Submental Electrical Stimulation in Obstructive Sleep Apnea: A Feasibility Study

BACKGROUND The therapeutic value of transcutaneous electrical stimulation of the genioglossus muscle in patients with obstructive sleep apnea (OSA) to reduce sleep-disordered breathing is unclear. METHODS Contraction of the genioglossus muscles during transcutaneous stimulation was investigated using ultrasonography in 11 healthy subjects (seven men, mean [SD] age 30 [6] years; BMI, 24.2 [3.5] kg/m(2)). Esophageal and gastric pressures were measured with balloon catheters, and transesophageal diaphragm electromyogram (EMGdi) was recorded during polysomnography in 11 patients with OSA (eight men, aged 51 [16] years; BMI, 42.0 [9.7] kg/m(2)) while transcutaneous electrical stimulation of the genioglossus was applied in non-rapid eye movement sleep (stage N2). RESULTS Ultrasonography measurements showed a significant increase in tongue diameter during stimulation (sagittal: 10.0% [2.8%]; coronal: 9.4 % [3.7%]). The measurements were reproducible and repeatable. In patients with OSA, snoring decreased during stimulation (P < .001) and oxygenation improved (P = .001); the respiratory disturbance index (RDI) fell from 28.1 (26.3) to 10.2 (10.2) events per hour during stimulation (P = .002), returning to 26.6 (26.0) events per hour after stimulation was stopped. Transdiaphragmatic pressure swing decreased from 24.1 (13.5) cm H(2)O to 19.7 (7.1) cm H(2)O (P = .022), increasing to 24.2 (10.8) cm H(2)O afterward, and EMGdi fell from 23.8% max (12.6% max) to 15.7% max (6.4% max) (P < .001), rising to 22.6% max (10.4% max) post stimulation. CONCLUSIONS Continuous transcutaneous electrical stimulation of the genioglossus contracts the genioglossus muscle and reduces ventilatory load and neural respiratory drive in patients with OSA.