Nicholas Hart

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.

Measurement of twitch transdiaphragmatic, esophageal, and endotracheal tube pressure with bilateral anterolateral magnetic phrenic nerve stimulation in patients in the intensive care unit.

ObjectiveIn the critically ill, respiratory muscle strength usually has been assessed by measuring maximum inspiratory pressure. The maneuver is volitional, and results can be unreliable. The nonvolitional technique of bilateral anterolateral magnetic stimulation of the phrenic nerves, producing twitch transdiaphragmatic pressure, has been successful in normal subjects and ambulatory patients. In this study we used the technique in the intensive care unit and explored the measurement of twitch endotracheal tube pressure as a less invasive technique to assess diaphragmatic contractility. DesignClinical study to quantify diaphragm strength in the intensive care unit. SettingPatients from three London teaching hospital intensive care units and high-dependency units. PatientsForty-one intensive care patients were recruited. Of these, 33 (20 men, 13 women) were studied. InterventionsEsophageal and gastric balloon catheters were passed through the anaesthetized nose, and an endotracheal tube occlusion device was placed in the ventilation circuit, next to the endotracheal tube. Two 43-mm magnetic coils were placed anteriorly on the patient’s neck, and the phrenic nerves were stimulated magnetically. Measurements and Main Results On phrenic nerve stimulation, twitch gastric pressure, twitch esophageal pressure, twitch transdiaphragmatic pressure, and twitch endotracheal tube pressure were measured. Forty-one consecutive patients consented to take part in the study, and twitch pressure data were obtained in 33 of these. Mean transdiaphragmatic pressure was 10.7 cm H2O, mean twitch esophageal pressure was 6.7 cm H2O, and mean twitch endotracheal tube pressure was 6.7 cm H2O. The mean difference between twitch esophageal pressure and twitch endotracheal tube pressure was 0.02 cm H2O. Correlation of the means of twitch endotracheal tube pressure to twitch esophageal pressure was 0.93, and that for twitch endotracheal tube pressure to transdiaphragmatic pressure was 0.78. ConclusionsTransdiaphragmatic pressure can be measured in the critically ill to give a nonvolitional assessment of diaphragm contractility, but not all patients can be studied. At present, the relationship of twitch endotracheal tube pressure to transdiaphragmatic pressure is too variable to reliably represent a less invasive measure of diaphragm strength.

Volume targeted versus pressure support non-invasive ventilation in patients with super obesity and chronic respiratory failure: a randomised controlled trial

Introduction Automatic titration modes of non-invasive ventilation, including average volume assured pressure support (AVAPS), are hybrid technologies that target a set volume by automated adjustment of pressure support (PS). These automated modes could offer potential advantages over fixed level PS, in particular, in patients who are super obese. Methods Consecutive patients with obesity hypoventilation syndrome were enrolled in a two-centre prospective single-blind randomised controlled trial of AVAPS versus fixed-level PS using a strict protocolised setup. Measurements The primary outcome was change in daytime arterial PCO2 (PaCO2) at 3 months. Body composition, physical activity (7-day actigraphy) and health-related quality of life (severe respiratory insufficiency questionnaire, SRI) were secondary outcome measures. Results 50 patients (body mass index 50±7 kg/m2; 55±11 years; 53% men) were enrolled with a mean PaCO2 of 6.9±0.8 kPa and SRI of 53±17. 46 patients (23 AVAPS and 23 PS) completed the trial. At 3 months, improvements in PaCO2 were observed in both groups (AVAPS ∆0.6 kPa, 95% CI 0.2 to 1.1, p<0.01 vs PS ∆0.6 kPa, 95% CI 0.1 to 1.1, p=0.02) but no between-group difference (∆−0.1 kPa, 95% CI −0.7 to 0.6, p=0.87). SRI also improved in both groups (AVAPS ∆11, 95% CI 6 to 17, p<0.001 vs PS ∆7, 95% CI 1 to 12, p=0.02; between groups ∆5, 95% CI −3 to 12, p=0.21). Secondary analysis of both groups combined showed improvements in daytime physical activity that correlated with reduction in fat mass (r=0.48; p=0.01). Conclusion The study demonstrated no differences between automated AVAPS mode and fixed-level PS mode using a strict protocolised setup in patients who were super obese. The data suggest that the management of sleep-disordered breathing may enhance daytime activity and promote weight loss in super-obese patients. Trial registration details available at http://www.controlled-trials.com/ISRCTN63940700

Effect of salmeterol on respiratory muscle activity during exercise in poorly reversible COPD

Background: Some patients with irreversible chronic obstructive pulmonary disease (COPD) experience subjective benefit from long acting bronchodilators without change in forced expiratory volume in 1 second (FEV1). Dynamic hyperinflation is an important determinant of exercise induced dyspnoea in COPD. We hypothesised that long acting bronchodilators improve symptoms by reducing dynamic hyperinflation and work of breathing, as measured by respiratory muscle pressure-time products. Methods: Sixteen patients with “irreversible” COPD (<10% improvement in FEV1 following a bronchodilator challenge; mean FEV1 31.1% predicted) were recruited into a randomised, double blind, placebo controlled, crossover study of salmeterol (50 μg twice a day). Treatment periods were of 2 weeks duration with a 2 week washout period. Primary outcome measures were end exercise isotime transdiaphragmatic pressure-time product and dynamic hyperinflation as measured by inspiratory capacity. Results: Salmeterol significantly reduced the transdiaphragmatic pressure-time product (294.5 v 348.6 cm H2O/s/min; p = 0.03), dynamic hyperinflation (0.22 v 0.33 litres; p = 0.002), and Borg scores during endurance treadmill walk (3.78 v 4.62; p = 0.02). There was no significant change in exercise endurance time. Improvements in isotime Borg score were significantly correlated to changes in tidal volume/oesophageal pressure swings, end expiratory lung volume, and inspiratory capacity, but not pressure-time products. Conclusions: Despite apparent “non-reversibility” in spirometric parameters, long acting bronchodilators can cause both symptomatic and physiological improvement during exercise in severe COPD.

Mechanisms of improvement of respiratory failure in patients with restrictive thoracic disease treated with non-invasive ventilation

Background: Nocturnal non-invasive ventilation (NIV) is an effective treatment for hypercapnic respiratory failure in patients with restrictive thoracic disease. We hypothesised that NIV may reverse respiratory failure by increasing the ventilatory response to carbon dioxide, reducing inspiratory muscle fatigue, or enhancing pulmonary mechanics. Methods: Twenty patients with restrictive disease were studied at baseline (D0) and at 5–8 days (D5) and 3 months (3M). Results: Mean (SD) daytime arterial carbon dioxide tension (Paco2) was reduced from 7.1 (0.9) kPa to 6.6 (0.8) kPa at D5 and 6.3 (0.9) kPa at 3M (p = 0.004), with the mean (SD) hypercapnic ventilatory response increasing from 2.8 (2.3) l/min/kPa to 3.6 (2.4) l/min/kPa at D5 and 4.3 (3.3) l/min/kPa at 3M (p = 0.044). No increase was observed in measures of inspiratory muscle strength including twitch transdiaphragmatic pressure, nor in lung function or respiratory system compliance. Conclusions: These findings suggest that increased ventilatory response to carbon dioxide is the principal mechanism underlying the long term improvement in gas exchange following NIV in patients with restrictive thoracic disease. Increases in respiratory muscle strength (sniff oesophageal pressure and sniff nasal pressure) correlated with reductions in the Epworth sleepiness score, possibly indicating an increase in the ability of patients to activate inspiratory muscles rather than an improvement in contractility.

Limitations of sniff nasal pressure in patients with severe neuromuscular weakness

Background: Inspiratory muscle strength in patients with neuromuscular disorders can be assessed using sniff inspiratory nasal pressure (Pnsn) and maximum inspiratory mouth pressure (PImax). However, the relative merits of Pnsn against PImax are not known in patients with severe neuromuscular disease. Objective: To investigate whether severity of disease modifies the relation between Pnsn and PImax. Methods: Vital capacity (VC), Pnsn, and PImax were measured in 258 patients with neuromuscular disorders. Results: Data were analysed from 241 patients, 17 being unable to perform PImax or Pnsn manoeuvres. The correlation between Pnsn and PImax was +0.94 (p<0.0001), with a mean (SD) difference between Pnsn and PImax of −4.8 (21.2) cm H2O (the limits of agreement were 37.6 and –47.2 cm H2O). VC (% predicted) was positively correlated with Pnsn/PImax (r  =  +0.86; p<0.0001), with a lower Pnsn/PImax value in patients with a VC <40% of predicted than in those with a VC >40% (0.80 (0.35) v 1.04 (0.41); p<0.0001). Conclusions: PImax is greater than Pnsn in patients with a severe restrictive ventilatory defect caused by neuromuscular disease. Pnsn may not accurately reflect inspiratory muscle strength in such patients and it is thus advisable to use both tests.

Observational study of the effect of obesity on lung volumes

Background Severe obesity causes respiratory morbidity and mortality. The impact of obesity on the mechanics of breathing is not fully understood. Patients and methods We undertook a comprehensive observational study of lung volumes and elasticity in nine obese and nine normal weight subjects, seated and supine, during spontaneous breathing. Seated and supine total lung capacity (TLC) and subdivisions were measured by multibreath helium dilution method. Using balloon catheters, oesophageal (Poes) and gastric (Pgas) pressures were recorded. Transpulmonary pressure (PL) was calculated as mouth pressure (Pmouth)-Poes, and complete expiratory PL volume curves were measured. Results The obese group had a body mass index (BMI) of 46.8 (17.2) kg/m2, and the normal group had a BMI of 23.2 (1.6) kg/m2 (p=0.001). Obese and normals were matched for age (p=0.233), gender (p=0.637) and height (p=0.094). The obese were more restricted than the normals (TLC 88.6 (16.9) vs 104.4 (12.3) %predicted, p=0.033; FEV1/FVC 79.6 (7.3) vs 82.5 (4.2) %, p=0.325), had dramatically reduced expiratory reserve volume (ERV 0.4 (0.4) vs 1.7 (0.6) L, p<0.001) and end-tidal functional residual capacity (FRC) was smaller (37.5 (6.9) vs 46.9 (4.6) %TLC, p=0.004) when seated, but was similar when supine (39.4 (7.7) vs 41.5 (4.3) %TLC, p=0.477). Gastric pressures at FRC were significantly elevated in the obese (seated 19.1 (4.7) vs 12.1 (6.2) cm H2O, p=0.015; supine 14.3 (5.7) vs 7.1 (2.6) cm H2O, p=0.003), as were end-expiratory oesophageal pressures at FRC (seated 5.2 (6.9) vs −2.0 (3.5) cm H2O, p=0.013; supine 14.0 (8.0) vs 5.4 (3.1) cm H2O, p=0.008). BMI correlated with end-expiratory gastric (seated R2=0.43, supine R2=0.66, p<0.01) and oesophageal pressures (seated R2=0.51, supine R2=0.62, p<0.01). Conclusions Obese subjects have markedly increased gastric and oesophageal pressures, both when upright and supine, causing dramatically reduced FRC and ERV, which increases work of breathing.

Skeletal muscle dysfunction in critical care: wasting, weakness, and rehabilitation strategies.

Understanding the trajectory of skeletal muscle loss, evaluating its relationship to the subsequent functional impairment, and understanding the underlying mechanisms of skeletal muscle wasting will provide goals for novel treatment strategies in the intensive care setting. A focused approach on the effect of critical illness on muscle morphology, muscle protein turnover, and the associated muscle-signaling pathways during the early and recovery stages of critical illness is required. This could potentially lead to targeted pharmacologic and nonpharmacologic strategies to treat, or even prevent, peripheral muscle wasting and weakness.

Neural respiratory drive as a physiological biomarker to monitor change during acute exacerbations of COPD

Background Acute exacerbations of chronic obstructive pulmonary disease have a significant negative impact on both patients and healthcare systems. Currently, there are no physiological biomarkers that effectively monitor clinical change or predict respiratory readmission. Acute exacerbations impose a change in the respiratory muscle load-capacity-drive relationship. It was hypothesised that lack of a fall in neural respiratory drive would identify patients at risk of treatment failure and early hospital readmission. Methods An observational study was performed at two UK teaching hospitals. Routine clinical physiological parameters and neural respiratory drive index (NRDI), calculated as the product of second intercostal space parasternal electromyography (EMG) activity normalised to the peak EMG activity during a maximum inspiratory sniff manoeuvre and respiratory rate, were recorded daily from admission to discharge. Results 30 acutely unwell patients of mean (SD) age 72 (10) years, forced expiratory volume in 1 s 0.60 (1.65) l, NRDI 455 (263) AU and median length of stay 6 days were studied. Changes in NRDI correlated with changes in Borg score (r=+0.60; p<0.001), discriminated between patients deemed to have clinically improved rather than deteriorated (mean difference 339 AU; 95% CI 234 to 444; p<0.001) and identified those patients readmitted within 14 days (mean difference 203 AU; 95% CI 39 to 366; p=0.017). Conclusions NRDI is a feasible clinical physiological parameter in patients with an acute exacerbation of chronic obstructive pulmonary disease and can provide useful information on treatment response and risk of readmission.