Gill Arbane

Evaluation of an early exercise intervention after thoracotomy for non-small cell lung cancer (NSCLC), effects on quality of life, muscle strength and exercise tolerance: Randomised controlled trial

Deterioration in exercise tolerance and impairment in quality of life (QoL) are common consequences of lobectomy. This study evaluates additional exercise and strength training after lung resection on QoL, exercise tolerance and muscle strength. Fifty-three (28 male) patients attending thoracotomy for lung cancer, mean age, range 64 (32-82) years; mean pack years (SD) 31.9 (26.8); BMI 25.6 (4.2); FEV1 2.0 (0.7) l were randomised to control (usual care) or intervention (twice daily training plus usual care). After discharge the intervention group received monthly home visits and weekly telephone calls, the control group received monthly telephone calls up to 12 weeks. Assessment pre-operatively, 5 day and 12 weeks post-operatively consisted of quadriceps strength using magnetic stimulation, 6 Minute Walking Distance (6MWD) and QoL-EORTC-QLQ-LC13. QoL was unchanged over 12 weeks; 6MWD showed significant deterioration at 5 days post-operatively compared with pre-operatively, mean difference (SD)-131.6 (101.8) m and -128.0 (90.7) m in active and control groups respectively (p=0.89 between groups) which returned to pre-operative levels by 12 weeks in both groups. Quadriceps strength over the 5 day in-patient period showed a decrease of -8.3 (11.3) kg in the control group compared to increase of 4.0 (21.2) kg in the intervention group (p=0.04 between groups). Strength training after thoracotomy successfully prevented the fall in quadriceps strength seen in controls, however, there was no effect on 6MWD or QoL. 6MWD returned to pre-operative levels by 12 weeks regardless of additional support offered.

Effects and moderators of exercise on quality of life and physical function in patients with cancer: An individual patient data meta-analysis of 34 RCTs

This individual patient data meta-analysis aimed to evaluate the effects of exercise on quality of life (QoL) and physical function (PF) in patients with cancer, and to identify moderator effects of demographic (age, sex, marital status, education), clinical (body mass index, cancer type, presence of metastasis), intervention-related (intervention timing, delivery mode and duration, and type of control group), and exercise-related (exercise frequency, intensity, type, time) characteristics. Relevant published and unpublished studies were identified in September 2012 via PubMed, EMBASE, PsycINFO, and CINAHL, reference checking and personal communications. Principle investigators of all 69 eligible trials were requested to share IPD from their study. IPD from 34 randomised controlled trials (n=4519 patients) that evaluated the effects of exercise compared to a usual care, wait-list or attention control group on QoL and PF in adult patients with cancer were retrieved and pooled. Linear mixed-effect models were used to evaluate the effects of the exercise on post-intervention outcome values (z-score) adjusting for baseline values. Moderator effects were studies by testing interactions. Exercise significantly improved QoL (β=0.15, 95%CI=0.10;0.20) and PF (β=0.18, 95%CI=0.13;0.23). The effects were not moderated by demographic, clinical or exercise characteristics. Effects on QoL (βdifference_in_effect=0.13, 95%CI=0.03;0.22) and PF (βdifference_in_effect=0.10, 95%CI=0.01;0.20) were significantly larger for supervised than unsupervised interventions. In conclusion, exercise, and particularly supervised exercise, effectively improves QoL and PF in patients with cancer with different demographic and clinical characteristics during and following treatment. Although effect sizes are small, there is consistent empirical evidence to support implementation of exercise as part of cancer care.

Effect of Home Noninvasive Ventilation With Oxygen Therapy vs Oxygen Therapy Alone on Hospital Readmission or Death After an Acute COPD Exacerbation: A Randomized Clinical Trial

Importance Outcomes after exacerbations of chronic obstructive pulmonary disease (COPD) requiring acute noninvasive ventilation (NIV) are poor and there are few treatments to prevent hospital readmission and death. Objective To investigate the effect of home NIV plus oxygen on time to readmission or death in patients with persistent hypercapnia after an acute COPD exacerbation. Design, Setting, and Participants A randomized clinical trial of patients with persistent hypercapnia (PaCO2 >53 mm Hg) 2 weeks to 4 weeks after resolution of respiratory acidemia, who were recruited from 13 UK centers between 2010 and 2015. Exclusion criteria included obesity (body mass index [BMI] >35), obstructive sleep apnea syndrome, or other causes of respiratory failure. Of 2021 patients screened, 124 were eligible. Interventions There were 59 patients randomized to home oxygen alone (median oxygen flow rate, 1.0 L/min [interquartile range {IQR}, 0.5-2.0 L/min]) and 57 patients to home oxygen plus home NIV (median oxygen flow rate, 1.0 L/min [IQR, 0.5-1.5 L/min]). The median home ventilator settings were an inspiratory positive airway pressure of 24 (IQR, 22-26) cm H2O, an expiratory positive airway pressure of 4 (IQR, 4-5) cm H2O, and a backup rate of 14 (IQR, 14-16) breaths/minute. Main Outcomes and Measures Time to readmission or death within 12 months adjusted for the number of previous COPD admissions, previous use of long-term oxygen, age, and BMI. Results A total of 116 patients (mean [SD] age of 67 [10] years, 53% female, mean BMI of 21.6 [IQR, 18.2-26.1], mean [SD] forced expiratory volume in the first second of expiration of 0.6 L [0.2 L], and mean [SD] PaCO2 while breathing room air of 59 [7] mm Hg) were randomized. Sixty-four patients (28 in home oxygen alone and 36 in home oxygen plus home NIV) completed the 12-month study period. The median time to readmission or death was 4.3 months (IQR, 1.3-13.8 months) in the home oxygen plus home NIV group vs 1.4 months (IQR, 0.5-3.9 months) in the home oxygen alone group, adjusted hazard ratio of 0.49 (95% CI, 0.31-0.77; P = .002). The 12-month risk of readmission or death was 63.4% in the home oxygen plus home NIV group vs 80.4% in the home oxygen alone group, absolute risk reduction of 17.0% (95% CI, 0.1%-34.0%). At 12 months, 16 patients had died in the home oxygen plus home NIV group vs 19 in the home oxygen alone group. Conclusions and Relevance Among patients with persistent hypercapnia following an acute exacerbation of COPD, adding home noninvasive ventilation to home oxygen therapy prolonged the time to readmission or death within 12 months. Trial Registration clinicaltrials.gov Identifier: NCT00990132

Safety and efficacy of auto-titrating noninvasive ventilation in COPD and obstructive sleep apnoea overlap syndrome

The deleterious effects of comorbid chronic obstructive pulmonary disease (COPD) and obstructive sleep apnoea (OSA) have long been recognised and are frequently encountered as a clinical scenario [1, 2]. Although continuous positive airways pressure can be used in order to abolish upper airways obstruction in OSA, it can have adverse effects on pulmonary mechanics in patients with airways obstruction [3]. Auto-titrating modes of noninvasive ventilation (NIV) that monitor tidal volume, respiratory rate and upper airway patency and can vary back up rate, inspiratory and expiratory positive airway pressure (IPAP and EPAP, respectively) may have clinical benefits. However, these auto-titration modes and the software algorithms driving the ventilators are being engineered and modified at a rapid rate. The clinician, therefore, needs to be reassured that these novel modes have an established safety and efficacy profile. We hypothesised that auto-titrating NIV would enhance overnight gas exchange, sleep quality, and patient comfort when compared to standard fixed-level NIV in COPD-OSA patients with chronic respiratory failure. Auto-titrating NIV controls sleep disordered breathing and augments patient sleep comfort in COPD-OSA overlap http://ow.ly/NtL24

Medium-term cost-effectiveness of an automated non-invasive ventilation outpatient set-up versus a standard fixed level non-invasive ventilation inpatient set-up in obese patients with chronic respiratory failure: a protocol description

Introduction Obesity is an escalating issue, with an accompanying increase in referrals of patients with obesity-related respiratory failure. Currently, these patients are electively admitted to hospital for initiation of non-invasive ventilation (NIV), but it is unknown whether outpatient initiation is as effective as inpatient set-up. We hypothesise that outpatient set-up using an autotitrating NIV device will be more cost-effective than a nurse-led inpatient titration and set-up. Methods and analysis We will undertake a multinational, multicentre randomised controlled trial. Participants will be randomised to receive the usual inpatient set-up, which will include nurse-led initiation of NIV or outpatient set-up with an automated NIV device. They will be stratified according to the trial site, gender and previous use of NIV or continuous positive airway pressure. Assuming a 10% dropout rate, a total sample of 82 patients will be required. Cost-effectiveness will be evaluated using standard treatment costs and health service utilisation as well as health-related quality of life measures (severe respiratory insufficiency (SRI) and EuroQol-5 dimensions (EQ-5D)). A change in the SRI questionnaire will be based on the analysis of covariance adjusting for the baseline measurements between the two arms of patients. Ethics and dissemination This study has been approved by the Westminster National Research Ethics Committee (11/LO/0414) and is the trial registered on the UKCRN portfolio. The trial is planned to start in January 2015 with publication of the trial results in 2017. Trial registration number ISRCTN 51420481.

S115 Hot-hmv uk trial secondary outcome analysis: early readmission is reduced by the addition of home mechanical ventilation to home oxygen therapy in copd patients with chronic respiratory failure following a life-threatening exacerbation

Introduction Hospital readmission following treatment for a life-threatening exacerbation of COPD with acute NIV is frequent and associated with an adverse impact in terms of lung function and health related quality of life. They have been identified as a priority area in the NHS with financial penalties for any patient readmitted within 28 days following discharge. Method A multicentre open labelled randomised controlled trial recruited patients with persistent hypercapnia (PaCO2 > 7 kPa) 2–4 weeks following resolution of acute acidosis. Patients were randomised to either home oxygen therapy (HOT) or HOT and home mechanical ventilation (HOT-HMV). HMV was titrated overnight to control nocturnal hypercapnia. Follow up was for 12 months. The primary outcome, 12-month admission free survival, has been reported previously demonstrating a significant treatment effect (ERS 2016). Secondary outcome analysis included 28-day all-cause hospital readmission and 12 month exacerbation rate. Results 116 patients were randomised (HOT = 59, HOT-HMV = 57), age 67 ± 10 years, FEV1 0.6 ± 0.2 L, PaCO2 7.9 ± 0.9 kPa. 28-day readmission was 22 (37%) in the HOT and 7 (12%) in the HOT-HMV arm (unadjusted HR 0.27, 0.12 to 0.63, p = 0.003; adjusted HR 0.26, 0.11 to 0.61, p = 0.002) (Figure 1). 12 month exacerbation rate was reduced from median 5 (1 to 9) per year in the HOT arm to 4 (2to 6) in the HOT-HMV arm (unadjusted HR 0.64 (0.44 to 0.94); p = 0.022; adjusted HR 0.66, 0.46 to 0.95, p = 0.026). Conclusion The addition of HMV to HOT in patients with persistent hypercapnia following an acute life-threatening exacerbation of COPD reduces both 28-day readmission and 12 month exacerbation frequency. These data strongly support a change in clinical practice in the management of patients with severe COPD and persistent hypercapnia. Abstract S115 Figure 1 Time to hospital re-admission by treatment arm

Polysomnography versus limited respiratory monitoring and nurse-led titration to optimise non-invasive ventilation set-up: a pilot randomised clinical trial

Polysomnography (PSG) is recommended for non-invasive ventilation (NIV) set-up in patients with chronic respiratory failure. In this pilot randomised clinical trial, we compared the physiological effectiveness of NIV set-up guided by PSG to limited respiratory monitoring (LRM) and nurse-led titration in patients with COPD–obstructive sleep apnoea (OSA) overlap. The principal outcome of interest was change in daytime arterial partial pressure of carbon dioxide (PaCO2) at 3 months. Fourteen patients with daytime PaCO2 >6 kPa and body mass index >30 kg/m2 were recruited. At 3 months, PaCO2 was reduced by −0.88 kPa (95% CI −1.52 to −0.24 kPa) in the LRM group and by −0.36 kPa (95% CI −0.96 to 0.24 kPa) in the PSG group. These pilot data provide support to undertake a clinical trial investigating the clinical effectiveness of attended limited respiratory monitoring and PSG to establish NIV in patients with COPD–OSA overlap. Trial number Results, NCT02444806.

Thoracic Oncology and Surgery

Pulmonary rehabilitation is an important component in the management of lung cancer. It aims to minimise physical and psychological impairments which commonly occur in patients following a diagnosis of lung cancer. There are well-established clinical guidelines regarding exercise for patients with cancer. These recommend at least 150 min of moderate intensity physical activity and two to three resistance training sessions per week, and avoidance of sedentary time. The evidence for exercise specifically in lung cancer is growing rapidly. It shows that pulmonary rehabilitation is associated with improvements in exercise capacity, muscle strength and symptoms, especially when delivered after surgery. Pulmonary rehabilitation before surgery (prehabilitation) is also associated with reduced post-operative complications and hospital length of stay. Pulmonary rehabilitation during chemotherapy or radiotherapy, and for patients with advanced palliative disease appears to be effective at reducing symptoms and improving and/or maintaining exercise capacity and muscle strength. This chapter begins by providing an overview to the topic of thoracic oncology and specifically focuses on lung cancer. The chapter summarises the symptoms of lung cancer, medical treatment and side-effects, common impairments, and the evidence for physical activity and exercise training. It also outlines a number of specific considerations for delivery of pulmonary rehabilitation in the lung cancer setting including patient assessment, exercise prescription, safety, and timing of delivery across the cancer disease trajectory.

Targeting Exercise Interventions to Patients With Cancer in Need: An Individual Patient Data Meta-Analysis

Background Exercise effects in cancer patients often appear modest, possibly because interventions rarely target patients most in need. This study investigated the moderator effects of baseline values on the exercise outcomes of fatigue, aerobic fitness, muscle strength, quality of life (QoL), and self-reported physical function (PF) in cancer patients during and post-treatment. Methods Individual patient data from 34 randomized exercise trials (n = 4519) were pooled. Linear mixed-effect models were used to study moderator effects of baseline values on exercise intervention outcomes and to determine whether these moderator effects differed by intervention timing (during vs post-treatment). All statistical tests were two-sided. Results Moderator effects of baseline fatigue and PF were consistent across intervention timing, with greater effects in patients with worse fatigue (Pinteraction = .05) and worse PF (Pinteraction = .003). Moderator effects of baseline aerobic fitness, muscle strength, and QoL differed by intervention timing. During treatment, effects on aerobic fitness were greater for patients with better baseline aerobic fitness (Pinteraction = .002). Post-treatment, effects on upper (Pinteraction < .001) and lower (Pinteraction = .01) body muscle strength and QoL (Pinteraction < .001) were greater in patients with worse baseline values. Conclusion Although exercise should be encouraged for most cancer patients during and post-treatments, targeting specific subgroups may be especially beneficial and cost effective. For fatigue and PF, interventions during and post-treatment should target patients with high fatigue and low PF. During treatment, patients experience benefit for muscle strength and QoL regardless of baseline values; however, only patients with low baseline values benefit post-treatment. For aerobic fitness, patients with low baseline values do not appear to benefit from exercise during treatment.

Neural respiratory drive and cardiac function in patients with obesity hypoventilation syndrome following initiation of noninvasive ventilation

Background Chronic hypercapnic respiratory failure (HRF) in obesity hypoventilation syndrome (OHS) is commonly treated using non-invasive ventilation (NIV). We hypothesised that treatment of OHS would improve neural respiratory drive index (NRDI) and cardiac function. Methods Fourteen patients (8 females) with OHS, who were admitted for initiation of domiciliary NIV, were prospectively studied. Patients had (mean ± SD): age (53±10 years), body mass index (BMI) (50.1±10.8 kg/m2), and pCO2 (7.3±0.9 kPa). NRDI was assessed by surface electromyogram of the parasternal intercostals. Cardiac function was assessed by transthoracic echocardiography (TTE). All measurements were performed at baseline, 6 weeks, and 3 months. Results NRDI improved on day one following NIV set-up comparing to baseline (484.2±214.8 vs. 316.5±106.5 AU) and this improvement was maintained at 6 weeks (369.1±173.2 AU) and at 3 months (351.2±167.1 AU) (P=0.004). No significant differences were identified in terms of cardiac function between baseline and 3 months [tricuspid annular plane systolic excursion (TAPSE) (24.6±5.8 vs. 23.0±4.0 mm, P=0.317); systolic pulmonary artery (PA) pressures (36.7±15.2 vs. 44.5±23.9 mmHg, P=0.163]. Conclusions NIV improves NRDI in patients with OHS, while the cardiac function over a three-month period remains unchanged.