Keir Lewis

Obesity, metabolic syndrome and sleep apnoea: all pro-inflammatory states.

Obesity is associated with significant morbidity and mortality and is increasing in prevalence worldwide. Associated conditions include insulin resistance (IR), diabetes, hypertension and dyslipidaemia; a clustering of these has recently been termed as metabolic syndrome. Weight gain is a major predictor of the metabolic syndrome with waist circumference being a more sensitive indicator than body mass index as it reflects both abdominal subcutaneous adipose tissue and visceral adipose tissue (VAT). VAT has more metabolic activity and secretes a number of hormones and pro‐inflammatory cytokines which are linked with the metabolic abnormalities listed above. Central obesity also increases the risk of obstructive sleep apnoea syndrome (OSAS), where the sleep disordered breathing may also independently lead to/or exacerbate IR, diabetes and cardiovascular risk. The contribution of OSAS to the metabolic syndrome has been under‐recognized. The putative mechanisms by which OSAS causes or exacerbates these other abnormalities are discussed. We propose that activation of nuclear factor kappa B by stress hypoxia and/or by increased adipokines and free fatty acids released by excess adipose tissue is the final common inflammatory pathway linking obesity, OSAS and the metabolic syndrome both individually and, in many cases, synergistically.

Predictors of poor attendance at an outpatient pulmonary rehabilitation programme

BACKGROUND Pulmonary rehabilitation (PR) is recommended for patients with respiratory disease who feel limited by breathlessness. Poor attendance wastes finite resources, increases waiting times and is probably associated with poorer clinical outcomes. We investigated what factors, identifiable from routine hospital data, predict poor attendance once enrolled in a pulmonary rehabilitation programme (PRP). METHODS Retrospective case note study of 239 patients (60% male) of mean (S.D.) age of 66.6 (8.7) years, mean FEV(1) 39.6 (14.6)% predicted, who attended a 6 (short) or 18 (long) week, 18 session, outpatient PRP. Attendance data was analysed using linear multiple regression analysis with the log transformed odds ratio of attendance as the dependant variable. RESULTS Overall median attendance was 16 out of 18 sessions. Being a current smoker (p<0.05), attending a long PRP (p<0.05), more previous hospital admissions (p<0.01), higher Medical Research Council (MRC) dyspnoea score (p<0.01) or enduring a long journey (p<0.001) were independent risk factors for low attendance. Lower body mass index (BMI) and distance from PR centre were of borderline importance (p<0.1) but age, gender, co-morbidity, respiratory diagnosis, FEV(1) and St. Georges Respiratory Questionnaire Score at baseline did not predict later attendance (p>0.2). CONCLUSIONS Attendance at PRPs is independently influenced by smoking status, the degree of breathlessness, frequency of hospital admissions, length of the programme and journey time.

Auto-servoventilation in heart failure with sleep apnoea: a randomised controlled trial

We tested the hypotheses that in patients with congestive heart failure (CHF) and sleep disordered breathing (SDB) auto-servoventilation (ASV) improves cardiac function and quality of life. Between March 2007 and September 2009, patients with stable CHF (left ventricular ejection fraction (LVEF) ≤40%) and SDB (apnoea/hypopnoea index ≥20 events·h−1) were randomised to receive either ASV (BiPAP ASV (Philips Respironics, Murrysville, PA, USA), n=37) and optimal medical management, or optimal medical management alone (n=35). Outcomes were assessed at baseline and 12 weeks. The apnoea/hypopnoea index assessed with polysomnography scored in one core laboratory was significantly more reduced in the ASV group (-39±16 versus -1±13 events·h−1; p<0.001) with an average use of 4.5±3.0 h·day−1. Both groups showed similar improvements of the primary end-point LVEF (+3.4±5 versus +3.5±6%; p=0.915) assessed with echocardiography. In the ASV group, reduction of N-terminal pro-brain natriuretic peptide (NT-proBNP) was significantly greater (-360±569 versus +135±625 ng·mL−1; p=0.010). No differences were observed between the groups in subjective quality of life. In patients with CHF and SDB, ASV reduced NT-proBNP levels, but improvement of LVEF or quality of life was not greater than in the control group. The data support that such patients can be randomised in large-scale, long-term trials of positive airway pressure therapy versus control to determine effects on cardiovascular outcome. Patients with heart failure and sleep apnoea can be randomised in long-term trials of positive airway pressure therapy http://ow.ly/nQnVg

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

Statement on smoking cessation in COPD and other pulmonary diseases and in smokers with comorbidities who find it difficult to quit

Chronic obstructive pulmonary disease (COPD), lung cancer, asthma and pulmonary tuberculosis are common pulmonary diseases that are caused or worsened by tobacco smoking. Growing observational evidence suggests that symptoms and prognosis of these conditions improve upon smoking cessation. Despite increasing numbers of (small) randomised controlled trials suggesting intensive smoking cessation treatments work in people with pulmonary diseases many patients are not given specific advice on the benefits or referred for intensive cessation treatments and, therefore, continue smoking. This is a qualitative review regarding smoking cessation in patients with COPD and other pulmonary disorders, written by a group of European Respiratory Society experts. We describe the epidemiological links between smoking and pulmonary disorders, the evidence for benefits of stopping smoking, how best to assess tobacco dependence and what interventions currently work best to help pulmonary patients quit. Finally, we describe characteristics and management of any “hardcore” smoker who finds it difficult to quit with standard approaches. Smoking cessation is crucial for respiratory patients: every patient must be given advice and help to quit http://ow.ly/ITgsW

Home telemonitoring and quality of life in stable, optimised chronic obstructive pulmonary disease

We conducted a six-month randomised controlled trial of home telemonitoring for patients with chronic obstructive pulmonary disease (COPD). A total of 40 stable patients with moderate to severe COPD who had completed pulmonary rehabilitation took part. They were randomised to receive standard care (controls) or standard care plus home telemonitoring (intervention). During the monitoring period, patients in the telemonitoring group recorded their symptoms and physical observations twice daily. The data were transmitted automatically at night via the home telephone line. Nurses could access the data through a website and receive alerting email messages if certain conditions were detected. The patients completed the St Georges Respiratory Questionnaire, Hospital Anxiety and Depression and the EuroQoL EQ-5D quality of life scores before and after pulmonary rehabilitation, and then periodically during the trial. There were significant and clinically important improvements in the scores immediately following pulmonary rehabilitation, but thereafter there were no differences in quality of life scores between the groups at any time, or consistently within either group over time. The study showed that telemonitoring was safe but, despite being well used, it was not associated with changes in quality of life in patients who had stable COPD.

Does Home Telemonitoring after Pulmonary Rehabilitation Reduce Healthcare Use in Optimized COPD?? A Pilot Randomized Trial

ABSTRACT Aim. To see if home telemonitors reduce healthcare use in those with optimized chronic obstructive pulmonary disease (COPD). Methods. We randomized 40 stable patients with moderate to severe COPD, who had completed at least 12 sessions of outpatient pulmonary rehabilitation (PR), to receive standard care (Controls) for 52 weeks or standard care plus Docobo HealthHUB monitors at home for 26 weeks followed by 26 weeks standard care (Tm Group). During the monitoring period, the Tm Group completed symptoms and physical observations twice daily which were stored and then uploaded at 2 am through a freephone landline. Nurses could access the data through a secure web site and received alerting e-mails if certain combinations of data occurred. Results. There were fewer primary care contacts for chest problems (p < 0.03) in the Tm group, but no differences between the groups in emergency room visits, hospital admissions, days in hospital or contacts to the specialist COPD community nurse team, during the monitoring period. After the monitors were removed, there were no differences between the groups for any of the health care contacts (p > 0.20 throughout). Conclusion. In stable, optimized COPD patients who have already completed PR, telemonitoring in addition to best care, reduces primary care chest contacts but not hospital or specialist team utilization.

A review of novel biological tools used in screening for the early detection of lung cancer.

Lung cancer is the most common cancer worldwide and causes more deaths per year than any other cancer. It has a very poor 5-year survival rate of 8–16%, partly because of comorbidity preventing curative treatments but mainly because of the disease presenting with symptoms only when it is at an advanced and incurable stage. When lung cancer is detected earlier and is amenable to radical treatments such as potentially curative surgery and radical radiotherapy, 5-year survival rates are much higher (up to 67%). Therefore reliable detection of lung cancer at this earlier (usually asymptomatic) stage of disease should be an important way to improve outcomes. This review discusses the principles of screening with respect to lung cancer, concentrating mainly on the biological modalities used to detect it. The lack of impact achieved by early studies using sputum cytology (in conjunction with chest radiographs) is described, and then newer technology used to measure other biomarkers in sputum, serum, exhaled breath and bronchial mucosa to diagnose (early) lung cancer is detailed. Many techniques show promise, but debate continues about which population to screen and what is the most (cost) effective modality to use. Moreover, no single biomarker or combination of biomarkers in screening has yet been shown to reduce lung cancer mortality in large prospective randomised studies.

Obstructive sleep apnoea in patients with type 2 diabetes: aetiology and implications for clinical care

Recent attention has been drawn to the close association between obstructive sleep apnoea (OSA) and type 2 diabetes mellitus (T2DM). Debate has included much discussion about cause and effect with mechanisms proposed whereby one condition might cause the other. However, both clearly share a common phenotype, namely, obesity that overlaps considerably with the other components of the metabolic syndrome, hypertension and hyperlipidaemia. It would therefore appear likely that all are manifestations of the same basic pathological processes. Possible interacting aetiological mechanisms are reviewed along with treatment options. A recent report by the International Diabetes Federation has made recommendations to raise awareness of possible OSA in patients with T2DM and also for screening for hypertension, hyperlipidaemia and T2DM in patients with known OSA. The clinical implications are discussed.

Machine learning methods on exhaled volatile organic compounds for distinguishing COPD patients from healthy controls

Exhaled volatile organic compounds (VOCs) have shown promise in diagnosing chronic obstructive pulmonary disease (COPD) but studies have been limited by small sample size and potential confounders. An investigation was conducted in order to establish whether combinations of VOCs could identify COPD patients from age and BMI matched controls. Breath samples were collected from 119 stable COPD patients and 63 healthy controls. The samples were collected with a portable apparatus, and then assayed by gas chromatography and mass spectroscopy. Machine learning approaches were applied to the data and the automatically generated models were assessed using classification accuracy and receiver operating characteristic (ROC) curves. Cross-validation of the combinations correctly predicted the diagnosis in 79% of COPD patients and 64% of controls and an optimum area under the ROC curve of 0.82 was obtained. Comparison of current and ex smokers within the COPD group showed that smoking status was likely to affect the classification; with correct prediction of smoking status in 85% of COPD subjects. When current smokers were omitted from the analysis, prediction of COPD was similar at 78% but correct prediction of controls was increased to 74%. Applying different analytical methods to the largest group of subjects so far, suggests VOC analysis holds promise for diagnosing COPD but smoking status needs to be balanced.