The Economic Potential of Smoking Cessation Interventions at the Point of Diagnosis of Non-Small Cell Lung Cancer.

OBJECTIVES: Stopping smoking has proven benefits in nearly all illnesses but the impact and health economic benefits of stopping smoking after a diagnosis of lung cancer are less well defined. We assessed the cost-effectiveness of smoking cessation (SC) services for patients with newly diagnosed lung cancer against current usual care, where patients are unlikely to receive SC service referral. METHODS: A health economic model was constructed in Excel. The modelled population comprised of patients with a new diagnosis of non-small cell lung cancer (NSCLC). Data from the LungCast data set (Clinical Trials Identifier NCT01192256) were used to estimate model inputs. A structured search of published literature identified inputs not represented in LungCast, including healthcare resource use and costs. Costs were estimated from a 2020/2021 UK National Health Service and Personal Social Services perspective. The model estimated the incremental quality-adjusted life-year (QALY) gained in patients with newly diagnosed NSCLC receiving targeted SC intervention than those receiving no intervention. Extensive one-way sensitivity analyses explored input and data set uncertainty. RESULTS: In the 5-year base case, the model estimated an incremental cost of £14 904 per QALY gained through SC intervention. Sensitivity analysis estimated an outcome range of between £9935 and £32 246 per QALY gained. The model was most sensitive to the estimates of relative quit rates and expected healthcare resource use. CONCLUSION: This exploratory analysis indicates that SC intervention for smokers with patients with newly diagnosed NSCLC should be a cost-effective use of UK National Health Service resources. Additional research with focused costing is needed to confirm this positioning.

Inspiratory muscle training enhances recovery post-COVID-19: a randomised controlled trial.

BACKGROUND: Many people recovering from coronavirus disease 2019 (COVID-19) experience prolonged symptoms, particularly breathlessness. We urgently need to identify safe and effective COVID-19 rehabilitative strategies. The aim of the current study was to investigate the potential rehabilitative role of inspiratory muscle training (IMT). METHODS: 281 adults (age 46.6±12.2 years; 88% female) recovering from self-reported COVID-19 (9.0±4.2 months post-acute infection) were randomised 4:1 to an 8-week IMT or a "usual care" waitlist control arm. Health-related quality-of-life and breathlessness questionnaires (King's Brief Interstitial Lung Disease (K-BILD) and Transition Dyspnoea Index (TDI)), respiratory muscle strength, and fitness (Chester Step Test) were assessed pre- and post-intervention. The primary end-point was K-BILD total score, with the K-BILD domains and TDI being key secondary outcomes. RESULTS: According to intention to treat, there was no difference between groups in K-BILD total score post-intervention (control: 59.5±12.4; IMT: 58.2±12.3; p<0.05) but IMT elicited clinically meaningful improvements in the K-BILD domains for breathlessness (control: 59.8±12.6; IMT: 62.2±16.2; p<0.05) and chest symptoms (control: 59.2±18.7; IMT: 64.5±18.2; p<0.05), along with clinically meaningful improvements in breathlessness according to TDI (control: 0.9±1.7 versus 2.0±2.0; p<0.05). IMT also improved respiratory muscle strength and estimated aerobic fitness. CONCLUSIONS: IMT may represent an important home-based rehabilitation strategy for wider implementation as part of COVID-19 rehabilitative strategies. Given the diverse nature of long COVID, further research is warranted on the individual responses to rehabilitation; the withdrawal rate herein highlights that no one strategy is likely to be appropriate for all.

Burden of nosocomial COVID-19 in Wales: results from a multicentre retrospective observational study of 2508 hospitalised adults.

The burden of nosocomial SARS-CoV-2 infection remains poorly defined. We report on the outcomes of 2508 adults with molecularly-confirmed SARS-CoV-2 admitted across 18 major hospitals, representing over 60% of those hospitalised across Wales between 1 March and 1 July 2020. Inpatient mortality for nosocomial infection ranged from 38% to 42%, consistently higher than participants with community-acquired infection (31%-35%) across a range of case definitions. Those with hospital-acquired infection were older and frailer than those infected within the community. Nosocomial diagnosis occurred a median of 30 days following admission (IQR 21-63), suggesting a window for prophylactic or postexposure interventions, alongside enhanced infection control measures.

The Noninvasive Ventilation Outcomes (NIVO) score: prediction of in-hospital mortality in exacerbations of COPD requiring assisted ventilation.

INTRODUCTION: Acute exacerbations of COPD (AECOPD) complicated by acute (acidaemic) hypercapnic respiratory failure (AHRF) requiring ventilation are common. When applied appropriately, ventilation substantially reduces mortality. Despite this, there is evidence of poor practice and prognostic pessimism. A clinical prediction tool could improve decision making regarding ventilation, but none is routinely used. METHODS: Consecutive patients admitted with AECOPD and AHRF treated with assisted ventilation (principally noninvasive ventilation) were identified in two hospitals serving differing populations. Known and potential prognostic indices were identified a priori. A prediction tool for in-hospital death was derived using multivariable regression analysis. Prospective, external validation was performed in a temporally separate, geographically diverse 10-centre study. The trial methodology adhered to TRIPOD (Transparent Reporting of a Multivariable Prediction Model for Individual Prognosis or Diagnosis) recommendations. RESULTS: Derivation cohort: n=489, in-hospital mortality 25.4%; validation cohort: n=733, in-hospital mortality 20.1%. Using six simple categorised variables (extended Medical Research Council Dyspnoea score 1-4/5a/5b, time from admission to acidaemia >12 h, pH <7.25, presence of atrial fibrillation, Glasgow coma scale ≤14 and chest radiograph consolidation), a simple scoring system with strong prediction of in-hospital mortality is achieved. The resultant Noninvasive Ventilation Outcomes (NIVO) score had area under the receiver operating curve of 0.79 and offers good calibration and discrimination across stratified risk groups in its validation cohort. DISCUSSION: The NIVO score outperformed pre-specified comparator scores. It is validated in a generalisable cohort and works despite the heterogeneity inherent to both this patient group and this intervention. Potential applications include informing discussions with patients and their families, aiding treatment escalation decisions, challenging pessimism and comparing risk-adjusted outcomes across centres.

Weekend admissions and mortality for major acute disorders across England and Wales: record linkage cohort studies.

BACKGROUND: To establish which major disorders are susceptible to increased mortality following acute admissions on weekends, compared with week days, and how this may be explained. METHODS: Cohorts based on national administrative inpatient and mortality data for 14,168,443 hospitalised patients in England and 913,068 in Wales who were admitted for 66 disorders that were associated with at least 200 deaths within 30 days of acute admission. The main outcome measure was the weekend mortality effect (defined as the conventional mortality odds ratio for admissions on weekends compared with week days). RESULTS: There were large, statistically significant weekend mortality effects (> 20%) in England for 22 of the 66 conditions and in both countries for 14. These 14 were 4 of 13 cancers (oesophageal, colorectal, lung and lymphomas); 4 of 13 circulatory disorders (angina, abdominal aortic aneurysm, peripheral vascular disease and arterial embolism & thrombosis); one of 8 respiratory disorders (pleural effusion); 2 of 12 gastrointestinal disorders (alcoholic and other liver disease); 2 of 3 ageing-related disorders (Alzheimer's disease and dementia); none of 7 trauma conditions; and one of 10 other disorders (acute renal failure). Across the disorders, 64% of the variation in weekend mortality effects in England and Wales was explained by reductions in admission rates at weekends and the medical disease category. CONCLUSIONS: The effect of weekend admission on 30 day mortality is seen mainly for cancers, some circulatory disorders, liver disease and a few other conditions which are mainly ageing- or cancer-related. Most of the increased mortality is associated with reduced admission rates at weekends and the medical disease category.

Pro-inflammatory effects of e-cigarette vapour condensate on human alveolar macrophages.

OBJECTIVE: Vaping may increase the cytotoxic effects of e-cigarette liquid (ECL). We compared the effect of unvaped ECL to e-cigarette vapour condensate (ECVC) on alveolar macrophage (AM) function. METHODS: AMs were treated with ECVC and nicotine-free ECVC (nfECVC). AM viability, apoptosis, necrosis, cytokine, chemokine and protease release, reactive oxygen species (ROS) release and bacterial phagocytosis were assessed. RESULTS: Macrophage culture with ECL or ECVC resulted in a dose-dependent reduction in cell viability. ECVC was cytotoxic at lower concentrations than ECL and resulted in increased apoptosis and necrosis. nfECVC resulted in less cytotoxicity and apoptosis. Exposure of AMs to a sub-lethal 0.5% ECVC/nfECVC increased ROS production approximately 50-fold and significantly inhibited phagocytosis. Pan and class one isoform phosphoinositide 3 kinase inhibitors partially inhibited the effects of ECVC/nfECVC on macrophage viability and apoptosis. Secretion of interleukin 6, tumour necrosis factor α, CXCL-8, monocyte chemoattractant protein 1 and matrix metalloproteinase 9 was significantly increased following ECVC challenge. Treatment with the anti-oxidant N-acetyl-cysteine (NAC) ameliorated the cytotoxic effects of ECVC/nfECVC to levels not significantly different from baseline and restored phagocytic function. CONCLUSIONS: ECVC is significantly more toxic to AMs than non-vaped ECL. Excessive production of ROS, inflammatory cytokines and chemokines induced by e-cigarette vapour may induce an inflammatory state in AMs within the lung that is partly dependent on nicotine. Inhibition of phagocytosis also suggests users may suffer from impaired bacterial clearance. While further research is needed to fully understand the effects of e-cigarette exposure in humans in vivo, we caution against the widely held opinion that e-cigarettes are safe.

Metabolomic-based biomarker discovery for non-invasive lung cancer screening: A case study.

BACKGROUND: Lung cancer (LC) is one of the leading lethal cancers worldwide, with an estimated 18.4% of all cancer deaths being attributed to the disease. Despite developments in cancer diagnosis and treatment over the previous thirty years, LC has seen little to no improvement in the overall five year survival rate after initial diagnosis. METHODS: In this paper, we extended a recent study which profiled the metabolites in sputum from patients with lung cancer and age-matched volunteers smoking controls using flow infusion electrospray ion mass spectrometry. We selected key metabolites for distinguishing between different classes of lung cancer, and employed artificial neural networks and leave-one-out cross-validation to evaluate the predictive power of the identified biomarkers. RESULTS: The neural network model showed excellent performance in classification between lung cancer and control groups with the area under the receiver operating characteristic curve of 0.99. The sensitivity and specificity of for detecting cancer from controls were 96% and 94% respectively. Furthermore, we have identified six putative metabolites that were able to discriminate between sputum samples derived from patients suffering small cell lung cancer (SCLC) and non-small cell lung cancer. These metabolites achieved excellent cross validation performance with a sensitivity of 80% and specificity of 100% for predicting SCLC. CONCLUSIONS: These results indicate that sputum metabolic profiling may have potential for screening of lung cancer and lung cancer recurrence, and may greatly improve effectiveness of clinical intervention. This article is part of a Special Issue entitled "System Genetics" Guest Editor: Dr. Yudong Cai and Dr. Tao Huang.

Development of an algorithm for determining smoking status and behaviour over the life course from UK electronic primary care records.

BACKGROUND: Patients' smoking status is routinely collected by General Practitioners (GP) in UK primary health care. There is an abundance of Read codes pertaining to smoking, including those relating to smoking cessation therapy, prescription, and administration codes, in addition to the more regularly employed smoking status codes. Large databases of primary care data are increasingly used for epidemiological analysis; smoking status is an important covariate in many such analyses. However, the variable definition is rarely documented in the literature. METHODS: The Secure Anonymised Information Linkage (SAIL) databank is a repository for a national collection of person-based anonymised health and socio-economic administrative data in Wales, UK. An exploration of GP smoking status data from the SAIL databank was carried out to explore the range of codes available and how they could be used in the identification of different categories of smokers, ex-smokers and never smokers. An algorithm was developed which addresses inconsistencies and changes in smoking status recording across the life course and compared with recorded smoking status as recorded in the Welsh Health Survey (WHS), 2013 and 2014 at individual level. However, the WHS could not be regarded as a "gold standard" for validation. RESULTS: There were 6836 individuals in the linked dataset. Missing data were more common in GP records (6%) than in WHS (1.1%). Our algorithm assigns ex-smoker status to 34% of never-smokers, and detects 30% more smokers than are declared in the WHS data. When distinguishing between current smokers and non-smokers, the similarity between the WHS and GP data using the nearest date of comparison was κ = 0.78. When temporal conflicts had been accounted for, the similarity was κ = 0.64, showing the importance of addressing conflicts. CONCLUSIONS: We present an algorithm for the identification of a patient's smoking status using GP self-reported data. We have included sufficient details to allow others to replicate this work, thus increasing the standards of documentation within this research area and assessment of smoking status in routine data.

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.

Impaired Blood Neutrophil Function in the Frequent Exacerbator of Chronic Obstructive Pulmonary Disease: A Proof-of-Concept Study.

PURPOSE: The underlying biological mechanisms of the frequent exacerbator phenotype of COPD remain unclear. We compared systemic neutrophil function in COPD patients with or without frequent exacerbations. METHODS: Whole blood from COPD frequent exacerbators (defined as ≥2 moderate-severe exacerbations in the previous 2 years) and non-exacerbators (no exacerbations in the preceding 2 years) was assayed for neutrophil function. Neutrophil function in healthy ex-smoking volunteers was also measured as a control (reference) group. RESULTS: A total of 52 subjects were included in this study: 26 frequent exacerbators, 18 non-exacerbators and 8 healthy controls. COPD frequent exacerbators had blunted blood neutrophil fMLP-stimulated oxidative burst compared to both non-exacerbators (p < 0.01) and healthy controls (p < 0.001). There were no differences between COPD frequent exacerbators and non-exacerbators in blood neutrophil PMA-stimulated oxidative burst, but both COPD groups had reduced responses compared to healthy controls (p < 0.001). Bacterial-stimulated neutrophil degranulation was greater in frequent exacerbators than non-exacerbators (p < 0.05). CONCLUSION: This study is the first to report aberrant receptor-mediated blood neutrophil function in the frequent exacerbator of COPD.

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.

Acute haemodynamic effects of continuous positive airway pressure in awake patients with heart failure.

BACKGROUND AND OBJECTIVE: Continuous positive airway pressure (CPAP) has been used to treat patients with chronic heart failure (CHF) and sleep-disordered breathing (SDB). CPAP treatment in severe CHF with concomitant SDB and atrial fibrillation has been linked to impairment of cardiac output (CO) as a potential cause for adverse outcome. The aim of the present study was to test whether incremental CPAP application in awake CHF patients with SDB, with and without atrial fibrillation, induces acute alterations of blood pressure (BP), heart rate (HR) and CO. METHODS: During daytime, we applied incremental CPAP (4-10 cmH2O) in 37 stable patients with CHF and SDB. BP and HR were assessed after each 1 cmH2O CPAP increase in 5-min intervals in the entire sample, and CO was assessed at one centre (n = 11). RESULTS: Neither mean BP, HR nor CO changed significantly with incremental CPAP (at 0 and 10 cmH2O: 85 ± 2 and 84 ± 2 mm Hg, P = 1.0, 63 ± 1 to 61 ± 2 b.p.m., P = 0.88 and 2.03 ± 0.5 and 2.35 ± 0.8 L/min/m2 , P = 0.92, respectively). No significant differences in maximum BP drop or HR drop between patients with sinus rhythm and atrial fibrillation were found. In 1 of 37 patients, a prespecified event of haemodynamic compromise (drop of mean BP >15 mm Hg) without clinical signs occurred. CONCLUSIONS: These results contribute to the evidence that CPAP does not cause haemodynamic compromise in the vast majority of normotensive CHF patients with SDB.

Effects of auto-servo ventilation on patients with sleep-disordered breathing, stable systolic heart failure and concomitant diastolic dysfunction: subanalysis of a randomized controlled trial.

BACKGROUND: Systolic heart failure (HF) is frequently accompanied by diastolic dysfunction and sleep-disordered breathing (SDB). OBJECTIVES: The objective of this subset analysis was to determine effect sizes of auto-servo ventilation (ASV and biphasic positive airway pressure ASV) on echocardiographic measures of diastolic function in patients with systolic HF and SDB. METHODS: Thirty-two patients with stable systolic HF, concomitant diastolic dysfunction [age 66 ± 9 years old, left ventricular (LV) ejection fraction: 30 ± 7% and New York Heart Association class II: 72%] and SDB (apnea-hypopnea index, AHI: 48 ± 19/h; 53% had predominantly obstructive sleep apnea) receiving either ASV (n = 19) or optimal medical treatment (control, n = 13) were analyzed in a randomized controlled clinical trial. Polysomnographic and echocardiographic measurements were obtained at baseline and after 12 weeks. RESULTS: AHI significantly improved in the ASV group compared to the control group (-39 ± 18 vs. -0.2 ± 13.2/h, p < 0.001). At baseline, 24 (75%) patients had impaired LV relaxation, and 8 (25%) had a pseudo-normalized filling pattern. At the 12-week control visit, diastolic function assessed by the isovolumetric relaxation time (-10.3 ± 26.1 vs. 9.3 ± 49.1, p = 0.48) and deceleration time (-43.9 ± 88.8 vs. 12.4 ± 68.8, p = 0.40) tended to improve after ASV treatment, but did not reach statistical significance. Likewise, the proportion of patients whose diastolic dysfunction improved was nonsignificantly higher in the ASV than in the control group, respectively (37 vs. 15%, p = 0.25). CONCLUSIONS: ASV treatment efficiently abolishes SDB in patients with stable systolic HF and concomitant diastolic dysfunction, and was associated with a statistically nonsignificant improvement in measures of diastolic dysfunction. Thus, these data provide estimates of effect size and justify the evaluation of the effects of ASV on diastolic function in larger randomized controlled trials.

Endothelial injury markers before and after nasal continuous positive airway pressure treatment for obstructive sleep apnoea hypopnoea syndrome.

PURPOSE: The purpose of this study was to evaluate whether serum amyloid A (SAA), C-reactive protein (CRP), vascular cell adhesion molecule-1 (VCAM-1) and intercellular adhesion molecule-1 (ICAM-1) levels are elevated in obstructive sleep apnoea hypopnoea syndrome (OSAHS), and whether they change following acute- and medium-term CPAP treatment. METHODS: Consecutive subjects (n = 40) referred to the Sleep Disordered Breathing Unit were included in the research. Sera were sampled in the afternoon prior to an in-hospital limited-channel sleep study and on the next morning. Those diagnosed with OSAHS were commenced on CPAP and had further blood samples collected in the morning after the first night and then after a month of treatment. RESULTS: We had 20 subjects with moderate/severe OSAHS (mean ± SD), 4% desaturation rate (4% DR) 44.3 ± 31.4 events/h, and 20 comparator subjects with symptoms but negative sleep studies, 4% DR 5.6 ± 2.9 events/h. There was no difference in the morning and afternoon vascular injury marker levels between the OSAHS and comparator groups. However, CRP (6.52 ± 9.53 vs. 5.58 ± 8.47, p = 0.04) and VCAM-1 (366.30 ± 90.11 vs. 339.60 ± 95.87, p = 0.02) levels showed significant diurnal variation within the OSAHS group with higher afternoon levels compared to morning measurements. There were no changes in any of the vascular injury marker levels following CPAP. CONCLUSIONS: This study demonstrates that OSAHS leads to endothelial dysfunction as reflected by higher afternoon than morning CRP and VCAM-1 levels. However, despite a good CPAP compliance, a month of treatment does not decrease vascular injury marker levels.

COVID-19 managed on respiratory wards and intensive care units: Results from the national COVID-19 outcome report in Wales from March 2020 to December 2021.

BACKGROUND: A COVID-19 hospital guideline was implemented across all 18 acute hospitals in Wales in March 2020, promoting ward management of COVID pneumonitis and data collected across the first 3 Waves of the pandemic (Wave 1 March 1st 2020 to November 1st 2020, Wave 2 November 2st 2020 to February 21st 2021 and Wave 3 June 1st 2021 to December 14th 2021). The aim of this paper is to compare outcomes for patients by admission setting and type of ventilatory support given, with a particular focus on CPAP therapy. METHODS: This is a retrospective observational study of those aged over 18 admitted to hospital with community acquired COVID-19 between March 2020 and December 2021. The outcome of interest was in-hospital mortality. Univariate logistic regression models were used to compare crude outcomes across the waves. Multivariable logistic regression models were used to assess outcomes by different settings and treatments after adjusting for Wave, age, sex, co-morbidity and deprivation. RESULTS: Of the 7,803 records collected, 5,887 (75.4%) met the inclusion criteria. Analysis of those cases identified statistically significant outcome improvements across the waves for all patients combined (Waves 1 to 3: 31.5% to 18.8%, p<0.01), all ward patients (28.9% to 17.7%, p<0.01), and all ICU patients (44.3% to 32.2%, p = 0.03). Sub group analyses identified outcome improvements in ward patients without any oxygen therapy (Waves 1 to 3: 22.2% to 12.7%, p<0.01), with oxygen therapy only (34.0% to 12.9%, p<0.01) and with CPAP only (63.5% to 39.2%, p<0.01). The outcome improvements for ICU patients receiving CPAP only (35.7% to 24.6%, p = 0.31) or invasive ventilation (61.6% to 54.6%, p = 0.43) were not statistically significant though the numbers being admitted to ICU were small. The logistic regression models identified important age and comorbidity effects on outcomes. The multivariable model that took these into account suggested no statistically significantly greater risk of death for those receiving CPAP on the ward compared to those receiving CPAP in ICU (OR 0.89, 95% CI: 0.49 to 1.60). CONCLUSIONS: There were successive reductions in mortality in inpatients over the three Waves reflecting new treatments and better management of complications. Mortality for those requiring CPAP was similar in respiratory wards and ICUs after adjusting for differences in their respective patient populations.

Genomic attributes of airway commensal bacteria and mucosa.

Microbial communities at the airway mucosal barrier are conserved and highly ordered, in likelihood reflecting co-evolution with human host factors. Freed of selection to digest nutrients, the airway microbiome underpins cognate management of mucosal immunity and pathogen resistance. We show here the initial results of systematic culture and whole-genome sequencing of the thoracic airway bacteria, identifying 52 novel species amongst 126 organisms that constitute 75% of commensals typically present in heathy individuals. Clinically relevant genes encode antimicrobial synthesis, adhesion and biofilm formation, immune modulation, iron utilisation, nitrous oxide (NO) metabolism and sphingolipid signalling. Using whole-genome content we identify dysbiotic features that may influence asthma and chronic obstructive pulmonary disease. We match isolate gene content to transcripts and metabolites expressed late in airway epithelial differentiation, identifying pathways to sustain host interactions with microbiota. Our results provide a systematic basis for decrypting interactions between commensals, pathogens, and mucosa in lung diseases of global significance.

Singing for lung health in COPD: a multicentre randomised controlled trial of online delivery.

BACKGROUND: Singing for lung health (SLH) is an arts-based breathing control and movement intervention for people with long-term respiratory conditions, intended to improve symptoms and quality of life. Online, remotely delivered programmes might improve accessibility; however, no previous studies have assessed the effectiveness of this approach. METHODS: We conducted an assessor-blind randomised controlled trial comparing the impact of 12 weeks of once-weekly online SLH sessions against usual care on health-related quality of life, assessed using the RAND 36-Item Short Form Health Survey (SF-36) Mental Health Composite (MHC) and Physical Health Composite (PHC) scores. RESULTS: We enrolled 115 people with stable chronic obstructive pulmonary disease (COPD), median (IQR) age 69 (62-74), 56.5% females, 80% prior pulmonary rehabilitation, Medical Research Council dyspnoea scale 4 (3-4), forced expiratory volume in 1 s % predicted 49 (35-63). 50 participants in each arm completed the study. The intervention arm experienced improvements in physical but not mental health components of RAND SF-36; PHC (regression coefficient (95% CI): 1.77 (95% CI 0.11 to 3.44); p=0.037), but not MHC (0.86 (95% CI -1.68 to 3.40); p=0.504). A prespecified responder analysis based on achieving a 10% improvement from baseline demonstrated a response rate for PHC of 32% in the SLH arm and 12.7% for usual care (p=0.024). A between-group difference in responder rate was not found in relation to the MHC (19.3% vs 25.9%; p=0.403). DISCUSSION AND CONCLUSION: A 12-week online SLH programme can improve the physical component of quality of life for people with COPD, but the overall effect is relatively modest compared with the impact seen in research using face-to-face group sessions. Further work on the content, duration and dose of online interventions may be useful. TRIAL REGISTRATION NUMBER: NCT04034212.

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.

Quitting smoking improves two-year survival after a diagnosis of non-small cell lung cancer.

BACKGROUND: Smoking at diagnosis is associated with worse survival in lung cancer but the effects of quitting smoking on survival remain unclear. METHODS: In a UK multi-centre study (NCT01192256) we followed all 2751 patients with newly diagnosed non-small cell lung cancer (NSCLC) for up to 2 years or until death as part of the observational trial. Patients were offered smoking cessation advice and treatments according to national guidelines and local services. Smoking status was verified by exhaled carbon monoxide levels. Kaplan-Meier survival analysis and Cox Proportional Hazards Modelling examined the effects of quitting smoking on survival at 2 years. FINDINGS: 646 were current smokers at the time of diagnosis. The unadjusted two-year Kaplan-Meier survivor functions for quitters (0.45, 95 %CI 0.37 to 0.53) and continuers (0.32, 0.28 to 0.36) were significantly different (log-rank test p < 0.01). Median survival times were 659 days for quitters and 348 days for continuers. After adjusting for age, sex, stage, performance status, curative intent surgery, radical radiotherapy and comorbidity, the hazard ratio for quitting at diagnosis (0.75, 95 % CI 0.58 to 0.98) indicated a statistically significant reduction in the risk of death across the two-year study period. INTERPRETATION: Quitting smoking is independently and significantly associated with improved survival regardless of stage in NSCLC. We recommend that smoking cessation advice and treatments should be offered to smokers with lung cancer. TRIAL REGISTRATION: ClinicalTrials.gov, identifier NCT01192256. FUNDING: This work was supported by a 2010 Global Research Award for Nicotine Dependence (GRAND), Pfizer.