Home treatment of COPD exacerbation selected by DECAF score: a non-inferiority, randomised controlled trial and economic evaluation.

BACKGROUND: Previous models of Hospital at Home (HAH) for COPD exacerbation (ECOPD) were limited by the lack of a reliable prognostic score to guide patient selection. Approximately 50% of hospitalised patients have a low mortality risk by DECAF, thus are potentially suitable. METHODS: In a non-inferiority randomised controlled trial, 118 patients admitted with a low-risk ECOPD (DECAF 0 or 1) were recruited to HAH or usual care (UC). The primary outcome was health and social costs at 90 days. RESULTS: Mean 90-day costs were £1016 lower in HAH, but the one-sided 95% CI crossed the non-inferiority limit of £150 (CI -2343 to 312). Savings were primarily due to reduced hospital bed days: HAH=1 (IQR 1-7), UC=5 (IQR 2-12) (P=0.001). Length of stay during the index admission in UC was only 3 days, which was 2 days shorter than expected. Based on quality-adjusted life years, the probability of HAH being cost-effective was 90%. There was one death within 90 days in each arm, readmission rates were similar and 90% of patients preferred HAH for subsequent ECOPD. CONCLUSION: HAH selected by low-risk DECAF score was safe, clinically effective, cost-effective, and preferred by most patients. Compared with earlier models, selection is simpler and approximately twice as many patients are eligible. The introduction of DECAF was associated with a fall in UC length of stay without adverse outcome, supporting use of DECAF to direct early discharge. TRIAL REGISTRATION NUMBER: Registered prospectively ISRCTN29082260.

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.

Lung function and plasma fibrinogen concentrations in the Newcastle Thousand Families birth cohort between age 49 and 51 years.

BACKGROUND AND OBJECTIVE: A number of studies have suggested inverse associations between lung function and inflammatory markers, including fibrinogen. In this study, we used data from the Newcastle Thousand Families birth cohort to assess the association between contemporaneous markers of lung function and fibrinogen while adjusting for potential confounding factors throughout life. METHODS: At age 49-51 years, complete data on lung function and plasma fibrinogen were available for 380 study members. These data were analysed in relation to each other, adjusted for sex and height, with further adjustment for potential confounders within linear regression models using robust estimates. RESULTS: Forced expiratory volume in 1 s was significantly inversely associated with plasma fibrinogen concentration after initial adjustments for sex and height (beta = -0.12, P = 0.011) and remained so after further adjustments for pack-years of cigarettes smoked and current smoking status. On further adjustment for standardized birthweight and duration breast-fed, the association approached statistical significance (P = 0.051). Adjusting for body mass index (BMI) resulted in a loss of significance (P = 0.09), but an unchanged regression coefficient, while, after adjustment for percent body fat, rather than BMI, the association was no longer significant (P = 0.20) and the coefficient reduced. CONCLUSIONS: The association between lung function and fibrinogen remains after adjustment for potential early-life confounders and smoking. However, it is not independent of contemporaneous measures of adiposity, with evidence of confounding by percent body fat. Further studies, with measures of adiposity, are required to confirm whether associations between markers of inflammation and lung function are due to residual confounding by adiposity.

Non-invasive ventilation in motor neuron disease: an update of current UK practice.

BACKGROUND: In motor neurone disease (MND), respiratory muscle weakness causes substantial morbidity, and death is usually due to respiratory failure. Non-invasive ventilation (NIV) improves symptoms, quality of life and survival, but previous surveys showed that few patients with MND received NIV. METHODS: A postal survey was conducted of the clinical application of NIV in MND among consultant neurologists in the UK. The results were compared with those of a similar survey done in 2000. FINDINGS: Over 12 months, 612 patients were referred for NIV of whom 444 were successfully established on treatment (72.5% success rate). 38% of responding neurologists assessed respiratory function at presentation and 20% routinely monitored respiratory function; 32% relied on symptoms as the only criterion for NIV referral and 43% used a combination of symptoms and physiological impairment. 75% of responding neurologists accessed specialist palliative care services for their patients towards the end of life and 69% at an earlier stage. INTERPRETATION: Compared with 2000, there has been a marked increase in the number of patients referred for, and currently using, NIV (2.6 and 3.4-fold, respectively). The proportion successfully established on NIV has also increased, suggesting more appropriate selection and/or improvement in the methods of using NIV in this challenging group of patients. However, monitoring of respiratory function is suboptimal and uncontrolled oxygen is sometimes used inappropriately before the terminal phase.

Lifecourse predictors of adult respiratory function: results from the Newcastle Thousand Families Study.

BACKGROUND: Impaired development in utero is suggested to increase the risk of poor respiratory health in adulthood, although a consensus has not been reached. A possible explanation for discrepancies between previous studies is inconsistent controlling for potential confounding factors, particularly childhood infections. Also, little is known regarding the relative importance of factors operating at different stages of the lifecourse. We have used detailed longitudinal data from the Newcastle Thousand Families cohort to assess the impact of birth weight, and various other factors acting throughout the lifecourse, on predicting forced expiratory volume in 1 s (FEV(1)). METHODS: Detailed information was collected prospectively during childhood, including birth weight, childhood infections and socioeconomic circumstances. At age 49-51 years, 412 study members attended for clinical examination and measurement of FEV(1). These data were analysed in relation to a range of factors from across the lifecourse using linear regression models. RESULTS: After adjustment for all other significant variables, increasing birth weight, standardised for sex and gestational age (p = 0.011), being breast fed for more than 4 weeks (p = 0.017), less frequent childhood lower respiratory tract infections (LRTI) (p = 0.015), non- smoking (p<0.001), lower body fat percentage (p = 0.010), male sex (p<0.001), no history of asthma (p = 0.013) and greater adult height (p<0.001) were all independently associated with higher adult FEV(1). CONCLUSION: Adult lung function is influenced by numerous factors during an individual's lifetime, acting both directly and indirectly throughout the lifecourse. As expected, sex, height and smoking were the most important predictors of FEV(1), but birth weight, breast feeding and childhood LRTIs also contributed significantly.

Effects of non-invasive ventilation on survival and quality of life in patients with amyotrophic lateral sclerosis: a randomised controlled trial.

BACKGROUND: Few patients with amyotrophic lateral sclerosis currently receive non-invasive ventilation (NIV), reflecting clinical uncertainty about the role of this intervention. We aimed to assess the effect of NIV on quality of life and survival in amyotrophic lateral sclerosis in a randomised controlled trial. METHODS: 92 of 102 eligible patients participated. They were assessed every 2 months and randomly assigned to NIV (n=22) or standard care (n=19) when they developed either orthopnoea with maximum inspiratory pressure less than 60% of that predicted or symptomatic hypercapnia. Primary validated quality-of-life outcome measures were the short form 36 mental component summary (MCS) and the sleep apnoea quality-of-life index symptoms domain (sym). Both time maintained above 75% of baseline (T(i)MCS and T(i)sym) and mean improvement (microMCS and microsym) were measured. FINDINGS: NIV improved T(i)MCS, T(i)sym, microMCS, microsym, and survival in all patients and in the subgroup with better bulbar function (n=20). This subgroup showed improvement in several measures of quality of life and a median survival benefit of 205 days (p=0.006) with maintained quality of life for most of this period. NIV improved some quality-of-life indices in those with poor bulbar function, including microsym (p=0.018), but conferred no survival benefit. INTERPRETATION: In patients with amyotrophic lateral sclerosis without severe bulbar dysfunction, NIV improves survival with maintenance of, and improvement in, quality of life. The survival benefit from NIV in this group is much greater than that from currently available neuroprotective therapy. In patients with severe bulbar impairment, NIV improves sleep-related symptoms, but is unlikely to confer a large survival advantage.

Evaluation of potential predictors of outcome of laser-assisted uvulopalatoplasty for snoring.

OBJECTIVE: Laser-assisted uvulopalatoplasty (LAUP) is a common treatment for snoring, but up to 50% of patients obtain little or no sustained benefit. We investigated whether pre-operative measurements from lateral cephalometry, acoustic rhinometry, analysis of snoring sounds, and body mass index (BMI) could predict which snorers benefited from LAUP. STUDY DESIGN AND SETTING: Fifty-five snoring patients were assessed pre- and 6 months post-LAUP. Snoring severity was assessed by objective sound level recorded during polysomnography, and a Snoring Symptoms Inventory (SSI) questionnaire. RESULTS: The outcome of surgery was assessed by changes in objective sound measurements and in SSI, 6 months after LAUP. CONCLUSIONS: Relationships between the predictive measurements and outcome were at best only weak and none had sufficient predictive value to be useful in clinical practice.

The development of a snoring symptoms inventory.

OBJECTIVE: To develop a patient-derived snoring questionnaire, the Snoring Symptoms Inventory (SSI), and explore its structure and relationship to the Epworth Sleepiness Scale (ESS); and to assess the sensitivity of the SSI to change. STUDY DESIGN AND SETTING: The SSI was developed from an open-ended questionnaire given to 120 habitual snorers. The 25 symptoms reported compose the SSI. This study examines 261 subsequent snorers assessed between April 1998 and August 2002, who completed both the SSI and the ESS. Fifty-five of them underwent laser uvulopalatoplasty and their preoperative and postoperative SSI results were compared. RESULTS: The total SSI score is the key outcome derived. Principal component analysis identified two further dimensions, one contrasting family/social with work-related problems and another comparing physical problems with embarrassment. The total score correlated weakly with the ESS. Laser uvulopalatoplasty significantly reduced patients' overall symptom severity and family and socially related problems. CONCLUSION: The SSI is a comprehensive and sensitive measure for assessing snoring, making it a useful clinical outcome tool for snoring treatment. SIGNIFICANCE: The SSI is a new, useful snoring questionnaire. EBM RATING: B-2b.

Comparison of manual sleep staging with automated neural network-based analysis in clinical practice.

We have compared sleep staging by an automated neural network (ANN) system, BioSleep (Oxford BioSignals) and a human scorer using the Rechtschaffen and Kales scoring system. Sleep study recordings from 114 patients with suspected obstructed sleep apnoea syndrome (OSA) were analysed by ANN and by a blinded human scorer. We also examined human scorer reliability by calculating the agreement between the index scorer and a second independent blinded scorer for 28 of the 114 studies. For each study, we built contingency tables on an epoch-by-epoch (30 s epochs) comparison basis. From these, we derived kappa (kappa) coefficients for different combinations of sleep stages. The overall agreement of automatic and manual scoring for the 114 studies for the classification {wake / light-sleep / deep-sleep / REM} was poor (median kappa = 0.305) and only a little better (kappa = 0.449) for the crude {wake / sleep} distinction. For the subgroup of 28 randomly selected studies, the overall agreement of automatic and manual scoring was again relatively low (kappa = 0.331 for {wake light-sleep / deep-sleep REM} and kappa = 0.505 for {wake / sleep}), whereas inter-scorer reliability was higher (kappa = -0.641 for {wake / light-sleep / deep-sleep / REM} and kappa = 0.737 for {wake / sleep}). We conclude that such an ANN-based analysis system is not sufficiently accurate for sleep study analyses using the R&K classification system.

Longitudinal change in quality of life following hospitalisation for acute exacerbations of COPD.

BACKGROUND: Current guidelines for management of patients hospitalised with acute exacerbations of chronic obstructive pulmonary disease (COPD) recommend that clinical decisions, including escalation to assisted ventilation, be informed by an estimate of the patients' likely postdischarge quality of life. There is little evidence to inform predictions of outcome in terms of quality of life, psychological well-being and functional status. Undue nihilism might lead to denial of potentially life-saving therapy, while undue optimism might prolong suffering when alternative palliation would be more appropriate. This study aimed to detail longitudinal changes in quality of life following hospitalisation for acute exacerbations of COPD. METHODS: We prospectively recruited two cohorts (exacerbations requiring assisted ventilation during admission and exacerbations not ventilated). Admission clinical data, and mortality and readmission details were collected. Quality of life, psychological well-being and functional status were formally assessed over the subsequent 12 months. Time-adjusted mean change in quality of life was examined. RESULTS: 183 patients (82 ventilated; 101 not ventilated) were recruited. On average, overall quality of life improved by a clinically important amount in those not ventilated and did not decline in ventilated patients. Both groups showed clinically important improvements in respiratory symptoms and an individual's sense of control over their condition, despite the tendency for functional status to decline. CONCLUSIONS: On average, postdischarge quality of life improved in non-ventilated and did not decline in ventilated patients. Certain quality of life domains (ie, symptoms and mastery) improved significantly. Better understanding of longitudinal change in postdischarge quality of life should help to inform decision-making.

Diagnosis of muscle diseases presenting with early respiratory failure.

Here we describe a clinical approach and differential diagnosis for chronic muscle diseases which include early respiratory failure as a prominent feature in their presentation (i.e. respiratory failure whilst still ambulant). These patients typically present to neurology or respiratory medicine out-patient clinics and a distinct differential diagnosis of neuromuscular aetiologies should be considered. Amyotrophic lateral sclerosis and myasthenia gravis are the important non-muscle diseases to consider, but once these have been excluded there remains a challenging differential diagnosis of muscle conditions, which will be the focus of this review. The key points in the diagnosis of these disorders are being aware of relevant symptoms, which are initially caused by nocturnal hypoventilation or diaphragmatic weakness; and identifying other features which direct further investigation. Important muscle diseases to identify, because their diagnosis has disease-specific management implications, include adult-onset Pompe disease, inflammatory myopathy, and sporadic adult-onset nemaline myopathy. Cases which are due to metabolic myopathy or muscular dystrophy are important to diagnose because of their implications for genetic counselling. Myopathy from sarcoidosis and colchicine each has a single reported case with this presentation, but should be considered because they are treatable. Disorders which have recently had their genetic aetiologies identified include hereditary myopathy with early respiratory failure (due to TTN mutations), the FHL1-related syndromes, and myofibrillar myopathy due to BAG3 mutation. Recently described syndromes include oculopharyngodistal muscular dystrophy that awaits genetic characterisation.

Childhood respiratory illness and lung function at ages 14 and 50 years: childhood respiratory illness and lung function.

BACKGROUND: Although childhood respiratory tract infections and low birth weight have both been associated with reduced adult lung function, little is known about the timing of these associations during life. We used data from the Newcastle Thousand Families Study to examine how these and other factors influenced FEV(1) at age 14 years and between 14 and 49 to 51 years. METHODS: Detailed information was collected prospectively during childhood. At age 14 years, 252 members of the cohort were recruited into a case-control study of respiratory health, which included measurement of FEV(1). One hundred twenty-two of these were measured again at age 49 to 51 years. Linear regression models were used to examine cross-sectional and longitudinal influences on FEV(1). RESULTS: Lower height (P < .001), lower BMI (P < .001), being breast fed for less than 4 weeks (P = .028), childhood history of severe respiratory illness (P = .014), childhood history of asthma (P = .004), childhood history of TB (P = .023), and birth into a lower social class (P = .049) were all significant independent predictors of lower FEV(1) at 14 years of age. Correspondingly, being a women (P < .001), and having a higher FEV(1) at age 14 years (P < .001), a lower standardized birth weight (P = .025), a greater lifetime number of cigarettes smoked (P = .007), and a childhood history of severe respiratory illness (P = .047) were all independently associated with a greater decline (or a smaller increase) in FEV(1) between age 14 and 49 to 51 years. CONCLUSIONS: This study suggests that the change in FEV(1) between youth and middle age depends on several factors acting throughout life, including FEV(1) in adolescence, sex, cigarette smoking, birth weight, and childhood respiratory health.

Platypnoea orthodeoxia in a patient with aortic root dilatation and a patent foramen ovale.

Platypnoea orthodeoxia syndrome is a rare condition in which shortness of breath and hypoxaemia occur when upright and resolve when prone. The hypoxaemia results from increased right to left shunting of deoxygenated blood, when standing, through a patent foramen ovale (PFO), atrial septal defect (ASD) or other right to left shunt, in the absence of raised right-heart pressure. We present the case of a patient with platypnoea orthodeoxia with marked shunting through a large PFO, evaluated by transesophageal and transthoracic echo.

Fatigue in primary biliary cirrhosis is associated with excessive daytime somnolence.

A significant proportion of patients with primary biliary cirrhosis (PBC) suffer from severe fatigue. The aim of this study was to characterize patterns of daytime sleep in patients with PBC (using both objective and subjective assessment approaches) and to study the association between sleep abnormality and fatigue severity. Fatigue severity was assessed in 48 female subjects with PBC (using a disease-specific quality of life instrument (the PBC-40) and a generic fatigue measure (Fatigue Impact Scale [FIS]) as well as 48 case-matched normal controls. All participants also completed the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS, which assesses daytime hypersomnolence). Objective sleep assessment was performed using accelerometry over 7 days. Global sleep quality assessed by the PSQI was significantly lower in the PBC group compared to controls (P < .0001). ESS scores were significantly higher in patients with PBC than controls (P = .0001), suggesting significantly greater daytime somnolence in the patients with PBC. Objective sleep assessment confirmed that subjects with PBC were sleeping on average almost twice as long as controls during the daytime. Both degree of daytime somnolence (ESS) and actual daytime sleep activity (accelerometry) correlated strongly with fatigue severity in the patient group (r2 = 0.5, P < .0001 and r2 = 0.2, P < .01, respectively). In conclusion, Sleep abnormality, in the form of excessive daytime somnolence, is present in a significant proportion of patients with PBC, with the degree of daytime somnolence correlating strongly with the degree of fatigue. Existing agents effective at reducing daytime somnolence (such as modafinil) hold potential for the treatment of fatigue in PBC.

Swallow-induced alterations in breathing in normal older people.

Respiratory parameters in 29 normal older subjects (mean age-73 years, SD = 5.7) were studied at rest, during single water swallows, and in continuous drinking. Respiration was recorded by intranasal air pressure changes and the moment of swallowing by pharyngoesophageal manometry. Compared with respiration at rest, respiratory rate increased immediately after 5 mL swallows as duration of breath cycles decreased from a mean of 3.8 s at rest to 3.5 s after swallowing (p = 0.003), but regularity of respiration was maintained. Deglutition apnea showed a trend toward increasing duration from a median of 1.06 to 1.24 s (p = 0.096) as bolus volume increased from 5 to 20 mL. Oxygen saturation levels were also compared, with a median fall of 2% during swallowing, but with larger and unexplained falls in several subjects. Direction of airflow monitoring showed 91% of single 5 mL swallows were followed by expiration, with postswallow inspiratory breaths occurring in 41% of subjects. Continuous swallowing of 100 mL of water from a cup and straw was typically performed with a pattern of multiple swallows per breath, with expiration occurring after 78.5% (cup) and 63.5% (straw) of swallows. This definition of swallowing-induced respiratory changes in normal older people forms a valuable basis for future comparison with elderly dysphagic patients.

Skeletal muscle mRNA levels for cathepsin B, but not components of the ubiquitin-proteasome pathway, are increased in patients with lung cancer referred for thoracotomy.

Muscle wasting is a common and prominent feature of advanced cancer, including lung cancer. Evidence from animal experiments suggests that accelerated proteolysis via the ubiquitin--proteasome pathway is the primary cause of cancer-related cachexia. However, there are few data on the role of this pathway in determining muscle wasting in human cancer. The present study was designed to measure whether skeletal muscle gene expression of components of the ubiquitin-proteasome pathway and/or the lysosomal proteolytic pathway was increased in patients with early lung cancer. A total of 36 patients with lung cancer referred for curative resection and 10 control subjects had biopsies of latissimus dorsi muscle taken at operation. mRNA levels of four components of the ubiquitin-proteasome pathway, i.e. polyubiquitin, C2 alpha proteasome subunit, 14 kDa ubiquitin-carrier protein and ubiquitin-activating protein, and of two lysosomal proteolytic enzymes, i.e. cathepsin B and cathepsin D, were measured using quantitative Northern blotting. mRNA levels for cathepsin B, but not for components of the ubiquitin--proteasome pathway, were higher in patients with cancer compared with controls (P=0.01). Among lung cancer patients, cathepsin B mRNA levels correlated with fat-free mass index (r = -0.57, P=0.003) and tumour stage (r(s)=0.45, P=0.03), and were higher in smokers (P=0.04). Thus gene expression of the lysosomal protease cathepsin B is increased in the skeletal muscle of patients with early lung cancer, and the strong inverse relationship with fat-free mass suggests that cathepsin B may have a role in inducing muscle wasting in the early stages of lung cancer.