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Background: The COPD Best Practice Tariff (BPT) is a pay-for-performance scheme in England that incentivises review by a respiratory specialist within 24 hours of admission and completion of a list of key care components prior to discharge, known as a discharge bundle, for patients admitted with acute exacerbation of COPD (AECOPD). We investigated whether the two components of the COPD BPT were associated with lower 30-day mortality and readmission in people discharged following AECOPD.Methods: Longitudinal study of national audit data containing details of AECOPD admissions in England and Wales between 01 February 2017 and 13 September 2017. Data were linked with national admissions and mortality data. Mixed-effects logistic regression, using a random intercept for hospital to adjust for clustering of patients, was used to determine the relationship between the COPD BPT criteria (combined and separately) and 30-day mortality and readmission. Models were adjusted for age, sex, socioeconomic status, length of stay, smoking status, Charlson comorbidity index, mental illness and requirement for oxygen or noninvasive ventilation during admission.Results: 28 345 patients discharged from hospital following AECOPD were included. 37% of admissions conformed to the two COPD BPT criteria. No relationship was observed between BPT conforming admissions and 30-day mortality (OR: 1.09 (95% CI 0.92 to 1.29)) or readmissions (OR: 0.96 (95% CI 0.90 to 1.02)). No relationship was observed between either of the individual COPD BPT components and 30-day mortality or readmissions. However, a specialist review at any time during admission was associated with lower inpatient mortality (OR: 0.69 (95% CI 0.58 to 0.81)).Conclusion: Completion of the combined COPD BPT criteria does not appear associated with a reduction in 30-day mortality or readmission. However, specialist review was associated with reduced inpatient mortality. While it is difficult to argue that discharge bundles do not improve care, this analysis questions whether the pay-for-performance model improves mortality or readmissions. [ABSTRACT FROM AUTHOR]

Objectives: To determine growth outcomes at 11 years of age in children born <27 weeks of gestation in England in 2006 (EPICure2) and to compare growth from birth to 11 years of age for births<26 weeks with those in England in 1995 (EPICure).Methods: 200 EPICure2 children assessed at 11 years alongside 143 term-born controls. Growth measures from birth to 11 years were compared for births<26 weeks between EPICure2 (n=112) and EPICure (n=176). Growth parameter z-scores were derived from 1990 UK standards.Results: Among EPICure2 children, mean z-scores for height and weight were close to the population standards (0.08 and 0.18 SD, respectively) but significantly below those of controls: difference in mean (Δ) z-scores for weight -0.42 SD (95% CI -0.68 to -0.17), for height -0.45 SD (-0.70 to -0.20) and for head circumference (HC) -1.05 SD (-1.35 to -0.75); mean body mass index (BMI) z-score in EPICure2 children was 0.18 SD, not significantly different from controls (0.43 SD, p=0.065). Compared with EPICure, EPICure2 children born <26 weeks at 11 years had higher z-scores for weight (Δ 0.72 (0.47, 0.96)), height (Δ 0.55 (0.29, 0.81)) and BMI (Δ 0.56 (0.24, 0.87)), which were not fully explained by perinatal/demographic differences between eras. Weight catch-up was greater from term-age to 2.5/3 years in EPICure2 than in EPICure (1.25 SD vs 0.53 SD; p<0.001). Poor HC growth was observed in EPICure2, unchanged from EPICure.Conclusions: Since 1995, childhood growth in weight, height and BMI have improved for births <26 weeks of gestation, but there was no improvement in head growth. [ABSTRACT FROM AUTHOR]

Objective: To determine whether improvements in school age outcomes had occurred between two cohorts of births at 22-25 weeks of gestation to women residents in England in 1995 and 2006.Design: Longitudinal national cohort studies.Setting: School-based or home-based assessments at 11 years of age.Participants: EPICure2 cohort of births at 22-26 weeks of gestation in England during 2006: a sample of 200 of 1031 survivors were evaluated; outcomes for 112 children born at 22-25 weeks of gestation were compared with those of 176 born in England during 1995 from the EPICure cohort. Classroom controls for each group acted as a reference population.Main Outcome Measures: Standardised measures of cognition and academic attainment were combined with parent report of other impairments to estimate overall neurodevelopmental status.Results: At 11 years in EPICure2, 18% had severe and 20% moderate impairments. Comparing births at 22-25 weeks in EPICure2 (n=112), 26% had severe and 21% moderate impairment compared with 18% and 32%, respectively, in EPICure. After adjustment, the OR of moderate or severe neurodevelopmental impairment in 2006 compared with 1995 was 0.76 (95% CI 0.45 to 1.31, p=0.32). IQ scores were similar in 1995 (mean 82.7, SD 18.4) and 2006 (81.4, SD 19.2), adjusted difference in mean z-scores 0.2 SD (95% CI -0.2 to 0.6), as were attainment test scores. The use of multiple imputation did not alter these findings.Conclusion: Improvements in care and survival between 1995 and 2006 are not paralleled by improved cognitive or educational outcomes or a reduced rate of neurodevelopmental impairment. [ABSTRACT FROM AUTHOR]

Objective: To investigate whether size at birth and growth trajectories in infancy and childhood are associated with determinants of cardiovascular and metabolic risks in young adults born extremely preterm (EP, <26 weeks of gestation).Methods: We used longitudinal data from the EPICure study of 129 EP survivors up to 19 years in the UK and Ireland in 1995. Determinants of cardiovascular and metabolic risks at 19 years included the presence of metabolic syndrome, body mass index (BMI) and systolic blood pressure (SBP). Predictors were birth weight for gestation and gain in weight z-scores in the following periods: birth-postmenstrual age of 40 weeks (term), infancy (term-2.5 years), early childhood (2.5-6.0 years) and late childhood (6-11 years).Results: Metabolic syndrome was present in 8.7% of EP participants at 19 years. Compared with subjects without metabolic syndrome, those with metabolic syndrome tended to have a smaller size at birth (difference in means: -0.55 SD, 95% CI -1.10 to 0.01, p=0.053) and a greater increase in weight z-scores from term to 2.5 years (difference in means: 1.00 SD, 95% CI -0.17 to 2.17, p=0.094). BMI at 19 years was positively related to growth from 2.5 to 6.0 years ( β : 1.03, 95% CI 0.31 to 1.75, p=0.006); an inverse association with birthweight z-scores was found in the lower socioeconomic status group ( β : -1.79, 95% CI -3.41 to -0.17, p=0.031). Central SBP was positively related to growth from 2.5 to 6.0 years ( β : 1.75, 95% CI 0.48 to 3.02, p=0.007).Conclusion: Size at EP birth and increased catch-up in weight from 2.5 to 6.0 years were associated with BMI and central SBP in early adulthood. [ABSTRACT FROM AUTHOR]

Objective: To investigate growth trajectories from age 2.5 to 19 years in individuals born before 26 weeks of gestation (extremely preterm; EP) compared with term-born controls.Methods: Multilevel modelling of growth data from the EPICure study, a prospective 1995 birth cohort of 315 EP participants born in the UK and Ireland and 160 term-born controls recruited at school age. Height, weight, head circumference and body mass index (BMI) z-scores were derived from UK standards at ages 2.5, 6, 11 and 19 years.Results: 129 (42%) EP children were assessed at 19 years. EP individuals were on average 4.0 cm shorter and 6.8 kg lighter with a 1.5 cm smaller head circumference relative to controls at 19 years. Relative to controls, EP participants grew faster in weight by 0.06 SD per year (95% CI 0.05 to 0.07), in head circumference by 0.04 SD (95% CI 0.03 to 0.05), but with no catch-up in height. For the EP group, because of weight catch-up between 6 and 19 years, BMI was significantly elevated at 19 years to +0.32 SD; 23.4% had BMI >25 kg/m2 and 6.3% >30 kg/m2 but these proportions were similar to those in control subjects. EP and control participants showed similar pubertal development in early adolescence, which was not associated with height at 19 years in either study group. Growth through childhood was related to birth characteristics and to neonatal feeding practices.Conclusions: EP participants remained shorter and lighter and had smaller head circumferences than reference data or controls in adulthood but had elevated BMI. [ABSTRACT FROM AUTHOR]

Objectives To establish a database network for the study of alpha-1 antitrypsin deficiency (AATD) and compare the results to CT lung density as the most direct measure of emphysema. Design A central electronic database was established to permit the upload of anonymised patient data from remote sites. Prospectively collected CT data were recorded onto disc, anonymised, analysed at the coordinating centre and compared with the clinical features of the disease. Setting Tertiary referral centres with expertise in the management of AATD focused on academic Biomedical Research Units and Wellcome Clinical Research Facilities. Participants Data were collected from 187 patients over 1 year from eight UK academic sites. This included patient demographics, postbronchodilator physiology, health status and CT. Analysis was undertaken at the coordinating centre in Birmingham. Results Patient recruitment in the 12 months reached 94% of target (set at 200) covering the whole spectrum of the disease from those with normal lung function to very severe chronic obstructive lung disease. CT scan suitable for analysis was available from 147 (79%) of the patients. CT density, analysed as the threshold for the lowest 15% of lung voxels, showed statistically significant relationships with the objective physiological parameters of lung function as determined by spirometric Global Initiative for Chronic Obstructive Lung Disease (GOLD) severity staging (p<0.001) and carbon monoxide gas transfer (p<0.01). Density also correlated with subjective measures of quality of life (p=0.02). Conclusions Establishment of the network for data collection and its transfer was highly successful facilitating future collaboration for the study of this rare disease and its management. CT densitometry correlated well with the objective clinical features of the disease supporting its role as the specific marker of the associated emphysema and its severity. Correlations with subjective measures of health, however, were generally weak indicating other factors play a role. [ABSTRACT FROM AUTHOR]

In the nineteenth century, it was recognised that acute attacks of chronic bronchitis were harmful. 140 years later, it is clearer than ever that exacerbations of chronic obstructive pulmonary disease (ECOPD) are important events. They are associated with significant mortality, morbidity, a reduced quality of life and an increasing reliance on social care. ECOPD are common and are increasing in prevalence. Exacerbations beget exacerbations, with up to a quarter of in-patient episodes ending with readmission to hospital within 30 days. The healthcare costs are immense. Yet despite this, the tools available to diagnose and treat ECOPD are essentially unchanged, with the last new intervention (non-invasive ventilation) introduced over 25 years ago.An ECOPD is 'an acute worsening of respiratory symptoms that results in additional therapy'. This symptom and healthcare utility-based definition does not describe pathology and is unable to differentiate from other causes of an acute deterioration in breathlessness with or without a cough and sputum. There is limited understanding of the host immune response during an acute event and no reliable and readily available means to identify aetiology or direct treatment at the point of care (POC). Corticosteroids, short acting bronchodilators with or without antibiotics have been the mainstay of treatment for over 30 years. This is in stark contrast to many other acute presentations of chronic illness, where specific biomarkers and mechanistic understanding has revolutionised care pathways. So why has progress been so slow in ECOPD? This review examines the history of diagnosing and treating ECOPD. It suggests that to move forward, there needs to be an acceptance that not all exacerbations are alike (just as not all COPD is alike) and that clinical presentation alone cannot identify aetiology or stratify treatment. [ABSTRACT FROM AUTHOR]

Large numbers of people are being discharged from hospital following COVID-19 without assessment of recovery. In 384 patients (mean age 59.9 years; 62% male) followed a median 54 days post discharge, 53% reported persistent breathlessness, 34% cough and 69% fatigue. 14.6% had depression. In those discharged with elevated biomarkers, 30.1% and 9.5% had persistently elevated d-dimer and C reactive protein, respectively. 38% of chest radiographs remained abnormal with 9% deteriorating. Systematic follow-up after hospitalisation with COVID-19 identifies the trajectory of physical and psychological symptom burden, recovery of blood biomarkers and imaging which could be used to inform the need for rehabilitation and/or further investigation. [ABSTRACT FROM AUTHOR]

Objective To evaluate if observed increased weekend mortality was associated with poorer quality of care for patients admitted to hospital with chronic obstructive pulmonary disease (COPD) exacerbation. Design Prospective case ascertainment cohort study. Setting 199 acute hospitals in England and Wales, UK. Participants Consecutive COPD admissions, excluding subsequent readmissions, from 1 February to 30 April 2014 of whom 13 414 cases were entered into the study. Main outcomes Process of care mapped to the National Institute for Health and Care Excellence clinical quality standards, access to specialist respiratory teams and facilities, mortality and length of stay, related to time and day of the week of admission. Results Mortality was higher for weekend admissions (unadjusted OR 1.20, 95% CI 1.00 to 1.43), and for case-mix adjusted weekend mortality when calculated for admissions Friday morning through to Monday night (adjusted OR 1.19, 95% CI 1.00 to 1.43). Median time to death was 6 days. Some clinical processes were poorer on Mondays and during normal working hours but not weekends or out of hours. Specialist respiratory care was less available and less prompt for Friday and Saturday admissions. Admission to a specialist ward or high dependency unit was less likely on a Saturday or Sunday. Conclusions Increased mortality observed in weekend admissions is not easily explained by deficiencies in early clinical guideline care. Further study of out-of-hospital factors, specialty care and deaths later in the admission are required if effective interventions are to be made to reduce variation by day of the week of admission. [ABSTRACT FROM AUTHOR]

Background: There are limited data on the burden of cardiovascular comorbidities in people with bronchiectasis. Our cross-sectional study estimates the burden of pre-existing diagnoses of coronary heart disease (CHD) and stroke in people with bronchiectasis compared with the general population. The historical cohort study investigates if individuals with bronchiectasis are at increased risk of incident CHD and stroke events.Methods: We used primary care electronic records from the Clinical Practice Research Datalink. The cross-sectional study used logistic regression to quantify the association between bronchiectasis and recorded diagnoses of CHD or stroke. Cox regression was used to investigate if people with bronchiectasis experienced increased incident CHD and strokes compared with the general population, adjusting for age, sex, smoking habit and other risk factors for cardiovascular disease.Results: Pre-existing diagnoses of CHD (OR 1.33, 95% CI 1.25 to 1.41) and stroke (OR 1.92, 95% CI 1.85 to 2.01) were higher in people with bronchiectasis compared with those without bronchiectasis, after adjusting for age, sex, smoking and risk factors for cardiovascular disease. The rate of first CHD and stroke were also higher in people with bronchiectasis (HR for CHD 1.44 (95% CI 1.27 to 1.63) and HR for stroke 1.71 (95% CI 1.54 to 1.90)).Conclusion: The risk of CHD and stroke are higher among people with bronchiectasis compared with the general population. An increased awareness of these cardiovascular comorbidities in this population is needed to provide a more integrated approach to the care of these patients. [ABSTRACT FROM AUTHOR]

Background: Long-term antibiotic therapy is used to prevent exacerbations of COPD but there is uncertainty over whether this reduces airway bacteria. The optimum antibiotic choice remains unknown. We conducted an exploratory trial in stable patients with COPD comparing three antibiotic regimens against placebo.Methods: This was a single-centre, single-blind, randomised placebo-controlled trial. Patients aged ≥45 years with COPD, FEV1<80% predicted and chronic productive cough were randomised to receive either moxifloxacin 400 mg daily for 5 days every 4 weeks, doxycycline 100 mg/day, azithromycin 250 mg 3 times a week or one placebo tablet daily for 13 weeks. The primary outcome was the change in total cultured bacterial load in sputum from baseline; secondary outcomes included bacterial load by 16S quantitative PCR (qPCR), sputum inflammation and antibiotic resistance.Results: 99 patients were randomised; 86 completed follow-up, were able to expectorate sputum and were analysed. After adjustment, there was a non-significant reduction in bacterial load of 0.42 log10 cfu/mL (95% CI -0.08 to 0.91, p=0.10) with moxifloxacin, 0.11 (-0.33 to 0.55, p=0.62) with doxycycline and 0.08 (-0.38 to 0.54, p=0.73) with azithromycin from placebo, respectively. There were also no significant changes in bacterial load measured by 16S qPCR or in airway inflammation. More treatment-related adverse events occurred with moxifloxacin. Of note, mean inhibitory concentrations of cultured isolates increased by at least three times over placebo in all treatment arms.Conclusions: Total airway bacterial load did not decrease significantly after 3 months of antibiotic therapy. Large increases in antibiotic resistance were seen in all treatment groups and this has important implications for future studies.Trial Registration Number: clinicaltrials.gov (NCT01398072). [ABSTRACT FROM AUTHOR]

Although survival has improved significantly in recent years, prematurity remains a major cause of infant and childhood mortality and morbidity. Preterm births (<37 weeks of gestation) account for 8% of live births representing >50 000 live births each year in the UK. Preterm birth, irrespective of whether babies require neonatal intensive care, is associated with increased respiratory symptoms, partially reversible airflow obstruction and abnormal thoracic imaging in childhood and in young adulthood compared with those born at term. Having failed to reach their optimal peak lung function in early adulthood, there are as yet unsubstantiated concerns of accelerated lung function decline especially if exposed to noxious substances leading to chronic respiratory illness; even if the rate of decline in lung function is normal, the threshold for respiratory symptoms will be crossed early. Few adult respiratory physicians enquire about the neonatal period in their clinical practice. The management of these subjects in adulthood is largely evidence free. They are often labelled as asthmatic although the underlying mechanisms are likely to be very different. Smoking cessation, maintaining physical fitness, annual influenza immunisation and a general healthy lifestyle should be endorsed irrespective of any symptoms. There are a number of clinical and research priorities to maximise the quality of life and lung health in the longer term not least understanding the underlying mechanisms and optimising treatment, rather than extrapolating from other airway diseases. [ABSTRACT FROM AUTHOR]

Objectives: The optimal method of identifying people with chronic obstructive pulmonary disease (COPD) from electronic primary care records is not known. We assessed the accuracy of different approaches using the Clinical Practice Research Datalink, a UK electronic health record database. Setting: 951 participants registered with a CPRD practice in the UK between 1 January 2004 and 31 December 2012. Individuals were selected for ≥1 of 8 algorithms to identify people with COPD. General practitioners were sent a brief questionnaire and additional evidence to support a COPD diagnosis was requested. All information received was reviewed independently by two respiratory physicians whose opinion was taken as the gold standard. Primary outcome measure: The primary measure of accuracy was the positive predictive value (PPV), the proportion of people identified by each algorithm for whom COPD was confirmed. Results: 951 questionnaires were sent and 738 (78%) returned. After quality control, 696 (73.2%) patients were included in the final analysis. All four algorithms including a specific COPD diagnostic code performed well. Using a diagnostic code alone, the PPV was 86.5% (77.5-92.3%) while requiring a diagnosis plus spirometry plus specific medication; the PPV was slightly higher at 89.4% (80.7-94.5%) but reduced case numbers by 10%. Algorithms without specific diagnostic codes had low PPVs (range 12.2-44.4%). Conclusions: Patients with COPD can be accurately identified from UK primary care records using specific diagnostic codes. Requiring spirometry or COPD medications only marginally improved accuracy. The high accuracy applies since the introduction of an incentivised disease register for COPD as part of Quality and Outcomes Framework in 2004. [ABSTRACT FROM AUTHOR]

Background The natural history and time course of the onset of exacerbation events of chronic obstructive pulmonary disease (COPD) is incompletely understood. Methods A prospective cohort of 212 patients with COPD was monitored using daily symptom diaries for a median of 2.8 years to characterise the time course of COPD exacerbation onset. Decision rules based on weighted self-reported symptoms were used to define opening and closing of exacerbation events. Event time intervals were analysed and logistic regression was used to determine the effects of patient covariates on exacerbation events. Results Patients recorded 4439 episodes of worsening respiratory symptoms from baseline; 2444 (55%) events resolved spontaneously and 1995 (45%) resulted in a COPD exacerbation. In 1115 of the 1995 COPD exacerbations (56%) the onset was sudden and the exacerbation threshold was crossed on the same day symptoms began. In contrast, 44% of exacerbations were characterised by gradual onset of symptoms (median duration from symptom onset to exacerbation 4 days). Patients who experienced sudden onset exacerbations had greater mean daily symptom scores (7.86 vs 6.55 points, p<0.001), greater peak symptom scores (10.7 vs 10.2 points, p=0.003), earlier peak symptoms (4.5 vs 8.0 days, p<0.001) and shorter median recovery times back to baseline health status (11 vs 13 days, p<0.001). Multivariable analysis showed that gradual onset exacerbations were statistically associated with a longer duration of exacerbation recovery (OR 1.28, 95% CI 1.06 to 1.54, p=0.010). Conclusions COPD exacerbations exhibit two distinct patternsdsudden and gradual onset. Sudden onset exacerbations are associated with increased respiratory symptoms but shorter exacerbation recovery times. INSET: Key messages. [ABSTRACT FROM AUTHOR]

Background: The α(1)-antitrypsin 11478G→A polymorphism may be associated with attenuated acute α(1)-antitrypsin responses. It was hypothesised that patients with chronic obstructive pulmonary disease (COPD) and this mutation have accelerated lung function decline.Objective: To assess whether the 11478G→A polymorphism is associated with attenuated α(1)-antitrypsin responses at COPD exacerbation, and therefore accelerated lung function decline.Methods: Lung function decline by genotype was examined in the English Longitudinal Study of Ageing (ELSA; n=1805) and Whitehall II (n=2733) studies. 204 patients with COPD were genotyped in the London cohort and serum α(1)-antitrypsin concentration was measured at baseline and (n=92) exacerbation.Results: The 11478G→A genotype frequencies did not vary between COPD cases and controls, or between COPD frequent and infrequent exacerbators. Subjects with the rare A allele experienced more rapid lung function decline in the Whitehall II (A vs non-A: 16 vs 4 ml/year p=0.02) but not ELSA (29 vs 34 ml/year, p=0.46) or London cohorts (26 vs 38 ml/year, p=0.06). Decline was not greater in frequent exacerbator A versus non-A carriers (20 vs 24 ml/year, p=0.58). Upregulation of α(1)-antitrypsin at exacerbation was not demonstrated, even in patients homozygous for the common allele (median exacerbation change -0.07 g/l 11478GG, p=0.87 and -0.09 g/l 11478AA/GA, p=0.92; p=0.90 for difference). In patients with the A allele, there was no correlation between serum α(1)-antitrypsin and serum interleukin 6 (IL-6) concentrations.Conclusion: The 11478G→A α(1)-antitrypsin polymorphism is not associated with increased risk of developing COPD, nor accelerated lung function decline. Serum α(1)-antitrypsin may not be upregulated early at COPD exacerbation. In patients with the 11478G→A polymorphism there was no relationship between the serum α(1)-antitrypsin and serum IL-6 concentrations. [ABSTRACT FROM AUTHOR]

The author reflects on the article related to the efficacy of anti-inflammatory and antibiotic for treatment of acute bronchitis, by C.Llor and colleagues, which was published in the 2013 issues of the journal "New England Journal of Medicine." Topics discussed include the role of antibiotics for the treatment of respiratory tract infections, the benefits of non-steroidal anti-inflammatory drugs for treating acute bronchitis and the use of randomised placebo controlled trial for the study.

Background We hypothesised that early life events are not routinely considered by most respiratory specialists. Methods Respiratory Specialists were surveyed via the British Thoracic Society (BTS) on whether they asked patients about birth weight, preterm birth and prenatal and postnatal complications. Results Only a small minority (mostly hospital paediatricians) of the 123 who replied asked most respiratory patients about one of more early life factors. Patient recall of the information when asked was low. Conclusions The survey results suggest little current consideration is given to early life factors in adult respiratory medicine, despite increasing evidence that early life factors do impact on later respiratory health. Improving training, increasing awareness and exploring new approaches to obtaining the information are required. [ABSTRACT FROM AUTHOR]