Admission blood eosinophil count, inpatient death and death at 1 year in exacerbating patients with COPD.

BACKGROUND: Blood eosinophil counts have been studied in patients with stable chronic obstructive pulmonary disease (COPD) and are a useful biomarker to guide inhaled corticosteroid use. Less is known about eosinophil counts during severe exacerbation. METHODS: In this retrospective study, 2645 patients admitted consecutively with COPD exacerbation across six UK hospitals were included in the study, and the clinical diagnosis was confirmed by a respiratory specialist. The relationship between admission eosinophil count, inpatient death and 1-year death was assessed. In a backward elimination, Poisson regression analysis using the log-link function with robust estimates, patients' markers of acute illness and stable-state characteristics were assessed in terms of their association with eosinopenia. RESULTS: 1369 of 2645 (52%) patients had eosinopenia at admission. Those with eosinopenia had a 2.5-fold increased risk of inpatient death compared with those without eosinopenia (12.1% vs 4.9%, RR=2.50, 95% CI 1.88 to 3.31, p<0.001). The same mortality risk with eosinopenia was seen among the subgroup with pneumonic exacerbation (n=788, 21.3% vs 8.5%, RR=2.5, 95% CI 1.67 to 2.24, p<0.001). In a regression analysis, eosinopenia was significantly associated with: older age and male sex; a higher pulse rate, temperature, neutrophil count, urea and C reactive protein level; a higher proportion of patients with chest X-ray consolidation and a reduced Glasgow Coma Score; and lower systolic and diastolic blood pressure measurements and lower oxygen saturation, albumin, platelet and previous admission counts. DISCUSSION: During severe COPD exacerbation, eosinopenia is common and associated with inpatient death and several markers of acute illness. Clinicians should be cautious about using eosinophil results obtained during severe exacerbation to guide treatment decisions regarding inhaled corticosteroid use.

Impact of COVID-19 on Hospital Admissions for COPD Exacerbation: Lessons for Future Care.

Background and Objectives: Chronic obstructive pulmonary disease (COPD) is a leading cause of death worldwide. Acute exacerbations (AECOPD) are common and often triggered by viral infection. During the COVID-19 pandemic social restrictions, including 'shielding' and 'lockdowns', were mandated. Multiple, worldwide studies report a reduction in AECOPD admissions during this period. This study aims to assess the effect of the pandemic and Lockdown on the rates of admission with AECOPD and severity of hospitalised exacerbations in the North-East of England. Materials and Methods: Data were extracted for patients presenting with a diagnosis of AECOPD or respiratory failure secondary to AECOPD during the 'COVID-19 period' (26/3/20-31/12/20) and a date-matched control period from the year previous. We present descriptive statistics and regression analysis of the effects of the COVID-19 period on the rates of hospital admission. Results: Compared to the matched control period, the COVID-19 period was associated with fewer AECOPD admissions (COVID-19 = 719, control = 1257; rate ratio 0.57, p < 0.001) and shorter length of stay (COVID-19 = 3.9 ± 0.2, control = 4.78 ± 0.2 days; p = 0.002), with similar in-hospital plus 30-day post-discharge mortality. Demographics were similar between periods. Only six patients had a positive COVID-19 PCR test. Conclusion: During the COVID-19 period there was a substantial reduction in AECOPD admissions, but no increase in overall severity of exacerbations or mortality. Rather than fear driving delayed hospital presentation, physical and behavioural measures taken during this period to limit transmission of COVID-19 are likely to have reduced transmission of other respiratory viruses. This has important implications for control of future AECOPD.

Clinical and molecular characterization of the R751L-CFTR mutation.

Cystic fibrosis (CF) arises from mutations in the CF transmembrane conductance regulator (CFTR) gene, resulting in progressive and life-limiting respiratory disease. R751L is a rare CFTR mutation that is poorly characterized. Our aims were to describe the clinical and molecular phenotypes associated with R751L. Relevant clinical data were collected from three heterozygote individuals harboring R751L (2 patients with G551D/R751L and 1 with F508del/R751L). Assessment of R751L-CFTR function was made in primary human bronchial epithelial cultures (HBEs) and Xenopus oocytes. Molecular properties of R751L-CFTR were investigated in the presence of known CFTR modulators. Although sweat chloride was elevated in all three patients, the clinical phenotype associated with R751L was mild. Chloride secretion in F508del/R751L HBEs was reduced compared with non-CF HBEs and associated with a reduction in sodium absorption by the epithelial sodium channel (ENaC). However, R751L-CFTR function in Xenopus oocytes, together with folding and cell surface transport of R751L-CFTR, was not different from wild-type CFTR. Overall, R751L-CFTR was associated with reduced sodium chloride absorption but had functional properties similar to wild-type CFTR. This is the first report of R751L-CFTR that combines clinical phenotype with characterization of functional and biological properties of the mutant channel. Our work will build upon existing knowledge of mutations within this region of CFTR and, importantly, inform approaches for clinical management. Elevated sweat chloride and reduced chloride secretion in HBEs may be due to alternative non-CFTR factors, which require further investigation.

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.

Oxygen therapy and inpatient mortality in COPD exacerbation.

BACKGROUND: In hospitalised patients with exacerbation of Chronic Obstructive Pulmonary Disease, European and British guidelines endorse oxygen target saturations of 88%-92%, with adjustment to 94%-98% if carbon dioxide levels are normal. We assessed the impact of admission oxygen saturation level and baseline carbon dioxide on inpatient mortality. METHODS: Patients were identified from the prospective Dyspnoea, Eosinopenia, Consolidation, Acidaemia and Atrial Fibrillation (DECAF) derivation study (December 2008-June 2010) and the mixed methods DECAF validation study (January 2012 to May 2014). In six UK hospitals, of 2645 patients with COPD exacerbation, 1027 patients were in receipt of supplemental oxygen at admission. All had a clinical history of COPD and obstructive spirometry. These patients were subdivided into the following groups: admission oxygen saturations of 87% or less, 88%-92%, 93%-96% or 97%-100%. Inpatient mortality was calculated for each group and expressed as ORs. The DECAF score and National Early Warning Score 2 (excluding oxygen saturation) were used in binary logistic regression to adjust for baseline risk. RESULTS: In patients with COPD receiving supplemental oxygen, oxygen saturations above 92% were associated with higher mortality and an adverse dose-response. Compared with the 88%-92% group, the adjusted risk of death (OR) in the 93%-96% and 97%-100% groups was 1.98 (95% CI 1.09 to 3.60, p=0.025) and 2.97 (95% CI 1.58 to 5.58, p=0.001). In the subgroup with normocapnia, the mortality signal remained significant in both the 93%-96% and 97%-100% groups. CONCLUSIONS: Inpatient mortality was lowest in those with oxygen saturations of 88%-92%. Even modest elevations in oxygen saturations above this range (93%-96%) were associated with an increased risk of death. A similar mortality trend was seen in both patients with hypercapnia and normocapnia. This shows that the practice of setting different target saturations based on carbon dioxide levels is not justified. Treating all patients with COPD with target saturations of 88%-92% will simplify prescribing and should improve outcome. TRIAL REGISTRATION NUMBER: UKCRN ID 14214.

Uptake of Clinical Prognostic Tools in COPD Exacerbations Requiring Hospitalisation.

Clinical prognostic tools are used to objectively predict outcomes in many fields of medicine. Whilst over 400 have been developed for use in chronic obstructive pulmonary disease (COPD), only a minority have undergone full external validation and just one, the DECAF score, has undergone an implementation study supporting use in clinical practice. Little is known about how such tools are used in the UK. We distributed surveys at two time points, in 2017 and 2019, to hospitals included in the Royal College of Physicians of London national COPD secondary care audit program. The survey assessed the use of prognostic tools in routine care of hospitalized COPD patients. Hospital response rates were 71/196 in 2017 and 72/196 in 2019. The use of the DECAF and PEARL scores more than doubled in decisions about unsupported discharge (7%-15.3%), admission avoidance (8.1%-17%) and readmission avoidance (4.8%-13.1%); it more than tripled (8.8%-27.8%) in decisions around hospital-at-home or early supported discharge schemes. In other areas, routine use of clinical prognostic tools was uncommon. In palliative care decisions, the use of the Gold Standards Framework Prognostic Indicator Guidance fell (5.6%-1.4%). In 2017, 43.7% of hospitals used at least one clinical prognostic tool in routine COPD care, increasing to 52.1% in 2019. Such tools can help challenge prognostic pessimism and improve care. To integrate these further into routine clinical care, future research should explore current barriers to their use and focus on implementation studies.Supplemental data for this article is available online at https://dx.doi.org/10.1080/15412555.2021.1959540.

Krebs von den Lungen-6 (KL-6) is a pathophysiological biomarker of early-stage acute hypersensitivity pneumonitis among pigeon fanciers.

BACKGROUND: Identifying early stages of hypersensitivity pneumonitis (HP) is hampered by variable presentation, heterogeneous or undetected causal antigens and lack of gold-standard biomarkers. Krebs von den Lungen (KL)-6 is pathophysiological biomarker of alveolar epithelial damage. Pigeon fanciers, susceptible to HP, provide a model to investigate early HP. OBJECTIVE: To test the hypothesis that plasma concentrations of KL-6 are increased in early-stage acute HP. METHODS: Clinical history, spirometry and blood samples were obtained from pigeon fanciers, 20 with intermittent acute symptoms indicative of developing HP, 27 with no symptoms and 10 healthy subjects with no avian exposure. Plasma KL-6 (units/mL) and pigeon antigen-specific IgG antibody were quantified by enzyme immunoassay. Blood lymphocytes were quantified by flow cytometry and antigen specificity by in vitro cytokine production. RESULTS: KL-6 was higher in fanciers than controls, median (IQR) 452 (244, 632) vs 274 (151, 377), P = .01. Although fanciers with symptoms had similar antigen exposure and lung function, they had higher KL-6 than those without, 632 (468, 1314) vs 320 (200, 480), P < .001. KL-6 correlated with IgG antibody titre in those with symptoms, r = .591, P = .006. High KL-6, irrespective of symptom category, was associated with higher antibody (P = .006) and lymphocyte proliferation (P = .041), and lower CD4+ T lymphocyte proportion (P = .032). CONCLUSION AND CLINICAL RELEVANCE: Raised KL-6 is associated with acute symptoms of early-stage HP, and its correlation with antibody may support therapeutic strategies when HP is suspected. KL-6 may act as a mechanistic biomarker of early pathogenesis by linking lung pathophysiological changes with an endotype of immune hypersensitivity.

Predictors of NIV Treatment in Patients with COPD Exacerbation Complicated by Respiratory Acidaemia.

Non-invasive ventilation (NIV) treatment decisions are poorly understood for patients with COPD exacerbation complicated by acute hypercapnic respiratory failure and respiratory acidaemia (ECOPD-RA). We identified 420 NIV-eligible patients from the DECAF study cohorts admitted with an ECOPD-RA. Using bivariate and multivariate analyses, we examined which indices were associated with clinicians' decisions to start NIV, including whether the presence of pneumonia was a deterrent. Admitting hospital, admission from institutional care, partial pressure of oxygen, cerebrovascular disease, pH, systolic blood pressure and white cell count were all associated with the provision of NIV. Of these indices, only pH was also a predictor of inpatient death. Those not treated with NIV included those with milder acidaemia and higher (and sometimes excessive) oxygen levels, and a frailer population with higher Extended Medical Research Council Dyspnoea scores, presumably deemed not suitable for NIV. Pneumonia was not associated with NIV treatment; 34 of 111 (30.6%) NIV-untreated patients had pneumonia, whilst 107 of 309 (34.6%) NIV-treated patients had pneumonia (p = 0.483). In our study, one in four NIV-eligible patients were not treated with NIV. Clinicians' NIV treatment decisions are not based on those indices most strongly associated with mortality risk. One of the strongest predictors of whether a patient received a life-saving treatment is which hospital they attended. Further research is required to aid in the risk stratification of this patient group which may help standardise and improve care.

Comparison of early warning scores in patients with COPD exacerbation: DECAF and NEWS score.

BACKGROUND: The National Early Warning Score 2 (NEWS2) includes two oxygen saturation scales; the second adjusts target saturations to 88%-92% for those with hypercapnic respiratory failure. Using this second scale in all patients with COPD exacerbation ('NEWS2All COPD') would simplify practice, but the impact on alert frequency and prognostic performance is unknown. Admission NEWS2 score has not been compared with DECAF (dyspnoea, eosinopenia, consolidation, acidaemia, atrial fibrillation) for inpatient mortality prediction. METHODS: NEWS, NEWS2 and NEWS2All COPD and DECAF were calculated at admission in 2645 patients with COPD exacerbation attending consecutively to one of six UK hospitals, all of whom met spirometry criteria for COPD. Alert frequency and appropriateness were assessed for all NEWS iterations. Prognostic performance was compared using the area under the receiver operating characteristic (AUROC) curve. Missing data were imputed using multiple imputation. FINDINGS: Compared with NEWS, NEWS2 reclassified 3.1% patients as not requiring review by a senior clinician (score≥5). NEWS2All COPD reduced alerts by 12.6%, or 16.1% if scoring for injudicious use of oxygen was exempted. Mortality was low in reclassified patients, with no patients dying the same day as being identified as low risk. NEWS2All COPD was a better prognostic score than NEWS (AUROC 0.72 vs 0.65, p<0.001), with similar performance to NEWS2 (AUROC 0.72 vs 0.70, p=0.090). DECAF was superior to all scores (validation cohort AUROC 0.82) and offered a more clinically useful range of risk stratification (DECAF=1.2%-25.5%; NEWS2=3.5%-15.4%). CONCLUSION: NEWS2All COPD safely reduces the alert frequency compared with NEWS2. DECAF offers superior prognostic performance to guide clinical decision-making on admission, but does not replace repeated measures of NEWS2 during hospitalisation to detect the deteriorating patient.

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.

A service evaluation of an integrated model of palliative care of cystic fibrosis.

BACKGROUND: Patients with advanced cystic fibrosis have severe symptoms with a complex trajectory of exacerbations and recovery. They are often awaiting lung transplantation, and many die without receiving specialist palliative care. AIM: We introduced an integrated model whereby palliative specialists joined the cystic fibrosis team to provide palliative care in parallel with standard care. DESIGN: A service evaluation of this model of care was undertaken in a prospective case series documenting symptoms and outcomes, the views of the cystic fibrosis team and the experience of the palliative specialists. SETTING/PARTICIPANTS: Over 3 years, 28 (10%) of 282 patients attending the cystic fibrosis centre had specialist palliative care. RESULTS: They had advanced lung disease (mean forced expiratory volume in 1 s (FEV1) = 0.86 L (25% predicted)), and 17 died: 6 were on a transplant waiting list at death; 10 were unsuitable and 1 died post transplantation. All who died over these 3 years had specialist palliative care. Four patients had successful transplants. Assessment showed a high prevalence of breathlessness, cough, pain, vomiting and fatigue, with a significant impact on daily life. The cystic fibrosis team rated this model of care highly, felt that palliative care should be members of the team, and thought that patients had found it helpful. The palliative specialists gained knowledge of cystic fibrosis, found it beneficial to meet patients earlier in the disease, and identified unmet needs in managing bereavement and the effects of deaths on other patients with cystic fibrosis. CONCLUSION: This model has been successful in overcoming the difficulties in access to specialist palliative care for patients with cystic fibrosis.

Early Supported Discharge/Hospital At Home For Acute Exacerbation of Chronic Obstructive Pulmonary Disease: A Review and Meta-Analysis.

A systematic review and meta-analysis was performed to assess the safety, efficacy and cost of Early Supported Discharge (ESD) and Hospital at Home (HAH) compared to Usual Care (UC) for patients with acute exacerbation of COPD (AECOPD). The structure of ESD/HAH schemes was reviewed, and analyses performed assuming return to hospital during the acute period (prior to discharge from home treatment) was, and was not, considered a readmission. The pre-defined search strategy completed in November 2014 included electronic databases (Medline, Embase, Amed, BNI, Cinahl and HMIC), libraries, current trials registers, national organisations, key respiratory journals, key author contact and grey literature. Randomised controlled trials (RCTs) comparing ESD/HAH to UC in patients admitted with AECOPD, or attending the emergency department and triaged for admission, were included. Outcome measures were mortality, all-cause readmissions to 6 months and cost. Eight RCTs were identified; seven reported mortality and readmissions. The structure of ESD/HAH schemes, particularly selection criteria applied and level of support provided, varied considerably. Compared to UC, ESD/HAH showed a trend towards lower mortality (RRMH = 0.66; 95% CI 0.40-1.09, p = 0.10). If return to hospital during the acute period was not considered a readmission, ESD/HAH was associated with fewer readmissions (RRMH = 0.74, 95% CI: 0.60-0.90, p = 0.003), but if considered a readmission, the benefit was lost (RRMH = 0.84; 95% CI 0.69-1.01, p = 0.07). Costs were lower for ESD/HAH than UC. ESD/HAH is safe in selected patients with an AECOPD. Further research is required to define optimal criteria to guide patient selection and models of care.

Recommendations for surveillance of pulmonary dysfunction among childhood, adolescent, and young adult cancer survivors: a report from the International Late Effects of Childhood Cancer Guideline Harmonization Group.

Childhood, adolescent, and young adult (CAYA) cancer survivors are at risk of pulmonary dysfunction. Current follow-up care guidelines are discordant. Therefore, the International Late Effects of Childhood Cancer Guideline Harmonization Group established and convened a panel of 33 experts to develop evidence-based surveillance guidelines. We critically reviewed available evidence regarding risk factors for pulmonary dysfunction, types of pulmonary function testing, and timings of surveillance, then we formulated our recommendations. We recommend that CAYA cancer survivors and healthcare providers are aware of reduced pulmonary function risks and pay vigilant attention to potential symptoms of pulmonary dysfunction, especially among survivors treated with allogeneic haematopoietic stem cell transplantation, thoracic radiotherapy, and thoracic surgery. Based on existing limited evidence and current lack of interventions, our panel recommends pulmonary function testing only for symptomatic survivors. Since scarce existing evidence informs our recommendation, we highlight the need for prospective collaborative studies to address pulmonary function knowledge gaps among CAYA cancer survivors.

Global mortality and readmission rates following COPD exacerbation-related hospitalisation: a meta-analysis of 65 945 individual patients.

Background: Exacerbations of COPD (ECOPD) have a major impact on patients and healthcare systems across the world. Precise estimates of the global burden of ECOPD on mortality and hospital readmission are needed to inform policy makers and aid preventive strategies to mitigate this burden. The aims of the present study were to explore global in-hospital mortality, post-discharge mortality and hospital readmission rates after ECOPD-related hospitalisation using an individual patient data meta-analysis (IPDMA) design. Methods: A systematic review was performed identifying studies that reported in-hospital mortality, post-discharge mortality and hospital readmission rates following ECOPD-related hospitalisation. Data analyses were conducted using a one-stage random-effects meta-analysis model. This study was conducted and reported in accordance with the PRISMA-IPD statement. Results: Data of 65 945 individual patients with COPD were analysed. The pooled in-hospital mortality rate was 6.2%, pooled 30-, 90- and 365-day post-discharge mortality rates were 1.8%, 5.5% and 10.9%, respectively, and pooled 30-, 90- and 365-day hospital readmission rates were 7.1%, 12.6% and 32.1%, respectively, with noticeable variability between studies and countries. Strongest predictors of mortality and hospital readmission included noninvasive mechanical ventilation and a history of two or more ECOPD-related hospitalisations <12 months prior to the index event. Conclusions: This IPDMA stresses the poor outcomes and high heterogeneity of ECOPD-related hospitalisation across the world. Whilst global standardisation of the management and follow-up of ECOPD-related hospitalisation should be at the heart of future implementation research, policy makers should focus on reimbursing evidence-based therapies that decrease (recurrent) ECOPD.

Determining the influence of environmental and patient specific factors on the polymicrobial communities of the cystic fibrosis airway.

The aim of this study was to investigate the polymicrobial communities in an adult Cystic Fibrosis population stratified by gender and the most common CFTR mutation, F508del. In this pilot study, DNA was extracted from sputum samples of 29 adult patients (16 male: 13 female) with an F508del mutation in a stable clinical state. Universal primers were used to amplify DNA from bacterial and fungal communities and the resulting fragments were analysed by denaturing gradient gel electrophoresis. Bacterial profiles showed a significant effect of gender (P = 0.046) and P. aeruginosa carriage (P = 0.034) on community structure. Bacterial communities were found to be randomly assembled. Fungal community analysis found that F508del homozygous patients had a greater diversity than heterozygous patients (P = 0.007). This study indicates that the bacterial lung communities of adult CF patients are randomly assembled but have distinct gender based differences. Furthermore, the fungal communities colonising the CF lung are more diverse in F508 homozygotes. This is the first paper to identify a reduced bacterial diversity in female patients with CF and to implicate more severe CFTR genotypes with increased risk of infection with multiple fungal species.