Stuart Schembri

Predictors of Mortality in Hospitalized Adults with Acute Exacerbation of Chronic Obstructive Pulmonary Disease. A Systematic Review and Meta-analysis

RATIONALE There is a need to identify clinically meaningful predictors of mortality following hospitalized COPD exacerbation. OBJECTIVES The aim of this study was to systematically review the literature to identify clinically important factors that predict mortality after hospitalization for acute exacerbation of chronic obstructive pulmonary disease (COPD). METHODS Eligible studies considered adults admitted to hospital with COPD exacerbation. Two authors independently abstracted data. Odds ratios were then calculated by comparing the prevalence of each predictor in survivors versus nonsurvivors. For continuous variables, mean differences were pooled by the inverse of their variance, using a random effects model. MEASUREMENTS AND MAIN RESULTS There were 37 studies included (189,772 study subjects) with risk of death ranging from 3.6% for studies considering short-term mortality, 31.0% for long-term mortality (up to 2 yr after hospitalization), and 29.0% for studies that considered solely intensive care unit (ICU)-admitted study subjects. Twelve prognostic factors (age, male sex, low body mass index, cardiac failure, chronic renal failure, confusion, long-term oxygen therapy, lower limb edema, Global Initiative for Chronic Lung Disease criteria stage 4, cor pulmonale, acidemia, and elevated plasma troponin level) were significantly associated with increased short-term mortality. Nine prognostic factors (age, low body mass index, cardiac failure, diabetes mellitus, ischemic heart disease, malignancy, FEV1, long-term oxygen therapy, and PaO2 on admission) were significantly associated with long-term mortality. Three factors (age, low Glasgow Coma Scale score, and pH) were significantly associated with increased risk of mortality in ICU-admitted study subjects. CONCLUSION Different factors correlate with mortality from COPD exacerbation in the short term, long term, and after ICU admission. These parameters may be useful to develop tools for prediction of outcome in clinical practice.

Cardiovascular events after clarithromycin use in lower respiratory tract infections: analysis of two prospective cohort studies

Objective To study the association of clarithromycin with cardiovascular events in the setting of acute exacerbations of chronic obstructive pulmonary disease and community acquired pneumonia. Design Analysis of two prospectively collected datasets. Setting Chronic obstructive pulmonary disease dataset including patients admitted to one of 12 hospitals around the United Kingdom between 2009 and 2011; Edinburgh pneumonia study cohort including patients admitted to NHS Lothian Hospitals between 2005 and 2009. Population 1343 patients admitted to hospital with acute exacerbations of chronic obstructive pulmonary disease and 1631 patients admitted with community acquired pneumonia. Main outcome measures Hazard ratios for cardiovascular events at one year (defined as hospital admissions with acute coronary syndrome, decompensated cardiac failure, serious arrhythmia, or sudden cardiac death) and admissions for acute coronary syndrome (acute ST elevation myocardial infarction, non-ST elevation myocardial infarction, and unstable angina). Secondary outcomes were all cause and cardiovascular mortality at one year. Results 268 cardiovascular events occurred in the acute exacerbations of chronic obstructive pulmonary disease cohort and 171 in the community acquired pneumonia cohort over one year. After multivariable adjustment, clarithromycin use in acute exacerbations of chronic obstructive pulmonary disease was associated with an increased risk of cardiovascular events and acute coronary syndrome—hazard ratios 1.50 (95% confidence interval 1.13 to 1.97) and 1.67 (1.04 to 2.68). After multivariable adjustment, clarithromycin use in community acquired pneumonia was associated with increased risk of cardiovascular events (hazard ratio 1.68, 1.18 to 2.38) but not acute coronary syndrome (1.65, 0.97 to 2.80). The association between clarithromycin use and cardiovascular events persisted after matching for the propensity to receive clarithromycin. A significant association was found between clarithromycin use and cardiovascular mortality (adjusted hazard ratio 1.52, 1.02 to 2.26) but not all cause mortality (1.16, 0.90 to 1.51) in acute exacerbations of chronic obstructive pulmonary disease. No association was found between clarithromycin use in community acquired pneumonia and all cause mortality or cardiovascular mortality. Longer durations of clarithromycin use were associated with more cardiovascular events. Use of β lactam antibiotics or doxycycline was not associated with increased cardiovascular events in patients with acute exacerbations of chronic obstructive pulmonary disease, suggesting an effect specific to clarithromycin. Conclusions The use of clarithromycin in the setting of acute exacerbations of chronic obstructive pulmonary disease or community acquired pneumonia may be associated with increased cardiovascular events. These findings require confirmation in other datasets.

Influenza but not pneumococcal vaccination protects against all-cause mortality in patients with COPD.

Background: Influenza and pneumococcal vaccination are recommended in patients with chronic obstructive pulmonary disease (COPD). A recent study from Tayside found a reduced risk of all-cause mortality with vaccination in patients with COPD. The Health Improvement Network (THIN) database was used to test this hypothesis in a different data source. Methods: The THIN database was searched for patients with COPD. Vaccination status against Pneumococcus and the annual influenza vaccination status were determined. Mortality rates were calculated in the periods December to March and April to November. Relative risks for the effect of vaccination on all-cause mortality were estimated by Poisson regression, adjusting for age, sex, year and serious co-morbidities. Results: 177 120 patients with COPD (mean age 65 years) were identified, with a mean follow-up of 6.8 years between 1988 and 2006. Vaccination rates against influenza rose from <30% before 1995 to >70% in 2005 in patients aged 60 years or more. The cumulative vaccination rate against pneumonia rose from almost zero to 70% in patients aged 70 years or more over the same period. For all-cause mortality the adjusted relative risks associated with influenza vaccination were 0.59 (95% CI 0.57 to 0.61) during the influenza season and 0.97 (95% CI 0.94 to 1.00) outside the season in patients not vaccinated against pneumonia, and 0.30 (95% CI 0.28 to 0.32) and 0.98 (95% CI 0.96 to 1.11), respectively, in patients vaccinated against pneumonia. The relative risk associated with pneumococcal vaccination was >1 at all times of the year. Conclusions: Influenza but not pneumococcal vaccination was associated with a reduced risk of all-cause mortality in COPD.

A predictive model of hospitalisation and death from chronic obstructive pulmonary disease.

RATIONALE A recent study showed that doctors are excessively pessimistic about the prognosis in patients with COPD and suggested that a simple tool to predict outcome is needed. METHODS In a prospective observational study, 3343 patients with an FEV1<80% of the predicted value and FEV1/FVC<70% were selected from a clinical network of patients screened for COPD in Tayside, Scotland. Data were collected during annual visits on demography, spirometry, smoking history, medical research council (MRC) dyspnoea scale, body mass index (BMI) and other variables. The main outcome measures were hospitalisations and death secondary to COPD. A proportional hazard model was used to identify significant risk factors. RESULTS Increasing age, low BMI, worsening MRC dyspnoea score, decreased FEV1, and prior respiratory or cardiovascular admission hospitalisation were predictors of poor outcome. Influenza vaccination was protective. CONCLUSION We have developed a model that estimates the risk of respiratory hospitalisation and death in patients with COPD.

Thrombocytosis is associated with increased short and long term mortality after exacerbation of chronic obstructive pulmonary disease: a role for antiplatelet therapy?

Introduction Evidence suggests that platelets play a significant role in inflammation in addition to their role in thrombosis. Systemic inflammation is linked to poor short and long term outcomes in COPD. Increased platelet activation has been reported in acute exacerbations of COPD (AECOPD). We investigated whether thrombocytosis is independently associated with poor outcomes following AECOPD. Methods An observational cohort study of patients hospitalised with AECOPD was performed. Patients were >40 years with spirometry confirmed COPD admitted between 2009 and 2011. Platelet count was recorded on admission. The primary outcome was 1-year all-cause mortality. Secondary outcomes included inhospital mortality and cardiovascular events. Analyses were conducted using logistic regression after adjustment for confounding variables. Results 1343 patients (49% male) were included. Median age was 72 years (IQR 63–79 years). 157 (11.7%) had thrombocytosis. Thrombocytosis was associated with both 1-year mortality and inhospital mortality; OR 1.53 (95% CI 1.03 to 2.29, p=0.030) and OR 2.37 (95% CI 1.29 to 4.34, p=0.005), respectively. Cardiovascular hospitalisation was not significantly increased (OR 1.13 (95% CI 0.73 to 1.76, p=0.600)) in patients with thrombocytosis. Aspirin or clopidogrel treatment correlated with a reduction in 1-year mortality (OR 0.63 (95% CI 0.47 to 0.85, p=0.003)) but not inhospital mortality (OR 0.69 (95% CI 0.41 to 1.11, p=0.124)). Conclusions After adjustment for confounders thrombocytosis was associated with increased 1-year mortality after exacerbation of COPD. Antiplatelet therapy was associated with significantly lower 1-year mortality and may have a protective role to play in patients with AECOPD.

Effects of chlorine and exercise on the unified airway in adolescent elite Scottish swimmers

To cite this article: Clearie KL, Vaidyanathan S, Williamson PA, Goudie A, Short P, Schembri S, Lipworth BJ. Effects of chlorine and exercise on the unified airway in adolescent elite Scottish swimmers.

A multidisciplinary intervention to reduce antibiotic duration in lower respiratory tract infections

OBJECTIVES Prolonged antibiotic courses are common in patients with lower respiratory tract infections (LRTIs) and contribute to antibiotic resistance and side effects. This study describes a multidisciplinary intervention to reduce antibiotic duration in LRTI patients. METHODS This was a prospective before-and-after intervention study conducted from November 2011 to December 2012. Antibiotic duration was recorded for 6 months for all LRTI admissions (pneumonia, exacerbation of chronic obstructive pulmonary disease, exacerbation of asthma, and other LRTIs), followed by the introduction of an intervention intended to reduce the duration of antibiotic treatment. The intervention incorporated an antibiotic duration based on the CURB65 score, automatic stop dates and pharmacist feedback to prescribers. RESULTS Two hundred and eighty-one patients were included in the pre-intervention group and 221 in the post-intervention group. The intervention resulted in a reduction in the duration of antibiotic treatment from 8.3 to 6.8 days (P < 0.001, 18.1% relative reduction). The rate of antibiotic-related adverse effects reduced from 31% to 19% (P = 0.03, 39.3% relative reduction). There was no increase in mortality or length of stay CONCLUSIONS A simple intervention can significantly reduce antibiotic duration and antibiotic-related side effects.

Simplification of the IDSA/ATS criteria for severe CAP using meta-analysis and observational data

The 2007 Infectious Diseases Society of America (IDSA)/American Thoracic Society (ATS) guidelines proposed “minor” criteria to predict intensive care unit (ICU) admission in patients with community-acquired pneumonia. These criteria were based on expert opinion. Consequently, the authors of the guidelines asked investigators to determine whether the score could be simplified by excluding noncontributory variables. Each IDSA/ATS minor criterion was validated using a random effects meta-analysis of seven studies. Variables present in <5% of cases or that were nonsignificantly associated with mortality/ICU admission were excluded. A simplified score excluding these variables was tested for prediction of mortality and ICU admission in an established database. Prediction was assessed using the area under the receiver operator characteristic curve (AUC). Leukopenia (<4000 cells·mm−3), thrombocytopenia (<100 000 cells·mm−3) and hypothermia <36°C occurred in <5% of cases. A simplified score excluding these variables was performed similarly for prediction of mortality, AUC 0.77 (95% CI 0.73–0.81) versus 0.78 (95% CI 0.74–0.82) (p=0.9) and intensive care unit admission, AUC 0.85 (95% CI 0.82–0.87) versus 0.85 (95% CI 0.82–0.88) (p=0.9). Additional predictors suggested by the IDSA/ATS were associated with mortality and ICU admission, but only incorporating acidosis (pH <7.35) altered the AUC (0.82 (95% CI 0.78–0.86) (p=0.6) for mortality and 0.86 (95% CI 0.82–0.88) (p=0.8) for ICU admission). No improvements were statistically significant. The IDSA/ATS criteria can be simplified by removing three infrequent variables. The IDSA/ATS criteria can be simplified by removing three infrequent variables http://ow.ly/s1dA1

Effect of Statins on Total Cholesterol Concentrations, Cardiovascular Morbidity, and All-Cause Mortality in Chronic Obstructive Pulmonary Disease: A Population-Based Cohort Study

BACKGROUND The benefit of statin use on total cholesterol (TC) concentration has not been studied previously in patients with chronic obstructive pulmonary disease (COPD). OBJECTIVE Our study aimed to evaluate statin-associated TC-concentration reduction and subsequent risk for cardiovascular (CV) morbidity and mortality in COPD. METHODS We performed a population-based cohort study using a record-linkage database in Tayside, Scotland. A total of 1017 COPD patients who had at least 2 separate TC measurements between 1993 and 2007 were studied. They were categorized into statin-exposed and statin-unexposed groups according to their statin use status during follow-up. Main outcomes were TC-concentration change from baseline, CV events, and all-cause mortality during follow-up. Multivariate Cox regression models with a time-dependent variable for statins were used to assess risk for outcomes. RESULTS Statin-associated TC concentrations decreased by 0.86 mmol/L (16%) in patients treated for primary prevention (PP) (n = 1274) and 0.52 mmol/L (11%) in patients treated for secondary prevention (SP) (n = 443), from 5.30 mmol/L and 4.68 mmol/L at baseline, respectively. TC concentrations also declined by 2% in patients free from established CV disease and by 5% in patients with established CV disease in the statin-unexposed groups. A risk reduction of recurrent CV events with statins was observed (adjusted hazard ratio [HR] = 0.35; 95% CI, 0.15-0.87), but not for PP (adjusted HR = 0.84; 95% CI, 0.37-1.89). Statins reduced CV mortality (adjusted HR = 0.32; 95% CI, 0.13-0.77) in SP but not PP. There were statistically significant reductions in all-cause mortality in both PP (adjusted HR = 0.61; 95% CI, 0.43-0.85) and SP (adjusted HR = 0.58; 95% CI, 0.35-0.97). CONCLUSIONS In patients with COPD, statins were protective from CV events and CV mortality in SP but not PP, and statins improved all-cause mortality in both PP and SP.

Neutrophil extracellular traps are associated with disease severity and microbiota diversity in patients with chronic obstructive pulmonary disease

&NA; Figure. No caption available. Background: Neutrophil extracellular traps (NETs) have been observed in the airway in patients with chronic obstructive pulmonary disease (COPD), but their clinical and pathophysiologic implications have not been defined. Objective: We sought to determine whether NETs are associated with disease severity in patients with COPD and how they are associated with microbiota composition and airway neutrophil function. Methods: NET protein complexes (DNA‐elastase and histone‐elastase complexes), cell‐free DNA, and neutrophil biomarkers were quantified in soluble sputum and serum from patients with COPD during periods of disease stability and during exacerbations and compared with clinical measures of disease severity and the sputum microbiome. Peripheral blood and airway neutrophil function were evaluated by means of flow cytometry ex vivo and experimentally after stimulation of NET formation. Results: Sputum NET complexes were associated with the severity of COPD evaluated by using the composite Global Initiative for Obstructive Lung Disease scale (P < .0001). This relationship was due to modest correlations between NET complexes and FEV1, symptoms evaluated by using the COPD assessment test, and higher levels of NET complexes in patients with frequent exacerbations (P = .002). Microbiota composition was heterogeneous, but there was a correlation between NET complexes and both microbiota diversity (P = .009) and dominance of Haemophilus species operational taxonomic units (P = .01). Ex vivo airway neutrophil phagocytosis of bacteria was reduced in patients with increased sputum NET complexes. Consistent results were observed regardless of the method of quantifying sputum NETs. Failure of phagocytosis could be induced experimentally by incubating healthy control neutrophils with soluble sputum from patients with COPD. Conclusion: NET formation is increased in patients with severe COPD and associated with more frequent exacerbations and a loss of microbiota diversity.