Background: In the assessment of severity in community acquired pneumonia (CAP), the modified British Thoracic Society (mBTS) rule identifies patients with severe pneumonia but not patients who might be suitable for home management. A multicentre study was conducted to derive and validate a practical severity assessment model for stratifying adults hospitalised with CAP into different management groups. Methods: Data from three prospective studies of CAP conducted in the UK, New Zealand, and the Netherlands were combined. A derivation cohort comprising 80% of the data was used to develop the model. Prognostic variables were identified using multiple logistic regression with 30 day mortality as the outcome measure. The final model was tested against the validation cohort. Results: 1068 patients were studied (mean age 64 years, 51.5% male, 30 day mortality 9%). Age >65 years (OR 3.5, 95% CI 1.6 to 8.0) and albumin <30 g/dl (OR 4.7, 95% CI 2.5 to 8.7) were independently associated with mortality over and above the mBTS rule (OR 5.2, 95% CI 2.7 to 10). A six point score, one point for each of Confusion, Urea >7 mmol/l, Respiratory rate >30/min, low systolic(<90 mm Hg) or diastolic (<60 mm Hg) Blood pressure), age >65 years (CURB-65 score) based on information available at initial hospital assessment, enabled patients to be stratified according to increasing risk of mortality: score 0, 0.7%; score 1, 3.2%; score 2, 3%; score 3, 17%; score 4, 41.5% and score 5, 57%. The validation cohort confirmed a similar pattern. Conclusions: A simple six point score based on confusion, urea, respiratory rate, blood pressure, and age can be used to stratify patients with CAP into different management groups.

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Background Retrospective studies suggest that plasma levels of N-terminal pro-brain natriuretic peptide (NT-proBNP) and cardiac troponin T are often elevated in patients with acute exacerbations of chronic obstructive pulmonary disease (COPD) and are associated with increased mortality. These cardiac biomarkers were investigated in an unselected cohort of patients admitted to hospital with exacerbations of COPD. Methods Consecutive patients with physician-diagnosed COPD exacerbation but without clinical evidence of acute cardiac disease admitted to a public hospital over a 1 year period were studied prospectively. NT-proBNP and troponin T were measured on admission. The primary end point was all-cause mortality at 30 days. Results Elevated NT-proBNP (>220 pmol/l) was present in 65/244 patients (27.5%) and significantly predicted 30-day mortality (OR 9.0, 95% CI 3.1 to 26.2, p<0.001). Elevated troponin T (>0.03 mg/l) was found in 40/241 patients (16.6%) and also predicted 30-day mortality (OR 6.3, 95% CI 2.4 to 16.5, p<0.001). These associations persisted after adjusting for other clinical and laboratory predictors of mortality (arterial CO 2 pressure (PaCO 2 ), body mass index and CURB65 score). NT-proBNP and troponin T levels appeared to have additive associations with mortality: 30-day mortality among patients with abnormalities of both NT-proBNP and troponin T was 15-fold higher than among patients with normal values. Conclusion Elevated levels of NT-proBNP and troponin T are strong predictors of early mortality among patients admitted to hospital with acute exacerbations of COPD independently of other known prognostic indicators. The pathophysiological basis for this is unknown, but indicates that cardiac involvement in exacerbations of COPD may be an important determinant of prognosis.

Streptococcus pneumoniae is the most common cause of community-acquired pneumonia but is undoubtedly underdiagnosed. Isolation of S. pneumoniae from blood is specific but lacks sensitivity, while isolation of S. pneumoniae from sputum may represent colonization. We evaluated a new immunochromatographic test (NOW S. pneumoniae urinary antigen test; Binax, Portland, Maine) that is simple to perform and that can detect S. pneumoniae antigen in urine within 15 min. Urine samples from 420 adults with community-acquired pneumonia and 169 control patients who did not have pneumonia were tested. Urine from 315 (75%) of the pneumonia patients and all controls was tested both before and after 25-fold concentration, while the remaining 105 samples were only tested without concentration. S. pneumoniae urinary antigen tests were positive for 120 (29%) patients with pneumonia and for none of the controls. Of the urine samples tested with and without concentration, 96 were positive, of which 6 were positive only after concentration. S. pneumoniae antigen was detected in the urine from 16 of the 20 (80%) patients with blood cultures positive for S. pneumoniae and from 28 of the 54 (52%) patients with sputum cultures positive for S. pneumoniae. The absence of S. pneumoniae antigen in the urine from controls suggests that the specificity is high. Concentration of urine prior to testing resulted in a small increase in yield. The NOW S. pneumoniae urinary antigen test should be a useful adjunct to culture for determining the etiology of community-acquired pneumonia in adults.Streptococcus pneumoniae has consistently been shown to be the most common cause of community-acquired pneumonia (CAP) in both adults and children. S. pneumoniae accounts for about two-thirds of cases where an etiologic diagnosis is made (12) and is likely to be the leading cause of pneumonia of otherwise unknown etiology (19). Despite being the single most important pathogen causing CAP, S. pneumoniae is undoubtedly underdiagnosed due to limitations of conventional diagnostic tests. Isolation of S. pneumoniae from blood lacks sensitivity, isolation of S. pneumoniae from sputum may represent colonization, and lung aspirates are rarely performed. In an effort to improve the diagnostic yield for patients with suspected pneumonia, there has been a considerable interest in alternative techniques, such as PCR and antigen detection.Detection of S. pneumoniae antigens in the urine of patients with pneumonia was first described in 1917 (8). Over the intervening years the detection of S. pneumoniae antigens (usually capsular polysaccharides) in urine has been extensively studied using a variety of techniques, including counterimmunoelectrophoresis, latex agglutination, coagglutination, and enzyme-linked immunosorbent assay (1, 2, 5, 6, 14, 23). To date, the performance of these tests has been variable, such that they have never received general acceptance.Recently, an immunochromatographic test, the NOW S.pneumoniae urinary antigen test (Binax, Inc., Portland, Maine), h...

Evidence before this study: Data sources and searches © 2019. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/ Two investigators searched MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials andWeb of Science using the search strategy described in the online supplement. Searches were conducted from 2000 to 30 th September 2018. No language restrictions were applied. Searches were supplemented with review of reference lists and by reviewing previous meta-analyses and guidelines. Clearly ineligible studies were excluded based on abstract review alone.We identified 266 references and after exclusion of non-relevant studies we identified 3 randomized controlled trials comparing long term treatment with macrolide antibiotics (>3 months duration) compared with placebo where the primary outcome was the reduction of exacerbations. We identified several existing aggregate meta-analyses that suggested that macrolides reduce the frequency of exacerbations of bronchiectasis. Neither the individual trials nor the existing meta-analyses reported on the effectiveness of macrolides in different subpopulations. Identifying which patients benefit from macrolides was identified as a key research priority in bronchiectasis. The current European Respiratory Society guidelines suggest consideration of macrolides for patients without Pseudomonas aeruginosa infection with a history of at least 3 exacerbations in the previous year. Added value of this study:We report the first individual patient data meta-analysis of long term macrolide therapy in bronchiectasis. Our data from 341 patients enrolled in randomized clinical trials in the Netherlands, NewZealand and Australia suggests that macrolide treatment compared to placebo for 6-12 months results in a 50% reduction in the frequency of exacerbations. Additional benefits included prolongation of the time to first exacerbation and statistically significant improvements in quality of life measured by the St Georges Respiratory Questionnaire. Lung function was not significantly improved. Analyses in prespecified subgroups including age, sex, disease severity and baseline microbiology suggested that macrolides effectively reduced exacerbations across all subgroups of patients. Importantly, macrolides had a significant and clinically meaningful impact in patients where macrolide are not currently considered as first line treatment, including patients with P. aeruginosa infection and patients with less than 3 exacerbations per year. Implications of all the available evidence:Our data suggests that macrolide therapy is highly effective in reducing the frequency of exacerbations in bronchiectasis. Given the strong evidence that exacerbations contribute to long term morbidity and mortality in bronchiectasis macrolides should be considered in patients with frequent or severe exacerbations. Current bronchiectasis guidelines recommend inhaled antibiotics as first line treatment for patients with P. aeruginosa...

Background and objective: Vitamin D regulates the production of the antimicrobial peptides cathelicidin and beta-defensin-2, which play an important role in the innate immune response to infection. We hypothesized that vitamin D deficiency would be associated with lower levels of these peptides and worse outcomes in patients admitted to hospital with community acquired pneumonia. Methods: Associations between mortality and serum levels of 25-hydroxyvitamin D, cathelicidin and betadefensin-2 were investigated in a prospective cohort of 112 patients admitted with community acquired pneumonia during winter. Results: Severe 25-hydroxyvitamin D deficiency (<30 nmol/L) was common in this population (15%) and was associated with a higher 30-day mortality compared with patients with sufficient 25-hydroxyvitamin D (>50 nmol/L) (odds ratio 12.7, 95% confidence interval: 2.2-73.3, P = 0.004). These associations were not explained by differences in age, comorbidities, or the severity of the acute illness. Neither cathelicidin nor beta-defensin-2 levels predicted mortality, although there was a trend towards increased mortality with lower cathelicidin (P = 0.053). Neither cathelicidin nor beta-defensin-2 levels correlated with 25-hydroxyvitamin D. Conclusions: 25-hydroxyvitamin D deficiency is associated with increased mortality in patients admitted to hospital with community acquired pneumonia during winter. Contrary to our hypothesis, 25-hydroxyvitamin D levels were not associated with levels of cathelicidin or beta-defensin-2.

This audit documented the general characteristics, assessment, management and outcome of the COPD admissions to a secondary New Zealand hospital. Further investigations into factors contributing to shorter length of stay and predictors of mortality are needed.

A simple 6-point score based on confusion, blood urea, respiratory rate, blood pressure and age can be used to stratify patients with COPD exacerbation into different management groups. The CURB65 score was as effective in predicting early mortality in our cohort of acute COPD exacerbations as it was in previous cohorts with community acquired pneumonia. Our findings suggest that CURB65 scores can help clinicians to assess patients with exacerbation of COPD.