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Introduction: In community-acquired pneumonia, severity assessment tools, such as CRB65, CURB65 and Pneumonia Severity Index (PSI), have been promoted to increase the proportion of patients treated in the community. The prognostic accuracy of these scores is established in hospitalized patients, but less is known about their use in out-patients. We aimed to study the accuracy of these severity tools to predict mortality in patients managed as out-patients.Methods: We performed a systematic review and meta-analysis according to MOOSE guidelines. From 1980 to 2010, we identified 13 studies reporting prognostic information for the CRB65, CURB65 and PSI severity scores in out-patients (either exclusively managed in the community or discharged from an emergency department <24 h after admission). Two reviewers independently collected data and assessed study quality. Performance characteristics across the studies were pooled using a random-effects model. Relationships between sensitivity and specificity were plotted using summary receiver operator characteristic curves (sROC).Results: Out-patient mortality ranged from 0% to 3.5%. Four studies were identified for CRB65, 2 for CURB65 and 10 for PSI. Mortality was low for out-patients in the low-risk CRB65 classes [CRB65 0 or 1: mortality occurred in 3 of 1494 patients (0.2%)] but higher in CRB65 Groups 2–4 [mortality 13 of 154 patients (8.4%)]. Similarly, mortality was low in PSI Classes I–III [mortality 8 of 3655 patients (0.2%)] managed as out-patients but higher in Classes IV and V [mortality 32 of 317 patients (10.1%)]. CRB65 showed pooled sensitivity of 81% (54–96%), pooled specificity of 91% (90–93%) and the area under the sROC was 0.91 [standard error (SE) 0.05]. For PSI, pooled sensitivity was 92% (64–100%), pooled specificity was 90% (89–91%) and area under the sROC was 0.92 (SE 0.03). There were insufficient studies to analyse CURB65.Conclusion: The limited data available suggest that CRB65 and PSI can identify groups of patients at low risk of mortality that can be safely managed in the community. [ABSTRACT FROM AUTHOR]

• CFTR-related disorders (RD) are a group of conditions caused by CFTR protein dysfunction, but to a level of dysfuncton not satisfying the diagnostic crtieria for cystic fibrosis (CF). • This paper discusses the individual disorders, including congenital absence of the vas deferens (CAVD), diffuse bronchiectasis, chronic or acute recurrent pancreatitis, allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling of the palms. • The CFTR functional and genetic evidence in support of each condition being a CFTR-RD are discussed and guidance for reaching the diagnosis is provided. • Gaps in our knowledge and future areas of research, including the role of CFTR modulators, are highlighted. This is the third paper in the series providing updated information and recommendations for people with cystic fibrosis transmembrane conductance regulator (CFTR)-related disorder (CFTR-RD). This paper covers the individual disorders, including the established conditions - congenital absence of the vas deferens (CAVD), diffuse bronchiectasis and chronic or acute recurrent pancreatitis - and also other conditions which might be considered a CFTR-RD, including allergic bronchopulmonary aspergillosis, chronic rhinosinusitis, primary sclerosing cholangitis and aquagenic wrinkling. The CFTR functional and genetic evidence in support of the condition being a CFTR-RD are discussed and guidance for reaching the diagnosis, including alternative conditions to consider and management recommendations, is provided. Gaps in our knowledge, particularly of the emerging conditions, and future areas of research, including the role of CFTR modulators, are highlighted. [ABSTRACT FROM AUTHOR]

Aim: The aim of our study was to determine the effectiveness of contact tracing for both pulmonary and non-pulmonary tuberculosis (TB).Methods: The authors studied contact tracing in South East of Scotland, Edinburgh TB Clinic, UK, for 3 years. New index cases of both pulmonary and non-pulmonary TB were identified from reviewing TB nurses records. Pulmonary involvement was excluded from all non-pulmonary cases. Active TB was diagnosed as per the national TB guidelines. Latent TB was diagnosed based on history, tuberculin skin test and interferon γ release assay. TB contacts were identified from reviewing TB nurses notes on index TB patients.A positive screening episode was defined as identification of either active or latent TB in a contact following relevant investigations.Results: Total number of positive screening episodes for pulmonary TB was 43.1% and non-pulmonary TB was 26.1%. Of these, 78.8% were household contacts and 21.2% were casual contacts.Conclusion: Contact tracing in low-prevalence TB countries, for both pulmonary and non-pulmonary TB, is an essential intervention to identify and reduce the number of infected patients that will progress to active disease. This is the key for effective TB control. [ABSTRACT FROM AUTHOR]

Non-cystic fibrosis bronchiectasis (NCFBE) with Pseudomonas aeruginosa has been associated with increased pulmonary exacerbation (PEx) and mortality risk. European Respiratory Society guidelines conditionally recommend inhaled antimicrobials for persons with NCFBE, P aeruginosa and three or more PEx/year. We report microbiological results of two randomized, 48-week placebo-controlled trials of ARD-3150 (inhaled liposomal ciprofloxacin) in individuals with NCFBE with P aeruginosa and PEx history [Lancet Respir Med 2019;7:213–26]. Respiratory secretions from 582 participants receiving up to six 28-day on/off treatment cycles were analysed for sputum P. aeruginosa , Streptococcus pneumoniae , Haemophilus influenzae , Moraxella catarrhalis , Staphylococcus aureus and Escherichia coli densities, P. aeruginosa susceptibilities to ciprofloxacin and nine other antimicrobials, and prevalence of other bacterial opportunists. Associations between PEx risk and sputum density, antimicrobial susceptibility and opportunist prevalence changes were studied. Sputum P. aeruginosa density reductions from baseline after ARD-3150 treatments ranged from 1.77 (95% CI 2.13–1.40) versus 0.54 (95% CI 0.89–0.19) log 10 CFU/g for placebo (second period) to 2.07 (95% CI 2.45–1.69) versus 0.70 (95% CI 1.11–0.29) log 10 CFU/g for placebo (fourth period) with only modest correlation between density reduction magnitude and PEx benefit. ARD-3150 (but not placebo) treatment was associated with increased P. aeruginosa ciprofloxacin MIC but not emergence of other bacterial opportunists across the study; ciprofloxacin MIC 50 increased from 0.5 to 1 mg/L, MIC 90 increased from 4 to 16 mg/L. Other antimicrobial MIC were mostly unaffected. Microbiological changes over 48 weeks of ARD-3150 treatment appear modest. Ciprofloxacin susceptibility (but not other antimicrobial susceptibility) decreases were observed that did not appear to preclude PEx risk reduction benefit. [ABSTRACT FROM AUTHOR]

Background and Aims: Suspected latent tuberculosis infection (LTBI) is a common reason for referral to TB clinics. Interferon-gamma release assays (IGRAs) are more specific than tuberculin skin tests (TSTs) for diagnosing LTBI. The aim of this study is to determine if IGRA changes practice in the management of cases referred to a TB clinic for possible LTBI.Design and Methods: A prospective study was performed over 29 months. All adult patients who had TST, CXR & IGRA were included. The original decision regarding TB chemoprophylaxis was made by TB team consensus, based on clinical history and TST. Cases were then analysed with the addition of IGRA to determine if this had altered management. An independent physician subsequently reviewed the cases.Results: Of 204 patients studied, 68 were immunocompromised. 120 patients had positive TSTs. Of these, 36 (30%) had a positive QFT and 84 (70%) had a negative QFT. Practice changed in 78 (65%) cases with positive TST, all avoiding TB chemoprophylaxis due to QFT. Of the immunocompromised patients, 17 (25%) underwent change of practice. No cases of active TB have developed.Conclusions: This study demonstrates a significant change of clinical practice due to IGRA use. Our findings support the NICE 2011 recommendations. [ABSTRACT FROM PUBLISHER]

Aim: The aim of our study was to assess the impact of 8-weekly intravenous (IV) antibiotics on exacerbation frequency and health-related quality of life in bronchiectasis.Methods: Patients were recruited prospectively from June 2008 to December 2010. Patients with recurrent exacerbations (five or more exacerbations per year) and subjectively reporting ill health between antibiotic courses were recruited. Eight-weekly IV antibiotics (for 14 days) were initiated. Patients were followed up for 1 year. Main outcome was reduction in exacerbation frequency and improvement in health-related quality of life (HRQoL) at 1 year after starting intravenous antibiotic therapy. Other outcomes recorded were forced expiratory volume in 1 s (FEV1), forced vital capacity (FVC), incremental shuttle walk test (ISWT), 24-h sputum volume, sputum microbiology, body mass index (BMI), markers of inflammation—white cell count (WCC), C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).Results: In total, 19 patients were recruited. Mean age was 64.1 years and 52.6% were female. With 8-weekly antibiotics, there was a significant reduction in the number of exacerbations [mean (SE): 9.3 (0.5) in the year before vs. 8.0 (0.4) in the year after; P = 0.02]. In 63.2%, Leicester Cough Questionnaire (LCQ) improved by &geq;1.3 U (P = 0.006)] and in 42.1% St. George’s Respiratory Questionnaire (SGRQ) improved by &geq;4 U (P = 0.03). Exercise capacity increased by 58.7 m (P = 0.004). There was no improvement in the other end points.Conclusion: Treatment with 8-weekly intravenous antibiotics in severe bronchiectasis reduced exacerbation frequency and improved exercise tolerance and health-related quality of life. [ABSTRACT FROM PUBLISHER]

Background: Biomarkers and clinical prediction rules have been proposed for severity assessment in acute pulmonary embolism (PE).Aim: The aim of this study was to compare biomarkers with the PE Severity Index (PESI), a validated scoring system for predicting 30-day mortality and to determine if addition of biomarkers to PESI would improve its predictive accuracy.Study Design and Methods: We conducted a retrospective analysis of normotensive patients admitted with PE confirmed by CT pulmonary angiogram, to three teaching hospitals between January 2005 and July 2007. All patients had admission levels of D-dimer and Troponin I and calculation of PESI score on admission. The outcome of interest was 30-day mortality.Results: There were 411 patients included in the study. Patients who died had higher levels of D-dimer (median 2947 ng/ml vs. 1464 ng/ml; P = 0.02), Troponin (57.1% positive vs. 13.8%; P < 0.0001) and higher PESI scores [median 109 vs. 83; P < 0.0001], compared to survivors. PESI had superior accuracy for predicting 30-day mortality than a combination of Troponin and D-dimer (AUC 0.80 vs. 0.75). Addition of Troponin to PESI further improved the predictive value of the score (AUC 0.85 for vs. AUC 0.80 for PESI alone).Conclusion: Biomarkers and clinical prediction rules predict outcome in acute PE. Addition of troponin to the PESI scoring system improves the predictive value for 30-day mortality and may be useful for guiding initial management of patients presenting with PE. [ABSTRACT FROM AUTHOR]