Multidimensional severity assessment in bronchiectasis: an analysis of seven European cohorts.

INTRODUCTION: Bronchiectasis is a multidimensional disease associated with substantial morbidity and mortality. Two disease-specific clinical prediction tools have been developed, the Bronchiectasis Severity Index (BSI) and the FACED score, both of which stratify patients into severity risk categories to predict the probability of mortality. METHODS: We aimed to compare the predictive utility of BSI and FACED in assessing clinically relevant disease outcomes across seven European cohorts independent of their original validation studies. RESULTS: The combined cohorts totalled 1612. Pooled analysis showed that both scores had a good discriminatory predictive value for mortality (pooled area under the curve (AUC) 0.76, 95% CI 0.74 to 0.78 for both scores) with the BSI demonstrating a higher sensitivity (65% vs 28%) but lower specificity (70% vs 93%) compared with the FACED score. Calibration analysis suggested that the BSI performed consistently well across all cohorts, while FACED consistently overestimated mortality in 'severe' patients (pooled OR 0.33 (0.23 to 0.48), p<0.0001). The BSI accurately predicted hospitalisations (pooled AUC 0.82, 95% CI 0.78 to 0.84), exacerbations, quality of life (QoL) and respiratory symptoms across all risk categories. FACED had poor discrimination for hospital admissions (pooled AUC 0.65, 95% CI 0.63 to 0.67) with low sensitivity at 16% and did not consistently predict future risk of exacerbations, QoL or respiratory symptoms. No association was observed with FACED and 6 min walk distance (6MWD) or lung function decline. CONCLUSION: The BSI accurately predicts mortality, hospital admissions, exacerbations, QoL, respiratory symptoms, 6MWD and lung function decline in bronchiectasis, providing a clinically relevant evaluation of disease severity.

ECFS standards of care on CFTR-related disorders: Identification and care of the disorders.

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.

Endotypes in bronchiectasis: moving towards precision medicine. A narrative review.

Bronchiectasis is a highly complex entity that can be very challenging to investigate and manage. Patients are diverse in their aetiology, symptoms, risk of complications and outcomes. "Endotypes"- subtypes of disease with distinct biological mechanisms, has been proposed as a means of better managing bronchiectasis. This review discusses the emerging field of endotyping in bronchiectasis. We searched PubMed and Google Scholar for randomized controlled trials (RCT), observational studies, systematic reviews and meta-analysis published from inception until October 2022, using the terms: "bronchiectasis", "endotypes", "biomarkers", "microbiome" and "inflammation". Exclusion criteria included commentaries and non-English language articles as well as case reports. Duplicate articles between databases were initially identified and appropriately excluded. Studies identified suggest that it is possible to classify bronchiectasis patients into multiple endotypes deriving from their co-morbidities or underlying causes to complex infective or inflammatory endotypes. Specific biomarkers closely related to a particular endotype might be used to determine response to treatment and prognosis. The most clearly defined examples of endotypes in bronchiectasis are the underlying causes such as immunodeficiency or allergic bronchopulmonary aspergillosis where the underlying causes are clearly related to a specific treatment. The heterogeneity of bronchiectasis extends, however, far beyond aetiology and it is now possible to identify subtypes of disease based on inflammatory mechanisms such airway neutrophil extracellular traps and eosinophilia. In future biomarkers of host response and infection, including the microbiome may be useful to guide treatments and to increase the success of randomized trials. Advances in the understanding the inflammatory pathways, microbiome, and genetics in bronchiectasis are key to move towards a personalized medicine in bronchiectasis.

Periodontal Effects of the Reversible Dipeptidyl Peptidase 1 Inhibitor Brensocatib in Bronchiectasis.

AIMS: Brensocatib is a reversible inhibitor of dipeptidyl peptidase 1 (cathepsin C), in development to treat chronic non-cystic fibrosis bronchiectasis. The phase 2, randomized, placebo-controlled WILLOW trial (NCT03218917) was conducted to examine whether brensocatib reduced the incidence of pulmonary exacerbations. Brensocatib prolonged the time to the first exacerbation and led to fewer exacerbations than placebo. Because brensocatib potentially affects oral tissues due to its action on neutrophil-mediated inflammation, we analyzed periodontal outcomes in the trial participants. MATERIALS AND METHODS: Patients with bronchiectasis were randomized 1:1:1 to receive once-daily oral brensocatib 10 or 25 mg or placebo. Periodontal status was monitored throughout the 24-week trial in a prespecified safety analysis. Periodontal pocket depth (PPD) at screening, week 8, and week 24 was evaluated. Gingival inflammation was evaluated by a combination of assessing bleeding upon probing and monitoring the Löe-Silness Gingival Index on 3 facial surfaces and the mid-lingual surface. RESULTS: At week 24, mean ± SE PPD reductions were similar across treatment groups: -0.07 ± 0.007, -0.06 ± 0.007, and -0.15 ± 0.007 mm with brensocatib 10 mg, brensocatib 25 mg, and placebo, respectively. The distribution of changes in PPD and the number of patients with multiple increased PPD sites were similar across treatment groups at weeks 8 and 24. The frequencies of gingival index values were generally similar across treatment groups at each assessment. An increase in index values 0-1 and a decrease in index values 2-3 over time and at the end of the study were observed in all groups, indicating improved oral health. CONCLUSIONS: In patients with non-cystic fibrosis bronchiectasis, brensocatib 10 or 25 mg had an acceptable safety profile after 6 months' treatment, with no changes in periodontal status noted. Improvement in oral health at end of the study may be due to regular dental care during the trial and independent of brensocatib treatment. KNOWLEDGE TRANSFER STATEMENT: The results of this study suggest that 24 weeks of treatment with brensocatib does not affect periodontal disease progression. This information can be used by clinicians when considering treatment approaches for bronchiectasis and suggests that the use of brensocatib will not be limited by periodontal disease risks. Nevertheless, routine dental/periodontal care should be provided to patients irrespective of brensocatib treatment.

Is community-acquired pneumonia an independent risk factor for cardiovascular disease?

Community-acquired pneumonia (CAP) is the most frequent infectious cause of death in western countries. The high mortality rate in CAP is commonly related to comorbid conditions such as cardiovascular disease. Clinical studies in both primary and secondary care settings have identified an increase in short- and long-term risk of cardiovascular events and death from vascular events following acute respiratory infections. The mechanism remains to be fully established, but it has been suggested that the inflammatory state in patients affected by CAP acts to promote platelet activation and thrombosis, and to narrow coronary arteries through vasoconstriction. Acute infections destabilise vascular endothelium and create an imbalance between myocardial oxygen supply and demand, leading to an increased risk of cardiovascular events. Acute infections have been shown to have both systemic effects and local effects on coronary vessels. These effects are mediated through both the host response to infection and, in some cases, direct effects of bacterial infection or bacterial products. In this review, we discuss the link between CAP and increased risk of cardiovascular events, drawing on existing evidence from clinical and mechanistic studies. Further studies into and increased awareness of this association is warranted to promote novel ways of protecting high-risk patients.

Increasing outpatient treatment of mild community-acquired pneumonia: systematic review and meta-analysis.

In order to identify, synthesise and interpret the evidence relating to strategies to increase the proportion of low-risk patients with community-acquired pneumonia treated in the community, we conducted a systematic review of intervention studies conducted between 1981-2010. Articles were included if they compared strategies to increase outpatient care with usual care. Outcomes were: the proportion of patients treated as outpatients, mortality, hospital readmissions, health related quality of life, return to usual activities and patient satisfaction with care. The main analysis included six studies. The interventions in these studies were generally complex, but all involved the use of a severity score to identify low-risk patients. Overall, a significantly larger numbers of patients were treated in the community with these interventions (OR 2.31, 95% CI 2.03-2.63). The interventions appear safe, with no significant differences in mortality (OR 0.83, 95% CI 0.59-1.17), hospital readmissions (OR 1.08, 95% CI 0.82-1.42) or patient satisfaction with care (OR 1.21, 95% CI 0.97-1.49) between the intervention and control groups. There was insufficient data regarding quality of life or return to usual activities. All studies had significant limitations. The available evidence suggests that interventions to increase the proportion of patients treated in the community are safe, effective and acceptable to patients.

Impact of inhaled corticosteroid use on outcome in COPD patients admitted with pneumonia.

The aim of this study was to investigate whether inhaled corticosteroid (ICS) use affects outcome in patients with chronic obstructive pulmonary disease (COPD) admitted with community-acquired pneumonia (CAP). This was a prospective, observational study of patients with spirometry-confirmed COPD presenting with a primary diagnosis of CAP in Lothian, UK. Outcome measures were compared between ICS users and non-ICS users. Of 490 patients included in the study, 76.7% were classified as ICS users. ICS users had higher Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage compared with non-ICS users (mean ± sd 3.2 ± 0.8 versus 2.6 ± 0.9; p<0.0001). There were no significant differences in pneumonia severity (mean ± sd Pneumonia Severity Index (PSI) 4.2 ± 0.8 versus 4.3 ± 0.8 (p = 0.3); mean ± sd CURB-65 score 2.1 ± 1.3 versus 2.3 ± 1.3 (p = 0.07)) or markers of systemic inflammation (median C-reactive protein 148 (interquartile range 58-268) mg·L(-1) versus 183 (IQR 85-302) mg·L(-1); p = 0.08) between ICS users and non-ICS users. On multivariable analysis, after adjustment for COPD severity and PSI, ICS use was not independently associated with 30-day mortality (OR 1.71, 95% CI 0.75-3.90; p = 0.2), 6-month mortality (OR 1.62, 95% CI 0.82-3.16; p = 0.2), requirement for mechanical ventilation and/or inotropic support (OR 0.73, 95% CI 0.33-1.62; p = 0.4) or development of complicated pneumonia (OR 0.71, 95% CI 0.25-1.99; p = 0.5). Prior ICS use had no impact on outcome in patients with COPD admitted with CAP.

Physician judgement is a crucial adjunct to pneumonia severity scores in low-risk patients.

This study investigates the reasons for hospitalisation in patients with low-risk (CURB-65 score 0-1) community-acquired pneumonia (CAP), with a view to identifying the potential for improving outpatient management. As part of a prospective observational study of CAP, we evaluated reasons for hospitalisation in these low-risk patients. 565 patients had low-risk CAP and 420 of these were admitted (for >12 h). 39.3% had additional markers of severity justifying admission, 29.5% of the admissions were required for further management that could not be provided rapidly in the community, 11.9% had unsafe social circumstances and 19.3% had no clinical reason justifying hospitalisation. 30-day mortality was increased in patients with additional severity markers (6.7%), which was significantly higher compared with 0% for patients awaiting investigations (p=0.009) and 0% without a clear indication for hospitalisation (p=0.04). In a logistic regression analysis, parameters associated with 30-day mortality were chronic cardiac comorbidity (adjusted odds ratio (aOR) 5.73, 95% CI 1.52-21.6; p=0.01), acidosis (aOR 5.14, 95% CI 1.44-18.3; p=0.01), hypoxia (aOR 9.86, 95% CI 2.39-40.7; p=0.002) and multilobar chest radiograph shadowing (aOR 4.54, 95% CI 1.21-17.1; p=0.03). This study supports recommendations from international guidelines that pneumonia severity scores should be used as an adjunct to clinical judgement, when deciding on hospitalisation.

Risk factors for complicated parapneumonic effusion and empyema on presentation to hospital with community-acquired pneumonia.

BACKGROUND: The aim of this study was to identify key factors on admission predicting the development of complicated parapneumonic effusion or empyema in patients admitted with community-acquired pneumonia. METHODS: A prospective observational study of patients admitted with community-acquired pneumonia in NHS Lothian, UK, was conducted. Multivariate regression analyses were used to evaluate factors that could predict the development of complicated parapneumonic effusion or empyema, including admission demographics, clinical features, laboratory tests and pneumonia-specific (Pneumonia Severity Index (PSI), CURB65 (New onset confusion, urea >7 mmol/l, Respiratory rate > or = 30 breaths/min, Systolic blood pressure < 90 mm Hg and/or diastolic blood pressure < or = 60 mm Hg and age > or = 65 years) and CRB65 (New onset confusion, Respiratory rate > or = 30 breaths/min, Systolic blood pressure <90 mm Hg and/or diastolic blood pressure < or = 60 mm Hg and age > or = 65 years)) and generic sepsis scoring systems (APACHE II (Acute Physiology and Chronic Health Evaluation II), SEWS (standardised early warning score) and systemic inflammatory response syndrome (SIRS)). RESULTS: 1269 patients were included in the study and 92 patients (7.2%) developed complicated parapneumonic effusion or empyema. The pneumonia-specific and generic sepsis scoring systems had no value in predicting complicated parapneumonic effusion or empyema. Multivariate logistic regression identified albumin <30 g/l adjusted odds ratio (AOR) 4.55 (95% CI 2.45 to 8.45, p < 0.0001), sodium <130 mmol/l AOR 2.70 (1.55 to 4.70, p = 0.0005), platelet count >400 x 10(9)/l AOR 4.09 (2.21 to 7.54, p < 0.0001), C-reactive protein >100 mg/l AOR 15.7 (3.69 to 66.9, p < 0.0001) and a history of alcohol abuse AOR 4.28 (1.87 to 9.82, p = 0.0006) or intravenous drug use AOR 2.82 (1.09 to 7.30, p = 0.03) as independently associated with development of complicated parapneumonic effusion or empyema. A history of chronic obstructive pulmonary disease was associated with decreased risk, AOR 0.18 (0.06 to 0.53, p = 0.002). A 6-point scoring system using these combined variables had good discriminatory value: area under the receiver operator characteristic curve (AUC) 0.84 (95% CI 0.81 to 0.86, p < 0.0001). CONCLUSION: This study has identified seven clinical factors predicting the development of complicated parapneumonic effusion or empyema. Independent validation is needed.

Admission hypoglycaemia is associated with adverse outcome in community-acquired pneumonia.

The aim of our study was to investigate if hypoglycaemia correlates with outcome in community-acquired pneumonia (CAP). We performed a prospective, observational study of consecutive patients presenting with a primary diagnosis of CAP in Lothian (UK). Admission plasma glucose was measured and, on this basis, patients were divided into two groups, hypoglycaemic (<4.4 mmol x L(-1) or <79.0 mg x dL(-1)) and nonhypoglycaemic (> or = 4.4 mmol x L(-1) or > or = 79.0 mg x dL(-1)). Outcomes of interest were 30-day mortality, need for mechanical ventilation and inotropic support. Multivariable logistic regression was used to compare these outcomes in hypoglycaemic patients to nonhypoglycaemic patients, adjusting for diabetes mellitus, prior statin use and Pneumonia Severity Index. In total, 1,050 patients were included in the study with 5.4% classified as hypoglycaemic. Increased rates of 30-day mortality (28.1% versus 7.5%, p<0.0001), need for mechanical ventilation (29.8% versus 6.5%, p<0.0001) and need for inotropic support (21.1% versus 4.8%, p<0.0001) were observed in hypoglycaemic patients compared with nonhypoglycaemic patients. On multivariable analysis, hypoglycaemia was independently associated with increased 30-day mortality (OR 2.25, 95% CI 1.1-4.7; p = 0.03), need for mechanical ventilation (OR 3.8, 95% CI 1.9-7.5; p = 0.0002) and need for inotropic support (OR, 2.9, 95% CI 1.4-6.3; p = 0.0006). Admission hypoglycaemia is associated with increased 30-day mortality, need for mechanical ventilation and inotropic support in patients presenting with CAP.

The impact of certain underlying comorbidities on the risk of developing hospitalised pneumonia in England.

BACKGROUND: UK specific data on the risk of developing hospitalised CAP for patients with underlying comorbidities is lacking. This study compared the likelihood of hospitalised all-cause community acquired pneumonia (CAP) in patients with certain high-risk comorbidities and a comparator group with no known risk factors for pneumococcal disease. METHODS: This retrospective cohort study interrogated data in the Hospital Episodes Statistics (HES) dataset between financial years 2012/13 and 2016/17. In total 3,078,623 patients in England (aged ≥18 years) were linked to their hospitalisation records. This included 2,950,910 individuals with defined risk groups and a comparator group of 127,713 people who had undergone tooth extraction with none of the risk group diagnoses. Risk groups studied were chronic respiratory disease (CRD), chronic heart disease (CHD), chronic liver disease (CLD), chronic kidney disease (CKD), diabetes (DM) and post bone marrow transplant (BMT). The patients were tracked forward from year 0 (2012/13) to Year 3 (2016/17) and all diagnoses of hospitalised CAP were recorded. A Logistic regression model compared odds of developing hospitalised CAP for patients in risk groups compared to healthy controls. The model was simultaneously adjusted for age, sex, strategic heath authority (SHA), index of multiple deprivation (IMD), ethnicity, and comorbidity. To account for differing comorbidity profiles between populations the Charlson Comorbidity Index (CCI) was applied. The model estimated odds ratios (OR) with 95% confidence intervals of developing hospitalised CAP for each specified clinical risk group. RESULTS: Patients within all the risk groups studied were more likely to develop hospitalised CAP than patients in the comparator group. The odds ratios varied between underlying conditions ranging from 1.18 (95% CI 1.13, 1.23) for those with DM to 5.48 (95% CI 5.28, 5.70) for those with CRD. CONCLUSIONS: Individuals with any of 6 pre-defined underlying comorbidities are at significantly increased risk of developing hospitalised CAP compared to those with no underlying comorbid condition. Since the likelihood varies by risk group it should be possible to target patients with each of these underlying comorbidities with the most appropriate preventative measures, including immunisations.

Microbiological changes observed over 48 weeks of treatment with inhaled liposomal ciprofloxacin in individuals with non-cystic fibrosis bronchiectasis and chronic Pseudomonas aeruginosa lung infection.

OBJECTIVES: 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]. METHODS: 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. RESULTS: 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) log10 CFU/g for placebo (second period) to 2.07 (95% CI 2.45-1.69) versus 0.70 (95% CI 1.11-0.29) log10 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 MIC50 increased from 0.5 to 1 mg/L, MIC90 increased from 4 to 16 mg/L. Other antimicrobial MIC were mostly unaffected. CONCLUSION: 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.

Systolic blood pressure is superior to other haemodynamic predictors of outcome in community acquired pneumonia.

INTRODUCTION: Admission blood pressure (BP) assessment is a central component of severity assessment for community acquired pneumonia. The aim of this study was to establish which readily available haemodynamic measure on admission is most useful for predicting severity in patients admitted with community acquired pneumonia. METHODS: A prospective observational study of patients admitted with community acquired pneumonia was conducted in Edinburgh, UK. The measurements compared were systolic and diastolic BP, mean arterial pressure and pulse pressure. The outcomes of interest were 30 day mortality and the requirement for mechanical ventilation and/or inotropic support. RESULTS: Admission systolic BP < 90 mm Hg, diastolic BP < or = 60 mm Hg, mean arterial pressure < 70 mm Hg and pulse pressure < or = 40 mm Hg were all associated with increased 30 day mortality and the need for mechanical ventilation and/or inotropic support on multivariate logistic regression. The AUC values for each predictor of 30 day mortality were as follows: systolic BP < 90 mm Hg 0.70; diastolic BP < or = 60 mm Hg 0.59; mean arterial pressure < 70 mm Hg 0.64; and pulse pressure < or = 40 mm Hg 0.60. The AUC values for each predictor of need for mechanical ventilation and/or inotropic support were as follows: systolic BP < 90 mm Hg 0.70; diastolic BP < or = 60 mm Hg 0.68; mean arterial pressure < 70 mm Hg 0.69; and pulse pressure < or = 40 mm Hg 0.59. A simplified CRB65 score containing systolic blood pressure < 90 mm Hg alone performed equally well to standard CRB65 score (AUC 0.76 vs 0.74) and to the standard CURB65 score (0.76 vs 0.76) for the prediction of 30 day mortality. The simplified CRB65 score was equivalent for prediction of mechanical ventilation and/or inotropic support to standard CRB65 (0.77 vs 0.77) and to CURB65 (0.77 vs 0.78). CONCLUSION: Systolic BP is superior to other haemodynamic predictors of 30 day mortality and need for mechanical ventilation and/or inotropic support in community acquired pneumonia. The CURB65 score can be simplified to a modified CRB65 score by omission of the diastolic BP criterion without compromising its accuracy.

A qualitative synthesis of gastro-oesophageal reflux in bronchiectasis: Current understanding and future risk.

Gastro-oesophageal reflux disease (GORD) is a common comorbidity in bronchiectasis, and is often associated with poorer outcomes. The cause and effect relationship between GORD and bronchiectasis has not yet been fully elucidated and a greater understanding of the pathophysiology of the interaction and potential therapies is required. This review explores the underlying pathophysiology of GORD, its clinical presentation, risk factors, commonly applied diagnostic tools, and a detailed synthesis of original articles evaluating the prevalence of GORD, its influence on disease severity and current management strategies within the context of bronchiectasis. The prevalence of GORD in bronchiectasis ranges from 26% to 75%. Patients with co-existing bronchiectasis and GORD were found to have an increased mortality and increased bronchiectasis severity, manifest by increased symptoms, exacerbations, hospitalisations, radiological extent and chronic infection, with reduced pulmonary function and quality of life. The pathogenic role of Helicobacter pylori infection in bronchiectasis, perhaps via aspiration of gastric contents, also warrants further investigation. Our index of suspicion for GORD should remain high across the spectrum of disease severity in bronchiectasis. Identifying GORD in bronchiectasis patients may have important therapeutic and prognostic implications, although clinical trial evidence that treatment targeted at GORD can improve outcomes in bronchiectasis is currently lacking.

Quality control for multiple breath washout tests in multicentre bronchiectasis studies: Experiences from the BRONCH-UK clinimetrics study.

INTRODUCTION: Multiple Breath Washout (MBW) to measure Lung Clearance Index (LCI) is increasingly being used as a secondary endpoint in multicentre bronchiectasis studies. LCI data quality control or "over-reading" is resource intensive and the impact is unclear. OBJECTIVES: To assess the proportion of MBW tests deemed unacceptable with over-reading, and to assess the change in LCI (number of turnovers), LCI coefficient of variation (CV%) and tidal volume (VT) CV% results after over-reading. METHODS: Data were analysed from 250 MBW tests (from 98 adult bronchiectasis patients) collected as part of the Bronch-UK Clinimetrics study in 5 UK centres. Each MBW test was over-read centrally using pre-defined criteria. MBW tests with <2 technically valid and repeatable trials were deemed unacceptable to include in analysis. In accepted tests, values for LCI, LCI CV% and VT CV% before and after over-reading, were compared. RESULTS: Insufficient data was collected in 10/250 tests. With over-reading, 30/240 (12%) were deemed unacceptable to include in analysis. In those accepted tests, overall the change in LCI, LCI CV% and VT CV% with over-reading was not statistically significant. When MBW new sites were compared to MBW expert sites, the change in LCI with over-reading was significantly greater in MBW new sites (p = 0.047). Data suggests that over-reading could be important up to at least 12 months post initiation of MBW activity. CONCLUSION: MBW over-reading was important in this study as 12% of tests were considered unacceptable. Over-reading improved test result accuracy in sites new to MBW.

Evaluation of serum inflammatory biomarkers as predictors of treatment outcome in pulmonary tuberculosis.

OBJECTIVE: To evaluate C-reactive protein (CRP), globulin and white blood cell (WBC) count as predictors of treatment outcome in pulmonary tuberculosis (PTB). METHODS: An observational study of patients with active PTB was conducted at a tertiary centre. All patients had serum CRP, globulin and WBC measured at baseline and at 2 months following commencement of treatment. The outcome of interest was requirement for extension of treatment beyond 6 months. RESULTS: There were 226 patients included in the study. Serum globulin 45 g/l was the only baseline biomarker evaluated that independently predicted requirement for treatment extension (OR 3.42, 95%CI 1.597.32, P 0.001). An elevated globulin level that failed to normalise at 2 months was also associated with increased requirement for treatment extension (63.9% vs. 5.1%, P 0.001), and had a low negative likelihood ratio (0.07) for exclusion of requirement for treatment extension. On multivariable analysis, an elevated globulin that failed to normalise at 2 months was independently associated with requirement for treatment extension (OR 6.13, 95%CI 2.2316.80, P 0.001). CONCLUSIONS: Serum globulin independently predicts requirement for treatment extension in PTB and outperforms CRP and WBC as a predictive biomarker. Normalisation of globulin at 2 months following treatment commencement is associated with low risk of requirement for treatment extension.

Symptoms of airway reflux predict exacerbations and quality of life in bronchiectasis.

AIM: We have explored the association of the upper airway symptoms related to cough with exacerbation frequency, sputum microbiology and inflammatory markers in patients with non cystic fibrosis bronchiectasis. METHODS: Patients with bronchiectasis completed the Hull Airway Reflux Questionnaire (HARQ). A score of >13 was taken to indicate the presence of reflux. Patients were followed-up with longitudinal spirometry, sputum culture and Leicester cough questionnaire (LCQ). Myeloperoxidase (MPO), free neutrophil elastase (NE) activity, Interleukin (IL)-8 and Tumour Necrosis Factor (TNF)-α was measured from spontaneous sputum samples. RESULTS: 163 completed the study. 59.5% were female. Mean age was 65.7 years. 73.6% reported airway reflux using HARQ. Patients with airway reflux had more severe cough symptoms as assessed by the LCQ [15.2 (3.5) vs. 19.4 (1.9)], p < 0.001. Sputum levels of MPO, NE, IL-8 and TNF-α were all significantly higher in the reflux positive group (p < 0.05 for all comparisons). In a multivariable logistic regression, airway reflux was independently associated with cough severity (-3.27, standard error 0.81, p = 0.0002). Airway reflux, age, FEV1 % predicted and colonization with Pseudomonas aeruginosa were independently associated with an increased risk of ≥3 bronchiectasis exacerbations in one year. CONCLUSION: The symptoms of airway reflux independently predict severity and exacerbation frequency in non cystic fibrosis bronchiectasis.

An evaluation of clinical stability criteria to predict hospital course in community-acquired pneumonia.

A number of different methods exist to assess clinical stability, a key component of pneumonia management. We compared the prognostic value of different stability criteria through a secondary analysis of the Edinburgh pneumonia study database. We studied four clinical stability criteria (Halm's criteria, the ATS criteria, CURB and 50% or more decrease in C-reactive protein from baseline). Outcomes included 30-day mortality, need for mechanical ventilation or vasopressor support (MV/VS), development of a complicated pneumonia, and a combined outcome of the above. A total of 1079 patients (49.8% male), with a median age of 68 years (IQR 53-80), were included. Ninety-three patients (8.6%) died by day 30, 91 patients (8.4%) required MV/VS and 99 patients (9.2%) developed a complicated pneumonia. Patients with increasing severity of pneumonia on admission, assessed by both CURB-65 and PSI, took a progressively longer time to achieve clinical stability assessed by any method (p < 0.001 for all criteria). Halm's criteria had the highest area under the curve (AUC) for prediction of 30-day mortality (AUC 0.95 (0.94-0.96)), need for MV/VS (AUC 0.96 (0.95-0.97)) and combined adverse outcome (AUC 0.96 (0.95-0.97)). C-reactive protein had the highest area under the curve for complicated pneumonia (AUC 0.96 (0.95-0.97)). Adding C-reactive protein to Halm's criteria increased the area under the curve, but the difference was only statistically significant for complicated pneumonia. All of the criteria performed well in predicting adverse outcomes in patients with pneumonia. Halm's criteria performed best when identifying patients at low risk of complications.