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Background: Clinical heterogeneity in bronchiectasis remains a challenge for improving the appropriate targeting of therapies and patient management. Antimicrobial peptides (AMPs) have been linked to disease severity and phenotype., Research Question: Can we identify clusters of patients based on the levels of AMPs, airway inflammation, tissue remodeling, and tissue damage to establish their relationship with disease severity and clinical outcomes?, Study Design and Methods: A prospective cohort of 128 stable patients with bronchiectasis were recruited across three centers in three different countries (Spain, Scotland, and Italy). A two-step cluster strategy was used to stratify patients according to levels of lactoferrin, lysozyme, LL-37, and secretory leukocyte protease inhibitor in sputum. Measurements of inflammation (IL-8, tumor growth factor β, and IL-6), tissue remodeling and damage (glycosaminoglycan, matrix metallopeptidase 9, neutrophil elastase, and total and bacterial DNA), and neutrophil chemotaxis were assessed., Results: Three clusters of patients were defined according to distinct airway profiles of AMPs. They represented groups of patients with gradually distinct airway infection and disease severity. Each cluster was associated with an airway profile of inflammation, tissue remodeling, and tissue damage. The relationships between soluble mediators also were distinct between clusters. This analysis allowed the identification of the cluster with the most deregulated local innate immune response. During follow-up, each cluster showed different risk of three or more exacerbations occurring (P = .03) and different times to first exacerbations (P = .03)., Interpretation: Bronchiectasis patients can be stratified in different clusters according to profiles of airway AMPs, inflammation, tissue remodeling, and tissue damage. The combination of these immunologic variables shows a relationship with disease severity and future risk of exacerbations., (Copyright © 2020 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

By 21 May 2020, severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) had caused more than 5 million cases of coronavirus 2019 (COVID-19) across more than 200 countries. Most countries with significant outbreaks have introduced social distancing or "lockdown" measures to reduce viral transmission. So the key question now is when, how and to what extent these measures can be lifted.Publicly available data on daily numbers of newly confirmed cases and mortality were used to fit regression models estimating trajectories, doubling times and the reproduction number (R 0 ) of the disease, before and under the control measures. These data ran up to 21 May 2020, and were sufficient for analysis in 89 countries.The estimates of R 0 before lockdown based on these data were broadly consistent with those previously published: between 2.0 and 3.7 in the countries with the largest number of cases available for analysis (USA, Italy, Spain, France and UK). There was little evidence to suggest that the restrictions had reduced R far below 1 in many places, with France having the most rapid reductions: R 0 0.76 (95% CI 0.72-0.82) based on cases, and 0.77 (95% CI 0.73-0.80) based on mortality.Intermittent lockdown has been proposed as a means of controlling the outbreak while allowing periods of increased freedom and economic activity. These data suggest that few countries could have even 1 week per month unrestricted without seeing resurgence of the epidemic. Similarly, restoring 20% of the activity that has been prevented by the lockdowns looks difficult to reconcile with preventing the resurgence of the disease in most countries., Competing Interests: Conflict of interest: M. Lonergan has nothing to disclose. Conflict of interest: J.D. Chalmers has received research grants from GlaxoSmithKline, Boehringer Ingelheim, AstraZeneca, Pfizer, Grifols, Bayer AG, Polyphor and Insmed; and received consultancy, congress travel or speaker fees from GlaxoSmithKline, Bayer Healthcare, Aradigm Corporation, Grifols, Pfizer, Boehringer Ingelheim, Napp and Insmed., (Copyright ©ERS 2020.)

Introduction: Neutrophil elastase activity in sputum can identify patients at high risk of airway infection and exacerbations in bronchiectasis. Application of this biomarker in clinical practice is limited, because no point-of-care test is available. We tested whether a novel semi-quantitative lateral flow device (neutrophil elastase airway test stick - NEATstik®) can stratify bronchiectasis patients according to severity, airway infection and exacerbation risk., Methods: Sputum samples from 124 patients with stable bronchiectasis enrolled in the UK and Spain were tested using the NEATstik®, which scores neutrophil elastase concentration from 0 (<8 µg·mL -1 elastase activity) to 10 (maximum detectable neutrophil elastase activity). High neutrophil elastase activity was regarded as a NEATstik® grade >6. Severity of disease, airway infection from sputum culture and exacerbations over the 12 months were recorded. An independent validation was conducted in 50 patients from Milan, Italy., Measurements and Main Results: Patients had a median age of 69 years and forced expiratory volume in 1 s (FEV 1 ) 69%. High neutrophil elastase activity was associated with worse bronchiectasis severity using the bronchiectasis severity index (p=0.0007) and FEV 1 (p=0.02). A high NEATstik® grade was associated with a significant increase in exacerbation frequency, incident rate ratio 2.75 (95% CI 1.63-4.64, p<0.001). The median time to next exacerbation for patients with a NEATstik® grade >6 was 103 days compared to 278 days. The hazard ratio was 2.59 (95% CI 1.71-3.94, p<0.001). Results were confirmed in the independent validation cohort., Conclusions: A novel lateral flow device provides assessment of neutrophil elastase activity from sputum in minutes and identifies patients at increasing risk of airway infection and future exacerbations., Competing Interests: Conflict of interest: A. Shoemark has nothing to disclose. Conflict of interest: E. Cant has nothing to disclose. Conflict of interest: L. Carreto has nothing to disclose. Conflict of interest: A. Smith has nothing to disclose. Conflict of interest: M. Oriano has nothing to disclose. Conflict of interest: H.R. Keir has nothing to disclose. Conflict of interest: L. Perea has nothing to disclose. Conflict of interest: E. Canto has nothing to disclose. Conflict of interest: L. Terranova has nothing to disclose. Conflict of interest: S. Vidal has nothing to disclose. Conflict of interest: K. Moffitt was employed by Proaxsis, during the conduct of the study. Conflict of interest: S. Aliberti has nothing to disclose. Conflict of interest: O Sibila has nothing to disclose. Conflict of interest: J.D. Chalmers reports grants and personal fees from GlaxoSmithKline, Boehringer Ingelheim, Pfizer, Bayer Healthcare, Grifols and Insmed, grants from AstraZeneca, personal fees from Napp and Aradigm Corporation, outside the submitted work., (Copyright ©ERS 2019.)

Background: The increasing prevalence and recognition of bronchiectasis in clinical practice necessitates a better understanding of the economic disease burden to improve the management and achieve better clinical and economic outcomes. This study aimed to assess the economic burden of bronchiectasis based on a review of published literature., Methods: A systematic literature review was conducted using MEDLINE, Embase, EconLit and Cochrane databases to identify publications (1 January 2001 to 31 December 2016) on the economic burden of bronchiectasis in adults., Results: A total of 26 publications were identified that reported resource use and costs associated with management of bronchiectasis. Two US studies reported annual incremental costs of bronchiectasis versus matched controls of US$5681 and US$2319 per patient. Twenty-four studies reported on hospitalization rates or duration of hospitalization for patients with bronchiectasis. Mean annual hospitalization rates per patient, reported in six studies, ranged from 0.3-1.3, while mean annual age-adjusted hospitalization rates, reported in four studies, ranged from 1.8-25.7 per 100,000 population. The average duration of hospitalization, reported in 12 studies, ranged from 2 to 17 days. Eight publications reported management costs of bronchiectasis. Total annual management costs of €3515 and €4672 per patient were reported in two Spanish studies. Two US studies reported total costs of approximately US$26,000 in patients without exacerbations, increasing to US$36,00-37,000 in patients with exacerbations. Similarly, a Spanish study reported higher total annual costs for patients with > 2 exacerbations per year (€7520) compared with those without exacerbations (€3892). P. aeruginosa infection increased management costs by US$31,551 to US$56,499, as reported in two US studies, with hospitalization being the main cost driver., Conclusions: The current literature suggests that the economic burden of bronchiectasis in society is significant. Hospitalization costs are the major driver behind these costs, especially in patients with frequent exacerbations. However, the true economic burden of bronchiectasis is likely to be underestimated because most studies were retrospective, used ICD-9-CM coding to identify patients, and often ignored outpatient burden and cost. We present a conceptual framework to facilitate a more comprehensive assessment of the true burden of bronchiectasis for individuals, healthcare systems and society.

Background and Objective: Acute exacerbations of chronic obstructive pulmonary disease (AECOPD) due to Pseudomonas aeruginosa (PA) are associated with worse outcomes. PA antibiotic resistance is important to determine treatment and may influence clinical outcomes. The aim was to study clinical characteristics and outcomes in patients with AECOPD associated with PA based on their antibiotic resistance., Methods: This was a prospective observational study including all patients with AECOPD and positive PA sputum culture admitted in a respiratory ward in a tertiary hospital in Barcelona during 2013-2014. PA was defined as resistant (PA-R) when the antibiogram showed ≥1 resistance., Results: Four hundred one patients with AECOPD were evaluated. Of them, 54 (13%) had a positive PA sputum culture. Eighty-two per cent were men, median age was 77 (SD 7) years old and FEV1 was less than 36% (SD 17) of predicted value. PA-R was isolated in 35 patients (66%), and PA-sensitive (PA-S) was isolated in 18 (34%) patients. No differences were found in demographics, lung function and comorbidities among groups. PA-R patients were more likely exposed to prior oral corticosteroids (77% vs 44%, P = 0.03) and antibiotics (77% vs 31%, P = 0.01), respectively. AECOPD patients associated with PA-S were more likely to die at 30 days (odds ratio 13.53, 95% confidence interval: 1.14-69.56, P = 0.03) and 90 days (odds ratio 7.09, 95% confidence interval: 1.33-37.89, P = 0.02), respectively., Conclusion: Pseudomonas aeruginosa-resistant affects patients with severe AECOPD and previous use of corticosteroids and antibiotics. The presence of PA-S is associated with higher mortality. These results may suggest increased virulence in PA-S strains causing acute infections., (© 2016 Asian Pacific Society of Respirology.)