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  • Closing the gap in surveillance of tuberculosis and HIV co-infection: a European perspective on the need for clinician–public health alliances
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Marieke J. van der Werf; Giovanni Sotgiu; Masoud Dara

    Clinicians and public health professionals need quality information on TB–HIV co-infection and should join forces http://ow.ly/Lacb30fKA3T

    更新日期:2017-11-16
  • Cardiac safety of bedaquiline: a systematic and critical analysis of the evidence
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Emanuele Pontali; Giovanni Sotgiu; Simon Tiberi; Lia D'Ambrosio; Rosella Centis; Giovanni B. Migliori

    Bedaquiline is well tolerated: evidence indicates a minority of patients discontinue use due to QT extension http://ow.ly/9NRT30fNv4y

    更新日期:2017-11-16
  • Inflammation, age and changing microbiology: the search for causation in the cystic fibrosis airways
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Geraint B. Rogers

    A survey of CF BALF reports lung microbiota to vary with age and inflammation but causality remains hard to pin down http://ow.ly/hEjX30fVMoL

    更新日期:2017-11-16
  • Airway microbiota across age and disease spectrum in cystic fibrosis
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Edith T. Zemanick; Brandie D. Wagner; Charles E. Robertson; Richard C. Ahrens; James F. Chmiel; John P. Clancy; Ronald L. Gibson; William T. Harris; Geoffrey Kurland; Theresa A. Laguna; Susanna A. McColley; Karen McCoy; George Retsch-Bogart; Kurtis T. Sobush; Pamela L. Zeitlin; Mark J. Stevens; Frank J. Accurso; Scott D. Sagel; J. Kirk Harris

    Our objectives were to characterise the microbiota in cystic fibrosis (CF) bronchoalveolar lavage fluid (BALF), and determine its relationship to inflammation and disease status. BALF from paediatric and adult CF patients and paediatric disease controls undergoing clinically indicated bronchoscopy was analysed for total bacterial load and for microbiota by 16S rDNA sequencing. We examined 191 BALF samples (146 CF and 45 disease controls) from 13 CF centres. In CF patients aged <2 years, nontraditional taxa (e.g. Streptococcus, Prevotella and Veillonella) constituted ∼50% of the microbiota, whereas in CF patients aged ≥6 years, traditional CF taxa (e.g. Pseudomonas, Staphylococcus and Stenotrophomonas) predominated. Sequencing detected a dominant taxon not traditionally associated with CF (e.g. Streptococcus or Prevotella) in 20% of CF BALF and identified bacteria in 24% of culture-negative BALF. Microbial diversity and relative abundance of Streptococcus, Prevotella and Veillonella were inversely associated with airway inflammation. Microbiota communities were distinct in CF compared with disease controls, but did not differ based on pulmonary exacerbation status in CF. The CF microbiota detected in BALF differs with age. In CF patients aged <2 years, Streptococcus predominates, whereas classic CF pathogens predominate in most older children and adults.

    更新日期:2017-11-16
  • Donor-specific and -nonspecific HLA antibodies and outcome post lung transplantation
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Stijn E. Verleden; Bart M. Vanaudenaerde; Marie-Paul Emonds; Dirk E. Van Raemdonck; Arne P. Neyrinck; Geert M. Verleden; Robin Vos

    Donor-specific antibodies (DSAs) against human leukocyte antigen (HLA) are associated with chronic lung allograft dysfunction (CLAD) and mortality post lung transplantation, but data concerning prevalence, time of onset, persistence and effects on long-term outcome remain scarce. We assessed the association between HLA antibodies and CLAD-free and graft survival in a cohort of 362 patients. We stratified our analysis according to DSA status, persistence of antibodies and timing of antibodies (pre-transplant, early or late post-transplant). Within our cohort, 61 (17%) patients developed DSAs (mostly against HLA-DQ), which was associated with worse CLAD-free and graft survival (p<0.0001 and p=0.059, respectively). Persistent (hazard ratio (HR) 3.386, 95% CI 1.928–5.948; p<0.0001) as well as transient (HR 2.998, 95% CI 1.406–6.393; p=0.0045) DSAs were associated with shorter CLAD-free survival compared with patients without DSAs. Persistent DSAs (HR 3.071, 95% CI 1.632–5.778; p=0.0005) but not transient DSAs were negatively associated with graft survival compared with patients without DSAs, likely due to the higher incidence of restrictive CLAD. HLA non-DSAs and pre-transplant HLA antibodies had no effect on post-transplant outcome. We demonstrated an important difference in prognosis between persistent and transient DSAs. Moreover, the observed association between DSAs and restrictive CLAD suggests an overlap between antibody-mediated rejection and restrictive CLAD that needs further investigation.

    更新日期:2017-11-16
  • The effect of treatment for sleep apnoea on determinants of blood pressure control
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Raquel Casitas; Elisabet Martínez-Cerón; Raúl Galera; Carolina Cubillos-Zapata; María Jesús González-Villalba; Isabel Fernández-Navarro; Begoña Sánchez; Aldara García-Sánchez; Ester Zamarrón; Francisco García-Río

    Our aim was to assess the effect of continuous positive airway pressure (CPAP) on the nocturnal evolution of peripheral chemosensitivity, renin–angiotensin–aldosterone system activity, sympathetic tone and endothelial biomarkers in obstructive sleep apnoea (OSA) patients with isolated nocturnal hypertension (INH) or day–night sustained hypertension (D-NSH). In a crossover randomised trial, 32 OSA patients newly diagnosed with hypertension and without antihypertensive treatment were randomly assigned to 12 weeks of CPAP or sham CPAP. Peripheral chemosensitivity was evaluated before and after sleep using the hypoxic withdrawal test (%ΔVI). At baseline, D-NSH patients showed higher %ΔVI before sleep and higher levels of aldosterone and diurnal catecholamines. CPAP only reduced the nocturnal increase of %ΔVI in INH patients (6.9%, 95% CI 1.0–12.8%; p=0.026). CPAP-induced change from baseline in %ΔVI after sleep was 7.5% (95% CI 2.6–12.2%, p=0.005) in the INH group and 5.7% (95% CI 2.2–9.3%, p=0.004) in the D-NSH group. In contrast, %ΔVI before sleep only decreased with CPAP in the D-NSH patients (3.0%, 95% CI 0.5–5.6%; p=0.023). In conclusion, CPAP reduces the nocturnal increase of peripheral chemosensitivity experienced by INH patients and corrects the high daytime sensitivity of patients with D-NSH. Differences in response to CPAP between these patients can help better understand the mechanisms of perpetuation of hypertension in sleep apnoea.

    更新日期:2017-11-16
  • Tuberculosis patients with unknown HIV status in the Netherlands: analysing underreporting and lack of testing
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Maike Arnoldussen; Henrieke Schimmel; Eline Op de Coul; Susan van den Hof; Gerard de Vries

    The epidemics of tuberculosis (TB) and HIV are closely linked, as HIV infection is the main risk factor for progression from latent TB infection to active TB disease [1]. Globally, 11% of the 10.4 million new TB cases in 2015 were HIV-infected, and 22% of the 1.8 million TB deaths were among HIV-infected patients [2]. Despite all efforts made by collaborative TB/HIV programmes, less than half of all TB patients worldwide are estimated to be tested for HIV infection [2, 3]. Only 19 of the 31 countries, representing a third of all TB patients in the European Union (EU) and European Economic Area (EEA), report HIV status, with 67.6% of patients in these countries having a known HIV status [4]. Better information on the burden of TB/HIV co-infections will aid the planning and evaluation of TB/HIV prevention and control activities in various countries [5–8]. Few HIV-co-infected TB patients are missed despite suboptimal testing and reporting in the Netherlands The authors would like to thank the public health nurses and physicians of the TB departments of the Municipal Public Health Services who participated in this study.

    更新日期:2017-11-16
  • Proof of concept that most borderline Quantiferon results are true antigen-specific responses
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Jonathan W. Uzorka; Lucia J.M. Kroft; Jaap A. Bakker; Erik W. van Zwet; Erik Huisman; Corine Knetsch-Prins; Cornelis J. van der Zwan; Tom H.M. Ottenhoff; Sandra M. Arend

    Interferon-γ release assays (IGRAs) such as Quantiferon (QFT) that detect T-cell responses to antigens specific for Mycobacterium tuberculosis (MTB) have superior specificity to the tuberculin skin test (TST). While IGRAs are technically robust and the test result is a simple positive or negative, the interpretation nevertheless requires thorough understanding of the test's characteristics [1]. An area of debate is that of “borderline” results near the cut-off value, mentioned first in the setting of serial screening of health care workers [2]. While different authors used different ranges of test results under this denominator, borderline results were generally attributed to random assay variability [3, 4]. In reproducibility studies, conversions and reversions were often seen around the manufacturer-recommended cut-off, with the advice to “interpret such results cautiously” [5, 6]. Most borderline Quantiferon results are antigen-specific responses, defying the common assumption of random variation The authors thank Robert van de Peppel at Dept of Infectious Diseases for the random selection among patients with a low negative or high positive QFT result, and Marita Danhof-Pont from the Dept of Health, Safety and the Environment for assistance with data collection at the OHS.

    更新日期:2017-11-16
  • Restricted magnetic resonance diffusion of lung consolidation is not specific for respiratory exacerbation
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Gaël Dournes; François Laurent

    We read with interest the recent publication by Ciet et al. [1] related to the diagnosis of respiratory tract exacerbation (RTE) in cystic fibrosis (CF) using diffusion-weighted magnetic resonance imaging (DWI). RTE is a difficult diagnosis and their results highlight the usefulness of magnetic resonance imaging (MRI) in radiation-free management of CF. In this study, the visual analysis of a DWI score had good diagnostic accuracy to discriminate between controls and RTE's and the authors must be congratulated for this result. However, in their study, the total acquisition time in the supine position to complete both T2 and DWI sequences was 30 min, which is very long in the clinical context of RTE if we are to obtain artefact-free images. In addition, only the largest restricted consolidations in the RTE group were selected for analysis, meaning that bronchi potentially thickened and mucus-filled during RTE were excluded. Last but not least, in order to assess the value of DWI as compared to a standard T2 sequence for diagnosing RTE, it is necessary to demonstrate whether or not the DWI “hotspots” could correspond to an artefact called the T2-shine-through effect [2]. Indeed, T2 has already been demonstrated as a biomarker for acute lung inflammation [3]. To solve this, the authors performed quantitative measurements of the apparent diffusion coefficient (ADC) in both controls and subjects undergoing RTE. In controls, ADC measurements were performed randomly inside the lung parenchyma when no hotspots were visible. Surprisingly, the receiver operating characteristic (ROC) curves of the ADC indicated 100% specificity for the diagnosis of RTE towards the lowest ADC values. This crucial point is unfortunately not discussed though it is a feature that corresponds neither to the literature [4–6] nor to the physical principle of this measurement. Indeed, the general mathematical formula to calculate an ADC value is: ADC= −1/b1·Ln(S1/S) where S1 and S correspond to the DWI signals at two b-values, where b is the gradient factor. Therefore, there are two mathematical possibilities under normal conditions: 1) Owing to the very short decay time of the lung signal due to susceptibility artefacts, there is a need for ultra-short echo times (of a microsecond order of magnitude) in order to obtain any signal from the lungs [7, 8]. The DWI echo time was 54 ms and thus the lung signal was a null value at all b-values. In agreement with this, the figures in the article display no vessel and no signal inside the lung (and, as a consequence, S1=S=0). 2) Due to additional noise, S1 and S may not be exactly equal to zero (as can also be seen in the figures of the article). Therefore S1=(s1+n1) and S=(s+n), where n represents the level of noise. Since noise is expected to be constant n≈n1 and, therefore, the mathematical formula for ADC becomes: ADC= −1/b·Ln(1)=0. Restriction of lung magnetic resonance diffusion is not specific for RTE but can correspond to a normal parenchyma

    更新日期:2017-11-16
  • Action levels for indoor radon: different risks for the same lung carcinogen?
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Alberto Ruano-Ravina; Karl T. Kelsey; Alberto Fernández-Villar; Juan M. Barros-Dios

    Radon is the second most important risk factor for lung cancer but recommended exposure differs in many countries http://ow.ly/VZ8y30fDdYz

    更新日期:2017-11-09
  • Digital health to end tuberculosis in the Sustainable Development Goals era: achievements, evidence and future perspectives
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Dennis Falzon; Giovanni Battista Migliori; Ernesto Jaramillo; Karin Weyer; Guy Joos; Mario Raviglione

    Use of digital technologies to support TB care and prevention can be a model for broader action to achieve the SDGs http://ow.ly/QEcE30fKnAZ

    更新日期:2017-11-09
  • Elucidating progression of early cystic fibrosis lung disease
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Kathryn Ramsey; Felix Ratjen; Philipp Latzin

    Findings that infants with CF followed up regularly have mild, transient lung function deficits are encouraging http://ow.ly/SOKN30fRn3I

    更新日期:2017-11-09
  • Pulmonary function deficits in newborn screened infants with cystic fibrosis managed with standard UK care are mild and transient
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Gwyneth Davies; Janet Stocks; Lena P. Thia; Ah-Fong Hoo; Andrew Bush; Paul Aurora; Lucy Brennan; Simon Lee; Sooky Lum; Philippa Cottam; Joanne Miles; Jane Chudleigh; Jane Kirkby; Ian M. Balfour-Lynn; Siobhán B. Carr; Colin Wallis; Hilary Wyatt; Angie Wade

    With the advent of novel designer molecules for cystic fibrosis (CF) treatment, there is huge need for early-life clinical trial outcomes, such as infant lung function (ILF). We investigated the degree and tracking of ILF abnormality during the first 2 years of life in CF newborn screened infants. Forced expiratory volume in 0.5 s (FEV0.5), lung clearance index (LCI) and plethysmographic functional residual capacity were measured at ∼3 months, 1 year and 2 years in 62 infants with CF and 34 controls. By 2 years there was no significant difference in FEV0.5 z-score between CF and controls, whereas mean LCI z-score was 0.81 (95% CI 0.45–1.17) higher in CF. However, there was no significant association between LCI z-score at 2 years with either 3-month or 1-year results. Despite minimal average group changes in any ILF outcome during the second year of life, marked within-subject changes occurred. No child had abnormal LCI or FEV0.5 on all test occasions, precluding the ability to identify “high-risk” infants in early life. In conclusion, changes in lung function are mild and transient during the first 2 years of life in newborn screened infants with CF when managed according to a standardised UK treatment protocol. Their potential role in tracking disease to later childhood will be ascertained by ongoing follow-up.

    更新日期:2017-11-09
  • Elevated lung clearance index in infants with cystic fibrosis shortly after birth
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Elisabeth Kieninger; Sophie Yammine; Insa Korten; Pinelopi Anagnostopoulou; Florian Singer; Urs Frey; Anne Mornand; Maura Zanolari; Isabelle Rochat; Daniel Trachsel; Dominik Mueller-Suter; Alexander Moeller; Carmen Casaulta; Philipp Latzin

    It is not known at what age lung function impairment may arise in children with cystic fibrosis (CF). We assessed lung function shortly after birth in infants with CF diagnosed by newborn screening. We performed infant lung function measurements in a prospective cohort of infants with CF and healthy controls. We assessed lung clearance index (LCI), functional residual capacity (FRC) and tidal breathing parameters. The primary outcome was prevalence and severity of abnormal lung function (±1.64 z-scores) in CF. We enrolled 53 infants with CF (mean age 7.8 weeks) and 57 controls (mean age 5.2 weeks). Compared to controls, LCI and FRC were elevated (mean difference 0.30, 95% CI 0.02–0.60; p=0.034 and 14.5 mL, 95% CI 7.7–21.3 mL; p<0.001, respectively), while ratio of time to peak tidal expiratory flow to expiratory time was decreased in infants with CF. In 22 (41.5%) infants with CF, either LCI or FRC exceeded 1.64 z-scores; three infants had both elevated LCI and FRC. Shortly after birth, abnormal lung function is prevalent in CF infants. Ventilation inhomogeneity or hyperinflation may serve as noninvasive markers to monitor CF lung disease and specific treatment effects, and could thus be used as outcome parameters for future intervention studies in this age group.

    更新日期:2017-11-09
  • TASK-1 (KCNK3) channels in the lung: from cell biology to clinical implications
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Andrea Olschewski; Emma L. Veale; Bence M. Nagy; Chandran Nagaraj; Grazyna Kwapiszewska; Fabrice Antigny; Mélanie Lambert; Marc Humbert; Gábor Czirják; Péter Enyedi; Alistair Mathie

    TWIK-related acid-sensitive potassium channel 1 (TASK-1 encoded by KCNK3) belongs to the family of two-pore domain potassium channels. This gene subfamily is constitutively active at physiological resting membrane potentials in excitable cells, including smooth muscle cells, and has been particularly linked to the human pulmonary circulation. TASK-1 channels are sensitive to a wide array of physiological and pharmacological mediators that affect their activity such as unsaturated fatty acids, extracellular pH, hypoxia, anaesthetics and intracellular signalling pathways. Recent studies show that modulation of TASK-1 channels, either directly or indirectly by targeting their regulatory mechanisms, has the potential to control pulmonary arterial tone in humans. Furthermore, mutations in KCNK3 have been identified as a rare cause of both familial and idiopathic pulmonary arterial hypertension. This review summarises our current state of knowledge of the functional role of TASK-1 channels in the pulmonary circulation in health and disease, with special emphasis on current advancements in the field.

    更新日期:2017-11-09
  • Final treatment outcomes of multidrug- and extensively drug-resistant tuberculosis patients in Latvia receiving delamanid-containing regimens
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Liga Kuksa; Linda Barkane; Norbert Hittel; Rajesh Gupta

    Latvia is a high-priority country in the fight against tuberculosis (TB) in Europe, with an estimated TB incidence of 41 per 100 000 in 2015 [1]. In spite of an improving TB control programme [2] and cure rates reaching 80% for new and retreatment TB cases notified in 2014, multidrug-resistant (MDR-) TB (defined as TB resistant to rifampicin and isoniazid) rates in Latvia remain high [1]. An estimated 8% of new cases and 30% of retreatment TB cases were at least rifampicin-resistant (RR) in 2015 [1]. Cure rates in Latvia were 68% for the 2013 RR/MDR-TB cohort [1]. Of all the MDR-TB patients registered in 2015, 25% had extensively drug-resistant (XDR-) TB (defined as MDR-TB with additional resistance to a fluoroquinolone and a second-line injectable drug) [1].Final treatment outcomes from the first cohort of delamanid MDR-TB patients in Latvia support its safety and efficacy

    更新日期:2017-11-09
  • Infertility in an adult cohort with primary ciliary dyskinesia: phenotype–gene association
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Gert Jan Vanaken; Laurence Bassinet; Mieke Boon; Rahma Mani; Isabelle Honoré; Jean-Francois Papon; Harry Cuppens; Martine Jaspers; Natalie Laurent; André Coste; Estelle Escudier; Serge Amselem; Bernard Maitre; Marie Legendre; Sophie Christin-Maitre

    Primary ciliary dyskinesia (PCD) is a rare autosomal recessive disorder (prevalence 1:10 000 to 1:40 000 births) characterised by impaired mucociliary clearance because of abnormal motile ciliary function [1, 2]. Five main ultrastructural PCD phenotypes have been described. Most result from a lack of dynein arms (DAs): no outer and inner DAs (2DAs), outer DAs alone (ODA) or inner DAs with microtubular disorganisation (IDA/MTD); or defects yielding an abnormal central complex (CC). Some patients with genetically confirmed PCD have apparently normal ciliary structure on electron microscopy (nEM). More than 30 genes encoding proteins involved in the structure or assembly of the axoneme, the ciliary internal cytoskeleton, are implicated in PCD [3]; their analysis enables identification of bi-allelic disease-causing mutations in 50–75% of patients. Approximately half of PCD cases are associated with situs inversus , thereby defining Kartagener's syndrome. Moreover, because motile cilia and sperm flagella share common axonemal structures, most PCD-affected males are thought to be infertile [4]. According to the literature, male infertility is caused by severe or total asthenozoospermia and is currently treated by recourse to in vitro fertilisation or intracytoplasmic sperm injection [5, 6]. However, spontaneous fatherhood of PCD patients has been reported.Infertility, observed in 75% of male and 61% of female PCD patients, is dependent on ultrastructural and gene defects We thank all the individuals and their families for their cooperation, as well as all the referring physicians. The researchers participate in the network of COST Action BEAT-PCD (Better Evidence to Advance Therapeutic Options for PCD; no. BM 1407). L. Bassinet, I. Honoré, J.-.F Papon, A. Coste, E. Escudier, S. Amselem, B. Maitre, M. Legendre and S. Christin-Maitre are members of the RadiCONetwork (Inserm, France).

    更新日期:2017-11-09
  • Recommending prolonged bedaquiline use for the treatment of highly resistant strains of tuberculosis
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Jennifer Furin; Erica Lessem; Vivian Cox

    We read with interest the article by Caminero et al. [1] proposing a standardised approach to treating both pre-extensively drug-resistant tuberculosis (pre-XDR-TB) and extensively drug-resistant tuberculosis (XDR-TB). This proposal is welcome considering the dearth of evidence-based recommendations on the optimal management of highly resistant tuberculosis (TB) [2]. Given the increasing recognition of the prevalence, morbidity and mortality associated with pre-XDR and XDR-TB, as well as the significant improvement in treatment outcomes with the use of novel and repurposed drugs [3], a clear policy for optimal management of these forms of TB is urgently needed.Treatment of XDR-TB by prolonged use of bedaquiline is appropriate for some individuals

    更新日期:2017-11-09
  • Bedaquiline: how better to use it
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Jose A. Caminero; Alberto Piubello; Anna Scardigli; Giovanni Battista Migliori

    We read with interest the correspondence by J. Furin and co-workers and we wish to thank them for their useful comments on our editorial proposing a rationale for a standardised regimen to manage difficult-to-treat cases affected by extensively drug-resistant tuberculosis (XDR-TB) or by so-called pre-extensively drug-resistant tuberculosis (pre-XDR; multidrug-resistant tuberculosis (MDR-TB) cases with additional resistance to fluoroquinolones or second-line injectable drugs) [1]. We agree with the comments by Furin and co-workers and the arguments discussing the possible use of the new drugs (bedaquiline and/or delamanid) for more than 6 months. Clinicians know very well how difficult it is to manage the treatment of these cases in view of their clinical complexity (with frequent adverse events), long duration and high cost [2–4]. Considering the new perspectives for treating MDR-TB and XDR-TB we fully agree that we are presently facing exciting times. We finally have a couple of new and repurposed drugs and we are slowly discovering how best to use them, as well as how effective and safe they are [4–7]. The necessary body of knowledge to support evidence-based recommendations will need time to be raised and this is reflected by the increase in new proposals and recommendations being issued [8, 9]. Among the different ingredients for a potential, future standardised regimen for MDR/XDR-TB cases, the biological plausibility of the core drugs to be used (bactericidal and sterilising) is particularly important (table 1) [1]. As both bedaquiline and delamanid have excellent characteristics, both their prolonged and/or combined use will be challenges that will need to be faced in the future. Slowly but surely new evidence is becoming available [2, 3] and we are confident that, given the high morbidity and mortality caused by MDR/XDR-TB, as well as the collaborative spirit animating clinicians, public health officers, policy makers, donors and members of the affected communities, better evidence will be raised to always ensure that the patient is adequately protected. Finally, the “off-label” use of drugs is sometimes necessary to manage patients for whom no other alternatives exist. Their use requires adequate capacity in terms of clinical expertise, laboratory support and infection control measures. We therefore hope that our proposal will soon be supported by the necessary evidence so as to be useful, safe and effective.Reflections on the best possible use of bedaquiline

    更新日期:2017-11-09
  • 更新日期:2017-11-09
  • COPD: algorithms and clinical management
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Rosa Faner; Alvar Agustí

    Can algorithms help the practicing clinician to prescribe the best treatment? http://ow.ly/44yF30fwCc9

    更新日期:2017-11-02
  • Multi-trigger and viral wheeze: describing symptoms or defining diseases?
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Daan Caudri

    Multi-trigger and viral wheeze track over time but it is unclear whether they represent separate disease entities http://ow.ly/El7w30eO9fb

    更新日期:2017-11-02
  • A simple algorithm for the identification of clinical COPD phenotypes
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Pierre-Régis Burgel; Jean-Louis Paillasseur; Wim Janssens; Jacques Piquet; Gerben ter Riet; Judith Garcia-Aymerich; Borja Cosio; Per Bakke; Milo A. Puhan; Arnulf Langhammer; Inmaculada Alfageme; Pere Almagro; Julio Ancochea; Bartolome R. Celli; Ciro Casanova; Juan P. de-Torres; Marc Decramer; Andrés Echazarreta; Cristobal Esteban; Rosa Mar Gomez Punter; MeiLan K. Han; Ane Johannessen; Bernhard Kaiser; Bernd Lamprecht; Peter Lange; Linda Leivseth; Jose M. Marin; Francis Martin; Pablo Martinez-Camblor; Marc Miravitlles; Toru Oga; Ana Sofia Ramírez; Don D. Sin; Patricia Sobradillo; Juan J. Soler-Cataluña; Alice M. Turner; Francisco Javier Verdu Rivera; Joan B. Soriano; Nicolas Roche

    This study aimed to identify simple rules for allocating chronic obstructive pulmonary disease (COPD) patients to clinical phenotypes identified by cluster analyses. Data from 2409 COPD patients of French/Belgian COPD cohorts were analysed using cluster analysis resulting in the identification of subgroups, for which clinical relevance was determined by comparing 3-year all-cause mortality. Classification and regression trees (CARTs) were used to develop an algorithm for allocating patients to these subgroups. This algorithm was tested in 3651 patients from the COPD Cohorts Collaborative International Assessment (3CIA) initiative. Cluster analysis identified five subgroups of COPD patients with different clinical characteristics (especially regarding severity of respiratory disease and the presence of cardiovascular comorbidities and diabetes). The CART-based algorithm indicated that the variables relevant for patient grouping differed markedly between patients with isolated respiratory disease (FEV1, dyspnoea grade) and those with multi-morbidity (dyspnoea grade, age, FEV1 and body mass index). Application of this algorithm to the 3CIA cohorts confirmed that it identified subgroups of patients with different clinical characteristics, mortality rates (median, from 4% to 27%) and age at death (median, from 68 to 76 years). A simple algorithm, integrating respiratory characteristics and comorbidities, allowed the identification of clinically relevant COPD phenotypes.

    更新日期:2017-11-02
  • Temporal stability of multitrigger and episodic viral wheeze in early childhood
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Ben D. Spycher; Cara Cochrane; Raquel Granell; Jonathan A.C. Sterne; Michael Silverman; Eva Pedersen; Erol A. Gaillard; John Henderson; Claudia E. Kuehni

    The distinction between episodic viral wheeze (EVW) and multitrigger wheeze (MTW) is used to guide management of preschool wheeze. It has been questioned whether these phenotypes are stable over time. We examined the temporal stability of MTW and EVW in two large population-based cohorts. We classified children from the Avon Longitudinal Study of Parents and Children (n=10 970) and the Leicester Respiratory Cohorts ((LRCs), n=3263) into EVW, MTW and no wheeze at ages 2, 4 and 6 years based on parent-reported symptoms. Using multinomial regression, we estimated relative risk ratios for EVW and MTW at follow-up (no wheeze as reference category) with and without adjusting for wheeze severity. Although large proportions of children with EVW and MTW became asymptomatic, those that continued to wheeze showed a tendency to remain in the same phenotype: among children with MTW at 4 years in the LRCs, the adjusted relative risk ratio was 15.6 (95% CI 8.3–29.2) for MTW (stable phenotype) compared to 7.0 (95% CI 2.6–18.9) for EVW (phenotype switching) at 6 years. The tendency to persist was weaker for EVW and from 2–4 years. Results were similar across cohorts. This suggests that MTW, and to a lesser extent EVW, tend to persist regardless of wheeze severity.

    更新日期:2017-11-02
  • Endoscopic ultrasound fine-needle aspiration by experienced pulmonologists: a cusum analysis
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Paul Leong; Sheetal Deshpande; Louis B. Irving; Philip G. Bardin; Michael W. Farmer; Barton R. Jennings; Daniel P. Steinfort

    Endobronchial ultrasound transbronchial needle aspiration (EBUS TBNA) is an established, minimally invasive way to sample intrathoracic abnormalities. The EBUS scope can be passed into the oesophagus to perform endoscopic ultrasound with bronchoscope-guided fine-needle aspiration (EUS-B-FNA). In cases of suspected lung cancer, a combination of the two techniques is now recommended by consensus guidelines. EBUS TBNA is usually performed by pulmonologists; however, the learning curve for EUS-B-FNA, which may be performed during the same procedure, has not been described. A multicentre, observational Australian study, using prospectively collected data from three experienced pulmonologists was conducted. Cumulative sum (cusum) analysis was used to generate visual learning curves. A total of 152 target lesions were sampled in 137 patients, with an overall sensitivity for malignancy of 94.8%. The sensitivity for malignant lesions outside of the 2009 International Association for the Study of Lung Cancer lymph node map (largely intraparenchymal lesions) was 92.9%. All three operators were competent by conventional cusum criteria. There was one case of pneumothorax, and no episodes of mediastinitis or oesophageal perforation were observed. Our data suggest that experienced pulmonologists can safely and accurately perform EUS-B-FNA, with a high diagnostic sensitivity for both lymph node and non-nodal lesions.

    更新日期:2017-11-02
  • Un-diagnosing persistent adult asthma
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Brian J. Lipworth; Sunny Jabbal

    The diagnosis of asthma is usually based on typical symptoms, family history, audible wheeze, peak flow, spirometry, possibly in conjunction with atopy and blood eosinophilia, as well as response to treatment. In cases for which the diagnosis is less clear-cut, other tests may be required, including impulse oscillometry (IOS), exhaled nitric oxide fraction (FeNO) and bronchial challenge testing (figure 1).A pragmatic process should be considered in patients with a questionable asthma diagnosis

    更新日期:2017-11-02
  • Children under 5 years are at risk for tuberculosis after occasional contact with highly contagious patients: outbreak from a smear-positive healthcare worker
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-11-01
    Roberto Luzzati; Giovanni Battista Migliori; Matteo Zignol; Daniela Maria Cirillo; Massimo Maschio; Riccardo Tominz; Giovanna Ventura; Valentino Patussi; Lia D'Ambrosio; Rosella Centis; Franco Michieletto; Alberto Trovato; Francesco Salton; Marina Busetti; Manuela Di Santolo; Mario Raviglione; Marco Confalonieri

    The World Health Organization (WHO), jointly with experts from tuberculosis (TB) low-incidence countries, developed a framework for TB elimination [1, 2].Children under 5 years of age are at risk for tuberculosis after occasional contact with highly contagious patients

    更新日期:2017-11-02
  • ERJ October Podcast: Lessons from IPF clinical trials over the past 25 years
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    European Respiratory Society

    As part of the October issue, the European Respiratory Journal presents the latest in its series of podcasts. Chief editor Marc Humbert discusses the lessons learned from clinical trials in idiopathic pulmonary fibrosis over the past 25 years with Prof. Ganesh Raghu from the University of Washington, Seattle, WA, USA.

    更新日期:2017-10-26
  • Next generation of anti-inflammatory therapy for COPD?
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Henrik Watz

    The MAPK inhibitor RV568 might be the next generation of anti-inflammatory therapy for COPD http://ow.ly/vccD30fNP3c

    更新日期:2017-10-26
  • Occupational exposure and asthma control
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Dick Heederik

    Poor control of asthma may be the result of ongoing exposure to disinfectants http://ow.ly/njzC30fJFMj

    更新日期:2017-10-26
  • The Art of Breathing: Synergy
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Tom Kotsimbos; Gary P. Anderson

    This is an image-based article and should be viewed in PDF form. Please click on the link to open the PDF version.

    更新日期:2017-10-26
  • RV568, a narrow-spectrum kinase inhibitor with p38 MAPK-α and -γ selectivity, suppresses COPD inflammation
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Catherine E. Charron; Paul Russell; Kazuhiro Ito; Simon Lea; Yasuo Kizawa; Charlie Brindley; Dave Singh

    Novel anti-inflammatory approaches targeting chronically activated kinase pathways in chronic obstructive pulmonary disease (COPD) are needed. We evaluated RV568, a p38 mitogen-activated protein kinase-α and -γ and SRC family kinase inhibitor, in cellular and in vivo models relevant to COPD and examined its safety and efficacy in COPD patients. The anti-inflammatory activities of RV568 were tested in primary cultured monocytes, macrophages and bronchial epithelial cells and in vivo in lipopolysaccharide and cigarette smoke-exposed murine models. RV568 was evaluated in a 14-day trial in COPD patients. RV568 showed potent anti-inflammatory effects in monocytes and macrophages, which were often greater than those of corticosteroids or the p38 inhibitor Birb796. RV568 combined with corticosteroid had anti-inflammatory effects suggestive of a synergistic interaction in poly I:C-stimulated BEAS-2B cells and in the cigarette smoke model. In COPD patients, inhaled RV568 (50 µg and 100 µg) improved pre-bronchodilator forced expiratory volume in 1 s (69 mL and 48 mL respectively) and significantly reduced sputum malondialdehyde (p<0.05) compared to placebo, although there were no changes in sputum cell counts. Adverse events during RV568 and placebo treatment were similar. RV568 shows potent anti-inflammatory effects on cell and animal models relevant to COPD. RV568 was well-tolerated and demonstrated a modest clinical benefit in a 14-day COPD clinical trial.

    更新日期:2017-10-26
  • Traffic-related air pollution exposure over a 5-year period is associated with increased risk of asthma and poor lung function in middle age
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Gayan Bowatte; Bircan Erbas; Caroline J. Lodge; Luke D. Knibbs; Lyle C. Gurrin; Guy B. Marks; Paul S. Thomas; David P. Johns; Graham G. Giles; Jennie Hui; Martine Dennekamp; Jennifer L. Perret; Michael J. Abramson; E. Haydn Walters; Melanie C. Matheson; Shyamali C. Dharmage

    Current evidence concerning the impact of exposure to traffic-related air pollution (TRAP) on adult respiratory morbidity mainly comes from cross-sectional studies. We sought to establish more robust measures of this association and potential gene–environment interactions using longitudinal data from an established cohort study. Associations between measures of TRAP (nitrogen dioxide (NO2) and distance to major roads) and wheeze, asthma prevalence and lung function were investigated in participants of the Tasmanian Longitudinal Health Study at 45- and 50-year follow-ups. Generalised estimating equations were used to quantify associations and the potential modifying effect of glutathione S-transferase gene variants. Living <200 m from a major road was associated with increased prevalence of current asthma and wheeze, and lower lung function. The association between living <200 m from a major road and current asthma and wheeze was more marked for carriers of the GSTT1 null and GSTP1 val/val or ile/val genotypes. Over the 5-year period, higher NO2 exposures were associated with increased current asthma prevalence. Higher NO2 exposure was associated with lower forced vital capacity for carriers of the GSTT1 null genotype. TRAP exposures were associated with increased risk of asthma, wheeze and lower lung function in middle-aged adults. The interaction with the GSTT1 genotype suggests that deficient antioxidant mechanisms may play a role in these adverse health effects.

    更新日期:2017-10-26
  • Association between lung cancer somatic mutations and occupational exposure in never-smokers
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Christophe Paris; Pascal Do; Bénédicte Mastroianni; Adrien Dixmier; Patrick Dumont; Eric Pichon; Christos Chouaid; Bruno Coudert; Pascal Foucher; Séverine Fraboulet; Myriam Locatelli-Sanchez; Nathalie Baize; Eric Dansin; Lionel Moreau; Michel Vincent; Pascale Missy; Franck Morin; Denis Moro-Sibilot; Sébastien Couraud

    Occupational exposure constitutes a common risk factor for lung cancer. We observed molecular alterations in 73% of never-smokers, 35% of men and 8% of women were exposed to at least one occupational carcinogen. We report herein associations between molecular patterns and occupational exposure. BioCAST was a cohort study of lung cancer in never-smokers that reported risk factor exposure and molecular patterns. Occupational exposure was assessed via a validated 71-item questionnaire. Patients were categorised into groups that were unexposed and exposed to polycyclic aromatic hydrocarbons (PAH), asbestos, silica, diesel exhaust fumes (DEF), chrome and paints. Test results were recorded for EGFR, KRAS, HER2, BRAF and PIK3 mutations, and ALK alterations. Overall, 313 out of 384 patients included in BioCAST were analysed. Asbestos-exposed patients displayed a significantly lower rate of EGFR mutations (20% versus 44%, p=0.033), and a higher rate of HER2 mutations (18% versus 4%, p=0.084). ALK alterations were not associated with any occupational carcinogens. The DEF-exposed patients were diagnosed with a BRAF mutation in 25% of all cases. Chrome-exposed patients exhibited enhanced HER2 and PIK3 mutation frequency. Given its minimal effects in the subgroups, we conclude that occupational exposure slightly affects the molecular pattern of lung cancers in never-smokers. In particular, asbestos-exposed patients have a lower chance of EGFR mutations.

    更新日期:2017-10-26
  • Idiopathic pulmonary fibrosis: lessons from clinical trials over the past 25 years
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Ganesh Raghu

    Idiopathic pulmonary fibrosis (IPF) is a progressive and ultimately fatal disease. A major breakthrough in treatment came when, after decades of clinical trials which failed to identify an efficacious treatment regimen, two therapies were successful in Phase-III trials. The advent of these therapies, nintedanib and pirfenidone, meant that for the first time IPF patients had two treatment options that could reduce disease progression. This review summarises the key lessons to be obtained from the clinical trials that led to the current international clinical practice guidelines for the treatment of IPF and provides insights for the design of future clinical trials that are needed if we are to improve outcomes that are clinically meaningful to IPF patients.

    更新日期:2017-10-26
  • Tuberculosis screening in asylum seekers in Germany, 2015: characteristics of cases and yield
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Lena Fiebig; Barbara Hauer; Marta Andrés; Walter Haas

    In 2015, according to the International Organization for Migration (IOM), 244 million people worldwide were international migrants, representing the highest number ever recorded [1]. The level of forced displacement globally was the highest since World War II, with a dramatic increase in the number of refugees, asylum seekers and internally displaced people. Germany became one of the largest recipients of first asylum seeking claims [2]. TB screening among asylum seekers in Germany identified 1255 cases in 2015, and may have decreased TB exposure We thank everyone who contributed to the screening, case management and TB surveillance and control in Germany. We also thank Doris Altmann (Robert Koch Institute, Berlin, Germany) for data preparation, Bonita Brodhun (Robert Koch Institute) for the management of TB notification data, Nita Perumal (Robert Koch Institute) for helpful comments on the manuscript, and Harald Lederer (Bundesamt für Migration und Flüchtlinge) for providing the numbers of registered asylum seekers. Author contributions were as follows. Lena Fiebig, Barbara Hauer and Walter Haas conceptualised the study. Lena Fiebig drafted the manuscript and performed the data analysis. Barbara Hauer performed the literature review. Marta Andrés helped in the data analysis. Barbara Ha, Marta Andrés and Walter Haas collaborated in writing the manuscript. All authors reviewed and approved the final manuscript.

    更新日期:2017-10-26
  • Mycobacterium tuberculosis transmission from patients with drug-resistant compared to drug-susceptible TB: a systematic review and meta-analysis
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Chiori Kodama; Berit Lange; Ioana D. Olaru; Palwasha Khan; Marc Lipman; James A. Seddon; Derek Sloan; Louis Grandjean; Rashida Abbas Ferrand; Katharina Kranzer

    The extent to which drug-resistant (DR) Mycobacterium tuberculosis strains cause infection and progression to tuberculosis (TB) disease in comparison to drug-susceptible (DS) strains is unknown. Studies in guinea pigs and in vitro experiments have suggested a reduced fitness of organisms that harbour mutations that confer drug resistance [1, 2]; it was therefore believed that transmitted drug resistance was a rare event. However, more recent work using molecular typing has shown transmission events occurring in the context of DR-TB [3]. Understanding the risk of transmission, infection and progression to disease in the context of DR-TB is important to guide control measures and help predict the evolution and magnitude of the multidrug-resistant (MDR)-TB epidemic. Hence, we performed a systematic review and meta-analysis to assess whether M. tuberculosis transmission and progression to TB disease (risk/rate of M. tuberculosis infection in all contacts, risk/rate of TB disease in all contacts and risk/rate of TB disease in infected contacts) differ between DR- and DS-TB. No evidence that drug-resistant TB results in fewer infections or cases in contacts than drug-susceptible TB We would like to acknowledge the valuable administrative support during the conduct of this study by Johannes Camp and Lucy Wong of University Hospital Freiburg. Contributions of authors: K. Kranzer conceived the idea for the systematic review. K. Kranzer, C. Kodama and B. Lange designed the study. K. Kranzer, C. Kodama and B. Lange performed screening and data extraction. C. Kodama and B. Lange assessed risk of bias. B. Lange and K. Kranzer performed the meta-analysis. I. Olaru, P. Khan, M. Lipman, J. Seddon, D. Sloan, L. Grandjean and R. Ferrand contributed to the analysis and manuscript writing. All authors read and approved the final version of the manuscript.

    更新日期:2017-10-26
  • Frequency and significance of indeterminate and borderline Quantiferon Gold TB IGRA results
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    James Brown; Kartik Kumar; Jacob Reading; Jennifer Harvey; Saraswathi Murthy; Santino Capocci; Susan Hopkins; Suranjith Seneviratne; Ian Cropley; Marc Lipman

    The Quantiferon Gold test is one of two commercially available tuberculosis (TB) interferon-γ release assays (IGRAs) recommended for the diagnosis of latent TB infection [1]. A Quantiferon Gold test is considered positive if the result is ≥0.35 IU·mL−1 [2]. However, longitudinal studies have shown that a significant number of test reversions and conversions occur if results just above or below this threshold are repeated [3, 4]. This variation may be due to random chance or other factors such as test-related errors, differences in absolute lymphocyte numbers and within-subject variability of the interferon-γ response [5, 6]. The high proportion of conversions and reversions around the 0.35 IU·mL−1 cut-off has led some to suggest that a borderline or equivocal range should be used [7], as this avoids treatment of individuals who do not have a ‘stable’ positive result, as well as failure to treat those just below the 0.35 threshold who would convert to a positive result if the test were repeated [6]. Borderline and equivocal results for the Quantiferon Gold test are common and repeated borderline tests often change We would like to thank Ronnie Chee, Mark Davis and Annabelle Mai for assistance with the recording, distribution and supervision of results.

    更新日期:2017-10-26
  • Large cell neuroendocrine carcinoma of the lung: chemotherapy regimen depends on how “large” your diagnostic criteria are
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Giulio Rossi; Lucia Longo; Fausto Barbieri; Federica Bertolini; Paolo Spagnolo

    We read with great interest the article by Derks et al . [1] on the efficacy of different chemotherapeutic regimens in a large series of 128 patients with stage IV large cell neuroendocrine carcinoma (LCNEC) of the lung. As outlined by the authors, in 2005, we dealt with the same dilemma when analysing 83 surgically resected LCNECs collected at two different institutions [2]. In our study, patients with metastatic disease treated either in an adjuvant setting or post-surgery with platinum/etoposide, a conventional regimen for small cell lung cancer (SCLC), showed a significant clinical benefit in terms of overall survival compared to patients treated with chemotherapeutic regimens used for non-small cell lung cancer (NSCLC). In contrast, Derks et al . [1] showed that patients with metastatic LCNEC receiving platinum/gemcitabine, a regimen commonly used in NSCLC, displayed a longer overall survival than those receiving SCLC-oriented chemotherapy. In our view, a number of reasons, discussed herein, may account for the apparent discrepancies between these and other studies [3]. In our study [2], LCNEC cases eventually represented less than one-quarter (83 (23.8%) out of 348) of all lung cancer cases identified based on morphological examination alone. In addition, although we applied strict diagnostic criteria, some cases required a consensus diagnosis among all three thoracic pathologists involved in the histological review, highlighting the difficulties encountered when making a diagnosis of LCNEC, even amongst expert pathologists [4]. In agreement with the last two World Health Organization (WHO) classifications of lung tumours [5] suggesting to limit/avoid the diagnosis of LCNEC on cytology/small biopsy, we included only surgically resected cases ( i.e . none of our original cases was in stage IV at the time of the diagnosis). Conversely, Derks et al . [1] and another recent study by Naidoo et al. [6] included only stage IV LCNEC cases diagnosed on biopsy. Diagnostic criteria influence the correct chemotherapy in LCNEC

    更新日期:2017-10-26
  • Why we should improve current practice of diagnosing and treating pulmonary large cell neuroendocrine carcinomas in patients with advanced disease
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Jules Derks; Robert Jan van Suylen; Erik Thunnissen; Michael den Bakker; Harry Groen; Egbert Smit; Ronald Damhuis; Esther van den Broek; Ernst-Jan Speel; Anne-Marie C. Dingemans

    In response to our manuscript on first-line chemotherapy treatment for metastatic pulmonary large cell neuroendocrine carcinoma (LCNEC) [1], Rossi and co-workers raised their concerns about the validity of our results by questioning the accuracy of LCNEC diagnosis on a biopsy specimen. We would like to thank the authors for their critical appraisal, underscoring the need to increase awareness among pulmonologists, oncologists and pathologists of the diagnostic issues and consequences of metastatic LCNEC diagnosed on a biopsy specimen. Current criteria for LCNEC diagnosed on a biopsy specimen are in need of improvement

    更新日期:2017-10-26
  • Treatment of sarcoidosis-associated pulmonary hypertension: so close, and yet so far
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Robert P. Baughman; Oksana A. Shlobin

    More evidence that sarcoidosis patients with pulmonary hypertension respond to therapy http://ow.ly/H40c30fetN4

    更新日期:2017-10-19
  • Morphine to relieve exertional dyspnoea in COPD: myth, dream or reality?
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Louis Laviolette; Pierantonio Laveneziana

    Opioids show promise in managing exertional dyspnoea; safety of widespread use in COPD patients remains unproven http://ow.ly/A9bX30fr7FR

    更新日期:2017-10-19
  • Hypoxia-induced PD-L1/PD-1 crosstalk impairs T-cell function in sleep apnoea
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Carolina Cubillos-Zapata; Jose Avendaño-Ortiz; Enrique Hernandez-Jimenez; Victor Toledano; Jose Casas-Martin; Anibal Varela-Serrano; Marta Torres; Isaac Almendros; Raquel Casitas; Isabel Fernández-Navarro; Aldara Garcia-Sanchez; Luis A. Aguirre; Ramón Farre; Eduardo López-Collazo; Francisco García-Rio

    Obstructive sleep apnoea (OSA) is associated with higher cancer incidence, tumour aggressiveness and cancer mortality, as well as greater severity of infections, which have been attributed to an immune deregulation. We studied the expression of programmed cell death (PD)-1 receptor and its ligand (PD-L1) on immune cells from patients with OSA, and its consequences on immune-suppressing activity. We report that PD-L1 was overexpressed on monocytes and PD-1 was overexpressed on CD8+ T-cells in a severity-dependent manner. PD-L1 and PD-1 overexpression were induced in both the human in vitro and murine models of intermittent hypoxia, as well as by hypoxia-inducible factor-1α transfection. PD-L1/PD-1 crosstalk suppressed T-cell proliferation and activation of autologous T-lymphocytes and impaired the cytotoxic activity of CD8+ T-cells. In addition, monocytes from patients with OSA exhibited high levels of retinoic acid related orphan receptor, which might explain the differentiation of myeloid-derived suppressor cells. Intermittent hypoxia upregulated the PD-L1/PD-1 crosstalk in patients with OSA, resulting in a reduction in CD8+ T-cell activation and cytotoxicity, providing biological plausibility to the increased incidence and aggressiveness of cancer and the higher risk of infections described in these patients.

    更新日期:2017-10-19
  • Combined measurement of carbon monoxide and nitric oxide lung transfer does not improve the identification of pulmonary hypertension in systemic sclerosis
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Bruno Degano; Thibaud Soumagne; Thomas Delaye; Patrick Berger; Thierry Perez; Alicia Guillien; Jean-Luc Pellegrin; David Launay; Nadine Magy-Bertrand; Christian Agard; Kiet Phong Tiev; Thông Hua-Huy; Catherine Tardiff; Véronique Diaz; Arnaud Chambellan; Anh Tuan Dinh-Xuan

    Screening is important to determine whether patients with systemic sclerosis (SSc) have pulmonary hypertension because earlier pulmonary hypertension treatment can improve survival in these patients. Although decreased transfer factor of the lung for carbon monoxide (TLCO) is currently considered the best pulmonary function test for screening for pulmonary hypertension in SSc, small series have suggested that partitioning TLCO into membrane conductance (diffusing capacity) for carbon monoxide (DMCO) and alveolar capillary blood volume (VC) through combined measurement of TLCO and transfer factor of the lung for nitric oxide (TLNO) is more effective to identify pulmonary hypertension in SSc patients compared with TLCO alone. Here, the objective was to determine whether combined TLCO–TLNO partitioned with recently refined equations could more accurately detect pulmonary hypertension than TLCO alone in SSc. For that purpose, 572 unselected consecutive SSc patients were retrospectively recruited in seven French centres. Pulmonary hypertension was diagnosed with right heart catheterisation in 58 patients. TLCO, TLNO and VC were all lower in SSc patients with pulmonary hypertension than in SSc patients without pulmonary hypertension. The area under the receiver operating characteristic curve for the presence of pulmonary hypertension was equivalent for TLCO (0.82, 95% CI 0.79–0.85) and TLNO (0.80, 95% CI 0.76–0.83), but lower for VC (0.75, 95% CI 0.71–0.78) and DMCO (0.66, 95% CI 0.62–0.70). Compared with TLCO alone, combined TLCO–TLNO does not add capability to detect pulmonary hypertension in unselected SSc patients.

    更新日期:2017-10-19
  • Management and long-term outcomes of sarcoidosis-associated pulmonary hypertension
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Athénaïs Boucly; Vincent Cottin; Hilario Nunes; Xavier Jaïs; Abdelatif Tazi; Grégoire Prévôt; Martine Reynaud-Gaubert; Claire Dromer; Catherine Viacroze; Delphine Horeau-Langlard; Christophe Pison; Emmanuel Bergot; Julie Traclet; Jason Weatherald; Gérald Simonneau; Dominique Valeyre; David Montani; Marc Humbert; Olivier Sitbon; Laurent Savale

    Studies reporting the effects of modern strategies with pulmonary arterial hypertension (PAH)-targeted therapies in sarcoidosis-associated pulmonary hypertension (S-APH) are limited. Clinical and haemodynamic data from newly diagnosed patients with severe S-APH (mean pulmonary artery pressure (mPAP) >35 mmHg or mPAP 25–35 mmHg with cardiac index <2.5 L·min−1·m−2) were collected from the French Pulmonary Hypertension Registry between 2004 and 2015. Data from 126 patients with severe S-APH were analysed (mean±sd age 57.5±11.6 years, 74% radiological stage IV). 97 patients (77%) received PAH-targeted therapy and immunosuppressive therapy was initiated or escalated in 33 patients at the time of pulmonary hypertension diagnosis. Four months after PAH-targeted therapy initiation, mean±sd pulmonary vascular resistance decreased from 9.7±4.4 to 6.9±3.0 Wood units (p<0.001), without significant improvement in exercise capacity. Among the 11 patients treated only with immunosuppressive therapy, a haemodynamic improvement was observed in four patients, including two with compressive lymph nodes. After a median follow-up of 28 months, 39 patients needed PAH-targeted therapy escalation, nine underwent lung transplantation and 42 had died. Survival at 1, 3 and 5 years was 93%, 74% and 55%, respectively. PAH-targeted therapy improved short-term pulmonary haemodynamics in severe S-APH without change in exercise capacity. Immunosuppressive therapy improved haemodynamics in selected patients. Pulmonary hypertension in sarcoidosis remains associated with a poor prognosis.

    更新日期:2017-10-19
  • Effect of morphine on breathlessness and exercise endurance in advanced COPD: a randomised crossover trial
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Sara J. Abdallah; Courtney Wilkinson-Maitland; Nathalie Saad; Pei Zhi Li; Benjamin M. Smith; Jean Bourbeau; Dennis Jensen

    The objective of the present study was to evaluate the effect of morphine on exertional breathlessness and exercise endurance in advanced chronic obstructive pulmonary disease (COPD). In a randomised crossover trial, we compared the acute effect of immediate-release oral morphine versus placebo on physiological and perceptual responses during constant-load cardiopulmonary cycle exercise testing (CPET) in 20 adults with advanced COPD and chronic breathlessness syndrome. Compared with placebo, morphine reduced exertional breathlessness at isotime by 1.2±0.4 Borg units and increased exercise endurance time by 2.5±0.9 min (both p≤0.014). During exercise at isotime, morphine decreased ventilation by 1.3±0.5 L·min−1 and breathing frequency by 2.0±0.9 breaths·min−1 (both p≤0.041). Compared with placebo, morphine decreased exertional breathlessness at isotime by ≥1 Borg unit in 11 participants (responders) and by <1 Borg unit in nine participants (non-responders). Baseline participant characteristics, including pulmonary function and cardiorespiratory fitness, were similar between responders and non-responders. A higher percentage of responders versus non-responders stopped incremental CPET due to intolerable breathlessness: 82 versus 33% (p=0.028). Immediate-release oral morphine improved exertional breathlessness and exercise endurance in some, but not all, adults with advanced COPD. The locus of symptom-limitation on laboratory-based CPET may help to identify patients most likely to benefit from morphine.

    更新日期:2017-10-19
  • What is precision medicine?
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Inke R. König; Oliver Fuchs; Gesine Hansen; Erika von Mutius; Matthias V. Kopp

    The term “precision medicine” has become very popular over recent years, fuelled by scientific as well as political perspectives. Despite its popularity, its exact meaning, and how it is different from other popular terms such as “stratified medicine”, “targeted therapy” or “deep phenotyping” remains unclear. Commonly applied definitions focus on the stratification of patients, sometimes referred to as a novel taxonomy, and this is derived using large-scale data including clinical, lifestyle, genetic and further biomarker information, thus going beyond the classical “signs-and-symptoms” approach. While these aspects are relevant, this description leaves open a number of questions. For example, when does precision medicine begin? In which way does the stratification of patients translate into better healthcare? And can precision medicine be viewed as the end-point of a novel stratification of patients, as implied, or is it rather a greater whole? To clarify this, the aim of this paper is to provide a more comprehensive definition that focuses on precision medicine as a process. It will be shown that this proposed framework incorporates the derivation of novel taxonomies and their role in healthcare as part of the cycle, but also covers related terms.

    更新日期:2017-10-19
  • Precision medicine in airway diseases: moving to clinical practice
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Alvar Agustí; Mona Bafadhel; Richard Beasley; Elisabeth H. Bel; Rosa Faner; Peter G. Gibson; Renaud Louis; Vanessa M. McDonald; Peter J. Sterk; Mike Thomas; Claus Vogelmeier; Ian D. Pavord

    On February 21, 2017, a European Respiratory Society research seminar held in Barcelona discussed how to best apply precision medicine to chronic airway diseases such as asthma and chronic obstructive pulmonary disease. It is now clear that both are complex and heterogeneous diseases, that often overlap and that both require individualised assessment and treatment. This paper summarises the presentations and discussions that took place during the seminar. Specifically, we discussed the need for a new taxonomy of human diseases, the role of different players in this scenario (exposome, genes, endotypes, phenotypes, biomarkers and treatable traits) and a number of unanswered key questions in the field. We also addressed how to deploy airway precision medicine in clinical practice today, both in primary and specialised care. Finally, we debated the type of research needed to move the field forward.

    更新日期:2017-10-19
  • Prospective study of body mass index and risk of sarcoidosis in US women
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Orianne Dumas; Krislyn M. Boggs; Yvette C. Cozier; Meir J. Stampfer; Carlos A. Camargo

    Sarcoidosis is a systemic inflammatory disorder, characterised by the formation of immune granulomas that can occur in various organs, but typically affects the lungs [1]. Although sarcoidosis resolves spontaneously in many cases, about one-third of patients experience chronic disease associated with significant morbidity [2]. A higher BMI is prospectively associated with an increased risk of developing sarcoidosis in women The Nurses’ Health Study II is coordinated at the Channing Division of Network Medicine, Brigham and Women's Hospital, Boston, MA. We would like to thank the participants and staff of the Nurses’ Health Study II for their valuable contributions.

    更新日期:2017-10-19
  • Effect of pirfenidone on cough in patients with idiopathic pulmonary fibrosis
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Mirjam J.G. van Manen; Surinder S. Birring; Carlo Vancheri; Virginia Vindigni; Elisabetta Renzoni; Anne-Marie Russell; Monique Wapenaar; Vincent Cottin; Marlies S. Wijsenbeek

    In patients with IPF, pirfenidone reduces objective 24-h cough counts and improves subjective measures of cough http://ow.ly/iiGu30f7Pea

    更新日期:2017-10-19
  • Do admission glucose levels aid in predicting mortality associated with community-acquired pneumonia?
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Douwe F. Postma; Cornelis H. van Werkhoven; Darren P.R. Troeman; Sanjay U.C. Sankatsing; Jan Jelrik Oosterheert; Marc J.M. Bonten

    Diabetes mellitus increases the risk of and mortality associated with community-acquired pneumonia (CAP) [1]. Hyperglycaemia negatively impacts both the innate and adaptive immune response, which could lead to decreased bacterial clearance and increased mortality from infection [2]. This can be extended to non-diabetic patients as well: hyperglycaemia on admission is an independent risk factor for higher complication rates, longer length of stay, and higher mortality in diabetics and non-diabetics with CAP [3–6]. Hypoglycaemia on admission has also been associated with an independent increased risk of mortality in patients with CAP [7, 8]. Currently, two severity scoring systems are widely used for predicting CAP mortality: the pneumonia severity index (PSI) and CURB-65 score (confusion, urea >7 mmol·L−1, respiratory rate ≥30 breaths·min−1, blood pressure <90 mmHg (systolic) or ≤60 mmHg (diastolic), age ≥65 years) [5, 9]. Admission glucose levels (AGL) are part of the PSI, as a categorical variable for hyperglycaemia, but not of CURB-65. We, therefore, investigated whether AGL contributes to these severity scores when both hypo- and hyperglycaemic states are appropriately modelled. Admission glucose levels do not improve discrimination of current severity scores in community-acquired pneumonia We would like to thank the members of the CAP-START study group for securing the conduct of the study in all participating hospitals. Additional thanks to Tim P. Morris, MRC Clinical Trials Unit at University College London, for his guidance on applying fractional polynomial estimation and selection in a multiple imputation context.

    更新日期:2017-10-19
  • Xpert MTB/RIF Ultra: the long-awaited game changer for tuberculous meningitis?
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Jerome H. Chin

    Mycobacterium tuberculosis (MTB) is the leading infectious cause of death globally and an estimated 10.4 million incident cases of tuberculosis (TB) and 1.8 million deaths occurred in 2015 [1]. Central nervous system TB, including tuberculous meningitis and brain tuberculomas, is challenging to diagnose and carries a high risk of severe disability and death [2]. Early diagnosis and prompt initiation of TB treatment offer the best chance of a good neurological outcome; however, an MTB culture of cerebrospinal fluid (CSF), the current reference standard for tuberculous meningitis, usually requires several weeks or longer for growth and is too slow for initial clinical decision-making. In addition, CSF microscopy using Ziehl–Neelsen staining has a very low sensitivity [2] and, as such, integration of clinical and laboratory findings, as well as neuroimaging results, is necessary in the majority of cases to make a probable or possible diagnosis of tuberculous meningitis in the absence of microbiological confirmation [2, 3]. Xpert MTB/RIF Ultra is a promising new technology to aid the diagnosis of tuberculous meningitis

    更新日期:2017-10-19
  • Pharmacological treatment optimisation for stable COPD: an endless story?
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Maeva Zysman; François Chabot; Bruno Housset; Capucine Morelot Panzini; Philippe Devillier; Nicolas Roche

    Local adaptations of global recommendations on COPD may be necessary to facilitate appropriation and implementation http://ow.ly/wgNE30eONaG

    更新日期:2017-10-12
  • Mucolytics for COPD: negotiating a slippery slope towards proof of efficacy
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Shawn D. Aaron

    Clinical trials have thus far not conclusively demonstrated that mucolytics are effective therapies for COPD http://ow.ly/wbLe30eKB7H

    更新日期:2017-10-12
  • Effect of erdosteine on the rate and duration of COPD exacerbations: the RESTORE study
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Roberto W. Dal Negro; Jadwiga A. Wedzicha; Martin Iversen; Giovanni Fontana; Clive Page; Arrigo F. Cicero; Edoardo Pozzi; Peter M.A. Calverley

    Oxidative stress contributes to chronic obstructive pulmonary disease (COPD) exacerbations and antioxidants can decrease exacerbation rates, although we lack data about the effect of such drugs on exacerbation duration. The RESTORE (Reducing Exacerbations and Symptoms by Treatment with ORal Erdosteine in COPD) study was a prospective randomised, double-blind, placebo-controlled study, enrolling patients aged 40–80 years with Global Initiative for Chronic Obstructive Lung Disease stage II/III. Patients received erdosteine 300 mg twice daily or placebo added to usual COPD therapy for 12 months. The primary outcome was the number of acute exacerbations during the study. In the pre-specified intention-to-treat population of 445 patients (74% male; mean age 64.8 years, forced expiratory volume in 1 s 51.8% predicted) erdosteine reduced the exacerbation rate by 19.4% (0.91 versus. 1.13 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.01), due to an effect on mild events; the reduction in the rate of mild exacerbations was 57.1% (0.23 versus 0.54 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.002). No significant difference was observed in the rate of moderate and severe exacerbations (0.68 versus 0.59 exacerbations·patient−1·year−1 for erdosteine and placebo, respectively; p=0.054) despite a trend in favour of the comparison group. Erdosteine decreased the exacerbation duration irrespective of event severity by 24.6% (9.55 versus 12.63 days for erdosteine and placebo, respectively; p=0.023). Erdosteine significantly improved subject and physician subjective severity scores (p=0.022 and p=0.048, respectively), and reduced the use of reliever medication (p<0.001), but did not affect the St George's Respiratory Questionnaire score or the time to first exacerbation. In patients with COPD, erdosteine can reduce both the rate and duration of exacerbations. The percentage of patients with adverse events was similar in both the placebo and erdosteine treatment groups.

    更新日期:2017-10-12
  • Impact and associations of eosinophilic inflammation in COPD: analysis of the AERIS cohort
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Viktoriya L. Kim; Ngaire A. Coombs; Karl J. Staples; Kristoffer K. Ostridge; Nicholas P. Williams; Stephen A. Wootton; Jeanne-Marie Devaster; Emmanuel Aris; Stuart C. Clarke; Andrew C. Tuck; Simon C. Bourne; Tom M.A. Wilkinson

    Eosinophilic inflammation in chronic obstructive pulmonary disease (COPD) predicts response to treatment, especially corticosteroids. We studied the nature of eosinophilic inflammation in COPD prospectively to examine the stability of this phenotype and its dynamics across exacerbations, and its associations with clinical phenotype, exacerbations and infection. 127 patients aged 40–85 years with moderate to very severe COPD underwent repeated blood and sputum sampling at stable visits and within 72 h of exacerbation for 1 year. Blood eosinophils ≥2% was prevalent at baseline, and predicted both predominantly raised stable-state eosinophils across the year (area under the curve 0.841, 95% CI 0.755–0.928) and increased risk of eosinophilic inflammation at exacerbation (OR 9.16; p<0.001). Eosinophils ≥2% at exacerbation and eosinophil predominance at stable visits were associated with a lower risk of bacterial presence at exacerbation (OR 0.49; p=0.049 and OR 0.25; p=0.065, respectively). Bacterial infection at exacerbation was highly seasonal (winter versus summer OR 4.74; p=0.011) in predominantly eosinophilic patients. Eosinophilic inflammation is a common and stable phenotype in COPD. Blood eosinophil counts in the stable state can predict the nature of inflammation at future exacerbations, which when combined with an understanding of seasonal variation provides the basis for the development of new treatment paradigms for this important condition.

    更新日期:2017-10-12
  • Characterisation of asthma subgroups associated with circulating YKL-40 levels
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Jose L. Gomez; Xiting Yan; Carole T. Holm; Nicole Grant; Qing Liu; Lauren Cohn; Vera Nezgovorova; Deborah A. Meyers; Eugene R. Bleecker; Gina M. Crisafi; Nizar N. Jarjour; Linda Rogers; Joan Reibman; Geoffrey L. Chupp

    The chitinase-like protein YKL-40 mediates airway inflammation and serum levels are associated with asthma severity. However, asthma phenotypes associated with YKL-40 levels have not been precisely defined. We conducted an unsupervised cluster analysis of asthma patients treated at the Yale Center for Asthma and Airways Disease (n=156) to identify subgroups according to YKL-40 level. The resulting YKL-40 clusters were cross-validated in cohorts from the Severe Asthma Research Programme (n=167) and the New York University/Bellevue Asthma Repository (n=341). A sputum transcriptome analysis revealed molecular pathways associated with YKL-40 subgroups. Four YKL-40 clusters (C1–C4) were identified. C3 and C4 had high serum YKL-40 levels compared with C1 and C2. C3 was associated with earlier onset and longer duration of disease, severe airflow obstruction, and near-fatal asthma exacerbations. C4 had the highest serum YKL-40 levels, adult onset and less airflow obstruction, but frequent exacerbations. An airway transcriptome analysis in C3 and C4 showed activation of non-type 2 inflammatory pathways. Elevated serum YKL-40 levels were associated with two distinct clinical asthma phenotypes: one with irreversible airway obstruction and another with severe exacerbations. The YKL-40 clusters are potentially useful for identification of individuals with severe or exacerbation-prone asthma.

    更新日期:2017-10-12
  • Th17 cytokines: novel potential therapeutic targets for COPD pathogenesis and exacerbations
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Olivier Le Rouzic; Muriel Pichavant; Emilie Frealle; Antoine Guillon; Mustapha Si-Tahar; Philippe Gosset

    Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory disease of the airways caused mainly by cigarette smoke exposure. COPD progression is marked by exacerbations of the disease, often associated with infections. Recent data show the involvement in COPD pathophysiology of interleukin (IL)-17 and IL-22, two cytokines that are important in the control of lung inflammation and infection. During the initiation and progression of the disease, increased IL-17 secretion causes neutrophil recruitment, leading to chronic inflammation, airways obstruction and emphysema. In the established phase of COPD, a defective IL-22 response facilitates pathogen-associated infections and disease exacerbations. Altered production of these cytokines involves a complex network of immune cells and dysfunction of antigen-presenting cells. In this review, we describe current knowledge on the involvement of IL-17 and IL-22 in COPD pathophysiology at steady state and during exacerbations, and discuss implications for COPD management and future therapeutic approaches.

    更新日期:2017-10-12
  • BRAF and NRAS mutations in circulating Langerhans-like CD1a+ cells in a patient with pulmonary Langerhans’ cell histiocytosis
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Li Zhang; Gustavo Pacheco-Rodriguez; Wendy K. Steagall; Jiro Kato; Thomas V. Colby; Mary Haughey; Joel Moss

    Pulmonary Langerhans’ cell histiocytosis (PLCH) presents as accumulation of Langerhans’ cells and other langerin-expressing dendritic cells (LCH cells) in the lungs that cause bilateral nodules and cavities, which are generally restricted to the upper lung fields of adult cigarette smokers [1–3]. The PLCH lung nodules appear to be the origin of the cavities, which could also have a cyst-like appearance that gives rise to a differential diagnosis that includes both cavitary and cystic lung diseases [3]. A characteristic histopathologic feature of PLCH is destruction of the wall of distal airways by infiltration of LCH cells [3]. Given the cellular aetiology, it has been proposed that LCH, and specifically PLCH, might represent a neoplastic or reactive condition [4, 5]. Currently, the diagnostic criteria of LCH include the demonstration of CD1a- and CD207-positive LCH cells in the LCH lesions [6]. As a lipid-presenting molecule, CD1a is abundantly expressed on langerin-expressing cells and accumulates in Birbeck granules, where it colocalises with langerin [6]. The BRAF mutations in LCH, including PLCH cases, were detected in 38% to 64% of LCH lesions in two independent studies [7, 8]. Recently, Mourah et al . [9] presented the remarkable finding that NRAS , in addition to BRAF mutations, occur in PLCH lesions. The findings of an abnormal cell and an oncogenic mutation are consistent with the proposal that LCH is a neoplastic disease. Detection of BRAF and NRAS in Langerhans-like cells from a patient with pulmonary Langerhans' cell histiocytosis We thank J. Philip McCoy and Leigh Samsel (both Flow Cytometry Core Facility, National Heart, Lung and Blood Institute, National Institutes of Health, Bethesda, MD, USA) for help with the FACS analysis.

    更新日期:2017-10-12
  • Evaluation of tuberculosis screening of immigrants in the Netherlands
    Eur. Respir. J. (IF 10.569) Pub Date : 2017-10-01
    Sarah van de Berg; Connie Erkens; Job van Rest; Susan van den Hof; Margreet Kamphorst; Sytze Keizer; Gerard de Vries

    In European Union/European Economic Area countries, a large proportion of patients with tuberculosis (TB) are born in or are citizens of a country different from the notifying country [1]. Immigrants have an increased risk for TB, depending on the TB incidence in their country of origin, conditions of their migration and duration of stay in the host country [2]. In low TB-incidence countries, systematic screening of immigrants at high risk for TB pre- or post-entry may be considered a key intervention in the progress towards TB elimination [3, 4]. However, current screening policies and practices in European low-incidence countries differ substantially [5, 6]. Evaluation of TB screening needed to periodically assess its effectiveness and inform policy decision

    更新日期:2017-10-12
Some contents have been Reproduced with permission of the American Chemical Society.
Some contents have been Reproduced by permission of The Royal Society of Chemistry.
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