Contrary to popular belief, ventilator-associated lower respiratory tract infections are less common in immunocompromised patients
In this issue of the European Respiratory Journal, Moreau et al. [1] describe the impact of immunosuppression on incidence, aetiology and outcome of ventilator-associated lower respiratory tract infections (VA-LRTIs). The authors report a lower incidence of VA-LRTIs in immunosuppressed patients, with an odds ratio of 0.64, which is in contradiction to their hypothesis and common belief. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 8, 2018 Category: Respiratory Medicine Authors: Bos, L. D. Tags: Respiratory infections and tuberculosis Editorials Source Type: research

New era for European Respiratory Society clinical practice guidelines: joining efficiency and high methodological standards
The objectives of CPGs are to improve the quality and efficiency of healthcare, to reduce unjustified variations in the practices of diagnosis and treatment, and to improve patient outcomes. In order to fulfil these objectives, CPGs have to be evidence-based and therefore need to be developed through an unbiased process, consisting of systematic reviews, a standardised evaluation of the evidence and transparent evidence to decision (EtD) process. The European Respiratory Society (ERS) is committed to the development of the highest quality CPGs [1] and adopted the GRADE (Grading of Recommendations Assessment, Development an...
Source: European Respiratory Journal - March 8, 2018 Category: Respiratory Medicine Authors: Miravitlles, M., Tonia, T., Rigau, D., Roche, N., Genton, C., Vaccaro, V., Welte, T., Gaga, M., Brusselle, G. Tags: Editorials Source Type: research

A well-designed/conducted study on alpha-1 antitrypsin epidemiology not quoted
We read with interest the outstanding European Respiratory Society (ERS) statement on α1-antitrypsin deficiency (AATD) led by R.A. Stockley and M. Miravitlles with the collaboration of 13 European experts on the subject [1]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 8, 2018 Category: Respiratory Medicine Authors: Blanco, I. Tags: Original Articles: Correspondence Source Type: research

Asbestos-related lung cancers are rarely associated with ALK, ROS1 and RET rearrangements
Lung cancer remains the main cause of cancer death. In addition to smoking, exposure to occupational carcinogens constitutes a major risk for lung cancer. Among occupational cancers, asbestos-related ones are the most frequent, accounting for about 5–7% of lung cancers. A better understanding of the molecular pathways implicated in the progression of cancer has greatly improved the therapeutic management of patients with advanced lung cancers, especially nonsmall cell lung cancer (NSCLC) of the adenocarcinoma subtype. Indeed, several therapies targeting the epidermal growth factor receptor (EGFR) or anaplastic lympho...
Source: European Respiratory Journal - March 8, 2018 Category: Respiratory Medicine Authors: Uguen, M., Dewitte, J.-D., Lodde, B., Marcorelles, P., Uguen, A. Tags: Original Articles: Correspondence Source Type: research

Markers of cardiovascular autonomic dysfunction predict COPD in middle-aged subjects
Autonomic dysfunction is commonly observed in chronic obstructive pulmonary disease (COPD) and may relate to the known comorbidity with coronary artery disease (CAD). We hypothesised that clinical markers of cardiovascular autonomic dysfunction predict COPD in the population, independently of CAD. In a population-based cohort of 24 768 subjects (mean age 45 years) without baseline airflow obstruction, we analysed the cross-sectional relationship of one-minute orthostatic systolic blood pressure (SBP) and diastolic blood pressure (DBP) changes and resting heart rate with forced vital capacity (FVC) and forced expirator...
Source: European Respiratory Journal - March 8, 2018 Category: Respiratory Medicine Authors: Ricci, F., Wollmer, P., Engström, G., Fedorowski, A., Hamrefors, V. Tags: COPD and smoking Original Articles: COPD Source Type: research

Differential diagnosis between newly diagnosed asthma and COPD using exhaled breath condensate metabolomics: a pilot study
Asthma and chronic obstructive pulmonary disease (COPD) are heterogeneous diseases with high pathological burden and healthcare costs [1–3]. In outpatient clinical practice, an accurate differential diagnosis is often very difficult, particularly in adult smokers, requiring specific lung function tests [4, 5]. Since nuclear magnetic resonance (NMR)-based metabolomics of exhaled breath condensate (EBC) discriminates adults with COPD [6–8] or asthma [9] from healthy subjects, we hypothesised that it is also able to differentiate asthma and COPD patients of different severities. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 8, 2018 Category: Respiratory Medicine Authors: Maniscalco, M., Paris, D., Melck, D. J., Molino, A., Carone, M., Ruggeri, P., Caramori, G., Motta, A. Tags: COPD and smoking, Asthma and allergy Original Articles: Research letters Source Type: research

Impact of immunosuppression on incidence, aetiology and outcome of ventilator-associated lower respiratory tract infections
The aim of this planned analysis of the prospective multinational TAVeM database was to determine the incidence, aetiology and impact on outcome of ventilator-associated lower respiratory tract infections (VA-LRTI) in immunocompromised patients. All patients receiving mechanical ventilation for>48 h were included. Immunocompromised patients (n=663) were compared with non-immunocompromised patients (n=2297). The incidence of VA-LRTI was significantly lower among immunocompromised than among non-immunocompromised patients (16.6% versus 24.2%; sub-hazard ratio 0.65, 95% CI 0.53–0.80; p
Source: European Respiratory Journal - March 8, 2018 Category: Respiratory Medicine Authors: Moreau, A.-S., Martin-Loeches, I., Povoa, P., Salluh, J., Rodriguez, A., Thille, A. W., Diaz Santos, E., Vedes, E., Lobo, S. M., Megarbane, B., Molero Silvero, E., Coelho, L., Argaud, L., Sanchez Iniesta, R., Labreuche, J., Rouze, A., Nseir, S., for the T Tags: Respiratory infections and tuberculosis Original Articles: Infection Source Type: research

Genetic regulation of IL1RL1 methylation and IL1RL1-a protein levels in asthma
In conclusion, asthma-associated IL1RL1 SNPs strongly regulate IL1RL1 methylation and serum IL1RL1-a levels, yet neither these IL1RL1-methylation CpG sites nor IL1RL1-a levels are associated with asthma. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 8, 2018 Category: Respiratory Medicine Authors: Dijk, F. N., Xu, C., Melen, E., Carsin, A.-E., Kumar, A., Nolte, I. M., Gruzieva, O., Pershagen, G., Grotenboer, N. S., Savenije, O. E. M., Anto, J. M., Lavi, I., Dobano, C., Bousquet, J., van der Vlies, P., van der Valk, R. J. P., de Jongste, J. C., Nawi Tags: Lung biology and experimental studies, Asthma and allergy Original Articles: Asthma Source Type: research

Impact of the mitochondria-targeted antioxidant MitoQ on hypoxia-induced pulmonary hypertension
Increased mitochondrial reactive oxygen species (ROS), particularly superoxide, have been suggested to mediate hypoxic pulmonary vasoconstriction (HPV), chronic hypoxia-induced pulmonary hypertension and right ventricular remodelling. We determined ROS in acute and chronic hypoxia, and investigated the effect of the mitochondria-targeted antioxidant MitoQ under these conditions. The effect of MitoQ or its inactive carrier substance, decyltriphenylphosphonium, on acute HPV (1% O2 for 10 min) was investigated in isolated blood-free perfused mouse lungs. Mice exposed to chronic hypoxia (10% O2 for 4 weeks) or after ...
Source: European Respiratory Journal - March 8, 2018 Category: Respiratory Medicine Authors: Pak, O., Scheibe, S., Esfandiary, A., Gierhardt, M., Sydykov, A., Logan, A., Fysikopoulos, A., Veit, F., Hecker, M., Kroschel, F., Quanz, K., Erb, A., Schäfer, K., Fassbinder, M., Alebrahimdehkordi, N., Ghofrani, H. A., Schermuly, R. T., Brandes, Tags: Lung biology and experimental studies, Pulmonary vascular disease Original Articles: Pulmonary hypertension Source Type: research

Treat the lungs, fool the brain and appease the mind: towards holistic care of patients who suffer from chronic respiratory diseases
In healthy people, breathing is the most natural thing in the world. No need to think about it. No need to be concerned about it. It is not even the object of conscious perception. But when breathing becomes difficult, when it produces suffering, nothing else mattersa. Life discolours and shrinks around an act of breathing that has become elusive and uncertain, but pervasive. Disability ensues, which adds "a variety of adverse psychosocial, spiritual, or other consequences" to the respiratory-related physical limitations [1]. Respiratory suffering, be it called dyspnoea, breathlessness or by any other name, is th...
Source: European Respiratory Journal - March 1, 2018 Category: Respiratory Medicine Authors: Similowski, T. Tags: COPD and smoking Editorials Source Type: research

"RESPIRE: breathing new life into bronchiectasis." Sanjay H. Chotirmall and James D. Chalmers. Eur Respir J 2018; 51: 1702444.
(Source: European Respiratory Journal)
Source: European Respiratory Journal - March 1, 2018 Category: Respiratory Medicine Tags: Author Corrections Source Type: research

Location or origin? What is critical for macrophage propagation of lung fibrosis?
Radiation-induced pulmonary fibrosis develops following radiotherapy for chest wall and lung malignancies, affects quality of life and is often lethal [1]. Similarly, idiopathic forms of lung fibrosis show progressive accumulation of extracellular matrix leading to respiratory insufficiency [2]. Currently, treatments for either radiation-induced or idiopathic forms of pulmonary fibrosis are limited and largely ineffective. Immunosuppressive therapies may be harmful in idiopathic pulmonary fibrosis [3], and are used in radiation-induced fibrosis with limited effect [4]. Growing evidence suggests macrophages are critical reg...
Source: European Respiratory Journal - March 1, 2018 Category: Respiratory Medicine Authors: Zhou, X., Moore, B. B. Tags: Lung biology and experimental studies, Interstitial and orphan lung disease Editorials Source Type: research

Reassessing Th1 versus Th17.1 in sarcoidosis: new tricks for old dogma
Immunologically, sarcoidosis has been classically defined by the presence of a Th1-dominant environment localised to sites of disease, characterised by overexpression of interferon (IFN) and Th1-promoting interleukin (IL)12 and IL18 [1]. Accordingly, the downstream effects of enhanced Th1 are also observed in sarcoidosis, such as the expression of Th1-associated chemokines (MIG/CXCL9, IP10/CXCL10, ITAC/CXCL11, MCP1/CCL2, MIP1α/CCL3, MIP1β/CCL4, RANTES/CCL5) and their respective receptors (CXCR3, CCR5). Conversely, the presence of augmented Th2 has never been firmly documented in the sarcoidosis lung. (Source: Eu...
Source: European Respiratory Journal - March 1, 2018 Category: Respiratory Medicine Authors: Chen, E. S. Tags: Interstitial and orphan lung disease Editorials Source Type: research

Achoo, achis, ATCHIN! Vaccine you...
Community-acquired pneumonia (CAP) is an important cause of morbidity, mortality and expenditure of health resources. Globally, lower respiratory tract infection, which includes CAP, was the fourth leading cause of death in 2015 [1]. In developed countries CAP is the leading cause of death by infectious disease [2], and in 2014 it was the eighth cause of death in the USA [3]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 1, 2018 Category: Respiratory Medicine Authors: Froes, F., Blasi, F., Torres, A. Tags: Respiratory infections and tuberculosis Editorials Source Type: research

Adverse respiratory effects of opioids for chronic breathlessness: learning lessons from chronic pain
Fear of fatal respiratory depression is a major driver limiting opioid prescription for persistent breathlessness in chronic obstructive pulmonary disease (COPD) [1–6], but is this fear warranted? In a recent systematic review and meta-analysis, Verberkt et al. [7] did not detect significant or clinically relevant respiratory adverse events associated with opioid treatment for chronic breathlessness in COPD. Rather, they concluded that "clinicians’ fears of respiratory obtundation with low-dose opioids seem to be unfounded". Here, we critically evaluate these conclusions. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 1, 2018 Category: Respiratory Medicine Authors: Pattinson, K. T. S., Rowland, M. J., Nickol, A. H., Quinlan, J. Tags: Original Articles: Correspondence Source Type: research

Mesenchymal stromal cell infusion modulates systemic immunological responses in stable COPD patients: a phase I pilot study
Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality due to limited therapeutic options for the persistent pulmonary and systemic inflammation that characterises this condition [1]. Recently, pre-clinical studies of mesenchymal stromal cells (MSCs) in COPD demonstrate efficacy in alleviating inflammation and reducing emphysema following either systemic or intra-tracheal administration [2, 3]. Human trials have demonstrated that MSCs did not improve spirometry following their administration to COPD patients; however, it was reported that C-reactive protein (CRP), a marker for sys...
Source: European Respiratory Journal - March 1, 2018 Category: Respiratory Medicine Authors: Armitage, J., Tan, D. B. A., Troedson, R., Young, P., Lam, K.-v., Shaw, K., Sturm, M., Weiss, D. J., Moodley, Y. P. Tags: Original Articles: Research letters Source Type: research

CSF1R inhibition prevents radiation pulmonary fibrosis by depletion of interstitial macrophages
Radiation-induced lung fibrosis (RIF) is a delayed side-effect of chest radiotherapy, frequently associated with macrophage infiltration. We aimed to characterise the role of pulmonary macrophages in RIF using human lung biopsies from patients receiving radiotherapy for thorax malignancies and a RIF model developed in C57BL/6 mice after 16-Gy thorax irradiation. High numbers of macrophages (both interstitial and alveolar) were detected in clinical and preclinical RIF. In the preclinical model, upregulation of T-helper (Th)2 cytokines was measured, whereas Th1 cytokines were downregulated in RIF tissue lysate. Bronchoalveol...
Source: European Respiratory Journal - March 1, 2018 Category: Respiratory Medicine Authors: Meziani, L., Mondini, M., Petit, B., Boissonnas, A., Thomas de Montpreville, V., Mercier, O., Vozenin, M.-C., Deutsch, E. Tags: Lung structure and function, Interstitial and orphan lung disease Original Articles: Basic science and interstitial lung disease Source Type: research

Effect modification of perinatal exposure to air pollution and childhood asthma incidence
We examined whether maternal and infant characteristics modified the association between perinatal exposure to air pollution and development of childhood asthma. 761 172 births occurring between 2006 and 2012 were identified in the province of Ontario, Canada. Associations between exposure to ambient air pollutants and childhood asthma incidence (up to age 6 years) were estimated using Cox regression models. 110 981 children with asthma were identified. In models adjusted for postnatal exposures, second-trimester exposures to particulate matter with a 50% cut-off aerodynamic diameter ≤2.5 μm (hazard ratio (...
Source: European Respiratory Journal - March 1, 2018 Category: Respiratory Medicine Authors: Lavigne, E., Belair, M.-A., Rodriguez Duque, D., Do, M. T., Stieb, D. M., Hystad, P., van Donkelaar, A., Martin, R. V., Crouse, D. L., Crighton, E., Chen, H., Burnett, R. T., Weichenthal, S., Villeneuve, P. J., To, T., Brook, J. R., Johnson, M., Cakmak, S Tags: Asthma and allergy, Paediatric pulmonology Original Articles: Asthma Source Type: research

First histopathological evidence of irreversible pulmonary vascular disease in dasatinib-induced pulmonary arterial hypertension
We report the case of a patient who developed dasatinib-induced severe PAH that progressed in spite of drug cessation and aggressive PAH-specific therapy and ultimately underwent lung transplantation. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 1, 2018 Category: Respiratory Medicine Authors: Daccord, C., Letovanec, I., Yerly, P., Bloch, J., Ogna, A., Nicod, L. P., Aubert, J.-D. Tags: Original Articles: Research letters Source Type: research

AHRR hypomethylation, lung function, lung function decline and respiratory symptoms
Epigenome-wide association studies have shown a consistent association between smoking exposure and hypomethylation in the aryl hydrocarbon receptor repressor (AHRR) gene (cg05575921). We tested the hypothesis that AHRR hypomethylation is associated with low lung function, steeper lung function decline, and respiratory symptoms in the general population. AHRR methylation extent was measured in 9113 individuals from the 1991–1994 examination of the Copenhagen City Heart Study, using bisulfite-treated leukocyte DNA. Spirometry at the time of blood sampling was available for all individuals. Lung function was measured a...
Source: European Respiratory Journal - March 1, 2018 Category: Respiratory Medicine Authors: Kodal, J. B., Kobylecki, C. J., Vedel-Krogh, S., Nordestgaard, B. G., Bojesen, S. E. Tags: Lung structure and function Original Articles: Lung function Source Type: research

Increased T-helper 17.1 cells in sarcoidosis mediastinal lymph nodes
In this study, we aimed to investigate 1) whether Th17.1 cells are also increased in the MLNs of sarcoidosis patients and 2) whether frequencies of the Th17.1 cells at diagnosis may correlate with disease progression. MLN cells from treatment-naive pulmonary sarcoidosis patients (n=17) and healthy controls (n=22) and peripheral blood mononuclear cells (n=34) and bronchoalveolar lavage fluid (BALF) (n=36) from sarcoidosis patients were examined for CD4+ T-cell subset proportions using flow cytometry. Higher proportions of Th17.1 cells were detected in sarcoidosis MLNs than in control MLNs. Higher Th17.1 cell proportions wer...
Source: European Respiratory Journal - March 1, 2018 Category: Respiratory Medicine Authors: Broos, C. E., Koth, L. L., van Nimwegen, M., in 't Veen, J. C. C. M., Paulissen, S. M. J., van Hamburg, J. P., Annema, J. T., Heller-Baan, R., Kleinjan, A., Hoogsteden, H. C., Wijsenbeek, M. S., Hendriks, R. W., van den Blink, B., Kool, M. Tags: Interstitial and orphan lung disease Original Articles: Interstitial lung disease Source Type: research

Adolescents and young adults: a neglected population group for tuberculosis surveillance
Tuberculosis (TB) remains a serious public health concern and it is considered the leading infectious cause of death globally. The World Health Organization (WHO) Global Tuberculosis Report of 2017 showed an estimated 10.4 million new TB cases for 2016, of which 6.7 million (64.4%) were males and 1.04 million (10%) were children 0–14 years of age [1]. Unfortunately, these figures represent estimates, an attempt to quantify the real number of TB cases, since the notifications provided from many national surveillance systems, including some of the high-burden TB countries, fail to capture many TB cases. This is ei...
Source: European Respiratory Journal - February 21, 2018 Category: Respiratory Medicine Authors: Garcia-Basteiro, A. L., Schaaf, H. S., Diel, R., Migliori, G. B. Tags: Respiratory infections and tuberculosis Editorials Source Type: research

Progress in the management of IPF-related acute exacerbations: a goal for patients, respirologists and intensivists
I appreciate the expressed views of F. Vincent and colleagues, regarding the need to address treatment consideration of acute exacerbation (AE) of idiopathic pulmonary fibrosis (IPF). While the mortality of patients manifesting AE of IPF is unfortunately high, F. Vincent and colleagues argue that supportive care in the intensive care unit (ICU) is an appropriate consideration, including noninvasive and/or mechanical ventilation for patients. Indeed, well-informed patients may opt for such aggressive supportive measures in the ICU, and for some patients listed for lung transplantation, such aggressive supportive m...
Source: European Respiratory Journal - February 21, 2018 Category: Respiratory Medicine Authors: Raghu, G. Tags: Interstitial and orphan lung disease Original Articles: Correspondence Source Type: research

"Pneumocystosis revealing immunodeficiency secondary to TERC mutation." Raphael Borie, Caroline Kannengiesser, Flore Sicre de Fontbrune, David Boutboul, Laure Tabeze, Florence Brunet-Possenti, Elodie Lainey, Marie Pierre Debray, Aurelie Cazes and Bruno Crestani. Eur Respir J 2017; 50: 1701443.
(Source: European Respiratory Journal)
Source: European Respiratory Journal - February 21, 2018 Category: Respiratory Medicine Tags: Author Corrections Source Type: research

Revising our approach to conducting therapeutic clinical research in COPD
Chronic obstructive pulmonary disease (COPD) is a major worldwide cause of death, and a leading cause of chronic disability and driver of high healthcare expenditures [1]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - February 21, 2018 Category: Respiratory Medicine Authors: Criner, G. J. Tags: COPD and smoking Editorials Source Type: research

Progress in the management of IPF-related acute exacerbations: a goal for patients, respirologists and intensivists
We read with interest the illuminating review on the pharmacological management of idiopathic pulmonary fibrosis (IPF) recently published in the European Respiratory Journal [1]. Raghu [1] did not detail the pharmacological management of acute exacerbations (AEs). AEs often lead to the question of whether to transfer the patient to the intensive care unit (ICU) for respiratory support, whether this is invasive mechanical ventilation (IMV) or not, and to the choice of adequate pharmacological agent(s) [2]. This is a critical issue for respirologists and intensivists as it is estimated that ~3 million patients suffer from th...
Source: European Respiratory Journal - February 21, 2018 Category: Respiratory Medicine Authors: Vincent, F., Nunes, H., Gaudry, S. Tags: Interstitial and orphan lung disease Original Articles: Correspondence Source Type: research

Sex differences and factors influencing the duration of the QT interval in patients on anti-tuberculosis therapy
In an ECG, the QT interval represents the depolarisation and repolarisation of the ventricles and is usually corrected for heart rate (QTc). Previous studies have shown that women have a reduced repolarisation reserve and greater susceptibility to the QTc prolongation effect of some drugs [1, 2]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - February 21, 2018 Category: Respiratory Medicine Authors: Alvarez-Uria, G., Midde, M. Tags: Respiratory infections and tuberculosis Original Articles: Research letters Source Type: research

The incidence of tuberculosis among adolescents and young adults: a global estimate
This study aimed to provide the first estimates of the global and regional incidence of tuberculosis among young people aged 10–24 years. Using the World Health Organization (WHO) database of tuberculosis notifications for 2012, we estimated the burden of tuberculosis among young people by WHO region. Adjustments were made for incomplete age disaggregation and underreporting, using supplementary data from several countries representing diverse tuberculosis epidemics. We estimate that 1.78 million (uncertainty interval (UI) 1.23–3.00 million) young people developed tuberculosis in 2012, accounting...
Source: European Respiratory Journal - February 21, 2018 Category: Respiratory Medicine Authors: Snow, K. J., Sismanidis, C., Denholm, J., Sawyer, S. M., Graham, S. M. Tags: Respiratory infections and tuberculosis Original Articles: Tuberculosis Source Type: research

Relapse-free cure from multidrug-resistant tuberculosis in Germany
Multidrug-resistant (MDR) tuberculosis (TB), defined by bacillary resistance against rifampicin and isoniazid, has been identified as a global threat to mankind [1]. According to the latest report by the European Centres for Disease Prevention and Control, and World Health Organization (WHO) regional office for Europe, only approximately 50% of MDR-TB patients in Europe reach favourable treatment outcomes [2]. Successful treatment outcomes are achieved for less than 25% of patients with extensively drug-resistant (XDR)-TB (MDR plus resistance against a least one fluoroquinolone and one second-line injectable drug) in the E...
Source: European Respiratory Journal - February 21, 2018 Category: Respiratory Medicine Authors: Heyckendorf, J., van Leth, F., Kalsdorf, B., Olaru, I. D., Günther, G., Salzer, H. J. F., Terhalle, E., Rolling, T., Glattki, G., Müller, M., Schuhmann, M., Avsar, K., Lange, C. Tags: Respiratory infections and tuberculosis Original Articles: Research letters Source Type: research

The role of air pollution and lung function in cognitive impairment
In conclusion, air pollution associated VCP was partially mediated by lung function. Further studies on the mechanisms underlying this pathway are required to develop new strategies to prevent air pollution induced cognitive impairment. (Source: European Respiratory Journal)
Source: European Respiratory Journal - February 21, 2018 Category: Respiratory Medicine Authors: Hüls, A., Vierkötter, A., Sugiri, D., Abramson, M. J., Ranft, U., Krämer, U., Schikowski, T. Tags: Lung structure and function Original Articles: Lung function Source Type: research

Sarcoidosis mortality in Sweden: a population-based cohort study
We aimed to investigate sarcoidosis mortality in a large, population-based cohort, taking into account disease heterogeneity. Individuals with incident sarcoidosis (n=8207) were identified from the Swedish National Patient Register using International Classification of Disease codes (2003-2013). In a subset, cases receiving treatment ±3 months from diagnosis were identified from the Prescribed Drug Register. Nonsarcoidosis comparators from the general population were matched to cases 10:1 on birth year, sex and county. Individuals were followed for all-cause death in the Cause of Death Register. Adjusted mortal...
Source: European Respiratory Journal - February 21, 2018 Category: Respiratory Medicine Authors: Rossides, M., Kullberg, S., Askling, J., Eklund, A., Grunewald, J., Arkema, E. V. Tags: Interstitial and orphan lung disease Original Articles: Interstitial lung disease Source Type: research

Primary ciliary dyskinesia with normal ultrastructure: three-dimensional tomography detects absence of DNAH11
In primary ciliary dyskinesia (PCD), motile ciliary dysfunction arises from ciliary defects usually confirmed by transmission electron microscopy (TEM). In 30% of patients, such as those with DNAH11 mutations, apparently normal ultrastructure makes diagnosis difficult. Genetic analysis supports diagnosis, but may not identify definitive causal variants. Electron tomography, an extension of TEM, produces three-dimensional ultrastructural ciliary models with superior resolution to TEM. Our hypothesis is that tomography using existing patient samples will enable visualisation of DNAH11-associated ultrastructural defects. Dual...
Source: European Respiratory Journal - February 21, 2018 Category: Respiratory Medicine Authors: Shoemark, A., Burgoyne, T., Kwan, R., Dixon, M., Patel, M. P., Rogers, A. V., Onoufriadis, A., Scully, J., Daudvohra, F., Cullup, T., Loebinger, M. R., Wilson, R., Chung, E. M. K., Bush, A., Mitchison, H. M., Hogg, C. Tags: Paediatric pulmonology Original Articles: Paediatrics Source Type: research

Small airways dysfunction: the link between allergic rhinitis and allergic asthma
Abnormal airway reactivity and overproduction of nitric oxide (NO) occurring in small airways have been found in asthma. If the "one airway, one disease" concept is consistent, such dysfunctions should also be detected in the peripheral airways of patients suffering from allergic rhinitis. We investigated whether peripheral airway reactivity and NO overproduction could be documented in distal airways in patients with allergic rhinitis. Exhaled NO fraction (FeNO) and the slope (S) of phase III of the single-breath washout test (SBWT) of helium (He) and sulfur hexafluoride (SF6) were measured in 31 patients with al...
Source: European Respiratory Journal - February 21, 2018 Category: Respiratory Medicine Authors: Haccuria, A., Van Muylem, A., Malinovschi, A., Doan, V., Michils, A. Tags: Asthma and allergy Original Articles: Asthma and allergy Source Type: research

Effectiveness versus efficacy trials in COPD: how study design influences outcomes and applicability
Guidelines for chronic obstructive pulmonary disease (COPD) management are based largely on results from double-blind randomised controlled trials (RCTs) of efficacy. These trials have high internal validity and test whether a drug is efficacious, but they are conducted in highly selected populations that may differ significantly from patients with COPD seen in routine practice. We compared the baseline characteristics, healthcare use and outcomes between the Salford Lung Study (SLS), an open-label effectiveness RCT, with six recent large-scale efficacy RCTs. We also calculated the proportion of SLS patients who would have...
Source: European Respiratory Journal - February 21, 2018 Category: Respiratory Medicine Authors: Woodcock, A., Boucot, I., Leather, D. A., Crawford, J., Collier, S., Bakerly, N. D., Hilton, E., Vestbo, J. Tags: COPD and smoking Original Articles: COPD Source Type: research

Living with breathlessness: a systematic literature review and qualitative synthesis
What is the experience of people living with breathlessness due to medical conditions, those caring for them and those treating them, with regard to quality of life and the nature of clinical interactions? Electronic databases (Ovid MEDLINE, Embase, CINAHL Plus and PsycINFO) were searched (January 1987 to October 2017; English language), for qualitative studies exploring the experience of chronic breathlessness (patients, carers and clinicians). Two independent reviewers screened titles, abstracts and papers retrieved against inclusion criteria. Disagreements were resolved with a third reviewer. Primary qualitative data we...
Source: European Respiratory Journal - February 21, 2018 Category: Respiratory Medicine Authors: Hutchinson, A., Barclay-Klingle, N., Galvin, K., Johnson, M. J. Tags: Respiratory clinical practice Reviews Source Type: research

ERJ February Podcast: Effectiveness versus efficacy
As part of the February issue, the European Respiratory Journal presents the latest in its series of podcasts. Chief editor Martin Kolb interviews the Jørgen Vestbo (The University of Manchester and Manchester University NHS Foundation Trust, Manchester, UK) about the important difference between standard efficacy trials and real-world effectiveness trials such as the Salford Lung Study. (Source: European Respiratory Journal)
Source: European Respiratory Journal - February 21, 2018 Category: Respiratory Medicine Tags: Electronic resources Source Type: research

Palliative care for people with COPD: effective but underused
Nearly 100 000 men and over 65 000 women die from chronic obstructive pulmonary disease (COPD) in Europe each year [1]; more die from one of its comorbidities but face the challenges of living and dying with severe COPD during their last years and months. Globally, COPD is the third most common cause of death worldwide and the Global Burden of Disease project estimated that, in 2015, COPD caused 3.2 million deaths, an increase of 11.6% compared with 1990 [2]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - February 14, 2018 Category: Respiratory Medicine Authors: Halpin, D. M. G. Tags: COPD and smoking Editorials Source Type: research

Putting the brake on accelerated lung function decline in asthma
The focus of most asthma care is on symptom control and exacerbation (attack) prevention. This focus is needed; asthma is a very common disease, still leads to an unnecessarily high symptom burden and is a cause of preventable deaths [1, 2]. This negative impact occurs despite the recognition that asthma is a heterogeneous disease with various subtypes [3] requiring different treatment approaches [4], with the development of multiple new targeted therapies [5]. Although the identification of biomarkers to help predict exacerbations and understand the interactions between asthma, risk and comorbidities is a key research pri...
Source: European Respiratory Journal - February 14, 2018 Category: Respiratory Medicine Authors: Shaw, D. Tags: Asthma and allergy Editorials Source Type: research

Tuberculosis re-treatment after exclusion of rifampicin resistance
We agree with Falzon et al. [1] that treatment of isoniazid-resistant tuberculosis (TB) is an important issue. The first-line re-treatment regimen for previously treated TB patients, which was known as the category II regimen, comprised 8 months of isoniazid, rifampicin and ethambutol supplemented by streptomycin for the initial 2 months, and pyrazinamide for the initial 3 months (2SHRZE/HRZE/5HRE). It was introduced in the collaborative programme of the International Union Against Tuberculosis and Lung Disease in which the first-line initial regimen for new TB patients was an 8-month regimen comprising 2&nb...
Source: European Respiratory Journal - February 14, 2018 Category: Respiratory Medicine Authors: Chiang, C.-Y., Trebucq, A. Tags: Respiratory infections and tuberculosis Original Articles: Correspondence Source Type: research

Dyspnoea modifies the recognition of fearful expressions by healthy humans
Brainstem neural oscillators normally generate resting breathing. Yet cortical premotor and motor respiratory-related networks can operate voluntary breathing and compensate for defective automatic respiratory drive [1, 2]. These networks are engaged when the respiratory system load-capacity balance is compromised, typically during experimental inspiratory loading [3] that is associated with dyspnoea of the "excessive inspiratory effort" type. An emerging body of evidence suggests that respiratory-related cortical activation (and by extension the corresponding dyspnoea) can have a cognitive cost [4–6], thou...
Source: European Respiratory Journal - February 14, 2018 Category: Respiratory Medicine Authors: Vinckier, F., Morelot-Panzini, C., Similowski, T. Tags: Respiratory clinical practice Original Articles: Research letters Source Type: research

Tracheal replacement
This article reviews the advantages and limitations of each technique used over the past few decades in clinical practice. The main limitation seems to be the capacity for tracheal tissue regeneration. The physiopathology behind this has yet to be fully understood. Research on stem cells sparked much interest and was thought to be a revolutionary technique; however, the poor long-term results of this approach highlight that there is a long way to go in this research field. Currently, an autologous tissue composite, with or without a tracheal allograft, is the only long-term working solution for every aetiology, despite its...
Source: European Respiratory Journal - February 14, 2018 Category: Respiratory Medicine Authors: Etienne, H., Fabre, D., Gomez Caro, A., Kolb, F., Mussot, S., Mercier, O., Mitilian, D., Stephan, F., Fadel, E., Dartevelle, P. Tags: Lung cancer Reviews Source Type: research

Immunotherapy: a new standard of care in thoracic malignancies?: A summary of the European Respiratory Society research seminar of the Thoracic Oncology Assembly
In May 2017, the second European Respiratory Society research seminar of the Thoracic Oncology Assembly entitled "Immunotherapy, a new standard of care in thoracic malignancies?" was held in Paris, France. This seminar provided an opportunity to review the basis of antitumour immunity and to explain how immune checkpoint inhibitors (ICIs) work. The main therapeutic trials that have resulted in marketing authorisations for use of ICIs in lung cancer were reported. A particular focus was on the toxicity of these new molecules in relation to their immune-related adverse events. The need for biological selection, cur...
Source: European Respiratory Journal - February 14, 2018 Category: Respiratory Medicine Authors: Costantini, A., Grynovska, M., Lucibello, F., Moises, J., Pages, F., Tsao, M. S., Shepherd, F. A., Bouchaab, H., Garassino, M., Aerts, J. G. J. V., Mazieres, J., Mondini, M., Berghmans, T., Meert, A.-P., Cadranel, J. Tags: Lung cancer Perspective Source Type: research

Asthma treatment impacts time to pregnancy: evidence from the international SCOPE study
Asthma is a common chronic disease affecting the lives of reproductive age women and is associated with 8–13% of pregnancies [1]. While maternal asthma has been consistently associated with significant perinatal morbidities and mortality [2, 3], impacts on fertility are conflicting. In light of limited and conflicting evidence, the aim of this study was to examine the impact of asthma and asthma medication use on fecundability and time to pregnancy. (Source: European Respiratory Journal)
Source: European Respiratory Journal - February 14, 2018 Category: Respiratory Medicine Authors: Grzeskowiak, L. E., Smithers, L. G., Grieger, J. A., Bianco-Miotto, T., Leemaqz, S. Y., Clifton, V. L., Poston, L., McCowan, L. M., Kenny, L. C., Myers, J., Walker, J. J., Norman, R. J., Dekker, G. A., Roberts, C. T. Tags: Original Articles: Research letters Source Type: research

Low uptake of palliative care for COPD patients within primary care in the UK
Mortality and symptom burden from chronic obstructive pulmonary disease (COPD) and lung cancer are similar but there is thought to be an inequality in palliative care support (PCS) between diseases. This nationally representative study assessed PCS for COPD patients within primary care in the UK. This was a cohort study using electronic healthcare records (2004–2015). Factors associated with receiving PCS were assessed using logistic regression for the whole cohort and deceased patients. There were 92 365 eligible COPD patients, of which 26 135 died. Only 7.8% of the whole cohort and 21.4% of deceased patients receiv...
Source: European Respiratory Journal - February 14, 2018 Category: Respiratory Medicine Authors: Bloom, C. I., Slaich, B., Morales, D. R., Smeeth, L., Stone, P., Quint, J. K. Tags: COPD and smoking Original Articles: COPD Source Type: research

Predictors of accelerated decline in lung function in adult-onset asthma
Little is known about the prognosis of adults with new-onset asthma. Cross-sectional studies suggest that these patients may exhibit accelerated decline in forced expiratory volume in 1 s (FEV1). However, risk factors for accelerated decline in lung function have not yet been identified. We aimed to identify these risk factors in a prospective 5-year follow-up study in 200 adults with newly diagnosed asthma. In the current study, clinical, functional and inflammatory parameters were assessed annually for 5 years. Linear mixed-effects models were used to identify predictors. Evaluable lung function sets of 141 pat...
Source: European Respiratory Journal - February 14, 2018 Category: Respiratory Medicine Authors: Coumou, H., Westerhof, G. A., de Nijs, S. B., Zwinderman, A. H., Bel, E. H. Tags: Asthma and allergy Original Articles: Asthma Source Type: research

Palatal prolapse as a signature of expiratory flow limitation and inspiratory palatal collapse in patients with obstructive sleep apnoea
This study demonstrates that expiratory palatal prolapse can be quantified noninvasively, is associated with EFL and predicts the presence of inspiratory isolated palatal collapse. (Source: European Respiratory Journal)
Source: European Respiratory Journal - February 14, 2018 Category: Respiratory Medicine Authors: Azarbarzin, A., Sands, S. A., Marques, M., Genta, P. R., Taranto-Montemurro, L., Messineo, L., White, D. P., Wellman, A. Tags: Sleep medicine Original Articles: Sleep Source Type: research

Lung transplantation after allogeneic stem cell transplantation: a pan-European experience
This study assesses survival in highly selected patients undergoing lung transplantation for LONIPCs after SCT. SCT patients undergoing lung transplantation at 20 European centres between 1996 and 2014 were included. Clinical data pre- and post-lung transplantation were reviewed. Propensity score-matched controls were generated from the Eurotransplant and Scandiatransplant registries. Kaplan–Meier survival analysis and Cox proportional hazard regression models evaluating predictors of graft loss were performed. Graft survival at 1, 3 and 5 years of 84%, 72% and 67%, respectively, among the 105 SCT patients prove...
Source: European Respiratory Journal - February 14, 2018 Category: Respiratory Medicine Authors: Greer, M., Berastegui, C., Jaksch, P., Benden, C., Aubert, J., Roux, A., Lhuillier, E., Hirschi, S., Reynaud-Gaubert, M., Philit, F., Claustre, J., LePalud, P., Stern, M., Knoop, C., Vos, R., Verschuuren, E., Fisher, A., Riise, G., Hansson, L., Iversen, M Tags: Interstitial and orphan lung disease Original Articles: Rare lung disease Source Type: research

Analysis of airway pathology in COPD using a combination of computed tomography, micro-computed tomography and histology
This study examined small airway pathology using a novel combination of multidetector row computed tomography (MDCT), micro-computed tomography (microCT) and histology. Airway branches visible on specimen MDCT were counted and the dimensions of the third- to fifth-generation airways were computed, while the terminal bronchioles (designated TB), preterminal bronchioles (TB-1) and pre-preterminal bronchioles (TB-2) were examined with microCT and histology in eight explanted lungs with end-stage COPD and seven unused donor lungs that served as controls. On MDCT, COPD lungs showed a decrease in the number of 2–2.5 m...
Source: European Respiratory Journal - February 14, 2018 Category: Respiratory Medicine Authors: Tanabe, N., Vasilescu, D. M., Kirby, M., Coxson, H. O., Verleden, S. E., Vanaudenaerde, B. M., Kinose, D., Nakano, Y., Pare, P. D., Hogg, J. C. Tags: COPD and smoking Original Articles: COPD Source Type: research

Heat shock protein-90 toward theranostics: a breath of fresh air in idiopathic pulmonary fibrosis
Heat shock proteins (HSPs), also known as stress proteins, constitute a complex network of proteins highly conversed across species that have been classified into different families according to their molecular weight: HSP110, HSP90, HSP70, HSP60, HSP40 and the small HSPs [1]. Although they are mainly known for their chaperone and cytoprotective properties, HSPs also participate in the regulation of many cellular signalling processes [2]. These proteins have been involved in various physiological as well as pathological conditions, including respiratory diseases such as asthma, chronic obstructive pulmonary disease, sarcoi...
Source: European Respiratory Journal - February 7, 2018 Category: Respiratory Medicine Authors: Bonniaud, P., Burgy, O., Garrido, C. Tags: Lung biology and experimental studies, Interstitial and orphan lung disease Editorials Source Type: research

Will we be singing a different tune on combined post- and pre-capillary pulmonary hypertension?
There have been many well-intended pursuits in medicine that should have panned out, but did not. Case in point: premature ventricular complexes (PVC) post-myocardial infarction were noted to be associated with increased risk of death, and thus the Cardiac Arrhythmia Suppression Trial (CAST) Study investigated if pharmacological PVC suppression with class I anti-arrhythmics would reduce the rate of arrhythmic death [1]. Surprisingly, the study showed that although PVCs were successfully suppressed, there were excess deaths due to arrhythmia and shock in such patients treated with encainide or flecainide [1]. (Source: ...
Source: European Respiratory Journal - February 7, 2018 Category: Respiratory Medicine Authors: Hsu, S., Tedford, R. J. Tags: Pulmonary vascular disease Editorials Source Type: research