Pulmonary fibrosis: "idiopathic" is not "cryptogenic"
The writer makes a powerful plea for clarity of thought based on clarity of language, arguing from the Socratic maxim that "the beginning of wisdom is the definition of terms". This etymological perspective is extremely apposite because the distinction between "cryptogenic" and "idiopathic" disease is seminal in the ongoing idiopathic pulmonary fibrosis (IPF) terminology debate. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 18, 2019 Category: Respiratory Medicine Authors: Wells, A. U., Brown, K. K., Flaherty, K. R., Kolb, M., Thannickal, V. J., on behalf of the IPF Consensus Working Group Tags: Original Articles: Correspondence Source Type: research

Molecular endpoints for establishing target engagement by novel idiopathic pulmonary fibrosis therapies
Idiopathic pulmonary fibrosis (IPF) is a disease of progressive lung remodelling characterised by metaplastic epithelial cells, re-epithelialised air spaces (microscopic honeycombing), lymphoid aggregates, leukocyte accumulation (including macrophages, dendritic cells and mast cells), angiogenesis, lymphangiogenesis, fibroblast foci and excess matrix deposition [1, 2]. On average, untreated patients diagnosed with IPF succumb to the disease within 3 years of diagnosis [2]. This dismal prognosis has improved following approval of pirfenidone and nintedanib for disease management [3, 4]. These drugs cut disease progression i...
Source: European Respiratory Journal - March 18, 2019 Category: Respiratory Medicine Authors: Wolters, P. J., Cottin, V. Tags: Interstitial and orphan lung disease Editorials Source Type: research

Chronic Airway Diseases Early Stratification (CADSET): a new ERS Clinical Research Collaboration
A recent editorial in the European Respiratory Journal highlighted the strategic importance of the Clinical Research Collaborations (CRCs) launched in 2013 by the European Respiratory Society (ERS) [1]. These have the aim of 1) promoting the exchange of research ideas among clinicians and affiliated scientists in Europe and/or globally; 2) building an infrastructure for prospective clinical research; 3) securing additional funding through national and European Union funding streams; and 4) facilitating the planning, implementation, evaluation and publication of clinical and translational studies at pan-European level and b...
Source: European Respiratory Journal - March 18, 2019 Category: Respiratory Medicine Authors: Agusti, A., Faner, R., Donaldson, G., Heuvelin, E., Breyer-Kohansal, R., Melen, E., Maitland-van der Zee, A. H., Vestbo, J., Allinson, J. P., Vanfleteren, L. E. G. W., van den Berge, M., Adcock, I. M., Lahousse, L., Brusselle, G., Wedzicha, J. A., on beha Tags: Editorials Source Type: research

TB, you're a long time cured
Despite official country-level estimates having been produced for nearly three decades, much remains uncertain about the true global burden of tuberculosis (TB). Official statistics focus on incidence and mortality, while health systems concentrate on supporting patients through treatment, such that less is known about the longer term damage inflicted by disease episodes. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 18, 2019 Category: Respiratory Medicine Authors: Trauer, J. M. Tags: Editorials Source Type: research

Tuberculosis research questions identified through the WHO policy guideline development process
High-quality research evidence is critical for improving global health and health equity, and for achieving the World Health Organization (WHO)'s objective of the attainment of the highest possible level of health by all peoples [1]. This need is most apparent when responding to complex epidemics such as tuberculosis (TB). TB is the leading killer among diseases caused by an infectious agent worldwide, the leading killer of people with HIV infection and a leading cause of death from airborne anti-microbial resistant infections, taking heavy tolls on human lives, communities and health systems at large [2, 3]. (Source: Euro...
Source: European Respiratory Journal - March 18, 2019 Category: Respiratory Medicine Authors: Gebreselassie, N., Falzon, D., Zignol, M., Kasaeva, T. Tags: Editorials Source Type: research

Tolerability of rifapentine-based regimens in latent tuberculosis infection treatment in the elderly
Management of latent tuberculosis infection (LTBI) is a core intervention in the pursuit of tuberculosis (TB) elimination and is one of the eight activities recommended by the World Health Organization [1]. We read with great interest the paper by Gao et al. [2] investigating two short-course regimens with rifapentine plus isoniazid for the treatment of LTBI in Chinese patients aged 50–70 years. They reported that due to the ever-increasing occurrence of adverse events, the 3-month once-weekly regimen and the 2-month twice-weekly regimen were truncated to 8 and 6 weeks, respectively. Gao et al. [2...
Source: European Respiratory Journal - March 18, 2019 Category: Respiratory Medicine Authors: Chan, P.-C., Lee, P.-H., Lu, M.-J., Huang, Y.-C., Feng, T.-Y., Chen, W.-W., Lee, C.-C., Huang, Y.-F., Chiang, C.-Y. Tags: Original Articles: Correspondence Source Type: research

Pulmonary fibrosis: "idiopathic" is not "cryptogenic"
A recent paper by Wolters et al. [1] has raised considerable interest and stirred some debate regarding whether or not the word "idiopathic" should still be part of the name of the disease that we currently call idiopathic pulmonary fibrosis (IPF) [2]. The authors stated that the term idiopathic no longer seemed to describe this progressive lung disease accurately, especially considering the increasing understanding of the causes and pathogenesis of IPF. In a perspective published in the European Respiratory Journal, Wells et al. [3] responded that IPF remains a truly idiopathic fibrotic disease, with no overall ...
Source: European Respiratory Journal - March 18, 2019 Category: Respiratory Medicine Authors: Cottin, V. Tags: Original Articles: Correspondence Source Type: research

The worldwide assessment of separation of patients from ventilatory assistance (WEAN SAFE) ERS Clinical Research Collaboration
Successful weaning of patients from invasive mechanical ventilation (IMV) represents a critical hurdle in the recovery process following severe respiratory failure [1–3] and is a key clinical challenge for intensive care unit (ICU) clinicians. Many of the serious complications of IMV are directly related to the duration of ventilation [4, 5]. Failure to successfully separate patients from IMV contributes directly or indirectly to poorer patient outcomes including, of course, longer duration of ventilation, longer length of ICU and hospital stay, and higher patient morbidity (dyspnoea, infection, muscle weakness) and ...
Source: European Respiratory Journal - March 18, 2019 Category: Respiratory Medicine Authors: Heunks, L., Bellani, G., Pham, T., Brochard, L., Laffey, J. G. Tags: Editorials Source Type: research

Patient-reported outcome measures in the recovery of adults hospitalised with community-acquired pneumonia: a systematic review
Symptomatic and functional recovery are important patient-reported outcome measures (PROMs) in community-acquired pneumonia (CAP) that are increasingly used as trial end-points. This systematic review summarises the literature on PROMs in CAP. Comprehensive searches in accordance with the PRISMA statement were conducted to March 2017. Eligible studies included adults discharged from hospital following confirmed CAP and reporting PROMs. 15 studies (n=5644 patients) were included; most were of moderate quality. Studies used a wide range of PROMs and assessment tools. At 4–6 weeks post-discharge, the commonest symp...
Source: European Respiratory Journal - March 18, 2019 Category: Respiratory Medicine Authors: Pick, H. J., Bolton, C. E., Lim, W. S., McKeever, T. M. Tags: Respiratory infections and tuberculosis Original Articles: Infection Source Type: research

A randomised, placebo-controlled study of omipalisib (PI3K/mTOR) in idiopathic pulmonary fibrosis
Phosphatidylinositol 3-kinases (PI3Ks) and mammalian target of rapamycin (mTOR) play a role in the pathogenesis of idiopathic pulmonary fibrosis (IPF). Omipalisib (GSK2126458) is a potent inhibitor of PI3K/mTOR. A randomised, placebo-controlled, double-blind, repeat dose escalation, experimental medicine study of omipalisib in subjects with IPF was conducted (NCT01725139) to test safety, tolerability, pharmacokinetics and pharmacodynamics. Omipalisib was dosed at 0.25 mg, 1 mg and 2 mg twice daily for 8 days in four cohorts of four subjects randomised 3:1 to receive omipalisib or placebo (two cohorts re...
Source: European Respiratory Journal - March 18, 2019 Category: Respiratory Medicine Authors: Lukey, P. T., Harrison, S. A., Yang, S., Man, Y., Holman, B. F., Rashidnasab, A., Azzopardi, G., Grayer, M., Simpson, J. K., Bareille, P., Paul, L., Woodcock, H. V., Toshner, R., Saunders, P., Molyneaux, P. L., Thielemans, K., Wilson, F. J., Mercer, P. F. Tags: Interstitial and orphan lung disease Original Articles: Interstitial lung diseases Source Type: research

Which definition of a central tumour is more predictive of occult mediastinal metastasis in nonsmall cell lung cancer patients with radiological N0 disease?
Conclusions We suggest that a central tumour should be defined using the inner one-third of the hemithorax adopted by drawing concentric lines from the midline. This is particularly useful for predicting occult N2 disease in patients with NSCLC. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 18, 2019 Category: Respiratory Medicine Authors: Shin, S. H., Jeong, D. Y., Lee, K. S., Cho, J. H., Choi, Y. S., Lee, K., Um, S.-W., Kim, H., Jeong, B.-H. Tags: Lung cancer Original Articles: Lung cancer Source Type: research

Effect of daily azithromycin therapy and adherence on readmission risk in COPD
Patients with chronic obstructive pulmonary disease (COPD) frequently experience unplanned hospital readmissions leading to increased morbidity [1]. The European COPD Audit found that 35% of patients admitted with acute exacerbation of COPD (AECOPD) were readmitted within 90 days [2]. In the USA, 22% of patients admitted with AECOPD experienced a 30-day readmission, motivating financial policies to incentivise readmission reduction [1]. Interventions to decrease the risk of readmissions have had mixed results [3]. In a previously published, double-blinded, placebo-controlled, randomised clinical trial (MACRO), azithro...
Source: European Respiratory Journal - March 18, 2019 Category: Respiratory Medicine Authors: Krishnan, J. K., Voelker, H., Connett, J. E., Niewoehner, D. E., Albert, R. K., Scanlon, P. D., Criner, G. J., Dransfield, M. T., Han, M. K., Martinez, F. J., for the COPD Clinical Research Network Investigators Tags: Original Articles: Research letters Source Type: research

Chronic pulmonary aspergillosis commonly complicates treated pulmonary tuberculosis with residual cavitation
Chronic pulmonary aspergillosis (CPA) complicates treated pulmonary tuberculosis (TB), with high 5-year mortality. We measured CPA prevalence in this group. 398 Ugandans with treated pulmonary TB underwent clinical assessment, chest radiography and Aspergillus-specific IgG measurement. 285 were resurveyed 2 years later, including computed tomography of the thorax in 73 with suspected CPA. CPA was diagnosed in patients without active TB who had raised Aspergillus-specific IgG, radiological features of CPA and chronic cough or haemoptysis. Author-defined CPA was present in 14 (4.9%, 95% CI 2.8–7.9%) resurvey patie...
Source: European Respiratory Journal - March 18, 2019 Category: Respiratory Medicine Authors: Page, I. D., Byanyima, R., Hosmane, S., Onyachi, N., Opira, C., Richardson, M., Sawyer, R., Sharman, A., Denning, D. W. Tags: Respiratory infections and tuberculosis Original Articles: Infection and tuberculosis Source Type: research

Phase 2 clinical trial of PBI-4050 in patients with idiopathic pulmonary fibrosis
We present results from our first clinical study of PBI-4050 in patients with idiopathic pulmonary fibrosis (IPF). This 12-week open-label study explored the safety, efficacy and pharmacokinetics of daily oral doses of 800 mg PBI-4050 alone and in combination with nintedanib or pirfenidone in patients with predominantly mild or moderate IPF. Nine patients received PBI-4050 alone, 16 patients received PBI-4050 with nintedanib and 16 patients received PBI-4050 with pirfenidone. PBI-4050 alone or in combination with nintedanib or pirfenidone was well tolerated. Pharmacokinetic profiles for PBI-4050 were similar...
Source: European Respiratory Journal - March 18, 2019 Category: Respiratory Medicine Authors: Khalil, N., Manganas, H., Ryerson, C. J., Shapera, S., Cantin, A. M., Hernandez, P., Turcotte, E. E., Parker, J. M., Moran, J. E., Albert, G. R., Sawtell, R., Hagerimana, A., Laurin, P., Gagnon, L., Cesari, F., Kolb, M. Tags: Interstitial and orphan lung disease Original Articles: Interstitial lung diseases Source Type: research

ERJ March Podcast: Novel therapies in idiopathic pulmonary fibrosis
As part of the March issue, the European Respiratory Journal presents the latest in its series of podcasts. Chief Editor Martin Kolb interviews Toby Maher (Royal Brompton Hospital and Imperial College London, UK) about two articles in this issue reporting the results of randomised controlled trials in idiopathic pulmonary fibrosis. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 18, 2019 Category: Respiratory Medicine Tags: Electronic resources Source Type: research

Urban air quality and health: two steps forward, one step back
Air pollution in the form of particulate matter (PM), nitrogen dioxide (NO2) and ground level ozone (O3) all cause harm to human health. Across Europe, high concentrations of these air pollutants continue to have a negative impact on citizens, especially those living in urban areas. Air pollution also has marked economic impacts, leading to shorter lives, increased medical costs and reduced productivity. Air pollution also negatively impacts ecosystems, damaging lakes and rivers, and reduces agricultural yields. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 14, 2019 Category: Respiratory Medicine Authors: Kelly, F. J. Tags: Editorials Source Type: research

Finding the needle in the haystack: BMP9 and 10 emerge from the genome in pulmonary arterial hypertension
Evidence is emerging for a circulating axis of vascular protection, in which the release of bone morphogenetic proteins (BMPs) 9 and 10 from the liver and right atrium, respectively, provides tonic quiescent signals to the vascular endothelium [1]. These ligands circulate in the plasma at physiologically active concentrations to stimulate BMP signalling in endothelial cells via a receptor complex comprising the activin receptor-like kinase 1 (ALK1; also known as ACVRL1) and the bone morphogenetic protein receptor type 2 (BMPR2) [2]. We now know that the ALK1/BMPR2 receptor complex, expressed almost exclusively on endotheli...
Source: European Respiratory Journal - March 14, 2019 Category: Respiratory Medicine Authors: Morrell, N. W. Tags: Pulmonary vascular disease Editorials Source Type: research

Pulmonary rehabilitation is effective in patients with tuberculosis pulmonary sequelae
We read with interest the study reported by Collin et al. [1], who carried out a survey on organisation and priorities of national tuberculosis (TB) programmes in Europe. With an estimated annual incidence of 10 million cases, TB is considered one of the three global infectious disease priorities, together with HIV/AIDS and malaria. However, TB incidence has significantly declined in the general European population during the past two decades, with a relative increase in vulnerable groups [2, 3]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 14, 2019 Category: Respiratory Medicine Authors: Visca, D., Zampogna, E., Sotgiu, G., Centis, R., Saderi, L., D'Ambrosio, L., Pegoraro, V., Pignatti, P., Munoz-Torrico, M., Migliori, G. B., Spanevello, A. Tags: Original Articles: Correspondence Source Type: research

Cluster and CART analyses identify large subgroups of adults with cystic fibrosis at low risk of 10-year death
Our goal was to identify subgroups of adults with cystic fibrosis (CF) at low risk of death within 10 years. Factor analysis for mixed data followed by Ward's cluster analysis was conducted using 25 variables from 1572 French CF adults in 2005. Rates of death by subgroups were analysed over 10 years. An algorithm was developed using CART (classification and regression tree) analysis to provide rules for the identification of subgroups of CF adults with low rates of death within 10 years. This algorithm was validated in 1376 Canadian CF adults. Seven subgroups were identified by cluster analysis in French CF ...
Source: European Respiratory Journal - March 14, 2019 Category: Respiratory Medicine Authors: Burgel, P.-R., Lemonnier, L., Dehillotte, C., Sykes, J., Stanojevic, S., Stephenson, A. L., Paillasseur, J.-L. Tags: Original Articles: Cystic fibrosis Source Type: research

Simple stool processing method for the diagnosis of pulmonary tuberculosis using GeneXpert MTB/RIF
The diagnosis of pulmonary tuberculosis (pTB) in young children often relies on clinical diagnosis because young children are usually unable to produce a sputum sample. Sputum induction or gastric aspiration can be applied to obtain a sample for microbiological diagnosis but these methods cause discomfort, stress and pain, and cannot be performed at the lowest levels of the healthcare system, thus limiting access to pTB diagnosis of children. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 14, 2019 Category: Respiratory Medicine Authors: Andriyoko, B., Janiar, H., Kusumadewi, R., Klinkenberg, E., de Haas, P., Tiemersma, E. Tags: Original Articles: Research letters Source Type: research

Introducing molecular testing of pyrazinamide susceptibility improves multidrug-resistant tuberculosis treatment outcomes: a prospective cohort study
The current treatment for multidrug-resistant tuberculosis (MDR-TB) takes a lengthy period of 18–24 months and has a poor cure rate of 50–60%. A multicenter, prospective cohort study was conducted to assess the role of testing for molecular susceptibility to pyrazinamide (PZA) in optimising treatment for MDR-TB. We assigned 76 patients to an optimised molecular susceptibility group and 159 patients to a regular treatment group where PZA susceptibility was not determined. Of these patients, 152 were matched after propensity score matching (76 in the optimised group and 76 in the regular group). Treatment su...
Source: European Respiratory Journal - March 14, 2019 Category: Respiratory Medicine Authors: Sun, F., Li, Y., Chen, Y., Guan, W., Jiang, X., Wang, X., Ren, P., Li, J., Shi, J., He, G., Wu, M., Tang, P., Wang, F., Sheng, Y., Huang, F., Zhou, Z., Huang, H., Hong, L., Liu, Q., Zhang, Y., Zhang, W. Tags: Respiratory infections and tuberculosis Original Articles: Tuberculosis Source Type: research

Reduced prevalence of latent tuberculosis infection in diabetes patients using metformin and statins
Diabetes mellitus increases the risk of tuberculosis (TB) disease and adverse TB outcomes [1]. Emerging evidence suggests diabetes is also associated with latent TB infection (LTBI), and population-based studies reported the prevalence of LTBI among US adults with diabetes to be more than twice that of adults without diabetes (11.6% versus 4.6%) [2, 3]. Given the rapid increase of global diabetes prevalence in regions with high TB burdens, clinical and public health interventions targeting this co-epidemic would avert substantial morbidity and mortality [4]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 14, 2019 Category: Respiratory Medicine Authors: Magee, M. J., Salindri, A. D., Kornfeld, H., Singhal, A. Tags: Original Articles: Research letters Source Type: research

Germline BMP9 mutation causes idiopathic pulmonary arterial hypertension
Conclusion We identify BMP9 as an IPAH culprit gene. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 14, 2019 Category: Respiratory Medicine Authors: Wang, X.-J., Lian, T.-Y., Jiang, X., Liu, S.-F., Li, S.-Q., Jiang, R., Wu, W.-H., Ye, J., Cheng, C.-Y., Du, Y., Xu, X.-Q., Wu, Y., Peng, F.-H., Sun, K., Mao, Y.-M., Yu, H., Liang, C., Shyy, J. Y.-J., Zhang, S.-Y., Zhang, X., Jing, Z.-C. Tags: Pulmonary vascular disease Original Articles: Pulmonary vascular disease Source Type: research

Widening the landscape of heritable pulmonary hypertension mutations in paediatric and adult cases
Conclusion Our results confirm that mutations are found in genes beyond BMPR2 in heritable PAH, emphasise the role of TBX4 and BMP9, and designate BMP10 as a new PAH gene. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 14, 2019 Category: Respiratory Medicine Authors: Eyries, M., Montani, D., Nadaud, S., Girerd, B., Levy, M., Bourdin, A., Tresorier, R., Chaouat, A., Cottin, V., Sanfiorenzo, C., Prevot, G., Reynaud-Gaubert, M., Dromer, C., Houeijeh, A., Nguyen, K., Coulet, F., Bonnet, D., Humbert, M., Soubrier, F. Tags: Pulmonary vascular disease Original Articles: Pulmonary vascular disease Source Type: research

Relative and absolute lung function change in a general population aged 60-102 years
Data on longitudinal lung function change in the elderly are scarce. Uncertainty remains about whether to use absolute or relative change and how it relates to subject demographics. We studied absolute and relative forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) change in a population-based geriatric sample using a repeated measurements model adjusted for age, sex, smoking habits, heart failure, hypertension, diabetes, coronary heart disease, educational level, occupation, alcohol consumption, C-reactive protein (CRP) and body mass index. 3736 participants aged 60–102 years completed ...
Source: European Respiratory Journal - March 14, 2019 Category: Respiratory Medicine Authors: Luoto, J., Pihlsgard, M., Wollmer, P., Elmstahl, S. Tags: Lung structure and function Original Articles: Lung structure and function Source Type: research

Lessons from tracheal tube development for understanding congenital tracheal malformations
Fibrillins constitute a family of extracellular proteins critical for the biogenesis of elastic fibres and for the activity regulation of growth factors of the transforming growth factor (TGF)-β superfamily. All three fibrillins are present during development of tissues and organs, including lung, aorta, bones and skin [1–3]. Typically, fibrillin-2 and -3 expression is limited to prenatal and early postnatal development in humans, whereas fibrillin-1 expression persists throughout adulthood. In mouse, the situation is simplified by the fact that fibrillin-3 is not expressed due to chromosomal rearrangement event...
Source: European Respiratory Journal - March 7, 2019 Category: Respiratory Medicine Authors: Kumra, H., Dinesh, N. E. H., Reinhardt, D. P. Tags: Editorials Source Type: research

Pulmonary hypertension associated with left heart disease: efforts to improve the meaning of haemodynamic phenotypes
We appreciate the thoughtful comments of J.C. Grignola and colleagues in their letter addressing our article [1]. First, we agree that pulmonary hypertension associated with left heart disease (PH-LHD) is associated with global pulmonary vascular remodelling involving pulmonary arteries, veins and capillaries, as recently reported by Fayyaz et al. [2]. In fact, we have previously observed increased wall thickness and intimal fibrosis of small pulmonary arteries, even in patients with isolated post-capillary pulmonary hypertension (Ipc-PH) or "passive" pulmonary hypertension (PH) [3]. However, significant pre...
Source: European Respiratory Journal - March 7, 2019 Category: Respiratory Medicine Authors: Gerges, C., Gerges, M., Lang, I. M. Tags: Original Articles: Correspondence Source Type: research

Towards precision medicine: CCL2, another brick in the wall?
The introduction of targeted treatment in lung cancer has substantially changed the outcome of disease and the lives of lung cancer patients. Having biomarkers that can identify the right candidates and that predict the response to a specific treatment is very important and currently, research focuses on the identification of reliable molecular markers. In this issue of the European Respiratory Journal, Lu et al. [1] provide insight into the mechanisms of action of a new medication, anlotinib, and propose a new, predictive biomarker, the C-C motif ligand 2 (CCL2). (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 7, 2019 Category: Respiratory Medicine Authors: Charpidou, A., Kotteas, E., Gaga, M. Tags: Editorials Source Type: research

Quantitative analysis of lung sounds for monitoring idiopathic pulmonary fibrosis: a prospective pilot study
Accurate monitoring of disease progression in idiopathic pulmonary fibrosis (IPF) is crucial for predicting prognosis and optimising management, including the initiation of therapies, the appropriate timing of supportive care and the prompt referral for lung transplantation. While forced vital capacity (FVC) via spirometry has been accepted as the most feasible and reliable tool to assess the deterioration in these patients in clinical practice as well as in randomised controlled trials [1, 2], in recent years both visual evaluation and computer-based analysis of high-resolution computed tomography (HRCT) parenchymal patte...
Source: European Respiratory Journal - March 7, 2019 Category: Respiratory Medicine Authors: Sgalla, G., Larici, A. R., Sverzellati, N., Bartholmai, B., Walsh, S. L. F., Nikolic, D., Barney, A., Fletcher, S., Jones, M., Davies, D. D., Richeldi, L. Tags: Original Articles: Research letters Source Type: research

Adjunctive vitamin D in tuberculosis treatment: meta-analysis of individual participant data
Conclusions Vitamin D did not influence time to sputum culture conversion overall, but it accelerated sputum culture conversion in patients with multidrug-resistant pulmonary TB. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 7, 2019 Category: Respiratory Medicine Authors: Jolliffe, D. A., Ganmaa, D., Wejse, C., Raqib, R., Haq, M. A., Salahuddin, N., Daley, P. K., Ralph, A. P., Ziegler, T. R., Martineau, A. R. Tags: Respiratory infections and tuberculosis Original Articles: Tuberculosis Source Type: research

Lung function and oral health in adolescents
Only a few studies have investigated the association between periodontal diseases (PD), such as gingivitis or periodontitis, and lung health. The latest systematic review identified 14 observational studies and reported a pooled OR of 2.08 (95% CI 1.48–2.91) for chronic obstructive pulmonary disease (COPD) [1]. More recent studies have confirmed the adverse effects of oral inflammation on lung disease [2], but not all [3]. Three interventional trials in adults showed the positive effects of periodontal therapy on lung function in patients with COPD. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 7, 2019 Category: Respiratory Medicine Authors: Heinrich, J., Thiering, E., Jörres, R. A., Schulz, H., Kühnisch, J., Standl, M. Tags: Original Articles: Research letters Source Type: research

Pulmonary hypertension associated with left heart disease: efforts to improve the meaning of haemodynamic phenotypes
We read with great interest the recent article by Gerges et al. [1] on partitioning pulmonary vascular resistance (PVR) at baseline and after inhaled nitric oxide (iNO) in patients with pulmonary hypertension associated with left heart disease (PH-LHD). The study highlighted that the increase of right ventricular (RV) afterload in isolated post-capillary PH (Ipc-PH) primarily depended on a passive backward transmission of left ventricular filling pressure and left atrial (LA) function, explaining the very high upstream resistance (Rup). Further afterload increase secondary to an elevated vessel resistance in combined ...
Source: European Respiratory Journal - March 7, 2019 Category: Respiratory Medicine Authors: Grignola, J. C., Trujillo, P., Domingo, E. Tags: Original Articles: Correspondence Source Type: research

Restricted visiting reduces nosocomial viral respiratory tract infections in high-risk neonates
Viral respiratory tract infections (VRTIs) are more prevalent in the neonatal intensive care unit (NICU) than previously thought, with up to 52% of infants having evidence of viral carriage [1, 2]. We and others have previously reported nosocomial VRTIs can cause significant morbidity [3], particularly in preterm infants, including escalation of respiratory support, longer hospital stay, increased requirement for home oxygen and greater healthcare costs [1, 4]. Viral carriage in the airways of children and adults may have few or no symptoms [3, 5], potentially implicating them as an inadvertent source of nosocomial VRTI wh...
Source: European Respiratory Journal - March 7, 2019 Category: Respiratory Medicine Authors: Szatkowski, L., McClaughry, R., Clarkson, M., Sharkey, D. Tags: Original Articles: Research letters Source Type: research

Making sense of cost-effectiveness analyses in respiratory medicine: a practical guide for non-health economists
We live in a world of great advances in respiratory care, but at the same time, we are facing increasing budget constraints. In such a world, the use of any intervention is associated with "opportunity loss": the benefit forgone by not using alternative interventions. Take the example of biologicals for severe asthma (e.g. mepolizumab) or lung cancer (e.g. nivolumab), with annual costs of around EUR 15 000 and>EUR 100 000 per patient, respectively. The concept of opportunity loss applies whenever decisions are made, either by physicians in clinical practice who have to decide which treatment patients...
Source: European Respiratory Journal - March 7, 2019 Category: Respiratory Medicine Authors: van Boven, J. F. M., van de Hei, S. J., Sadatsafavi, M. Tags: ERJ Methods Source Type: research

The added value of comorbidities in predicting survival in idiopathic pulmonary fibrosis: a multicentre observational study
Conclusions The inclusion of comorbidities in TORVAN models significantly improved the discriminative performance in prediction of risk of death compared to GAP. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 7, 2019 Category: Respiratory Medicine Authors: Torrisi, S. E., Ley, B., Kreuter, M., Wijsenbeek, M., Vittinghoff, E., Collard, H. R., Vancheri, C. Tags: Interstitial and orphan lung disease Original Articles: Interstitial lung diseases Source Type: research

Role of anlotinib-induced CCL2 decrease in anti-angiogenesis and response prediction for nonsmall cell lung cancer therapy
Conclusions Our study reports a novel anti-angiogenesis mechanism of anlotinib via inhibiting CCL2 in an NCI-H1975-derived xenograft model and suggests that changes in serum CCL2 levels may be used to monitor and predict clinical outcomes in anlotinib-administered refractory advanced NSCLC patients using third-line therapy or beyond. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 7, 2019 Category: Respiratory Medicine Authors: Lu, J., Zhong, H., Chu, T., Zhang, X., Li, R., Sun, J., Zhong, R., Yang, Y., Alam, M. S., Lou, Y., Xu, J., Zhang, Y., Wu, J., Li, X., Zhao, X., Li, K., Lu, L., Han, B. Tags: Lung cancer Original Articles: Lung cancer Source Type: research

Serum levels of hyaluronic acid are associated with COPD severity and predict survival
Hyaluronic acid (HA) and its degradation products play an important role in lung pathophysiology and airway remodelling in chronic obstructive pulmonary disease (COPD). We investigated if HA and its degrading enzyme hyaluronidase (HYAL)-1 are associated with COPD severity and outcome. Serum HA was assessed in a discovery cohort of 80 COPD patients at stable state and exacerbations. HA, HYAL-1 and HYAL-1 enzymatic activity were evaluated at stable state, exacerbations and 4 weeks after exacerbations in 638 COPD patients from the PROMISE validation cohort. In the discovery cohort, serum HA was higher at exacerbations co...
Source: European Respiratory Journal - March 7, 2019 Category: Respiratory Medicine Authors: Papakonstantinou, E., Bonovolias, I., Roth, M., Tamm, M., Schumann, D., Baty, F., Louis, R., Milenkovic, B., Boersma, W., Stieltjes, B., Kostikas, K., Blasi, F., Aerts, J. G., Rohde, G. G. U., Lacoma, A., Torres, A., Welte, T., Stolz, D. Tags: COPD and smoking Original Articles: COPD Source Type: research

Fibrillin-2 is a key mediator of smooth muscle extracellular matrix homeostasis during mouse tracheal tubulogenesis
Epithelial tubes, comprised of polarised epithelial cells around a lumen, are crucial for organ function. However, the molecular mechanisms underlying tube formation remain largely unknown. Here, we report on the function of fibrillin (FBN)2, an extracellular matrix (ECM) glycoprotein, as a critical regulator of tracheal tube formation. We performed a large-scale forward genetic screen in mouse to identify regulators of respiratory organ development and disease. We identified Fbn2 mutants which exhibit shorter and narrowed tracheas as well as defects in tracheal smooth muscle cell alignment and polarity. We found that FBN2...
Source: European Respiratory Journal - March 7, 2019 Category: Respiratory Medicine Authors: Yin, W., Kim, H.-T., Wang, S., Gunawan, F., Li, R., Buettner, C., Grohmann, B., Sengle, G., Sinner, D., Offermanns, S., Stainier, D. Y. R. Tags: Lung biology and experimental studies Original Articles: Basic science Source Type: research

Biomarkers in community-acquired pneumonia: still searching for the one
Community-acquired pneumonia (CAP) remains a major cause of morbidity and mortality worldwide [1]. Despite advances in antibiotic treatment and medical care, the mortality of CAP is still high in hospitalised patients, especially in those with severe illness [2]. Appropriate initial severity assessment is a crucial step in pneumonia management, since it has been demonstrated that an early recognition of severe CAP patients improves their clinical outcomes [3]. Several tools have been developed to evaluate disease severity, in particular focusing on predicting hospital admission and mortality [4]. However, recent studies ha...
Source: European Respiratory Journal - February 28, 2019 Category: Respiratory Medicine Authors: Sibila, O., Restrepo, M. I. Tags: Editorials Source Type: research

The significant global economic burden of bronchiectasis: a pending matter
Bronchiectasis should no longer be considered an "orphan lung disease" in view of its prevalence globally [1]. For instance, the prevalence of bronchiectasis has been found to range from 67 to 566.1 per 100 000 inhabitants in Europe and North America (i.e. Germany [2], Spain [3], the UK [4] and the USA [5]), and has reached 1200 per 100 000 inhabitants among those aged 40 years or older in China [6]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - February 28, 2019 Category: Respiratory Medicine Authors: Guan, W.-j., Han, X.-r., de la Rosa-Carrillo, D., Martinez-Garcia, M. A. Tags: Respiratory infections and tuberculosis Editorials Source Type: research

Economic burden of bronchiectasis in Germany
Estimates of healthcare costs for incident bronchiectasis patients are currently not available for any European country. Out of a sample of 4 859 013 persons covered by German statutory health insurance companies, 231 new bronchiectasis patients were identified in 2012. They were matched with 685 control patients by age, sex and Charlson Comorbidity Index, and followed for 3 years. The total direct expenditure during that period per insured bronchiectasis patient was EUR18 634.57 (95% CI EUR15 891.02–23 871.12), nearly one-third higher (ratio of mean 1.31, 95% CI 1.02–1.68) than for a matched control (p50%...
Source: European Respiratory Journal - February 28, 2019 Category: Respiratory Medicine Authors: Diel, R., Chalmers, J. D., Rabe, K. F., Nienhaus, A., Loddenkemper, R., Ringshausen, F. C. Tags: Respiratory infections and tuberculosis Original Articles: Infection and bronchiectasis Source Type: research

MEK5 promotes lung adenocarcinoma
Lung cancer represents the leading cause of cancer death worldwide [1]. Because of that, intense efforts are being devoted to the development of novel therapeutic strategies to fight the disease [2]. In this respect, identification of new oncogenic drivers offers therapeutic opportunities in tumours in which those molecules or other cooperating elements play a pathophysiological role. Here, we show that the MEK5 mitogen-activated protein kinase kinase has a pivotal role in lung cancer. (Source: European Respiratory Journal)
Source: European Respiratory Journal - February 28, 2019 Category: Respiratory Medicine Authors: Sanchez-Fdez, A., Ortiz-Ruiz, M. J., Re-Louhau, M. F., Ramos, I., Blanco-Munez, O., Ludena, D., Abad, M., Sanchez-Martin, M., Pandiella, A., Esparis-Ogando, A. Tags: Original Articles: Research letters Source Type: research

Fibroblast growth factor 21 predicts outcome in community-acquired pneumonia: secondary analysis of two randomised controlled trials
This study aims to characterise the pattern of FGF21 in pneumonia and associations with disease severity and outcome. This is a secondary analysis of two independent multicentre randomised controlled trials in patients presenting to the emergency department with CAP. Primary and secondary efficacy parameters included 30-day mortality, length of hospital stay, time to clinical stability and duration of antibiotic treatment. A total of 509 patients were included in the analysis. FGF21 levels at admission strongly correlated with disease severity, as measured by the Pneumonia Severity Index. Increased levels of FGF21 were ass...
Source: European Respiratory Journal - February 28, 2019 Category: Respiratory Medicine Authors: Ebrahimi, F., Wolffenbuttel, C., Blum, C. A., Baumgartner, C., Mueller, B., Schuetz, P., Meier, C., Kraenzlin, M., Christ-Crain, M., Betz, M. J. Tags: Lung biology and experimental studies, Respiratory infections and tuberculosis Original Articles: Respiratory infection Source Type: research

Computed tomography abnormalities antedating mesothelioma diagnosis: a perspective on the natural history
Malignant pleural mesothelioma (MPM) is an aggressive and fatal disease that typically presents with breathlessness, chest pain or both [1]. It is usually a unilateral disease but 3% of patients have malignant disease bilaterally at presentation [2]. The latency period between exposure to asbestos and MPM development is 20–40 years. (Source: European Respiratory Journal)
Source: European Respiratory Journal - February 28, 2019 Category: Respiratory Medicine Authors: Hassan, M., Tsikrika, S., Asciak, R., Mercer, R. M., El-Ganady, A., Rahman, N. M. Tags: Original Articles: Research letters Source Type: research

ERS statement on exercise training and rehabilitation in patients with severe chronic pulmonary hypertension
Objectives of this European Respiratory Society task force were to summarise current studies, to develop strategies for future research and to increase availability and awareness of exercise training for pulmonary hypertension (PH) patients. An evidence-based approach with clinical expertise of the task force members, based on both literature search and face-to-face meetings was conducted. The statement summarises current knowledge and open questions regarding clinical effects of exercise training in PH, training modalities, implementation strategies and pathophysiological mechanisms. In studies (784 PH patients in total, ...
Source: European Respiratory Journal - February 28, 2019 Category: Respiratory Medicine Authors: Grünig, E., Eichstaedt, C., Barbera, J.-A., Benjamin, N., Blanco, I., Bossone, E., Cittadini, A., Coghlan, G., Corris, P., D'Alto, M., D'Andrea, A., Delcroix, M., de Man, F., Gaine, S., Ghio, S., Gibbs, S., Gumbiene, L., Howard, L. S., Johnson, M. Tags: Original Articles: ERS statement Source Type: research

Bacterial load and defective monocyte-derived macrophage bacterial phagocytosis in biomass smoke-related COPD
Lower airway colonisation with species of potentially pathogenic bacteria (PPB) is associated with defective bacterial phagocytosis, in monocyte-derived macrophages (MDMs) and alveolar macrophages, from tobacco smoke-associated chronic obstructive pulmonary disease (S-COPD) subjects. In the developing world, COPD among nonsmokers is largely due to biomass smoke (BMS) exposure; however, little is known about PPB colonisation and its association with impaired innate immunity in these subjects. We investigated the PPB load (Streptococcus pneumoniae, Haemophilus influenzae, Moraxella catarrhalis and Pseudomonas aeruginosa) in ...
Source: European Respiratory Journal - February 28, 2019 Category: Respiratory Medicine Authors: Ghosh, B., Gaike, A. H., Pyasi, K., Brashier, B., Das, V. V., Londhe, J. D., Juvekar, S., Shouche, Y. S., Donnelly, L. E., Salvi, S. S., Barnes, P. J. Tags: COPD and smoking Original Articles: COPD Source Type: research

Surgical lung biopsy for interstitial lung disease: when considered necessary, should these be done in larger and experienced centres only?
Ascertaining an accurate diagnosis for people confronted with new onset interstitial lung disease (ILD) is central to informing discussions around prognosis and treatment choices. In people with idiopathic pulmonary fibrosis (IPF), treatment with both pirfenidone and nintedanib has been shown to reduce the rate of disease progression [1, 2], whereas historical use of immunosuppression was shown in the landmark PANTHER study to be harmful [3]. In other conditions, such as hypersensitivity pneumonitis or sarcoidosis, an accurate diagnosis helps to inform prognosis, allow removal from harmful exposure, and justify considerati...
Source: European Respiratory Journal - February 21, 2019 Category: Respiratory Medicine Authors: Hutchinson, J., Hubbard, R., Raghu, G. Tags: Editorials Source Type: research

Moving forward from drug-centred to patient-centred research: A white paper initiated by EORTC and developed together with the BioMed Alliance members
Maximising the potential of precision medicine for patients and healthcare services is a major societal challenge. It requires a holistic approach to the development of therapeutic strategies and a re-thinking of the entire process, including the role of the respective stakeholders and the way they interact, from the early steps of drug development to access in real life. First, the new technologies that inform us about the biology of the disease and enable better treatments plead for a reversal of the "protocols search patients" approach, to "patients searching (the best possible) treatments and protocols&q...
Source: European Respiratory Journal - February 21, 2019 Category: Respiratory Medicine Authors: Lacombe, D., O'Morain, C., Casadei, B., Hill, K., Mateus, E., Lories, R., Brusselle, G. Tags: Editorials Source Type: research

Effects of short-term continuous positive airway pressure withdrawal on cerebral vascular reactivity measured by blood oxygen level-dependent magnetic resonance imaging in obstructive sleep apnoea: a randomised controlled trial
Impaired cerebral vascular reactivity (CVR) increases long-term stroke risk. Obstructive sleep apnoea (OSA) is associated with peripheral vascular dysfunction and vascular events. The aim of this trial was to evaluate the effect of continuous positive airway pressure (CPAP) withdrawal on CVR. 41 OSA patients (88% male, mean age 57±10 years) were randomised to either subtherapeutic or continuation of therapeutic CPAP. At baseline and after 2 weeks, patients underwent a sleep study and magnetic resonance imaging (MRI). CVR was estimated by quantifying the blood oxygen level-dependent (BOLD) MRI response to b...
Source: European Respiratory Journal - February 21, 2019 Category: Respiratory Medicine Authors: Thiel, S., Lettau, F., Rejmer, P., Rossi, C., Haile, S. R., Schwarz, E. I., Stöberl, A. S., Sievi, N. A., Boss, A., Becker, A. S., Winklhofer, S., Stradling, J. R., Kohler, M. Tags: Sleep medicine Original Articles: Sleep Source Type: research

Cloud algorithm-driven oximetry-based diagnosis of obstructive sleep apnoea in symptomatic habitually snoring children
The ability of a cloud-driven Bluetooth oximetry-based algorithm to diagnose obstructive sleep apnoea syndrome (OSAS) was examined in habitually snoring children concurrently undergoing overnight polysomnography. Children clinically referred for overnight in-laboratory polysomnographic evaluation for suspected OSAS were simultaneously hooked to a Bluetooth oximeter linked to a smartphone. Polysomnography findings were scored and the apnoea/hypopnoea index (AHIPSG) was tabulated, while oximetry data yielded an estimated AHIOXI using a validated algorithm. The accuracy of the oximeter in identifying correctly patients with O...
Source: European Respiratory Journal - February 21, 2019 Category: Respiratory Medicine Authors: Xu, Z., Gutierrez-Tobal, G. C., Wu, Y., Kheirandish-Gozal, L., Ni, X., Hornero, R., Gozal, D. Tags: Sleep medicine Original Articles: Sleep Source Type: research