High rifampicin-resistant TB cure rates and prevention of severe ototoxicity after replacing the injectable by linezolid in early stage of hearing loss
The short treatment regimen (STR) achieves a>80% cure in rifampicin-resistant tuberculosis (RR-TB) patients. However, ototoxicity induced by the injectable is a concern. This is the first study to evaluate the replacement of injectables by linezolid in patients with audiometry abnormalities at baseline or during the treatment. We conducted a retrospective cohort study of all RR-TB patients started on the STR between 2016 and June, 2019, in Niger. Patients underwent audiometry every 2 months in 2016 and every month since 2017. Of 195 patients, 16.9% (33 out of 195) received linezolid from the start (n=17), or switch...
Source: European Respiratory Journal - January 21, 2021 Category: Respiratory Medicine Authors: Souleymane, M. B., Piubello, A., Lawan, I. M., Hassane-Harouna, S., Assao-Neino, M. M., Soumana, A., Hamidou-Harouna, Z., Gagara-Issoufou, A., Ortuno-Gutierrez, N., Roggi, A., Schwoebel, V., Mamadou, S., Lynen, L., De Jong, B., Van Deun, A., Decroo, T. Tags: Respiratory infections and tuberculosis Original Articles: Tuberculosis Source Type: research

Chronic thromboembolic pulmonary hypertension and totally implantable central venous access systems
(Source: European Respiratory Journal)
Source: European Respiratory Journal - January 21, 2021 Category: Respiratory Medicine Authors: Jevnikar, M., Montani, D., Savale, L., Seferian, A., Jutant, E.-M., Boucly, A., Preda, M., Weatherald, J., Bulifon, S., Parent, F., Brenot, P., Fadel, E., Sitbon, O., Simonneau, G., Humbert, M., Jaïs, X. Tags: Original Articles: Research letters Source Type: research

Ivacaftor modifies cystic fibrosis neutrophil phenotype in subjects with R117H residual function CFTR mutations
(Source: European Respiratory Journal)
Source: European Respiratory Journal - January 21, 2021 Category: Respiratory Medicine Authors: Hardisty, G. R., Law, S. M., Carter, S., Grogan, B., Singh, P. K., McKone, E. F., Gray, R. D. Tags: Original Articles: Research letters Source Type: research

Serum mitochondrial DNA predicts the risk of acute exacerbation and progression of idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) is a progressive, fatal interstitial lung disease with a median survival of 3–5 years [1]. Its disease course is highly variable, as some patients experience rapid deterioration in lung function while others experience more gradual decline [2]. The development of acute exacerbation of IPF (AE-IPF), a highly lethal complication of unknown aetiology, has been shown to accelerate disease progression [3]. Presently, there are no accepted biomarkers that predict clinical deterioration [4], thus indicating an important, unmet need in the management of this devastating disease. (Sour...
Source: European Respiratory Journal - January 21, 2021 Category: Respiratory Medicine Authors: Sakamoto, K., Furukawa, T., Yamano, Y., Kataoka, K., Teramachi, R., Walia, A., Suzuki, A., Inoue, M., Nakahara, Y., Ryu, C., Hashimoto, N., Kondoh, Y. Tags: Original Articles: Research letters Source Type: research

Incidence of osteoporosis and fragility fractures in asthma: a UK population-based matched cohort study
We report the impact of age, sex, glucocorticoids and the risk of specific fractures. Results Patients with asthma had a higher risk of osteoporosis (adjusted hazard ratio (aHR) 1.18, 95% CI 1.13–1.23) and were 12% (aHR 1.12, 95% CI 1.07–1.16) more likely to sustain fragility fractures than the general population. Age modified the effect of asthma on osteoporosis and fragility fractures, such that the effect was stronger in younger people (pinteraction
Source: European Respiratory Journal - January 21, 2021 Category: Respiratory Medicine Authors: Chalitsios, C. V., McKeever, T. M., Shaw, D. E. Tags: Asthma and allergy Original Articles: Asthma Source Type: research

Oestrogen-mediated upregulation of the Mas receptor contributes to sex differences in acute lung injury and lung vascular barrier regulation
Epidemiological data from the SARS-CoV-2 outbreak suggest sex differences in mortality and vulnerability; however, sex-dependent incidence of acute respiratory distress syndrome (ARDS) remains controversial and the sex-dependent mechanisms of endothelial barrier regulation are unknown. In premenopausal women, increased signalling of angiotensin (Ang)(1–7) via the Mas receptor has been linked to lower cardiovascular risk. Since stimulation of the Ang(1–7)/Mas axis protects the endothelial barrier in acute lung injury (ALI), we hypothesised that increased Ang(1–7)/Mas signalling may protect females over mal...
Source: European Respiratory Journal - January 21, 2021 Category: Respiratory Medicine Authors: Erfinanda, L., Ravindran, K., Kohse, F., Gallo, K., Preissner, R., Walther, T., Kuebler, W. M. Tags: Lung biology and experimental studies, Acute lung injury and critical care Original Articles: Acute lung injury and basic science Source Type: research

Treatment options in type-2 low asthma
Monoclonal antibodies targeting IgE or the type-2 cytokines interleukin (IL)-4, IL-5 and IL-13 are proving highly effective in reducing exacerbations and symptoms in people with severe allergic and eosinophilic asthma, respectively. However, these therapies are not appropriate for 30–50% of patients in severe asthma clinics who present with non-allergic, non-eosinophilic, "type-2 low" asthma. These patients constitute an important and common clinical asthma phenotype, driven by distinct, yet poorly understood pathobiological mechanisms. In this review we describe the heterogeneity and clinical characteristi...
Source: European Respiratory Journal - January 21, 2021 Category: Respiratory Medicine Authors: Hinks, T. S. C., Levine, S. J., Brusselle, G. G. Tags: Series Source Type: research

Identification of asthma phenotypes based on extrapulmonary treatable traits
The objective of this study was to identify and characterise clusters based on clinical, functional, anthropometrical and psychological characteristics in participants with moderate-to-severe asthma. This was a cross-sectional multicentre study involving centres from Brazil and Australia. Participants (n=296) with moderate-to-severe asthma were consecutively recruited. Physical activity and sedentary time, clinical asthma control, anthropometric data, pulmonary function and psychological and health status were evaluated. Participants were classified by hierarchical cluster analysis and the clusters compared using ANOVA, Kr...
Source: European Respiratory Journal - January 21, 2021 Category: Respiratory Medicine Authors: Freitas, P. D., Xavier, R. F., McDonald, V. M., Gibson, P. G., Cordova-Rivera, L., Furlanetto, K. C., de Oliveira, J. M., Carvalho-Pinto, R. M., Cukier, A., Stelmach, R., Carvalho, C. R. F. Tags: Asthma and allergy Original Articles: Asthma Source Type: research

E-cigarette use and respiratory disorders: an integrative review of converging evidence from epidemiological and laboratory studies
Conclusions The evidence from epidemiological studies meets established criteria for consistency, strength of effect, temporality, and in some cases a dose–response gradient. Biological plausibility is indicated by evidence from multiple laboratory studies. We conclude that e-cigarette use has consequences for asthma and COPD, which is of concern for respirology and public health. (Source: European Respiratory Journal)
Source: European Respiratory Journal - January 21, 2021 Category: Respiratory Medicine Authors: Wills, T. A., Soneji, S. S., Choi, K., Jaspers, I., Tam, E. K. Tags: State of the Art Source Type: research

Biomarkers in lung cancer screening: the importance of study design
In most randomised controlled trials of low radiation dose computed tomography (LDCT) screening for lung cancer, eligibility has been determined by age and tobacco smoking criteria [1, 2]. A number of multivariable risk prediction models have been developed that are more sensitive and specific, but are still heavily dependent on smoking and age [3]. Some have been used successfully in trials and pilot programmes and have yielded higher detection rates, although they may also select people with more comorbidities [4–6]. Using biomarkers to select people for lung cancer screening is an important area for research becau...
Source: European Respiratory Journal - January 14, 2021 Category: Respiratory Medicine Authors: Baldwin, D. R., Callister, M. E., Crosbie, P. A., O'Dowd, E. L., Rintoul, R. C., Robbins, H. A., Steele, R. J. C. Tags: Original Articles: Lung cancer Source Type: research

Increased focus on non-animal models for COVID-19 and non-COVID lung research
This report from the European Commission's Joint Research Centre EU Reference Laboratory (EURL ECVAM), and its accompanying dataset [2], identifies well-established current and emerging in vitro, in silico and ex vivo non-animal models for respiratory disease modelling, and reinforces the concept of "reduce, refine, or replace" animals used for scientific purposes. The 3R approach is not only embraced by the European Commission, but also the respiratory research community, as evidenced by many European Respiratory Society publications as well as frequent ERS Congress sessions and research seminars on the topic. (...
Source: European Respiratory Journal - January 14, 2021 Category: Respiratory Medicine Authors: Gribaldo, L., Hurley, K., Hiemstra, P., Greene, C. Tags: Original Articles: Correspondence Source Type: research

User-life of ICS/LABA inhaler devices should be considered when prescribed as relievers
Inhaled corticosteroid/formoterol (ICS/FOR) combination medications were initially developed as maintenance therapy; more recently they are also used as relievers in Europe and this use is proposed in the USA. ICS coupled with FOR (a long-acting β2-agonist) is recommended by the 2020 Global Initiative for Asthma (GINA) guidelines [1] for steps 2–5 as maintenance and reliever (SMART) and is recommended for steps 3 and 4 in the 2020 USA National Asthma Education and Prevention Program (NAEPP) [2]. While SMART has regulatory approval in Europe, it does not in the USA. (Source: European Respiratory Journal)
Source: European Respiratory Journal - January 14, 2021 Category: Respiratory Medicine Authors: Pleasants, R. A., Tilley, S. L., Hickey, A. J., Usmani, O. S. Tags: Original Articles: Correspondence Source Type: research

Genetically proxied interleukin-6 receptor inhibition: opposing associations with COVID-19 and pneumonia
The inflammatory cytokine interleukin-6 (IL-6) is central to orchestrating the immune system [1]. The pathophysiological process underlying severe coronavirus disease 2019 (COVID-19), caused by the severe acute respiratory syndrome coronavirus 2, consists of an exaggerated host immune response and elevated circulating levels of inflammatory cytokines, including IL-6 [2, 3]. As such, immunomodulatory agents are being investigated for the treatment of COVID-19. Glucocorticoids may limit inflammation-mediated lung injury in patients with severe COVID-19, and consequently reduce progression to respiratory failure and death. Th...
Source: European Respiratory Journal - January 14, 2021 Category: Respiratory Medicine Authors: Larsson, S. C., Burgess, S., Gill, D. Tags: Original Articles: Research letters Source Type: research

Household air pollution and adult respiratory health
In modern society, we spend most of our time indoors, especially in the home environment. Since most studies on respiratory effects of household air pollution (HAP) have investigated children, more studies are needed on HAP and adult respiratory health, especially prospective studies. One review concluded that the indoor factors most consistently associated with adult asthma include fuel combustion, dampness and mould, and second hand tobacco smoke (SHS) [1]. Another recent review concluded that SHS increases the risk of asthma exacerbations, respiratory symptoms and healthcare utilisation, and that other indoor pollutants...
Source: European Respiratory Journal - January 14, 2021 Category: Respiratory Medicine Authors: Norbäck, D., Wang, J. Tags: Editorials Source Type: research

Validation of Lung EpiCheck, a novel methylation-based blood assay, for the detection of lung cancer in European and Chinese high-risk individuals
Conclusions Lung EpiCheck demonstrated strong performance in lung cancer prediction in case–control European and Chinese samples, detecting high proportions of early-stage NSCLC and SCLC and significantly improving predictive accuracy when added to established risk factors. Prospective studies are required to confirm these findings. Utilising such a simple and inexpensive blood test has the potential to improve compliance and broaden access to screening for at-risk populations. (Source: European Respiratory Journal)
Source: European Respiratory Journal - January 14, 2021 Category: Respiratory Medicine Authors: Gaga, M., Chorostowska-Wynimko, J., Horvath, I., Tammemagi, M. C., Shitrit, D., Eisenberg, V. H., Liang, H., Stav, D., Levy Faber, D., Jansen, M., Raviv, Y., Panagoulias, V., Rudzinski, P., Izbicki, G., Ronen, O., Goldhaber, A., Moalem, R., Arber, N., Haa Tags: Lung cancer Original Articles: Lung cancer Source Type: research

Effect of type and dosage of newly prescribed inhaled corticosteroids on obstructive lung disease and pneumonia hospitalisations in older individuals with asthma, COPD or both: a retrospective study of health administrative data
The safety and risk–benefit profiles associated with different types and dosages of inhaled corticosteroids (ICS) in older individuals with asthma and COPD remain unknown [1, 2]. Limited evidence suggests that adults with asthma prescribed medium or high ICS doses are at risk of clinically important systemic side-effects that do not plateau with higher doses as efficacy outcomes do [3]. Older patients with COPD have been shown to have increased risk of pneumonia with both budesonide and fluticasone [4]; however, the risk seems greater with the latter [2, 4–6]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - January 14, 2021 Category: Respiratory Medicine Authors: Kendzerska, T., Aaron, S. D., To, T., Licskai, C., Stanbrook, M. B., Hogan, M.-E., Tan, W. C., Bourbeau, J., Gershon, A. S., for the Canadian Respiratory Research Network and CanBREATHE (the Canadian Best Respiratory Research Evaluation and Analyst Team o Tags: Original Articles: Research letters Source Type: research

Maternal antibiotic use during pregnancy and asthma in children: population-based cohort study and sibling design
Antibiotic use during pregnancy may affect asthma risk in offspring. However, epidemiological studies yielded conflicting findings, with an observed association possibly confounded by shared familial factors. We sought to assess the association between maternal antibiotic use during pregnancy and childhood asthma in the offspring, by accounting for time-stable familial factors. We conducted a population-based cohort study and sibling study using data from Danish nationwide registers, which comprised 407 804 liveborn singletons from 2005 to 2011. Antibiotic use during pregnancy was defined as at least one antibiotic prescri...
Source: European Respiratory Journal - January 14, 2021 Category: Respiratory Medicine Authors: Momen, N. C., Liu, X. Tags: Asthma and allergy, Paediatric pulmonology Original Articles: Paediatrics and asthma Source Type: research

Omalizumab restores the ability of human plasmacytoid dendritic cells to induce Foxp3+Tregs
Allergic sensitisation and viral respiratory tract infections represent the main risk factors for asthma development and severity. IgE plays a key role in the pathophysiology of allergic asthma and allergic multimorbidities [1, 2]. Omalizumab, a recombinant humanised monoclonal antibody against IgE, has been used to treat allergic asthma in children and adults for many years [3–5]. Omalizumab restores the capacity of human plasmacytoid dendritic cells (pDCs) to produce interferon (IFN)-α, increasing their antiviral activity and reducing viral-induced asthma exacerbations [6, 7]. pDCs prime T-helper cell (Th)1 o...
Source: European Respiratory Journal - January 14, 2021 Category: Respiratory Medicine Authors: Lopez-Abente, J., Benito-Villalvilla, C., Jaumont, X., Pfister, P., Tassinari, P., Palomares, O. Tags: Original Articles: Research letters Source Type: research

Earlier diagnosis of lung cancer in a randomised trial of an autoantibody blood test followed by imaging
We report on the results of a phase IV biomarker evaluation of whether using the EarlyCDT-Lung test and any subsequent computed tomography (CT) scanning to identify those at high risk of lung cancer reduces the incidence of patients with stage III/IV/unspecified lung cancer at diagnosis compared with the standard clinical practice at the time the study began. The Early Diagnosis of Lung Cancer Scotland (ECLS) trial was a randomised controlled trial of 12 208 participants at risk of developing lung cancer in Scotland in the UK. The intervention arm received the EarlyCDT-Lung test and, if test-positive, low-dose CT scanning ...
Source: European Respiratory Journal - January 14, 2021 Category: Respiratory Medicine Authors: Sullivan, F. M., Mair, F. S., Anderson, W., Armory, P., Briggs, A., Chew, C., Dorward, A., Haughney, J., Hogarth, F., Kendrick, D., Littleford, R., McConnachie, A., McCowan, C., McMeekin, N., Patel, M., Rauchhaus, P., Ritchie, L., Robertson, C., Robertson Tags: Lung cancer Original Articles: Lung cancer Source Type: research

Exposure to household air pollution over 10 years is related to asthma and lung function decline
Conclusions Exposures to wood heating, gas cooking and heating, and tobacco smoke over 10 years increased the risks of persistent asthma, lung function decline and % reversibility, with evidence of interaction by GST genes and ventilation. (Source: European Respiratory Journal)
Source: European Respiratory Journal - January 14, 2021 Category: Respiratory Medicine Authors: Dai, X., Bui, D. S., Perret, J. L., Lowe, A. J., Frith, P. A., Bowatte, G., Thomas, P. S., Giles, G. G., Hamilton, G. S., Tsimiklis, H., Hui, J., Burgess, J., Win, A. K., Abramson, M. J., Walters, E. H., Dharmage, S. C., Lodge, C. J. Tags: Epidemiology, occupational and environmental lung disease, Asthma and allergy Original Articles: Asthma and pollution Source Type: research

Hyperglycaemia in cystic fibrosis adversely affects BK channel function critical for mucus clearance
Large-conductance, Ca2+-activated, voltage-dependent K+ (BK) channel function is critical for adequate airway hydration and mucociliary function. In airway epithelia, BK function is regulated by its -subunit, leucine-rich repeat-containing protein 26 (LRRC26). Since patients with cystic fibrosis (CF)-related diabetes mellitus (CFRD) have worse lung function outcomes, this study determined the effects of hyperglycaemia on BK function in CF bronchial epithelial (CFBE) cells in vitro and evaluated the correlation between glycaemic excursions and mRNA expression of LRRC26 in the upper airways of CF and CFRD patients. CFBE cell...
Source: European Respiratory Journal - January 14, 2021 Category: Respiratory Medicine Authors: Bengtson, C. D., Kim, M. D., Anabtawi, A., He, J., Dennis, J. S., Miller, S., Yoshida, M., Baumlin, N., Salathe, M. Tags: Original Articles: Cystic fibrosis Source Type: research

NADPH oxidase DUOX1 sustains TGF-{beta}1 signalling and promotes lung fibrosis
Interstitial lung fibroblast activation coupled with extracellular matrix production is a pathological signature of pulmonary fibrosis, and is governed by transforming growth factor (TGF)-β1/Smad signalling. TGF-β1 and oxidative stress cooperate to drive fibrosis. Cells can produce reactive oxygen species through activation and/or induction of NADPH oxidases, such as dual oxidase (DUOX1/2). Since DUOX enzymes, as extracellular hydrogen peroxide (H2O2­­)-generating systems, are involved in extracellular matrix formation and in wound healing in different experimental models, we hypothesised that DUOX-based ...
Source: European Respiratory Journal - January 14, 2021 Category: Respiratory Medicine Authors: Louzada, R. A., Corre, R., Ameziane El Hassani, R., Meziani, L., Jaillet, M., Cazes, A., Crestani, B., Deutsch, E., Dupuy, C. Tags: Lung biology and experimental studies, Interstitial and orphan lung disease Original Articles: Interstitial lung disease and basic science Source Type: research

Imaging of pulmonary hypertension in adults: a position paper from the Fleischner Society
Pulmonary hypertension (PH) is defined by a mean pulmonary artery pressure greater than 20 mmHg and classified into five different groups sharing similar pathophysiologic mechanisms, haemodynamic characteristics, and therapeutic management. Radiologists play a key role in the multidisciplinary assessment and management of PH. A working group was formed from within the Fleischner Society based on expertise in the imaging and/or management of patients with PH, as well as experience with methodologies of systematic reviews. The working group identified key questions focusing on the utility of CT, MRI, and nuclear medicin...
Source: European Respiratory Journal - January 5, 2021 Category: Respiratory Medicine Authors: Remy-Jardin, M., Ryerson, C. J., Schiebler, M. L., Leung, A. N. C., Wild, J. M., Hoeper, M. M., Alderson, P. O., Goodman, L. R., Mayo, J., Haramati, L. B., Ohno, Y., Thistlethwaite, P., van Beek, E. J. R., Knight, S. L., Lynch, D. A., Rubin, G. D., Humber Tags: Task Force Report Source Type: research

Similar distribution of peripheral blood eosinophil counts in European and East Asian populations from investigations of large-scale general population studies: the Nagahama Study
We read with interest the study by Hartl et al. [1] entitled "Blood eosinophil count in the general population: typical values and potential confounders", recently published in the European Respirator Journal. This is an excellent paper showing the distribution of blood eosinophil counts in the general population, including more than 10 000 participants. The authors found a right-skewed, non-normal distribution with the tail towards the higher counts. (Source: European Respiratory Journal)
Source: European Respiratory Journal - January 5, 2021 Category: Respiratory Medicine Authors: Sunadome, H., Sato, S., Matsumoto, H., Murase, K., Kawaguchi, T., Tabara, Y., Chin, K., Matsuda, F., Hirai, T. Tags: Original Articles: Correspondence Source Type: research

Impact of the COVID-19 pandemic on tuberculosis laboratory services in Europe
The coronavirus disease 2019 (COVID-19) pandemic and associated response have undoubtedly had a dramatic multidimensional impact on healthcare services globally, severely disrupting care for many chronic diseases [1, 2]. Direct impact on communicable diseases, such as tuberculosis (TB), especially in developing countries disproportionally affected by TB, is not yet fully understood but is very likely to put national TB programmes under immense pressure and lead to an increase in TB deaths of 8–20% in the near future [3–5]. This predicted increase is largely caused by delays in diagnosis and treatment of new TB ...
Source: European Respiratory Journal - January 5, 2021 Category: Respiratory Medicine Authors: Nikolayevskyy, V., Holicka, Y., van Soolingen, D., van der Werf, M. J., Ködmön, C., Surkova, E., Hillemann, D., Groenheit, R., ERLTB-Net-2 study participants, Cirillo, D. Tags: Original Articles: Research letters Source Type: research

Idiopathic pulmonary fibrosis: prime time for a precision-based approach to treatment with N-acetylcysteine
Oxidative stress, the total sum of molecular and cellular processes that result from excess oxidant production and antioxidant depletion, has long been implicated in the pathogenesis of idiopathic pulmonary fibrosis (IPF) [1, 2]. Bronchoalveolar lavage fluid from patients with IPF exhibits enhanced oxidative activity, and high levels of the oxidants hydrogen peroxide, superoxide and hydroxyl radicals induce injury to alveolar epithelial cells [3]. At the same time, glutathione levels are depleted in the lower respiratory tract of IPF patients compared to healthy subjects and correlate with disease severity [4, 5]. Excess p...
Source: European Respiratory Journal - January 5, 2021 Category: Respiratory Medicine Authors: Podolanczuk, A. J., Noth, I., Raghu, G. Tags: Editorials Source Type: research

Tobacco control and the ERS: new problems and old foes
The European Respiratory Society (ERS) Tobacco Control Committee (TCC) has a key role in coordinating ERS activities related to tobacco control. In addition to working across ERS Assemblies, it monitors the implementation of the Framework Convention on Tobacco Control by European Union (EU) member states, and works with international organisations such as the Framework Convention Alliance. As the incoming chair of the ERS TCC, this article highlights my personal view on the areas to be addressed by the TCC over the next 3 years. (Source: European Respiratory Journal)
Source: European Respiratory Journal - January 5, 2021 Category: Respiratory Medicine Authors: Grigg, J. Tags: Editorials Source Type: research

Reducing Pseudomonas sputum density in bronchiectasis
In patients with bronchiectasis, chronic infection by Pseudomonas aeruginosa is strongly associated with poor clinical outcomes, including more symptoms, worse quality of life, enhanced lung function decline, more frequent exacerbations and a three-fold increase in mortality [1, 2]. Therefore, treatment of chronic P. aeruginosa airway infection has long been regarded as a key priority in the management of bronchiectasis [3, 4]. To this end, a number of previous studies have used inhaled or nebulised antibiotics in these patients, but results are conflicting [5–9]. Most of these studies failed to reach their primary e...
Source: European Respiratory Journal - January 5, 2021 Category: Respiratory Medicine Authors: Sibila, O. Tags: Editorials Source Type: research

Use of a whole genome sequencing-based approach for Mycobacterium tuberculosis surveillance in Europe in 2017-2019: an ECDC pilot study
Whole genome sequencing (WGS) can be used for molecular typing and characterisation of Mycobacterium tuberculosis complex (MTBC) strains. We evaluated the systematic use of a WGS-based approach for MTBC surveillance involving all European Union/European Economic Area (EU/EEA) countries and highlight the challenges and lessons learnt to be considered for the future development of a WGS-based surveillance system. WGS and epidemiological data of patients with rifampicin-resistant (RR) and multidrug-resistant (MDR) tuberculosis (TB) were collected from EU/EEA countries between January 2017 and December 2019. WGS-based genetic ...
Source: European Respiratory Journal - January 5, 2021 Category: Respiratory Medicine Authors: Tagliani, E., Anthony, R., Kohl, T. A., de Neeling, A., Nikolayevskyy, V., Ködmön, C., Maurer, F. P., Niemann, S., van Soolingen, D., van der Werf, M. J., Cirillo, D. M., on behalf of the ECDC molecular surveillance project participants Tags: Respiratory infections and tuberculosis Original Articles: Tuberculosis Source Type: research

Sleep-related breathing disorders and pulmonary hypertension
Sleep-related breathing disorders (SBDs) include obstructive apnoea, central apnoea and sleep-related hypoventilation. These nocturnal events have the potential to increase pulmonary arterial pressure (PAP) during sleep but also in the waking state. "Pure" obstructive sleep apnoea syndrome (OSAS) is responsible for a small increase in PAP whose clinical impact has not been demonstrated. By contrast, in obesity hypoventilation syndrome (OHS) or overlap syndrome (the association of chronic obstructive pulmonary disease (COPD) with obstructive sleep apnoea (OSA)), nocturnal respiratory events contribute to the devel...
Source: European Respiratory Journal - January 5, 2021 Category: Respiratory Medicine Authors: Adir, Y., Humbert, M., Chaouat, A. Tags: Review Source Type: research

Exhaled breath analysis by use of eNose technology: a novel diagnostic tool for interstitial lung disease
Conclusions eNose technology can completely distinguish ILD patients from healthy controls and can accurately discriminate between different ILD subgroups. Hence, exhaled breath analysis using eNose technology could be a novel biomarker in ILD, enabling timely diagnosis in the future. (Source: European Respiratory Journal)
Source: European Respiratory Journal - January 5, 2021 Category: Respiratory Medicine Authors: Moor, C. C., Oppenheimer, J. C., Nakshbandi, G., Aerts, J. G. J. V., Brinkman, P., Maitland-van der Zee, A.-H., Wijsenbeek, M. S. Tags: Interstitial and orphan lung disease Original Articles: Interstitial lung disease Source Type: research

Rapid genomic first- and second-line drug resistance prediction from clinical Mycobacterium tuberculosis specimens using Deeplex-MycTB
The emergence of multidrug-resistant (MDR) and extensively drug-resistant (XDR) Mycobacterium tuberculosis complex (Mtbc) isolates challenges tuberculosis (TB) control worldwide [1] and requires the rapid determination of extensive resistance profiles [2], enabling prompt initiation of effective treatment regimens. Phenotypic drug susceptibility testing (pDST) takes up to 6 weeks [3], and is unreliable and/or not standardised for several drugs, according to World Health Organization (WHO) guidelines [4]. Molecular DST (mDST) assays, like Xpert MTB/RIF (Cepheid) or MTBDRplus/sl line probe assays (LPAs; Hain Lifesciences) ca...
Source: European Respiratory Journal - January 5, 2021 Category: Respiratory Medicine Authors: Feuerriegel, S., Kohl, T. A., Utpatel, C., Andres, S., Maurer, F. P., Heyckendorf, J., Jouet, A., Badalato, N., Foray, L., Fouad Kamara, R., Conteh, O. S., Supply, P., Niemann, S. Tags: Original Articles: Research letters Source Type: research

Pragmatic global dosing recommendations for the 3-month, once-weekly rifapentine and isoniazid preventive TB regimen in children
The End TB Strategy, proposed by the World Health Organization (WHO) in 2014, calls for a 90% reduction in tuberculosis (TB)-related deaths and an 80% reduction in TB incidence by 2030 [1]. TB remains a leading cause of death in children under 5 years of age [2], and interventions to eliminate preventable child deaths from TB are urgently needed. Additional and effective TB prevention measures are crucial for the End TB Strategy goals to be met [3]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - January 5, 2021 Category: Respiratory Medicine Authors: Radtke, K. K., Hibma, J. E., Hesseling, A. C., Savic, R. M. Tags: Original Articles: Research letters Source Type: research

Efficacy and safety of TOBI Podhaler in Pseudomonas aeruginosa-infected bronchiectasis patients: iBEST study
The study aimed to determine the efficacy of a safe and well-tolerated dose and regimen of tobramycin inhalation powder (TIP) on Pseudomonas aeruginosa sputum density in patients with bronchiectasis. This is a phase II, double-blind, randomised study in bronchiectasis patients aged ≥18 years with chronic P. aeruginosa infection. Patients were randomised 1:1:1 to either cohort A: three capsules of TIP once daily (84 mg); cohort B: five capsules once daily (140 mg) or cohort C: four capsules twice daily (224 mg). Within each cohort, patients were further randomised 2:2:1 either to TIP continuously, TIP...
Source: European Respiratory Journal - January 5, 2021 Category: Respiratory Medicine Authors: Loebinger, M. R., Polverino, E., Chalmers, J. D., Tiddens, H. A. W. M., Goossens, H., Tunney, M., Ringshausen, F. C., Hill, A. T., Pathan, R., Angyalosi, G., Blasi, F., Elborn, S. J., Haworth, C. S., on behalf of the iBEST-1 Trial Team Tags: CF and non-CF bronchiectasis Original Articles: Bronchiectasis Source Type: research

Pirfenidone plus inhaled N-acetylcysteine for idiopathic pulmonary fibrosis: a randomised trial
Conclusions Combination treatment with inhaled N-acetylcysteine and pirfenidone is likely to result in worse outcomes for IPF. (Source: European Respiratory Journal)
Source: European Respiratory Journal - January 5, 2021 Category: Respiratory Medicine Authors: Sakamoto, S., Kataoka, K., Kondoh, Y., Kato, M., Okamoto, M., Mukae, H., Bando, M., Suda, T., Yatera, K., Tanino, Y., Kishaba, T., Hattori, N., Taguchi, Y., Saito, T., Nishioka, Y., Kuwano, K., Kishi, K., Inase, N., Sasaki, S., Takizawa, H., Johkoh, T., S Tags: Interstitial and orphan lung disease Original Articles: Interstitial lung disease Source Type: research

Automated closed-loop versus standard manual oxygen administration after major abdominal or thoracic surgery: an international multicentre randomised controlled study
Introduction Hypoxaemia and hyperoxaemia may occur after surgery, with related complications. This multicentre randomised trial evaluated the impact of automated closed-loop oxygen administration after high-risk abdominal or thoracic surgeries in terms of optimising the oxygen saturation measured by pulse oximetry time within target range. Methods After extubation, patients with an intermediate to high risk of post-operative pulmonary complications were randomised to "standard" or "automated" closed-loop oxygen administration. The primary outcome was the percentage of time within the oxygenation range,...
Source: European Respiratory Journal - January 5, 2021 Category: Respiratory Medicine Authors: L'Her, E., Jaber, S., Verzilli, D., Jacob, C., Huiban, B., Futier, E., Kerforne, T., Pateau, V., Bouchard, P.-A., Consigny, M., Lellouche, F. Tags: Original Articles: Thoracic sugery Source Type: research

Correction of CFTR function in intestinal organoids to guide treatment of cystic fibrosis
Conclusions Measurements of residual CFTR function and rescue of function by CFTR modulators in intestinal organoids correlate closely with clinical data. Our results for reference genotypes concur with previous results. CFTR function measured in organoids can be used to guide precision medicine in patients with CF, positioning organoids as a potential in vitro model to bring treatment to patients carrying rare CFTR mutations. (Source: European Respiratory Journal)
Source: European Respiratory Journal - January 5, 2021 Category: Respiratory Medicine Authors: Ramalho, A. S., Fürstova, E., Vonk, A. M., Ferrante, M., Verfaillie, C., Dupont, L., Boon, M., Proesmans, M., Beekman, J. M., Sarouk, I., Vazquez Cordero, C., Vermeulen, F., De Boeck, K., on behalf of the Belgian Organoid Project Tags: Lung biology and experimental studies, CF and non-CF bronchiectasis Original Articles: Cystic fibrosis and basic science Source Type: research

Stability of eosinophilic inflammation in COPD bronchial biopsies
We thank E.H. Walters and co-workers for their interest in our recently published research letter "Stability of eosinophilic inflammation in COPD bronchial biopsies" [1]. We would like to provide clarity on several points raised. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 24, 2020 Category: Respiratory Medicine Authors: Higham, A., Singh, D. Tags: Original Articles: Correspondence Source Type: research

Pandemic trials: evidence-based medicine on steroids
Research is the only exit strategy from current coronavirus disease 2019 (COVID-19) restrictions. The second wave of COVID-19 infections currently affecting most of Europe emphasises that COVID-19, the disease caused by infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is likely to require strict control measures impacting on the daily life of most citizens until either a highly effective approach to treatment or effective vaccines are in widespread use [1–3]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 24, 2020 Category: Respiratory Medicine Authors: Chalmers, J. D. Tags: Editorials Source Type: research

A new Cochrane review on electronic cigarettes for smoking cessation: should we change our practice?
In 2014, a Cochrane review concluded that there was evidence from two randomised controlled trials (RCTs) that electronic cigarettes help smokers to stop smoking long term. The confidence in the result was rated "low". In 2016, the same conclusion was reached. In the recently published 2020 update [1], the authors write that they included 50 completed studies, representing 12 430 participants. When you read closer, the smoking cessation conclusions are based on 12 RCTs, and half of these were small studies. The authors judged only four of the studies to be at low risk of bias [2–5]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 24, 2020 Category: Respiratory Medicine Authors: Pisinger, C., Vestbo, J. Tags: Original Articles: Correspondence Source Type: research

A golden age of asthma research
More than a decade ago, there was a widely held opinion among respiratory clinicians and researchers that asthma was, for the most part, solved and not worth investing intellectual or financial capital into research. There was certainly a small proportion of the asthma population (
Source: European Respiratory Journal - December 24, 2020 Category: Respiratory Medicine Authors: O'Byrne, P. M., Pavord, I. D. Tags: Editorials Source Type: research

Stability of eosinophilic inflammation in COPD bronchial biopsies
In their recent research letter, Higham et al. [1], provide valuable data analysing in detail the sources of variability in eosinophil counts in the lamina propria of large airway biopsies from COPD patients, described as "inflammation". The population of COPD they studied seems somewhat atypical from the average COPD patient in having a high median blood eosinophil count of 400 per μL and median bronchodilator reversibility of 15%, potentially consistent with an atopy/asthma-overlap phenotype. Even so, there is arguably no evidence for an inflammatory process being present in the airway sub-epithelial tissue ...
Source: European Respiratory Journal - December 24, 2020 Category: Respiratory Medicine Authors: Walters, E. H., Shukla, S. D., Ward, C. Tags: Original Articles: Correspondence Source Type: research

Performance of prediction models for COVID-19: the Caudine Forks of the external validation
Healthcare systems worldwide have observed significant changes to meet demands due to the coronavirus disease 2019 (COVID-19) pandemic. The uncertainty surrounding optimal treatment, the rapid public health urgency and clinical emergencies have caused a chaotic disruption of the cases and their related contacts at inpatient and outpatient settings. Developing more tailored healthcare plans based on the currently available scientific evidence, could help improve clinical efficacy, treatment outcomes, prognosis, and health efficiency. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 24, 2020 Category: Respiratory Medicine Authors: Martin, G. P., Sperrin, M., Sotgiu, G. Tags: Editorials Source Type: research

Systematic evaluation and external validation of 22 prognostic models among hospitalised adults with COVID-19: an observational cohort study
The number of proposed prognostic models for coronavirus disease 2019 (COVID-19) is growing rapidly, but it is unknown whether any are suitable for widespread clinical implementation. We independently externally validated the performance of candidate prognostic models, identified through a living systematic review, among consecutive adults admitted to hospital with a final diagnosis of COVID-19. We reconstructed candidate models as per original descriptions and evaluated performance for their original intended outcomes using predictors measured at the time of admission. We assessed discrimination, calibration and net benef...
Source: European Respiratory Journal - December 24, 2020 Category: Respiratory Medicine Authors: Gupta, R. K., Marks, M., Samuels, T. H. A., Luintel, A., Rampling, T., Chowdhury, H., Quartagno, M., Nair, A., Lipman, M., Abubakar, I., van Smeden, M., Wong, W. K., Williams, B., Noursadeghi, M., on behalf of The UCLH COVID-19 Reporting Group Tags: Respiratory infections and tuberculosis Original Articles: Infectious disease Source Type: research

Novel rare genetic variants in idiopathic pulmonary fibrosis
Idiopathic pulmonary fibrosis (IPF) is a rare disease of epithelial injury leading to persistent fibrosis, remodelling of the lung parenchyma, and chronic respiratory failure [1]. IPF can be differentiated from other forms of interstitial fibrosis by the presence of radiological and histopathological features of usual interstitial pneumonia (UIP), and the absence of known initiators (e.g. occupational dusts, autoimmunity; reviewed in [2]). Despite attempts to define IPF as a uniform disease entity based on clinical and radiological criteria [3], clinicians continue to struggle with significant variability in radiological a...
Source: European Respiratory Journal - December 24, 2020 Category: Respiratory Medicine Authors: Kristof, A. S. Tags: Editorials Source Type: research

Intravenous methylprednisolone pulse as a treatment for hospitalised severe COVID-19 patients: results from a randomised controlled clinical trial
Introduction There are no determined treatment agents for severe COVID-19. It is suggested that methylprednisolone, as an immunosuppressive treatment, can reduce the inflammation of the respiratory system in COVID-19 patients. Methods We conducted a single-blind, randomised controlled clinical trial involving severe hospitalised patients with confirmed COVID-19 at the early pulmonary phase of the illness in Iran. The patients were randomly allocated in a 1:1 ratio by the block randomisation method to receive standard care with methylprednisolone pulse (intravenous injection, 250 mg·day–1 for 3 days)...
Source: European Respiratory Journal - December 24, 2020 Category: Respiratory Medicine Authors: Edalatifard, M., Akhtari, M., Salehi, M., Naderi, Z., Jamshidi, A., Mostafaei, S., Najafizadeh, S. R., Farhadi, E., Jalili, N., Esfahani, M., Rahimi, B., Kazemzadeh, H., Mahmoodi Aliabadi, M., Ghazanfari, T., Sattarian, M., Ebrahimi Louyeh, H., Raeeskaram Tags: Respiratory infections and tuberculosis Original Articles: Infectious disease Source Type: research

Functional assessment and phenotypic heterogeneity of SFTPA1 and SFTPA2 mutations in interstitial lung diseases and lung cancer
This study, which expands the molecular and clinical spectrum of SP-A disorders, shows that pathogenic SFTPA1 or SFTPA2 mutations share similar consequences for SP-A secretion in cell models and in lung tissue immunostaining, whereas they are associated with a highly variable phenotypic expression of disease, ranging from severe forms requiring lung transplantation to incomplete penetrance. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 24, 2020 Category: Respiratory Medicine Authors: Legendre, M., Butt, A., Borie, R., Debray, M.-P., Bouvry, D., Filhol-Blin, E., Desroziers, T., Nau, V., Copin, B., Dastot-Le Moal, F., Hery, M., Duquesnoy, P., Allou, N., Bergeron, A., Bermudez, J., Cazes, A., Chene, A.-L., Cottin, V., Crestani, B., Dalph Tags: Interstitial and orphan lung disease, Genetics Original Articles: Interstitial lung disease and genetics Source Type: research

Cellular senescence: friend or foe to respiratory viral infections?
Cellular senescence permanently arrests the replication of various cell types and contributes to age-associated diseases. In particular, cellular senescence may enhance chronic lung diseases including COPD and idiopathic pulmonary fibrosis. However, the role cellular senescence plays in the pathophysiology of acute inflammatory diseases, especially viral infections, is less well understood. There is evidence that cellular senescence prevents viral replication by increasing antiviral cytokines, but other evidence shows that senescence may enhance viral replication by downregulating antiviral signalling. Furthermore, cellula...
Source: European Respiratory Journal - December 24, 2020 Category: Respiratory Medicine Authors: Kelley, W. J., Zemans, R. L., Goldstein, D. R. Tags: Perspective Source Type: research

Impact of socioeconomic status in patients hospitalised for COVID-19 in the Greater Paris area
In the USA, coronavirus disease 2019 (COVID-19) is more likely to affect and kill African Americans [1], which raises the question of the contribution of several factors, including genetic background, socioeconomic status (SES), and comorbidities [2]. According to the French National Institute of Statistics and Economic Studies (INSEE) the highest excess mortality rate in France, during March and April 2020, linked to COVID-19 was found in the Seine-Saint-Denis (SSD) district [3]. SSD is the poorest district of Greater Paris [4]. We hypothesise that precarity influences the initial severity of COVID-19. (Source: European Respiratory Journal)
Source: European Respiratory Journal - December 24, 2020 Category: Respiratory Medicine Authors: Sese, L., Nguyen, Y., Giroux Leprieur, E., Annesi-Maesano, I., Cavalin, C., Goupil de Bouille, J., Demestier, L., Dhote, R., Tandjaoui-Lambiotte, Y., Bauvois, A., Pepin, M., Curac, S., Beaune, S., Duchemann, B., Nunes, H. Tags: Original Articles: Research letters Source Type: research

Trends in worldwide asthma prevalence
This review of trends in worldwide asthma prevalence starts with defining how asthma prevalence is measured in populations and how it is analysed. Four population studies of asthma across at least two regions are described: European Community Respiratory Health Survey (ECRHS), the International Study of Wheezing in Infants (EISL), the International Study of Asthma and Allergies in Childhood (ISAAC) and the World Health Survey (WHS). Two of these (ISAAC and WHS) covered all the regions of the world; each using its own standardised questionnaire-based methodology with cross-sectional study design, suitable for large populati...
Source: European Respiratory Journal - December 24, 2020 Category: Respiratory Medicine Authors: Asher, M. I., Garcia-Marcos, L., Pearce, N. E., Strachan, D. P. Tags: Series Source Type: research