New definitions of pre-extensively and extensively drug-resistant tuberculosis: update from the World Health Organization
Multidrug-resistant tuberculosis (MDR-TB), defined as Mycobacterium tuberculosis with resistance to at least isoniazid and rifampicin [1], emerged as a threat to tuberculosis (TB) control worldwide in the 1990s [2]. This form of TB required the use of second-line drugs that were less effective, more toxic and costlier than first-line isoniazid- and rifampicin-based regimens. MDR-TB was one of the first infectious conditions to alert national authorities worldwide to the importance of antimicrobial resistance as a public health challenge of the future, further emphasised by outbreaks of MDR-TB in the USA and Europe [3&ndash...
Source: European Respiratory Journal - April 8, 2021 Category: Respiratory Medicine Authors: Viney, K., Linh, N. N., Gegia, M., Zignol, M., Glaziou, P., Ismail, N., Kasaeva, T., Mirzayev, F. Tags: Editorials Source Type: research

Utilising biomarkers to predict right heart maladaptive phenotype: a step toward precision medicine
Pulmonary hypertension (PH) is associated with pressure overload of the right ventricle (RV), which initially provokes adaptive RV changes, such as increased wall thickness and contractility [1] In this regard, adaptive RV hypertrophy is characterised by preserved cardiac output, maintained RV ejection fraction, and, as a consequence, largely maintained exercise capacity. In some patients, or in the later course of the disease, however, persistently increased afterload results in maladaptive, pathological remodelling processes, RV uncoupling, and right heart failure. These changes are associated with worse outcomes [1] and...
Source: European Respiratory Journal - April 8, 2021 Category: Respiratory Medicine Authors: Pullamsetti, S. S., Tello, K., Seeger, W. Tags: Editorials Source Type: research

Reduction in asthma admissions during the COVID-19 pandemic: consequence of public health measures in Singapore
We read with interest the study by Izquierdo et al. [1] that reported a lower proportion of patients with concurrent asthma and coronavirus disease 2019 (COVID-19), compared to other chronic diseases. During the ongoing pandemic, various studies have also observed a lower occurrence of persons with asthma amongst hospitalised COVID-19 cases [2, 3]. Several hypotheses have been postulated to account for these observations, including lower susceptibility to COVID-19 amongst patients with asthma [2, 3] and a remission in rates of common circulating respiratory viral infections (RVIs) [4]. RVIs are potential triggers of asthma...
Source: European Respiratory Journal - April 8, 2021 Category: Respiratory Medicine Authors: Wee, L. E., Conceicao, E. P., Tan, J. Y., Sim, J. X. Y., Venkatachalam, I. Tags: Original Articles: Correspondence Source Type: research

Vitamin D status and seroconversion for COVID-19 in UK healthcare workers
The coronavirus disease 2019 (COVID-19) pandemic is a global health emergency, resulting in over 50 million infections and over 1.2 million deaths as of mid-November 2020 [1]. Healthcare workers are at a high risk of COVID-19 with large numbers of deaths reported around Europe and the UK, particularly among staff in the Black, Asian and minority ethnic (BAME) demographic group [2]. COVID-19 has disproportionately affected BAME individuals even after accounting for age, sex, social deprivation and comorbidity [3]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - April 8, 2021 Category: Respiratory Medicine Authors: Faniyi, A. A., Lugg, S. T., Faustini, S. E., Webster, C., Duffy, J. E., Hewison, M., Shields, A., Nightingale, P., Richter, A. G., Thickett, D. R. Tags: Original Articles: Research letters Source Type: research

Complications of nasal and pharyngeal swabs: a relevant challenge of the COVID-19 pandemic?
The coronavirus disease 2019 (COVID-19) pandemic comprises approximately 50 million confirmed cases and over 1.2 million deaths as of 10 November, 2020 [1], affecting healthcare systems worldwide in an unprecedented way. In the absence of effective treatments or preventive measures, all attempts to control the pandemic are based on reliable diagnostic procedures, particularly RT-PCR of upper respiratory specimens, which is considered the diagnostic gold standard [2]. A previously unimaginable number of these diagnostic procedures has been performed since the beginning of the pandemic and there is a clear trend towards furt...
Source: European Respiratory Journal - April 8, 2021 Category: Respiratory Medicine Authors: Föh, B., Borsche, M., Balck, A., Taube, S., Rupp, J., Klein, C., Katalinic, A. Tags: Original Articles: Research letters Source Type: research

The management of mild asthma
Inhaled corticosteroids (ICSs) have been recommended as a maintenance treatment, either alone or together with long-acting inhaled β2-agonists, for all asthma patients. Short-acting β2-agonists (SABAs) are rapid-onset bronchodilators, which provide symptom relief, but have no anti-inflammatory properties, yet are the most widely used as-needed reliever treatment for asthma and often the only treatment prescribed. Asthma patients can find adhering to daily preventative medication with ICS difficult and will often revert to using as-needed SABA as their only treatment, increasing their risk of exacerbations. The pu...
Source: European Respiratory Journal - April 8, 2021 Category: Respiratory Medicine Authors: O'Byrne, P. M., Reddel, H. K., Beasley, R. Tags: Series Source Type: research

Childhood maltreatment and lung function: findings from the general population
Conclusions Our findings call into question the association of childhood maltreatment with obstructive lung diseases as indicated by prior research relying on self-reported diagnoses. We consider several explanations for these discrepancies. (Source: European Respiratory Journal)
Source: European Respiratory Journal - April 8, 2021 Category: Respiratory Medicine Authors: Spitzer, C., Ewert, R., Völzke, H., Frenzel, S., Felix, S. B., Lübke, L., Grabe, H. J. Tags: Lung structure and function Original Articles: Lung structure and function Source Type: research

Targeted proteomics of right heart adaptation to pulmonary arterial hypertension
This study investigates the circulating proteomic profile associated with right heart maladaptive phenotype (RHMP) in PAH. Plasma proteomic profiling was performed using multiplex immunoassay in 121 (discovery cohort) and 76 (validation cohort) PAH patients. The association between proteomic markers and RHMP, defined by the Mayo right heart score (combining RV strain, New York Heart Association (NYHA) class and N-terminal pro-brain natriuretic peptide (NT-proBNP)) and Stanford score (RV end-systolic remodelling index, NYHA class and NT-proBNP), was assessed by partial least squares regression. Biomarker expression was meas...
Source: European Respiratory Journal - April 8, 2021 Category: Respiratory Medicine Authors: Amsallem, M., Sweatt, A. J., Arthur Ataam, J., Guihaire, J., Lecerf, F., Lambert, M., Ghigna, M. R., Ali, M. K., Mao, Y., Fadel, E., Rabinovitch, M., de Jesus Perez, V., Spiekerkoetter, E., Mercier, O., Haddad, F., Zamanian, R. T. Tags: Pulmonary vascular disease Original Articles: Pulmonary hypertension Source Type: research

Omics-based tracking of Pseudomonas aeruginosa persistence in "eradicated" cystic fibrosis patients
In conclusion, nearly half of CF patients with supposed eradication may not truly be cleared of their original bacteria according to omics-based monitoring. This distinct cohort that is persistently infected would probably benefit from tailored antibiotic therapy. (Source: European Respiratory Journal)
Source: European Respiratory Journal - April 8, 2021 Category: Respiratory Medicine Authors: Bartell, J. A., Sommer, L. M., Marvig, R. L., Skov, M., Pressler, T., Molin, S., Johansen, H. K. Tags: CF and non-CF bronchiectasis Original Articles: Cystic fibrosis Source Type: research

Therapeutic drug monitoring and fluoroquinolones for multidrug-resistant tuberculosis
We read the paper by Davies Forsman et al. [1] and could not agree more with their findings. The authors report that in the studied geographical area and clinical population, the dose of levofloxacin and moxifloxacin should be increased to achieve the optimal exposure target in order to effectively treat multidrug-resistant tuberculosis, and suggested therapeutic drug monitoring (TDM) to avert any adverse event [1, 2]. The target drug exposure and dose in the study were selected based on the evidence collected using pharmacokinetic/pharmacodynamic studies in both pre-clinical models and in the clinic [3]. (Source: European...
Source: European Respiratory Journal - April 1, 2021 Category: Respiratory Medicine Authors: Srivastava, S., Gumbo, T. Tags: Original Articles: Correspondence Source Type: research

The PELICAN (Prematurity's Effect on the Lungs In Children and Adults Network) ERS Clinical Research Collaboration: understanding the impact of preterm birth on lung health throughout life
An estimated 15 million babies (~11%) are born preterm each year (before 37 weeks of gestation), the rates of which are increasing worldwide [1]. Enhanced perinatal care, including antenatal corticosteroids, postnatal surfactant and improved respiratory management, have markedly improved survival outcomes since the 1990s, particularly for babies born very preterm (
Source: European Respiratory Journal - April 1, 2021 Category: Respiratory Medicine Authors: Simpson, S. J., Hallberg, J., on behalf of the PELICAN Clinical Research Collaboration Tags: Editorials Source Type: research

Defining optimal fluoroquinolone exposure against Mycobacterium tuberculosis: contribution of murine studies
We read with interest the research letter published by Davies Forsman et al. [1] in the European Respiratory Journal. The authors determined the proportion of multidrug-resistant tuberculosis patients treated with moxifloxacin or levofloxacin who attained an optimal exposure for these drugs. The target exposure corresponded to the area under the curve (AUC0–24h)/minimal inhibitory concentration (MIC) ratio generating the optimal bactericidal activity. The authors based their calculations on the AUC0–24h/MIC ratio measured in a preclinical model called Hollow Fiber System (HFS), an in vitro model used to assess ...
Source: European Respiratory Journal - April 1, 2021 Category: Respiratory Medicine Authors: Maitre, T., Guglielmetti, L., Veziris, N. Tags: Original Articles: Correspondence Source Type: research

The battle of new biomarkers for right heart failure in pulmonary hypertension: is the queen of hearts NT-proBNP defeated at last?
Pulmonary hypertension (PH) induces right ventricular (RV) pressure overload. Initially, the right ventricle is able to adapt to the augmented afterload by increasing contractility to maintain cardiac output [1]. Consequently, RV function is preserved through adaptive RV hypertrophy, with minimal dilation and fibrosis. Nevertheless, due to maintained pressure overload, RV adaptation eventually fails, and patients die from right heart failure. RV adaptation is heterogeneous among PH patients and the transition from the adaptive to the maladaptive RV phenotype is not fully understood. Several pathological processes have been...
Source: European Respiratory Journal - April 1, 2021 Category: Respiratory Medicine Authors: Llucia-Valldeperas, A., van Wezenbeek, J., Goumans, M.-J., de Man, F. S. Tags: Editorials Source Type: research

Relationship between supernormal lung function and long-term risk of hospitalisations and mortality: a population-based cohort study
Cardiovascular and respiratory diseases are major contributors to global deaths [1]. Although low lung function is a risk factor for early death, like hypertension and hypercholesterolaemia [2], evaluation of lung function in primary care is not prioritised as highly as blood pressure or cholesterol measurements [3]. Also, public health authorities have remained silent on major health challenges other than smoking relevant for development and preservation of normal lung function from birth to old age. It is now increasingly evident that low lung function in childhood may affect general health throughout life [4–8]. I...
Source: European Respiratory Journal - April 1, 2021 Category: Respiratory Medicine Authors: Colak, Y., Nordestgaard, B. G., Vestbo, J., Lange, P., Afzal, S. Tags: Original Articles: Research letters Source Type: research

Plasma metabolomics exhibit response to therapy in chronic thromboembolic pulmonary hypertension
This study investigated the plasma metabolome of CTEPH patients, estimated reversibility to an effective treatment and explored the source of metabolic perturbations. We performed untargeted analysis of plasma metabolites in CTEPH patients compared to healthy controls and disease comparators. Changes in metabolic profile were evaluated in response to PEA. A subset of patients were sampled at three anatomical locations and plasma metabolite gradients calculated. We defined and validated altered plasma metabolite profiles in patients with CTEPH. 12 metabolites were confirmed by receiver operating characteristic analysis to d...
Source: European Respiratory Journal - April 1, 2021 Category: Respiratory Medicine Authors: Swietlik, E. M., Ghataorhe, P., Zalewska, K. I., Wharton, J., Howard, L. S., Taboada, D., Cannon, J. E., UK National Cohort Study of PAH, Morrell, N. W., Wilkins, M. R., Toshner, M., Pepke-Zaba, J., Rhodes, C. J. Tags: Pulmonary vascular disease Original Articles: Pulmonary hypertension Source Type: research

A genome-wide association study of severe asthma exacerbations in Latino children and adolescents
Severe asthma exacerbations are a major cause of school absences and healthcare costs in children, particularly those in high-risk racial/ethnic groups. To identify susceptibility genes for severe asthma exacerbations in Latino children and adolescents, we conducted a meta-analysis of genome-wide association studies (GWAS) in 4010 Latino youth with asthma in four independent cohorts, including 1693 Puerto Ricans, 1019 Costa Ricans, 640 Mexicans, 256 Brazilians and 402 members of other Latino subgroups. We then conducted methylation quantitative trait locus, expression quantitative trait locus and expression quantitative tr...
Source: European Respiratory Journal - April 1, 2021 Category: Respiratory Medicine Authors: Yan, Q., Forno, E., Herrera-Luis, E., Pino-Yanes, M., Qi, C., Rios, R., Han, Y.-Y., Kim, S., Oh, S., Acosta-Perez, E., Zhang, R., Hu, D., Eng, C., Huntsman, S., Avila, L., Boutaoui, N., Cloutier, M. M., Soto-Quiros, M. E., Xu, C.-J., Weiss, S. T., Lasky-S Tags: Asthma and allergy Original Articles: Asthma Source Type: research

Burden of respiratory syncytial virus infection in community-dwelling older adults in Europe (RESCEU): an international prospective cohort study
Conclusion This European study showed that RSV is prevalent in community-dwelling older adults and rarely causes severe disease. This suggests that watchful waiting, using a continuity of care approach to identify those who do need more intensive care, is often justified when RSV is suspected in family practice. (Source: European Respiratory Journal)
Source: European Respiratory Journal - April 1, 2021 Category: Respiratory Medicine Authors: Korsten, K., Adriaenssens, N., Coenen, S., Butler, C., Ravanfar, B., Rutter, H., Allen, J., Falsey, A., Pircon, J.-Y., Gruselle, O., Pavot, V., Vernhes, C., Balla-Jhagjhoorsingh, S., Öner, D., Ispas, G., Aerssens, J., Shinde, V., Verheij, T., Bont Tags: Original Articles: Pulmonary infections Source Type: research

The respiratory microbiota during and following mechanical ventilation for respiratory infections in children
The lower respiratory tract (LRT) harbours distinct, dynamic low-density microbial communities, established through micro-aspiration from the upper respiratory tract (URT) [1–3]. However, during intubation and mechanical ventilation, the endotracheal tube temporarily alters the anatomical continuity between URT and LRT, and may provide a bridge for airborne microbes and a barrier for micro-aspiration. Shortly after intubation for a severe LRT infection (LRTI) in children, the microbiota of the nasopharynx and LRT were shown to be very similar [4]. However, it remains unknown how the respiratory microbial community de...
Source: European Respiratory Journal - April 1, 2021 Category: Respiratory Medicine Authors: de Koff, E. M., Man, W. H., van Houten, M. A., Jansen, N. J. G., Arp, K., Hasrat, R., Sanders, E. A. M., Bogaert, D. Tags: Original Articles: Research letters Source Type: research

Validation of the BRODERS classifier (Benign versus aggRessive nODule Evaluation using Radiomic Stratification), a novel HRCT-based radiomic classifier for indeterminate pulmonary nodules
Conclusions The BRODERS radiomic predictive model performs well on an independent dataset and may facilitate the management of indeterminate pulmonary nodules. (Source: European Respiratory Journal)
Source: European Respiratory Journal - April 1, 2021 Category: Respiratory Medicine Authors: Maldonado, F., Varghese, C., Rajagopalan, S., Duan, F., Balar, A. B., Lakhani, D. A., Antic, S. L., Massion, P. P., Johnson, T. F., Karwoski, R. A., Robb, R. A., Bartholmai, B. J., Peikert, T. Tags: Lung imaging Original Articles: Lung imaging Source Type: research

Trends in mediastinal nodal staging and its impact on unforeseen N2 and survival in lung cancer
Introduction Guidelines for invasive mediastinal nodal staging in resectable nonsmall cell lung cancer (NSCLC) have changed over the years. The aims of this study were to describe trends in invasive staging and unforeseen N2 (uN2) and to assess a potential effect on overall survival. Methods A nationwide Dutch cohort study included all clinical stage IA–IIIB NSCLC patients primarily treated by surgical resection between 2005 and 2017 (n=22 555). We assessed trends in invasive nodal staging (mediastinoscopy 2005–2017; endosonography 2011–2017), uN2 and overall survival and compared outcomes in the entire ...
Source: European Respiratory Journal - April 1, 2021 Category: Respiratory Medicine Authors: Bousema, J. E., Aarts, M. J., Dijkgraaf, M. G. W., Annema, J. T., van den Broek, F. J. C. Tags: Lung cancer Original Articles: Lung cancer Source Type: research

Long-term prognosis of new adult-onset asthma in obese patients
Background Obesity has been associated with poor outcomes of asthma in cross-sectional studies, but long-term effect of obesity on asthma remains unknown. Aims To study the effects of obesity, found at the time of diagnosis of adult-onset asthma, on 12-year prognosis by focusing on oral corticosteroid (OCS) use and respiratory-related hospital admissions. Methods Patients diagnosed with adult-onset asthma (n=203) were divided into three categories based on diagnostic body mass index (BMI) (
Source: European Respiratory Journal - April 1, 2021 Category: Respiratory Medicine Authors: Ilmarinen, P., Pardo, A., Tuomisto, L. E., Vähätalo, I., Niemelä, O., Nieminen, P., Kankaanranta, H. Tags: Asthma and allergy Original Articles: Asthma Source Type: research

Clinical phenotypes of extrapulmonary sarcoidosis: an analysis of a French, multi-ethnic, multicentre cohort
Sarcoidosis is a rare disease of unknown cause with wide heterogeneity in clinical features and outcomes. We aimed to explore sarcoidosis phenotypes and their clinical relevance with particular attention to extrapulmonary subgroups. The Epidemiology of Sarcoidosis (EpiSarc) study is a French retrospective multicentre study. Sarcoidosis patients were identified through national hospitalisation records using appropriate codes from 11 hospital centres between 2013 and 2016 according to a standardised protocol. Medical charts were reviewed. The phenotypes of sarcoidosis were defined using a hierarchical cluster analysis. A tot...
Source: European Respiratory Journal - April 1, 2021 Category: Respiratory Medicine Authors: Lhote, R., Annesi-Maesano, I., Nunes, H., Launay, D., Borie, R., Sacre, K., Schleinitz, N., Hamidou, M., Mahevas, M., Devilliers, H., Bonniaud, P., Lhote, F., Haroche, J., Rufat, P., Amoura, Z., Valeyre, D., Cohen Aubart, F. Tags: Interstitial and orphan lung disease Original Articles: Interstitial lung disease Source Type: research

CILP1 as a biomarker for right ventricular maladaptation in pulmonary hypertension
The aim of our study was to analyse the protein expression of cartilage intermediate layer protein (CILP)1 in a mouse model of right ventricular (RV) pressure overload and to evaluate CILP1 as a biomarker of cardiac remodelling and maladaptive RV function in patients with pulmonary hypertension (PH). Pulmonary artery banding was performed in 14 mice; another nine mice underwent sham surgery. CILP1 protein expression was analysed in all hearts using Western blotting and immunostaining. CILP1 serum concentrations were measured in 161 patients (97 with adaptive and maladaptive RV pressure overload caused by PH; 25 with left v...
Source: European Respiratory Journal - April 1, 2021 Category: Respiratory Medicine Authors: Keranov, S., Dörr, O., Jafari, L., Troidl, C., Liebetrau, C., Kriechbaum, S., Keller, T., Voss, S., Bauer, T., Lorenz, J., Richter, M. J., Tello, K., Gall, H., Ghofrani, H. A., Mayer, E., Wiedenroth, C. B., Guth, S., Lörchner, H., Po0 Tags: Pulmonary vascular disease Original Articles: Pulmonary hypertension Source Type: research

PaO2/FIO2 ratio: the mismeasure of oxygenation in COVID-19
We read with interest A. Tulaimat's letter concerning our recent editorial in the European Respiratory Journal [1]. A. Tulaimat makes several insightful comments on problems with criteria used for entering patients into randomised controlled trials of noninvasive ventilation. Among these, he notes that arterial-to-inspired oxygen (PaO2/FIO2) ratio varied between 170 and 400 among enrollees [2]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 25, 2021 Category: Respiratory Medicine Authors: Tobin, M. J., Jubran, A., Laghi, F. Tags: Original Articles: Correspondence Source Type: research

Examining the intubation decision in randomised clinical trials
Tobin et al. [1] pointed in their editorial to the limitations of randomised trials in determining the effect of noninvasive modalities on the intubation of patients with respiratory failure. My colleagues and I have recently examined many design aspects of 53 randomised trials that evaluated the effect of noninvasive ventilation and high flow oxygen therapy on the outcomes of patients with acute respiratory failure [2]. Our findings support many of the points highlighted in the editorial. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 25, 2021 Category: Respiratory Medicine Authors: Tulaimat, A. Tags: Original Articles: Correspondence Source Type: research

"The patient tells it! The importance of patient's quality of life perception in pulmonary arterial hypertension risk assessment." Silvia Ulrich and Ekkehard Grunig. Eur Respir J 2021; 57: 2004376
(Source: European Respiratory Journal)
Source: European Respiratory Journal - March 25, 2021 Category: Respiratory Medicine Tags: Author correction Source Type: research

Transthoracic shear wave ultrasound: a noninvasive tool to differentiate between benign and malignant subpleural lung lesions
Ultrasound is a well-established imaging modality that uses high frequency sound waves. The technique relies on acoustic physical characteristics like reflection, compression, rarefication and impedance to visualise and characterise different tissue types within the human body. This information may be additional, or even unique, when compared with other imaging modalities, such as projection radiography, computed tomography (CT) and magnetic resonance imaging (MRI). Ultrasound has many advantages: it does not use ionising X-rays, is readily available, is less expensive than CT and MRI, and gives information in real-time. U...
Source: European Respiratory Journal - March 25, 2021 Category: Respiratory Medicine Authors: Verschakelen, J. A. Tags: Editorials Source Type: research

Hypoxic burden and heart rate variability predict stroke incidence in sleep apnoea
Obstructive sleep apnoea (OSA) is increasingly recognised as a risk factor for stroke [1]. However, the incidence of stroke in patients investigated for OSA has been assessed in a limited number of studies reporting conflicting results on the association between the apnoea–hypopnoea index (AHI) and stroke incidence [1–3]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 25, 2021 Category: Respiratory Medicine Authors: Blanchard, M., Gerves-Pinquie, C., Feuilloy, M., Le Vaillant, M., Trzepizur, W., Meslier, N., Goupil, F., Pigeanne, T., Balusson, F., Oger, E., Sabil, A., Girault, J.-M., Gagnadoux, F., on behalf of the ERMES study group Tags: Original Articles: Research letters Source Type: research

Early COVID-19 lockdown in Greece and idiopathic pulmonary fibrosis: a beneficial "impact" beyond any expectation
Idiopathic pulmonary fibrosis (IPF) is an irreversibly progressive diffuse lung disease characterised by a usual interstitial pneumonia (UIP) pattern. IPF presents with an ominous prognosis with a median survival of around 5 years [1]. The development of an acute exacerbation, histologically diffuse alveolar damage (DAD) upon UIP, represents the most devastating of its complications and leads to death in the majority of patients admitted to the intensive care unit (ICU) [2–4]. Viral infections in the setting of an altered host lung microbiome are likely important triggers of acute exacerbations of IPF and subseq...
Source: European Respiratory Journal - March 25, 2021 Category: Respiratory Medicine Authors: Papiris, S. A., Bouros, D., Markopoulou, K., Kolilekas, L., Papaioannou, A. I., Tzilas, V., Tzouvelekis, A., Fouka, E., Papakosta, D., Daniil, Z., Steiropoulos, P., Gogali, A., Papanikolaou, I. C., Xyfteri, A., Haritou, A., Korbila, I., Tomos, I. P., Louk Tags: Original Articles: Research letters Source Type: research

COPD: still an unpredictable journey
COPD is the fourth leading cause of death and affects nearly 400 million worldwide, causing much disability as well as early mortality [1]. Management should be tailored to each patient to improve outcomes, for instance by stratifying patients according to the risk of acute exacerbations of COPD, in order to prescribe treatments including inhaled corticosteroids or phosphodiesterase-4 inhibitors earlier. Treatment is particularly important before the patient's first acute exacerbation, as each subsequent exacerbation damages the lungs and treatment is less effective thereafter [2–4]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 25, 2021 Category: Respiratory Medicine Authors: Bottle, A., Quint, J. Tags: Editorials Source Type: research

Minimal clinically important differences for Dyspnea-12 and MDP scores are similar at 2 weeks and 6 months: follow-up of a longitudinal clinical study
Chronic breathlessness is a dominating symptom that restricts daily life for many people with cardiorespiratory disease [1]. Different dimensions of the symptom, such as the intensity, sensory qualities and emotional responses, can be assessed using the instruments Dyspnea-12 (D-12) [2] and the Multidimensional Dyspnea Profile (MDP) [3], which share similarities in the underlying constructs of what is measured [4] and have emerged as widely used instruments for multi-dimensional measurement of breathlessness. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 25, 2021 Category: Respiratory Medicine Authors: Ekström, M., Bornefalk, H., Sköld, C. M., Janson, C., Blomberg, A., Sandberg, J., Bornefalk-Hermansson, A., Currow, D. C., Johnson, M. J., Sundh, J. Tags: Original Articles: Research letters Source Type: research

Solitary pulmonary nodule imaging approaches and the role of optical fibre-based technologies
Solitary pulmonary nodules (SPNs) are a clinical challenge, given there is no single clinical sign or radiological feature that definitively identifies a benign from a malignant SPN. The early detection of lung cancer has a huge impact on survival outcome. Consequently, there is great interest in the prompt diagnosis, and treatment of malignant SPNs. Current diagnostic pathways involve endobronchial/transthoracic tissue biopsies or radiological surveillance, which can be associated with suboptimal diagnostic yield, healthcare costs and patient anxiety. Cutting-edge technologies are needed to disrupt and improve, existing c...
Source: European Respiratory Journal - March 25, 2021 Category: Respiratory Medicine Authors: Fernandes, S., Williams, G., Williams, E., Ehrlich, K., Stone, J., Finlayson, N., Bradley, M., Thomson, R. R., Akram, A. R., Dhaliwal, K. Tags: State of the Art Source Type: research

Application of transthoracic shear-wave ultrasound elastography in lung lesions
Conclusions This study validated the application of transthoracic shear-wave ultrasound elastography for assessing lung malignancy. A cut-off point of 65 kPa is suggested for predicting lung malignancy. Furthermore, for pulmonary air bronchogram lesions with high elasticity, tissue proofing should be considered because of the high possibility of malignancy. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 25, 2021 Category: Respiratory Medicine Authors: Kuo, Y.-W., Chen, Y.-L., Wu, H.-D., Chien, Y.-C., Huang, C.-K., Wang, H.-C. Tags: Lung imaging Original Articles: Lung imaging Source Type: research

Real world effects of COPD medications: a cohort study with validation against results from randomised controlled trials
Real-world data provide the potential for generating evidence on drug treatment effects in groups excluded from trials, but rigorous, validated methodology for doing so is lacking. We investigated whether non-interventional methods applied to real-world data could reproduce results from the landmark TORCH COPD trial. We performed a historical cohort study (2000–2017) of COPD drug treatment effects in the UK Clinical Practice Research Datalink (CPRD). Two control groups were selected from CPRD by applying TORCH inclusion/exclusion criteria and 1:1 matching to TORCH participants, as follows. Control group 1: people wit...
Source: European Respiratory Journal - March 25, 2021 Category: Respiratory Medicine Authors: Wing, K., Williamson, E., Carpenter, J. R., Wise, L., Schneeweiss, S., Smeeth, L., Quint, J. K., Douglas, I. Tags: COPD and smoking Original Articles: COPD Source Type: research

Markers of disease activity in COPD: an 8-year mortality study in the ECLIPSE cohort
Conclusions In COPD, 1- and 3-year changes in exacerbation frequency, systemic inflammation, BODE and SGRQ scores and FEV1 decline are independent markers of disease activity associated with 8-year all-cause mortality. These disease activity markers are generally independent and not predictable from baseline measurements. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 25, 2021 Category: Respiratory Medicine Authors: Celli, B., Locantore, N., Yates, J. C., Bakke, P., Calverley, P. M. A., Crim, C., Coxson, H. O., Lomas, D. A., MacNee, W., Miller, B. E., Mullerova, H., Rennard, S. I., Silverman, E. K., Wouters, E., Tal-Singer, R., Agusti, A., Vestbo, J., for the Evaluat Tags: COPD and smoking Original Articles: COPD Source Type: research

Reply: Survival and course of lung function in the presence or absence of antifibrotic treatment in patients with idiopathic pulmonary fibrosis
We thank S. Suissa and D. Assayag, as well as J. Borchardt, for their interest in our study and for giving us the opportunity to respond to their comments regarding the potential impact of immortal time bias and lead time bias on the observed difference between idiopathic pulmonary fibrosis (IPF) patients treated with or without antifibrotic drugs under real-life conditions. As a key finding of the INSIGHTS-IPF Registry follow-up analysis, we had reported that survival was significantly higher in IPF patients receiving antifibrotic therapy when compared with propensity-matched IPF patients not receiving such drugs [1]. (So...
Source: European Respiratory Journal - March 18, 2021 Category: Respiratory Medicine Authors: Behr, J., Pittrow, D., Klotsche, J. Tags: Original Articles: Correspondence Source Type: research

Comment on: Survival and course of lung function in the presence or absence of antifibrotic treatment in patients with idiopathic pulmonary fibrosis
With great interest I recently read the observations of the INSIGHTS-IPF registry published in the August 2020 issue of the European Respiratory Journal [1]. However, the paper represents an instructive example of how peer review occasionally may fail to prevent publication of unfounded conclusions. Though lead-time bias is mentioned as a potential limitation of the study in the discussion (possibly following peer review) and though lead-time bias is evident looking at the published data, the authors conclude that their study shows a significantly lower all-cause mortality in IPF patients with antifibrotic therapy, and tha...
Source: European Respiratory Journal - March 18, 2021 Category: Respiratory Medicine Authors: Borchardt, J. Tags: Original Articles: Correspondence Source Type: research

Mortality benefit with antifibrotics in idiopathic pulmonary fibrosis: real world evidence or bias?
We read with interest the analysis conducted by Behr et al. [1] of the INSIGHTS-IPF registry of patients with idiopathic pulmonary fibrosis (IPF), particularly of the effectiveness of antifibrotic treatment on mortality. It showed that users of antifibrotics, namely pirfenidone and nintedanib, have a significantly lower risk of death (hazard ratio 0.63, 95% CI 0.45–0.87; p=0.005) compared with non-users. This 37% reduction in all-cause mortality is quite remarkable for an observational study in the context of regular clinical practice, despite the short mean duration of follow-up of 1.2 years and the expected co...
Source: European Respiratory Journal - March 18, 2021 Category: Respiratory Medicine Authors: Suissa, S., Assayag, D. Tags: Original Articles: Correspondence Source Type: research

Targeted next-generation sequencing: a Swiss army knife for mycobacterial diagnostics?
The genus Mycobacterium encompasses almost 200 species that fall into four main groups [1]. Specifically, the Mycobacterium tuberculosis complex (MTBC), the causative agent of tuberculosis (TB) and leading cause of death by a single infectious agent, is distinguished from mycobacteria causing Buruli ulcer and leprosy [2, 3]. The remaining species are referred to as nontuberculous mycobacteria (NTM), which mainly cause lung disease and have become more frequent in many parts of the world, particularly amongst older patients [4]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 18, 2021 Category: Respiratory Medicine Authors: Mohamed, S., Köser, C. U., Salfinger, M., Sougakoff, W., Heysell, S. K. Tags: Editorials Source Type: research

Socioeconomic disadvantage and lung health: accumulating evidence to support health policy
It is becoming increasingly clear that the social determinants of health are associated with lung health [1, 2] The lungs are extremely sensitive to the lived experience of individuals, particularly to environmental influences, including pollution, poverty, and occupational and smoking exposures. Understanding the factors that are associated with a reduction in lung function may provide novel insights into the impact of social determinants on overall health. Social determinants of health are closely related to socioeconomic position and systemic inequalities, both within and between countries, which have further been exace...
Source: European Respiratory Journal - March 18, 2021 Category: Respiratory Medicine Authors: Stanojevic, S. Tags: Editorials Source Type: research

Effect of non-uniform cyst distribution in lymphangioleiomyomatosis on pulmonary function: a cross-sectional study
Lymphangioleiomyomatosis (LAM) is a rare multi-system lung disease that may involve the kidneys (e.g. angiomyolipomas; AML) and lymphatics (e.g. lymphangioleiomyomas, chylous effusions). LAM occurs with increased frequency in patients with tuberous sclerosis complex (TSC), an autosomal-dominant neurocutaneous disorder, associated with mutations in the TSC1 and TSC2 genes [1, 2]. LAM predominantly affects women of childbearing age, although it is found as well in post-menopausal women. Patients with LAM develop cysts throughout their lungs, leading to a reduction of pulmonary function, e.g. forced expiratory volume in 1&nbs...
Source: European Respiratory Journal - March 18, 2021 Category: Respiratory Medicine Authors: Hasani, A. M., Matthew, B., Goljamali, M., Chen, Y.-C., Stylianou, M., Pirooznia, M., Taveira-DaSilva, A., Chen, M. Y., Wen, H., Moss, J. Tags: Original Articles: Research letters Source Type: research

The clear and persistent impact of air pollution on chronic respiratory diseases: a call for interventions
Air pollution is ubiquitous and is responsible for noticeable acute and chronic adverse health effects [1]. Heart diseases and stroke are the most common reasons for morbidity and mortality attributable to air pollution, followed by respiratory diseases, but recently other pathologies have been added to the list. Additionally, air pollution contributes to climate change, another threat to public health. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 18, 2021 Category: Respiratory Medicine Authors: Annesi-Maesano, I., Forastiere, F., Balmes, J., Garcia, E., Harkema, J., Holgate, S., Kelly, F., Khreis, H., Hoffmann, B., Maesano, C. N., McConnell, R., Peden, D., Pinkerton, K., Schikowski, T., Thurston, G., Van Winkle, L. S., Carlsten, C. Tags: Editorials Source Type: research

Phagosome-regulated mTOR signalling during sarcoidosis granuloma biogenesis
Conclusions Sarcoidosis granulomas exhibit enhanced and sustained intracellular antigen processing and presentation capacities, and related phagolysosome assembly and acidification are required to support mTORc1 signalling to promote sarcoidosis granuloma formation. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 18, 2021 Category: Respiratory Medicine Authors: Crouser, E. D., Locke, L. W., Julian, M. W., Bicer, S., Sadee, W., White, P., Schlesinger, L. S. Tags: Lung biology and experimental studies, Interstitial and orphan lung disease Original Articles: Interstitial lung disease and basic science Source Type: research

Deep amplicon sequencing for culture-free prediction of susceptibility or resistance to 13 anti-tuberculous drugs
Conventional molecular tests for detecting Mycobacterium tuberculosis complex (MTBC) drug resistance on clinical samples cover a limited set of mutations. Whole-genome sequencing (WGS) typically requires culture. Here, we evaluated the Deeplex Myc-TB targeted deep-sequencing assay for prediction of resistance to 13 anti-tuberculous drugs/drug classes, directly applicable on sputum. With MTBC DNA tests, the limit of detection was 100–1000 genome copies for fixed resistance mutations. Deeplex Myc-TB captured in silico 97.1–99.3% of resistance phenotypes correctly predicted by WGS from 3651 MTBC genomes. On 429 is...
Source: European Respiratory Journal - March 18, 2021 Category: Respiratory Medicine Authors: Jouet, A., Gaudin, C., Badalato, N., Allix-Beguec, C., Duthoy, S., Ferre, A., Diels, M., Laurent, Y., Contreras, S., Feuerriegel, S., Niemann, S., Andre, E., Kaswa, M. K., Tagliani, E., Cabibbe, A., Mathys, V., Cirillo, D., de Jong, B. C., Rigouts, L., Su Tags: Respiratory infections and tuberculosis Original Articles: Pulmonary infections and tuberculosis Source Type: research

Evaluation of the latent tuberculosis screening and treatment strategy for asylum seekers in Stockholm, Sweden 2015-2018: a record linkage study of the care cascade
Conclusion The low attrition in patient-dependent cascade steps shows that the voluntary approach works well. Low LTBI treatment attainment is due to the current conservative local treatment policy, which means the vast majority are IGRA-tested without an intention to treat for LTBI. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 18, 2021 Category: Respiratory Medicine Authors: Nederby Öhd, J., Hergens, M.-P., Luksha, Y., Buxbaum, C., Shedrawy, J., Jonsson, J., Bruchfeld, J., Lönnroth, K. Tags: Respiratory infections and tuberculosis Original Articles: Pulmonary infections and tuberculosis Source Type: research

Temporal airway microbiome changes related to ventilator-associated pneumonia in children
We sought to determine whether temporal changes in the lower airway microbiome are associated with ventilator-associated pneumonia (VAP) in children. Using a multicentre prospective study of children aged 31 days to 18 years requiring mechanical ventilation support for>72 h, daily tracheal aspirates were collected and analysed by sequencing of the 16S rRNA gene. VAP was assessed using 2008 Centers for Disease Control and Prevention paediatric criteria. The association between microbial factors and VAP was evaluated using joint longitudinal time-to-event modelling, matched case–control comparisons an...
Source: European Respiratory Journal - March 18, 2021 Category: Respiratory Medicine Authors: Mourani, P. M., Sontag, M. K., Williamson, K. M., Harris, J. K., Reeder, R., Locandro, C., Carpenter, T. C., Maddux, A. B., Ziegler, K., Simoes, E. A. F., Osborne, C. M., Ambroggio, L., Leroue, M. K., Robertson, C. E., Langelier, C., DeRisi, J. L., Kamm, Tags: Paediatric pulmonology Original Articles: Paediatric lung disease Source Type: research

Life-course socioeconomic disadvantage and lung function: a multicohort study of 70 496 individuals
Conclusion Life-course socioeconomic disadvantage is associated with lower lung function and predicts a significant number of years of lung function loss in adulthood and at older ages. (Source: European Respiratory Journal)
Source: European Respiratory Journal - March 18, 2021 Category: Respiratory Medicine Authors: Rocha, V., Fraga, S., Moreira, C., Carmeli, C., Lenoir, A., Steptoe, A., Giles, G., Goldberg, M., Zins, M., Kivimäki, M., Vineis, P., Vollenweider, P., Barros, H., Stringhini, S., for the LIFEPATH Consortium Tags: COPD and smoking Original Articles: Airways disease Source Type: research

Exploratory study of the effectiveness of nebulised saline in children with neurodisability
Respiratory morbidity is an important cause of hospitalisation and death in children with neurodisability [1]. Such children may have impaired respiratory function and inefficient cough due to weak bulbar and respiratory musculature, increased upper airway collapsibility and low lung compliance [2, 3]. Nebulised hypertonic saline (HS), usually 3% or 7%, is used to manage and prevent respiratory exacerbations in conditions such as cystic fibrosis (CF) and non-CF bronchiectasis. In patients with CF and non-CF bronchiectasis, nebulised HS has been associated with better airway clearance and lung function [4–8]. (Source:...
Source: European Respiratory Journal - March 18, 2021 Category: Respiratory Medicine Authors: Galaz Souza, N., Bush, A., Tan, H.-L. Tags: Original Articles: Research letters Source Type: research

Reply to: Noxious cold stimulation: pro-con perspectives on the hypothermic effect on experimentally evoked cough
In this study we demonstrated that a painful cold stimulus, applied to the hand, inhibited cough responses to capsaicin in humans, and that this phenomenon (known as conditioned pain modulation, CPM) was impaired in patients with refractory chronic cough. Interestingly, the recent study performed by Dong et al. [2] also investigated the effects of cold on the cough reflex. They found placing guinea pigs in a cold environment had the opposite effect, heightening cough responses to cinnamaldehyde in animals repeatedly exposed to citric acid; the citric acid exposure being an attempt to emulate the hyperexcitability of the co...
Source: European Respiratory Journal - March 11, 2021 Category: Respiratory Medicine Authors: Satia, I., Iovoli, E., Holt, K., Woodcock, A. A., Belcher, J., Smith, J. A. Tags: Original Articles: Correspondence Source Type: research

Mononuclear phagocytic system and fibrosis: back to the future?
Bronchiolitis obliterans syndrome (BOS) is a chronic lung allograft dysfunction following lung transplantation [1–3], with histopathological characteristics of obliterative bronchiolitis (OB) that includes small airway epithelial disruption, submucosal inflammation and fibrosis, and obstruction of airway lumen. Clinical diagnosis is based on persistent decline of the allograft lung function measured by forced expiratory volume in 1 s and/or forced expiratory flow at 25–75% of forced vital capacity. 50% or more of lung transplantation recipients who survive beyond 5 years develop BOS, accounting for signifi...
Source: European Respiratory Journal - March 11, 2021 Category: Respiratory Medicine Authors: Ask, K., Vierhout, M., Dvorkin-Gheva, A., Shi, W. Tags: Editorials Source Type: research