The Severe Asthma Questionnaire: sensitivity to change and minimal clinically important difference
The Severe Asthma Questionnaire (SAQ) is a validated measure of the health-related quality of life of people living with severe asthma [1]. The minimal clinically important difference (MCID) of the SAQ has not been calculated. The MCID is useful for representing clinical as opposed to statistical significance. There are two main ways of calculating the MCID. Distribution methods define the MCID in terms of the relationship between the distribution of scores and mean change score. These methods are purely statistical and the relationship and formulae that constitute the MCID is determined by convention. By contrast, the anc...
Source: European Respiratory Journal - June 17, 2021 Category: Respiratory Medicine Authors: Masoli, M., Lanario, J. W., Hyland, M. E., Menzies-Gow, A., Mansur, A. H., Allen, D., Dodd, J. W., Hayes, G., Valderas, J. M., Lamb, S. E., Jones, R. C. Tags: Original Articles: Research letters Source Type: research

Methacholine reactivity in lymphangioleiomyomatosis is inversely related to FEV1 and VEGF-D
Lymphangioleiomyomatosis (LAM) is a multisystem disease characterised by cystic lung destruction, leading to respiratory failure, and associated with kidney (e.g. angiomyolipomas (AML)) and lymphatic involvement (e.g. lymphangioleiomyomas, chylous effusions) [1, 2]. LAM occurs sporadically or in association with tuberous sclerosis complex (TSC), an autosomal-dominant disorder characterised by mutations of the TSC1 or TSC2 genes. Lung destruction results from the proliferation of LAM cells, which possess neoplastic properties and are found in LAM lung nodules, in association with fibroblasts, mast cells, lymphocytes and lym...
Source: European Respiratory Journal - June 17, 2021 Category: Respiratory Medicine Authors: Cassandro, R., Elia, D., Caminati, A., Pacheco-Rodriguez, G., Stylianou, M., Moss, J., Harari, S. Tags: Original Articles: Research letters Source Type: research

Single-cell RNA sequencing identifies macrophage transcriptional heterogeneities in granulomatous diseases
Both sarcoidosis and chronic beryllium disease (CBD) are granulomatous diseases with overlapping clinical features; however, their clinical courses differ. CBD may have slow clinical progression and rarely resolves, while sarcoidosis has variable progression and may resolve depending on the stage of the disease [1]. These commonalities and differences imply differences in antigen(s), and potentially clearance and persistence. Alveolar macrophages play an important role in this process, driving innate [2] and adaptive immune responses [3]. Furthermore, subpopulations of macrophages may promote granulomatous inflammation and...
Source: European Respiratory Journal - June 17, 2021 Category: Respiratory Medicine Authors: Liao, S.-Y., Atif, S. M., Mould, K., Konigsberg, I. R., Fu, R., Davidson, E., Li, L., Fontenot, A. P., Maier, L. A., Yang, I. V. Tags: Original Articles: Research letters Source Type: research

TNF-mediated alveolar macrophage necroptosis drives disease pathogenesis during respiratory syncytial virus infection
We report that RSV infection triggers necroptosis in primary mouse macrophages and human monocytes in a RIPK1-, RIPK3- and MLKL-dependent manner. Moreover, necroptosis pathways are harmful to RSV clearance from alveolar macrophages. Additionally, Ripk3–/– mice were protected from RSV-induced weight loss and presented with reduced viral loads in the lungs. Alveolar macrophage depletion also protected mice from weight loss and decreased lung RSV virus load. Importantly, alveolar macrophage depletion abolished the upregulation of Ripk3 and Mlkl gene expression induced by RSV infection in the lung tissue. Autocrine...
Source: European Respiratory Journal - June 17, 2021 Category: Respiratory Medicine Authors: Santos, L. D., Antunes, K. H., Muraro, S. P., de Souza, G. F., da Silva, A. G., Felipe, J. d. S., Zanetti, L. C., Czepielewski, R. S., Magnus, K., Scotta, M., Mattiello, R., Maito, F., de Souza, A. P. D., Weinlich, R., Vinolo, M. A. R., Porto, B. N. Tags: Lung biology and experimental studies, Respiratory infections and tuberculosis Original Articles: Infection and basic science Source Type: research

Epidemiology of pleural empyema in English hospitals and the impact of influenza
This study aimed to assess changes in incidence and management of pleural empyema in England over the past 10 years and the potential impact of influenza on rates. Hospital Episode Statistics data were used to identify patients admitted to English hospitals with pleural empyema between 2008 and 2018. Linear regression was used to analyse the relationship between empyema rates and influenza incidence recorded by Public Health England. The relationship between influenza and empyema was further explored using serological data from a prospective cohort study of patients presenting with pleural empyema. Between April 2008 ...
Source: European Respiratory Journal - June 17, 2021 Category: Respiratory Medicine Authors: Arnold, D. T., Hamilton, F. W., Morris, T. T., Suri, T., Morley, A., Frost, V., Vipond, I. B., Medford, A. R., Payne, R. A., Muir, P., Maskell, N. A. Tags: Original Articles: Pleural disease Source Type: research

ERS statement on chronic thromboembolic pulmonary hypertension
Chronic thromboembolic pulmonary hypertension (CTEPH) is a rare complication of acute pulmonary embolism, either symptomatic or not. The occlusion of proximal pulmonary arteries by fibrotic intravascular material, in combination with a secondary microvasculopathy of vessels
Source: European Respiratory Journal - June 17, 2021 Category: Respiratory Medicine Authors: Delcroix, M., Torbicki, A., Gopalan, D., Sitbon, O., Klok, F. A., Lang, I., Jenkins, D., Kim, N. H., Humbert, M., Jais, X., Vonk Noordegraaf, A., Pepke-Zaba, J., Brenot, P., Dorfmuller, P., Fadel, E., Ghofrani, H.-A., Hoeper, M. M., Jansa, P., Madani, M., Tags: Original Articles: ERS statement Source Type: research

Rescue of multiple class II CFTR mutations by elexacaftor+tezacaftor+ivacaftor mediated in part by the dual activities of elexacaftor as both corrector and potentiator
Positive results in pre-clinical studies of the triple combination of elexacaftor, tezacaftor and ivacaftor, performed in airway epithelial cell cultures obtained from patients harbouring the class II cystic fibrosis transmembrane conductance regulator (CFTR) mutation F508del-CFTR, translated to impressive clinical outcomes for subjects carrying this mutation in clinical trials and approval of Trikafta. Encouraged by this correlation, we were prompted to evaluate the effect of the elexacaftor, tezacaftor and ivacaftor triple combination on primary nasal epithelial cultures obtained from individuals with rare class II CF-ca...
Source: European Respiratory Journal - June 17, 2021 Category: Respiratory Medicine Authors: Laselva, O., Bartlett, C., Gunawardena, T. N. A., Ouyang, H., Eckford, P. D. W., Moraes, T. J., Bear, C. E., Gonska, T. Tags: Original Articles: Cystic fibrosis Source Type: research

Real world effectiveness of anti-IL-5/5R therapies is independent of co-eligibility for anti-IgE therapy
Mepolizumab and benralizumab are monoclonal antibodies (mAbs) approved for the treatment of severe eosinophilic asthma (SEA), targeting interleukin (IL)-5 and IL-5R, respectively [1]. In appropriately selected patients, their use leads to significant reductions in asthma exacerbations and maintenance oral corticosteroid (mOCS) dose [2, 3]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - June 10, 2021 Category: Respiratory Medicine Authors: Hearn, A. P., Hug, O. D., Somani, Z. A., Kavanagh, J., d'Ancona, G., Roxas, C., Green, L., Thomson, L., Fernandes, M., Kent, B. D., Dhariwal, J., Nanzer, A. M., Jackson, D. J. Tags: Original Articles: Research letters Source Type: research

The coming-of-age of bedaquiline: a tale with an open ending
Bedaquiline can probably be considered the biggest breakthrough in tuberculosis drug development of the past decades. The first compound of a new anti-tuberculosis drug class, diarylquinolines, bedaquiline binds the mycobacterial ATP synthase, inducing major conformational changes and ultimately impacting the bacterial respiration pathway [1, 2]. After being developed in 2005 [3], bedaquiline showed promising results in phase II trials [4, 5], and was granted accelerated approval in 2012 by the US Food and Drug Administration (FDA) and conditional approval in 2014 by the European Medicines Agency. In the following years, t...
Source: European Respiratory Journal - June 10, 2021 Category: Respiratory Medicine Authors: Guglielmetti, L., Varaine, F. Tags: Respiratory infections and tuberculosis Editorials Source Type: research

Shifting the paradigm: unilateral infiltrates and ARDS?
Acute respiratory distress syndrome (ARDS) may present in up to 10% of patients admitted to the intensive care unit and is associated with high mortality [1]. According to a prospective, international, and multicentre cohort conducted by LUNG SAFE investigators, patients with ARDS face a mortality that ranges from approximately 35% in mild cases to 46% in severe cases. Currently, the Berlin definition is the accepted definition and classification of ARDS [2]. The classification comprises severity stratification of ARDS per PaO2/FIO2 (arterial oxygen tension to fraction of inspired oxygen) ratio by three categories: mild, m...
Source: European Respiratory Journal - June 10, 2021 Category: Respiratory Medicine Authors: Torres, A., Barbeta, E., Welte, T. Tags: Editorials Source Type: research

Methylxanthines in COPD: yes to caffeine, no to theophylline
Many readers of this journal and many of our patients will partake of a daily dose of 1,3,7-trimethylxanthine, perhaps in the form of drip coffee, espresso, Yerba mate, or Oolong tea. Several decades ago, medical providers would have commonly followed their morning caffeinated beverage by prescribing oral 1,3-dimethylxanthine, also known as theophylline, to many of their patients with COPD. With subsequent development of more effective and less toxic inhaler-based treatments for COPD, theophylline use has dramatically decreased in high-income countries, but not in low-to-middle income countries (LMICs). Nevertheless, inter...
Source: European Respiratory Journal - June 10, 2021 Category: Respiratory Medicine Authors: Kunisaki, K. M., Sin, D. D. Tags: COPD and smoking Editorials Source Type: research

Effect of corrected Global Lung Function Initiative reference equations on carbon monoxide transfer factor interpretation
The carbon monoxide transfer factor (TLCO) reference equations published by the Global Lung Function Initiative (GLI) in 2017 [1] have a number of advantages compared to previously published equations [2–8], including that they are derived from a large dataset (9710 subjects), use modern equipment, cover a wide age range (5–85 years) obviating the need for separate paediatric and adult equations, and use more sophisticated statistical techniques to account for variation and skewness across the age range. Following the publication of the GLI equations there were a number of studies, such as ours, that exami...
Source: European Respiratory Journal - June 10, 2021 Category: Respiratory Medicine Authors: Ruehland, W. R., Lanteri, C. J., Matsas, P., Brazzale, D. J. Tags: Original Articles: Research letters Source Type: research

Epigenetics and pulmonary diseases in the horizon of precision medicine: a review
We describe epigenetic mechanisms known to be associated with pulmonary diseases and discuss how network analysis could improve our understanding of lung diseases. (Source: European Respiratory Journal)
Source: European Respiratory Journal - June 10, 2021 Category: Respiratory Medicine Authors: Benincasa, G., DeMeo, D. L., Glass, K., Silverman, E. K., Napoli, C. Tags: Reviews Source Type: research

The effect of low-dose corticosteroids and theophylline on the risk of acute exacerbations of COPD: the TASCS randomised controlled trial
Background The highest burden of chronic obstructive pulmonary disease (COPD) occurs in low- and middle-income countries. Low-cost oral medications, if effective, could enable affordable, accessible COPD treatment. Methods In this randomised, three-arm, double-blind, double-dummy, placebo-controlled study conducted in 37 centres in China, symptomatic patients with moderate to very severe COPD were randomised 1:1:1 to placebo twice daily plus placebo once daily, low-dose theophylline 100 mg twice daily plus placebo once daily or low-dose theophylline 100 mg twice daily plus low-dose oral prednisone 5 mg once...
Source: European Respiratory Journal - June 10, 2021 Category: Respiratory Medicine Authors: Jenkins, C. R., Wen, F.-Q., Martin, A., Barnes, P. J., Celli, B., Zhong, N.-S., Zheng, J.-P., Scaria, A., Di Tanna, G.-L., Bradbury, T., Berend, N., on behalf of the TASCS study investigators Tags: COPD and smoking Original Articles: COPD Source Type: research

Outcome of acute hypoxaemic respiratory failure: insights from the LUNG SAFE Study
Background Current incidence and outcome of patients with acute hypoxaemic respiratory failure requiring mechanical ventilation in the intensive care unit (ICU) are unknown, especially for patients not meeting criteria for acute respiratory distress syndrome (ARDS). Methods An international, multicentre, prospective cohort study of patients presenting with hypoxaemia early in the course of mechanical ventilation, conducted during four consecutive weeks in the winter of 2014 in 459 ICUs from 50 countries (LUNG SAFE). Patients were enrolled with arterial oxygen tension/inspiratory oxygen fraction ratio ≤300 mmHg, ne...
Source: European Respiratory Journal - June 10, 2021 Category: Respiratory Medicine Authors: Pham, T., Pesenti, A., Bellani, G., Rubenfeld, G., Fan, E., Bugedo, G., Lorente, J. A., Fernandes, A. d. V., Van Haren, F., Bruhn, A., Rios, F., Esteban, A., Gattinoni, L., Larsson, A., McAuley, D. F., Ranieri, M., Thompson, B. T., Wrigge, H., Brochard, L Tags: Acute lung injury and critical care Original Articles: Critical care Source Type: research

Impact of bedaquiline on treatment outcomes of multidrug-resistant tuberculosis in a high-burden country
Background Evaluation of novel anti-tuberculosis (TB) drugs for the treatment of multidrug-resistant (MDR)-TB continues to be of high interest on the TB research agenda. We assessed treatment outcomes in patients with pulmonary MDR-TB who received bedaquiline-containing treatment regimens in the Republic of Moldova, a high-burden MDR-TB country. Method We systematically analysed the SIMETB national electronic TB database and performed a retrospective propensity score-matched comparison of treatment outcomes in a cohort of patients with MDR-TB who started treatment during 2016–2018 with a bedaquiline-containing regim...
Source: European Respiratory Journal - June 10, 2021 Category: Respiratory Medicine Authors: Chesov, D., Heyckendorf, J., Alexandru, S., Donica, A., Chesov, E., Reimann, M., Crudu, V., Botnaru, V., Lange, C. Tags: Respiratory infections and tuberculosis Original Articles: Tuberculosis Source Type: research

Pulse oximetry is an essential tool that saves lives: a call for standardisation
Pneumonia is a leading global cause of morbidity and mortality, particularly amongst adults aged>70 years and children. Annual deaths due to pneumonia in these groups was estimated at more than one million and 672 000 worldwide for both groups, respectively, in 2019 [1]. The importance of pneumonia is highlighted by impact of the current coronavirus disease 2019 (COVID-19) pandemic on vulnerable populations. Yet, despite the high impact of pneumonia worldwide, diagnosing pneumonia, especially in children in low- and middle-income countries, remains a big challenge. Frequent clinical signs of pneumonia (cough and di...
Source: European Respiratory Journal - June 4, 2021 Category: Respiratory Medicine Authors: Cilloniz, C., Simonds, A., Hansen, K., Alouch, J., Zar, H., Nakanishi, Y., Levine, S., Cohen, M., Dela Cruz, C., Evans, S. E., Sanguinetti, M., Vila, J., Diez Manglano, J., Ferrer, R., Criado, L., Polo Garcia, J., Correcher, Z., Rodriguez-Hurtado, D., Ter Tags: Original Articles: Correspondence Source Type: research

The association between inhaled corticosteroid and osteoporosis and fracture
We read with great interest the study investigating the association between inhaled corticosteroid (ICS) and the risk of osteoporosis and fracture among COPD patients [1]. Multivariate analysis in this study demonstrated a significant dose–effect relationship between ICS and the risk of osteoporosis-related events. Compared to non-ICS users, high-dose ICS treatment was significantly associated with any osteoporosis-related event (risk ratio 1.52, 95% CI 1.24–1.62; while the corresponding estimate for low-dose ICS was 1.27, 95% CI 1.13–1.56) [1]. Overall, it is a well-designed study; however, we have one m...
Source: European Respiratory Journal - June 4, 2021 Category: Respiratory Medicine Authors: Wang, C.-Y., Lai, C.-C. Tags: Original Articles: Correspondence Source Type: research

The role of cardiopulmonary exercise test in identifying pulmonary veno-occlusive disease
Pulmonary veno-occlusive disease (PVOD) is a rare form of pulmonary hypertension that shares some clinical and haemodynamic features with idiopathic pulmonary arterial hypertension (PAH). However, suspicion of PVOD is crucial, considering that PAH-specific treatment may precipitate life-threatening pulmonary oedema and lung transplant should be considered from diagnosis [1, 2]. (Source: European Respiratory Journal)
Source: European Respiratory Journal - June 4, 2021 Category: Respiratory Medicine Authors: Perez-Olivares, C., Segura de la Cal, T., Flox-Camacho, A., Nuche, J., Tenorio, J., Martinez Menaca, A., Cruz-Utrilla, A., de la Cruz-Bertolo, J., Perez Nunez, M., Consortium, S. P., Arribas-Ynsaurriaga, F., Escribano Subias, P. Tags: Original Articles: Research letters Source Type: research

Evidence of air pollution exposure and new asthma onset: further justification for cleaner air
The relationship between air pollution and health is being questioned by some, and the cost of further progress increases as the ambient levels decline, so it is important to document all the health benefits associated with cleaner air. It is well-established in the medical literature that exposure to outdoor air pollution is associated with multiple adverse health outcomes in adults [1–3]. But, in practice, we are largely restricted to "looking under the lamppost" of published studies of a limited list of routinely documented acute health outcomes (such as daily hospital admissions and death counts) in qua...
Source: European Respiratory Journal - June 4, 2021 Category: Respiratory Medicine Authors: Thurston, G. D., Lee, A. Tags: Editorials Source Type: research

Fine particulate matter and out-of-hospital cardiac arrest of respiratory origin
We examined the association between short-term exposure to PM2.5 and bystander-witnessed respiratory origin OHCAs, including eventual prognosis. We also investigated differences between PM2.5 exposure-related cardiac and respiratory origin OHCAs. (Source: European Respiratory Journal)
Source: European Respiratory Journal - June 4, 2021 Category: Respiratory Medicine Authors: Kojima, S., Michikawa, T., Matsui, K., Ogawa, H., Yamazaki, S., Nitta, H., Takami, A., Ueda, K., Tahara, Y., Yonemoto, N., Nonogi, H., Nagao, K., Ikeda, T., Kobayashi, Y., for the Japanese Circulation Society With Resuscitation Science Study (JCS-ReSS) Gr Tags: Original Articles: Research letters Source Type: research

Improving adherence to asthma medications: same-old, same-old?
The paper by Moore et al. [1] in this issue of the European Respiratory Journal reports on the effect of various forms of feedback on actual use of asthma medications in research participants with moderate asthma. The primary outcome for the trial was actual adherence, assessed as the proportion (reported as a percentage) of doses taken compared to doses prescribed, after both a run-in period and 3 months of the trial, during the second 3-month period of the trial. Other secondary outcome variables included the Asthma Control Test (ACT) and peak expiratory flow rate (PEFR). The number of participants with a severe exa...
Source: European Respiratory Journal - June 4, 2021 Category: Respiratory Medicine Authors: Weatherall, M. Tags: Editorials Source Type: research

Targeting cystic fibrosis inflammation in the age of CFTR modulators: focus on macrophages
Cystic fibrosis (CF) is a life-shortening, multi-organ, autosomal recessive disease caused by mutations in the cystic fibrosis transmembrane conductance regulator (CFTR) gene. The most prominent clinical manifestation in CF is the development of progressive lung disease characterised by an intense, chronic inflammatory airway response that culminates in respiratory failure and, ultimately, death. In recent years, a new class of therapeutics that have the potential to correct the underlying defect in CF, known as CFTR modulators, have revolutionised the field. Despite the exciting success of these drugs, their impact on air...
Source: European Respiratory Journal - June 4, 2021 Category: Respiratory Medicine Authors: Gillan, J. L., Davidson, D. J., Gray, R. D. Tags: Reviews Source Type: research

Prevalence, progression and impact of chronic cough on employment in Northern Europe
We investigated the prevalence of chronic cough and its association with work ability and sick leave in the general population. Data were analysed from the Respiratory Health In Northern Europe (RHINE) III cohort (n=13 500), of which 11 252 participants had also participated in RHINE II 10 years earlier, a multicentre study in Northern Europe. Participants answered a questionnaire on chronic cough, employment factors, smoking and respiratory comorbidities. Nonproductive chronic cough was found in 7% and productive chronic cough in 9% of the participants. Participants with nonproductive cough were more often female and...
Source: European Respiratory Journal - June 4, 2021 Category: Respiratory Medicine Authors: Johansson, H., Johannessen, A., Holm, M., Forsberg, B., Schlünssen, V., Jogi, R., Clausen, M., Lindberg, E., Malinovschi, A., Emilsson, O. I. Tags: Respiratory clinical practice Original Articles: Cough Source Type: research

World Health Organization recommendations on the treatment of drug-resistant tuberculosis, 2020 update
Antimicrobial resistance is a major public health problem globally. Likewise, forms of tuberculosis (TB) resistant to first- and second-line TB medicines present a major challenge for patients, healthcare workers and healthcare services. In November 2019, the World Health Organization (WHO) convened an independent international expert panel to review new evidence on the treatment of multidrug- (MDR) and rifampicin-resistant (RR) TB, using the Grading of Recommendations Assessment, Development and Evaluation approach. Updated WHO guidelines emerging from this review, published in June 2020, recommend a shorter treatment reg...
Source: European Respiratory Journal - June 4, 2021 Category: Respiratory Medicine Authors: Mirzayev, F., Viney, K., Linh, N. N., Gonzalez-Angulo, L., Gegia, M., Jaramillo, E., Zignol, M., Kasaeva, T. Tags: Task Force Report Source Type: research

A randomised controlled trial of the effect of a connected inhaler system on medication adherence in uncontrolled asthmatic patients
This study evaluated the effect of different elements of a connected inhaler system (CIS), comprising clip-on inhaler sensors, a patient-facing app and a healthcare professional (HCP) dashboard, on adherence to asthma maintenance therapy. This was an open-label, parallel-group, 6-month, randomised controlled trial in adults with uncontrolled asthma (asthma control test (ACT) score less than 20) on fixed-dose inhaled corticosteroids/long-acting β-agonist maintenance therapy (n=437). All subjects received fluticasone furoate/vilanterol ELLIPTA dry-powder inhalers for maintenance and salbutamol/albuterol metered-dose inh...
Source: European Respiratory Journal - June 4, 2021 Category: Respiratory Medicine Authors: Moore, A., Preece, A., Sharma, R., Heaney, L. G., Costello, R. W., Wise, R. A., Ludwig-Sengpiel, A., Mosnaim, G., Rees, J., Tomlinson, R., Tal-Singer, R., Stempel, D. A., Barnes, N. Tags: Asthma and allergy Original Articles: Asthma Source Type: research

Long-term exposure to low-level air pollution and incidence of asthma: the ELAPSE project
Background Long-term exposure to ambient air pollution has been linked to childhood-onset asthma, although evidence is still insufficient. Within the multicentre project Effects of Low-Level Air Pollution: A Study in Europe (ELAPSE), we examined the associations of long-term exposures to particulate matter with a diameter
Source: European Respiratory Journal - June 4, 2021 Category: Respiratory Medicine Authors: Liu, S., Jorgensen, J. T., Ljungman, P., Pershagen, G., Bellander, T., Leander, K., Magnusson, P. K. E., Rizzuto, D., Hvidtfeldt, U. A., Raaschou-Nielsen, O., Wolf, K., Hoffmann, B., Brunekreef, B., Strak, M., Chen, J., Mehta, A., Atkinson, R. W., Bauweli Tags: Asthma and allergy Original Articles: Asthma Source Type: research

Machine learning can predict disease manifestations and outcomes in lymphangioleiomyomatosis
Background Lymphangioleiomyomatosis (LAM) is a rare multisystem disease with variable clinical manifestations and differing rates of progression that make management decisions and giving prognostic advice difficult. We used machine learning to identify clusters of associated features which could be used to stratify patients and predict outcomes in individuals. Patients and methods Using unsupervised machine learning we generated patient clusters using data from 173 women with LAM from the UK and 186 replication subjects from the US National Heart, Lung, and Blood Institute (NHLBI) LAM registry. Prospective outcomes were a...
Source: European Respiratory Journal - June 4, 2021 Category: Respiratory Medicine Authors: Chernbumroong, S., Johnson, J., Gupta, N., Miller, S., McCormack, F. X., Garibaldi, J. M., Johnson, S. R. Tags: Interstitial and orphan lung disease Original Articles: Rare lung diseases Source Type: research

Functional respiratory imaging provides novel insights into the long-term respiratory sequelae of bronchopulmonary dysplasia
Rationale Bronchopulmonary dysplasia (BPD) is a common complication of preterm birth. Lung function and imaging are classically used to assess BPD. Functional respiratory imaging (FRI) combines a structural and functional assessment of the airways and their vasculature. We aimed to assess BPD using FRI and to correlate these findings with the clinical presentation. Methods We included 37 adolescents with a history of preterm birth (22 BPD cases and 15 preterm controls). The study protocol included a detailed history, lung function testing and computed tomography (CT) (at total lung capacity (TLC) and functional residual c...
Source: European Respiratory Journal - June 4, 2021 Category: Respiratory Medicine Authors: Vanhaverbeke, K., Slaats, M., Al-Nejar, M., Everaars, N., Snoeckx, A., Spinhoven, M., El Addouli, H., Lauwers, E., Van Eyck, A., De Winter, B. Y., Van Hoorenbeeck, K., De Dooy, J., Mahieu, L., Mignot, B., De Backer, J., Mulder, A., Verhulst, S. Tags: Lung imaging Original Articles: Imaging Source Type: research

IL-17A from innate and adaptive lymphocytes contributes to inflammation and damage in cystic fibrosis lung disease
Conclusions We identify innate and adaptive sources of IL-17A in CF lung disease. Our data demonstrate that IL-17A contributes to airway neutrophilia, macrophage activation and structural lung damage in CF-like lung disease in mice. These results suggest IL-17A as a novel target for anti-inflammatory therapy of CF lung disease. (Source: European Respiratory Journal)
Source: European Respiratory Journal - June 4, 2021 Category: Respiratory Medicine Authors: Hagner, M., Albrecht, M., Guerra, M., Braubach, P., Halle, O., Zhou-Suckow, Z., Butz, S., Jonigk, D., Hansen, G., Schultz, C., Dittrich, A.-M., Mall, M. A. Tags: Lung biology and experimental studies, CF and non-CF bronchiectasis Original Articles: Cystic fibrosis and basic science Source Type: research

Repeat bronchoalveolar lavage in idiopathic pulmonary fibrosis: proceed with caution?
Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive fibrosing interstitial lung disease with a median life expectancy of 3–5 years [1]. In recent years, management of IPF has been transformed with the worldwide approval of two anti-fibrotic therapies. In parallel, advances in the understanding of IPF pathogenesis have identified numerous targets for potential therapeutic intervention [2]. However, the adoption of anti-fibrotic therapies as the standard of care for patients with IPF has further increased the complexity of investigating novel therapeutics in clinical trials. New, innovative clinical tria...
Source: European Respiratory Journal - May 27, 2021 Category: Respiratory Medicine Authors: Jones, M. G., Kolb, M. Tags: Editorials Source Type: research

Eradication success for non-tuberculous mycobacteria in children with cystic fibrosis
Non-tuberculous mycobacteria (NTM) are an emerging pathogen worldwide in both cystic fibrosis (CF) and non-CF pulmonary disease (PD), with reports suggesting an increasing prevalence [1, 2]. It is an opportunistic infection acquired from the environment [3], though conflicting evidence remains around person-to-person transmission [4, 5]. Recent evidence suggests that Mycobacterium abscessus complex (MABSC) may be the most detrimental airway infection to lung function in CF [6], yet its treatment remains poorly evidenced. (Source: European Respiratory Journal)
Source: European Respiratory Journal - May 27, 2021 Category: Respiratory Medicine Authors: Hughes, D. A., Bokobza, I., Carr, S. B. Tags: Original Articles: Research letters Source Type: research

Validation of the Bronchiectasis Impact Measure (BIM): a novel patient-reported outcome measure
Conclusion The BIM is a simple patient-reported outcome. This study validates the internal consistency, reliability, construct validity and response of the tool at acute exacerbation. Further validation of the tool is now required. (Source: European Respiratory Journal)
Source: European Respiratory Journal - May 27, 2021 Category: Respiratory Medicine Authors: Crichton, M. L., Dudgeon, E. K., Shoemark, A., Chalmers, J. D. Tags: CF and non-CF bronchiectasis Original Articles: Bronchiectasis Source Type: research

Target inhibition of galectin-3 by inhaled TD139 in patients with idiopathic pulmonary fibrosis
Galectin (Gal)-3 is a profibrotic β-galactoside-binding lectin that plays a key role in the pathogenesis of idiopathic pulmonary fibrosis (IPF) and IPF exacerbations. TD139 is a novel and potent small-molecule inhibitor of Gal-3. A randomised, double-blind, multicentre, placebo-controlled, phase 1/2a study was conducted to assess the safety, tolerability, pharmacokinetics and pharmacodynamics of inhaled TD139 in 36 healthy subjects and 24 patients with IPF. Six dose cohorts of six healthy subjects were evaluated (4:2 TD139:placebo ratio) with single doses of TD139 (0.15–50 mg) and three dose cohorts of eigh...
Source: European Respiratory Journal - May 27, 2021 Category: Respiratory Medicine Authors: Hirani, N., MacKinnon, A. C., Nicol, L., Ford, P., Schambye, H., Pedersen, A., Nilsson, U. J., Leffler, H., Sethi, T., Tantawi, S., Gravelle, L., Slack, R. J., Mills, R., Karmakar, U., Humphries, D., Zetterberg, F., Keeling, L., Paul, L., Molyneaux, P. L. Tags: Interstitial and orphan lung disease Original Articles: Interstitial lung disease Source Type: research

High eosinophil counts predict decline in FEV1: results from the CanCOLD study
Introduction The aim of this study was to examine the association between blood eosinophil levels and the decline in lung function in individuals aged>40 years from the general population. Methods The study evaluated the eosinophil counts from thawed blood in 1120 participants (mean age 65 years) from the prospective population-based Canadian Cohort of Obstructive Lung Disease (CanCOLD) study. Participants answered interviewer-administered respiratory questionnaires and performed pre-/post-bronchodilator spirometric tests at 18-month intervals; computed tomography (CT) imaging was performed at baseline. Statistica...
Source: European Respiratory Journal - May 27, 2021 Category: Respiratory Medicine Authors: Tan, W. C., Bourbeau, J., Nadeau, G., Wang, W., Barnes, N., Landis, S. H., Kirby, M., Hogg, J. C., Sin, D. D., on behalf of the CanCOLD Collaborative Research Group Tags: COPD and smoking Original Articles: COPD Source Type: research

Artificial intelligence for thoracic radiology: from research tool to clinical practice
Artificial intelligence (AI) presents an attractive opportunity for providing decision support to radiologists, who are often overburdened by the ever-increasing number of radiographs that are requested each year [1]. Interpretation errors, reporting delays and backlogs, particularly of chest radiographs (CXR), continue to be a major problem faced by busy radiology departments. (Source: European Respiratory Journal)
Source: European Respiratory Journal - May 20, 2021 Category: Respiratory Medicine Authors: Calandriello, L., Walsh, S. L. F. Tags: Lung imaging Editorials Source Type: research

Increased detection of pulmonary tuberculosis amongst hospitalised inpatients during the COVID-19 pandemic
We read with interest the article by Nikolayevskyy et al. [1] reporting significant disruption to clinical tuberculosis (TB) services during the coronavirus disease 2019 (COVID-19) pandemic. Reductions in TB diagnoses during the pandemic have been reported worldwide [1–4]. These findings have been attributed to a reduction in admissions due to lockdown, the spillover effect of public health measures against severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on other respiratory infectious diseases, and diversion of resources towards the COVID-19 response [1–4]. During the pandemic, healthcare systems ...
Source: European Respiratory Journal - May 20, 2021 Category: Respiratory Medicine Authors: Wee, L. E., Goh, K. C. M., Conceicao, E. P., Tan, J. B. X., Sng, L.-H., Venkatachalam, I. Tags: Original Articles: Correspondence Source Type: research

Cannabis use and lung cancer: time to stop overlooking the problem?
After tobacco, cannabis is the most widely used drug worldwide, and the move to legalise it is growing in more and more countries. The literature about the involvement of cannabis smoking on the development of lung cancer is scarce and most often reassuring [1–3], even though the concentration of carcinogens in cannabis smoke is unquestionably greater than that in tobacco smoke [4]. Moreover, recent studies on cannabis tend to focus on possible therapeutic effects [5]. Studies of the carcinogenic impact of cannabis are indeed limited by its frequent association with tobacco smoking and by its illegal status in most c...
Source: European Respiratory Journal - May 20, 2021 Category: Respiratory Medicine Authors: Betser, L., Glorion, M., Mordant, P., Caramella, C., Ghigna, M.-R., Besse, B., Planchard, D., Le Pavec, J., Chapelier, A., Friard, S., Gounant, V., Castier, Y., Levy, A., Mercier, O., Fabre, D., Fadel, E., Pradere, P. Tags: Original Articles: Research letters Source Type: research

Methods for studying pulmonary lymphatics
(Source: European Respiratory Journal)
Source: European Respiratory Journal - May 20, 2021 Category: Respiratory Medicine Authors: Maldonado-Zimbron, V. E., Hong, J., Russell, P., Trevaskis, N. L., Windsor, J. A., Phillips, A. R. J. Tags: ERJ Methods Source Type: research

Cough hypersensitivity and suppression in COPD
This study investigated the ability of patients with COPD to suppress cough during a cough challenge test in comparison to patients with CRC and healthy subjects. This study also investigated whether cough reflex hypersensitivity is associated with chronic cough in COPD. Participants with COPD (n=27) and CRC (n=11) and healthy subjects (n=13) underwent capsaicin challenge tests with and without attempts to self-suppress cough in a randomised order over two visits, 5 days apart. For patients with COPD, the presence of self-reported chronic cough was documented, and objective 24-h cough frequency was measured. Amongst p...
Source: European Respiratory Journal - May 20, 2021 Category: Respiratory Medicine Authors: Cho, P. S. P., Fletcher, H. V., Patel, I. S., Turner, R. D., Jolley, C. J., Birring, S. S. Tags: Respiratory clinical practice Original Articles: Cough Source Type: research

Same-day repeatability of fractional exhaled nitric oxide in severe asthma
Fractional exhaled nitric oxide (FENO) is a single-breath test used in asthma diagnosis and management. Whilst a number of studies in mild to moderate asthma have demonstrated excellent repeatability of FENO by assessing intra-device reproducibility from consecutive blows [1–3], the reported between-session and diurnal variability have been inconsistent [4–9]. Asthma is a highly variable disease. The excessive diurnal variability in airflow obstruction is a marker for disease severity, poor control and mortality. Diurnal variability of FENO is also a predictor for poor asthma control [8]. We have demonstrated t...
Source: European Respiratory Journal - May 20, 2021 Category: Respiratory Medicine Authors: Wang, R., Alahmadi, F., Niven, R., Fowler, S. J. Tags: Original Articles: Research letters Source Type: research

Development and validation of a deep learning algorithm detecting 10 common abnormalities on chest radiographs
We aimed to develop a deep learning algorithm detecting 10 common abnormalities (DLAD-10) on chest radiographs, and to evaluate its impact in diagnostic accuracy, timeliness of reporting and workflow efficacy. DLAD-10 was trained with 146 717 radiographs from 108 053 patients using a ResNet34-based neural network with lesion-specific channels for 10 common radiological abnormalities (pneumothorax, mediastinal widening, pneumoperitoneum, nodule/mass, consolidation, pleural effusion, linear atelectasis, fibrosis, calcification and cardiomegaly). For external validation, the performance of DLAD-10 on a same-day computed tomog...
Source: European Respiratory Journal - May 20, 2021 Category: Respiratory Medicine Authors: Nam, J. G., Kim, M., Park, J., Hwang, E. J., Lee, J. H., Hong, J. H., Goo, J. M., Park, C. M. Tags: Lung imaging Original Articles: Lung imaging Source Type: research

Compassionate use of delamanid in adults and children for drug-resistant tuberculosis: 5-year update
Conclusions The use of delamanid combined with other active drugs has the potential to achieve high rates of culture negativity in difficult-to-treat drug-resistant TB cases, with a favourable safety profile. (Source: European Respiratory Journal)
Source: European Respiratory Journal - May 20, 2021 Category: Respiratory Medicine Authors: Ghosh, S., Breitscheidel, L., Lazarevic, N., Martin, A., Hafkin, J., Hittel, N. Tags: Respiratory infections and tuberculosis Original Articles: Tuberculosis Source Type: research

Cochrane review update leaves big questions unanswered regarding vaping: implications for medical practitioners
We read with great interest the recent correspondence by Pisinger and Vestbo [1], published in the European Respiratory Journal, which summarises the findings of a Cochrane review on electronic cigarettes for smoking cessation [2]. We strongly agree with Pisinger and Vestbo [1] that the authors have not presented a balanced scientific view and have overlooked the dangers of early, such as e-cigarette or vaping associated lung injury (EVALI), and long-term electronic cigarette use. This is an important public health issue, and we would like to further enhance this discussion. (Source: European Respiratory Journal)
Source: European Respiratory Journal - May 13, 2021 Category: Respiratory Medicine Authors: McAlinden, K. D., Barnsley, K., Weber, H. C., Haug, G., Chia, C., Eapen, M. S., Sohal, S. S. Tags: Original Articles: Correspondence Source Type: research

Putting the spotlight on macrophage-derived cathepsin in the pathophysiology of obliterative bronchiolitis
While the experience of lung transplantation (LTx) is growing worldwide, long-term outcomes are not improving accordingly. Next to oncological and infectious complications, chronic rejection, clinically defined as chronic lung allograft dysfunction (CLAD), remains the major bottleneck to improving long-term outcomes [1, 2]. Increased recognition of clinical phenotypes of CLAD assists in predicting patient prognosis; however, mechanistically, we are still far from unravelling the pathophysiological processes underlying CLAD. Indeed, the internationally endorsed recognition of an obstructive (bronchiolitis obliterans syndrom...
Source: European Respiratory Journal - May 13, 2021 Category: Respiratory Medicine Authors: Brugiere, O., Verleden, S. E. Tags: Editorials Source Type: research

Plasma ACE2 activity is persistently elevated following SARS-CoV-2 infection: implications for COVID-19 pathogenesis and consequences
Coronavirus disease 2019 (COVID-19) causes persistent endothelial inflammation, lung, cardiovascular, kidney and neurological complications, and thromboembolic phenomena of unclear pathogenesis [1]. Severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2) utilises the catalytic site of full-length membrane-bound angiotensin converting enzyme 2 (ACE2) for host cell entry [2], which is thought to downregulate membrane-bound ACE2, and thus contribute to ongoing inflammation due to loss of a degradative pathway for angiotensin II. In healthy individuals, ACE2 exists primarily in its membrane-bound form with very low levels...
Source: European Respiratory Journal - May 13, 2021 Category: Respiratory Medicine Authors: Patel, S. K., Juno, J. A., Lee, W. S., Wragg, K. M., Hogarth, P. M., Kent, S. J., Burrell, L. M. Tags: Original Articles: Research letters Source Type: research

Genome-wide association study of asthma exacerbations despite inhaled corticosteroid use
Conclusions The intergenic region of CACNA2D3 and WNT5A was revealed as a novel locus for asthma exacerbations despite ICS treatment in European populations. Genes associated were related to trichostatin A, suggesting that this drug could regulate the molecular mechanisms involved in treatment response. (Source: European Respiratory Journal)
Source: European Respiratory Journal - May 13, 2021 Category: Respiratory Medicine Authors: Hernandez-Pacheco, N., Vijverberg, S. J., Herrera-Luis, E., Li, J., Sio, Y. Y., Granell, R., Corrales, A., Maroteau, C., Lethem, R., Perez-Garcia, J., Farzan, N., Repnik, K., Gorenjak, M., Soares, P., Karimi, L., Schieck, M., Perez-Mendez, L., Berce, V., Tags: Genetics, Asthma and allergy Original Articles: Asthma and genetics Source Type: research

R-Crizotinib predisposes to and exacerbates pulmonary arterial hypertension in animal models
Pulmonary hypertension (PH) is a life-threatening disease of multiple aetiologies. Regardless of the underlying cause, PH is characterised by vasoconstriction and progressive thickening of the pulmonary vessel wall, all of which is initiated by the loss of pulmonary artery endothelial cells (PAECs) [1]. Indeed, a large body of work has shown that damaged or apoptotic PAECs initiate the remodelling process through the release of growth, fibrogenic and pro-inflammatory factors that directly induce contraction and enhance survival and proliferation of adjacent pulmonary artery smooth muscle cells (PASMCs) and fibroblasts [1, ...
Source: European Respiratory Journal - May 13, 2021 Category: Respiratory Medicine Authors: Awada, C., Grobs, Y., Wu, W.-H., Habbout, K., Romanet, C., Breuils-Bonnet, S., Tremblay, E., Martineau, S., Paulin, R., Bonnet, S., Provencher, S., Potus, F., Boucherat, O. Tags: Original Articles: Research letters Source Type: research

Residential air pollution increases the risk for persistent pulmonary hypertension after pulmonary endarterectomy
Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition and a rare complication of pulmonary embolism [1]. It is characterised by increased pulmonary vascular resistance (PVR), due to unresolved fibro-thrombotic material obstructing large pulmonary arteries, and secondary microvasculopathy. Various factors are suspected to be involved in the pathogenesis and progression of CTEPH, including inflammatory thrombosis, dysregulated fibrinolysis and deficient angiogenesis [2]. The gold standard therapy is a surgical approach, namely pulmonary endarterectomy (PEA), consisting of removal of obstructin...
Source: European Respiratory Journal - May 13, 2021 Category: Respiratory Medicine Authors: Swinnen, K., Bijnens, E., Casas, L., Nawrot, T. S., Delcroix, M., Quarck, R., Belge, C. Tags: Original Articles: Research letters Source Type: research

Two sides of the same coin? A review of the similarities and differences between idiopathic pulmonary fibrosis and rheumatoid arthritis-associated interstitial lung disease
Rheumatoid arthritis associated interstitial lung disease (RA-ILD) and idiopathic pulmonary fibrosis (IPF) are distinct diseases; however, they share several clinical, radiographic and genetic features. For instance, usual interstitial pneumonia (UIP), which is an ILD pattern required for a diagnosis of IPF, is also the most common ILD pattern in RA-ILD. The presence of UIP in RA-ILD is a poor prognostic sign with outcomes similar to those seen in IPF. The recent finding of a shared genetic susceptibility between IPF and RA-ILD has sparked additional interest in this relationship. This review outlines these similarities an...
Source: European Respiratory Journal - May 13, 2021 Category: Respiratory Medicine Authors: Matson, S., Lee, J., Eickelberg, O. Tags: State of the Art Source Type: research