ERJ Open Research最新文献

Background: Respiratory syncytial virus (RSV) is the primary cause of hospitalisation due to acute bronchiolitis and viral pneumonia in infants and young children. Recently, a maternal RSV vaccine (Pfizer's Abrysvo) has been approved to protect infants from birth up to 6 months of age. However, there is currently no vaccine or antiviral therapy against RSV for children aged >6 months. Therefore, there is an urgent need for novel antiviral therapies against RSV infection for young children.

Methods: We hypothesised that blocking a host protein called B-Raf kinase would inhibit RSV replication and protect airway epithelial cells against infection. We investigated the in vitro effects of dabrafenib, a US Food and Drug Administration-approved B-Raf kinase inhibitor, against RSV. Human airway epithelial cell lines and primary nasal epithelial cells were infected with RSV and treated with dabrafenib. Real-time PCR, plaque assay, quantitative mass spectrometry, ELISA and immunofluorescence were performed.

Results: Dabrafenib impaired RSV infection and replication (p=0.0003), while protecting cells against RSV-induced lytic cell death (p<0.0001). Proteomics and PCR analyses revealed that dabrafenib decreased the expression of the interferon-stimulated genes IFIT1 (p<0.0001) and ISG15 (p<0.0001) and corresponding proteins in airway epithelial cells. Therapeutic treatment with dabrafenib differentially modulated the release of type I and III interferons.

Conclusions: Collectively, our data indicate that B-Raf kinase is involved in RSV replication, interferon-stimulated gene induction, and type I and III interferon release in airway epithelial cells following infection. We propose that repurposing dabrafenib as a host-directed antiviral against RSV may be valuable in reducing disease pathogenesis associated with RSV infection.

TDM use in NTM management varies globally, with over half using it despite significant barriers. Safety seemed the main reason. Standardised protocols and clear guidelines are needed for effective and consistent TDM implementation. https://bit.ly/3TFYN2j.

Introduction: Learning-centred education is a paramount component of pulmonary rehabilitation. A variability in educational needs exists among patients with a chronic respiratory disease referred for pulmonary rehabilitation and their significant others. Healthcare professionals play a crucial role in meeting these needs by facilitating opportunities for learner-centred education. This study aimed to explore the perceptions of healthcare professionals involved in pulmonary rehabilitation regarding optimisation of patient education for people with a chronic respiratory disease referred for pulmonary rehabilitation and their significant others.

Methods: Focus groups were conducted, which took place on-site at Ciro, a centre of expertise for patients with chronic organ failure, and online. Focus groups consisted of 1) an interprofessional team of healthcare professionals affiliated with Ciro; and 2) hospital-based healthcare professionals who refer patients to Ciro for pulmonary rehabilitation. Focus groups were audiotaped, transcribed verbatim and analysed thematically by two independent researchers.

Results: Three focus groups were held, involving 17 healthcare professionals representing various disciplines. Four main themes were identified: facilitators for optimal patient education, barriers for optimal patient education, involving significant others in patient education and healthcare professionals' preferences for education.

Discussion: To enhance patient education in pulmonary rehabilitation, key recommendations include adopting personalised education, integrating e-health applications to complement face-to-face education and strengthening interprofessional collaboration for continuous and accessible education for both patients and their significant others.

The disproportionate burden of tuberculosis among migrants in the World Health Organization (WHO) European Region underscores the urgent need to address the public health challenges associated with global migration. Recommendations for screening of pulmonary tuberculosis (TB) and TB infection (TBI) are highly variable across European countries, highlighting the need for standardised practices and coordinated efforts to reduce TB risk more effectively. This study aims to produce a harmonised set of recommendations to contribute to elaboration for policy action using the Delphi method. It brings together a multidisciplinary panel of 33 TB experts from academia, healthcare, non-governmental organisations and government agencies across 22 countries to formulate consensus-based recommendations. The panel created 19 consensus statements and 36 recommendations for governments, health systems and other stakeholders. The recommendations span four key domains: 1) policy, 2) health systems and health professionals, 3) screening procedures and priority populations and 4) continued treatment and care. This study recommends a unified, evidence-based approach to TB screening in migrants, with free access to diagnosis and treatment, culturally sensitive care, use of digital tools and coordinated efforts across health systems to ensure effective and equitable TB control in Europe. Thus, the experts emphasised key recommendations that strike a balance between immediate health system interventions, screening procedures and cultural inclusivity to more effectively address TB among migrants. The findings of this study offer actionable policies to address gaps and weaknesses in Europe's response to tuberculosis among migrants, advancing efforts to eliminate TB as a public health threat.

Background: Amniotic epithelial cells are fetal-derived stem cells, capable of differentiating into all three germ layers, including mature epithelial cell populations. Here, we hypothesised that the amniotic epithelium might serve as a surrogate tissue source for investigating transcriptional profiles in the respiratory epithelium of newborns.

Methods: In this study, we compared gene expression profiles and weighted gene coexpression network structure in paired amniotic and newborn nasal epithelial samples from 85 participants in the Airway Epithelium Respiratory Illnesses and Allergy (AERIAL) cohort.

Results: In total, 11 867 genes (79.7%) were commonly expressed in both amniotic and nasal epithelium, with uniquely expressed genes (2563 and 458, respectively) enriched for biological functions related to the specialist function of each tissue (e.g. developmental programs and ciliation, respectively). We observed a strong overlap in weighted gene coexpression network structure between both tissues, with 10 coexpression modules identified by consensus network analysis. Genes commonly expressed in both tissues and/or found in the consensus network modules were enriched for biologically relevant gene signatures and pathways related to airway function. We observed significant overlap in gene expression and network structure between the amniotic epithelium and published datasets of epithelial samples from lower airways and other epithelial tissues, including skin and oesophagus, suggesting a global epithelial signature.

Conclusion: We observed significant overlap in gene expression and network structure between paired amniotic and nasal epithelial samples, supporting the potential of amnion as a noninvasive and abundant tissue surrogate. Future studies investigating amnion-based biomarkers for respiratory exposures in utero and childhood disease outcomes are needed to extend these results towards clinical translation.

Sarcopenia in ILD is associated with reduced respiratory and peripheral muscle strength but does not independently exacerbate sensory or affective dyspnoea https://bit.ly/4mBtcLE.

Neutrophils in IPF patients exhibit functional distinctions, suggesting a mechanism for their recruitment into the lungs. This study underscores the need for further research into the role of neutrophils in the progression of IPF. https://bit.ly/4ldKo9b.

Background: Patients' experiences of living with pulmonary hypertension are likely to vary by geography and aetiology. The Pulmonary Hypertension Global Patient Survey (PH GPS) aims to understand patients' perspectives and experiences, to drive healthcare improvements.

Methods: PH GPS was collaboratively designed through a multidisciplinary, iterative, consensus-building process and beta-tested by patients. Themes included healthcare provision, self-monitoring and research. It was predominantly disseminated by pulmonary hypertension organisations to patients or their proxies across all pulmonary hypertension groups. Descriptive statistics provided a narrative summary of key results.

Results: Data regarding 3329 adult (mean age 52.2 years; 81.7% female) and 135 paediatric patients were analysed, with this article focusing on the adult cohort. Most pulmonary arterial hypertension (PAH) patients reported diagnosis within 12 months of symptom onset. Variability was seen in survey response, pulmonary hypertension management and research participation, favouring the Global North and pulmonary hypertension groups 1 and 4. Genetic testing was reported by 33.9% (401 out of 1183) of patients, where eligible. 58% were experienced in self-monitoring their health. 20.6% of patients with pulmonary hypertension have completed patient-reported outcome measures (PROMs), with 7% feeling they changed management. 19.1% of adult patients have participated in research; however, 72.2% who have not participated would be willing to do so if invited.

Discussion: PH GPS is the largest survey of its kind in the pulmonary hypertension field, representing a globally collaborative endeavour. It highlights achievements such as efficient PAH diagnostic time frames. Shortcomings include underappreciating quality of life reported via PROMs. The Global South and pulmonary hypertension groups 2 and 3 were relatively underrepresented. Encouragingly, patients' experiences of navigating healthcare were often positive, as demonstrated by a willingness to participate in research and being empowered to take charge of their health: findings which cross geographical divides.

Background: COPD and cardiovascular disease (CVD) are leading causes of death with overlapping and syndemic pathophysiological interactions. Inhaled triple therapies containing inhaled corticosteroids (ICS), long-acting muscarinic antagonists (LAMA) and long-acting β₂-agonists (LABA) reduce COPD exacerbation rates and improve lung function versus dual LAMA/LABA therapy. The effect of inhaled triple therapies on combined cardiac and pulmonary (i.e., cardiopulmonary) events in people with COPD and elevated cardiopulmonary risk has not been prospectively tested in randomised clinical trials.

Methods: THARROS is a multinational, event-driven cardiopulmonary outcomes trial evaluating budesonide/glycopyrronium/formoterol fumarate dihydrate (BGF) triple therapy versus glycopyrronium/formoterol fumarate dihydrate dual therapy in patients with COPD and elevated cardiopulmonary risk not using ICS-containing maintenance therapy. Eligibility requirements include symptomatic COPD (COPD Assessment Test scores ≥10) without a requirement for prior COPD exacerbations, blood eosinophils ≥100 cells·mm^-3, established CVD or CVD risk based on clinical characteristics, clinical risk scores or imaging-based risk criteria. The composite primary end-point is time to first severe cardiac or COPD event and includes three event types, including severe cardiac events (heart failure acute healthcare visit/hospitalisation, myocardial infarction hospitalisation), severe COPD exacerbations and cardiopulmonary death. Approximately 5000 patients will be randomised to achieve 632 participants with ≥1 primary severe adjudicated cardiopulmonary event.

Conclusion: This first-of-its-kind cardiopulmonary outcomes trial will determine the effect of BGF on a novel composite end-point comprising severe cardiopulmonary events in a broad COPD population with elevated cardiopulmonary risk not currently using ICS-containing maintenance therapy.

Azithromycin has already demonstrated promise in both the prophylaxis and therapy of CLAD, thereby warranting further comprehensive investigations into its dual effect in this evolving era https://bit.ly/45Y4FLw.