Early career member highlights from the 22nd ERS Lung Science Conference: development of chronic lung diseases - from life-spanning mechanisms to preventive therapy.

https://bit.ly/4cbMjpS.

Considerations for building and using integrated single-cell atlases.

The rapid adoption of single-cell technologies has created an opportunity to build single-cell 'atlases' integrating diverse datasets across many laboratories. Such atlases can serve as a reference for analyzing and interpreting current and future data. However, it has become apparent that atlasing approaches differ, and the impact of these differences are often unclear.

Optical Control of TRPM8 Channels with Photoswitchable Menthol.

Transient receptor potential melastatin 8 (TRPM8) channels are well known as sensors for cold temperatures and cooling agents such as menthol and icilin and these channels are tightly regulated by the membrane lipid phosphoinositol-4,5-bisphosphate (PIP). Since TRPM8 channels emerged as promising drug targets for treating pain, itching, obesity, cancer, dry eye disease, and inflammation, we aimed at developing a high-precision TRPM8 channel activator, to achieve spatiotemporal control of TRPM8 activity with light. In this study, we designed, synthesized and characterized the first photoswitchable TRPM8 activator azo-menthol (AzoM).

The more stars, the brighter! Interview with the ECM award winner 2023.

https://bit.ly/4f0AiVY.

Heterogeneity-driven phenotypic plasticity and treatment response in branched-organoid models of pancreatic ductal adenocarcinoma.

In patients with pancreatic ductal adenocarcinoma (PDAC), intratumoural and intertumoural heterogeneity increases chemoresistance and mortality rates. However, such morphological and phenotypic diversities are not typically captured by organoid models of PDAC. Here we show that branched organoids embedded in collagen gels can recapitulate the phenotypic landscape seen in murine and human PDAC, that the pronounced molecular and morphological intratumoural and intertumoural heterogeneity of organoids is governed by defined transcriptional programmes (notably, epithelial-to-mesenchymal plasticity), and that different organoid phenotypes represent distinct tumour-cell states with unique biological features in vivo.

Unravelling the Information Contained in the Single Items of the COPD Assessment Test for Different Outcomes and Smoking Status in Patients with COPD: Results from COSYCONET.

Background: The COPD Assessment Test (CAT) comprises eight questions. We evaluated the information that each of the questions and the total score contributed to outcomes and characteristics of chronic obstructive lung disease (COPD), including their dependence on smoking status.

Methods: Patients with COPD of the COSYCONET cohort with Global Initiative for Chronic Obstructive Lung Disease (GOLD) grades 1-4 and the former grade 0 were included.

Association of Patients' Knowledge on the Disease and Its Management with Indicators of Disease Severity and Individual Characteristics in Patients with Chronic Obstructive Pulmonary Disease (COPD): Results from COSYCONET 2.

Background: In patients with chronic diseases, including those with chronic obstructive pulmonary disease (COPD), knowledge on the disease and its self-management is considered as relevant for improving disease control and long-term outcome. We studied to which extent components of knowledge depended on potential predictors, such as participation in educational programs and disease severity. For example, the perception of exacerbations or GOLD grade might modulate the content and reliability of COPD understanding.

European Respiratory Society Research Seminar on Preventing Pediatric Asthma.

This report is a summary of the presentations given at the European Respiratory Society's Research Seminar on Asthma Prevention. The seminar reviewed both epidemiological and mechanistic studies and concluded that; (i) reducing exposure of pregnant women and children to air pollution will reduce incident asthma, (ii) there are promising data that both fish oil and a component of raw cow's milk prevent asthma, and (iii) modulating trained immunity by either mimicking helminth infection or oral and sublingual bacterial products is a promising area of research.

Persistence of spike protein at the skull-meninges-brain axis may contribute to the neurological sequelae of COVID-19.

SARS-CoV-2 infection is associated with long-lasting neurological symptoms, although the underlying mechanisms remain unclear. Using optical clearing and imaging, we observed the accumulation of SARS-CoV-2 spike protein in the skull-meninges-brain axis of human COVID-19 patients, persisting long after viral clearance. Further, biomarkers of neurodegeneration were elevated in the cerebrospinal fluid from long COVID patients, and proteomic analysis of human skull, meninges, and brain samples revealed dysregulated inflammatory pathways and neurodegeneration-associated changes.

LungVis 1.0: an automatic AI-powered 3D imaging ecosystem unveils spatial profiling of nanoparticle delivery and acinar migration of lung macrophages.

Targeted (nano-)drug delivery is essential for treating respiratory diseases, which are often confined to distinct lung regions. However, spatio-temporal profiling of drugs or nanoparticles (NPs) and their interactions with lung macrophages remains unresolved. Here, we present LungVis 1.

Skin Markers of Premature Ageing in Patients with COPD: Results Form COSYCONET.

Chronic obstructive pulmonary disease (COPD) is commonly associated with ageing, with the prevalence and severity increasing by age. Smoking-induced premature ageing is thought to contribute to COPD, particularly lung emphysema. This study aimed to explore the relationship between lung function impairment and skin texture, as a marker of biological or premature ageing, in COPD patients.

Molecular Dynamics Simulations Elucidate the Molecular Organization of Poly(beta-amino ester) Based Polyplexes for siRNA Delivery.

Cationic polymers are known to efficiently deliver nucleic acids to target cells by encapsulating the cargo into nanoparticles. However, the molecular organization of these nanoparticles is often not fully explored. Yet, this information is crucial to understand complex particle systems and the role influencing factors play at later stages of drug development.

Importance of the neutrophil-to-lymphocyte ratio as a marker for microbiological specimens in critically ill patients after liver or lung transplantation.

Purpose: The correct and early diagnosis of an infection is pivotal for patients, especially if the patients are immunocompromised. Various infection markers are used in clinics with different advantages and disadvantages. The neutrophil-to-lymphocyte ratio (NLR) is a cost effective parameter easily obtained without further investments.

Proposal of a radiation-free screening protocol for early detection of interstitial lung involvement in seropositive and ACPA-positive rheumatoid arthritis.

Background: Seropositive rheumatoid arthritis (RA) is associated with significant cardiovascular and pulmonary morbidity. However, screening for early detection of pulmonary involvement especially interstitial lung disease (ILD) is not established in RA.

Methods: We propose a non-invasive radiation-free approach to screen for interstitial lung involvement (ILI) by means of pulmonary function tests (PFT) and pleuro-pulmonary transthoracic ultrasound (LUS) with additional cardiopulmonary exercise tests (CPET) with ECG, and echocardiography.

Therapeutic drug monitoring of elexacaftor, tezacaftor, and ivacaftor before, during, and after pregnancy in women with cystic fibrosis: An observational study.

Background: Elexacaftor/tezacaftor/ivacaftor (ETI) has improved health and increased life expectancy in many patients with cystic fibrosis (pwCF). Family planning issues have become more important since then. Many women decide to remain on modulator therapy during pregnancy despite insufficient evidence-based recommendations for continuing ETI during pregnancy and lactation.

Probe set selection for targeted spatial transcriptomics.

Targeted spatial transcriptomic methods capture the topology of cell types and states in tissues at single-cell and subcellular resolution by measuring the expression of a predefined set of genes. The selection of an optimal set of probed genes is crucial for capturing the spatial signals present in a tissue. This requires selecting the most informative, yet minimal, set of genes to profile (gene set selection) for which it is possible to build probes (probe design).

Simultaneous Occurrence of Mutations in Mutant NSCLC: Case Reports.

mutation and amplification have been identified as distinct molecular targets in lung cancer with different therapeutic and prognostic values. The coexistence of and mutations is extremely rare, and therefore, no data exist on the best treatment in these cases.

Novel immunotherapeutic approaches in lung cancer: driving beyond programmed death-1/programmed death ligand-1 and cytotoxic T-lymphocyte-associated Protein-4.

Purpose Of Review: In this review, our aim is to highlight the latest novel immunotherapeutic approaches for advanced nonsmall cell lung cancer (NSCLC) beyond anti-programmed death-1 (PD-1)/programmed death ligand-1 (PD-L1) and anti- cytotoxic T-lymphocyte-associated Protein-4 (CTLA4).

Recent Findings: Immune checkpoint inhibitors (ICIs) revolutionized the treatment of advanced NSCLC. Despite that, patients develop primary or acquired resistance to ICIs.

[Management of adult bronchiectasis - Consensus-based Guidelines for the German Respiratory Society (DGP) e. V. (AWMF registration number 020-030)].

Bronchiectasis is an etiologically heterogeneous, chronic, and often progressive respiratory disease characterized by irreversible bronchial dilation. It is frequently associated with significant symptom burden, multiple complications, and reduced quality of life. For several years, there has been a marked global increase in the prevalence of bronchiectasis, which is linked to a substantial economic burden on healthcare systems.

Expression Profiling Identified TRPM7 and HER2 as Potential Targets for the Combined Treatment of Cancer Cells.

TRPM7 is a divalent cation-permeable channel that is highly active in cancer cells. The pharmacological inhibitors of TRPM7 have been shown to suppress the proliferation of tumor cells, highlighting TRPM7 as a new anticancer drug target. However, the potential benefit of combining TRPM7 inhibitors with conventional anticancer therapies remains unexplored.