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Oxidative stress driven by several environmental and local airway factors associated with chronic obstructive bronchiolitis, a hallmark feature of COPD, plays a crucial role in disease pathomechanisms. Unbalance between oxidants and antioxidant defense mechanisms amplifies the local inflammatory processes, worsens cardiovascular health, and contributes to COPD-related cardiovascular dysfunctions and mortality. The current review summarizes recent developments in our understanding of different mechanisms contributing to oxidative stress and its countermeasures, with special attention to those that link local and systemic processes. Major regulatory mechanisms orchestrating these pathways are also introduced, with some suggestions for further research in the field.

The complement system is a key link between innate and adaptive immunity, contributing to pathogen elimination, immune regulation, and tissue homeostasis. Its activation is not only crucial in infections, such as COVID-19, but also plays a major role in the pathomechanism of several non-infectious respiratory diseases, such as asthma, COPD, sarcoidosis and lung cancer. Complement components can modulate the quality of the adaptive immune responses, including through the regulation of T2 immunity and eosinophilic inflammation, thereby linking natural defense to complex immune processes. In recent years, it has become increasingly clear that dysregulated complement activity contributes to inflammation, thrombosis and tissue damage in a wide range of respiratory diseases. The study of the various components of this cascade system may therefore be promising from both a diagnostic and therapeutic point of view. Some of its components may serve as biomarkers for distinguishing between different phenotypes of certain lung diseases, while their targeted inhibition or modulation may open the way towards new treatment options. A better understanding of the complement system's integrative and regulatory role not only allows for a deeper insight into immunological interactions but may also bring us closer to phenotype-oriented, immunology-based pulmonology, which may have real clinical benefits in the future.

The important roles of bacterial outer membrane vesicles (OMVs) in various diseases and their emergence as a promising platform for vaccine development and targeted drug delivery necessitates the development of imaging techniques suitable for quantifying their biodistribution with high precision. To address this requirement, we aimed to develop an OMV specific radiolabeling technique for positron emission tomography (PET). A novel bacterial strain ( E. coli BL21(DE3) ΔnlpI, ΔlpxM ) was created for efficient OMV production, and OMVs were characterized using various methods. SpyCatcher was anchored to the OMV outer membrane using autotransporter-based surface display systems. Synthetic SpyTag-NODAGA conjugates were tested for OMV surface binding and 64 Cu labeling efficiency. The final labeling protocol shows a radiochemical purity of 100% with a ~ 29% radiolabeling efficiency and excellent serum stability. The in vivo biodistribution of OMVs labeled with 64 Cu was determined in mice using PET/MRI imaging which revealed that the biodistribution of radiolabeled OMVs in mice is characteristic of previously reported data with the highest organ uptakes corresponding to the liver and spleen 3, 6, and 12 h following intravenous administration. This novel method can serve as a basis for a general OMV radiolabeling scheme and could be used in vaccine- and drug-carrier development based on bioengineered OMVs.

The vast majority of hormone positive and HER2 negative advanced breast cancers can be controlled well by endocrine therapy combined with the groundbreaking use of CDK4/6 inhibitors in the metastatic first-line setting. Approximately 50%–60% of these patients have “bone-only” metastatic disease. In oligometastatic cases or if a certain number of uncontrolled lesions develop during the aforementioned therapy, ablative radiotherapy can be delivered or, in symptomatic cases, urgent irradiation is needed with palliative intent. To achieve the most effective results, parallel with good quality of life, the timing of radiotherapy must be determined precisely, taking into account that different cell cycles are involved during different treatment modalities; therefore, optimization of treatment schedules ensures longer and safer post-progression overall survival. The key question is whether the two treatment modalities are safe concurrently or whether they should be administered separately, and if so, what is the optimal sequence and why? This manuscript aims to answer this important question, with a focus on quality of life. Existing publications focus on safety and toxicity profiles, and efficacy is detailed only tangentially and minimally.

The aim of this study was to develop and characterize a Prussian Blue based biocompatible and chemically stable T1 magnetic resonance imaging (MRI) contrast agent with near infrared (NIR) optical contrast for preclinical application. The physical properties of the Prussian blue nanoparticles (PBNPs) (iron (II); iron (III);octadecacyanide) were characterized with dynamic light scattering (DLS), zeta potential measurement, atomic force microscopy (AFM), and transmission electron microscopy (TEM). In vitro contrast enhancement properties of PBNPs were determined by MRI. In vivo T1-weighted contrast of the prepared PBNPs was investigated by MRI and optical imaging modality after intravenous administration into NMRI-Foxn1 nu/nu mice. The biodistribution studies showed the presence of PBNPs predominantly in the cardiovascular system. Briefly, in this paper we show a novel approach for the synthesis of PBNPs with enhanced iron content for T1 MRI contrast. This newly synthetized PBNP platform could lead to a new diagnostic agent, replacing the currently used Gadolinium based substances.

Electrophysiology provides a direct readout of neuronal activity at a temporal precision only limited by the sampling rate. However, interrogating deep brain structures, implanting multiple targets or aiming at unusual angles still poses significant challenges for operators, and errors are only discovered by post-hoc histological reconstruction. Here, we propose a method combining the high-resolution information about bone landmarks provided by micro-CT scanning with the soft tissue contrast of the MRI, which allowed us to precisely localize electrodes and optic fibers in mice in vivo. This enables arbitrating the success of implantation directly after surgery with a precision comparable to gold standard histology. Adjustment of the recording depth with micro-drives or early termination of unsuccessful experiments saves many working hours, and fast 3-dimensional feedback helps surgeons avoid systematic errors. Increased aiming precision enables more precise targeting of small or deep brain nuclei and multiple targeting of specific cortical or hippocampal layers. Király et al. propose a method combining micro-CT and MRI imaging to precisely localize electrodes and optic fibers in the mouse brain in vivo. This allows assessing the success of targeting after surgery, depth adjustment of movable probes and identifying systematic errors in the surgical process.

Cerenkov luminescence imaging (CLI) is a promising approach to image-guided surgery and pathological sampling. It could offer additional advantages when combined to whole-body isotope tomographies. We aimed to obtain evidence of its applicability in lymphoma patho-diagnostics, thus we decided to investigate the radiodiagnostic potential of combined PET or SPECT/CLI in an experimental, novel spontaneous high-grade B-cell lymphoma mouse model (Bc.DLFL1). We monitored the lymphoma dissemination at early stage, and at clinically relevant stages such as advanced stage and terminal stage with in vivo 2-deoxy-2-[ 18 F]fluoro- d -glucose (FDG) positron emission tomography (PET)/magnetic resonance imaging (MRI) and 67 Ga-citrate single photon emission computed tomography (SPECT)/MRI. In vivo imaging was combined with ex vivo high resolution CLI. The use of CLI with 18 F-Fluorine (F-18) and 67 Ga-Gallium isotopes in the selection of infiltrated lymph nodes for tumor staging and pathology was thus tested. At advanced stage, FDG PET/MRI plus ex vivo CLI allowed accurate detection of FDG accumulation in lymphoma-infiltrated tissues. At terminal stage we detected tumorous lymph nodes with SPECT/MRI and we could report in vivo detection of the Cerenkov light emission of 67 Ga. CLI with 67 Ga-citrate revealed lymphoma accumulation in distant lymph node locations, unnoticeable with only MRI. Flow cytometry and immunohistochemistry confirmed these imaging results. Our study promotes the combined use of PET and CLI in preclinical studies and clinical practice. Heterogeneous FDG distribution in lymph nodes, detected at sampling surgery, has implications for tissue pathology processing and it could direct therapy. The results with 67 Ga also point to the opportunities to further apply suitable SPECT radiopharmaceuticals for CLI.

The Strengthening the Screening of Lung Cancer in Europe (SOLACE) initiative, supported by Europe’s Beating Cancer Plan, is dedicated to advancing lung cancer screening. This initiative brings together the most extensive pan-European network of respiratory and radiology experts, involving 37 partners from 15 countries. SOLACE aims to enhance equitable access to lung cancer screening by developing targeted recruitment strategies for underrepresented and high-risk populations. Through comprehensive work packages, SOLACE integrates scientific research, pilot studies, and sustainability efforts to bolster regional and national screening efforts across EU member states.Critical relevance statementThe SOLACE project aims to facilitate the optimization and implementation of equitable lung cancer screening programs across the heterogeneous healthcare landscape in EU member states.Key PointsThe effectiveness of lung cancer screening is supported by both scientific evidence and now increasing legislative support.SOLACE aims to develop, test, and disseminate tools to facilitate the realization of lung cancer screening at both a national and regional level.Previously underrepresented populations in lung cancer screening will be targeted by tailored recruitment strategies.SOLACE forms the first pan-European network of experts poised to drive real-world implementation of lung cancer screening.

Randomized controlled trials (RCTs) are essential for the approval of new therapies; however, because of their design, they provide little insight concerning disease epidemiology/etiology and current clinical practice. Particularly, in lung disease, rigid inclusion/exclusion criteria can limit the generalizability of pivotal trial data. Noninterventional studies (NIS), conducted through the well-established mechanism of patient registries, are undervalued as a means to close data gaps left by RCTs by providing essential data that can guide patient care at different levels from clinical decision-making to health-care policy. While NIS contribute valuable data in all disease areas, their importance in rare diseases cannot be underestimated. In respiratory disease, registries have been essential in understanding the natural history and different phenotypes of rare conditions, such as alpha 1 antitrypsin deficiency, cystic fibrosis, and idiopathic pulmonary fibrosis. Importantly, additional therapeutic outcome data were generated. While measures for enhancing data quality in RCTs have evolved significantly, the approach and effectiveness of registries is variable. Within this article, we review the contribution of registries to pulmonary disease and make recommendations for their effective management. Additionally, we assess limitations of registry data as well as challenges to registry operation, including the impact of the European Union General Data Protection Regulation.

Cancers, chronic diseases and respiratory infections are major causes of mortality and present diagnostic and therapeutic challenges for health care. There is an unmet medical need for non-invasive, easy-to-use biomarkers for the early diagnosis, phenotyping, predicting and monitoring of the therapeutic responses of these disorders. Exhaled breath sampling is an attractive choice that has gained attention in recent years. Exhaled nitric oxide measurement used as a predictive biomarker of the response to anti-eosinophil therapy in severe asthma has paved the way for other exhaled breath biomarkers. Advances in laser and nanosensor technologies and spectrometry together with widespread use of algorithms and artificial intelligence have facilitated research on volatile organic compounds and artificial olfaction systems to develop new exhaled biomarkers. We aim to provide an overview of the recent advances in and challenges of exhaled biomarker measurements with an emphasis on the applicability of their measurement as a non-invasive, point-of-care diagnostic and monitoring tool.