The importance of translational science within the respiratory field.

The Translational Science Working Group at the European Respiratory Society (ERS) aims to bridge the gap between basic and clinical science by providing a platform where scientists, clinicians and experts in the respiratory field can actively shape translational research. For the 2023 Congress, dedicated translational science sessions were created and sessions of interest to many assemblies from the clinical and the scientific point of view were tagged as translational sessions, attracting clinical and scientific experts to the same room to discuss relevant topics and strengthening translational efforts among all ERS assemblies.

Reversibility of the Enlargement of the Pulmonary Artery in COVID-19 Pneumonia as a Marker of Remission of the Disease.

Coronavirus disease 2019 (COVID-19) pneumonia is associated with extensive pulmonary microangiopathy and the enlargement of the pulmonary artery (PA), while its progression after the remission of the disease has not been investigated yet. The aim was to assess the diametral increase in the PA in COVID-19 pneumonia, as revealed on chest computed tomography (CT), and further investigate its progression. This was a retrospective cohort study of patients with COVID-19 pneumonia, without prior history of pulmonary hypertension, who underwent CT pulmonary angiography before, during, and after the infection. Pulmonary embolism was excluded in all cases. The main PA diameter (MPAD) was assessed in consecutive chest imaging. Statistical analysis was performed with the non-parametric Wilcoxon and Kruskal-Wallis tests, while correlations were performed with the non-parametric Spearman test. A mean ± SD MPAD of 3.1 ± 0.3 cm in COVID-19 pneumonia was significantly decreased to 2.8 ± 0.3 cm in the post-infectious state after 2-18 months in 31 patients (p-value: <0.0001). In a subgroup of six patients with more than one post-COVID-19 CT, a significant further decline in the diameter was observed (p-value: 0.0313). On the other hand, in accordance with the literature, a significant increase in the MPAD during COVID-19 pneumonia was noted in a group of 10 patients with a pre-COVID-19 CT (p-value: 0.0371). The enlargement of the PA is a common finding in COVID-19 pneumonia that regresses after the remission of the disease, indicating that this reversible cardiovascular event is a potential marker of disease activity, while its course in long COVID is yet to be determined.

Immunomodulatory actions of myeloid-derived suppressor cells in the context of innate immunity.

Myeloid-derived suppressor cells (MDSCs) are notable innate immune cells, which are further divided into two subpopulations, i.e., monocytic and granulocytic. These cells are traditionally considered to mainly suppress the T-cell responses. However, more updated data indicate that their properties are rather immunomodulatory than solely immunosuppressive. Indeed, MDSCs display extensive crosstalk with other either innate or adaptive immune cells, and, according to the situation under which they are triggered, they may enhance or attenuate the immune response. However, their positive role in host's defense mechanisms under specific conditions is rarely discussed in the literature. In this mini-review, the authors briefly summarise the mechanisms of action of MDSCs under distinct conditions, such as infections and malignancies, with a particular emphasis on their role as components of the innate immunity system.

Molecular and Genetic Biomarkers in Idiopathic Pulmonary Fibrosis: Where Are We Now?

Idiopathic pulmonary fibrosis (IPF) represents a chronic progressive fibrotic interstitial lung disease of unknown cause with an ominous prognosis. It remains an unprecedent clinical challenge due to its delayed diagnosis and unpredictable clinical course. The need for accurate diagnostic, prognostic and predisposition biomarkers in everyday clinical practice becomes more necessary than ever to ensure prompt diagnoses and early treatment. The identification of such blood biomarkers may also unravel novel drug targets against IPF development and progression. So far, the role of diverse blood biomarkers, implicated in various pathogenetic pathways, such as in fibrogenesis (S100A4), extracellular matrix remodelling (YKL-40, MMP-7, ICAM-1, LOXL2, periostin), chemotaxis (CCL-18, IL-8), epithelial cell injury (KL-6, SP-A, SP-D), autophagy and unfolded protein response has been investigated in IPF with various results. Moreover, the recent progress in genetics in IPF allows for a better understanding of the underlying disease mechanisms. So far, the causative mutations in pulmonary fibrosis include mutations in telomere-related genes and in surfactant-related genes, markers that could act as predisposition biomarkers in IPF. The aim of this review is to provide a comprehensive overview from the bench to bedside of current knowledge and recent insights on biomarkers in IPF, and to suggest future directions for research. Large-scale studies are still needed to confirm the exact role of these biomarkers.

Association of Broad-Spectrum Antibiotic Therapy and Vitamin E Supplementation with Vitamin K Deficiency-Induced Coagulopathy: A Case Report and Narrative Review of the Literature.

Vitamin K is a lipid-soluble vitamin that is normally maintained within appropriate levels by means of dietary intake and bacterial production in the intestinal microflora. It holds a central role in coagulation homeostasis, and thus its depletion leads to hypocoagulation and haemorrhagic diathesis. The association of antibiotic therapy and vitamin E supplementation with vitamin K deficiency was previously described in animal experiments, clinical studies, and case reports. Broad-spectrum antibiotic therapy potentially leads to intestinal microflora dysbiosis and restriction of vitamin K-producing bacterial populations, resulting in decreased vitamin K levels, whereas antibiotics of the cephalosporin class with 1-N-methyl-5-thiotetrazole (NMTT) or 2-methyl-1,3,4-thiadiazole (MTD) side groups inhibit vitamin K function. Vitamin E supplementation interferes with both the bioavailability and function of vitamin K, yet its mechanisms are not fully understood. We present the case of a 45-year-old male patient, with a history of epilepsy and schizophrenia, catatonically incapacitated and immobilised, who was hospitalised in our centre for the investigation and management of aspiration pneumonia. He demonstrated a progressively worsening prolongation of international normalised ratio (INR), which was attributed to both broad-spectrum antibiotic therapy and vitamin E supplementation and was reversed upon administration of vitamin K. We highlight the need for close monitoring of coagulation parameters in patients receiving broad-spectrum antibiotic therapy, especially those with underlying malnutritive or malabsorptive conditions, and we further recommend the avoidance of NMTT- or MTD-containing antibiotics or vitamin E supplementation, unless absolutely necessary, in those patients.

New Perspectives on Myeloid-Derived Suppressor Cells and Their Emerging Role in Haematology.

Myeloid-derived suppressor cells (MDSCs) are immature cells of myeloid origin that have gained researchers' attention, as they constitute promising biomarkers and targets for novel therapeutic strategies (i.e., blockage of development, differentiation, depletion, and deactivation) in several conditions, including neoplastic, autoimmune, infective, and inflammatory diseases, as well as pregnancy, obesity, and graft rejection. They are characterised in humans by the typical immunophenotype of CD11b+CD33+HLA-DR-/low and immune-modulating properties leading to decreased T-cell proliferation, induction of T-regulatory cells (T-regs), hindering of natural killer (NK) cell functionality, and macrophage M2-polarisation. The research in the field is challenging, as there are still difficulties in defining cell-surface markers and gating strategies that uniquely identify the different populations of MDSCs, and the currently available functional assays are highly demanding. There is evidence that MDSCs display altered frequency and/or functionality and could be targeted in immune-mediated and malignant haematologic diseases, although there is a large variability of techniques and results between different laboratories. This review presents the current literature concerning MDSCs in a clinical point of view in an attempt to trigger future investigation by serving as a guide to the clinical haematologist in order to apply them in the context of precision medicine as well as the researcher in the field of experimental haematology.

Pediatric asthma symptom control during lockdown for the COVID-19 pandemic in Spring 2020: A prospective community-based study in Cyprus and Greece.

OBJECTIVES: To prospectively quantify at the community level changes in asthma symptom control and other morbidity indices, among asthmatic schoolchildren in response to coronavirus disease 2019 (COVID-19) lockdown measures. METHODS: In Spring 2019 and Spring 2020, we prospectively assessed monthly changes in pediatric asthma control test (c-ACT), asthma medication usage, infections and unscheduled visits for asthma among schoolchildren with active asthma in Cyprus and Greece. We compared asthma symptom control and other morbidity indices before and during lockdown measures, while participants' time spent at home was objectively assessed by wearable sensors. RESULTS: A total of 119 asthmatic children participated in the study during Spring 2020. Compared to a mean baseline (pre-COVID-19 lockdown) c-ACT score of 22.70, adjusted mean increases of 2.58 (95% confidence interval [CI]: 1.91, 3.26, p < 0.001) and 3.57 (95% CI: 2.88, 4.27, p < 0.001) in the 2nd and 3rd monthly assessments were observed after implementation of lockdown measures. A mean increase in c-ACT score of 0.32 (95% CI: 0.17, 0.47, p < 0.001) was noted per 10% increase in the time spent at home. Improvement was more profound in children with severe asthma, while significant reductions in infections, asthma medication usage and unscheduled visits for asthma were also observed. During Spring 2019, 39 children participated in the study in the absence of lockdown measures and no changes in c-ACT or other indices of disease severity were observed. CONCLUSIONS: Clinically meaningful improvements in asthma symptom control, among asthmatic schoolchildren were observed during the COVID-19 lockdown measures in Spring 2020. Improvements were independently associated with time spent at home and were more profound in the children with severe asthma.

Use of wearable sensors to assess compliance of asthmatic children in response to lockdown measures for the COVID-19 epidemic.

Between March and April 2020, Cyprus and Greece health authorities enforced three escalated levels of public health interventions to control the COVID-19 pandemic. We quantified compliance of 108 asthmatic schoolchildren (53 from Cyprus, 55 from Greece, mean age 9.7 years) from both countries to intervention levels, using wearable sensors to continuously track personal location and physical activity. Changes in 'fraction time spent at home' and 'total steps/day' were assessed with a mixed-effects model adjusting for confounders. We observed significant mean increases in 'fraction time spent at home' in Cyprus and Greece, during each intervention level by 41.4% and 14.3% (level 1), 48.7% and 23.1% (level 2) and 45.2% and 32.0% (level 3), respectively. Physical activity in Cyprus and Greece demonstrated significant mean decreases by - 2,531 and - 1,191 (level 1), - 3,638 and - 2,337 (level 2) and - 3,644 and - 1,961 (level 3) total steps/day, respectively. Significant independent effects of weekends and age were found on 'fraction time spent at home'. Similarly, weekends, age, humidity and gender had an independent effect on physical activity. We suggest that wearable technology provides objective, continuous, real-time location and activity data making possible to inform in a timely manner public health officials on compliance to various tiers of public health interventions during a pandemic.