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Introduction and ObjectivesMyeloid-derived suppressor cells (MDSCs) are immature cells with immunosuppressive properties, divided into polymorphonuclear (PMN-) and monocytic (M-) subpopulations. Based on a limited number of disease-specific studies, they appear to be involved in a wide spectrum of lung diseases. We aimed to standardise a simple measuring protocol of MDSCs in the lungs and the systemic circulation and to comparatively investigate their differences among distinct lung diseases.MethodsIn 16 patients with lung diseases, MDSCs were measured in peripheral blood (PB) and bronchoalveolar lavage (BAL) via flow cytometry and immunophenotypically defined as CD45+CD3−CD19−CD20−CD56−CD16−HLA-DR−CD33+CD11b+CD15+Lox-1+ PMN-MDSCs and CD45+CD3−CD19−CD20−CD56−CD16−HLA-DR−CD33+CD11b+CD14+ M-MDSCs, as shown in figure 1a. Total MDSCs were calculated as the sum of the two subpopulations. Their suppressive character was confirmed via T-cell suppression assay. BAL cell populations were also defined. Further clinical and laboratory data were collected, including diagnosis, stage of disease, findings from microbiological, cytological, and histological examinations, disease course, and end outcomes. The data were analysed with the non-parametric Wilcoxon signed ranks test for paired samples and the Kruskal-Wallis test for comparison between multiple groups.ResultsOur study population included 4 patients with bronchiectasis, 6 patients with lung cancer, and 6 patients with interstitial lung diseases (ILD). MDSCs from all study subgroups showed normal capacity to suppress T cells. All MDSC subsets, including total MDSCs, M-MDSCs, and PMN-MDSCs, were statistically significantly increased in BAL compared to PB, as depicted in figure 1b, indicating the lung accumulation of these cells (p-value: <0.05 in all disease groups). Interestingly, total MDSCs in the BAL were statistically significantly differentiated between the three patient groups, as depicted in figure 1c, with the group of patients with ILD presenting the higher counts (p-value: 0.001).Abstract P251 Figure 1[Image Omitted. See PDF.]ConclusionsOur preliminary data show for the first time that MDSCs could potentially be used as differential diagnostic biomarkers in lung diseases. Additional data are needed to develop disease- and sample-specific reference values of MDSCs and further investigate their quantitative alterations in different entities.

Introduction and ObjectivesMyeloid-derived suppressor cells (MDSCs) are immature cells of the myeloid lineage with immunosuppressive properties, divided into polymorphonuclear and monocytic subpopulations, and are commonly involved in chronic inflammatory diseases. We aimed to systematically review the literature to assess the quantitative and qualitative alterations of MDSCs and their involvement in allergic airway diseases, i.e. asthma and allergic rhinitis.MethodsThe systematic review protocol was registered in PROSPERO, and the PRISMA guidelines for systematic reviews were followed. The databases MEDLINE via PubMed, Embase, and Scopus were systematically searched for original research studies involving the measurement of human MDSCs in allergic airway diseases by the end of 2024. A narrative synthesis of the extracted data from the included studies was performed.ResultsAmong a total of 429 records screened, 8 studies were considered eligible to be included in the review. The studies were run from 2011 to 2021 and cumulatively included 212 patients with asthma and 90 patients with allergic rhinitis. Healthy controls (cumulatively 203) were included in 7 studies, while 4 studies also included patients with other respiratory diseases for comparison, i.e. chronic obstructive pulmonary disease (35 patients), pneumonia (65 patients), and respiratory viral infections (27 patients). Out of 6 studies about asthma, MDSC counts were found either increased or increasing after allergen challenge in bronchoalveolar lavage (2 studies) and in peripheral blood mononuclear cells (3 studies), while the monocytic MDSC subpopulation was found downregulated in isolated white blood cells in only 1 study. The 2 studies about allergic rhinitis used diverse experimental set-ups and were not comparable.ConclusionsIncreased counts of MDSCs are mostly found in asthma, pointing towards the role of these immunomodulatory cells in its pathogenesis, despite the heterogeneity of the methodology among the different studies. Further research and harmonisation of the markers and techniques for the identification of MDSCs is needed, as they may be used as novel biomarkers and therapeutic targets in these disease entities.

Gender wage gap is a socio economic reality still exists not only in European but also in international labour market which affects all relative stakeholders' efforts for social cohesion, socio economic innovations, integrity and solidarity economy despite discriminations and disparities. Closing the gender pay gap gives greater profitability to the economy as a whole. This complex phenomenon requires a multifaceted approach to address various kinds of inequalities between men and women in the labour market. Women always have been key actors in employment and economic growth and their skills and talent are necessary for the economic and social development of our societies. However, this is not reflected in their wages and position in the labour market. The underestimation of women's work and the undervaluation of women's skills is a lost advantage for the economy and for society at large. This paper studies the case of Cyprus by estimating the factors cause gender wage gap and glass ceiling effect through analysing micro data from 2010 Earnings Survey. We estimate pooled quantile regressions with gender dummies, as well as separate quantile regressions by gender, and we carry out a decomposition analysis by applying the Oaxaca-Blinder decomposition technique. Even after extensive controls for gender differences in age, education (both level and field), sector, industry, and occupation, we find that the glass ceiling effect we see in the raw data persists to a considerable extent. Measures and policy proposals are represented for closing the gender pay gap in order to add value and contribute to the development of a more equal and cohesive society which could entrench a social, solid and sustainable economy.

Background Specialized clinical care for cystic fibrosis (CF) in Cyprus, a small island country, has been implemented since the 1990s. However, only recently, a national CF patient registry has been established for the systematic recording of patients’ data. In this study, we aim to present data on the epidemiological, genotypic and phenotypic features of CF patients in the country from the most recent data collection in 2019, with particular emphasis on notable rare or unique cases. Results Overall, data from 52 patients are presented, 5 of whom have deceased and 13 have been lost to follow-up in previous years. The mean age at diagnosis was 7.2 ± 12.3 years, and the mean age of 34 alive patients by the end of 2019 was 22.6 ± 13.2 years. Patients most commonly presented at diagnosis with acute or persistent respiratory symptoms (46.2%), failure to thrive or malnutrition (40.4%), and dehydration or electrolyte imbalance (32.7%). Sweat chloride levels were diagnostic (above 60 mmol/L) in 81.8% of examined patients. The most common identified mutation was p.Phe508del (F508del) (45.2%), followed by p.Leu346Pro (L346P) (6.7%), a mutation detected solely in individuals of Cypriot descent. The mean BMI and FEV 1 z-scores were 0.2 ± 1.3 and − 2.1 ± 1.7 across all age groups, respectively, whereas chronic Pseudomonas aeruginosa colonization was noted in 26.9% of patients. The majority of patients (74.5%) were eligible to receive at least one of the available CFTR modulator therapies. In 25% of patients we recovered rare or unique genotypic profiles, including the endemic p.Leu346Pro (L346P), the rare CFTR-dup2, the co-segregated c.4200_4201delTG/c.489 + 3A > G, and the polymorphism p.Ser877Ala. Conclusions CF patient registries are particularly important in small or isolated populations, such as in Cyprus, with rare or unique disease cases. Their operation is necessary for the optimization of clinical care provided to CF patients, enabling their majority to benefit from evolving advances in precision medicine.

Background Colistin is recommended in the empirical treatment of ventilator-associated pneumonia (VAP) with a high prevalence of carbapenem-resistant gram-negative bacilli (CR-GNB). However, the efficacy and safety of colistin are not well defined. Methods A multicenter prospective randomized trial conducted in 32 European centers compared the efficacy and safety of colistin (4.5 million unit loading dose followed by a maintenance dose of 3 million units every 8 h) versus meropenem (2 g every 8 h), both in combination with levofloxacin (500 mg every 12 h) for 7–14 days in patients with late VAP. Between May 2012 and October 2015, 232 patients were randomly assigned to the 2 treatment groups. The primary endpoint was mortality at 28 days after randomization in the microbiologically modified intention-to-treat (mMITT) population. Secondary outcomes included clinical and microbiological cure, renal function at the end of the treatment, and serious adverse events. The study was interrupted after the interim analysis due to excessive nephrotoxicity in the colistin group; therefore, the sample size was not achieved. Results A total of 157 (67.7%) patients were included in the mMITT population, 36 of whom (22.9%) had VAP caused by CR-GNB. In the mMITT population, no significant difference in mortality between the colistin group (19/82, 23.2%) and the meropenem group (19/75, 25.3%) was observed, with a risk difference of − 2.16 (− 15.59 to 11.26, p  = 0.377); the noninferiority of colistin was not demonstrated due to early termination and limited number of patients infected by carbapenem-resistant pathogens. Colistin plus levofloxacin increased the incidence of renal failure (40/120, 33.3%, versus 21/112, 18.8%; p  = 0.012) and renal replacement therapy (11/120, 9.1%, versus 2/112, 1.8%; p  = 0.015). Conclusions This study did not demonstrate the noninferiority of colistin compared with meropenem, both combined with levofloxacin, in terms of efficacy in the empirical treatment of late VAP but demonstrated the greater nephrotoxicity of colistin. These findings do not support the empirical use of colistin for the treatment of late VAP due to early termination. Trial registration ClinicalTrials.gov, NCT01292031 . Registered 9 February 2011.

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.

The high variety of mutations found in the Cystic Fibrosis Transmembrane Regulator (CFTR) gene is responsible for the clinical heterogeneity observed in people with Cystic Fibrosis (CF) and the atypical manifestations in CFTR-related disorders (CFTR-RD). The intronic c.489+3A>G (c.621+3A>G) variant has been reported to have questionable pathogenicity, although its alleged severity was probably due to its co-segregation in cis with another undetected mutation, as previously reported from countries in the Mediterranean region. In the island of Cyprus, several rare CFTR variants have been previously identified, among them the c.489+3A>G in co-segregation with the pathogenic p.Cys1400Ter (cDNA name = c.4200₄201del or legacy name = 4332delTG) mutation. We aimed to investigate the prevalence of these variants in Cyprus and describe their clinical impact in patients and carriers. The intronic variant c.489+3A>G has been so far identified to co-segregate with the pathogenic p.Cys1400Ter mutation in the same allele in six unrelated Cypriot families and in total of 20 subjects. Three of them were diagnosed with CF, presenting with persistent respiratory symptoms, pancreatic insufficiency and a second CF-causing mutation. Two were diagnosed with CFTR-RD, presenting with bronchiectasis, intermediate sweat test and a second mutation known to cause CFTR-RD. Also, four carriers had a high suspicion of CFTR-RD, with bronchiectasis or emphysema and intermediate sweat test, although due to the lack of another CFTR mutation and a second functional test, definite diagnosis has not been made. Haplotype analysis provided evidence of a common haplotype in all individuals with co-segregation of the c.489+3A>G variant with p.Cys1400Ter mutation. The intronic c.489+3A>G variant co-segregates extensively with p.Cys1400Ter in Cyprus as an ancestral combination due to a possible founder effect. Before providing genetic counselling to subjects identified through population screening to harbour the c.489+3A>G variant, extensive analysis of CFTR including gene rearrangements should be performed to identify possible other mutations in cis, especially in Mediterranean countries where this complex allele is probably common. Further research is warranted to fully delineate the clinical implications of the in cis co-segregation of p.Cys1400Ter with c.489+3A>G, even in the absence of pathogenic variants in the other CFTR allele.

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.

Sarcoidosis is a heterogeneous granulomatous disease of unknown aetiology, characterised by a highly variable clinical behaviour. While some patients experience a self‑limited course, others develop chronic and relapsing disease. At present, no precise phenotyping strategy exists in clinical practice to reliably predict which patients will progress to chronicity. The aim of this study was to identify distinct phenotypic clusters sharing common clinical characteristics and to evaluate the predictive value of these clusters for disease outcomes. This is a retrospective, single-center study. Histologically confirmed sarcoidosis patients (  = 68), diagnosed between January 2022 and December 2023 at the 5th Pulmonary Medicine Department of SOTIRIA Chest Diseases Hospital of Athens, were included. All patients had >2 years of follow-up. Multiple correspondence analysis (MCA) followed by hierarchical clustering on principal components (HCPC) was performed to identify phenotypic clusters. Logistic regression was performed to identify the prognostic factors of chronicity. A total of 68 consecutive patients with sarcoidosis were included in the study. The mean age at diagnosis was 57.6 ± 11.1 years, with the majority being females (61.8%). Thoracic involvement, including either intrathoracic lymph nodes and/or the lungs, was the most frequently detected. Overall, fatigue, cough, and arthralgia were among the most frequently reported symptoms. Two phenotypic clusters were identified, including 63 (92.6%) and 5 (7.4%) patients. Cluster 1 was characterised by minimal extrapulmonary involvement, whereas Cluster 2 showed a higher frequency of multi-organ disease, including liver (80%), musculoskeletal (75%), spleen (67%), cardiac (50%) and skin (43%) involvement. Cluster stability was moderate to weak. The clustering phenotype was not associated with chronicity. However, involvement of lymph nodes only was associated with reduced odds of chronicity (OR 0.17, 95% CI 0.02-0.69), while arthritis was strongly associated with increased chronicity risk (OR 17.02, 95% CI 2.04-471.07). Exploratory 3-cluster analysis suggested a potential arthritis-predominant phenotype, although of low stability. Two distinct phenotypes in sarcoidosis are identified by using cluster analysis. In a sensitivity analysis that allowed for three clusters, a third cluster, characterised by the presence of arthritis and predominant eye and skin involvement, emerged. Interestingly, the presence of lone intrathoracic or extrathoracic lymphadenopathy appears to be significantly protective against chronicity.

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.