Association of sleep duration and quality with immunological response after vaccination against severe acute respiratory syndrome coronavirus-2 infection.

Growing evidence suggests that sleep could affect the immunological response after vaccination. The aim of this prospective study was to investigate possible associations between regular sleep disruption and immunity response after vaccination against coronavirus disease 2019 (COVID-19). In total, 592 healthcare workers, with no previous history of COVID-19, from eight major Greek hospitals were enrolled in this study. All subjects underwent two Pfizer-BioNTech messenger ribonucleic acid (mRNA) COVID-19 vaccine BNT162b2 inoculations with an interval of 21 days between the doses. Furthermore, a questionnaire was completed 2 days after each vaccination and clinical characteristics, demographics, sleep duration, and habits were recorded. Blood samples were collected and anti-spike immunoglobulin G antibodies were measured at 20 ± 1 days after the first dose and 21 ± 2 days after the second dose. A total of 544 subjects (30% males), with median (interquartile range [IQR]) age of 46 (38-54) years and body mass index of 24·84 (22.6-28.51) kg/m2 were eligible for the study. The median (IQR) habitual duration of sleep was 6 (6-7) h/night. In all, 283 participants (52%) had a short daytime nap. In 214 (39.3%) participants the Pittsburgh Sleep Quality Index score was >5, with a higher percentage in women (74·3%, p < 0.05). Antibody levels were associated with age (r = -0.178, p < 0.001), poor sleep quality (r = -0.094, p < 0.05), insomnia (r = -0.098, p < 0.05), and nap frequency per week (r = -0.098, p < 0.05), but after adjusting for confounders, only insomnia, gender, and age were independent determinants of antibody levels. It is important to emphasise that insomnia is associated with lower antibody levels against COVID-19 after vaccination.

Positron Emission-Computed Tomography, Cryobiopsy versus Bronchoalveolar Lavage and Computed Tomography Findings for Interstitial Lung Disease: A Long-Term Follow-Up.

Background and Objectives: Interstitial lung diseases have always been an issue for pulmonary and rheumatology physicians. Computed tomography scans with a high-resolution protocol and bronchoalveolar lavage have been used along with biochemical blood tests to reach a diagnosis. Materials and Methods: We included 80 patients in total. First, all patients had their diagnosis with computed tomography of the thorax, serological/ immunological blood tests and bronchoalveolar lavage. However; after 3 months, all were divided into 2 groups: those who had bronchoalveolar lavage again and those who had cryobiopsy instead of bronchoalveolar lavage (40/40). Positron emission-computed tomography was also performed upon the first and second diagnosis. The patients' follow-up was 4 years from diagnosis. Results: Patients suffered most from chronic obstructive pulmonary disease (56, 70%), while lung cancer was rarely encountered in the sample (7, 9.75%). Age distribution ranged between 53 and 68 years with a mean value of 60 years. The computed tomography findings revealed 25 patients with typical diagnosis (35.2%), 17 with interstitial pulmonary fibrosis (23.9%) and 11 with probable diagnosis (11%). The cryobiopsy technique led to a new diagnosis in 28 patients (35% of the total sample). Patients who had a new diagnosis with cryobiopsy had a mean survival time of 710 days (<1460). Positron emission-computed tomography SUV uptake was positively associated with the cryobiopsy technique/new disease diagnosis and improved all respiratory functions. Discussion: Positron emission-computed tomography is a tool that can be used along with respiratory functions for disease evaluation. Conclusions: Cryobiopsy is a safe tool for patients with interstitial lung disease and can assist in the diagnosis of interstitial lung diseases. The survival of patients was increased in the cryobiopsy group versus only bronchoalveolar lavage for disease diagnosis.

Treg-dependent immunosuppression triggers effector T cell dysfunction via the STING/ILC2 axis.

Lung cancer remains the leading cause of cancer-related deaths and despite extensive research, the survival rate of lung cancer patients remains significantly low. Recent data reveal that aberrant Kras signaling drives regulatory T cells (Tregs) present in lung tumor microenvironment to establish immune deregulation and immunosuppression but the exact pathogenic mechanism is still unknown. In this study, we investigate the role of oncogenic Kras in Treg-related immunosuppression and its involvement in tumor-associated metabolic reprogramming. Findings reveal Tregs to prompt GATA3/NOS2-related immunosuppression via STING inhibition which triggers a decline in CD4+ T infiltration, and a subsequent increase in lung metastatic burden. Enhanced Treg expression was also associated with low T/MDSC ratio through restriction of CD8+CD44+CD62L- T effector cells, contributing to a tumor-promoting status. Specifically, TIM3+/LAG3+ Tregs prompted Kras-related immunosuppressive chemoresistance and were associated with T cell dysfunction. This Treg-dependent immunosuppression correlated with CD8 T cell exhaustion phenotype and ILC2 augmentation in mice. Moreover, enhanced Treg expression promoted activation-induced cell death (AICD) of T lymphocytes and guided lymph node metastasis in vivo. Overall, these findings demonstrate the multifaceted roles of Tregs in sustaining lung immunosuppressive neoplasia through tumor microenvironment remodeling and provide new opportunities for effective metastasis inhibition, especially in chemoresistant tumors.

Asthma and rhinitis in Greek furniture workers.

Objective: The detection of asthma and rhinitis in furniture workers exposed to chemicals in the area of Thessaloniki Greece and the determination of the most useful tests for diagnosing the above occupational diseases.Methods: Eighty-three workers (76 men), 35 exposed to chemicals (CW), 23 to wood dust (WW), and 25 office workers (OW), serving as controls, filled in a specialized European Community Respiratory Health Survey (ECRHS) questionnaire for asthma and were submitted to clinical evaluation, spirometry, bronchodilation test, PEF computer algorithm OASYS-2, FeNO, skin prick tests (SPTs), rhinomanometry and methacholine inhalation challenge. Working conditions and protective measurements were also recorded. According to the results of all conducted tests, each subject was distributed to a subgroup: (a) normal, (b) asthma, (c) rhinitis, (d) asthma and rhinitis. Comparisons were performed among work groups.Results: The presence of asthma and/or rhinitis was higher among CW and WW compared to OW (p = 0.004). Significant differences among groups were observed in the questions «better weekend¼ (p < 0.034) and "improvement on vacation¼ (p < 0.000), in OASYS-2 Score (p < 0.000), in ABC Score (p < 0.000), and in methacholine score (p < 0.022). Rhinomanometry, FeNO, spirometry, and spirometry after bronchodilation had no significant differences among groups. Working conditions, ventilation system, work practice, use and type of mask revealed no significant differences.Conclusion: Asthma and rhinitis are significantly common among CW. Protective measurements used were not adequate to prevent asthma and or work related rhinitis. Early diagnosis might contribute to disease prevention and control.

Reduction in Hospitalizations for Respiratory Diseases during the First COVID-19 Wave in Greece.

INTRODUCTION: During the first COVID-19 wave, a considerable decline in hospital admissions was observed worldwide. AIM: This retrospective cohort study aimed to assess if there were any changes in the number of patients hospitalized for respiratory diseases in Greece during the first CO-VID-19 wave. METHODS: In the present study, we evaluated respiratory disease hospitalization rates across 9 tertiary hospitals in Greece during the study period (March-April 2020) and the corresponding period of the 2 previous years (2018-2019) that served as the control periods. Demographic data and discharge diagnosis were documented for every patient. RESULTS: Of the 1,307 patients who were hospitalized during the study period, 444 (35.5%) were males with a mean (±SD) age of 66.1 ± 16.6 years. There was a 47 and 46% reduction in all-cause respiratory morbidity compared to the corresponding periods of 2018 and 2019, respectively. The mean incidence rate for respiratory diseases during the study period was 21.4 admissions per day, and this rate was significantly lower than the rate during the same period in 2018 (40.8 admissions per day; incidence rate ratio [IRR], 0.525; 95% confidence interval [CI], 0.491-0.562; p < 0.001) or the rate during 2019 (39.9 admissions per day; IRR, 0.537; 95% CI, 0.502-0.574; p < 0.001). The greatest reductions (%) in the number of daily admissions in 2020 were observed for sleep apnoea (87% vs. 2018 and 84% vs. 2019) followed by admissions for asthma (76% vs. 2018 and 79% vs. 2019) and chronic obstructive pulmonary disease (60% vs. 2018 and 51% vs. 2019), while the lowest reductions were detected in hospitalizations for pulmonary embolism (6% vs. 2018 and 23% vs. 2019) followed by tuberculosis (25% vs. both 2018 and 2019). DISCUSSION/CONCLUSION: The significant reduction in respiratory admissions in 2020 raises the reasonable question of whether some patients may have avoided seeking medical attention during the COVID-19 pandemic and suggests an urgent need for transformation of healthcare systems during the pandemic to offer appropriate management of respiratory diseases other than COVID-19.

The presence of insomnia and depression contributes to the acceptance of an initial treatment trial of continuous positive airway pressure therapy in patients with obstructive sleep apnea.

The presence of comorbid insomnia and sleep apnea (COMISA) reduces the initial acceptance of continuous positive airway pressure (CPAP) therapy in 39-58% of patients with obstructive sleep apnea (OSA). Depressive disorders are reported in 5 to 63% of patients with OSA. Here we studied the co-occurrence of depression and insomnia in OSA patients and its impact on treatment acceptance in a real-life controlled trial. METHODS: In this prospective, uncontrolled study, participants were recruited from January to December 2018, among adult patients who visited our sleep lab. Participants underwent polysomnography study and completed the Epworth Sleepiness Scale (ESS), Athens Insomnia Scale (AIS), and Zung Depression Rating Scale (ZDRS). All subjects were categorized into 8 groups: no OSA/no depression (apnea-hypopnea index [AHI] < 5/h, n = 34), mild OSA/no depression (AHI = 5-14/h, n = 22), moderate OSA/no depression (AHI = 15-29/h, n = 44), severe OSA/no depression (AHI ≥ 30/h, n = 45), no OSA/mild depression (AHI < 5/h, n = 31), mild OSA/mild depression (AHI = 5-14/h, n = 24), moderate OSA/mild depression (AHI = 15-29/h, n = 31), and severe OSA/mild depression (AHI ≥ 30/h, n = 40). RESULTS: Over the one-year period, 272 participants (200 men, mean age 52.9 ± 13.0 years, BMI 33.6 ± 7.2 kg/m2) were enrolled. When the above 8 groups were subcategorized into the presence or absence of insomnia, we found no differences in CPAP trial acceptance between subgroups except in patients from the mild depression/severe OSA/insomnia subgroup who denied CPAP therapy more frequently (chi-squared test p = 0.016). We found, with a moderate efficiency indicated by the ROC curve, that patients with AHI > 15/h, AIS ≥ 11, and ZDRS > 44 were more likely to refuse an initial trial of CPAP treatment because of COMISA and depression (ROC curve area = 0.710, p = 0.049). CONCLUSION: This study demonstrates that it is important to recognize a depressive mood disorder in patients with moderate/severe OSA and COMISA as the coexistence of these comorbidities impairs the rate of initial acceptance of CPAP treatment. Additionally, our study suggests the cut-off values from the AIS and ZDRS questionnaires to help lead clinicians to an early diagnostic evaluation of COMISA patients for the presence of depressive mood disorder.

Long-term efficacy and safety of omalizumab in patients with allergic asthma: A real-life study.

Background: The efficacy and safety of omalizumab in patients with severe allergic asthma have been established in both randomized controlled trials and real-life studies. Objective: To evaluate the sustained effectiveness and safety of long-term treatment with omalizumab in a real-world setting. Methods: In this retrospective study, we included patients treated with omalizumab for at least 8 years in four asthma clinics in Greece. Pulmonary function, asthma control, oral corticosteroids (OCS) dose, and exacerbations were recorded before treatment, 6 months later, and annually thereafter. Adverse events were also recorded. Results: Forty-five patients (66.7% women), mean ± standard deviation (SD) age 55.3 ± 12.2 years, were included. The duration of treatment with omalizumab was 10.6 ± 1.2 years. The annual exacerbation rate decreased from 4.1 before omalizumab initiation to 1.1 after 1 year of treatment and remained low up to the 8th year of treatment (p < 0.001). From the 19 patients who were receiving OCS at baseline, 21.1% patients discontinued after 6 months, 47.4% were still on OCS after 4 years of therapy, and 31.6% were on OCS after 8 years. With regard to the OCS dose, 36.8% of the patients reduced the dose ≥ 50% after 6 months and 68.4% achieved 50% reduction after 2 years. The mean daily OCS dose before omalizumab initiation was 7.8 mg of prednisolone or the equivalent, reduced to 4.7 mg/day after 6 months, which reached 1.6 mg/day after 8 years (p < 0.001). Treatment with omalizumab resulted in significant improvements of asthma control and lung function. No severe adverse events were reported. Conclusion: In this real-life study, omalizumab resulted in significant and sustained improvements in asthma exacerbations, asthma control, and lung function, and had a steroid sparing effect and a good safety profile.

Mepolizumab in Severe Eosinophilic Asthma: A 2-Year Follow-Up in Specialized Asthma Clinics in Greece: An Interim Analysis.

INTRODUCTION: Mepolizumab is a monoclonal antibody against IL-5 for the treatment of severe eosinophilic asthma. The aim of the current study was to present a predesigned interim analysis of the data of patients who have completed 1 year of therapy with mepolizumab. METHODS: This study is a prospective multicenter, noninterventional 2-year observational study and aims to describe the clinical benefit and safety profile of mepolizumab in patients with severe eosinophilic asthma. RESULTS: Compared to the year preceding the initiation of treatment, the annual rate of exacerbations decreased significantly, from 4.3 ± 2.3 to 1.3 ± 1.8; p < 0.0001. Forty-two patients received maintenance dose of oral corticosteroids (OCS) at baseline. From these patients at the end of 1 year of therapy with mepolizumab, 17 patients (40%) had achieved OCS discontinuation. A reduction in the median dose of OCS was also achieved. After 1 year of treatment with mepolizumab, the asthma control test score significantly increased from 16.3 ± 3.7 to 21.2 ± 3.8 (p < 0.0001). This marked clinical improvement was paralleled by a significant reduction of blood eosinophil count. All patients showed a considerable improvement of airflow limitation. In respect to adverse events of treatment with mepolizumab, 19 patients (27%) were recorded to have at least one such occurrence during their 1-year treatment. CONCLUSIONS: We have shown that in patients with severe eosinophilic asthma, 1 year of treatment with mepolizumab was safe, resulted in significant reduction of the annual exacerbation rate, reduction (or even discontinuation) of the needed dose of OCS, and improvements of asthma control and lung function.

Acute effects of e-cigarette vaping on pulmonary function and airway inflammation in healthy individuals and in patients with asthma.

BACKGROUND AND OBJECTIVE: The acute effects of e-cigarettes have not been scientifically demonstrated yet. The aim of this study was to assess the acute changes in pulmonary function and airway inflammation in patients with asthma after vaping one e-cigarette. METHODS: Twenty-five smokers suffering from stable moderate asthma according to GINA guidelines with no other comorbidities and 25 healthy smokers matched with the baseline characteristics of the asthmatic patients were recruited. PFT, IOS, FeNO and EBC were performed before and after vaping one e-cigarette with nicotine. pH and concentrations of IL-1ß, IL-4, IL-5, IL-6, IL-8, IL-10, IL-13, IL-17A, TNF-α, ISO8 and LTB4 were measured in EBC. RESULTS: FFEV1/FVC ratio and PEF were reduced in asthmatic patients after e-cigarette. Z5Hz and R5Hz, R10Hz and R20Hz increased in both groups. FeNO and EBC pH increased by 3.60 ppb (P = 0.001) and 0.15 (P = 0.014) in asthmatic patients after e-cigarette, whereas they decreased in control group by 3.28 ppb (P < 0.001) and 0.12 (P = 0.064), respectively. The concentrations of IL-10, TNF-α and ISO8 in EBC increased in asthmatic patients after e-cigarette and the changes in concentrations of IL-1ß and IL-4 differed significantly between the two groups. CONCLUSION: E-cigarette vaping resulted in acute alteration of both pulmonary function and airway inflammation in stable moderate asthmatic patients.

Importance of the relationship between symptoms and self-reported physical activity level in stable COPD based on the results from the SPACE study.

BACKGROUND: The burden of symptoms and risk of exacerbations are the main drivers of the overall assessment of the Chronic Obstructive Pulmonary Disease (COPD) and the adequate treatment approaches per current Global Initiative for Chronic Obstructive Lung Disease (GOLD). Physical activity has emerged as both functional outcome and non-pharmacological intervention in COPD patients, despite the lack of standardized measures or guidelines in clinical practice. This study aimed to explore in more depth the 24-h respiratory symptoms, the physical activity level (PAL) and the relationship between these two determinants in stable COPD patients. METHODS: This was a multinational, multicenter, observational, cross-sectional study conducted in ten European countries and Israel. Dedicated questionnaires for each part of the day (morning, daytime, night) were used to assess respiratory symptoms. PAL was evaluated with self- and interview-reported tools [EVS (exercise as vital sign) and YPAS (Yale Physical Activity Survey)], and physician's judgement. Patients were stratified in ABCD groups by 2013 and 2017 GOLD editions using the questionnaires currently recommended: modified Medical Research Council dyspnea scale and COPD Assessment Test. RESULTS: The study enrolled 2190 patients (mean age: 66.9 years; male: 70.0%; mean % predicted FEV1: 52.6; GOLD groups II-III: 84.5%; any COPD treatment: 98.9%). Most patients (> 90%) reported symptoms in any part of the 24-h day, irrespective of COPD severity. PAL evaluations showed discordant results between patients and physicians: 32.9% of patients considered themselves completely inactive, while physicians judged 11.9% patients as inactive. By YPAS, the overall study population spent an average of 21.0 h/week performing physical activity, and 68.4% of patients were identified as sedentary. In any GOLD ABCD group, the percentage of inactive patients was high. Our study found negative, weak correlations between respiratory symptoms and self-reported PAL (p < 0.001). CONCLUSIONS: Despite regular treatment, the majority of stable COPD patients with moderate to severe disease experienced daily variable symptoms. Physical activity level was low in this COPD cohort, and yet overestimated by physicians. With evidence indicating the negative consequences of inactivity, its adequate screening, a more active promotion and regular assessment of physical activity are urgently needed in COPD patients for better outcomes. TRIAL REGISTRATION: NCT03031769 , retrospectively registered, 23 Jan 2017.

Comparison of diagnostic validity of mannitol and methacholine challenges and relationship to clinical status and airway inflammation in steroid-naïve asthmatic patients.

OBJECTIVES: The purpose of this study was to demonstrate and compare the diagnostic validity of two bronchial challenges and to investigate their correlation with patient clinical status, atopy and inflammation markers. METHODS: Eighty-eight patients, 47 women and 41 men, mean age 38.56 ± 16.73 years who presented with asthma related symptoms and were not on any anti-asthma medication, were challenged with mannitol and methacholine on separate days. Medical history regarding asthmatic symptoms, physical examination, skin prick tests and FeNO levels were also assessed. The clinical diagnosis of asthma was based on bronchodilator reversibility test. RESULTS: Sixty-seven patients were diagnosed with asthma and 21 without asthma. Both methacholine (P < 0.014) and mannitol (P < 0.000) challenges were significant in diagnosing asthma. The positive/negative predictive value was 93.33%/41.86% for methacholine, 97.72%/45.45% for mannitol and 97.05%/45.45%. for both methods assessed together. Worthy of note that 22% of asthmatics had both tests negative. There was a negative correlation between PC20 of methacholine and the FeNO level P < 0.001, and positive with the PD15 of mannitol P < 0.001 and the pre-test FEV1% pred P < 0.005, whereas PD15 of mannitol was negatively correlated with the FeNO level P < 0.001. Furthermore, dyspnea was the only asthmatic symptom associated with FeNO level P < 0.035 and the positivity of mannitol P < 0.014 and methacholine P < 0.04. CONCLUSIONS: Both challenge tests were equivalent in diagnosing asthma. Nevertheless, specificity appeared to be slightly higher in mannitol challenge.

Monitoring changes in quality of life in patients with lung cancer by using specialised questionnaires: implications for clinical practice.

BACKGROUND: Quality of life (QoL) in lung cancer patients is overlooked due to the severity of the disease. Changes in factors comprising QoL need further exploration to determine therapy targets. METHODS AND MATERIALS: QoL was assessed in 282 patients referred to a specialised centre in Greece for chemotherapy using three reliable scales: Functional Assessment of Cancer Therapy-Lung (FACT-L, Greek version 4), Short Form (SF-36) Health Survey and Hospital Anxiety and Depression Scale (HAD)S. RESULTS: Comparing QoL scores, it was observed that in comparison to the first chemotherapy, there was a statistically significant deterioration in patients' physical well-being (p < 0.0001) at the following chemotherapies. In contrast, there was a statistically significant improvement in patients' emotional well-being (p < 0.0001), mental health (p < 0.0001) and social functioning (p = 0.006) in the chemotherapies following the first. Observations deriving from survival analyses agree with literature findings: small cell lung cancer (SCLC) patients had significantly shorter survival than non-SLSC (NSCLC) patients, initial performance status was consistent with survival, radiotherapy improved survival, existence of metastases hindered survival, and the number of chemotherapies and QoL scores were positively correlated with survival. CONCLUSIONS: Although patients' physical functioning deteriorated after chemotherapy, their psychological state, mental health and social functioning improved in comparison with their first chemotherapy. This may be due to the fear of the unknown and the stress patients experience before their treatment. Regarding survival analysis results, it could be stated that the better QoL scores, the longer the survival. The findings underline the importance of psychological support after diagnosis and during the initiation of treatment. This may result in a better QoL, hence leading to prolongation of survival.

Hybrid Nanogel Drug Delivery Systems: Transforming the Tumor Microenvironment through Tumor Tissue Editing.

The future of drug delivery offers immense potential for the creation of nanoplatforms based on nanogels. Nanogels present a significant possibility for pharmaceutical advancements because of their excellent stability and effective drug-loading capability for both hydrophobic and hydrophilic agents. As multifunctional systems, composite nanogels demonstrate the capacity to carry genes, drugs, and diagnostic agents while offering a perfect platform for theranostic multimodal applications. Nanogels can achieve diverse responsiveness and enable the stimuli-responsive release of chemo-/immunotherapy drugs and thus reprogramming cells within the TME in order to inhibit tumor proliferation, progression, and metastasis. In order to achieve active targeting and boost drug accumulation at target sites, particular ligands can be added to nanogels to improve the therapeutic outcomes and enhance the precision of cancer therapy. Modern "immune-specific" nanogels also have extra sophisticated tumor tissue-editing properties. Consequently, the introduction of a multifunctional nanogel-based drug delivery system improves the targeted distribution of immunotherapy drugs and combinational therapeutic treatments, thereby increasing the effectiveness of tumor therapy.

Association of Fetal Lung Development Disorders with Adult Diseases: A Comprehensive Review.

Fetal lung development is a crucial and complex process that lays the groundwork for postnatal respiratory health. However, disruptions in this delicate developmental journey can lead to fetal lung development disorders, impacting neonatal outcomes and potentially influencing health outcomes well into adulthood. Recent research has shed light on the intriguing association between fetal lung development disorders and the development of adult diseases. Understanding these links can provide valuable insights into the developmental origins of health and disease, paving the way for targeted preventive measures and clinical interventions. This review article aims to comprehensively explore the association of fetal lung development disorders with adult diseases. We delve into the stages of fetal lung development, examining key factors influencing fetal lung maturation. Subsequently, we investigate specific fetal lung development disorders, such as respiratory distress syndrome (RDS), bronchopulmonary dysplasia (BPD), congenital diaphragmatic hernia (CDH), and other abnormalities. Furthermore, we explore the potential mechanisms underlying these associations, considering the role of epigenetic modifications, transgenerational effects, and intrauterine environmental factors. Additionally, we examine the epidemiological evidence and clinical findings linking fetal lung development disorders to adult respiratory diseases, including asthma, chronic obstructive pulmonary disease (COPD), and other respiratory ailments. This review provides valuable insights for healthcare professionals and researchers, guiding future investigations and shaping strategies for preventive interventions and long-term care.

Expression patterns and clinical implications of PDL1 and DLL3 biomarkers in small cell lung cancer retrospectively studied: Insights for therapeutic strategies and survival prediction.

Lung cancer is a leading cause of cancer-related deaths globally, includes small cell lung cancer (SCLC), characterized by its aggressive nature and advanced disease at diagnosis. However, the identification of reliable biomarkers for SCLC has proven challenging, as no consistent predictive biomarker has been established. Nonetheless, certain tumor-associated antigens, including programmed death-ligand 1 (PDL1) and Delta-Like Ligand 3 (DLL3), show promise for targeted antibody-based immunotherapy. To ensure optimal patient selection, it remains crucial to comprehend the relationship between PDL1 and DLL3 expression and clinicopathological characteristics in SCLC. In this study, we investigated the expression patterns of PDL1 and DLL3 biomarkers in endobronchial samples from 44 SCLC patients, examining their association with clinical characteristics and survival. High PDL1 expression (>1%) was observed in 14% of patients, while the majority the SCLC patients (73%) exhibited high DLL3 expression (>75%). Notably, we found a positive correlation between high PDL1 expression (>1%) and overall survival. However, we did not observe any significant differences in the biomarkers expression concerning age, sex, disease status, smoking status, or distant metastases. Further subgroup analysis revealed that a high co-expression of both PDL1 (>1%) and DLL3 (100%) antigens was associated with improved overall survival. This suggests that SCLC expressing PDL1 and DLL3 antigens may exhibit increased sensitivity to therapy, indicating their potential as therapeutic targets. Thus, our findings provide novel insights into the simultaneous evaluation of PDL1 and DLL3 biomarkers in SCLC patients. These insights have significant clinical implications for therapeutic strategies, survival prediction, and development of combination immunotherapies.

Prognostic Value of KRAS Mutations in Relation to PDL1 Expression and Immunotherapy Treatment in Adenocarcinoma and Squamous Cell Carcinoma Patients: A Greek Cohort Study.

BACKGROUND: Factors that could predict which patients will benefit from Immune Checkpoint Inhibitors (ICIs) are not fully understood. This study aimed to investigate the prognostic value of KRAS biomarker in patients with advanced non-small cell lung cancer (NSCLC) in relation to clinical characteristics, treatment response and PDL1 expression. PATIENTS AND METHODS: The study included 100 patients with NSCLC who received immunotherapy with or without chemotherapy as 1st line treatment. In biopsy samples, the PDL1 biomarker expression rate and somatic mutations of KRAS gene were determined. RESULTS: The mean age of the patients was 67 ± 8 years. Patients were all male and 66% were found with adenocarcinoma whereas 34% with squamous cell carcinoma. The KRAS G12C mutation was found with the highest percentage (73%). In the Kaplan-Meier survival analysis, patients with PDL1 > 49% in combination with a negative KRAS result had a median overall survival of 40 months compared to patients with a positive KRAS result (9 months, p < 0.05). In addition, patients diagnosed with adenocarcinoma, PDL1 < 49% and negative KRAS result had a median overall survival of 39 months compared to patients with a positive result (28 months, p < 0.05). CONCLUSIONS: Our study suggests that the presence of KRAS mutations in advanced NSCLC patients has a poor prognostic value, regardless of their PDL1 expression values, after receiving immunotherapy as first-line treatment.

Nebulisation of Paclitaxel, Sotatercept and Iloprost for pulmonary hypertension for lung cancer. From In vitro to In vivo.

Background: Pulmonary hypertension is common symptom among several diseases. The consequences are severe for several organs. Pulmonary hypertension is usually under-diagnosed and the main symptom observed is dyspnea with or without exercise. Currently we have several treatment modalities administered orally, via inhalation, intravenously and subcutaneously. In advanced disease then heart or lung transplantation is considered. The objective of the study was to investigate the optimum method of aerosol production for the drugs: iloprost, paclitaxel and the novel sotatercept. Materials and Methods: In our experiment we used the drugs iloprost, paclitaxel and the novel sotatercept, in an experimental concept of nebulization. We performed nebulization experiments with 3 jet nebulizers and 3 ultrasound nebulizers with different combinations of residual cup designs, and residual cup loadings in order to identify which combination produces droplets of less than 5µm in mass median aerodynamic diameter. Results: We concluded that paclitaxel cannot produce small droplets and is also still very greasy and possible dangerous for alveoli. However; iloprost vs sotatercept had smaller droplet size formation at both inhaled technologies (1.37<2.23 and 1.92<3.11, jet and ultrasound respectively). Moreover; residual cup designs C and G create the smallest droplet size in both iloprost and sotatercept. There was no difference for the droplet formation between the facemask and cone mouthpieces. Discussion: Iloprost and sotatercept can be administered as aerosol in any type of nebulisation system and they are both efficient with the residual cups loaded with small doses of the drug (2.08 and 2.12 accordingly).

Open and Closed Triple Inhaler Therapy in Patients with Uncontrolled Asthma.

Long-acting muscarinic antagonists (LAMAs) are a class of inhalers that has recently been included as add-on therapy in the GINA guidelines, either in a single inhaler device with inhaled corticosteroids plus long-acting ß2-agonists (ICS + LABA) (closed triple inhaler therapy) or in a separate one (open triple inhaler therapy). This review summarizes the existing evidence on the addition of LAMAs in patients with persistently uncontrolled asthma despite ICS + LABA treatment based on clinical efficacy in the reduction of asthma symptoms and exacerbations, the improvement in lung function, and its safety profile.