Influenza as an important factor causing increased risk of patients' deaths, excessive morbidity and prolonged hospital stays.

Introduction: Influenza infection is associated with potential serious complications, increased hospitalization rates and a higher risk of death. Material and methods: A retrospective comparative analysis of selected indicators of hospitalization at the University Hospital in Wroclaw was conducted on patients with confirmed influenza infection and a control group during the 2018-2019 influenza season. The threshold for statistical significance of differences between the groups was set at p < 0.05. Results: The types of influenza viruses confirmed in the hospital patients were remarkably similar to those occurring in the general population in Poland. The largest numbers of influenza cases were observed at the departments related to internal medicine where patients with cardiac, lung and renal diseases were hospitalized. The risk of death among the patients with confirmed influenza infection was significantly higher than among the other patients. The highest risk of death was observed among the patients with confirmed influenza infection at the departments related to internal medicine. Considering patients from the entire hospital, the mean length of hospital stay for those with confirmed influenza was 2.13-fold longer than for those in the control group. Comparisons of the median, minimum and maximum lengths of hospitalization between the patients with confirmed influenza infection and the control group reveal even more distinct differences. Conclusions: Significant differences in the selected indicators of hospitalization were observed between the patients with confirmed influenza infection and the control group; they are associated with serious social costs, such as prolonged hospital stay and a higher risk of death during hospitalization in Poland.

Coalition Shaping the Vaccination Landscape.

In 2022, the National Program for Influenza Prevention coalition will have its 10th anniversary; it is one of Poland's oldest educational initiatives. The National Program for Influenza Prevention was initiated to prevent a further decline and promote influenza prevention in the A(H1N1) post-pandemic years. In this review, we summarize the structure and operational model of the coalition and identify core functional elements that make it a key non-governmental organization involved in the prophylactics of communicable diseases. The coalition-based organization can operate in a complex environment, such as vaccinations requiring scientific, economic, social, and psychological involvement, and communications with different groups. Anchored to the history of the National Program for Influenza Prevention, we review Poland's vaccination landscape changes from the last ten years.

The Significance of the Alter miR let-7a and miR-335 Expression Level Regulating the CCR7/CCL19 Axis as Potential Biomarkers of Tumor Progression in NSCLC.

The chemokine receptor 7/C-C ligand 19 chemokine (CCR7/CCL19) has been implicated in the development and progression of NSCLC. Its expression is regulated by various epigenetic factors including miRNAs. The aim of this study was to assess the expression of CCR7/CCL19 in cancer tissue in relation to that of miRNAs (miR-let-7a, miR-335) as transcriptional regulators. The expression of the tested miRNAs was also evaluated in serum exosomes. Sixty patients (n = 60) were enrolled in the study. The total expression of the studied mRNA and miRNAs were evaluated using qPCR. Tumor tissue fragments, macroscopically unchanged adjacent tissue, and serum were used as controls. Higher CCR7 and CCL19 mRNA expression levels were observed in tumor tissue compared to control. According to stages of the disease (AJCC tumor staging), the greatest expression level of the studied genes' mRNA was observed in patients with stage III. In NSCLC patients, lower miR let-7a expression level was observed in tumor tissue compared to serum; however, miR-335 expression level was higher (p < 0.05). The expression level of miR-335 positively correlated with tumor size (T features according to pTNM staging) and AJCC tumor staging, while miR let-7a had a negative correlation (p > 0.05) with liquid biopsy. Significantly greater miR-335 expression level and lower miR let-7a expression level in serum were observed in patients with metastases to lymph nodes. Our findings reveal a significant correlation between the expression levels of the mRNA of the studied genes and miRNAs. Changes in miR-335 and miR let-7a expression levels in the serum exosomes of NSCLC patients in relation to lymph node metastases and tumor stage may serve as a non-invasive molecular biomarker of tumor progression.

Diagnostic value of PPARδ and miRNA-17 expression levels in patients with non-small cell lung cancer.

The PPARδ gene codes protein that belongs to the peroxisome proliferator-activated receptor (PPAR) family engaged in a variety of biological processes, including carcinogenesis. Specific biological and clinical roles of PPARδ in non-small cell lung cancer (NSCLC) is not fully explained. The association of PPARα with miRNA regulators (e.g. miRNA-17) has been documented, suggesting the existence of a functional relationship of all PPARs with epigenetic regulation. The aim of the study was to determine the PPARδ and miR-17 expression profiles in NSCLC and to assess their diagnostic value in lung carcinogenesis. PPARδ and miR-17 expressions was assessed by qPCR in NSCLC tissue samples (n = 26) and corresponding macroscopically unchanged lung tissue samples adjacent to the primary lesions served as control (n = 26). PPARδ and miR-17 expression were significantly lower in NSCLC than in the control (p = 0.0001 and p = 0.0178; respectively). A receiver operating characteristic (ROC) curve analysis demonstrated the diagnostic potential in discriminating NSCLC from the control with an area under the curve (AUC) of 0.914 for PPARδ and 0.692 for miR-17. Significant increase in PPARδ expression in the control for current smokers vs. former smokers (p = 0.0200) and increase in miR-17 expression in control tissue adjacent to adenocarcinoma subtype (p = 0.0422) were observed. Overexpression of miR-17 was observed at an early stage of lung carcinogenesis, which may suggest that it acts as a putative oncomiR. PPARδ and miR-17 may be markers differentiating tumour tissue from surgical margin and miR-17 may have diagnostic role in NSCLC histotypes differentiation.

Effectiveness of pulmonary rehabilitation in patients with chronic obstructive pulmonary disease after lobectomy due to non-small cell lung cancer - a single-center retrospective study.

INTRODUCTION: The procedure of lung parenchyma resection may result in impairment of physical capacity and quality of life. In patients with operable non-small cell lung cancer (NSCLC), lobectomy is an elective procedure. Chronic obstructive pulmonary disease (COPD) is a common coexisting condition in patients with NSCLC. Effectiveness of post-operative pulmonary rehabilitation (PR) in patients who underwent lobectomy due to NSCLC and suffering from COPD as compared to individuals without COPD has not been determined yet. The aim of the study was to compare effectiveness of post-operative PR in patients with COPD after lobectomy due to NSCLC (COPD[+] L [+]) with individuals with COPD without lung parenchyma resection (COPD(+) L(-)) and those who underwent lobectomy due to NSCLC and not suffering from COPD (COPD[-] L[+]). MATERIAL AND METHODS: Thirty-seven patients with non-small cell lung cancer (21 patients with and 16 patients without COPD) who underwent lobectomy and 29 subjects with COPD referred to the Lung Diseases Treatment and Rehabilitation Centre in Lodz in 2018-2019 were included in this retrospective analysis. The patients participated in a 3-week inpatient pulmonary rehabilitation (PR) program which included breathing exercises, physical workout, relaxation exercises, education, psychological support and nutrition consulting. The evaluation included lung function measurements, six-minute walking test (6MWT) and the St. George's Respiratory Questionnaire (SGRQ) score. The results obtained before the rehabilitation were compared to those achieved after the 3-week PR program and compared between the study groups. RESULTS: A significant increase in the distance covered during 6MWT was observed in all the three groups studied: COPD(+) L(+) (Δ = 62.52 ± 14.58 m); COPD(-) L(+) (Δ = 73.67 ± 11.58 m); and COPD(+) L(-) (Δ = 59.93 ± 10.02 m) (p < 0.001 for all). Similarly, a statistically and clinically significant improvement in the total SGRQ score was recorded: COPD(+) L(+) ∆ = -12.05 ± 3.96 points; p < 0.05 and COPD(-) L(+) ∆ = -12.30 ± 4.85 points; p < 0.01 and COPD(+) (L-) ∆= -14.07 ± 3.36 points (p < 0.001). No significant differences in the outcome improvement between the study groups were identified. CONCLUSIONS: The results of the study show that COPD(+) L(+) patients gained benefits from post-operative PR comparable to COPD(+) L(-) and COPD(-) L(+) subjects by improving their physical capacity and quality of life.

Serum Extracellular Vesicle-Derived miRNAs in Patients with Non-Small Cell Lung Cancer-Search for Non-Invasive Diagnostic Biomarkers.

The aim of the study was a search for diagnostic and/or prognostic biomarkers in patients with non-small cell lung cancer (NSCLC) patients, based on circulating microRNAs (miRs: miR-23a, miR-361, miR-1228 and miR-let7i) in extracellular vesicles (EVs). Serum EVs were isolated from NSCLC patients (n = 31) and control subjects (n = 21). RNA was isolated from EVs and reverse transcription reaction was performed. Relative levels of miR-23a, miR-361, miR-1228 and miR-let7i were assessed in real-time qPCR using TaqMan probes. Analysis was based on the 2-ΔΔCT method. Statistically significant lower levels of miR-23a and miR-let7i were observed among NSCLC patients vs. control group: miR-23a, 0.054 vs. 0.107; miR-let7i, 0.193 vs. 0.369 (p = 0.003, p = 0.005, respectively). A receiver operating characteristic (ROC) curve analysis demonstrated the diagnostic potential of each individual serum EV-derived miRNA with an area under the curve AUC = 0.744 for miR-23a (p = 0.0003), 0.733 for miR-let7i (p = 0.0007). The decreased level of miR-23a in patients correlated with metastasis to lymph nodes and with AJCC tumor staging system. The results demonstrate that miR-23a and miR-let7i may prove clinically useful as significant, non-invasive markers in NSCLC diagnosis. Additionally, changing profile level of miR-23a that correlates with cancer development may be considered as an NSCLC progression marker.

Expression of inflammatory interleukins and selected miRNAs in non-small cell lung cancer.

Tumours are characterised by an ability to avoid immune destruction and the presence of cancer-associated inflammation. Better understanding of the link between lung cancer and such inflammation is vital for early detection and personalized treatment. Thus, we examined the mRNA expression of interleukins IL-1ß, IL-6, IL-17 and miR-9, miR-122 as potential useful biomarkers of NSCLC. Tumour tissues, non-cancerous tissue and blood samples were collected from 39 patients with primary NSCLC undergoing surgical treatment. The selected RNA was isolated from tissue samples and selected miRNAs from peripheral blood exosomes. This RNA was transcribed to cDNA and quantified using RT-qPCR. Significantly higher expression of the selected interleukins was observed in non-cancerous than tumour tissue, and IL-6 was significantly higher in the tumour tissue of patients with a history of ≤ 40 pack-years (PYs) (2.197, IQR: 0.821-4.415) than in those with > 40 PYs (0.461, IQR: 0.372-0.741; p = 0.037). It is clear that inflammatory processes play a role in NSCLC, as indicated by the upregulation of IL-1ß and IL-6 in tumour and adjacent tissue, and that smoking has a strong influence on inflammation in tumourigenesis, demonstrated by the upregulation of IL-6 in tumour samples among patients with ≤ 40 PYs compared to > 40 PYs.

Eosinopenia and neutrophil-to-lymphocyte count ratio as prognostic factors in exacerbation of COPD.

Exacerbations of Chronic Obstructive Pulmonary Disease (AECOPDs) are one of the most important clinical aspects of the disease, and when requiring hospital admission, they significantly contribute to mortality among COPD patients. Our aim was to assess the role of eosinopenia and neutrophil-to-lymphocyte count (NLR) as markers of in-hospital mortality and length of hospitalization (LoH) among patients with ECOPD requiring hospitalization. We included 275 patients. Eosinopenia was associated with in-hospital deaths only when coexisted with lymphocytopenia, with the specificity of 84.4% (95% CI 79.6-88.6%) and the sensitivity of 100% (95% CI 35.9-100%). Also, survivors presented longer LoH (P < 0.0001). NLR ≥ 13.2 predicted in-hospital death with the sensitivity of 100% (95% CI 35.9-100%) and specificity of 92.6% (95% CI 88.8-95.4%), however, comparison of LoH among survivors did not reach statistical significance (P = 0.05). Additionally, when we assessed the presence of coexistence of eosinopenia and lymphocytopenia first, and then apply NLR, sensitivity and specificity in prediction of in-hospital death was 100% (95% CI 35.9-100) and 93.7% (95% CI 90.1-96.3), respectively. Moreover, among survivors, the occurrence of such pattern was associated with significantly longer LoH: 11 (7-14) vs 7 (5-10) days (P = 0.01). The best profile of sensitivity and specificity in the prediction of in-hospital mortality in ECOPD can be obtained by combined analysis of coexistence of eosinopenia and lymphocytopenia with elevated NLR. The occurrence of a such pattern is also associated with significantly longer LoH among survivors.

The role of bronchoscopy in diagnosis of chronic cough in adults: a retrospective single-center study.

INTRODUCTION: Cough is one of the most frequent symptoms reported to pulmonologists. The role of bronchoscopy in the diagnostic work-up of chronic cough is not clearly defined. The aim of this study was to evaluate the utility of fiberoptic bronchoscopy (FOB) and additional testing of samples collected during FOB in the differential diagnosis of chronic cough in adults. MATERIAL AND METHODS: This was a single-center retrospective study. Out of 7115 conventional white light FOB examinations, we finally selected 198 with cough as the only indication. RESULTS: In 40.9% of bronchoscopic examinations, no visible cause of cough was found. Visual signs of chronic bronchitis (CB) were detected in 57.6% of reports. Only in 3 cases (1.5%) bronchoscopy revealed a potential cause of chronic cough other than CB. Mycobacterium tuberculosis or other mycobacteria were spotted in none of the samples. In 91.1% of bronchoalveolar lavage (BAL) cytologic examinations, at least one cell count abnormality was detected, but only in case of increased percentage of eosinophils, it might be considered clinically relevant. In 53% of bacteriological culture results, at least one potentially pathogenic bacterium was isolated. CONCLUSIONS: The present study results strengthen the evidence that FOB combined with additional testing of airway specimens obtained during FOB is not a powerful tool in the differential diagnosis of chronic cough, and FOB as a diagnostic tool may be overused. The appropriate timing and decision regarding referral for FOB and additional testing of achieved material requires careful clinical consideration.

Flu Vaccinations in Pharmacies-A Review of Pharmacists Fighting Pandemics and Infectious Diseases.

The phenomenon of population ageing observed over recent years involves growing healthcare needs and the limited staffing and financing of healthcare systems, and as such demands some functional changes in the healthcare model in many countries. This situation is particularly significant in the face of a pandemic, e.g., flu, and currently COVID-19.As well as social education, preventive vaccinations are the most effective method of fighting the infectious diseases posing a special threat to seniors. Despite this, the vaccination coverage level in most European countries is relatively low. This is largely due to patients having limited access to vaccinations. In some countries, implementing vaccinations in pharmacies and by authorized pharmacists has significantly improved vaccination coverage rates and herd immunity, while lowering the cost of treating infections and the resulting complications, as well as minimizing the phenomenon of inappropriate antibiotic therapies. This article presents the role of pharmacists in the prevention of infectious diseases, pointing out the measurable effects of engaging pharmacists in conducting preventive vaccinations, as well as analyzing the models of implementing and conducting vaccinations in pharmacies in selected countries, and depicting recommendations regarding vaccinations developed by international organizations. The presented data is used to suggest requirements for the implementation of preventive vaccinations in community pharmacies.

Expression of selected miRNA, RARß and FHIT genes in BALf of squamous cell lung cancer (squamous-cell carcinoma, SCC) patients: a pilot study.

Two suppressor genes which often undergo epigenetic silencing during the early stages of lung carcinogenesis are those encoding retinoic acid receptor-ß (RARß) and Fhit protein (FHIT). RARß expression is regulated by miRNA-34a and miRNA-141, and FHIT expression by miRNA-143 and miRNA-217. The aim of the study was to assess how selected miRNAs regulate the expression of their targeted genes in bronchoalveolar lavage fluid (BALf), obtained from patients with SCC of the lung. It also examines the relationship between the genetic findings and the clinical and pathomorphological features of the tumor. A total of 50 BALf samples were taken: 25 from patients with SCC and 25 from healthy donors. The expression (RQ) of the selected genes was analyzed by qPCR, as well as the miRNA level, with a particular emphasis on the relationship between the expression of the genes themselves and their corresponding miRNAs; in addition, the expression of the genes and miRNAs were compared with the pathomorphological features of the tumor and the clinical features of patients. Analysis of the RQ values showed downregulation of RARß, FHIT and miRNA-34a and increased expression of miRNA-141, miRNA-143 and miRNA-217 in all BALf samples (P > 0.05). No correlation was found between the expression of the selected genes and corresponding miRNAs, history of smoking, cancer stage, age and sex of the patients. The presence of the selected genes and miRNAs in BALf material does not seem to have diagnostic potential in patients with SCC; however, the results should be verified on a larger group of patients.

An assessment of the relationship between the expression of CCR7/CCL19 axis and selected regulatory miRNAs in non-small cell lung cancer.

CC chemokine receptor type 7 (CCR7) and its ligands has been implicated in the occurrence and progression of NSCLC. Previous studies have revealed that the diagnostic value of CCR7/CCL19 axis in lung tumorigenesis remains controversial. The present study evaluates the relationship between the mRNA expression of CCR7/CCL19 axis and selected regulatory miRNAs in NSCLC patients. It analyzes the expression level of CCR7 mRNA and its ligand in tumor tissue in relation to expression level of two miRNAs: miR let-7a and miR-335, as transcriptional regulators of study genes. Twenty-seven patients (n = 27) were enrolled. The expression of the studied genes and miRNAs was evaluated by qPCR. Tumour tissue fragments, adjacent macroscopically-unchanged lung tissue (control) and patient serum were used as biological material for study. Elevated expression of CCR7 and CCL19 mRNA was observed in patients with metastasis to lymph nodes. We noticed upregulated miR-335 expression and downregulated miR let-7a expression in patient serum with regard to AJCC tumor staging. Higher miR-335 expression and lower miR let-7a expression level was observed in patients with metastasis to lymph node. The presence of changes observed in the expression level of miR-335 and miR let-7a in the serum of NSCLC patients in relation to lymph node metastases and tumor stage may serve as a non-invasive molecular biomarker of tumor progression; however, this observation requires further investigation.

Overexpression of chitotriosidase and YKL-40 in peripheral blood and sputum of healthy smokers and patients with chronic obstructive pulmonary disease.

Background: Despite the absence of endogenous chitin in humans, chitinases are present in the serum of healthy subjects and their levels are increased in a variety of chronic inflammatory conditions. It has been shown that chitotriosidase and structurally related chitinase-like protein-YKL-40 contribute to the pathogenesis of COPD. However, details regarding the relation of their systemic and local airways levels remain unknown. Objectives: To examine peripheral blood and sputum chitotriosidase and YKL-40 expression in smokers and patients with COPD. Methods: Forty patients with COPD, 20 healthy smokers and 10 healthy never-smokers were studied. Serum and induced sputum chitotriosidase protein and activity levels, YKL-40 concentrations, and their gene expression in sputum cells and peripheral blood mononuclear cells (PBMC) were evaluated. Results: Both chitotriosidase protein levels and activity were higher in sputum obtained from COPD subjects compared to healthy never-smokers (P<0.05 and P<0.01, respectively). A similar pattern was observed for PBMC chitotriosidase mRNA expression (P<0.001). YKL-40 serum concentrations were elevated in healthy smokers and COPD subjects compared to healthy never-smokers (P<0.001 and P<0.01, respectively). In sputum, YKL-40 levels were increased in COPD compared to healthy never-smokers (P<0.01). PBMC YKL-40 mRNA expression was increased in COPD and healthy smokers compared to healthy never-smokers (P<0.0001). No associations were found between chitotriosidase or YKL-40 peripheral blood levels and sputum levels. Conclusions: Our results demonstrate that chitotriosidase and YKL-40 are overexpressed in peripheral blood and airways in both healthy smokers and COPD subjects which may indicate smoking-related activation of macrophages, neutrophils, and epithelial cells.

Epithelial alarmin levels in exhaled breath condensate in patients with idiopathic pulmonary fibrosis: A pilot study.

INTRODUCTION: Interleukin (IL)-25, IL-33 and thymic stromal lymphopoietin (TSLP) are epithelial alarmins involved in innate immune responses and have been shown to play an important role in chronic lung diseases. No data are available regarding their levels in exhaled breath condensate (EBC) in idiopathic pulmonary fibrosis (IPF). OBJECTIVES: To examine IL-25, IL-33 and TSLP levels in the EBC obtained from patients with IPF and compare them to those in healthy controls, patients with asthma and chronic obstructive pulmonary disease (COPD). METHODS: Twenty-three patients with asthma, 25 patients with COPD, 15 patients with IPF and 16 healthy controls were studied. Concentrations of alarmins in the EBC were evaluated by means of ELISA. RESULTS: IL-25 EBC levels were numerically lowest in IPF (25.33 ± 8.84 pg/ml). However, they did not differ significantly from healthy subjects (43.18 ± 5.53 pg/ml), but were significantly lower compared to asthma (72.07 ± 6.03 pg/ml; P < .001). IL-33 EBC levels were significantly increased in IPF (3.41 ± 0.55 pg/ml) compared to healthy controls (1.20 ± 0.60 pg/ml; P < .01) but did not differ from asthma (3.68 pg/ml) and COPD levels (2.47 ± 0.34 pg/ml). There were significant correlations between IL-33 EBC levels and lung diffusion capacity of carbon monoxide (DLco ) absolute (r = .63; P < .05) and % of predicted values (r = .67; P < .01) as well as with time since diagnosis (r = -.59; P < .05) in IPF subjects. TSLP was undetectable in examined samples. CONCLUSION: IL-25 and IL-33 are detectable in the EBC obtained from IPF subjects. Increased levels of IL-33 compared to healthy controls indicate its possible role in the pathobiology of IPF.

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.

IL-33 Mediated Inflammation in Chronic Respiratory Diseases-Understanding the Role of the Member of IL-1 Superfamily.

Interleukin 33 (IL-33) is an alarmin cytokine from the IL-1 family. IL-33 is localized in the nucleus and acts there as a gene regulator. Following injury, stress or cell death, it is released from the nucleus, and exerts its pro-inflammatory biological functions via the transmembrane form of the ST2 receptor, which is present mainly as attached to immune cells. In recent years, IL-33 became a focus of many studies due to its possible role in inflammatory disorders. Among respiratory disorders, the contribution of IL-33 to the development of asthma, in particular, has been most identified. Increased level of IL-33 in lung epithelial cells and blood serum has been observed in asthma patients. The IL-33/ST2 interaction activated the Th2 mediated immune response and further production of many pro-inflammatory cytokines. Single nucleotide polymorphisms in the IL-33 gene cause a predisposition to the development of asthma. Similarly, in chronic pulmonary obstructive disease (COPD), both increased expression of IL-33 and the ST2 receptor has been observed. Interestingly, cigarette smoke, a key inducer of COPD, not only activates IL-33 production by epithelial and endothelial cells, but also induces the expression of IL-33 in peripheral blood mononuclear cells. Knowledge regarding its contribution in other respiratory disorders, such as obstructive sleep apnea, remains greatly limited. Recently it was shown that IL-33 is one of the inflammatory mediators by which levels in blood serum are increased in OSA patients, compared to healthy control patients. This mini review summarizes current knowledge on IL-33 involvement in chosen chronic respiratory disorders and proposes this interleukin as a possible link in the pathogenesis of these diseases.

A Strong Decrease in TIMP3 Expression Mediated by the Presence of miR-17 and 20a Enables Extracellular Matrix Remodeling in the NSCLC Lesion Surroundings.

Background: Lung cancer is one of the most common causes of death worldwide with a relatively high fatality rate and a mean 5-years survival of about 18%. One of the hallmarks of cancer is the extracellular matrix (ECM) remodeling, which is crucial for metastasis. This process may be regulated by miRs targeting metalloproteinases (MMPs) associated with the ECM breakdown and metastatic process or blocking the action of tissue inhibitors of metalloproteinases (TIMPs). Search for early biomarkers is essential in detecting non-small cell lung cancer (NSCLC) and distinguishing its subtypes: Adenocarcinoma (AC) from Squamous Cell Carcinoma (SCC), enabling targeted chemotherapy. Methods: MiR-17 and miR-20a targeting MMP2 and TIMP3 were selected by TCGA data analysis with further validation using miRTarBase and literature. The study group comprised 47 patients with primary NSCLC (AC and SCC subtypes). RNA was isolated from the tumor and normal-looking neighboring tissue (NLNT) free of cancer cells. MiRs from peripheral blood exosomes were extracted on admission and 5-7 days after surgery. Gene and miRs expression were assessed in qPCR using TaqMan probes. Results: The MMP2 has been expressed on a similar level in NLNT, as in cancer. While, TIMP3 expression was decreased both in cancer tissue and NLNT, with significantly lower expression in cancer. TIMP3 downregulation in NLNT and in SCC subtype correlated negatively with miR-20a. The preoperative miR-17 expression was significantly higher among patients with SCC compared to AC. Receiver operating characteristic (ROC) analysis of miR-17 as AC subtype classifier revealed 90% specificity and 48% sensitivity in optimal cut-off point with area under ROC curve (AUC): 0.71 (95%CI: 0.55-0.87). Within NSCLC subtypes: a strong negative correlation between pack-years (PY) and TIMP3 expression was observed for NLNT in the SCC group. Conclusion: The TIMP3 silencing observed in the NLNT and its negative correlation with presurgical expression of miR-20a (from serum exosomes), suggest that miRs can influence ECM remodeling at a distance from the center of the lesion. The miRs expression pattern in serum obtained before surgery significantly differs between AC and SCC subtypes. Moreover, decreased TIMP3 expression in NLNT (in SCC group) negatively correlates with the amount of tobacco smoked in a lifetime in PY.

Serum levels and gene expression of pentraxin 3 are elevated in COPD.

PURPOSE: Pentraxin 3 (PTX-3) is an acute phase protein that belongs to the pentraxin superfamily. It is synthesized locally at the site of inflammation and its levels are related to the damage of blood vessels. There are only a few studies examining the relationship between PTX-3 and chronic obstructive pulmonary disease (COPD). The aim of this study was to evaluate the serum levels of PTX-3 and relative PTX-3 gene expression in COPD patients and their correlations with cigarette smoking history and lung function. MATERIALS/METHODS: A total number of 34 participants were enrolled into this study. Only stable patients without comorbidities were recruited. After obtaining written informed consent all planned procedures were performed (pre- and post-bronchodilator spirometry, blood samples for PTX-3 serum levels and PTX-3 gene expression measurements, demographical data, medical history, COPD patients were also asked for CAT and MMRC questionnaires). RESULTS: PTX-3 serum levels were significantly higher in the COPD group (29.22 (5.47) ng/ml vs. 14.64 (3.64) ng/ml). PTX-3 gene relative quantification (RQ) values were also significantly higher in the COPD group (0.15 (1.33) vs. -2.80 (1.99)). No differences in CRP serum levels were found between the control group and the COPD group. CONCLUSIONS: Our study demonstrates that serum levels of PTX-3 and the relative expression values of its gene are elevated in COPD, and can be related to cigarette smoking history.

Is bronchoscopy always justified in diagnosis of haemoptysis? Response to the letter of Solidoro and Guerrera.

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The Expression Levels of IL-4/IL-13/STAT6 Signaling Pathway Genes and SOCS3 Could Help to Differentiate the Histopathological Subtypes of Non-Small Cell Lung Carcinoma.

BACKGROUND: The interleukin (IL)-4/IL-13/signal transducer and activator of transcription (STAT) 6 signaling pathway and the SOCS3 gene, one of its main regulators, constitute an important link between the inflammation process in the epithelial cells and inflammatory-related tumorigenesis. The present study is the first to evaluate IL-4, IL-13, STAT6, and SOCS3 mRNA expression in non-small cell lung carcinoma (NSCLC) histopathological subtypes. METHODS: Gene expression levels were assessed using TaqMan® probes by quantitative reverse transcription PCR (qRT-PCR) in lung tumor samples and unchanged lung tissue samples. RESULTS: Increased expression of IL-4, IL-13, and STAT6 was observed in all histopathological NSCLC subtypes (squamous cell carcinoma [SCC], adenocarcinoma [AC], and large cell carcinoma [LCC]). Significantly higher expression of IL-13 and STAT6 (p = 0.019 and p = 0.008, respectively) was found in SCC than in LCC. No statistically significant differences were found for IL-4. Significantly higher SOCS3 expression was found in LCC than in AC (p = 0.027). A negative correlation (rho = -0.519) was observed for the STAT6 and SOCS3 genes in SCC (p = 0.005). No associations were found between gene expression and tumor staging (post-operative Tumor Node Metastasis [pTNM], American Joint Committee on Cancer [AJCC]), patients' age, sex, or history of smoking. CONCLUSIONS: As the number of LCC cases in our study was quite low, the statistically significant results obtained should be confirmed in a larger group of patients, particularly as the relationships identified between increased IL-4, IL-13, and STAT6 mRNA expression and decreased SOCS3 expression suggest that these genes may serve as potential diagnostic markers for differentiating between NSCLC histopathological subtypes.