Survival of Patients with Cystic Fibrosis Depending on Mutation Type and Nutritional Status.

The purpose of the study was to evaluate the influence of nutrition and of the severity of mutation type on survival rate in cystic fibrosis (CF) patients. Data were longitudinally collected from 60 hospitalized adult CF patients, aged 18-50. The variables consisted of body mass index (BMI) ratio, Cole's BMI cut-off points, severity of mutation type, and survival rate of CF patients. We found that the mean BMI was strongly associated with the severity of mutation type and was significantly lower in patients with severe mutations of grade I and II. The mutation type significantly affected the patients' survival rate; survival was greater in patients with mild and undefined mutation types. The BMI and Cole's cut-off points also had a significant influence on survival rate. CF patients, who suffered from malnutrition and emaciation, had a shorter survival rate than those with proper nutritional status. In conclusion, the study findings confirmed a significant effect of nutritional status and of mutation type on survival rate of CF patients.

Carotid artery intima-media thickness in hypertensive patients with obstructive sleep apnea.

In this study we determined the relationship between the severity of obstructive sleep apnea (OSA) and body mass index (BMI), systolic and diastolic blood pressure (SBP, DBP), and carotid intima-media thickness (cIMT) in 30 hypertensive male patients, aged 30-70, with newly diagnosed OSA (15 with moderate OSA - Group A, and 15 with severe OSA - Group B) and 20 non-OSA hypertensive individuals (Group C). We revealed significant differences in cIMT between Groups B and C (0.9 ± 0.3 vs. 0.6 ± 0.1 mm and 1.0 ± 0.4 vs. 0.6 ± 0.2 mm in the right and left common carotid arteries, respectively; p <0.05). Increased carotid intima-media thickness in severe OSA was accompanied by higher systolic and diastolic blood pressures compared with both moderate OSA and control subjects. We conclude that in severe OSA increased blood pressure goes in tandem with the thickness of carotid intima-media, which helps explain increased cardiovascular risk in these patients.

Impulse oscillometry in the diagnosis of airway resistance in chronic obstructive pulmonary disease.

Spirometry is a standard lung function test for diagnosis and staging of chronic obstructive pulmonary disease (COPD). Impulse oscillometry (IOS) can be complementary to spirometry, especially in patients at advanced age and with physical or mental disorders who cannot be diagnosed through spirometry. The aim of this study was to compare IOS and spirometry in the assessment of airway obstruction in COPD. The study was conducted in 112 stable COPD patients, including 29 females and 83 males of the mean age of 69±11 years. The oscillometric evaluation included total (R5), peripheral (R5-R20), and negative reactance (X5), which were compared with the predicted forced expiratory volume in 1 s (FEV1%pred). The findings show a significantly negative correlation between FEV1%pred and the R5, R5-R20, and X5. COPD patients had increased R5, R5-R20, and X5. The severity of bronchial obstruction found by impulse oscillometry correlated well the spirometric assessment. IOS is a simple to perform test that may be helpful for functional examination of COPD patients.

Plasma selectins in patients with obstructive sleep apnea.

Obstructive sleep apnea (OSA) is an independent risk factor in the pathogenesis of -cardiovascular diseases. The aim of the study was to analyze three specific adhesion molecules involved in the development of an atherosclerotic plaque: E-selectin (endothelium), L-selectin (leukocyte surface), and P-selectin (from platelet), circulating in plasma in patients at different OSA severity. Eighty non-smoking male Caucasians aged 30-64 were enrolled into the study after clinical, biochemical, and polysomnographic examinations. The patients were divided into four groups based on the results of apnea/hypopnea index (AHI): OSA-0 with AHI 0-4.9 (n = 20), OSA-1 with AHI 5-15 (n = 21), OSA-2 with AHI 16-30 (n = 18), OSA-3 with AHI ≥ 31 (n = 21). Complete blood count, oral glucose tolerance test, fasting lipid profile, C-reactive protein and insulin, and plasma concentrations of soluble E-selectin, P-selectin and L-selectin were measured. We found a progressive increase in the concentrations of all three selectins with the severity of OSA. In conclusion, the level of plasma adhesion molecules may be indicative of OSA severity and may contribute to cardiovascular sequelae.

Lung impairment in scleroderma.

Scleroderma typically manifests as fibrosis of the skin, but may also involve other organs, particularly the lungs. Interstitial lung disease and functional abnormalities are observed in the majority of patients. The aim of this study was to evaluate radiological changes in the lungs and their correlation with functional disorders in scleroderma patients. The study was conducted in 37 scleroderma patients (F/M-31/6). High resolution computed tomography (HRCT), Warrick score system and spirometry, body plethysmography, and lung diffusion examinations (DLco) were performed. The HRCT showed septal and subpleural lines in 70%, ground-glass opacities in 51%, and honeycomb lungs in 30% of the cases. The DLco values were decreased in 92% of the patients. Total lung capacity (TLC) showed a restrictive pattern in 24% of the patients, and only in 11% of them obstruction predominated. The Warrick score correlated inversely with both DLco (r=0.36; p>0.05). Interstitial lung disease often coexists with scleroderma and is accompanied by functional lung abnormalities.

Should the dosage of propofol be higher and independent of immunosuppressive therapy in adult cystic fibrosis patients undergoing sedation during flexible video bronchoscopy?

OBJECTIVE: Flexible video bronchoscopy (FVB) performed under sedation is a useful procedure in adults with cystic fibrosis (CF). Propofol dosage for CF is poorly described, although it is of high importance for professionals. The study aimed to assess whether propofol dosage should be higher in adults CF undergoing sedation during FVB. PATIENTS AND METHODS: 50 adult CF and non-CF patients undergoing sedation during FVB were included. Clinical features of studied patients were assessed. In CF group spirometry, liver enzymes, inflammatory biomarkers, albumin, protein concentration, WBC were estimated. Propofol and fentanyl dosage was calculated. Multiple regression model was performed. RESULTS: CF patients were characterized by a lower mean value of body weight and lower mean requirement of total propofol (135 mg in CF vs. 145 mg in non-CF). Calculated propofol dose per kg of body weight was significantly higher in CF (2.43 mg/kg vs. 2.04 mg/kg) and did not depend on the bronchopulmonary disease stage. Propofol dose per kg of body weight was predicted by CF status (CF vs. non-CF), sex, and age. CONCLUSIONS: Adult CF patients not receiving immunosuppressive therapy require higher propofol dose per kg of body weight compared to non-CF, independently on bronchopulmonary disease stage showing a narrow therapeutic window for propofol in CF group.

Endothelium-derived markers and antioxidant status in the blood of obstructive sleep apnea males.

OBJECTIVE: The relationship between obstructive sleep apnea (OSA) and cardiovascular disease is intensively discussed. Endothelial leukocyte adhesion molecule (E-selectin) is one of factors facilitating leukocyte migration to the subendothelial layer which could be considered proatherogenic. The aim of the study was to determine E-selectin levels and total plasma antioxidant status (TAS) in the blood of different stage OSA patients. METHODS: Non-smoking, OSA-suspected males, aged 30-63, were selected for the study. An EMBLA polysomnographic system was used to establish the severity of apneic episodes. The results of apnea/hypopnea index (AHI) allowed dividing patients into the following groups: OSA-0 with AHI 0-4.9 (n=14), OSA-1 with AHI 5-15 (n=14), OSA-2 with AHI 16-30 (n=13), OSA-3 with AHI > or =30 (n=13). Complete blood count (CBC), glycemia during oral glucose tolerance test, fasting plasma lipid profile, uric acid, and high sensitivity C-reactive protein (hsCRP) were estimated among routine parameters. We determined plasma concentrations of E-selectin and total antioxidant status. RESULTS: We found progressively decreasing concentrations of TAS (P=0.03) and increased concentrations of E-selectin (P=0.0001) from OSA-0 to OSA-3 subjects. No correlation between E-selectin and metabolic parameters was noted. - CONCLUSION: In the studied OSA groups, E-selectin appeared an independent proatherogenic factor.

Adipocytokines in sleep apnea syndrome.

OBJECTIVE: Biomarkers of adipose tissue may affect glucose and lipid metabolism and present pro-inflammatory properties, thus could be involved in the pathobiochemistry of cardiovascular disease (CVD). The coexistence of sleep apnea syndrome (OSA) and metabolic risk factors of CVD is worth explaining. The aim of the study was to compare the serum adipocytokines in subjects with and without OSA, who had all elevated body mass index (BMI). METHODS: Overweight (BMI: 25.0-29.9 kg/m2) and obese (BMI: 30.0-39.9 kg/m2) OSA-suspected Caucasian males, aged 30-63, with no acute disease or chronic disorder underwent polysomnographic evaluation to select OSA-positive (AHI > or = 5) and OSA-negative (AHI <5) subjects. Four subgroups were created of 18 persons each: Over(weight)-OSA-Neg, Over-OSA-Pos, Obese-OSA-Neg, Obese-OSA-Pos. In all subjects, plasma carbohydrate and lipid metabolism parameters, and serum uric acid, resistin and leptin concentrations were determined. RESULTS: A decreased resistin level was observed in Over-OSA-Pos vs. Over-OSA-Neg subjects (P=0.037) as well as in Obese-OSA-Pos vs. Obese-OSA-Neg (P=0.045). No differences in leptin concentrations were observed. A positive correlation between leptin and BMI was in both overweight subgroups and a negative one between resistin and fasting glucose was in both obese subgroups. CONCLUSIONS: OSA may decrease the serum resistin level in subjects with excess body mass and also may contribute to glucose metabolism, but has no influence on the leptin level.

Diagnostic value of plasma expression of microRNAs complementary to Drosha and Dicer in lung cancer patients.

OBJECTIVE: Lung cancer (LC) is diagnosed mostly in advanced, non-operable stage, with poor prognosis. The analysis of microRNAs may be a useful tool for early and non-invasive detection of cancer. Dicer and Drosha are enzymes with an essential role for microRNA biogenesis. The aim of our study was to analyze the expression of miRNA-27a-3p, miRNA-31, miRNA-182, miRNA-195 with the ability to reciprocal regulation of Dicer and Drosha expression in lung cancer patients. PATIENTS AND METHODS: The relative expression of microRNAs was detected by qPCR in plasma of 160 LC patients. The U-Mann Whitney test was used to compare the relative expression between particular groups of lung cancer patients and healthy individuals. The diagnostic value of microRNAs examination was analyzed using a receiver operating curve. RESULTS: We demonstrated that the plasma levels of miRNA-27, miRNA-31 and miRNA-182 were significantly higher and miRNA-195 significantly lower in the whole group of LC patients and in patients with early stages of NSCLC, in comparison with healthy donors. ROC analysis showed that four studied microRNAs have a potential diagnostic value for early stages of NSCLC with AUC=0.95 for miRNA-27a (94% sensitivity and 81% specificity, p=0.0001), 0.71 for miRNA-31 (73% sensitivity and 61% specificity, p=0.001) 0.77 for miRNA-182 (70% sensitivity and 79% specificity, p=0.0001) and 0.82 for miRNA-195 (74% sensitivity and 80% specificity, p=0.0001). CONCLUSIONS: We have proved that the expression of miRNA-27a-3p, miRNA-31, miRNA-182, and miRNA-195 in patients with LC is different from the expression of these molecules in healthy people. The examination of these microRNAs in plasma could be used in non-invasive lung cancer diagnosis.

Serum from patients with chronic obstructive pulmonary disease promotes proangiogenic behavior of the vascular endothelium.

OBJECTIVE: It has been documented that COPD is a risk factor for lung cancer. In COPD patients, changes in lung angiogenesis - a critical process in the development of lung cancer - have been poorly investigated. We aimed to determine whether serum from COPD patients could promote the proangiogenic capabilities of endothelial cells in vitro. PATIENTS AND METHODS: The research was carried out using sera from COPD patients and healthy volunteers, endothelial cells EA.hy926, and bronchial epithelial cells. The concentration of angiogenic molecules was quantified using ELISA tests. The proliferation and migration of EA.hy926 were tested using fluorescence-based methods. Tube formation was analyzed with a commercially available assay. RESULTS: Sera from COPD patients and conditioned media generated by epithelial cells exposed to these sera stimulate proliferation, but not migration, of EA.hy926. This coincided with increased tube formation in both experimental regimens. The sera from COPD patients contained increased levels of CCL2, CCL21, and HGF, whereas the conditioned media generated by epithelial cells treated with these sera exhibited increased levels of CCL2, CCL21, CXCL8, FGF, and sICAM-1. The concentration of angiogenic markers in the sera and conditioned media, and their effect on the behavior of the endothelium were independent of smoking status (COPD and controls), stage of obstruction, and disease group (COPD). CONCLUSIONS: The increased incidence of lung malignancy in COPD patients may be associated, at least to some extent, with the direct and indirect proangiogenic activity of their sera (via alterations in the secretome of epithelial cells).

Regulatory T cells in malignant pleural effusions subsequent to lung carcinoma and their impact on the course of the disease.

Tumors exert suppressive effects on the host immune system and tumor progression can be linked to functional impairments of immune cells. Regulatory T cells (Treg) are a subpopulation of T lymphocytes and play a key role in suppressing immune responses against autoimmune diseases and cancer. The aim of the study was to investigate the prevalence of Treg in malignant and benign pleural effusions and to evaluate the relationship between Treg frequency and disease advance. Pleural effusions from 76 patients were subjected to a routine laboratory diagnosis and analyzed by conventional cytology. Biological materials were divided into three groups: malignant pleural effusions with malignant cells, effusions from patients with malignancy but without malignant cells, and non-malignant pleural effusions. The frequency of Treg in malignant pleural effusions was significantly higher compared to non-malignant effusions. In general, the increase in Treg frequency was correlated with a decrease in the percentage of lymphocytes and an increase in T CD4+ and T CD4+ CD25+ cells. The highest percentage of Treg was observed among patients with the most advanced clinical stage of lung cancer in terms of size and location of a primary tumor, T4. A Kaplan-Meier survival analysis showed a statistically significant trend towards an adverse outcome for patients representing higher Treg counts. Overall, our results support the extraordinary potential of Treg control in future anticancer therapy.

Methylation of the DCLK1 promoter region in circulating free DNA and its prognostic value in lung cancer patients.

INTRODUCTION: The possibility of detection of suppressor genes methylation in circulating free DNA (cf-DNA) of cancer patients and the lack of methylation in healthy individuals makes this epigenetic alternation an ideal diagnostic marker of neoplastic processes. Moreover, hypermethylation in several genes promoter was described as a biomarker of lung cancer. Methylation in the gene encoding doublecortin-like kinase 1 (DCLK1) is observed in patients with colorectal cancer and cholangiocarcinoma. However, there are no studies concerning DCLK1 methylation in lung cancer patients. The aims of the study was to evaluate the frequency of DCLK1 promoter methylation in cf-DNA of lung cancer patients and of healthy persons as well as the usefulness of this test for predicting the lung cancer course. MATERIALS AND METHODS: DCLK1 methylation status was evaluated in DNA isolated from peripheral blood plasma from 65 lung cancer patients and 95 healthy individuals. After DNA bisulfitation, DCLK1 methylation was determined using the qMSP-PCR technique. Moreover, the presence of DCLK1 methylation was correlated with the overall survival (OS) probability of lung cancer patients. RESULTS: DCLK1 promoter methylation was detected in 32 lung cancer patients (49.2 %) and 8 healthy individuals (8.4 %). The methylation of the region before transcription start site (TSS) and the region after TSS of DCLK1 gene was detected in 28 and 11 patients, respectively. In seven cases (10.8 %), the DCLK1 promoter methylation in both regions was reported simultaneously. The methylation was observed slightly frequently in patients with small cell lung cancer (75 % of SCLC patients). The median overall survival of patients with DCLK1 promoter methylation was lower than that of patients without DCLK1 gene modification (p = <0.001, HR = 4.235). CONCLUSIONS: The evaluation of DCLK1 promoter region methylation may be useful in both early diagnosis and prediction of the course of lung cancer.

Circulating adipokines and organ involvement in patients with systemic sclerosis.

BACKGROUND: In recent years, mediators synthesized in the adipose tissue, the so-called adipokines, have been reported to play important roles in the pathogenesis of autoimmune rheumatic diseases. OBJECTIVE: To compare serum leptin, adiponectin and resistin levels in patients with systemic sclerosis (SSc) and healthy controls. To find possible relationship between serum levels of adipokines and organ involvement with focus on interstitial lung disease in SSc patients. PATIENTS AND METHODS: Lung involvement was assessed functionally (body plethysmography, diffusing capacity of the lung for carbon monoxide (DLCO) and six-minute walk test) and radiologically (using average disease extent on high resolution computed tomography (HRCT) of the lungs according to the percentage of interstitial changes) in 29 SSc patients. Quantitative sandwich ELISA was used to measure resistin, leptin and adiponectin concentrations in sera of patients and 30 healthy controls. RESULTS: We found no statistically significant differences in serum resistin, leptin and adiponectin levels between SSc patients and the controls. However, serum adiponectin concentrations were significantly lower in active than in inactive patients, they also correlated positively with vital capacity (VC) (p=0.04) and negatively with Valentini activity score (p=0.04). Serum resistin levels were significantly elevated in patients with digital ulcers (p=0.03) and serum concentrations of leptin were associated with the duration of SSc symptoms other than Raynaud's phenomenon (p<0.01) CONCLUSIONS: Serum adiponectin should be further investigated as a candidate for SSc activity marker and resistin may play a role in ulcer development in SSc patients.

Lung cancer risk in nonsmokers and GSTM1 and GSTT1 genetic polymorphism.

Glutathione S-transferase (GST) polymorphism may contribute to the individual variability in detoxifying lung carcinogens. This effect might be particularly relevant at low-level exposure to environmental carcinogens, such as in nonsmokers exposed to environmental tobacco smoke (ETS). We conducted a case-control study among 122 nonsmoking lung cancer cases and 121 nonsmoking controls from eight countries. Information on environmental exposures was obtained through a personal interview. The presence of GSTM1 and GSTT1 genes was determined using multiplex PCR. GSTM1-positive samples were then analyzed for *1A and *1B polymorphism using an allele-specific amplification-PCR method. GSTM1*2 (null) individuals had an odds ratio (OR) of lung cancer of 1.5 [95% confidence interval (CI), 0.9-2.7]; the risk associated with this genotype was higher for cases with squamous and small cell carcinomas (OR, 2.3; 95% CI, 0.9-6.1) than for cases with adenocarcinomas. It was also elevated in individuals with long-term exposure to indoor wood combustion (OR, 3.1; 95% CI, 0.9-9.9), in subjects who mainly lived in a rural setting (OR, 3.6; 95% CI, 1.0-13), and in cases exposed to occupational carcinogens (OR, 10.7; 96% CI, 0.4-260) but not in subjects exposed to ETS. GSTT1*2 subjects did not show a risk of lung cancer. Our study suggests that the effect of GSTM1 polymorphism in nonsmokers is similar to that found in smokers. It does not seem to interact with ETS exposure, although we cannot exclude that it does in association with exposure to other specific environmental carcinogens.

Vitamin A (retinol) level in colon and lung cancer patient sera.

Serum vitamin A (retinol) level was determined in colon and lung cancer patients. As a control served young healthy people and non cancer hospital patients at the age similar to those with tumors. Vitamin A content in cancer patients was found to be statistically lower as compared to control groups.

[Evaluation of occurrence of fungal infection in patients with lung cancer]. / Ocena wystepowania zakazenia grzybiczego u chorych z rakiem pluc.

The study was aimed at determination of frequency and size of fungal infection in patients with lung carcinoma, as compared with the control group. The study involved 20 patients with histologically confirmed lung carcinoma and--as a control group--20 patients with other lung diseases and healthy volunteers. Quantitative mycological investigation of sputum and bronchial rinsings were performed threefold. The degree of infection of these materials was determined on a Sabouraud medium. Candida-like fungi were determined basing on API 20 AUX test. In majority of patients with lung carcinoma, presence of pathogenic fungi, mostly from the genus Candida, was detected in sputum or bronchial secretions. In one third of cases infection was severe or very severe which was dependent of the stage of disease advancement. In control group severe infection was observed only sporadically.

[Trial of evaluating co-existent fungal infection during course of neoplastic disease in patients with lung cancer]. / Próba oceny wplywu wspólistniejacego zakazenia grzybiczego na przebieg choroby nowotworowej u chorych z rakiem pluc.

The study was aimed at determination of possible connection between co-existing fungal infection in patients with lung carcinoma with course of neoplastic disease and ability to achieve remission by application of different methods of treatment. The study involved 25 patients with histologically confirmed lung carcinoma. Their sputum and bronchial rinsings were tested mycologically. The tests were performed at the moment of diagnosis of the diseases, during and after treatment. In all patients occurrence and type of Candida infections was investigated. Dynamics of fungal infection was measured by a scale from minimal to very severe. In about 1/3 of patients at the moment of diagnosis of the disease, severe or very severe infection was seen which was dependent of stage of the disease advancement. These preliminary studies seem to indicate that presence of severe or very severe fungal infection is not favourable prognostically and frequently correlates with a progress of neoplastic changes and worse response to treatment.

[In vitro susceptibility to antifungal agents of Candida strains isolated from patients with various diseases of the respiratory tract]. / Wrazliwosc na leki przeciwgrzybicze in vitro szczepów Candida wyizolowanych od chorych na rózne choroby ukladu oddechowego.

The aim of the study was the estimation of in vitro susceptibility to antifungal agents of yeast isolated from sputum of 70 respiratory diseases patients using the disc-diffusion method-antimycogram. The following agents were tested: amphotericin B, 5-fluorocytosine, nystatin, ketoconazole, fluconazole. Only Candida strains were isolated from sputum, 82% of them were Candida albicans. We noted differences in susceptibility to antimycotics of Candida strains. The best antimycotic in vitro was 5-fluorocytosine. 54% of isolated Candida strains were resistant to 1 or more antimycotics.

[Multifocal colonization and hydrolytic activity of Candida strains isolated from lung cancer patients]. / Wieloogniskowe wystepowanie i aktywnosc hydrolityczna grzybów z rodzaju Candida wyizolowanych od chorych na raka pluca.

UNLABELLED: The aim was looking for correlation between hydrolytic activity and multifocal Candida invasions in 33 lung cancer patients (LC) before treatment. Materials used in this study were pharyngeal and rectal swab, sputum, bronchial secretion and urine. Isolation and identification of fungi were performed using ID C 32 test and the hydrolytic activity using API ZYM test. RESULTS: 1/ there were only Candida strains, especially C. albicans (78,8 %) isolated 2/ Candida in more than one sample were present in 74%, in three or four in 27,7% of LC. 3/ Candida strains produced 17 among 19 investigated enzymes 4/ there were statistically significant correlations between the activity of some hydrolytic enzymes and number of Candida foci observed. CONCLUSIONS: 1/ the results confirmed the influence of Candida hydrolytic activity on the course of infection. 2/ hydrolytic enzymes activity is one of important Candida pathogenicity factors.