Nikolaos Tzanakis

The ENFUMOSA cross-sectional European multicentre study of the clinical phenotype of chronic severe asthma

Since severe asthma is a poorly understood, major health problem, 12 clinical specialist centres in nine European countries formed a European Network For Understanding Mechanisms Of Severe Asthma (ENFUMOSA). In a cross-sectional observational study, a total of 163 subjects with severe asthma were compared with 158 subjects whose asthma was controlled by low doses of inhaled corticosteroids (median dose of beclomethasone equivalents 666 µg). Despite being treated with higher doses of inhaled corticosteroids (median dose 1773 µg) and for a third of the severe asthmatics also being treated with regular, oral-steroid therapy (median daily dose 19 mg), the subjects with severe asthma met the inclusion criteria. The criteria required subjects to have undergone at least one asthma exacerbation in the past year requiring oral steroid treatment. Females dominated the severe asthma group (female/male ratio 4.4:1 versus 1.6:1 in the controlled asthmatics), and compared with controlled asthmatics, they had a predominantly neutrophilic inflammation (sputum neutrophils, 36 versus 28%) and evidence of ongoing mediator release but less atopy. From these findings and other physiological and clinical data reported in this paper, it is suggested that severe asthma might be a different form of asthma rather than an increase in asthma symptoms. The findings prompt for longitudinal studies and interventions to define the mechanisms in severe asthma.

Protective effect of fruits, vegetables and the Mediterranean diet on asthma and allergies among children in Crete

Background: Atopy is not uncommon among children living in rural Crete, but wheeze and rhinitis are rare. A study was undertaken to examine whether this discrepancy could be attributed to a high consumption of fresh fruit and vegetables or adherence to a traditional Mediterranean diet. Methods: A cross-sectional survey was performed in 690 children aged 7–18 years in rural Crete. Parents completed a questionnaire on their child’s respiratory and allergic symptoms and a 58-item food frequency questionnaire. Adherence to a Mediterranean diet was measured using a scale with 12 dietary items. Children underwent skin prick tests with 10 common aeroallergens. Results: 80% of children ate fresh fruit (and 68% vegetables) at least twice a day. The intake of grapes, oranges, apples, and fresh tomatoes—the main local products in Crete—had no association with atopy but was protective for wheezing and rhinitis. A high consumption of nuts was found to be inversely associated with wheezing (OR 0.46; 95% CI 0.20 to 0.98), whereas margarine increased the risk of both wheeze (OR 2.19; 95% CI 1.01 to 4.82) and allergic rhinitis (OR 2.10; 95% CI 1.31 to 3.37). A high level of adherence to the Mediterranean diet was protective for allergic rhinitis (OR 0.34; 95% CI 0.18 to 0.64) while a more modest protection was observed for wheezing and atopy. Conclusion: The results of this study suggest a beneficial effect of commonly consumed fruits, vegetables and nuts, and of a high adherence to a traditional Mediterranean diet during childhood on symptoms of asthma and rhinitis. Diet may explain the relative lack of allergic symptoms in this population.

Factors that influence disease-specific quality of life or health status in patients with COPD: a systematic review and meta-analysis of Pearson correlations

BACKGROUND A major goal in the management of chronic obstructive pulmonary disease (COPD) is to ensure that the burden of the disease for patients with COPD is limited and that patients will have the best possible quality of life. AIMS To explore all the possible factors that could influence disease-specific quality of life and health status in patients with COPD. METHODS A systematic review of the literature and a meta-analysis were performed to explore the factors that could have a positive or negative effect on quality of life and/or health status in patients with COPD. RESULTS Quality of life and health status are determined by certain factors included gender, disease severity indices, lung function parameters, body mass index, smoking, symptoms, co-morbidity, depression, anxiety, and exacerbations. Factors such as dyspnoea, depression, anxiety and exercise tolerance were found to be more correlated with health status than the widely used spirometric values. Forced expiratory volume in one second had a weak to modest Pearson weighted correlation coefficient which ranged from -0.110 to -0.510 depending on the questionnaire used. CONCLUSIONS The broad range of determining factors suggests that, in order to reach the management goals, health status should be measured in addition to lung function in patients with COPD.

Assessing health status in COPD. A head-to-head comparison between the COPD assessment test (CAT) and the clinical COPD questionnaire (CCQ)

BackgroundHealth status provides valuable information, complementary to spirometry and improvement of health status has become an important treatment goal in COPD management. We compared the usefulness and validity of the COPD Assessment Test (CAT) and the Clinical COPD Questionnaire (CCQ), two simple questionnaires, in comparison with the St. George Respiratory Questionnaire (SGRQ).MethodsWe administered the CAT, CCQ and SGRQ in patients with COPD stage I-IV during three visits. Spirometry, 6 MWT, MRC scale, BODE index, and patients perspectives on questionnaires were recorded in all visits. Standard Error of Measurement (SEM) was used to calculate the Minimal Clinical Important Difference (MCID) of all questionnaires.ResultsWe enrolled 90 COPD patients. Cronbachs alpha for both CAT and CCQ was high (0.86 and 0.89, respectively). Patients with severe COPD reported worse health status compared to milder subgroups. CAT and CCQ correlated significantly (rho =0.64, p < 0.01) and both with the SGRQ (rho = 0.65; CAT and rho = 0.77; CCQ, p < 0.01). Both questionnaires exhibited a weak correlation with lung function (rho = −0.35;CAT and rho = −0.41; CCQ, p < 0.01). Their reproducibility was high; CAT: ICC = 0.94 (CI 0.92-0.96), total CCQ ICC = 0.95 (0.92-0.96) and SGRQ = 0.97 (CI 0.95-0.98). The MCID calculated using the SEM method showed results similar to previous studies of 3.76 for the CAT, 0.41 for the CCQ and 4.84 for SGRQ. Patients suggested both CAT and CCQ as easier tools than SGRQ in terms of complexity and time considerations. More than half of patients preferred CCQ instead of CAT.ConclusionsThe CAT and CCQ have similar psychometric properties with a slight advantage for CCQ based mainly on patients’ preference and are both valid and reliable questionnaires to assess health status in COPD patients.

Prognostic Value of Serum Tumor Markers in Patients with Lung Cancer

Background: The role of tumor markers in the diagnosis and prognosis of lung cancer is under investigation. Objectives: The aim of this study was to investigate the diagnostic and prognostic significance of pre-therapeutic levels of various serum tumor markers, CYFRA 21-1, neuron-specific enolase (NSE), tissue polypeptide antigen (TPA), carcinoembryonic antigen (CEA), CA 125 and squamous cell carcinoma antigen (SCCAg), in patients with lung cancer. Methods: We studied 102 consecutive patients (mean age 65.2 ± 11 years) with newly diagnosed lung cancer (96 males, 94%, with a mean age of 66.3 ± 10.5 years). All patients had a 5-year follow-up. Measurements of the serum tumor markers were performed on initial diagnosis. Results: Eighty-four patients (82%) had non-small-cell lung cancer (NSCLC) and 18 (18%) small-cell lung cancer (SCLC). From the 84 patients with NSCLC, 34 patients (33%) had squamous-cell lung cancer, 23 (22%) adenocarcinoma and 23 (22%) large-cell carcinomas. The overall median survival was 8.5 months. All SCLC patients had extensive disease with a median survival of 10.1 months and NSCLC patients of 8.4 months. Significant differences in the mean values of NSE and CYFRA 21-1 were observed between SCLC and NSCLC. In NSCLC, CYFRA 21-1, TPA, CA 125 and SCCAg serum levels were related to the stage of the disease at diagnosis, and CYFRA 21-1, NSE, TPA and CA-125 were related to a poor outcome. None of the above tumor markers was related to survival in the SCLC group. Conclusion: CYFRA 21-1 and NSE may help to differentiate cell types in lung cancer patients. Also, CYFRA 21-1 with TPA and CA 125 may provide useful information regarding the staging of the disease at diagnosis and the prognosis of patients with NSCLC.

Survivin -31G/C promoter polymorphism and sporadic colorectal cancer

IntroductionSurvivin is an apoptotic inhibitor, plays an important role in cell cycle regulation, and may be involved in the development and progression of cancer. A common polymorphism at the survivin gene promoter (-31 G/C) has been shown to influence survivin expression and the risk for cancer.AimThe aim of the present study was to investigate whether this polymorphism could be involved in the sporadic colorectal cancer (CRC) development, prognosis, and survival.Materials and methodsThe -31G/C polymorphism of survivin promoter was analyzed by polymerase chain reaction (PCR) restriction fragment length polymorphism method in biopsies from 312 patients with sporadic CRC and 362 healthy individuals. Survivin messenger RNA (mRNA) expression in CRC tissues was detected by quantitative reverse transcriptase PCR.Results and discussionThe genotype frequencies for -31GG, -31GC, and -31CC were 21.79%, 41.99%, and 36.22% in CRC patients and 33.98%, 45.03%, and 20.99% in healthy subjects, respectively. The frequencies of the survivin -31C allele and CC genotype were significantly higher in CRC patients than in healthy subjects (p < 0.0001). Homozygotes for the -31CC survivin genotype, expressed 1.6-fold higher mRNA levels of survivin compared to cases with the -31GG and -31GC genotypes.ConclusionThe -31CC genotype of survivin promoter is associated with CRC and may be a risk factor for CRC.

Isolation of myeloid and plasmacytoid dendritic cells from human bronchoalveolar lavage fluid.

Studies of bronchoalveolar lavage fluid (BALF) dendritic cells (DC) have been hampered by the scarcity of DC and the lack of DC‐specific surface markers. Four surface Ag have been recently described as specific markers for distinct subsets of DC and have been used for the isolation and characterization of fresh noncultured DC from lung resection specimens: BDCA‐1 (CD1c) and BDCA‐3 for myeloid DC type 1 and type 2, respectively, and BDCA‐2 and BDCA‐4 for plasmacytoid DC. The aim of this study was to develop a new method for the isolation of BALF DC, using immunomagnetic separation of BDCA+ cells. Mononuclear cells were obtained from BALF after Ficoll‐Paque density gradient centrifugation. Monocytes, T cells and B cells were magnetically labelled and depleted. The unlabelled cell fraction was incubated with BDCA‐1, BDCA‐3 and BDCA‐4 beads and the total BDCA+ DC were retained. The ability of isolated DC to induce T‐cell responses was evaluated by coculturing the isolated DC with immunomagnetically sorted naive T cells. The above procedure resulted in a population of viable DC that showed a strong capacity in induce T‐cell responses. Functionally intact human BALF myeloid DC types 1 and 2 as well as plasmacytoid DC can be easily obtained by immunomagnetic isolation. Considering that bronchoalveolar lavage is a minimally invasive procedure, these cells are optimal candidates with which to elucidate the properties and capabilities of pulmonary DC.

Airway inflammation and hyperresponsiveness to adenosine 5'-monophosphate in chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is often accompanied by bronchial hyperresponsiveness (BHR). Measurement of BHR may give information about airway inflammation.

Effects of Greek orthodox christian church fasting on serum lipids and obesity

BackgroundNo study to date has focused on the impact of Greek Orthodox Christian fasting on serum lipoproteins and obesity yet.Methods120 Greek adults were followed longitudinally for one year. Sixty fasted regularly in all fasting periods (fasters) and 60 did not fast at all (controls). The three major fasting periods under study were: Christmas (40 days), Lent (48 days) and Assumption (August, 15 days). A total of 6 measurements were made during one year including pre- and end-fasting blood collection, serum lipoprotein analyses and anthropometric measurements.ResultsStatistically significant end-fasting total and LDL cholesterol differences were found in fasters. Fasters compared to controls presented 12.5% lower end-total cholesterol (p < 0.001), 15.9% lower end-LDL cholesterol (p < 0.001) and 1.5% lower end-BMI (p < 0.001). The end- LDL/HDL ratio was lower in fasters (6.5%, p < 0.05) while the change in end- HDL cholesterol in fasters (4.6% decline) was not significant. Similar results were found when the pre- and end-fasting values of fasters were compared. No change was found in control subjects.ConclusionsAdherence to Greek Orthodox fasting periods contributes to a reduction in the blood lipid profile including a non-significant reduction in HDL cholesterol and possible impact on obesity.

Managing comorbidities in COPD

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality worldwide. Age and smoking are common risk factors for COPD and other illnesses, often leading COPD patients to demonstrate multiple coexisting comorbidities. COPD exacerbations and comorbidities contribute to the overall severity in individual patients. Clinical trials investigating the treatment of COPD routinely exclude patients with multiple comorbidities or advanced age. Clinical practice guidelines for a specific disease do not usually address comorbidities in their recommendations. However, the management and the medical intervention in COPD patients with comorbidities need a holistic approach that is not clearly established worldwide. This holistic approach should include the specific burden of each comorbidity in the COPD severity classification scale. Further, the pharmacological and nonpharmacological management should also include optimal interventions and risk factor modifications simultaneously for all diseases. All health care specialists in COPD management need to work together with professionals specialized in the management of the other major chronic diseases in order to provide a multidisciplinary approach to COPD patients with multiple diseases. In this review, we focus on the major comorbidities that affect COPD patients. We present an overview of the problems faced, the reasons and risk factors for the most commonly encountered comorbidities, and the burden on health care costs. We also provide a rationale for approaching the therapeutic options of the COPD patient afflicted by comorbidity.