Geoepidemiology and space-time analysis of Primary biliary cirrhosis in Crete, Greece.

BACKGROUND & AIMS: The prevalence of Primary biliary cirrhosis varies in different geographical areas. This might reflect genetic or environmental risk factors. We aimed to define Primary biliary cirrhosis prevalence and incidence, describe patient's spatial distribution, generate prediction maps and detect any possible routing pattern of time-spatial appearance of the disease in Crete, Greece. METHODS: From 1990-2010, 245 Primary biliary cirrhosis patients diagnosed and followed up at the Gastroenterology Department of the University Hospital and the District Hospitals of the island, were contacted and 222 were included in the time-spatial analysis. To map their spatial distribution per 5-year periods, geospatial models were applied in Gis-ArcMap 9.3 software. Kriging Interpolation methods were used to generate prediction maps for the disease in Crete. Areas of high and low probability of disease occurrence were estimated through multicriteria modelling. The disease route was defined by Gis-ArcMap's toolbox. RESULTS: Prevalence was found to be 365 cases per million, with a mean incidence of 20.88 (range 3.79-35.99). Prediction map estimates from 1.22 to 11 patients per 50 km2 all over Crete. Areas of high risk of disease occurrence are located in the Eastern part, while low risk in the Western part of the island. DISCUSSION: Prevalence and incidence of Primary biliary cirrhosis in Crete are among the higher published in Europe. Given the homogeneous and stable study population and the geopolitics of the island, the heterogeneity in the time-spatial distribution and the route of disease appearance strongly suggest a role for environmental causative agents.

Alpha1-antitrypsin deficiency in Greece: Focus on rare variants.

PURPOSE: A1Antitrypsin deficiency (AATD) pathogenic mutations are expanding beyond the PI*Z and PI*S to a multitude of rare variants. AIM: to investigate genotype and clinical profile of Greeks with AATD. METHODS: Symptomatic adult-patients with early-emphysema defined by fixed airway obstruction and computerized-tomography scan and lower than normal serum AAT levels were enrolled from reference centers all over Greece. Samples were analyzed in the AAT Laboratory, University of Marburg-Germany. RESULTS: Included are 45 adults, 38 homozygous or compound heterozygous for pathogenic variants and 7 heterozygous. Homozygous were 57.9% male, 65.8% ever-smokers, median (IQR) age 49.0(42.5-58.5) years, AAT-levels 0.20(0.08-0.26) g/L, FEV1(%predicted) 41.5(28.8-64.5). PI*Z, PI*Q0, and rare deficient allele's frequency was 51.3%, 32.9%,15.8%, respectively. PI*ZZ genotype was 36.8%, PI*Q0Q0 21.1%, PI*MdeficientMdeficient 7.9%, PI*ZQ0 18.4%, PI*Q0Mdeficient 5.3% and PI*Zrare-deficient 10.5%. Genotyping by Luminex detected: p.(Pro393Leu) associated with MHeerlen (M1Ala/M1Val); p.(Leu65Pro) with MProcida; p.(Lys241Ter) with Q0Bellingham; p.(Leu377Phefs*24) with Q0Mattawa (M1Val) and Q0Ourem (M3); p.(Phe76del) with MMalton (M2), MPalermo (M1Val), MNichinan (V) and Q0LaPalma (S); p.(Asp280Val) with PLowell (M1Val); PDuarte (M4), YBarcelona (p.Pro39His). Gene-sequencing (46.7%) detected Q0GraniteFalls, Q0Saint-Etienne, Q0Amersfoort(M1Ala), MWürzburg, NHartfordcity and one novel-variant (c.1A>G) named Q0Attikon.Heterozygous included PI*MQ0Amersfoort(M1Ala), PI*MMProcida, PI*Mp.(Asp280Val), PI*MOFeyzin. AAT-levels were significantly different between genotypes (p = 0.002). CONCLUSION: Genotyping AATD in Greece, a multiplicity of rare variants and a diversity of rare combinations, including unique ones were observed in two thirds of patients, expanding knowledge regarding European geographical trend in rare variants. Gene sequencing was necessary for genetic diagnosis. In the future the detection of rare genotypes may add to personalize preventive and therapeutic measures.

Predictors of laterality of motor block during epidural analgesia in a mixed surgical population.

BACKGROUND: Predictors of laterality of motor block during epidural analgesia are currently unknown, as studies so far have yielded conflicting results. We aimed to evaluate predictors of post-operative asymmetric lower extremity motor blockade in a mixed surgical population. METHODS: This is a retrospective analysis of 578 consecutive patients with post-operative epidural analgesia for a variety of surgical procedures. A priori determined potential predictors of unilateral motor block were age, gender, body mass index, type of surgical procedure, vertebral level of puncture, catheter insertion depth into the epidural space and concentration of local anaesthetic. Logistic regression analysis was employed for evaluating predictors of laterality. RESULTS: Unilateral motor block occurred in 29.2% of the patients. Univariate logistic regression analysis showed that young age, female gender, gynaecologic procedures, a low puncture level, an increased depth of catheter insertion and a high ropivacaine concentration (2 mg/ml vs. less than 2 mg/ml) were significantly associated with increased incidence of laterality. Multivariate analysis revealed that age (OR = 0.73 per decade increase, P = 0.00001), the vertebral level of epidural puncture (OR = 1.37 per lowering vertebral level, P < 0.000001) and the depth of catheter insertion (OR = 1.46 per centimetre deeper, P = 0.001) were independent predictors of unilateral motor block. CONCLUSION: These results suggest that young patients with lumbar epidural analgesia or deep catheter insertion should be frequently monitored for the occurrence of laterality of motor block. Also, these results provide support for a prospective study to determine the optimal catheter insertion depth to decrease the risk of unilateral motor block.

Heart rate variability may identify patients who will develop severe bradycardia during spinal anaesthesia.

BACKGROUND AND OBJECTIVES: The reported incidence of cardiac arrest during spinal anaesthesia is 6.4+1.2 per 10,000 patients. Many of these arrests occurred in healthy young patients during minor surgery. This raises the question of whether some of them were avoidable. We investigated the value of Heart Rate Variability (HRV) to identify patients prone to developing severe bradycardia during spinal anaesthesia. METHODS: Eighty ASA I-II patients, 21-60 years of age, undergoing elective surgery under spinal anaesthesia were studied. The HRV was assessed for 25 min before the spinal block. Two spectral components of HRV were calculated: a low-frequency (LF) and a high-frequency (HF) component. Patients were grouped according to whether bradycardia did or did not develop during spinal anaesthesia. RESULTS: Nineteen patients developed severe bradycardia (<45 b.p.m.). The mean value of HF before spinal anaesthesia was significantly increased in the bradycardic group (P<0.05). The correlation between baseline heart rate (HR(baseline)) and minimum heart rate and LF, HF during spinal anaesthesia was significant (P<0.01). A receiver operator curve characteristic analysis showed a sensitivity and specificity of HF and HR(baseline) of 65% and 74%, respectively, to predict bradycardia <45 b.p.m. after spinal anaesthesia. CONCLUSIONS: The present study shows that HF and clinical factors such as patient's HR(baseline) could identify patients prone to developing severe bradycardia during spinal anaesthesia.

Small airways' function in Obstructive Sleep Apnea-Hypopnea Syndrome.

INTRODUCTION AND OBJECTIVES: Most of the studies of the pathophysiology of Obstructive Sleep Apnea-Hypopnea Syndrome (OSAHS) focus on the collapsibility and obstruction of the upper airways. The aim of our study was the investigation of small airways' function in patients with OSAHS. MATERIALS AND METHODS: We studied 23 patients (mean age, 51.6 years) diagnosed with mild to severe OSAHS, without comorbidities and 8 controls (mean age, 45.9 years). All subjects underwent full polysomnography sleep study; spirometry and maximum flow/volume curves while breathing room air and a mixture of 80%He-20%O2. The volume of equal flows (VisoV⋅) of the two curves and the difference of flows at 50% of FVC (ΔV˙max50) were calculated, as indicates of small airways' function. RESULTS: The results showed that VisoV⋅ was significantly increased in patients with OSAHS compared with controls (18.79±9.39 vs. 4.72±4.68, p=0.004). No statistically significantly difference was found in ΔV˙max50% (p=0.551); or the maximum Expiratory flow at 25-75% of FVC (p=0.067) and the maximum expiratory flow at 50% of FVC (p=0.174) breathing air. CONCLUSIONS: We conclude that at the time of the diagnosis of OSAHS, the function of the small airways is affected. This could be due to breathing at low lung volumes and the cyclic closure/opening of the small airways and may affect the natural history of OSAHS. The findings could lead to new therapeutic implications, targeting directly the small airways.

Increased bronchoalveolar lavage fluid CD1c expressing dendritic cells in idiopathic pulmonary fibrosis.

BACKGROUND: Chronic inflammation is implicated in idiopathic pulmonary fibrosis (IPF) pathogenesis and is associated with persistent activation of immune responses. These are largely controlled by dendritic cells (DCs). Although large numbers of DCs infiltrate the lungs of patients with IPF, there are no similar reports in bronchoalveolar lavage fluid (BALF). OBJECTIVES: We aimed to investigate DC populations in BALF of IPF patients. METHODS: CD1c(+) myeloid DCs, BDCA3(high) myeloid DCs, BDCA2(+) plasmacytoid DCs and CD83(+) mature DCs were identified by flow cytometry in the BALF of 10 IPF patients and 10 controls. DC numbers were expressed as percentages of total BALF leukocytes. RESULTS: CD1c(+) myeloid DCs were increased in IPF patients versus controls [median (ranges in parentheses) 1.16% (0.25-3.97) vs. 0.61% (0.19-1.10), p = 0.01]. There was also a trend towards increased BDCA3(high) myeloid DCs [0.57% (0.23-0.88) vs. 0.28% (0.07-0.96), p = 0.07]. No differences were reported in BDCA2(+) DCs and CD83(+) DCs between IPF patients and controls. CONCLUSIONS: IPF is associated with an increase in percentages of BALF myeloid DCs. Considering that such an increase was not observed in CD83(+) mature DCs, most of these DCs should be immature.

Prognostic significance of p53 and Ki67 proteins expression in Greek gastric cancer patients.

AIM: The variability of prognosis of gastric cancer (GC) within a pathological stage necessitates the identification of subgroups of patients with a more aggressive disease. The role of p53 and Ki67 expression in gastric carcinoma is far from being fully established. The aim of the present study was to evaluate the expression of p53 and Ki67 in gastric cancer and correlate the findings with several clinicopathological features and prognosis. MATERIALS AND METHODS: Tissue samples from 93 patients treated by gastric resection for gastric carcinoma between 1996 and 2001 were used. Formalin-fixed paraffin-embedded tumors were studied by immunohistochemistry, using monoclonal antibodies to p53 and Ki67. The results were correlated with clinicopathological features and survival. RESULTS: Stronger expression of p53 was related with tumor size greater than 5 cm and advanced stage. Stronger expression of Ki67 correlated with higher ratio of the number of metastatic lymph nodes to the total number of dissected lymph nodes (metastatic lymph node [MLN] ratio) and advanced stage. Moreover, p53 and Ki67 overexpression, tumor size greater than 5 cm, MLN ratio, depth of invasion, lymph node metastasis, stage III and IV and infiltrative macroscopic appearance were adverse prognostic factors. The levels of p53 and Ki67, the MLN ratio, the tumor size (above 5 cm) and the stage of the disease were identified as independent prognostic factors of survival. CONCLUSIONS: In gastric cancer, the expression of p53 and Ki67 provides significant information about prognosis. The routine evaluation of p53 and Ki67 levels could be a useful tool in identification of patient with more aggressive disease and contribute to a better therapeutic approach.

Microsatellite DNA instability and COPD exacerbations.

Increased frequency of microsatellite DNA instability (MSI) has been detected in the sputum of chronic obstructive pulmonary disease (COPD) patients. The aim of the present study was to investigate the relationship between MSI in sputum cells and exacerbation frequency, which is an important parameter in the clinical course of the disease. Induced sputum samples and peripheral blood obtained from 36 patients with COPD at stable state were analysed. The control group consisted of 30 nonsmoking healthy subjects. DNA was extracted and analysed for MSI using the following microsatellite markers: RH70958, D5S207, D6S2223, D6S344, D6S263, G29802, D13S71, D14S588, D14S292 and D17S250. Following MSI analysis, exacerbations were recorded for 3 yrs in total. No MSI was detected in healthy nonsmokers. A total of 18 (50%) out of 36 patients exhibited MSI in their sputum cells. Patients who exhibited MSI showed significantly increased frequency of exacerbations compared with patients that did not. In addition, a significantly increased frequency of purulent and of severe type exacerbations was found in patients exhibiting MSI. Patients positive for marker G29802, D13S71 or D14S588 presented increased exacerbation frequency. The significant association between microsatellite DNA instability and chronic obstructive pulmonary disease exacerbations indicates that somatic mutations could be involved in the pathogenesis and natural history of the disease.

Adipose DHA inversely associated with depression as measured by the Beck Depression Inventory.

This study attempts to detect potential associations between depression and adipose docosahexaenoic acid (c22:6 n-3) (DHA), a valid indicator for long-term dietary intake of DHA, in a profoundly religious group that strictly adheres to the Orthodox Christian Church (OCC) rituals and lifestyle. A total of 24 strict fasters and 27 control subjects were included in the study. The two study groups did not differ with regard to depressive symptoms distribution. Adipose tissue DHA was inversely associated with depression, while adherence to the OCC diet was strongly correlated with adipose DHA levels compared to controls. In conclusion, increased long-term dietary DHA intake was associated with decreased depression occurrence, whereas adherence to the OCC dietary recommendations, which allows for frequent fish and seafood consumption, was associated with increased adipose and dietary DHA levels, known for their essential role on optimal neuronal function and protection against a number of chronic diseases.

Risk factors for smoking among school adolescents in Greece.

OBJECTIVE: We conducted this study among school adolescents to identify factors, which influence schoolchildren to smoke. METHODS: We carried out a cross-sectional study in a sample of 924 students of all classes (ages 12-18 years old) in 15 public high schools in a semi-urban area in Crete, Greece, using a questionnaire. The questionnaire comprised of 46 questions covering children's lifestyle habits regarding daily activities and leisure time, frequency of risk-taking behaviour, knowledge about the hazards and long-term consequences of smoking. RESULTS: 23.9% of participants were experimental smokers and 18.6% were current smokers. 11.4% of the total population was daily smokers. There was a significant increase in the prevalence of experimental and current smokers with school grades, while peaks in last grades were observed. Boys started smoking earlier than girls, mean (standard error) age 13.4 (2.3) years vs. 14.1 (2.3) years, P = 0.01. Stepwise logistic regression analysis showed a positive relationship between current smoking and having brother or sister smoking [odds ratio (95% confidence interval) 2.7 (1.7-4.4) and 1.8 (1.1-3.3) respectively], having more than three friends who were smokers [2.6 (2-3.4)] and last school grade [1.4 (1.2-1.7)]. Students appeared to be informed about long-term smoking hazards and had negative views on children who smoke especially in the lower grades. CONCLUSIONS: Prevention programmes should be imposed early in elementary schools while cessation policies should target at all grades, in particular at critical grades depending on population-specific characteristics.

Exacerbations and lung function decline in COPD: new insights in current and ex-smokers.

AIM: To investigate whether there is a significant relationship between an increased frequency of exacerbations and the rate of forced expiratory volume in 1s (FEV(1)) decline in COPD patients. METHODS-MEASUREMENTS: About 102 COPD patients (44 smokers, 58 ex-smokers) participated in a 3-year prospective study. Exacerbations were identified as worsening of patient's respiratory symptoms as recorded on diary cards. Spirometry was performed every 6 months. The effect of frequent exacerbations on lung function was investigated using random effects models. RESULTS: The median (mean(95% CI)) annual exacerbation rate was 2.85 (3.1 (2.7-3.6)). Patients with an annual exacerbation rate over the median rate had significantly lower baseline post-bronchodilation FEV(1)(%pred), higher MRC dyspnoea score and chronic cough compared to patients who had an annual exacerbation rate less than the median. The average annual rate of FEV(1)(%pred), adjusted for smoking decline (DeltaFEV(1)), was found significantly increased in frequent compared to infrequent exacerbators (P=0.017). The highest DeltaFEV(1) was observed in smokers frequent exacerbators and a significant interaction between exacerbation frequency and DeltaFEV(1) was also observed in ex-smokers. CONCLUSIONS: Our findings suggest that an increased frequency of exacerbations is significantly associated with FEV(1) decline even in ex-smokers. Thus, smoking and frequent exacerbations may have both negative impact on lung function. Smoking cessation and prevention of exacerbations should be a major target in COPD.

Lung cancer and tobacco smoking in Crete, Greece: reflections from a population-based cancer registry from 1992 to 2013.

BACKGROUND: The Cancer Registry of Crete is a regional population database that collects cancer morbidity/mortality data along with several risk factors. The current study assessed the geographical variation of lung cancer among ever and never smokers in Crete during the last 20 years. METHOD: Lung cancer patient records (1992-2013) including information on medical history and smoking habits were obtained from the Cancer Registry of Crete. Age-Adjusted Incidence Rates (AAIR), prevalence of smoking among lung cancer patients and the Population-Attributable Fraction (PAF%) of tobacco smoking were estimated. Kaplan-Meier curves, grouped per smoking status were constructed, and spatio-temporal analyses were carried out to assess the geographical variations of lung cancer and smoking (a = 0.05). RESULTS: New lung cancer cases in Crete accounted for 9% of all cancers (AAIRboth genders = 40.2/100,000/year, AAIRmales = 73.1/100,000/year, AAIRfemales = 11.8/100,000/year). Ever smokers presented significantly higher incidence compared to ex-smokers (p = 0.02) and never smokers (p < 0.001). The highest increase was observed in ever smokers (AAIR1992 = 19.2/100,000/year, AAIR2013 = 25.4/100,000/year, p = 0.03), while never smokers presented the lowest increase from 1992 to 2013 (AAIR1992 = 5.3/100,000/year, AAIR2013 = 6.8/100,000/year, p = 0.2). The PAF% of lung cancer mortality is 86% for both genders (males: 89%, females: 78%). AAIRs ranged from 25 to 50/100,000/year, while significant geographical differences were observed among the municipalities of Crete (p = 0.02). Smokers living in the south-east urban regions presented higher risk of dying from lung cancer (RR = 2.2; 95%CI = 1.3-3.5). CONCLUSIONS: The constant increase of lung cancer rates among both genders, especially in females, outlines the need for targeted, geographically-oriented, life-style preventive measures. Design of population-based screening programs, tobacco awareness campaigns and smoking cessation programs in lung cancer hot spots could be guide by these findings.

The role of compliance with PAP use on blood pressure in patients with obstructive sleep apnea: is longer use a key-factor?

Scientific data about the effects of positive airway pressure (PAP) treatment on blood pressure (BP) control are continuously increasing; however, they are controversial. We aimed to determine the long-term effects of compliance with PAP therapy on BP in both hypertensive and normotensive patients with obstructive sleep apnea-hypopnea syndrome (OSAHS). One thousand one hundred sixty eight consecutive patients with newly diagnosed OSAHS, who had been recommended PAP therapy, were followed up for a minimum of 2 years. Patients with previous cardiovascular disease were excluded. BP was measured at baseline and after 2 years of PAP treatment. In addition, the correlation between the changes in BP with different levels of PAP compliance was assessed. At the end of the follow-up period, in the hypertensive group of patients (n=586), a significant decrease was shown in systolic (-11.2 mm Hg, P<0.001) and diastolic BP (-4.2 mm Hg, P<0.001). Furthermore, in the patients without hypertension (n=528), a significant decrease was noted both in systolic and diastolic BP (-3.6, P<0.001 and -2.4, P<0.001, respectively). A correlation between the magnitude of change in systolic and diastolic BP and hours of use of PAP (r=0.14, P=0.002 and r=0.1, P=0.025, respectively) was observed in all patients. Long-term use of PAP treatment, as well as increased hours of PAP in patients with OSAHS use showed significant reductions in BP not only in patients with hypertension, but also in normotensive patients. Therefore a significant potential reduction in cardiovascular mortality and morbidity should be expected in these patients.

Impaired mRNA Expression of the Migration Related Chemokine Receptor CXCR4 in Mesenchymal Stem Cells of COPD Patients.

Defective tissue repair and remodeling are main aspects of Chronic Obstructive Pulmonary Disease (COPD) pathophysiology. Bone marrow mesenchymal stem cells (BM-MSCs) have been implicated in this direction, as their functional impairment and recruitment could possibly contribute to disease development and progression. The present study characterizes for the first time the expression of migration related chemokine receptors and their ligands in BM-MSCs from COPD patients. CXCR4/SDF1a and CCR7/CCL19-CCL21 mRNA levels were evaluated in BM-MSCs obtained from twelve COPD patients and seven healthy donors. SDF1a protein levels in sera and BM-MSCs' conditioned media were also evaluated. CXCR4, SDF1a, CCL19, and CCL21 mRNA levels were significantly reduced in COPD BM-MSCs while CCR7 levels were undetectable. Notably, SDF1a protein levels were marginally elevated in both patient sera and BM-MSCs' conditioned media while the increase in SDF1a serum levels significantly correlated with disease severity in COPD. Our findings show posttranscriptional regulation of SDF1a levels in BM-MSCs of COPD patients and significant downregulation of SDF1a and CXCR4 mRNA indicating an involvement of the SDF1a signaling pathway in the disease pathophysiology.

Clearance of technetium-99m-DTPA in pulmonary sarcoidosis.

BACKGROUND: The aim of this study was to explore the possible association of the lung clearance of 99mTc-DTPA scan with HRCT lung abnormalities and with the pulmonary function tests [PFTs] in patients with sarcoidosis. METHODS: We studied prospectively 15 patients [5 males, 10 females] of median age 46yr [range 27-67] with histologically proved sarcoidosis. HRCT scoring included the sum of the severity and extent of lymph node enlargement and parenchymal involvement. RESULTS: The mean DTPA clearance half-time [tau 1/ <40 min] was found [mean [SD]] 38.3+/-4.5min. The lymph node enlargement was found 34% and the parenchymal involvement 12%. DTPA clearance was negatively correlated with the parenchymal involvement [r= -0.651, p=0.0091]. The HRCT parenchymal abnormalities were found significantly correlated with PFTs [FVC [r= -0.65, p=0.008] and TLCO [r= -0.76, p=0.02]. CONCLUSIONS: Our data suggest a moderate association between 99mTc-DTPA scan and HRCT in pulmonary sarcoidosis. However, further studies in large scale of sarcoid patients are needed to clarify the role of this novel methodology in the evaluation and follow-up of this disorder.

Respiratory muscle strength in hypothyroidism.

To investigate respiratory muscle strength in patients with hypothyroidism, global respiratory muscle strength was assessed by measuring mouth pressure during PImax and PEmax efforts. Maximum pressures, VC, FEV1, FVC, T3, T4, and TSH were measured in 43 hypothyroid patients. Measurements were made before and three months after replacement therapy with thyroxine. The results showed that the mean value of PImax and PEmax increased after treatment. Significant change was found in the mean value of VC, FEV1, and FVC after treatment but not in the FEV1/FVC ratio. A highly statistically significant linear relationship was found between PImax and TSH and between PEmax and TSH as well as between PImax and T3 and PEmax and T3. We conclude that hypothyroidism affects respiratory muscle strength and that this weakness is linearly related to thyroid hormone levels. Respiratory muscle weakness is present in both inspiratory and expiratory muscles and is reversible with treatment.

Microsatellite DNA instability in COPD.

STUDY OBJECTIVES: Cigarette smoking is the prime cause of COPD; however, only a few smokers develop the disease. In a previous study, we demonstrated that microsatellite DNA instability (MSI) is a detectable phenomenon in sputum cells of COPD patients. Therefore, we hypothesize that this genetic alteration may indicate susceptibility to COPD. DESIGN: In order to investigate this hypothesis, we compared smokers who developed COPD with smokers who did not develop COPD (referred to as non-COPD smokers). SETTING: Seven highly polymorphic microsatellite markers were targeted on the DNA of sputum cells and of WBCs. PATIENTS AND PARTICIPANTS: We studied 60 non-COPD smokers and 59 severe COPD patients with a similar smoking history (mean +/- SD) of 48+/-25 and 54+/-33 pack-years, respectively (p = 0.77). Non-COPD smokers were tested once; COPD smokers were tested twice, with an interval of 24 months between tests. RESULTS: MSI was detected in 14 COPD patients (24%) but in none of the non-COPD smokers. In 10 COPD patients, MSI was exhibited by one microsatellite marker; in the remaining 4 COPD patients, MSI was exhibited by two different alleles. The most commonly affected marker was THRA1 on chromosome 17 (43%). No significant differences were found between MSI-positive and MSI-negative COPD patients for clinical or laboratory parameters, survival, and development of lung cancer. No change in the microsatellite alleles was found between the tests performed with a 24-month interval. CONCLUSIONS: This study demonstrated that MSI was found exclusively in the sputum cells of smokers with COPD. The results support the hypothesis that MSI could be part of the complex genetic basis of COPD, and it could be a marker of the genetic alteration caused by smoking that allows COPD to develop.

Short-term effects of wood smoke exposure on the respiratory system among charcoal production workers.

STUDY OBJECTIVES: We aimed to investigate the short-term respiratory effects of heavy, occupational wood smoke exposure among traditional charcoal production workers. PATIENTS AND SETTING: A total of 22 charcoal workers (mean age, 41 years; 9 current smokers, 5 ex-smokers, and 8 nonsmokers) were studied and compared with a control group of 35 farmers residing in Perama, Rethymnon, Crete. RESULTS: The charcoal workers were exposed to wood smoke for an average of 14 h/d during a mean of 23.7 days required for the burning of kilns. The workers under study were found to have significantly more cough (odds ratio [OR], 4.8; 95% confidence interval [CI], 1.2 to 19.7), sputum production (OR, 6; 95% CI, 1.4 to 26.5), wheezing (OR, 7.7; 95% CI, 1.4 to 41.5), dyspnea (OR, 28.7; 95% CI, 5.4 to 153), and hemoptysis (OR, 2.7; 95% CI, 0.7 to 55) than the control group. The prevalence of respiratory symptoms such as cough, sputum production, wheezing, and dyspnea in the charcoal workers was significantly elevated during the exposure period (OR, 5.4; 95% CI, 1.1 to 17.7; OR, 5.7; 95% CI, 1 to 31; OR, 9.8; 95% CI, 1 to 88; and OR, 36.7; 95% CI, 1 to 327, respectively). The mean +/- SD percent of predicted values of FVC, FEV(1), FEV(1)/FVC ratio, and forced expiratory flow at 25 to 75% of FVC during the exposure period were significantly lower than those before exposure: 106 +/- 10.8 vs 101 +/- 11.9, p < 0.01; 104 +/- 16 vs 97 +/- 15, p < 0.001; 81 +/- 9 vs 78 +/- 8, p < 0.001; and 95 +/- 27 vs 80 +/- 25, p < 0.01, respectively. The mean +/- SD value of peak expiratory flow at midday and in the evening during the exposure were significantly lower than before: 524 +/- 131 L/min vs 548 +/- 108 L/min, p = 0.03; and 521 +/- 135 L/min vs 547 +/- 131 L/min, p = 0.02, respectively. CONCLUSIONS: Our results suggest that wood smoke exposure in charcoal workers is associated with increased respiratory symptoms and decreased pulmonary function. Longitudinal studies are needed to determine potential long-term adverse respiratory effects.

Cisplatin-etoposide alternating with topotecan in patients with extensive stage small cell lung cancer (SCLC). A multicenter phase II study.

PURPOSE: In order to investigate the feasibility of a potentially non-cross resistant drug regimen, we alternated cycles of cisplatin-etoposide with topotecan as front-line treatment in patients with extensive stage small cell lung cancer (SCLC). PATIENTS AND METHODS: Thirty-six previously untreated patients with extensive stage SCLC received cisplatin 75 mg/m(2) IV on day 1 and etoposide 100 mg/m(2) IV on days 1-3 on cycles one, three, five and seven and topotecan 1.5 mg/m(2) IV on days 1-5 on cycles two, four, six and eight. Cycles were repeated every 21 days. Patients' median age was 60 years and performance status (WHO) was 0 for 13, 1 for 20 and 2 for three patients. All patients were evaluable for response and toxicity. RESULTS: Five (14%) patients achieved a complete response and 18 (50%) a partial response for an overall response rate of 64% (95% confidence interval: 48.2-79.6%). After a median follow up of 10 months, the median duration of response was 5.5 months, the time to tumor progression 8 months and the probability of 1-year survival 48.9%. A total of 126 cycles of cisplatin-etoposide and 117 cycles of topotecan were administered with a median number of 4 cycles/patient for each regimen. There were no toxic deaths. Treatment delays due to toxicity occurred in 13 (10%) cycles after cisplatin-etoposide and 16 (14%) cycles after topotecan while doses were reduced in seven (6%) and five (4%) cycles, respectively. Grade 3-4 neutropenia, thrombocytopenia and febrile neutropenia complicated 13, 1 and 3% of cisplatin-etoposide cycles and 28, 6 and 1% of topotecan, respectively. Non-hematologic toxicity was mild. The delivered dose intensity was 96% for cisplatin and etoposide and 98% for topotecan. CONCLUSIONS: The alternating administration of cisplatin-etoposide and topotecan is a feasible, active and well-tolerated regimen in patients with extensive stage SCLC.

Induced sputum in the investigation of airway inflammation of COPD.

During the last decade, the method of sputum induction (SI) has offered the opportunity to study inflammation in patients with chronic obstructive pulmonary disease (COPD). This paper reviews methodological aspects of SI and summarizes its uses in the research of inflammation in COPD, including sputum cellularity and soluble markers. SI is a relatively safe, reliable, and reproducible technique, used to investigate different aspects of airway inflammation. Although various methods of induction and processing have been proved safe and highly reproducible, a generally accepted method is needed. Sputum analysis has given evidence for increased numbers of macrophages and neutrophils in COPD patients compared to normal subjects. In some studies, increased numbers of eosinophils have been also reported. Changes in various mediators have been found in sputum supernatant of COPD patients (IL-8, LTB-4 and TNF-a). The clinical usefulness of the method in the follow-up of the disease has not been explored extensively. A number of observations in patients with different clinical characteristics could be proven useful in identifying patterns of inflammation associated with different prognosis. Finally, SI could also guide treatment; such as, sputum eosinophilia in COPD could predict response to inhaled corticosteroids.