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1.  Differential expression of hypoxia-inducible factor 1α in non-small cell lung cancer and small cell lung cancer 
Clinics  2012;67(12):1373-1378.
OBJECTIVES:
The aim of this study was to compare the expression of hypoxia-inducible factor 1α and vascular endothelial growth factor in small cell lung cancer and subtypes of non-small cell lung cancer and examine their relationships with clinicopathologic factors, response to treatment and survival.
METHODS:
We examined samples obtained by bronchial endoscopic biopsy from 55 patients with inoperable lung cancer (16 with adenocarcinoma, 17 with squamous cell carcinoma, and 22 with small cell lung cancer). Hypoxia-inducible factor 1α and vascular endothelial growth factor were detected using immunohistochemistry. The diagnosis, treatment, and follow-up of patients were conducted according to the standard practice.
RESULTS:
A significant difference (p = 0.022) in hypoxia-inducible factor 1α expression was observed between non-small cell lung cancer (75.8% positive) and small cell lung cancer (45.5% positive). The frequency of hypoxia-inducible factor 1α nuclear expression was 88.2% in squamous cell carcinoma, 62.5% in adenocarcinoma, and 45.5% in small cell lung cancer. A significant correlation was observed between hypoxia-inducible factor 1α and vascular endothelial growth factor expression (Fisher's exact test, p = 0.001) when all types of lung cancer were examined, either collectively or separately.
CONCLUSIONS:
The expression of hypoxia-inducible factor-1α differs significantly between subtypes of lung cancer. These findings could help elucidate the biology of the different types of non-operable lung carcinomas and have implications for the design of new therapeutic approaches for lung cancer.
doi:10.6061/clinics/2012(12)05
PMCID: PMC3521798  PMID: 23295589
Hypoxia-Inducible Factor 1α; Lung Cancer; Vascular Endothelial Growth Factor; Small Cell Lung Cancer; Non-small Cell Lung Cancer
2.  Two-year mortality of patients with COPD in primary health care: an observational study 
Background
Chronic obstructive pulmonary disease (COPD) remains a significant cause of morbidity and mortality, with high rates of underdiagnosis. There are no studies about following up COPD patients in primary health care. The aim of the current study was to estimate two-year mortality for COPD patients in primary care and assess the parameters associated with mortality.
Methods
A total of 263 patients with a new COPD diagnosis were followed up for two years. Follow-up included phone contacts every six months for assessment of vital status, and re-examination visits every year after the initial diagnosis. Visits included performance on spirometry, assessment of smoking status, evaluation of adherence with treatment, and assessment of the number of exacerbations during the previous year.
Results
One hundred and eighteen patients with COPD completed the study. The overall mortality was 27.9%. Most patients had quit smoking two years after the initial diagnosis, whereas the percentage of patients showing high adherence with treatment was 68%. Parameters associated with two-year mortality were age and coronary heart disease comorbidity.
Conclusion
The mortality of patients with COPD in primary care remains significantly high, whereas adherence with treatment remains significant low. Age, smoking status, and a history of depression are major determinants of mortality in primary health care.
doi:10.2147/IJGM.S27411
PMCID: PMC3468116  PMID: 23055771
chronic obstructive pulmonary disease; mortality; primary health care; depression
3.  Exhaled breath condensate pH as a biomarker of COPD severity in ex-smokers 
Respiratory Research  2011;12(1):67.
Endogenous airway acidification, as assessed by exhaled breath condensate (EBC) pH, is present in patients with stable COPD. The aim of this study was to measure EBC pH levels in a large cohort of COPD patients and to evaluate associations with functional parameters according to their smoking status.
EBC was collected from 161 patients with stable COPD and 112 controls (current and ex-smokers). EBC pH was measured after Argon deaeration and all subjects underwent pulmonary function testing.
EBC pH was lower in COPD patients compared to controls [7.21 (7.02, 7.44) vs. 7.50 (7.40, 7.66); p < 0.001] and ex-smokers with COPD had lower EBC pH compared to current smokers [7.16 (6.89, 7.36) vs 7.24 (7.09, 7.54), p = 0.03]. In ex-smokers with COPD, EBC pH was lower in patients with GOLD stage III and IV compared to patients with stage I disease (p = 0.026 and 0.004 respectively). No differences were observed among current smokers with different disease severity. EBC pH levels in ex-smokers were associated with static hyperinflation (as expressed by IC/TLC ratio), air trapping (as expressed by RV/TLC ratio) and diffusing capacity for carbon monoxide, whereas no associations were observed in current smokers.
Endogenous airway acidification is related to disease severity and to parameters expressing hyperinflation and air trapping in ex-smokers with COPD. The possible role of EBC pH in COPD needs to be further evaluated in longitudinal studies.
doi:10.1186/1465-9921-12-67
PMCID: PMC3120669  PMID: 21600044
4.  Body Composition in Severe Refractory Asthma: Comparison with COPD Patients and Healthy Smokers 
PLoS ONE  2010;5(10):e13233.
Background
Body composition is an important parameter for patients with chronic obstructive pulmonary disease (COPD) whereas the association between asthma and obesity is not fully understood. The impact of severe refractory asthma (SRA) on fat free mass (FFM) has not been investigated.
Methodology and Principal Findings
213 subjects (70 healthy smokers, 71 COPD patients and 72 asthma patients) without significant comorbidities were included in the study. In all patients, body composition assessment (using bioelectrical impendance analysis, skinfold and anthropometric measurements) and spirometry were performed. Differences in fat free mass index (FFMI) between groups were assessed and determinants of FFMI in asthma were evaluated. Patients with SRA had lower values of FFMI compared to patients with mild-to-moderate asthma [18.0(17.3–18.3)–19.5(18.4–21.5), p<0.001], despite the fact that they were more obese. The levels of FFMI in SRA were lower than those of GOLD stage I–III COPD and comparable to those of stage IV COPD patients [18.0(17.3–18.3)–18.8(17.8–20.1), p = ns]. These differences were present even after proper adjustments for sex, age, smoking status, daily dose of inhaled corticosteroids (ICS) and daily use of oral corticosteroids (OCS). In multivariate analysis, independent predictors of FFMI in asthmatic patients were age, use of OCS and the presence of SRA, but not smoking, sex or cumulative dose of ICS used.
Conclusions and Significance
SRA is related to the presence of low FFMI that is comparable to that of GOLD stage IV COPD. The impact of this observation on asthma mechanisms and outcomes should be further investigated in large prospective studies.
doi:10.1371/journal.pone.0013233
PMCID: PMC2950851  PMID: 20949085
5.  Prevalence of chronic diseases and morbidity in primary health care in central Greece: An epidemiological study 
Background
In Greece there is lack of large epidemiological studies regarding morbidity and mortality in primary health care. The aim of the present study was to estimate the prevalence and morbidity of the most common diseases in a large population sample from primary health care.
Methods
Four primary health centres were randomly selected. During one year period, 12 visits were performed in each centre, one per month, in random order and all visitors willing to participate in the study were included. Data on morbidity of each subject were recorded after performing an interview with the participant and checking his medical records, medical history and current medication. Diseases were coded using the international classification of primary care (ICPC) system.
Results
In total 20,299 subjects were recorded. The results revealed significant variations in morbidity between genders and age groups. However, in all age groups, diseases of the circulatory system were most prevalent, followed by endocrine, metabolic, musculoskeletal and respiratory diseases. Osteoporosis was significantly more prevalent in females compared to males, whereas skin and eye disorders were more prevalent in subjects below 65 years old. COPD prevalence was very low compared to worldwide data.
Conclusions
The present study revealed great variations in the prevalence of the diseases between genders and age groups. Our data justify the urgent need for the development of electronic health records that may help in the design of new prevention strategies in primary health care.
doi:10.1186/1472-6963-10-252
PMCID: PMC2939599  PMID: 20799979
6.  Association of TLR4-T399I Polymorphism with Chronic Obstructive Pulmonary Disease in Smokers 
Tobacco smoking has been considered the most important risk factor for chronic obstructive pulmonary disease (COPD) development. However, not all smokers develop COPD and other environmental and genetic susceptibility factors underlie disease pathogenesis. Recent studies have indicated that the impairment of TLR signaling might play a crucial role in the development of emphysema. For this purpose we investigated the prevalence and any possible associations of common TLR polymorphisms (TLR2-R753Q, TLR4-D299G, and TLR4-T399I) in a group of 240 heavy smokers (>20 pack years), without overt atherosclerosis disease, of whom 136 had developed COPD and 104 had not. The presence of TLR4-T399I polymorphism was associated with a 2.4-fold increased risk for COPD development (P = .044), but not with disease stage or frequency of exacerbations. Considering that infections contribute to COPD and emphysema pathogenesis, our findings possibly indicate that dysfunctional polymorphisms of innate immune genes can affect the development of COPD in smokers. Although this finding warrants further investigation, it highlights the importance of impaired innate immunity towards COPD development.
doi:10.1155/2009/260286
PMCID: PMC2822240  PMID: 20169003

Results 1-6 (6)