Effects of short-term air pollution exposure on symptoms development in the course of idiopathic pulmonary fibrosis.

BACKGROUND: Lately a potential detrimental effect of air pollution to idiopathic pulmonary fibrosis emerged. We aimed to assess the effects of short-term air pollution exposure to the clinical course of IPF. RESEARCH DESIGN AND METHODS: IPF patients were followed intensively for four nonconsecutive study periods between 13 July 2020 and 5 September 2021. Short-term exposure to O3, NO2 and PM10 concentrations was estimated using spatio-temporal land use regression models. Associations among symptoms, lung function, oxygen saturation, and short-term personal air pollutant exposure were assessed through multiple mixed effects logistic regression models. RESULTS: Data for up to 24 IPF patients (mean age: 72.2 ± 7.6 years) were analyzed. We detected positive significant associations between cough and a 10 µg/m3 increase in same day mean level of NO2 (OR = 1.59, 95%CI: 1.00-2.53), PM10 (OR = 2.42, 95%CI: 1.54-3.79), and O3 (OR = 1.63, 95%CI: 1.14-2.32). A 10 µg/m3 increase in same day mean level of NO2 was also associated with the risk of appearance of wheezing (OR = 3.01, 95%CI: 1.00-9.04), while exposure to O3 was associated with common cold (OR = 6.30, 95%CI: 3.59-11.07). No significant associations were detected between short-term exposure to air pollutants and forced vital capacity or saturation of oxygen. CONCLUSIONS: Short-term exposure to increased concentrations of air pollutants is an independent risk factor for IPF symptoms' aggravation.

Associations between exposure to blue spaces and natural and cause-specific mortality in Greece: An ecological study.

BACKGROUND: A growing body of evidence suggests that exposure to natural environments, such as green space, may have a beneficial role in health. However, there is limited evidence regarding the effects of exposure to blue spaces and mortality. We investigated the association of exposure to blue spaces with natural and cause-specific mortality in Greece using an ecological study design METHODS: Mortality and socioeconomic data were obtained from 1,035 municipal units (MUs) from the 2011 census data. To define exposure to "blue" we used a rate of the land cover categories related to blue space from the COoRdination and INformation on the Environmental (CORINE) 2012 map per 10,000 persons in the municipal unit. We further assessed the exposure to blue space in the MUs that are located in the coastline of Greece using the distance to the coast as a proxy for proximity to blue space. the Annual PM2.5, NO2, BC and O3 concentrations for 2010 were predicted by land use regression models while the normalized difference vegetation index was used to assess greenness. We applied single and two exposure Poisson regression models accounting for spatial autocorrelation and adjusting for unemployment and lung cancer mortality rates, percentages of the population aged 25-64 with upper secondary or tertiary education attainment and of those born in Greece, and urbanicity. The analysis was conducted for the whole country and separately by varying geographical definitions. RESULTS: An interquartile range (IQR) increase of blue space per 10,000 persons was associated with decreased risk in natural mortality (Relative Risk (RR): 0.98 (95% confidence interval (CI): 0.98, 0.99), as well as in mortality due to cardiovascular causes, respiratory causes and diseases of the nervous system 0.98 (95% CI: 0.97, 0.99); 0.97 (95% CI: 0.95, 0.99); 0.94 (95% CI: 0.88, 1.00) respectively). We estimated protective associations for ischemic heart disease (IHD) mortality (RR = 0.98, 95% CI: 0.97, 1.00 per IQR); COPD mortality (RR = 0.97, 95% CI: 0.93, 1.00 per IQR) and mortality from cerebrovascular disease (RR = 0.97 (95% CI: 0.96, 0.99 per IQR). We estimated protective associations for the distance from the coast and mortality from the diseases of the nervous system (RR = 0.75, 95% CI: 0.61, 0.92, ≤1 km from the coast versus >1 km). Our results were stronger for inhabitants of the islands, the coastline and in the rural areas of Greece while the estimates were robust to co-exposure adjustment. CONCLUSIONS: We estimated statistically significant protective effects of exposure to blue space on mortality from natural, cardiovascular and respiratory causes, diseases of the nervous system, cerebrovascular and ischemic heart disease for in Greece with higher estimates in the coastline and the islands. Further research is needed to elaborate our findings.

The Impact of COVID-19 Pandemic on Surgical Treatment of Resectable Non-Small Cell Lung Cancer in Greece.

Background: The coronavirus disease (COVID-19) pandemic has posed an unprecedented challenge to health systems, and has significantly affected the healthcare of lung cancer patients. The aim of our study was to assess the impact of COVID-19 on early lung cancer patients' surgical treatment. Methods: All consecutive patients with early-stage non-small cell lung cancer eligible for surgical treatment stage I/II and resectable stage III, referred to our department during the first wave of COVID-19 between February to May 2020, were included and compared with those on the exact corresponding quarter in 2019, one year before the pandemic. Waiting time to surgical treatment, increase of tumor's size and increase on lung cancer stage were recorded and compared. All subjects were followed up for 12 months. Multiple linear and logistic regression models were applied to assess the differences in the management of the studied groups adjusting for potential confounders. Results: Sixty-one patients with early-stage lung cancer were included in the study; 28 (median age 67 years, SD: 7.1) during the pandemic and 33 (median age 67.1 years, SD: 7.5) one year earlier. A significantly longer period of waiting for treatment and an increase in tumor size were observed during the pandemic compared to before the pandemic [median time 47 days, interquartile rate (IQR): 23−100] vs. [median time 18 days, IQR: 11−23], p < 0.001. No significant differences were detected in the increase of the stage of lung cancer between the subgroups. Conclusion: The COVID-19 pandemic had a significant impact on surgical and oncological care, leading to significant delays on treatment and an increase in tumor size in early-stage lung cancer patients.

Long-term personal air pollution exposure and risk for acute exacerbation of idiopathic pulmonary fibrosis.

BACKGROUND: Urban air pollution is involved in the progress of idiopathic pulmonary fibrosis (IPF). Its potential role on the devastating event of Acute Exacerbation of IPF (AE-IPF) needs to be clarified. This study examined the association between long-term personal air pollution exposure and AE- IPF risk taking into consideration inflammatory mediators and telomere length (TL). METHODS: All consecutive IPF-patients referred to our Hospital from October 2013-June 2019 were included. AE-IPF events were recorded and inflammatory mediators and TL measured. Long-term personal air pollution exposures were assigned to each patient retrospectively, for O3, NO2, PM2.5 [and PM10, based on geo-coded residential addresses. Logistic regression models assessed the association of air pollutants' levels with AE-IPF and inflammatory mediators adjusting for potential confounders. RESULTS: 118 IPF patients (mean age 72 ± 8.3 years) were analyzed. We detected positive significant associations between AE-IPF and a 10 µg/m3 increase in previous-year mean level of NO2 (OR = 1.52, 95%CI:1.15-2.0, p = 0.003), PM2.5 (OR = 2.21, 95%CI:1.16-4.20, p = 0.016) and PM10 (OR = 2.18, 95%CI:1.15-4.15, p = 0.017) independent of age, gender, smoking, lung function and antifibrotic treatment. Introduction of TL in all models of a subgroup of 36 patients did not change the direction of the observed associations. Finally, O3 was positively associated with %change of IL-4 (p = 0.014) whilst PM2.5, PM10 and NO2 were inversely associated with %changes of IL-4 (p = 0.003, p = 0.003, p = 0.032) and osteopontin (p = 0.013, p = 0.013, p = 0.085) respectively. CONCLUSIONS: Long-term personal exposure to increased concentrations of air pollutants is an independent risk factor of AE-IPF. Inflammatory mediators implicated in lung repair mechanisms are involved.

Long-term exposure to ozone and children's respiratory health: Results from the RESPOZE study.

BACKGROUND: Although there is evidence on the effects of short-term ozone (O3) exposures on children's respiratory health, few studies have reported results on the effects of long-term exposures. We report the effects of long-term exposure to O3 on respiratory health outcomes in 10-11-year old children. METHODS: We conducted a panel study in a sample of the general population of school children in two cities with high average O3 concentrations, Athens and Thessaloniki, Greece. All 186 participating students were followed up intensively for 5 weeks spreading across a school year. Data was collected through questionnaires, weekly personal O3 measurements, spirometry, FeNO and time-activity diaries. Long-term O3 exposure was assessed using fixed site measurements and modeling, calibrated for personal exposures. The associations between measured lung function parameters and lung function growth over the study period, as well as FeNO and the occurrence of symptoms with long-term O3 exposure were assessed through the application of multiple mixed effects 2-level regression models, adjusting for confounders and for short-term exposures. RESULTS: A 10 µg/m3 increase in calibrated long-term O3exposure, using measurements from fixed site monitors was associated with lower FVC and FEV1 by 17 mL (95% Confidence Interval: 5-28) and 13 mL (3-21) respectively and small decreases in lung growth: 0.008% (0.002-0.014%) for FVC and 0.006% (0.000-0.012%) in FEV1 over the study period. No association was observed with PEF, FeNO or the occurrence of symptoms. A similar pattern was observed when the exposure estimates from the dispersion models were employed. CONCLUSIONS: Our study provides evidence that long-term O3 exposure is associated with reduced lung volumes and growth.

Air pollution and Parkinson's disease: A systematic review and meta-analysis up to 2018.

BACKGROUND: Recent epidemiological findings investigate effects of exposure to air pollution on neurodegenerative disease. We performed a systematic review and meta-analysis to investigate the association between air pollution exposure and Parkinson's disease (PD). METHODS: We performed an extensive literature search in PubMed and Google Scholar databases and further searched for unpublished results in conference abstracts until November 2018. We identified 102 unique studies referring to air pollution and PD, from which 15 were included in the meta-analyses. We applied random-effects models to combine risk estimates and investigated between studies heterogeneity. We assessed publication bias through plots and the Egger's test in cases of sufficient number of studies. We assessed associations accounting for multi-pollutant exposures and effect modification patterns by sex and smoking habits. RESULTS: We identified 13 reports investigating associations of PD with long-term exposure to regulated air pollutants whilst two reported associations for short-term exposure to PM2.5. The pooled relative risk (RR) for incidence of PD following an increase in long-term exposure for 10 µg/m3 in PM2.5 was 1.06 (95% Confidence Interval (CI): 0.99, 1.14) and in NO2 1.01 (95%CI: 0.98, 1.03), while for 5 ppb increase in O3 1.01 (95% CI: 1.00, 1.02) and for 1 mg/m3 in CO 1.34 (95% CI: 0.85, 2.10); the pooled RR for a hospital admission due to PD after a 10 µg/m3 increase in PM2.5 short-term exposure was 1.03 (95% CI: 1.01, 1.05). There was high heterogeneity between study-specific results for most of the analyses, attributed to different populations under study. Effects were robust to multi-pollutant adjustment while there were indications of higher particles' effects among non smokers. CONCLUSIONS: We found weak evidence for an association between air pollution, mostly originating from traffic, and PD. Although meta-analysis increases power to detect small associations in rare outcomes, further research is needed to elaborate our suggestive associations. Such results are of public health significance since population aging in developed countries is expected to increase incidence of PD.

Uveal Melanoma: GNAQ and GNA11 Mutations in a Greek Population.

BACKGROUND/AIM: Uveal melanoma is the most common primary adult intraocular malignancy. It is known to have a strong metastatic potential, fatal for the vast majority of patients. In recent years, meticulous cytogenetic and molecular profiling has led to precise prognostication, that unfortunately is not matched by advancements in adjuvant therapies. G Protein subunits alpha Q (GNAQ) and alpha 11 (GNA11) are two of the major driver genes that contribute to the development of uveal melanoma. Understanding their prognostic significance can allow tailored management and facilitate their use in the on-going quest of targeted uveal melanoma therapies. MATERIALS AND METHODS: Formalin-fixed, paraffin-embedded specimens were obtained from 47 patients of Greek origin, with uveal melanoma. GNAQ and GNA11 genes were screened for mutations in exons 4 and 5, by polymerase chain reaction and Sanger sequencing. RESULTS: The overall mutation frequency of GNAQ/GNA11 genes was 42.4%. A novel mutation c.625_626delinsGC was identified in GNA11. No correlation was observed between the mutation status and metastasis occurrence or overall survival time of patients. CONCLUSION: Mutations in GNAQ and GNA11 genes in this Greek population present frequencies that qualify them as potential targets for customized therapy.

Long-term exposure to traffic-related air pollution and cardiovascular health in a Greek cohort study.

Our objective is to evaluate the association of exposure to traffic-related air pollution with the incidence of fatal and non-fatal ischemic heart disease (IHD), stroke and total cardiovascular disease (CVD) events in a Greek cohort. We used data from the European Prospective Investigation on Nutrition and Cancer (EPIC) for 2752 subjects followed from 1997 to 2011, whose residence was in 10 municipalities of the Greater Athens area. Air pollution exposure estimation was based on a spatio-temporal land use regression model linking geo-coded residential addresses to long-term average NO2 and PM10 concentrations. We conducted Cox proportional hazards regression analysis, adjusting for potential confounders. Hazard ratios (HR) above 1 (not all statistically significant) were associated with higher PM10 exposure for all outcomes. Weaker associations were found with NO2 exposure. Specifically, the estimated HR for a CVD event associated with 10 µg/m(3) increase in long-term exposure to PM10 was 1.50 (1.05-2.16, p-value: 0.027). The relationship was more evident for subjects ≤50 years old at recruitment. Associations of PM10 and NO2 exposure with IHD events were found only among women with HRs respectively of 2.24 (0.89-5.64, p-value: 0.086) and 1.54 (1.01-2.37, p-value: 0.046) associated with 10 µg/m(3) increase in the corresponding pollutant. In conclusion, the present study suggests that long-term exposure to traffic-related air pollution has an impact on CVD and IHD morbidity, particularly among women and younger subjects.

Air pollution and lung cancer incidence in 17 European cohorts: prospective analyses from the European Study of Cohorts for Air Pollution Effects (ESCAPE).

BACKGROUND: Ambient air pollution is suspected to cause lung cancer. We aimed to assess the association between long-term exposure to ambient air pollution and lung cancer incidence in European populations. METHODS: This prospective analysis of data obtained by the European Study of Cohorts for Air Pollution Effects used data from 17 cohort studies based in nine European countries. Baseline addresses were geocoded and we assessed air pollution by land-use regression models for particulate matter (PM) with diameter of less than 10 µm (PM10), less than 2·5 µm (PM2·5), and between 2·5 and 10 µm (PMcoarse), soot (PM2·5absorbance), nitrogen oxides, and two traffic indicators. We used Cox regression models with adjustment for potential confounders for cohort-specific analyses and random effects models for meta-analyses. FINDINGS: The 312 944 cohort members contributed 4 013 131 person-years at risk. During follow-up (mean 12·8 years), 2095 incident lung cancer cases were diagnosed. The meta-analyses showed a statistically significant association between risk for lung cancer and PM10 (hazard ratio [HR] 1·22 [95% CI 1·03-1·45] per 10 µg/m(3)). For PM2·5 the HR was 1·18 (0·96-1·46) per 5 µg/m(3). The same increments of PM10 and PM2·5 were associated with HRs for adenocarcinomas of the lung of 1·51 (1·10-2·08) and 1·55 (1·05-2·29), respectively. An increase in road traffic of 4000 vehicle-km per day within 100 m of the residence was associated with an HR for lung cancer of 1·09 (0·99-1·21). The results showed no association between lung cancer and nitrogen oxides concentration (HR 1·01 [0·95-1·07] per 20 µg/m(3)) or traffic intensity on the nearest street (HR 1·00 [0·97-1·04] per 5000 vehicles per day). INTERPRETATION: Particulate matter air pollution contributes to lung cancer incidence in Europe. FUNDING: European Community's Seventh Framework Programme.

Nasal polyps: heredity, allergies, and environmental and occupational exposure.

OBJECTIVE: To determine the role of heredity, allergies, smoking, and environmental and occupational exposure in the epidemiology of nasal polyposis. STUDY DESIGN: A case-control study comprising 100 patients with nasal polyps admitted to three Athens hospitals and 102 controls from the general population. Gender, educational level, family history, allergies, smoking, occupational activities, and environmental exposure were examined as eventual determinants. The prevalence of each determinant was compared between cases and controls using multiple logistic regression, and odds ratios (ORs) were estimated. RESULTS: A total of 13.3% of the patients and none of the controls had a history of polyps in the family. According to multiple logistic regression, the OR for certain allergies was 19.1 and for probable allergy was 9.0, with the prevalence among patients being 64% and 12%, respectively. The OR for certain environmental exposures was 15.0 and for occupational exposures was 21.4. Occupational exposure to chemicals was a predominant factor among patients. No significant difference was found between nasal polyps and educational level or smoking habits. CONCLUSIONS: The development of nasal polyps seems to be strongly related to family history and a history of allergies, but the role of smoking remains controversial. Occupational and environmental exposures probably enhance the appearance of the disease on the basis of genetic predisposition.

Clinical significance of ephrin (eph)-A1, -A2, -a4, -a5 and -a7 receptors in pancreatic ductal adenocarcinoma.

Ephrin (Eph) receptors have been reported to be frequently overexpressed in a wide variety of cancer types, being associated with tumor growth, invasion, metastasis and angiogenesis. The aim of the present study was to evaluate the clinical significance of Eph-A1, -A2, -A4, -A5 and -A7 expression in pancreatic ductal adenocarcinoma. Eph-A1, -A2, -A4, -A5 and -A7 expression and staining intensity were assessed immunohistochemically in tumoral samples of 67 pancreatic adenocarcinoma patients and were statistically analyzed in relation to clinicopathological characteristics, tumor proliferative capacity and patients' survival. Eph receptors were abundantly expressed in pancreatic ductal adenocarcinoma cases examined. Eph-A1 staining intensity was significantly associated with tumor size (pT, p = 0.008) and tumor histopathological stage (pStage, p = 0.012). Eph-A2 expression was significantly associated with patients' age (p = 0.007), while Eph-A4 and Eph-A5 with tumor proliferative capacity (p = 0.019 and p = 0.011, respectively). Pancreatic adenocarcinoma patients with moderate/intense Eph-A5 or Eph-A7 staining presented significantly shorter survival times compared to those with negative/mild one (log-rank test, p = 0.024 and p = 0.009, respectively). Multivariate analysis identified Eph-A5 and Eph-A7 staining intensity as independent prognostic factors (p = 0.048 and p = 0.004, respectively). In conclusion, the present study revealed that Eph receptors were associated with pancreatic cancer characteristics, supporting evidence for their potential clinical application in management and prognosis of pancreatic adenocarcinoma patients.

Mediterranean diet and inflammatory response in myocardial infarction survivors.

BACKGROUND: Within the framework of the multi-centre AIRGENE project we studied the association of the Mediterranean diet on plasma levels of various inflammatory markers, in myocardial infarction (MI) survivors from six geographic areas in Europe. METHODS: From 2003 to 2004, 1003 patients were repeatedly clinically examined. On every clinical visit (on average 5.8 times), blood EDTA-plasma samples were collected. High sensitivity C-reactive protein (CRP), interleukin (IL)-6 and fibrinogen concentrations were measured based on standardized procedures. Dietary habits were evaluated through a semi-quantitative Food Frequency Questionnaire (FFQ), whereas adherence to the Mediterranean diet was assessed by a diet score. RESULTS: A protective effect of adherence to the Mediterranean diet was found. For each unit of increasing adherence to the Mediterranean diet score there was a reduction of 3.1% in the average CRP levels (95% CI 0.5-5.7%) and of 1.9% in the average IL-6 levels (95% CI 0.5-3.4%) after adjusting for centre, age, sex, body mass index, physical activity, smoking status, diabetes and medication intake. No significant association was observed between the diet score and fibrinogen levels. Moderate intake of red wine (1-12 wine glasses per month) was associated with lower levels of CRP, IL-6 and fibrinogen. CONCLUSIONS: Adherence to the traditional Mediterranean diet was associated with a reduction of the concentrations of inflammatory markers in MI survivors. This may, in part, explain the beneficial effects of this diet on various chronic diseases such as atherosclerosis and cancer, and expands its role to secondary prevention level.

Clinical significance of MCM-2 and MCM-5 expression in colon cancer: association with clinicopathological parameters and tumor proliferative capacity.

Minichromosome maintenance (MCM) proteins are essential components of DNA replication, being related to cell proliferation, and serve as useful markers for cancer screening, surveillance, and prognosis. Our aim was to examine the clinical significance of MCM-2 and MCM-5 protein expression in colon cancer and to evaluate the association with various clinicopathological characteristics and tumor proliferative capacity. Immunohistochemical expression of MCM-2 and MCM-5 was performed on paraffin-embedded malignant tissue sections obtained from 96 patients with colon cancer. MCM-2 and MCM-5 expression was correlated with different clinicopathological characteristics, proliferative capacity (Ki-67 labeling index), and p53 cell-cycle regulator expression. MCM-2 and Ki-67 expression was significantly associated with the tumors' histological grade (P = 0.003), existence of nodular metastases (N) (P = 0.003 and P = 0.030, respectively), malignancy on adenoma (P = 0.029 and P = 0.024, respectively), and vascular invasion (P = 0.010 and P = 0.011, respectively). MCM-2 expression was additionally associated with Dukes' stage (P = 0.005). Significant positive relationships were found between the expression of MCM-2 or MCM-5 proteins and that of Ki-67 protein (r = 0.963, P-value < 0.001, and r = 0.738, P-value < 0.001, respectively), as well as between MCM-2 and MCM-5 proteins (r = 0.745, P-value < 0.001). Significant positive relationships were also observed between the expression of MCM-2 or MCM-5 proteins and that of p53 protein; however, they were consistently lower than the corresponding with Ki-67 protein. No significant association was observed between MCM-5 protein expression and the clinicopathological characteristics examined. The current data suggest that MCM-2 protein expression is significantly associated with important clinicopathological characteristics for patients' management, being correlated with the cell proliferation state in colon cancer.

Determinants of the acute-phase protein C-reactive protein in myocardial infarction survivors: the role of comorbidities and environmental factors.

BACKGROUND: C-reactive protein (CRP), a sensitive marker of the acute-phase response, has been associated with future cardiovascular endpoints independently of other risk factors. A joint analysis of the role of risk factors in predicting mean concentrations and variation of high-sensitivity CRP (hsCRP) in serum has not been carried out previously. METHODS: We used data from 1003 myocardial infarction (MI) survivors who had hsCRP measured monthly up to 8 times and multivariate mixed effects statistical models to study the role of time-variant and -invariant factors on the geometric mean of and the intraindividual variation in hsCRP concentrations. RESULTS: Patients with > or =6.5% glycosylated hemoglobin (HbA1c) had 26.2% higher hsCRP concentrations (95% CI, 7.2%-48.6%) and 20.7% greater variation in hsCRP values (P = 0.0034) than patients with lower baseline Hb A(1c) values (<6.5%). Similar but less pronounced differences were seen in patients with a self-reported diagnosis of type 2 diabetes. hsCRP concentrations showed less variation in patients who reported angina pectoris, congestive heart failure, or emphysema (-11.0%, -24.9%, and -41.6%, respectively, vs patients without these conditions) but greater variation in males and smokers (+24.8% and +27.3%, respectively, vs females and nonsmokers). Exposures in the 24 h before blood sampling, including exposure to environmental tobacco smoke, alcohol consumption, and extreme stress, did not have a major impact. CONCLUSIONS: One or 2 hsCRP measurements may not be sufficient to adequately characterize different patient groups after MI with similar precisions. We found hsCRP concentrations to be especially variable in males, smokers, and patients with increased Hb A(1c) values.