Hasan Bayram

Meteorological conditions, climate change, new emerging factors, and asthma and related allergic disorders. A statement of the World Allergy Organization

The prevalence of allergic airway diseases such as asthma and rhinitis has increased dramatically to epidemic proportions worldwide. Besides air pollution from industry derived emissions and motor vehicles, the rising trend can only be explained by gross changes in the environments where we live. The world economy has been transformed over the last 25 years with developing countries being at the core of these changes. Around the planet, in both developed and developing countries, environments are undergoing profound changes. Many of these changes are considered to have negative effects on respiratory health and to enhance the frequency and severity of respiratory diseases such as asthma in the general population.Increased concentrations of greenhouse gases, and especially carbon dioxide (CO2), in the atmosphere have already warmed the planet substantially, causing more severe and prolonged heat waves, variability in temperature, increased air pollution, forest fires, droughts, and floods – all of which can put the respiratory health of the public at risk. These changes in climate and air quality have a measurable impact not only on the morbidity but also the mortality of patients with asthma and other respiratory diseases. The massive increase in emissions of air pollutants due to economic and industrial growth in the last century has made air quality an environmental problem of the first order in a large number of regions of the world. A body of evidence suggests that major changes to our world are occurring and involve the atmosphere and its associated climate. These changes, including global warming induced by human activity, have an impact on the biosphere, biodiversity, and the human environment. Mitigating this huge health impact and reversing the effects of these changes are major challenges.This statement of the World Allergy Organization (WAO) raises the importance of this health hazard and highlights the facts on climate-related health impacts, including: deaths and acute morbidity due to heat waves and extreme meteorological events; increased frequency of acute cardio-respiratory events due to higher concentrations of ground level ozone; changes in the frequency of respiratory diseases due to trans-boundary particle pollution; altered spatial and temporal distribution of allergens (pollens, molds, and mites); and some infectious disease vectors. According to this report, these impacts will not only affect those with current asthma but also increase the incidence and prevalence of allergic respiratory conditions and of asthma. The effects of climate change on respiratory allergy are still not well defined, and more studies addressing this topic are needed. Global warming is expected to affect the start, duration, and intensity of the pollen season on the one hand, and the rate of asthma exacerbations due to air pollution, respiratory infections, and/or cold air inhalation, and other conditions on the other hand.

Comparison of ciliary activity and inflammatory mediator release from bronchial epithelial cells of nonatopic nonasthmatic subjects and atopic asthmatic patients and the effect of diesel exhaust particles in vitro.

BACKGROUND Recent studies have suggested that asthmatic patients may be more susceptible to the adverse effects of air pollutants, including diesel exhaust particles (DEP). The underlying mechanisms, however, are not clear. METHODS We cultured bronchial epithelial cells from bronchial biopsy specimens of well-characterized groups of nonatopic, nonasthmatic individuals and atopic patients with mild asthma and compared the ciliary beat frequency (CBF) and release of IL-8, GM-CSF, regulated on activation, normal T-cell expressed and secreted (RANTES), and soluble intercellular adhesion molecule-1 (sICAM-1) from these cells both before and after exposure for 24 hours to 10 to 100 micrograms/mL DEP in vitro. RESULTS The baseline CBF was not found to be significantly different in the bronchial epithelial cell cultures of nonasthmatic and asthmatic individuals. Incubation with DEP significantly attenuated the CBF of both the nonasthmatic and asthmatic bronchial epithelial cell cultures at all concentrations of DEP investigated and were maximal (55.5% and 45.2%, respectively) after incubation with 100 micrograms/mL DEP. The bronchial epithelial cell cultures of asthmatic patients constitutively released significantly greater amounts of IL-8, GM-CSF, and sICAM-1 than bronchial epithelial cell cultures of nonasthmatic subjects. The cultures of only asthmatic patients additionally released RANTES. Incubation of the asthmatic cultures with 10 micrograms/mL DEP significantly increased the release of IL-8 (from 102.0 to 167.8 pg/micrograms cellular protein; P <.01), GM-CSF (from 0.43 to 1.87 pg/micrograms cellular protein; P <.01), and sICAM-1 (from 14.7 to 38.1 pg/micrograms cellular protein; P <.02) after 24 hours. Incubation with 50 to 100 micrograms/mL DEP, however, significantly decreased the release of IL-8 and RANTES from these cultures. In contrast, only the higher concentrations of 50 to 100 micrograms/mL DEP significantly increased release of IL-8 (from 37.9 to 71.5 pg/micrograms cellular protein; P <.05) and GM-CSF (from 0.06 to 0. 34 pg/micrograms cellular protein; P <.05) from the bronchial epithelial cells of nonasthmatic individuals. CONCLUSIONS These results suggest that bronchial epithelial cells of asthmatic subjects are different from bronchial epithelial cells of nonasthmatic subjects with regard to the amounts and types of proinflammatory mediators they can release and that the increased sensitivity of bronchial epithelial cells of asthmatic subjects to DEP may possibly result in exacerbation of their disease symptoms.

Malignant Pleural Mesothelioma Caused by Environmental Exposure to Asbestos in the Southeast of Turkey: CT Findings in 117 Patients

Background and Objectives: Malignant pleural mesothelioma (MPM) is reported to be common in the southeast of Turkey, as a result of environmental asbestos exposure. The aim of this study was to evaluate the computed tomography (CT) features of MPM in patients with a history of asbestos exposure. Methods: The CT scans of 117 patients who had a diagnosis of MPM were retrospectively evaluated. Additionally, CT findings of histologic subtypes were compared. Results: The most common CT findings included pleural effusion (n = 104, 89%), pleural thickening (n = 96, 82%), mediastinal pleural involvement (n = 77, 66%) and interlobar fissural involvement (n = 62, 53%). Histologic subtype analysis was performed in 89 patients; of these, epithelial, sarcomatous and mixed types were identified in 46, 23 and 20 patients, respectively. An analysis of CT findings demonstrated that the involvement of mediastinal pleural (91%), interlobar fissure (87%) and lung parenchyma (48%) was significantly more frequent in sarcomatous type, as compared to epithelial (61% and p < 0.01; 35 and 4%, p < 0.0001, respectively) and mixed types (65% and p < 0.05; 10% and p < 0.0001; 10% and p < 0.01, respectively). Furthermore, there was a significant correlation between pericardial involvement and chest wall involvement (r = 0.42, p < 0.05) in sarcomatous type. Similarly, lymphadenopathy and parenchymal involvement (r = 0.23, p < 0.02), pericardial and chest wall involvement (r = 0.25, p < 0.01), chest wall and interlobar fissural involvement (r = 0.25, p < 0.01) were significantly correlated, when CT findings of all histologic subtypes were combined. Conclusions: These results suggest that although CT findings of MPM vary, they may provide valuable clues to the diagnosis, at least in patients with a history of asbestos exposure. In addition, the presence of extensive lesions may suggest MPM of sarcomatous subtype.

Effect of loratadine on nitrogen dioxide-induced changes in electrical resistance and release of inflammatory mediators from cultured human bronchial epithelial cells

BACKGROUND Recent studies have demonstrated that some antihistamines can attenuate histamine-induced release of inflammatory mediators from bronchial epithelial cells. OBJECTIVE The purpose of study was to test the hypothesis that loratadine may influence pollution-induced inflammation of the airways by modulating epithelial membrane integrity and the synthesis and/or release of inflammatory mediators from airway epithelial cells. METHODS We have cultured human bronchial epithelial cell (HBEC) cultures from surgical explants and investigated the effect of loratadine on NO2-induced changes in both electrical resistance of HBEC cultures and release of IL-8, RANTES, and soluble intercellular adhesion molecule-1 (sICAM-1) from these cells after exposure for 6 hours to either air or 400 ppb NO2. RESULTS Exposure for 6 hours to NO2 significantly decreased the electrical resistance of HBEC cultures by 18.1% from baseline (P <.05). Incubation with 0.25 to 25 micromol/L loratadine did not alter the NO2-induced decrease in the electrical resistance of HBEC cultures. NO2 also significantly increased the release of IL-8 from a control value of 52.5 pg/microgram cellular protein to 81.9 pg/microgram cellular protein (P <.05), RANTES from a control value of 0.023 pg/microgram cellular protein to 0.062 pg/microgram cellular protein (P <.05), and sICAM-1 from a control value of 7.7 pg/microgram cellular protein to 16.3 pg/microgram cellular protein (P <.05). The NO2-induced release of all 3 mediators was significantly attenuated by incubation of HBECs with 25 micromol/L loratadine. Incubation with 2.5 micromol/L loratadine also significantly attenuated the NO2-induced release of RANTES and sICAM-1, but not IL-8. CONCLUSIONS These results suggest that loratadine has the potential to reduce airway inflammation by modulating the release of inflammatory cytokines from airway epithelial cells.

An official American Thoracic Society workshop report: Climate change and human health.

This document presents the proceedings from the American Thoracic Society Climate Change and Respiratory Health Workshop that was held on May 15, 2010, in New Orleans, Louisiana. The purpose of the one-day meeting was to address the threat to global respiratory health posed by climate change. Domestic and international experts as well as representatives of international respiratory societies and key U.S. federal agencies convened to identify necessary research questions concerning climate change and respiratory health and appropriate mechanisms and infrastructure needs for answering these questions. After much discussion, a breakout group compiled 27 recommendations for physicians, researchers, and policy makers. These recommendations are listed under main issues that the workshop participants deemed of key importance to respiratory health. Issues include the following: (1) the health impacts of climate change, with specific focus on the effect of heat waves, air pollution, and natural cycles; (2) mitigation and adaptation measures to be taken, with special emphasis on recommendations for the clinical and research community; (3) recognition of challenges specific to low-resource countries when coping with respiratory health and climate change; and (4) priority research infrastructure needs, with special discussion of international needs for cooperating with present and future environmental monitoring and alert systems.

Comparison of the Effectiveness of Some Pleural Sclerosing Agents Used for Control of Effusions in Malignant Pleural Mesothelioma: A Review of 117 Cases

Background and Objectives: Management of malignant pleural mesothelioma (MPM) has been an important clinical issue regardless of the treatment modality employed. We aimed to investigate the efficacy of oxytetracycline (OT), Corynebacterium parvum (CP), and nitrogen mustard (NM) in the management of pleural effusion associated with MPM. Methods: One hundred and seventeen patients who had stage-2 MPM or over according to the Butchart staging system and unilateral or bilateral pleural effusion took part in the study. The patients received either OT (35 mg/kg), CP (7 mg), or NM (0.4 mg/kg) through a chest tube for pleurodesis. The association between several clinical parameters and patient survival was also investigated. Results: OT was applied to 59, CP to 29 and NM to 29 cases. A statistical analysis of the results obtained by these agents have demonstrated that OT (30 days, 81%; 90 days, 76.2%) and CP (30 days, 86.2%; 90 days, 79.3%) led to a significantly higher rate of successful pleurodesis as compared to NM (30 days, 48.2%; 90 days, 41.3%; p <0.05). Although the procedure was generally well tolerated by the patients, the NM-treated group experienced significantly more nausea-vomiting (46.1%) and hypotension (35.8%) compared to patients who received OT (nausea-vomiting and hypotension 4.3%; p < 0.001) and CP (nausea-vomiting and hypotension 5.1%; p < 0.001). Furthermore, we found that thrombocytosis, chest pain and weight loss were significantly associated with poor prognosis, whereas epithelial type had a positive effect on survival. Conclusion: These results suggest that OT and CP may be used as effective sclerosing agents for pleurodesis in the control of pleural effusions associated with MPM, without major side effects.

High-Resolution Computed Tomography in Cases with Environmental Exposure to Asbestos in Turkey

Background and Objectives: Although all parts of the lung can be affected as a consequence of asbestos exposure, most CT protocols tend to scan only the middle and lower parts of the thorax. The aim of this study was to investigate parenchymal and pleural lesions of persons exposed to environmental asbestos, using a high-resolution computed tomography (HRCT) protocol scanning the whole thorax. Methods: We analyzed the chest radiographs and HRCT scans of 26 patients who presented bilaterally with multiple pleural plaques related to environmental asbestos exposure. Results: Twenty-four cases (92%) had an abnormal HRCT suggestive of asbestosis. Apart from common HRCT changes related to asbestosis, we detected apical pleural thickening (APT) in 9 cases as well as a coarse honeycomb pattern adjacent to APT in 7 of these cases. Cavitary lesions due to pulmonary tuberculosis were observed on HRCT scans from 4 patients in total. Neither apical pulmonary fibrosis nor cavitary lesions were visible on chest radiographs. Conclusions: We suggest that the HRCT protocol for examining asbestos-exposed individuals with pleural plaques on chest X-rays should include the whole thorax, since the asbestos-related pathologies may involve all parts of the lung.

Effect of serum on diesel exhaust particles (DEP)-induced apoptosis of airway epithelial cells in vitro.

Patients with chronic airway diseases may be more susceptible to adverse effects of air pollutants including diesel exhaust particles (DEP). We investigated effects of foetal calf serum (FCS) on DEP-induced changes in airway epithelial cell apoptosis and inflammation. DEP (50-200 μg/ml) increased A549 cell viability in the absence of FCS. In the presence of 3.3%FCS, DEP (50-400 μg/ml) decreased A549 cell viability. N-acetylcysteine (NAC, 33 mM) and the c-jun N-terminal kinase (JNK) inhibitor (SP600125, 33 μM) further decreased the viability in the presence of DEP (200 μg/ml) and 3.3% FCS. Under serum-free (SF) condition, DEP (50 μg/ml) reduced apoptotic cells; however, when 3.3% FCS added to the culture medium, this effect was abolished. DEP (200 μg/ml) induced mRNA expression of p21(CIP1/WAF1) both in absence or presence of 3.3% FCS and enhanced JNK2 mRNA expression only in the presence of 3.3% FCS. Under SF condition, DEP (50 μg/ml) induced mRNA expression for p27 and p53, whereas cyclin E mRNA expression was inhibited by DEP (50 and 200 μg/ml). Furthermore, DEP (200 μg/ml) decreased the release of interleukin (IL)-8 in the absence of FCS. In conclusion, FCS modulates effects of DEP on cell death, cell cycle and apoptosis regulating proteins, and IL-8 release by activating oxidant stress pathways, JNK and NF-κB. Extravasation of serum, as occurs in the inflamed airways of patients with chronic airway diseases such as asthma and COPD, may render airway epithelial cells more susceptible to the deleterious effects of DEP.

Synthesis, molecular modeling, and biological evaluation of novel chiral thiosemicarbazone derivatives as potent anticancer agents.

A series of new chiral thiosemicarbazones derived from homochiral amines in both enantiomeric forms were synthesized and evaluated for their in vitro antiproliferative activity against A549 (human alveolar adenocarcinoma), MCF-7 (human breast adenocarcinoma), HeLa (human cervical adenocarcinoma), and HGC-27 (human stomach carcinoma) cell lines. Some of compounds showed inhibitory activities on the growth of cancer cell lines. Especially, compound exhibited the most potent activity (IC50 4.6 μM) against HGC-27 as compared with the reference compound, sindaxel (IC50 10.3 μM), and could be used as a lead compound to search new chiral thiosemicarbazone derivatives as antiproliferative agents.

The efficacy of single-high dose inhaled corticosteroid versus oral prednisone treatment on exhaled leukotriene and 8-isoprostane levels in mild to moderate asthmatic children with asthma exacerbation

BACKGROUND The anti-inflammatory effect of high-dose inhaled corticosteroids (ICS) in children with asthma exacerbation is unknown. We aimed to investigate the efficacy of single-high dose ICS versus oral prednisone treatment followed by a course of six day high-dose ICS or oral prednisone (P) treatment on the concentrations of Cys-LTs and 8-isoprostane levels in the exhaled breath condensate (EBC) of children with asthma exacerbation. METHODS Ninety-four children with moderate-severe asthma exacerbation were evaluated with asthma scores, peak expiratory flow rate (PEF), forced expiratory volume in first second (FEV1) and exhaled Cys-LT and 8-isoprostane levels before and after treatment. EBC was collected from 52 patients before and four hours after treatment with inhaled fluticasone propionate (FP) (4000 μg) or P and after six days of treatment with FP-1000 μg/day or P. Cys-LTs and 8-isoprostane concentrations were determined using a specific immunoassay kit. RESULTS Both single high-dose FP (n=59) and p (n=35) treatment resulted in a significant improvement in asthma score (p<0.0001), PEF (p<0.0001), and FEV1 (p<0.0001). Cys-LT concentration in the EBC decreased significantly both after the initial treatment (p=0.001), and at the end of the six-day period in the FP group (p<0.0001). 8-Isoprostane concentration was lower only after six days of treatment with FP-1000 μg/day in the FP group (p=0.023). There was a significant decrease in exhaled Cys-LTs after four hours (p=0.012) and six days of P treatment (p=0.018) in children with asthma exacerbation. CONCLUSIONS High-dose ICS treatment may be useful in the treatment of children with asthma exacerbation. The effects start as early as after four hours. The suppression of Cys-LTs production contributes to the early effects. Suppression of both Cys-LTs and oxidants may favourably contribute to the effects observed later.