Chronic obstructive pulmonary disease in patients with lung cancer: prevalence, impact and management challenges

Dionisios Spyratos, Eleni Papadaki, Sofia Lampaki, Theodoros Kontakiotis Pulmonary Department, Lung Cancer Oncology Unit, Aristotle University of Thessaloniki, G. Papanicolaou Hospital, Thessaloniki, Greece Abstract: Chronic obstructive pulmonary disease (COPD) and lung cancer share a common etiological factor (cigarette smoking) and usually coexist in everyday clinical practice. The prevalence of COPD among newly diagnosed patients with lung cancer sometimes exceeds 50%. COPD is an independent risk factor (2–4 times higher than non-COPD subjects) for lung cancer development.The presence of emphysema in addition to other factors (e.g., smoking history, age) could be incorporated into risk scores in order to define the most appropriate target group for lung cancer screening using low-dose computed tomography. Clinical management of patients with coexistence of COPD and lung cancer requires a multidisciplinary oncology board that includes a pulmonologist. Detailed evaluation (lung function tests, cardiopulmonary exercise test) and management (inhaled drugs, smoking cessation, pulmonary rehabilitation) of COPD should be taken into account for lung cancer treatment (surgical approach, radiotherapy). Keywords: lung cancer, COPD, coexistence, risk factor, therapy decisions&nbsp

mTOR pathway: A current, up-to-date mini-review

Mammalian target of rapamycin (mTOR) is a protein serine/threonine kinase that was initially identified as the cellular target of rapamycin. This kinase regulates cell growth, proliferation, motility and survival, as well as the gene transcription and protein synthesis that are activated in response to hormones, growth factors and nutrients. Results from preclinical studies have indicated that factors antagonizing the mTOR pathway exert an antitumor effect on lung cancer. Furthermore, primary clinical trials of mTOR inhibitors have demonstrated that the inhibitors may be effective against lung carcinoma. The present study explores the association between mTOR and lung carcinogenesis and describes the clinical trials of mTOR inhibitors. © 2014, Spandidos Publications. All rights reserved

Dynamic relocalization of cytosolic type III secretion system components prevents premature protein secretion at low external pH

Abstract Many bacterial pathogens use a type III secretion system (T3SS) to manipulate host cells. Protein secretion by the T3SS injectisome is activated upon contact to any host cell, and it has been unclear how premature secretion is prevented during infection. Here we report that in the gastrointestinal pathogens Yersinia enterocolitica and Shigella flexneri , cytosolic injectisome components are temporarily released from the proximal interface of the injectisome at low external pH, preventing protein secretion in acidic environments, such as the stomach. We show that in Yersinia enterocolitica , low external pH is detected in the periplasm and leads to a partial dissociation of the inner membrane injectisome component SctD, which in turn causes the dissociation of the cytosolic T3SS components. This effect is reversed upon restoration of neutral pH, allowing a fast activation of the T3SS at the native target regions within the host. These findings indicate that the cytosolic components form an adaptive regulatory interface, which regulates T3SS activity in response to environmental conditions

Sex differences of continuous positive airway pressure treatment on flow-mediated dilation in patients with obstructive sleep apnea syndrome

Anastasios Kallianos,1 Athanasios Panoutsopoulos,1 Christoforos Mermigkis,2 Konstantinos Kostopoulos,1 Chrysanthi Papamichail,1 Ioannis Kokkonouzis,3 Christoforos Kostopoulos,1 Ioannis Nikolopoulos,4 Antonis Papaiwannou,5 Sofia Lampaki,5 John Organtzis,5 Georgia Pitsiou,5 Paul Zarogoulidis,5 Georgia Trakada1 1Sleep Disorders Unit, Department of Clinical Therapeutics, “Alexandra” General Hospital, Athens School of Medicine, 2Sleep Disorders Unit, Pulmonary Department, 401 General Army Hospital, 3Pulmonary Department, 251 Hellenic Air Force General Hospital, 4Sleep Disorders Unit, “Sotiria” Regional Chest Diseases Hospital of Athens, Athens, Greece; 5Pulmonary Department – Oncology Unit, George Papanikolaou General Hospital of Thessaloniki, Aristotle University of Thessaloniki, Thessaloniki, GreeceIntroduction: There is growing research evidence suggesting the presence of endothelial dysfunction and systemic inflammation in patients with obstructive sleep apnea syndrome (OSAS). Continuous positive airway pressure (CPAP) is the most effective method for treating OSAS; nonetheless, the effects of CPAP on the aforementioned pathophysiologic pathways as well as on the systemic disease that result or coexist with the OSAS remain elusive.Aim: To assess the effect of 3-month CPAP therapy on endothelial-dependent dilation, plasma levels of inflammatory markers, blood pressure (BP), and glucose control on male and female patients with OSAS.Methods: Our study group consisted of 40 (24 males and 16 females) patients with no prior history of cardiovascular disease, with an apnea–hypopnea index ≥15, who were assigned to receive CPAP treatment. Measurements of flow-mediated dilation (FMD), 24-hour ambulatory BP, and blood analysis were performed at baseline and 3 months after CPAP therapy.Results: Baseline FMD values were negatively correlated with the apnea–hypopnea index (r=−0.55, P=0.001). After 3 months of CPAP, there was an increase in the FMD values (5.40%±2.91% vs 3.13%±3.15%, P<0.05) and a significant reduction in the patients’ 24-hour systolic BP (122.82±11.88 mmHg vs 130.24±16.75 mmHg, P<0.05), diastolic BP (75.44±9.14 mmHg vs 79.68±11.09 mmHg, P<0.05), and pulse pressure (47.38±9.77 mmHg vs 52.72±11.38 mmHg, P<0.05); daytime systolic BP (125.76±12.69 mmHg vs 132.55±17.00 mmHg, P<0.05) and diastolic BP (77.88±10.39 mmHg vs 82.25±11.01 mmHg, P<0.05); nighttime systolic BP (118.17±13.16 mmHg vs 126.22±17.42 mmHg, P<0.05) and pulse pressure (46.61±10.76 mmHg vs 52.66±11.86 mmHg, P<0.05); and C-reactive protein and HbA1c levels (0.40 [0.40–0.70] mg/L vs 0.60 [0.40–0.84] mg/L and 5.45%±0.70% vs 5.95%±1.08%, respectively; P<0.05). When divided by sex, only male patients produced similar statistically significant results, while female patients failed to show such associations.Conclusion: Our results suggest that CPAP therapy improves the endothelial function, the BP, and the glucose control in male patients with OSAS. Further research is warranted in order to verify these results and to further elucidate the impact of CPAP on the cardiovascular risk of male and female patients with OSAS. Keywords: obstructive sleep apnea syndrome, CPAP, CRP, blood pressure, glucose contro

Roflumilast, a phosphodiesterase-4 inhibitor, induces phagocytic activity in Greek COPD patients

Konstantinos Porpodis,1 Kalliopi Domvri,1 Paul Zarogoulidis,1 Dimitrios Petridis,2 Katerina Tsirgogianni,1 Antonis Papaioannou,1 Olga Hatzizisi,3 Ioannis Kioumis,1 Alexandra Liaka,3 Violeta Kikidaki,3 Sofia Lampaki,1 John Organtzis,1 Konstantinos Zarogoulidis1 1Pulmonary Department-Oncology Unit, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, 2Department of Food Technology, School of Food Technology and Nutrition, Alexander Technological Educational Institute, 3Pulmonary Department, Immunology and Histocompatibility Laboratory, G Papanikolaou General Hospital, Aristotle University of Thessaloniki, Thessaloniki, Greece Background: A new approach to the treatment of COPD includes controlling inflammation because of its important role in exacerbation of the disease. Recently, roflumilast has been added as a therapeutic option for COPD. Roflumilast is an oral phosphodiesterase-4 inhibitor that targets inflammatory cells involved in triggering exacerbations of COPD. The objective of the current study was to evaluate roflumilast for its contribution to phagocytic activity in COPD patients.Methods: Twenty-one patients diagnosed with COPD received roflumilast once daily for 6 months in combination with fluticasone (an inhaled corticosteroid), salmeterol (a long-acting β2-agonist), and tiotropium (a long-acting muscarinic antagonist) or combinations of these agents. The main inclusion criterion was stable disease for at least the previous 30 days. Neutrophils and spirometric changes, ie, forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC), were measured in the COPD patients at indicated time points. The first sample was taken before receiving roflumilast, the second 3 months later, and the third after 6 months. Examination of defective phagocytosis was done by flow cytometry using a FagoFlowEx® kit. The statistical analysis was performed using Statistica software. Results: Our results indicate that phagocytic activity was increased after 3 and 6 months of treatment when compared with baseline (P<0.001). Similarly, FVC and FEV1 were also increased during the 6-month period, but only FVC differed significantly from baseline (P<0.001).Conclusion: Although the number of patients in this study was limited, our results indicate that roflumilast induces phagocytic activity, which improves lung function. Keywords: COPD, roflumilast, phosphodiesterase-4 inhibitor

Inhaled tyrosine kinase inhibitors for pulmonary hypertension: A possible future treatment

Pulmonary hypertension is a disease with severe consequences for the human body. There are several diseases and situations that induce pulmonary hypertension and are usually underdiagnosed. Treatments include conventional medical therapies and oral, inhaled, intravenous, and subcutaneous options. Depending on its severity, heart or lung transplant may also be an option. A possible novel treatment could be tyrosine kinase inhibitors. We conducted experiments with three jet nebulizers and three ultrasound nebulizers with erlotinib, gefitinib, and imatinib. Different residual cup designs and residual cup loadings were used in order to identify the best combination to produce droplets of less than 5 µm in mass median aerodynamic diameter. We found that gefitinib could not be transformed into a powder, so conversion to an aerosol form was not possible. Our experiments indicated that imatinib is superior to erlotinib with regard to small droplet size formation using both inhaled technologies (1.37 µm <2.23 µm and 1.92 µm <3.11 µm, jet and ultrasound, respectively) and, at jet devices (1.37 µm <1.92 µm). Cup designs C and G contribute best to small droplet creation uniquely supporting and equally well the activity of both drugs. The disadvantage of the large droplets formed for erlotinib was offset when combined with residual cup C (1.37 µm instead of 2.23 µm). At a 2 mL dose, the facemask and cone mouthpieces performed best and evenly; the facemask and low dose were the best choice (2.08 µm and 2.12 µm, respectively). Erlotinib and imatinib can be administered as an aerosols, and further in vivo experimentation is necessary to investigate the positive effects of these drugs in the treatment of pulmonary hypertension. © 2014 Pitsiou et al