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Background In outpatients with chronic obstructive pulmonary disease (COPD), blood eosinophilia is considered as a biomarker of response to systemic corticosteroid therapy. However, little is known on whether blood eosinophilia is also predictive of positive clinical outcome in severe acute exacerbations of COPD requiring hospitalization. We hypothesized that blood eosinophil-positive severe acute exacerbations of COPD differ from eosinophil-negative ones in terms of response to therapy and clinical outcomes. Methods To test our experimental hypothesis, we retrospectively analyzed medical records of patients with COPD admitted to our ward because of severe exacerbation, over a two-year period of observation. After evaluation of inclusion and exclusion criteria, 132 patients were selected and divided in cases (blood eosinophilia ≥2% at admission; n = 20) and controls (blood eosinophilia <2% at admission; n = 112). Results Cases had a shorter hospital stay than controls (geometric mean = 8.9 ± 1.5 versus 11.3 ± 1.5 days; p = 0.028). In addition, cases had a significantly lower consumption of systemic corticosteroids (geometric mean = 19.2 ± 4.0 versus 35.7 ± 2.5 mg per day of hospitalization; p = 0.012). Conclusions In severe acute exacerbations of COPD requiring hospitalization, blood eosinophilia identifies a subgroup of subjects characterized by a prompt response to treatment with shorter hospital stay. [ABSTRACT FROM AUTHOR]

Background/Objective: This study was aimed at exploring to what extent populations enrolled in randomized controlled trials (RCTs) of inhalation combination treatment for mild/moderate asthma in adults are fully representative of 'real-life' populations. The following is a retrospective analysis of the clinical records of outpatient subjects with an ascertained diagnosis of asthma. Methods: A retrospective analysis was performed. Stable conditions, such as smoking habit and chronic diseases other than asthma, were identified as exclusion criteria for RCTs. The selected criteria were then applied to asthmatic outpatients, yielding a population that was potentially eligible for RCTs. Results: Out of 1,909 subjects, 824 (43.2%) met at least one of the exclusion criteria for RCTs. Cigarette smoking (occurring in 34.3% of the entire population), lung diseases other than asthma (5.0%), anxiety and depression (3.3%), arrhythmias (2.3%), and coronary artery disease (1.2%) would have been the most frequent causes for exclusion from RCTs. The proportion of patients excluded from RCTs appears to increase with age, reaching 57.1% in patients aged >85 years. Conclusions: In a real-life setting, >40% of subjects with mild/moderate asthma are currently treated by protocols based on the results of RCTs for which they would not have been eligible. This proportion increases in elderly patients with comorbidities. These findings limit the generalizability of RCTs and advocate that complementary pragmatic studies be conducted. © 2015 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

Age represents an exclusion criterion in randomized clinical trials designed to test the efficacy and safety of inhaled drugs in asthma. As a consequence, data on efficacy and safety of inhaled corticosteroid (ICS) and long-acting β2 agonist (LABA) combinations in elderly asthmatics are scanty. Older age is associated with an increased proportion of comorbid conditions; in addition, all organ functions undergo a process of senescence, thus reducing their ability to metabolize the agents. Overall, these age-associated conditions may variably, and often unpredictably, affect the metabolism and excretion of respiratory drugs. However, pharmacological treatment of asthma does not follow specific recommendations in the elderly. In the elderly, the ICS/LABA combinations may carry an increased risk of local indesiderable effects, primarily due to the lack of coordination between activation of the device and inhalation, and systemic adverse events, mainly due to the greater amount of active drug that is available because of the age-associated changes in organ functions as well as drug-to-drug and drug-toconcomitant disease interactions. The extra-fine formulations of ICSs/LABAs, which allow for a more favorable drug deposition in the lungs at a reduced dose, may contribute to overcome this issue. This review revises the efficacy and safety of treatment with ICSs/LABAs, focusing on the main pharmacodynamic and pharmacokinetic properties of the drugs and highlighting the potential risks in the elderly asthmatic population. [ABSTRACT FROM AUTHOR]

Inhaled corticosteroids (ICSs) are widely used in the treatment of patients with chronic obstructive pulmonary diseases. However, high-dose regimens and long-term use of ICSs have the potential to cause a variety of local and systemic side effects such as candidiasis, cataracts, glaucoma, and osteoporosis. The use of ICSs can also be associated with the risk of bone fractures, diabetes mellitus and pneumonia. These ICS-related side effects are of particular importance in elderly patients due to the presence of comorbidities and age-related behavioral, cognitive, and psychological problems, which can all interact with inhaled treatment. We reviewed the available literature on the clinically relevant side effects of ICSs in the elderly to provide practical measures to properly monitor and manage the risk of ICSs in the geriatric population. Inspection of the mouth, monitoring of ocular pressure, and use of bone-protective drugs may be necessary in patients on prolonged ICS therapy. Above all, the use of the lowest possible ICS dose and a careful re-assessment of the inhalation procedure should be recommended. Taken together, these observations suggest that physicians should use ICSs appropriately for those patients in whom the benefit will outweigh the risk, especially chronic obstructive pulmonary disease (COPD) patients with previous frequent exacerbations. Given the paucity of information on the topic and the need to extrapolate the results from studies with broader age ranges, we strongly encourage the design of specifically tailored clinical studies in the elderly. [ABSTRACT FROM AUTHOR]

Inhaled corticosteroids (ICSs) are widely used in the treatment of patients with chronic obstructive pulmonary diseases. However, high-dose regimens and long-term use of ICSs have the potential to cause a variety of local and systemic side effects such as candidiasis, cataracts, glaucoma, and osteoporosis. The use of ICSs can also be associated with the risk of bone fractures, diabetes mellitus and pneumonia. These ICS-related side effects are of particular importance in elderly patients due to the presence of comorbidities and age-related behavioral, cognitive, and psychological problems, which can all interact with inhaled treatment. We reviewed the available literature on the clinically relevant side effects of ICSs in the elderly to provide practical measures to properly monitor and manage the risk of ICSs in the geriatric population. Inspection of the mouth, monitoring of ocular pressure, and use of bone-protective drugs may be necessary in patients on prolonged ICS therapy. Above all, the use of the lowest possible ICS dose and a careful re-assessment of the inhalation procedure should be recommended. Taken together, these observations suggest that physicians should use ICSs appropriately for those patients in whom the benefit will outweigh the risk, especially chronic obstructive pulmonary disease (COPD) patients with previous frequent exacerbations. Given the paucity of information on the topic and the need to extrapolate the results from studies with broader age ranges, we strongly encourage the design of specifically tailored clinical studies in the elderly. [ABSTRACT FROM AUTHOR]

Gemcitabine is a chemotherapy agent commonly used in the treatment of non-small cell lung cancer (NSCLC) that has been demonstrated to induce apoptosis in NSCLC cells by increasing functionally active Fas expression. The aim of this study was to evaluate the Fas/Fas ligand (FasL) system involvement in gemcitabine-induced lung cancer cell killing. NSCLC H292 cells were cultured in the presence or absence of gemcitabine. FasL mRNA and protein were evaluated by real-time PCR, and by Western blot and flow cytometry, respectively. Apoptosis of FasL-expressing cells was evaluated by flow cytometry, and caspase-8 and caspase-3 activation by Western blot and a colorimetric assay. Cytotoxicity of lymphokine-activated killer (LAK) cells and malignant pleural fluid lymphocytes against H292 cells was analysed in the presence or absence of the neutralizing anti-Fas ZB4 antibody, by flow cytometry. Gemcitabine increased FasL mRNA and total protein expression, the percentage of H292 cells bearing membrane-bound FasL ( mFasL) and of mFasL-positive apoptotic H292 cells, as well as caspase-8 and caspase-3 cleavage. Moreover, gemcitabine increased CH11-induced caspase-8 and caspase-3 cleavage and proteolytic activity. Cytotoxicity of LAK cells and pleural fluid lymphocytes was increased against gemcitabine-treated H292 cells and was partially inhibited by ZB4 antibody. These results demonstrate that gemcitabine: (i) induces up-regulation of FasL in lung cancer cells triggering cell apoptosis via an autocrine/paracrine loop; (ii) induces a Fas-dependent apoptosis mediated by caspase-8 and caspase-3 activation; (iii) enhances the sensitivity of lung cancer cells to cytotoxic activity of LAK cells and malignant pleural fluid lymphocytes, partially via Fas/FasL pathway. Our data strongly suggest an active involvement of the Fas/FasL system in gemcitabine-induced lung cancer cell killing. [ABSTRACT FROM AUTHOR]

CD94/NKG2A is an inhibitory receptor expressed by NK cells and cytotoxic lymphocytes and, upon activation by HLA-E, downregulates the cytolytic activities of these cells thus representing a tumour immune escape mechanism. This study was aimed at assessing whether cytotoxic lymphocytes (CD8+) and NK cells from malignant pleural effusions have a deregulated expression of CD94/NKG2A. The expression of membrane CD94/NKG2A and perforin was evaluated by flow-cytometry in CD8+ and NK cells from pleural effusions and autologous peripheral blood of cancer (n =19) and congestive heart failure (CHF) (n =11) patients. Intracellular CD94/NKG2A expression was evaluated by flow-cytometry in pleural effusion CD8+ and NK cells from cancer patients (n =10). Cytotoxic activity against cancer cells exerted by pleural and autologous peripheral blood T lymphocytes from cancer patients was assessed by flow-cytometry assay. Pleural CD8+ from cancer patients showed a reduced expression of membrane CD94/NKG2A and perforin when compared to autologous peripheral blood and CHF pleural effusions. Reduced numbers of NK cells were present in pleural effusions from both cancer and CHF patients. Pleural NK from cancer patients showed a reduced expression of membrane CD94/NKG2A and perforin when compared to autologous peripheral blood. Pleural T lymphocytes from cancer patients exhibited a reduced cytotoxic activity against cancer cells when compared to autologous peripheral blood T lymphocytes. The intracellular expression of CD94/NKG2A in CD8+ and NK cells from cancer patients was higher than membrane expression. In conclusion, this study provides compelling evidences of new mechanisms underlying the reduced host defence against cancer within the pleural space. [Copyright &y& Elsevier]

We describe the case of an adolescent who was admitted to the hospital because of sudden occurrence of chest pain, dyspnea and subcutaneous emphysema. On admission, physical examination revealed subcutaneous crepitations in the superior part of the rib cage, and auscultation of the chest showed widespread wheezing. The radiological assessment confirmed the diagnosis of pneumomediastinum and pneumothorax. A follow-up CT scan performed one week after the admission showed almost complete resolution of the radiological alterations. At the following visits, the patient was asymptomatic, but reported to have suffered from frequent episodes of rhinorrea, sneezing, nasal blockage, and sometimes, chest tightness, especially during exposure to pets and/or windy weather. Skin prick testing showed sensitivities to dermatophagoides pteronyssinus and farinae, grass pollen and dog dander. Spirometry documented significant improvement in lung function after short-acting bronchodilator, allowing for the diagnosis of asthma to be made. Although pneumomediastinum may be a complication of various respiratory diseases, including asthma, it has never been reported as the first presentation of underlying bronchial asthma. Herein, the physiopathological mechanisms, the diagnostic procedures and treatment of pneumomediastinum in asthma are discussed. We suggest that the diagnosis of asthma should be considered in the differential diagnosis of pneumomediastinum in adolescence. [ABSTRACT FROM AUTHOR]