Formoterol in the management of chronic obstructive pulmonary disease

Bronchodilators represent the hallmark of symptomatic treatment of Chronic Obstructive Pulmonary Disease (COPD). There are four categories of bronchodilators: anticholinergics, methylxanthines, short-acting β2-agonists, and long-acting β2-agonists such as formoterol. Significant research has been performed to investigate the efficacy, safety and tolerability of formoterol in the therapeutic field of COPD. Formoterol exhibits a rapid onset of bronchodilation similar to that observed with salbutamol, yet its long bronchodilatory duration is comparable to salmeterol. In addition, formoterol presents with a clear superiority in lung function improvement compared with either ipratropium bromide or oral theophylline, while its efficacy improves when administered in combination with ipratropium. Formoterol has been shown to better reduce dynamic hyperinflation, which is responsible for exercise intolerance and dyspnea in COPD patients, compared with other bronchodilators, whereas it exerts synergistic effect with tiotropium. Moreover, formoterol reduces exacerbations, increases days free of use of rescue medication and improves patients’ quality of life and disease symptoms. Formoterol has a favorable safety profile and is better tolerated than theophylline. Collectively, data extracted from multicenter clinical trials support formoterol as a valid therapeutic option in the treatment of COPD

Effect and Safety of Mycophenolate Mofetil in Idiopathic Pulmonary Fibrosis

Background. Idiopathic pulmonary fibrosis (IPF) is a progressive fibrotic interstitial lung disease with ineffective treatment. Mycophenolate mofetil (MMF) is an immunomodulatory agent which inhibits lymphocyte proliferation. Objective. We sought to determine the safety and efficacy profile of MMF in IPF patients. Methods. We retrospectively identified ten patients, who met the ATS/ERS 2000 criteria for IPF and received MMF 2 gr/day for 12 months. All of them had routine laboratory, pulmonary function and radiological (high resolution computed tomography-HRCT) data available and were enrolled in the study. Forced vital capacity (FVC), total lung capacity (TLC), diffusion capacity of the lung for carbon monoxide (DLCO), 6-minute walking distance (6MWD), HRCT scans and routine laboratory data at treatment onset were compared with respective values 12 months after treatment onset. Results. There were no significant alterations in FVC, TLC, DLCO and 6MWD pre- and 6 and 12 months post-treatment. HRCT evaluation showed deterioration of the total extent of disease (P = 0.002) and extent of ground-glass opacity (P = 0.02). No cases of clinically significant infection, leucopenia, or elevated liver enzymes were recorded. Conclusions. MMF is a safe therapeutic modality which failed to show a beneficial effect both in functional and radiological parameters in a small cohort of IPF patients

Effect and Safety of Mycophenolate Mofetil or Sodium in Systemic Sclerosis-Associated Interstitial Lung Disease: A Meta-Analysis

Background. Interstitial lung disease (ILD) is the most common complication of systemic sclerosis (SSc) with treatment ineffective. Objective: The aim of this meta-analysis was to provide an estimate of the safety and efficacy profile of Mycophenolate Mofetil (MMF) or sodium (MMS) in SSc-ILD patients. Materials and Methods. All studies were reviewed systematically. The main end-points were safety and efficacy profile as estimated by forced vital capacity (FVC)% and diffusion capacity of the lung for carbon monoxide (DLCO)% of the predicted normal value (%pred.) before and after treatment in patients with SSc-ILD. Quality assessment and data extraction were performed independently by two reviewers. Results. Seventeen studies were reviewed systematically. Six studies, one prospective, were eligible for analysis encompassing 69 patients, including 10 subjects from our, yet unpublished, retrospective study. There was no statistically significant difference in both efficacy outcomes of interest, including FVC% pred. (weighted mean difference 1.48, 95% confidence interval (CI): −2.77 to 5.72, P = 0.49) and DLCO % pred. (weighted mean difference −0.83, 95% CI: −4.75 to 3.09, P = 0.93). No cases of clinically significant side effects were documented. Conclusions. Meta-analysis data suggest that MMF is a safe therapeutic modality which was associated with functional stabilization in patients with SSc-ILD

Comparative analysis of induced sputum and bronchoalveolar lavage fluid (BALF) profile in asbestos exposed workers

<p>Abstract</p> <p>Background</p> <p>Biological monitoring of healthy workers exposed to hazardous dusts lack validated screening tools. Induced sputum (IS) cellular profile was compared with bronchoalveolar lavage fluid (BALF) profile in asbestos exposed workers in order to assess its usefulness in monitoring workers exposed to asbestos for a long period of time.</p> <p>Methods</p> <p>IS and BALF analysis was performed in 39 workers of a car brakes and clutches factory that uses chrysotile asbestos. Selection criteria were an employment history of > 15 years and the absence of a diagnosis of pneumonoconiosis. The type of cells, the existence of dust cells, of iron laden macrophages and of asbestos bodies were assessed and compared between IS and BALF samples.</p> <p>Results</p> <p>35 IS samples (90%) had dust cells, 34 (87%) iron laden macrophages and in 8 samples (21%) asbestos bodies were found. In most samples neutrophils were dominated. Samples with asbestos bodies (ABs) had significantly higher lymphocytes and lower neutrophils count compared with the samples without ABs. Macrophages and neutrophils in IS and BALF exhibited significant inter-relations (Spearman's rho: 0.26-0.29, p < 0.05) while IS lymphocytes count showed an inverse relation with BALF neutrophils (Spearman's rho: -0.36). Neutrophils and dust cells were highly correlated between the samples (Spearman's rho: 0.35, p < 0.05) while IS dust cells and lymphocytes were inversely related (Spearman's rho: -0.36, p < 0.05). More years of employment in the company was related with more neutrophils (Spearman's rho: 0.26) and less lymphocytes (Spearman's rho: -0.33) count. In multivariate analysis the presence of AB in IS samples was strongly related to the presence of asbestos bodies and lymphocytes count in BALF samples.</p> <p>Conclusions</p> <p>IS and BALF analysis showed a similar cellular profile indicating that IS sampling in exposed workers to asbestos as a less invasive and expensive method may be useful in providing an insight both for inhalation of dusts and inflammatory processes in the lung.</p

Acute effect of smoking on plasma Obestatin levels

Background Smoking and smoking cessation are considered to be associated with weight changes. We have recently shown that smoking acutely increases plasma levels of ghrelin, a known orexigenic hormone. Obestatin is a peptide encoded by the ghrelin gene, which opposes ghrelin effects on food intake. We conducted a study in adult volunteers measuring plasma levels of obestatin immediately after initiation of smoking. Methods 31 volunteers (mean age 32.2 ± 9.2 years and mean BMI 25.7 ± 4.1), 17 smokers and 14 non-smokers, were enrolled in our study. The 2 groups were matched in age and BMI. Plasma obestatin concentrations were determined at baseline (T0), 2 (T2), 5 (T5), 15 (T15), and 60 (T60) minutes after the initiation of smoking. Results In all 31 subjects, no significant difference in the mean values of plasma obestatin levels was observed from baseline at T2, T5, T15 and T60 after initiation of smoking (overall p = 0.15). However, a trend for higher obestatin levels was noted in smokers vs non-smokers (overall p = 0.069), which was not related to the pack-years. Conclusion On the contrary with ghrelin's response after smoking initiation, there is no such an acute response of plasma obestatin levels

Simultaneous EGFR and VEGF Alterations in Non-Small Cell Lung Carcinoma Based on Tissue Microarrays

Background: Epidermal growth factor receptor (EGFR) overexpression is observed in significant proportions of non-small cell lung carcinomas (NSCLC). Furthermore, overactivation of vascular endothelial growth factor (VEGF) leads to increased angiogenesis implicated as an important factor in vascularization of those tumors.Patients and Methods: Using tissue microarray technology, forty-paraffi n (n = 40) embedded, histologically confirmed primary NSCLCs were cored and re-embedded into a recipient block. Immunohistochemistry was performed for the determination of EGFR and VEGF protein levels which were evaluated by the performance of computerized image analysis. EGFR gene amplification was studied by chromogenic in situ hybridization based on the use of EGFR gene and chromosome 7 centromeric probes.Results: EGFR overexpression was observed in 23/40 (57.5%) cases and was correlated to the stage of the tumors (p = 0.001), whereas VEGF was overexpressed in 35/40 (87.5%) cases and was correlated to the stage of the tumors (p = 0.005) and to the smoking history of the patients (p = 0.016). Statistical significance was assessed comparing the protein levels of EGFR and VEGF (p = 0.043, k = 0.846). EGFR gene amplification was identified in 2/40 (5%) cases demonstrating no association to its overall protein levels (p = 0.241), whereas chromosome 7 aneuploidy was detected in 7/40 (17.5%) cases correlating to smoking history of the patients (p = 0.013).Conclusions: A significant subset of NSCLC is characterized by EGFR and VEGF simultaneous overexpression and maybe this is the eligible target group for the application of combined anti-EGFR/VEGF targeted therapies at the basis of genetic deregulation (especially gene amplification for EGFR)

Stem cell therapy for idiopathic pulmonary fibrosis: a protocol proposal

<p>Abstract</p> <p>Background</p> <p>Idiopathic pulmonary fibrosis represents a lethal form of progressive fibrotic lung disorder with gradually increasing incidence worldwide. Despite intense research efforts its pathogenesis is still elusive and controversial reflecting in the current disappointing status regarding its treatment. Patients and Methods: We report the first protocol proposal of a prospective, unicentric, non-randomized, phase Ib clinical trial to study the safety and tolerability of the adipose-derived stem cells (ADSCs) stromal vascular fraction (SVF) as a therapeutic agent in IPF. After careful patient selection based on functional criteria (forced vital capacity-FVC > 50%, diffuse lung capacity for carbon monoxide-DL_CO> 35% of the predicted values) all eligible subjects will be subjected to lipoaspiration resulting in the isolation of approximately 100- 500 gr of adipose tissue. After preparation, isolation and labelling ADSCs-SVF will be endobronchially infused to both lower lobes of the fibrotic lungs. Procedure will be repeated thrice at monthly intervals. Primary end-point represent safety and tolerability data, while exploratory secondary end-points include assessment of clinical functional and radiological status. Results: Preliminary results recently presented in the form of an abstract seem promising and tantalizing since there were no cases of clinically significant allergic reactions, infections, disease acute exacerbations or ectopic tissue formation. In addition 6 months follow-up data revealed a marginal improvement at 6-minute walking distance and forced vital capacity.</p> <p>Conclusions</p> <p>Adipose tissue represents an abundant, safe, ethically uncontested and potentially beneficial source of stem cells for patients with IPF. Larger multicenter phase II and III placebo-controlled clinical trials are sorely needed in order to prove efficacy. However, pilot safety studies are of major importance and represent the first hamper that should be overcome to establish a rigid basis for larger clinical trials.</p