Millares L.,Fundacio Parc Tauli |
Millares L.,CIBER ISCIII |
Millares L.,Autonomous University of Barcelona |
Millares L.,Fundacio Institute dInvestigacio Germans Trias I Pujol |
And 20 more authors.
European Journal of Clinical Microbiology and Infectious Diseases | Year: 2014
The bronchial microbiome in severe COPD during stability and exacerbation in patients chronically colonised by Pseudomonas aeruginosa (PA), has not been defined. Our objective was to determine the characteristics of the bronchial microbiome of severe COPD patients colonised and not colonised by P. aeruginosa and its changes during exacerbation. COPD patients with severe disease and frequent exacerbations were categorised according to chronic colonisation by P. aeruginosa. Sputum samples were obtained in stability and exacerbation, cultured, and analysed by 16S rRNA gene amplification and pyrosequencing. Sixteen patients were included, 5 of them showing chronic colonisation by P. aeruginosa. Pseudomonas genus had significantly higher relative abundance in stable colonised patients (p=0.019), but no significant differences in biodiversity parameters were found between the two groups (Shannon, 3 (2-4) vs 3 (2-3), p=0.699; Chao1, 124 (77-159) vs 140 (115-163), p=0.364). In PA-colonised patients bronchial microbiome changed to a microbiome similar to non-PA-colonised patients during exacerbations. An increase in the relative abundance over 20 % during exacerbation was found for Streptococcus, Pseudomonas, Moraxella, Haemophilus, Neisseria, Achromobacter and Corynebacterium genera, which include recognised potentially pathogenic microorganisms, in 13 patients colonised and not colonised by P. aeruginosa with paired samples. These increases were not identified by culture in 5 out of 13 participants (38.5 %). Stable COPD patients with severe disease and PA-colonised showed a similar biodiversity to non-PA-colonised patients, with a higher relative abundance of Pseudomonas genus in bronchial secretions. Exacerbation in severe COPD patients showed the same microbial pattern, independently of previous colonisation by P. aeruginosa. © 2014 The Author(s).
Milares L.,Fundacio Parc Tauli |
Milares L.,Autonomous University of Barcelona |
Rosel A.,CIBER ISCIII |
Rosel A.,Hospital Universitari Bellvitge |
And 11 more authors.
Oncology Reports | Year: 2014
Assessment of the methylation status of genes related to the development of lung cancer (LC) in bronchial secretions has been proposed as a biomarker for early detection. Several techniques are available to detect gene methylation, and the method chosen may have an effect on the results. A cross-sectional study was conducted in which the methylation status of DAPK, CDKN2A (p16) and RASSF1A genes in sputum and bronchial washing (BW) from subjects at risk for LC was analyzed. The methylation results of both samples were compared, considering BW as the reference. Results obtained by methylation-sensitive PCR (MSP) were validated by methylation-sensitive high-resolution melting (MS-HRM). The methylation results obtained in sputum and BW samples did not show statistically significant differences for any of the three genes analyzed in 65 subjects (McNemar test >0.05). Concordant results between sputum and BW were found in 40 patients for DAPK (61%), in 52 patients for p16 (80%) and in 63 patients for RASSF1 (97%). More methylated samples were found in BW, however, and sputum sensitivities and specificities for the identification of methylation status were 44 and 72% for DAPK gene, 21 and 94% for p16 and 100 and 98% for RASSF1A, respectively. When MSP results were validated by MS-HRM, DAPK and p16 gene samples methylated by MSP appeared to be unmethylated by MS-HRM. One sample showing methylation of RASSF1A gene also showed methylation when tested following MS-HRM procedure. Sputum and BW samples may be considered equally valid for the identification of methylated genes in bronchial secretions. The low sensitivity of sputum for the assessment of the methylation status of DAPK and p16 genes, however, suggests that the analysis of two or more sputum samples, or of a BW obtained semi-invasively, would be needed to attain higher reliability, together with the use of confirmatory techniques for positive results.
Garcia-Nunez M.,Fundacio Parc Tauli |
Garcia-Nunez M.,CIBER ISCIII |
Garcia-Nunez M.,Autonomous University of Barcelona |
Garcia-Nunez M.,Fundacio Institute DInvestigacio Germans Trias i Pujol |
And 22 more authors.
Journal of Clinical Microbiology | Year: 2014
Bronchial colonization by potentially pathogenic microorganisms (PPMs) is often demonstrated in chronic obstructive pulmonary disease (COPD), but culture-based techniques identify only a portion of the bacteria in mucosal surfaces. The aim of the study was to determine changes in the bronchial microbiome of COPD associated with the severity of the disease. The bronchial microbiome of COPD patients was analyzed by 16S rRNA gene amplification and pyrosequencing in sputum samples obtained during stable disease. Seventeen COPD patients were studied (forced expiratory volume in the first second expressed as a percentage of the forced vital capacity [FEV1%] median, 35.0%; interquartile range [IQR], 31.5 to 52.0), providing a mean of 4,493 (standard deviation [SD], 2,598) sequences corresponding to 47 operational taxonomic units (OTUs) (SD, 17) at a 97% identity level. Patients were dichotomized according to their lung function as moderate to severe when their FEV1%values were over the median and as advanced when FEV1%values were lower. The most prevalent phyla in sputum were Proteobacteria (44%) and Firmicutes (16%), followed by Actinobacteria (13%). A greater microbial diversity was found in patients with moderate-to-severe disease, and alpha diversity showed a statistically significant decrease in patients with advanced disease when assessed by Shannon (ρ0.528; P=0.029, Spearman correlation coefficient) and Chao1 (ρ0.53; P=0.028, Spearman correlation coefficient) alpha-diversity indexes. The higher severity that characterizes advanced COPD is paralleled by a decrease in the diversity of the bronchial microbiome, with a loss of part of the resident flora that is replaced by a more restricted microbiota that includes PPMs. Copyright © 2014, American Society for Microbiology. All Rights Reserved.
Lopez-Aguilar J.,Fundacio Parc Tauli |
Lopez-Aguilar J.,Autonomous University of Barcelona |
Lopez-Aguilar J.,Hospital Of Sabadell |
Lopez-Aguilar J.,CIBER ISCIII |
And 14 more authors.
Respiratory Physiology and Neurobiology | Year: 2015
We determined whether the combination of low dose partial liquid ventilation (PLV) with perfluorocarbons (PFC) and prone positioning improved lung function while inducing minimal stress. Eighteen pigs with acute lung injury were assigned to conventional mechanical ventilation (CMV) or PLV (5 or 10. ml/kg of PFC). Positive end-expiratory pressure (PEEP) trials in supine and prone positions were performed. Data were analyzed by a multivariate polynomial regression model. The interplay between PLV and position depended on the PEEP level. In supine PLV dampened the stress induced by increased PEEP during the trial. The PFC dose of 5. ml/kg was more effective than the dose 10. ml/kg. This effect was not observed in prone. Oxygenation was significantly higher in prone than in supine position mainly at lower levels of PEEP. In conclusion, MV settings should take both gas exchange and stress/strain into account. When protective CMV fails, rescue strategies combining prone positioning and PLV with optimal PEEP should improve gas exchange with minimal stress. © 2015 Elsevier B.V.
PubMed | Hospital Universitario La Paz, CIBER ISCIII, Fundacio Parc Tauli and Genomics and Health Area
Type: Journal Article | Journal: PloS one | Year: 2015
The course of chronic obstructive pulmonary disease (COPD) is frequently aggravated by exacerbations, and changes in the composition and activity of the microbiome may be implicated in their appearance. The aim of this study was to analyse the composition and the gene content of the microbial community in bronchial secretions of COPD patients in both stability and exacerbation. Taxonomic data were obtained by 16S rRNA gene amplification and pyrosequencing, and metabolic information through shotgun metagenomics, using the Metagenomics RAST server (MG-RAST), and the PICRUSt (Phylogenetic Investigation of Communities by Reconstruction of Unobserved States) programme, which predict metagenomes from 16S data. Eight severe COPD patients provided good quality sputum samples, and no significant differences in the relative abundance of any phyla and genera were found between stability and exacerbation. Bacterial biodiversity (Chao1 and Shannon indexes) did not show statistical differences and beta-diversity analysis (Bray-Curtis dissimilarity index) showed a similar microbial composition in the two clinical situations. Four functional categories showed statistically significant differences with MG-RAST at KEGG level 2: in exacerbation, Cell growth and Death and Transport and Catabolism decreased in abundance [1.6 (0.2-2.3) vs 3.6 (3.3-6.9), p = 0.012; and 1.8 (0-3.3) vs 3.6 (1.8-5.1), p = 0.025 respectively], while Cancer and Carbohydrate Metabolism increased [0.8 (0-1.5) vs 0 (0-0.5), p = 0.043; and 7 (6.4-9) vs 5.9 (6.3-6.1), p = 0.012 respectively]. In conclusion, the bronchial microbiome as a whole is not significantly modified when exacerbation symptoms appear in severe COPD patients, but its functional metabolic capabilities show significant changes in several pathways.
PubMed | Hospital Universitari Of Bellvitge Idibell, University of Barcelona, Autonomous University of Barcelona, CIBER ISCIII and 3 more.
Type: | Journal: Lung cancer (Amsterdam, Netherlands) | Year: 2016
The risk for lung cancer is incremented in high degree dysplasia (HGD) and in subjects with hypermethylation of multiple genes. We sought to establish the association between them, as well as to analyze the DNA aberrant methylation in sputum and in bronchial washings (BW).Cross sectional study of high risk patients for lung cancer in whom induced sputum and autofluorescence bronchoscopy were performed. The molecular analysis was determined on DAPK1, RASSF1A and p16 genes using Methylation-specific PCR.A total of 128 patients were enrolled in the study. Dysplasia lesions were found in 79 patients (61.7%) and high grade dysplasia in 20 (15.6%). Ninety eight patients out of 128 underwent molecular analysis. Methylation was observed in bronchial secretions (sputum or BW) in 60 patients (61.2%), 51 of them (52%) for DAPK1, in 20 (20.4%) for p16 and in three (3.1%) for RASSF1A. Methylated genes only found in sputum accounted for 38.3% and only in BW in 41.7%, and in both 20.0%. In the 11.2% of the patients studied, HGD and a hypermethylated gene were present, while for the 55.1% of the sample only one of both was detected and for the rest of the subjects (33.6%), none of the risk factors were observed.Our data determines DNA aberrant methylation panel in bronchial secretions is present in a 61.2% and HGD is found in 15.6%. Although both parameters have previously been identified as risk factors for lung cancer, the current study does not find a significative association between them. The study also highlights the importance of BW as a complementary sample to induced sputum when analyzing gene aberrant methylation.
Agency: European Commission | Branch: FP7 | Program: CPCSA | Phase: ICT-2013.5.1 | Award Amount: 2.59M | Year: 2014
NyMPHA project will define the framework of pre-commercial procurement for the provisioning of next generation services advocated for mental health treatment with a special focus on bipolar disorder based on the use of new technologies, open standards and open platforms. In particular, NyMPHA will focus on a first instance in identifying the different requirements involved in the structuring of mental health services with a focus on bipolar disorder treatment including medical, technological, patients, legal, ethical, policy, risk management and business-orientation needs in order to construct a reference model of service provisioning useful in different European contexts. This model will be utilized to produce a Call for Tender for the PCP aiming to provide a set of pilot experimentations implementing mobile ehealth services for bipolar disorder treatment in a real-world context.
Agency: European Commission | Branch: H2020 | Program: PCP | Phase: SC1-PM-12-2016 | Award Amount: 4.66M | Year: 2017
Patient Empowerment Individualized tackling of unnecessary stress, in particular when related to healthcare procedures, promises to enhance the autonomy and quality of life of many people and yield a significant contribution to self-empowerment, thus relieving careers and related persons from personal assistance. Not at least, also a considerable economic relief (see Impact). This is the topic the STARS consortium is determined to deal with. Of course, as will be shown, the objective is complex and ambitious and has to meet challenges from smart vital signs measuring to wireless real-time transfer of large data amounts to big data management. Nevertheless, concerning the expectable positive impact there is a large potential of revenue for the efforts. And, regarding present technological progress, it seems absolutely feasible to face this challenge when doing this inby a concerted, multidisciplinary, cross-linked effort. To achieve the aim, our proposal addresses an advanced, eHealth based concept for tailored avoidance and/or reduction of healthcare related stress, beginning as early as in the preclinical phase, proceeding during their hospitalisation until the end of the aftercare period. I.a. it can be expected that, recovery time will be shortened, harmful side-effects of sedating drugs will be prevented and costs will be reduced, which in sum will be an important contribution to a cost-effective healthcare system in the next decades.
Agency: European Commission | Branch: FP7 | Program: CPCSA | Phase: ICT-2013.5.1 | Award Amount: 2.49M | Year: 2013
A growing body of evidence suggests outcome improvement in Intensive Care Unit (ICU) patients by means of telemedicine. At present a highly interoperable, manufacturer-independent telemedicine-platform for detection of ICU-patients at increased risk is missing. Encouraging results in other eHealth-projects influenced the decision to use pre-commercial procurement (PCP), in order to provide best possible solution for THALEA.\n\nClearly identified demand and strategy detected by international ICU experts, consented by multidisciplinary stakeholders (IT-experts, excellence cluster eHealth, insurance companies and ministries) during pre-consortium meeting ensures a perfect match of demand, strategy and funding instrument in an early phase of the project. Besides inacceptable high mortality in ICU patients, telemedicine has the ability to mitigate problematic pan-European challenges, like demographic changes, shortage of ICU professionals, and scarcity of financial resources.\n\nBringing market participant and stakeholders (procurers, ICU-specialist, IT-specialist) in close collaboration, PCP within THALEA will create an appropriate common solution fulfilling demands of a telemedical research framework. Focus on interoperability and scalability will lay foundations for future follow-up projects in telemedicine. Compliance with Directive 95/46/EC is granted by limiting access to sensitive data to health professionals with obligation of professional secrecy and data transfer bound to provision of care in a tele-ICU service.\n\nTHALEA will help to close a knowledge-gap in Europe as well as to close up to research superiority projects in the US. By PCP, dissemination of this promising technology will be spread in Europe thus helping doctors to save more lives and as a result enable more patients living at home independently. An eHealth PCP-pilot for tele-ICU enhances dissemination of PCP as funding instrument beyond the innovative field of ICU-telemedicine.