Research Center Biomedica En Red Of Enfermedades Respiratorias

Madrid, Spain

Research Center Biomedica En Red Of Enfermedades Respiratorias

Madrid, Spain
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Almendros I.,University of Barcelona | Almendros I.,Research Center Biomedica En Red Of Enfermedades Respiratorias | Gozal D.,University of Chicago
Respiratory Physiology and Neurobiology | Year: 2017

The deleterious effects of intermittent hypoxia (IH) on cancer biology have been primarily evaluated in the context of the aberrant circulation observed in solid tumors which results in recurrent intra-tumoral episodic hypoxia. From those studies, IH has been linked to an accelerated tumor progression, metastasis and resistance to therapies. More recently, the role of IH in cancer has also been studied in the context of obstructive sleep apnea (OSA), since IH is a hallmark characteristic of this condition. Such recent studies are undoubtedly adding more information regarding the role of IH on tumor malignancy. In terms of the IH patterns associated with OSA, this altered oxygenation paradigm has been recently proposed as a determinant factor in fostering cancer incidence and progression from both in vitro and in vivo experimental models. Here, we summarize all the available evidence to date linking IH effects on several types of cancer. © 2017 Elsevier B.V.


Martinez-Garcia M.-A.,Polytechnic University of Valencia | Martinez-Garcia M.-A.,Research Center Biomedica En Red Of Enfermedades Respiratorias | Catalan-Serra P.,Requena General Hospital | Soler-Cataluna J.-J.,Requena General Hospital | And 6 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2012

Rationale: Obstructive sleep apnea (OSA) is a risk factor for cardiovascular death in middle-aged subjects, but it is not known whether it is also a risk factor in the elderly. Objectives: To investigate whether OSA is a risk factor for cardiovascular death and to assesswhether continuous positive airway pressure (CPAP) treatment is associated with a change in risk in the elderly. Methods: Prospective, observational study of a consecutive cohort of elderly patients (≥65 yr) studied for suspicion of OSA between 1998 and 2007. Patients with an apnea-hypopnea index (AHI) less than 15 were the control group. OSA was defined as mild to moderate (AHI, 15-29) or severe (AHI, ≥30). Patients with OSA were classified as CPAP-treated (adherence ≥ 4 h/d) or untreated (adherence < 4 h/dor not prescribed). Participants were monitored until December 2009. The end point was cardiovascular death. A multivariate Cox survival analysis was used to determine the independent impact of OSA and CPAP treatment on cardiovascular mortality. Measurements and Main Results: A total of 939 elderly were studied (median follow-up, 69 mo). Compared with the control group, the fully adjusted hazard ratios for cardiovascular mortality were 2.25 (confidence interval [CI], 1.41 to 3.61) for the untreated severe OSA group, 0.93 (CI, 0.46 to 1.89) for the CPAP-treated group, and 1.38 (CI, 0.73 to 2.64) for the untreated mild to moderate OSA group. Conclusions: Severe OSA not treated with CPAP is associated with cardiovascular death in the elderly, and adequate CPAP treatment may reduce this risk. Copyright © 2012 by the American Thoracic Society.


Domenech M.,CSIC - Biological Research Center | Domenech M.,Research Center Biomedica En Red Of Enfermedades Respiratorias | Garcia E.,CSIC - Biological Research Center | Garcia E.,Research Center Biomedica En Red Of Enfermedades Respiratorias
Frontiers in Microbiology | Year: 2017

Streptococcus pneumoniae is a common human pathogen and a major causal agent of life-threatening infections that can either be respiratory or non-respiratory. It is well known that the Helix pomatia (edible snail) agglutinin (HPA) lectin shows specificity for terminal αGalNAc residues present, among other locations, in the Forssman pentasaccharide (αGalNAc1→3βGalNAc1→3αGal1→4βGal1→4βGlc). Based on experiments involving choline-independent mutants and different growth conditions, we propose here that HPA recognizes the αGalNAc terminal residues of the cell wall teichoic and lipoteichoic acids of S. pneumoniae. In addition, experimental evidence showing that pneumococci can be specifically labeled with HPA when growing as planktonic cultures as well as in mixed biofilms of S. pneumoniae and Haemophilus influenzae has been obtained. It should be underlined that pneumococci were HPA-labeled despite of the presence of a capsule. Although some non-pneumococcal species also bind the agglutinin, HPA-binding combined with fluorescence microscopy constitutes a suitable tool for identifying S. pneumoniae and, if used in conjunction with Gram staining and/or other suitable technique like antigen detection, it may potentially facilitate a fast and accurate diagnosis of pneumococcal infections. © 2017 Domenech and García.


Lange P.,Copenhagen University | Lange P.,Hvidovre Hospital | Lange P.,Frederiksberg Hospital | Celli B.,Frederiksberg Hospital | And 23 more authors.
New England Journal of Medicine | Year: 2015

BACKGROUND Chronic obstructive pulmonary disease (COPD) is thought to result from an accelerated decline in forced expiratory volume in 1 second (FEV1) over time. Yet it is possible that a normal decline in FEV1 could also lead to COPD in persons whose maximally attained FEV1 is less than population norms. METHODS We stratified participants in three independent cohorts (the Framingham Offspring Cohort, the Copenhagen City Heart Study, and the Lovelace Smokers Cohort) according to lung function (FEV1 ≥80% or <80% of the predicted value) at cohort inception (mean age of patients, approximately 40 years) and the presence or absence of COPD at the last study visit. We then determined the rate of decline in FEV1 over time among the participants according to their FEV1 at cohort inception and COPD status at study end. RESULTS Among 657 persons who had an FEV1 of less than 80% of the predicted value before 40 years of age, 174 (26%) had COPD after 22 years of observation, whereas among 2207 persons who had a baseline FEV1 of at least 80% of the predicted value before 40 years of age, 158 (7%) had COPD after 22 years of observation (P<0.001). Approximately half the 332 persons with COPD at the end of the observation period had had a normal FEV1 before 40 years of age and had a rapid decline in FEV1 thereafter, with a mean (±SD) decline of 53±21 ml per year. The remaining half had had a low FEV1 in early adulthood and a subsequent mean decline in FEV1 of 27±18 ml per year (P<0.001), despite similar smoking exposure. CONCLUSIONS Our study suggests that low FEV1 in early adulthood is important in the genesis of COPD and that accelerated decline in FEV1 is not an obligate feature of COPD. Copyright © 2015 Massachusetts Medical Society.


Perez-Dorado I.,CSIC - Institute of Physical Chemistry "Rocasolano" | Perez-Dorado I.,Medical Research Council Laboratory of Molecular Biology | Gonzalez A.,CSIC - Biological Research Center | Gonzalez A.,Research Center Biomedica En Red Of Enfermedades Respiratorias | And 13 more authors.
Nature Structural and Molecular Biology | Year: 2010

The first structure of a pneumococcal autolysin, that of the LytC lysozyme, has been solved in ternary complex with choline and a pneumococcal peptidoglycan (PG) fragment. The active site of the hydrolase module is not fully exposed but is oriented toward the choline-binding module, which accounts for its unique in vivo features in PG hydrolysis, its activation and its regulatory mechanisms. Because of the unusual hook-shaped conformation of the multimodular protein, it is only able to hydrolyze non-cross-linked PG chains, an assertion validated by additional experiments. These results explain the activation of LytC by choline-binding protein D (CbpD) in fratricide, a competence-programmed mechanism of predation of noncompetent sister cells. The results provide the first structural insights to our knowledge into the critical and central function that LytC plays in pneumococcal virulence and explain a long-standing puzzle of how murein hydrolases can be controlled to avoid self-lysis during bacterial growth and division. © 2010 Nature America, Inc. All rights reserved.


Agusti A.,University of Barcelona | Agusti A.,Research Center Biomedica En Red Of Enfermedades Respiratorias | Vestbo J.,Copenhagen University | Vestbo J.,University of Manchester
American Journal of Respiratory and Critical Care Medicine | Year: 2011

Over the past decade there has been much research and interest in COPD. As a result, the understanding and management of the disease has improved significantly. Yet, there aremanyuncertainties and controversies that require further work. This review discusses these controversies and anticipates some of the changes that may occur in the near future in the field of COPD.


Monleon D.,Universitario Of Valencia | Morales J.M.,University of Valencia | Gonzalez-Segura A.,University of Valencia | Gonzalez-Darder J.M.,Universitario Of Valencia | And 4 more authors.
Cancer Research | Year: 2010

Meningiomas are often considered benign tumors curable by surgery, but most recurrent meningiomas correspond to histologic benign tumors. Because alterations in chromosome 14 among others have suggested clinical aggressiveness and recurrence, determining both the molecular phenotype and the genetic profile may help distinguish tumors with aggressive metabolism. The aim of this study was to achieve higher specificity in the detection of meningioma subgroups by measuring chromosomal instabilities by fluorescence in situ hybridization and cytogenetics and metabolic phenotypes by high-resolution magic angle spinning spectroscopy. We studied 46 meningioma biopsies with these methodologies. Of these, 34 were of WHO grade 1 and 12 were of WHO grade 2. Genetic analysis showed a subgroup of histologic benign meningioma with chromosomal instabilities. The metabolic phenotype of this subgroup indicated an aggressive metabolism resembling that observed for atypical meningioma. According to the metabolic profiles, these tumors had increased energy demand, higher hypoxic conditions, increased membrane turnover and cell proliferation, and possibly increased resistance to apoptosis. Taken together, our results identify distinct metabolic phenotypes for otherwise benign meningiomas based on cytogenetic studies and global metabolic profiles of intact tumors. Measuring the metabolic phenotype of meningioma intact biopsies at the same time as histopathologic analysis may allow the early detection of clinically aggressive tumors. ©2010 AACR.


Bodro M.,Hospital Universitari Of Bellvitge | Sabe N.,Hospital Universitari Of Bellvitge | Tubau F.,Research Center Biomedica En Red Of Enfermedades Respiratorias | Llado L.,Hospital Universitari Of Bellvitge | And 4 more authors.
Transplantation | Year: 2013

BACKGROUND: Although infections due to the six ESKAPE pathogens have recently been identified as a serious emerging problem, information regarding bacteremia caused by these organisms in solid-organ transplant (SOT) recipients is lacking. We sought to determine the frequency, risk factors, and outcomes of bacteremia due to drug-resistant ESKAPE (rESKAPE) organisms in liver, kidney, and heart adult transplant recipients. METHODS: All episodes of bacteremia prospectively documented in hospitalized SOT recipients from 2007 to 2012 were analyzed. RESULTS: Of 276 episodes of bacteremia, 54 (19.6%) were due to rESKAPE strains (vancomycin-resistant Enterococcus faecium [0], methicillin-resistant Staphylococcus aureus [5], extended-spectrum β-lactamase-producing Klebsiella pneumoniae [10], carbapenem-resistant Acinetobacter baumannii [8], carbapenem- and quinolone-resistant Pseudomonas aeruginosa [26], and derepressed chromosomal β-lactam and extended-spectrum β-lactamase-producing Enterobacter species [5]). Factors independently associated with rESKAPE bacteremia were prior transplantation, septic shock, and prior antibiotic therapy. Patients with rESKAPE bacteremia more often received inappropriate empirical antibiotic therapy than the others (41% vs. 21.6%; P=0.01). Overall case-fatality rate (30 days) was higher in patients with rESKAPE bacteremia (35.2% vs. 14.4%; P=0.001). CONCLUSIONS: Bacteremia due to rESKAPE pathogens is frequent in SOT recipients and causes significant morbidity and mortality. rESKAPE organisms should be considered when selecting empirical antibiotic therapy for hospitalized SOT recipients presenting with septic shock, particularly those with prior transplantation and antibiotic use. Copyright © 2013 by Lippincott Williams & Wilkins.


Sanchez-Salcedo P.,University of Navarra | Wilson D.O.,University of Pittsburgh | De-Torres J.P.,University of Navarra | Weissfeld J.L.,University of Pittsburgh | And 11 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2015

Rationale: Lung cancer (LC) screening using low-dose chest computed tomography is now recommended in several guidelines using the National Lung Screening Trial (NLST) entry criteria (age, 55-74; ≥30 pack-years; tobacco cessation within the previous 15 yr for former smokers). Concerns exist about their lack of sensitivity. Objectives: To evaluate the performance of NLST criteria in two different LC screening studies from Europe and the United States, and to explore the effect of using emphysema as a complementary criterion. Methods: Participants from the Pamplona International Early Lung Action Detection Program (P-IELCAP; n = 3,061) and the Pittsburgh Lung Screening Study (PLuSS; n = 3,638) were considered. LC cumulative frequencies, incidence densities, and annual detection rates were calculated in three hypothetical cohorts, including subjects whometNLST criteria alone, those withcomputed tomography-detected emphysema, and those who met NLST criteria and/or had emphysema. Measurements and Main Results: Thirty-six percent and 59% of P-IELCAP and PLuSS participants, respectively, met NLST criteria. Among these, higher LC incidence densities and detection rates were observed. However, applying NLST criteria to our original cohorts would miss asmany as 39% of all LC. Annual screening of subjects meeting either NLST criteria or having emphysema detected most cancers (88% and 95% of incident LC of P-IELCAP and PLuSS, respectively) despite reducing the number of screened participants by as much as 52%. Conclusions: LC screening based solely on NLST criteria could miss a significant number of LC cases. Combining NLST criteria and emphysema to select screening candidates results in higher LC detection rates and a lower number of cancers missed. Copyright © 2015 by the American Thoracic Society.


Blanco I.,University of Barcelona | Gimeno E.,University of Barcelona | Munoz P.A.,Research Center Biomedica En Red Of Enfermedades Respiratorias | Pizarro S.,University of Barcelona | And 7 more authors.
American Journal of Respiratory and Critical Care Medicine | Year: 2010

Rationale: Sildenafil, a phosphodiesterase-5 inhibitor, could be useful for treating pulmonary hypertension (PH) in chronic obstructive pulmonary disease (COPD). However, vasodilators may inhibit hypoxic pulmonary vasoconstriction and impair gas exchange in this condition. Objectives: To assess the acute hemodynamic and gas exchange effects of sildenafil in patients with COPD-associated PH. Methods: We conducted a randomized, dose comparison trial in 20 patients with COPD-associated PH. Eleven patients were assigned to 20 mg, and 9 patients to 40 mg, of sildenafil. Pulmonary hemodynamics and gas exchange, including ventilation-perfusion (V̇A/Q̇) relationships, were assessed at rest and during constant-work rate exercise, before and 1 hour after sildenafil administration. Measurements and Main Results: Both sildenafil doses reduced the mean pulmonary arterial pressure (PAP) at rest and during exercise, without differences between them. Overall, PAP decreased -6mmHg (95% confidenc einterval [95%CI], -7 to -4) at rest and -11mmHg (95% CI, -14 to 28) during exercise. After sildenafil, PaO2 decreased -6mmHg (95% CI, -8 to -4) at rest because of increased perfusion in units with low V̇A/Q̇ ratio, without differences between doses. No change in PaO2 (95% CI, -3 to 0.2 mm Hg) or V̇A/Q̇ relationships occurred during exercise after sildenafil. Changes induced by sildenafil in PaO2 and V̇A/Q̇ distributions at rest correlated with their respective values at baseline. Conclusions: In patients with COPD-associated PH, sildenafil improves pulmonary hemodynamics at rest and during exercise. This effect is accompanied by the inhibition of hypoxic vasoconstriction, which impairs arterial oxygenation at rest. The use of sildenafil in COPD should be done cautiously and under close monitoring of blood gases. Clinical trial registered with www.clinicaltrials.gov (NCT00491803).

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