Estudio de los mecanismos implicados en la génesis y evolución del asma (proyecto MEGA): creación y seguimiento a largo plazo de una cohorte de pacientes asmáticos

The general aim of this study is to create a cohort of asthma patients with varying grades of severity in order to gain greater insight into the mechanisms underlying the genesis and course of this disease.The specific objectives focus on various studies, including imaging, lung function, inflammation, and bronchial hyperresponsiveness, to determine the relevant events that characterize the asthma population, the long-term parameters that can determine changes in the severity of patients, and the treatments that influence disease progression. The study will also seek to identify the causes of exacerbations and how this affects the course of the disease.Patients will be contacted via the outpatient clinics of the 8 participating institutions under the auspices of the Spanish Respiratory Diseases Networking System (CIBER). In the inclusion visit, a standardized clinical history will be obtained, a clinical examination, including blood pressure, body mass index, complete respiratory function tests, and FENO will be performed, and the Asthma Control Test (ACT), Morisky-Green test, Asthma Quality of Life Questionnaire (Mini AQLQ), the Sino-Nasal Outcome Test 22 (SNOT-22), and the Hospital Anxiety and Depression scale (HADS) will be administered. A specific electronic database has been designed for data collection. Exhaled breath condensate, urine and blood samples will also be collected. Non-specific bronchial hyperresponsiveness testing with methacholine will be performed and an induced sputum sample will be collected at the beginning of the study and every 24 months. A skin prick test for airborne allergens and a chest CT will be performed at the beginning of the study and repeated every 5 years.     

Contribution of growth phases to adult size

Based on the data of the First Zurich Longitudinal Growth Study we investigate how interindividual differences in adult size arise in the variables leg height, sitting height and standing height, arm length, biiliac width and bihumeral width. Specifically, we are also interested in the question of whether across sexes and variables the same growth phases and the same parameters are predictive for achieving a certain adult size. A rather complex pattern emerges, demonstrating that regulation of growth is not the same for boys and girls and moreover is not the same for the six anthropometric variables studied. Prepubertal growth is characterized by its intensity (average velocity) and by its duration. Whereas duration has by itself no appreciable influence on adult size, prepubertal intensity determines adult size to a high degree across all variables and both sexes. The intensity of prepubertal growth determines adult size to a larger degree for boys than for girls. For a given size at the end of the prepubertal period, a small duration enhances the chance of obtaining a large adult size. Compared with prepubertal growth, the amount of variance of adult size explained is small for pubertal parameters, and - with respect to linear measures - significant for girls only. A small duration of prepubertal growth is in the following mainly compensated by a stronger pubertal spurt (PS), to a varying degree across variables. The overall picture which emerges indicates that sitting height - and to a lesser extent bihumeral width - develop in a more irregular fashion than the variables biiliac width and leg height.     

A novel host-protein assay outperforms routine parameters for distinguishing between bacterial and viral lower respiratory tract infections

Bacterial and viral lower respiratory tract infections (LRTIs) are often clinically indistinguishable, leading to antibiotic overuse. We compared the diagnostic accuracy of a new assay that combines 3 host-biomarkers (TRAIL, IP-10, CRP) with parameters in routine use to distinguish bacterial from viral LRTIs. Study cohort included 184 potentially eligible pediatric and adult patients. Reference standard diagnosis was based on adjudication by an expert panel following comprehensive clinical and laboratory investigation (including respiratory PCRs). Experts were blinded to assay results and assay performers were blinded to reference standard outcomes. Evaluated cohort included 88 bacterial and 36 viral patients (23 did not fulfill inclusion criteria; 37 had indeterminate reference standard outcome). Assay distinguished bacterial from viral LRTI patients with sensitivity of 0.93 ± 0.06 and specificity of 0.91 ± 0.09, outperforming routine parameters, including WBC, CRP and chest x-ray signs. These findings support the assay's potential to help clinicians avoid missing bacterial LRTIs or overusing antibiotics.     

Effects of trophic 2,2′, 4,4′-tetrabromodiphenyl ether (BDE-47) exposure in Oreochromis niloticus: A multiple biomarkers analysis

Polybrominated diphenyl esters are emerging environmental contaminants with few toxicological data, being a concern for the scientific community. This study evaluated the effects of BDE-47 on the health of Oreochromis niloticus fish. The animals were exposed to three doses of BDE-47 (0, 0.253, 2.53, 25.3 ng g⁻¹) every 10 days, for 80 days. The BDE-47 affected the hepatosomatic and gonadosomatic index in female and the condition factor by intermediate dose in both sexes. The levels of estradiol decreased and the T4 are increased, but the vitellogenin production was not modulated in male individuals. Changes in AChE, GST, LPO and histopathology were observed while the integrated biomarker response index suggests that the lowest dose of BDE-47 compromised the activity of antioxidant enzymes. The oral exposure to BDE-47 in environmental concentrations is toxic to O. niloticus and the use of multiple biomarkers is an attribution in ecotoxicology studies and biomonitoring programs.     

Evaluation of matrix metalloproteases as early biomarkers for bone regeneration during the applied Masquelet therapy for non-unions

IntroductionIn the current study, we sought to determine if serum concentrations of MMPs correlate with bone regeneration occurring during the course of the Masquelet-therapy and to identify if MMPs may serve as early biomarkers reflecting successful bone regeneration and tissue remodeling.Material and methodsThis study was designed as a prospective clinical observer study. We compared serum samples over the time of treatment, as a matched-pair analysis, from 10 patients who were treated successfully with the Masquelet-therapy (Responder) with 10 patients who did not respond to the Masquelet-therapy (Non-Responder). The quantitative measurement was performed with Luminex Performance Human High Sensitivity Assays according to manufacturer’s instructions. The lab technician performing the Luminex assays was blinded to both patient data and clinical outcome.ResultsAnalysis of the expression pattern of MMP-2, -8 and -9 showed significant differences between groups. Two days after the first step of the Masquelet therapy Responder showed peak values of MMP-8 and MMP-9 that where significantly higher (p = 0.003 and p = 0.042, respectively) than in Non-Responder. In contrast serum levels of MMP-2 were lower after the first step of the Masquelet therapy in the Non-Responder group. The ratio of MMP-9 and MMP-2 was significantly higher in the Responder group two days after step I (p = 0.031) as well as 4 weeks after step II (p = 0.030).ConclusionThe findings of the current study emphasize the potential role of MMPs as biomarkers in bone remodeling. In particular, a distinct expression of MMP-2 correlates with successful bone regeneration, whereas initial overexpression of MMP-2 serum levels might identify patients that have a higher risk for a poor outcome of the Masquelet-therapy. Furthermore, we were able to introduce the serum analysis of the ratio of MMP-9 and MMP-2 as promising novel modality for early prediction of the outcome of the Masquelet therapy. Further analysis of this ratio over time subsequent to the second step might serve as an early indicator of a favorable response to the induced membrane technique.     

Significance of molecular biomarkers in idiopathic pulmonary fibrosis: A mini review

Idiopathic pulmonary fibrosis (IPF) is a chronic, irreversible condition with poor prognosis that is characterized by a variable clinical course in each patient, which renders it a complex disease with unknown causes. Despite the proven efficacy of novel antifibrotic therapies, including pirfenidone and nintedanib, the diagnosis and follow-up of IPF remain challenging. Hence, the identification of molecular biomarkers for early detection of IPF and to predict biologically determined individual clinical courses, has recently piqued the interest of researchers. Previous studies have demonstrated the diagnostic and prognostic efficacy of blood proteins such as KL-6, Surfactant protein (SP)-A, and SP-D, in patients with IPF. Due to their use in clinical practice in Japan, for approximately twenty years, a significant amount of data about these biomarkers has been accumulated. This paper reviews the recent literature on molecular biomarkers for IPF that have been developed in Japan as well as other potential molecular biomarkers.     

Study of the Normal Human Kidney and Kidney Cancer with Monoclonal Antibodies

The ability to establish immortal tissue culture lines of human renal cancer as well as short-term lines of autologous normal kidney epithelium offers a unique system to probe the differences between a neoplastic cell and its normal counterpart. Monoclonal antibodies have been prepared against cell surface differentiation antigens of normal and neoplastic human kidney. The detected antigens have been biochemically characterized, and the molecular phenotypes of these cells is being unraveled. Differences in gene expression are becoming apparent between the normal and neoplastic kidney cell. Preliminary results indicate that these differences appear to have clinical significance.     

Biomarkers in Occupational Volatile Organic Chemical Exposure

Evidence exists that in certain groups of workers exposed to volatile organic chemicals, there is subclinical renal damage and dysfunction. Also, there is activation of biological mechanisms that are suggested links between volatile organic chemical exposure and renal disease. Notably, the workers studied are employed in factories where exposures are considered controlled, with on-site professional health and safety management. Recent studies continue to indicate an increased risk of renal disease in those exposed to volatile organic chemicals.