International Consensus Document on Obstructive Sleep Apnea

"Artículo escrito por un elevado número de autores, solo se referencian el que aparece en primer lugar, el nombre del grupo de colaboración, si le hubiere, y los autores pertenecientes a la UAM"El objetivo principal de este documento internacional de consenso sobre apnea obstructiva del sue˜no esproporcionar unas directrices que permitan a los profesionales sanitarios tomar las mejores decisionesen la asistencia de los pacientes adultos con esta enfermedad según un resumen crítico de la literaturamás actualizada. El grupo de trabajo de expertos se ha constituido principalmente por 17 sociedadescientíficas y 56 especialistas con amplia representación geográfica (con la participación de 4 sociedadesinternacionales), además de un metodólogo experto y un documentalista del Centro Cochrane Iberoame-ricano. El documento consta de un manuscrito principal, con las novedades más relevantes, y una seriede manuscritos online que recogen las búsquedas bibliográficas sistemáticas de cada uno de los aparta-dos del documento internacional de consenso. Este documento no cubre la edad pediátrica ni el manejodel paciente en ventilación mecánica crónica no invasiva (que se publicarán en sendos documentos deconsenso aparte).The main aim of this international consensus document on obstructive sleep apnea is to provide guidelines based on a critical analysis of the latest literature to help health professionals make the best decisions in the care of adult patients with this disease. The expert working group was formed primarily of 17 scientific societies and 56 specialists from a wide geographical area (including the participation of 4 international societies), an expert in methodology, and a documentalist from the Iberoamerican Cochrane Center. The document consists of a main section containing the most significant innovations and a series of online manuscripts that report the systematic literature searches performed for each section of the international consensus document. This document does not discuss pediatric patients or the management of patients receiving chronic non-invasive mechanical ventilation (these topics will be addressed in separate consensus documents)

Serum micrornas as tool to predict early response to benralizumab in severe eosinophilic asthma

Severe eosinophilic asthma poses a serious health and economic problem, so new therapy approaches have been developed to control it, including biological drugs such as benralizumab, which is a monoclonal antibody that binds to IL-5 receptor alpha subunit and depletes peripheral blood eosinophils rapidly. Biomarkers that predict the response to this drug are needed so that microRNAs (miRNAs) can be useful tools. This study was performed with fifteen severe eosinophilic asthmatic patients treated with benralizumab, and serum miRNAs were evaluated before and after treatment by semi-quantitative PCR (qPCR). Patients showed a clinical improvement after benralizumab administration. Additionally, deregulation of miR-1246, miR-5100 and miR-338-3p was observed in severe asthmatic patients after eight weeks of therapy, and a correlation was found between miR-1246 and eosinophil counts, including a number of exacerbations per year in these severe asthmatics. In silico pathway analysis revealed that these three miRNAs are regulators of the MAPK signaling pathway, regulating target genes implicated in asthma such as NFKB2, NFATC3, DUSP1, DUSP2, DUSP5 and DUSP16. In this study, we observed an altered expression of miR-1246, miR-5100 and miR-338-3p after eight weeks of benralizumab administration, which could be used as early response markers.This manuscript was funded by Fondo de Investigación Sanitaria–FIS and FEDER (Fondo Europeo de Desarrollo Regional) [PI15/00803, PI18/00044, and FI16/00036], CIBER de Enfermedades Respiratorias (CIBERES), Merck Health Foundation funds, and Ministerio de Ciencia, Innovación y Universidades (RTC-2017-6501-1

Capacidad de difusión del monóxido de carbono en el pulmón: influencia del volumen alveolar y factor de corrección, comparación entre métodos, contribuciones a la estandarización

Tesis doctoral inédita leída en la Universidad Autónoma de Madrid, Facultad de Medicina, Departamento de Medicina. Fecha de lectura: 22 de Julio de 198

Multiple-breath washout experiments in rat lungs

Multiple-breath washouts were performed on 30 Wistar rats postmortem in a study in which breaths of 90% O2-5% He-5% SF6 were given. Preliminary comparison of alveolar plateau slopes obtained from anesthetized rats in vivo and postmortem showed that ventilation distribution remains the same within 1 h after the animals were killed. For maneuvers with different preinspiratory lung volumes and end-inspiratory breathholding, we computed the normalized N2 slope (Sn) and Fowler and Bohr dead spaces [VD(F)(n) and VD(B)(n), respectively] as a function of breath number (n). For all maneuvers analyzed, Sn of all gases increased in the first two or three breaths and reached a horizontal asymptote thereafter. The value of Sn decreased, both with increasing preinspiratory lung volume and breath hold of 4 s. The fact that the horizontal Sn asymptote is reached after only two or three breaths suggests the absence of convection-dependent inhomogeneities (CDI) in rat lungs. This contrasts with multiple-breath washout experiments in humans, where interregional (gravity-dependent CDI) and intraregional CDI generate a marked increase in Sn throughout the entire washout. Also, in contrast with results in humans, VD(F) and VD(B) were independent of n. The present work suggests that rats may be used to study diffusion- and convection-dependent inhomogeneities without the influence of CDI or gas exchange.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Single-breath washout experiments in rat lungs

Single-breath washouts were performed on 30 Wistar rats postmortem in studies in which breaths of 90% O2-5% He-5% SF6 were given. We investigated the effects of variations in preinspiratory lung volume, inspired volume, end-inspiratory breath-hold time, and inspiratory and expiratory flows on the alveolar plateau slopes for N2, He, and SF6. The main result is that the slope for He was always larger than the slope for SF6, except for large breath-hold times (~15 s), contrary to previous findings in other species. Slopes for the three gases decreased with increasing inspiratory and expiratory flows when flows were >1 ml/s. There was a strong correlation between the magnitude of a slope and its curvilinearity, suggesting that the concentration heterogeneity in the lung that causes the slope is due to interaction between diffusion and convection. The results seem incompatible with heterogeneities of parenchymal elasticity, which have been said to contribute to alveolar slopes in dog lungs but appear to be completely explainable as the result of diffusion-convection interaction in an asymmetric lung structure that has acini widely spread along the tracheobronchial tree.SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Single-breath washouts in a rotating stretcher

SCOPUS: ar.jinfo:eu-repo/semantics/publishe

Early Detection of Susceptibility to Acute Lung Inflammation by Molecular Imaging in Mice Exposed to Cigarette Smoke

Matrix metalloproteinases (MMPs) are extracellular proteolytic enzymes involved in acute lung inflammation in response to cigarette smoke exposure (CSE). We present the in vivo detection of MMP activity using a specific MMP-activatable, near-infrared, polymer-based proteolytic probe in strains of mice with different susceptibility to developing smoking-induced emphysema (susceptible mice, C57BL/6j, and resistant mice, 129S2/SvHsd) to characterize the distinctive profile of CSE-induced acute inflammation. In vivo imaging of pulmonary inflammation expressing MMPs revealed a significantly different median ratio twofold higher in smoker than in nonsmoker susceptible mice (C57BL/6j) and no significant differences between the smoker and the nonsmoker group in resistant mice (129S2/SvHsd). Ex vivo imaging of the lungs of each group of mice confirmed the same in vivo experiment results obtained for both strains of mice. In the biochemical study of lung tissue, the proteolytic signal colocalized with the endogenously expressed MMP protein levels, with MMP-9 levels that are 2.2 times higher than in the nonsmoke-exposed group in C57BL/6j mice and no significant differences in the 129S2/SvHsd mice. The MMP-activatable probe provides a useful reagent for the in vivo and ex vivo detection of MMP-selective proteolytic activity. We are able to distinguish between susceptible and resistant strains of mice in terms of the profile of MMP activity in the early stages of pulmonary disease

Similar ventilation distribution in normal subjects prone and supine during tidal breathing

Multiple-breath washout (MBW) tests, with end-expiratory lung volume at functional residual capacity (FRC) and 90% 02, 5% He, and 5% SF6 as an inspired gas mixture, were performed in healthy volunteers in supine and prone postures. The semilog plot of MBW N2 concentrations was evaluated in terms of its curvilinearity. The MBW N2 normalized slope analysis yielded indexes of acinar and conductive ventilation heterogeneity (Verbanck S, Schuermans D, Van Muylem A, Paiva M, Noppen M, and Vincken W. JApp Physiol 83: 1907-1916, 1997). Also, the difference between SF6 and He normalized phase III slopes was computed in the first MBW expiration. Only MBW tests with similar FRC in the prone and supine postures (P > 0.1; n = 8) were considered. Prone and supine postures did not reveal any significant differences in curvilinearity, N2 normalized slope-derived indexes of conductive or acinar ventilation heterogeneity, nor SF6-He normalized phase III slope difference in the first MBW expiration (P > 0.1 for all). The absence of significant changes in any of the MBW indexes suggests that ventilation heterogeneity is similar in the supine and prone postures of normal subjects breathing near FRC.SCOPUS: ar.jinfo:eu-repo/semantics/publishe