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 MEGA Project: A Study of the Mechanisms Involved in the Genesis and Disease Course of Asthma. Asthma Cohort Creation and Long-Term Follow-Up

El objetivo general del estudio es la creación de una cohorte de pacientes con asma con distintos grados de gravedad, que permita incrementar los conocimientos sobre los mecanismos subyacentes a la génesis y evolución de esta patología. Los objetivos específicos se centran en llevar a cabo diferentes estudios en términos de imagen, de función pulmonar, inflamación e hiperrespuesta bronquial, para determinar los eventos relevantes que dan forma a esta población asmática, los parámetros a largo plazo que pueden determinar los cambios en la gravedad de los pacientes y que tratamientos pueden influir en la progresión de la enfermedad. El estudio también tratará de identificar las causas de las exacerbaciones y cómo esto afecta a la evolución de la enfermedad. Los pacientes serán contactados a través de las consultas externas de las 8instituciones participantes en el marco del CIBER de Enfermedades Respiratorias. En la visita de inclusión, se realizará una historia clínica estandarizada, un examen clínico exhaustivo, incluyendo la presión arterial, el índice de masa corporal, las pruebas funcionales respiratorias completas y la medición de la FENO, y se administrarán los cuestionarios Test de control del asma (ACT), Morisky Green, Cuestionario de calidad de vida en pacientes con asma (Mini AQLQ), el Cuestionario sino-nasal Outcome Test 22 (SNOT-22) y la escala de ansiedad y depresión (HAD). Para la recogida de los datos se ha diseñado una base de datos electrónica específica. Se recogerán también muestras de aire exhalado condensado, orina y sangre. Al inicio del estudio y cada 24 meses, se realizará una prueba de hiperrespuesta bronquial inespecífica con metacolina y se recogerá una muestra de esputo inducido. Al inicio del estudio se realizarán prick test a neumoalérgenos y una tomografía computarizada torácica que se repetirá a los 5 años

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

The MEGA Project: A Study of the Mechanisms Involved in the Genesis and Disease Course of Asthma. Asthma Cohort Creation and Long-Term Follow-Up. / 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.

Anxiety, Depression, and Asthma Control: Changes After Standardized Treatment.

BACKGROUND: It has been documented that anxiety and depression are prevalent in patients with asthma and are associated with greater frequency of exacerbations, increased use of health care resources, and poor asthma control. OBJECTIVE: To examine the association of asthma diagnosis with symptoms of depression/anxiety and asthma control not only at baseline but also over a 6-month period of specialist supervision. METHODS: We enrolled 3182 patients with moderate to severe asthma. All were evaluated with spirometry, the Asthma Control Test, and the Hospital Anxiety and Depression Scale at baseline and at 6 months. Treatments were decided by specialists according to published guidelines. RESULTS: At baseline, 24.2% and 12% of the patients were diagnosed with anxiety and depression, respectively, according to the Hospital Anxiety and Depression Scale. After 6 months, anxiety and depression improved, affecting 15.3% and 8.1% of patients, respectively (P < .001); mean FEV1 and asthma control also improved (FEV1 from 81.6% ± 20.9% to 86% ± 20.8%; Asthma Control Test score from 15.8 ± 4.7 to 19.4 ± 4.4; both P < .001). Patients with anxiety and depression used significantly more health care resources and had more exacerbations. A multivariate analysis showed that patients with anxiety, depression, and lower FEV1 (odds ratio, 0.20, 0.34, 0.62, respectively; P < .001) were independently associated with poor asthma control. A multiple linear regression analysis showed that anxiety had a nearly 4-fold greater influence over asthma control than depression (0.326/0.85 = 4.075). CONCLUSION: Under standardized asthma care and after a specific visit with the specialist, patients present significant improvement in these psychological disorders and exhibit better asthma control and functional parameters.

Mucus hypersecretion in asthma is associated with rhinosinusitis, polyps and exacerbations.

BACKGROUND: Bronchial hypersecretion is a poorly studied symptom in asthma. The aim of the study was to determine the specific characteristics of asthmatics with bronchial hypersecretion. METHODS: A total of 142 asthmatics (21.8% men; mean age 49.8 years) were prospectively followed for one year. Mucus hypersecretion was clinically classified into two severity categories: daily sputum production and frequent expectoration but not every day. Clinical and pulmonary function variables associated with mucus hypersecretion were assessed by multiple logistic regression analysis. RESULTS: Daily cough was recorded in 28.9% of patients and sputum production daily or most of the days in 52.1%. Patients with mucus hypersecretion had more dyspnoea, poorer asthma control and quality of life, had suffered from more exacerbations and showed anosmia associated with chronic rhinosinusitis and nasal polyposis more frequently. Factors associated to mucus hypersecretion were anosmia, one exacerbation or more in the previous year and FEV1/FVC <70% (AUC 0.75, 95% CI 0.66-0.85) for the first definition of hypersecretion, and anosmia, poor asthma control and age (AUC 0.75, 95% CI 0.67-0.83) for the second definition. CONCLUSIONS: Mucus hypersecretion is frequent in patients with asthma, and is associated with chronic upper airways disease, airway obstruction, poor asthma control and more exacerbations.

Utilidad del esputo inducido en la práctica clínica habitual / Utility of Induced Sputum in Routine Clinical Practice

Objetivos: Determinar la utilidad general y específica (diagnóstica y/o terapéutica) del recuento de las células inflamatorias (RCI) del esputo inducido (EI) en situación de asistencia clínica real. Métodos: Estudio retrospectivo que incluyó a los 171 pacientes que durante un año se les recogió un EI para determinar su RCI en un servicio de Neumología de un hospital de referencia. Observadores independientes al equipo médico habitual establecieron si la información proporcionada por el RCI del EI fue útil en la toma de decisiones diagnósticas y terapéuticas. Resultados: Las causas más frecuentes que motivaron la solicitud del RCI del EI fueron: asma 103 (59,20%); asma de control difícil 34 (19,54%); tos crónica 19 (10,9%), y reflujo gastroesofágico 15 (8,6%). En 115 (67,3%) pacientes el RCI del EI resultó clínicamente útil (valoración general); en 98 (57,3%) proporcionó información diagnóstica, y en 85 (49,7%), información terapéutica relevante. En el asma, asma de control difícil, tos crónica y reflujo gastroesofágico fue útil en el 71,8, el 67,6, el 47,4 y el 60%, respectivamente. Conclusiones: La información proporcionada por el RCI del EI resulta de gran utilidad en la práctica clínica, particularmente en el asma y la tos crónica. Estos resultados podrían proporcionar argumentos para recomendar la incorporación de la técnica en los servicios de Neumología de referencia y en las unidades de excelencia de asma)

Objective: To determine the general and specific utility in diagnosis and/or treatment of induced sputum (IS) inflammatory cell counts in routine clinical practice. Methods: Retrospective study of 171 patients referred for clinical sputum induction over a 1-year period in the pulmonology department of a referral hospital. Independent observers established whether the information provided by IS inflammatory cell count was useful for making diagnostic and therapeutic decisions. Results: The most frequent reasons for determination of IS inflammatory cell count were: asthma 103 (59.20%); uncontrolled asthma 34 (19.54%); chronic cough 19 (10.9%), and gastroesophageal reflux 15 (8.6%). In 115 patients (67.3%) it was generally useful for diagnosis and/or treatment; in 98 patients (57.3%) it provided diagnostic information and in 85 patients (49.7%) it assisted in therapeutic decision-making. In asthma, uncontrolled asthma, chronic cough and gastroesophageal reflux, the results were useful in 71.8%, 67.6%, 47.4% and 60%, respectively. Conclusion: The information provided by IS inflammatory cell count is extremely useful in clinical practice, especially in asthma and chronic cough. These results may justify the inclusion of the IS technique in pulmonology departments and asthma units of referral centers

Variabilidad del fenotipo inflamatorio del asma en el esputo inducido. Frecuencia y causas / Variability in Asthma Inflammatory Phenotype in Induced Sputum. Frequency and Causes

Introducción: Estudios recientes han constatado variabilidad del fenotipo inflamatorio del asma en el recuento de las células inflamatorias del esputo inducido (EI). El objetivo del presente estudio fue determinar la frecuencia y los factores que condicionan la variabilidad del fenotipo inflamatorio del EI. Métodos: Estudio observacional retrospectivo que incluyó 61 pacientes asmáticos a los que se les practicó un mínimo de dos EI en un período de 5 años. Los pacientes fueron clasificados según su fenotipo inflamatorio y posteriormente agrupados según la variabilidad del fenotipo (eosinofílicos persistentes, no eosinofílicos persistentes y eosinofílicos intermitentes). De todos los casos incluidos se recogieron datos demográficos y clínico-funcionales, así mismo se valoró los factores que pudiesen influir en la variabilidad del EI. Resultados: De los 61 pacientes, 31 (50,8%) presentaron un cambio del fenotipo inflamatorio inicial. De estos, 16 (51,6%) eran eosinofílicos, 5 (16,1%) neutrofílicos; 1 (3,2%) mixto y 9 (29,1%) paucigranulocíticos. Según la variabilidad, 18 pacientes (29,5%) se clasificaron como eosinofílicos persistentes, 17 (27,9%) no eosinofílicos persistentes y 26 (42,6%) eosinofílicos intermitentes. El tabaquismo y una exacerbación asmática reciente se asociaron significativamente con mayor riesgo de variabilidad del fenotipo inflamatorio del EI (OR = 6,44; p = 0,013; IC95% = 1,49-27,80 y OR = 5,84; p = 0,022; IC95%=1,29-26,37, respectivamente). Conclusión: La mitad de los pacientes asmáticos modifican el fenotipo inflamatorio del EI, predominando los de fenotipo eosinofílico. Esta variabilidad se asocia al tabaquismo y a una exacerbación asmática reciente. Los datos sugieren que estos factores podrían influir en la determinación del fenotipo inflamatorio del EI en la práctica clínica habitual

Introduction: Recent studies have found variability in asthma inflammatory phenotypes determined by the inflammatory cells in induced sputum (IS). The aim of this study was to determine the frequency and factors affecting inflammatory phenotype variability in IS. Methods: Retrospective observational study that included 61 asthmatic patients who underwent at least two IS tests over a period of 5 years. They were classified according to their baseline inflammatory phenotype and subsequently grouped according to phenotype variability (persistent eosinophilic, persistent non-eosinophilic and intermittent eosinophilic). Demographic, clinical and functional data and factors potentially influencing IS variability were collected in all cases. Results: Of the 61 patients, 31 (50.8%) had a change with respect to baseline inflammatory phenotype. Of these, 16 (51.6%) were eosinophilic, 5 (16.1%) neutrophilic, 1 (3.2%) mixed and 9 (29.1%) paucigranulocytic. According to phenotype variability, 18 patients (29.5%) were classified as persistent eosinophilic, 17 (27.9%) non-persistent eosinophilic, and 26 (42.6%) intermittent eosinophilic. Smoking and recent asthma exacerbation were significantly associated with increased risk of variability of the IS inflammatory phenotype (OR = 6.44; p = .013; 95% CI = 1.49-27.80 and OR = 5.84; p = .022; 95% CI = 1.29-26.37, respectively). Conclusion: Half of asthma patients, predominantly those with eosinophilic phenotype, present a change in IS inflammatory phenotype. This variability is associated with smoking and recent asthma exacerbation. Data suggest these factors can modify the classification of IS inflammatory phenotype in clinical practice

Clinical and inflammatory features of asthma with dissociation between fractional exhaled nitric oxide and eosinophils in induced sputum.

BACKGROUND: Measurement of the fractional exhaled nitric oxide (FeNO) and eosinophils in induced sputum are noninvasive markers for assessing airway inflammation in asthma. The clinical usefulness of the correlation between raised FeNO and sputum eosinophilia is controversial. We aimed to examine dissociation between FeNO and sputum eosinophils in a clinical series of asthma patients and to determine whether dissociation between these noninvasive markers was associated with clinical and inflammatory differences in these patients. METHODS AND FINDINGS: A total of 110 patients with asthma were included in a cross-sectional study. All of them were on maintenance treatment for asthma. All patients underwent the following on the same day: FeNO, induced sputum, spirometry, serum total IgE levels and skin prick test. The level of asthma control was determined by the Asthma control Test Questionnaire. In 46 (41.8%) patients, a discrepancy between FeNO and sputum eosinophil count was observed, of those, 34 (73.9%) had a FeNO <50 ppb and high eosinophil count, and were characterized by having a predominance of nonallergic asthma with bronchial eosinophilic inflammatory phenotype. Also, 12 (26.1%) patients had FeNO ≥50 ppb and sputum eosinophilia within the normal reference values, and were characterized by having a predominance of atopy with a paucigranulocytic inflammatory phenotype. CONCLUSIONS: A high percentage of patients with dissociation between results of FeNO and sputum eosinophils was observed. These patients showed differential clinical and inflammatory features.

Utility of Induced Sputum in Routine Clinical Practice. / Utilidad del esputo inducido en la práctica clínica habitual.

OBJECTIVE: To determine the general and specific utility in diagnosis and/or treatment of induced sputum (IS) inflammatory cell counts in routine clinical practice. METHODS: Retrospective study of 171 patients referred for clinical sputum induction over a 1-year period in the pulmonology department of a referral hospital. Independent observers established whether the information provided by IS inflammatory cell count was useful for making diagnostic and therapeutic decisions. RESULTS: The most frequent reasons for determination of IS inflammatory cell count were: asthma 103 (59.20%); uncontrolled asthma 34 (19.54%); chronic cough 19 (10.9%), and gastroesophageal reflux 15 (8.6%). In 115 patients (67.3%) it was generally useful for diagnosis and/or treatment; in 98 patients (57.3%) it provided diagnostic information and in 85 patients (49.7%) it assisted in therapeutic decision-making. In asthma, uncontrolled asthma, chronic cough and gastroesophageal reflux, the results were useful in 71.8%, 67.6%, 47.4% and 60%, respectively. CONCLUSION: The information provided by IS inflammatory cell count is extremely useful in clinical practice, especially in asthma and chronic cough. These results may justify the inclusion of the IS technique in pulmonology departments and asthma units of referral centers.

Variability in Asthma Inflammatory Phenotype in Induced Sputum. Frequency and Causes.

INTRODUCTION: Recent studies have found variability in asthma inflammatory phenotypes determined by the inflammatory cells in induced sputum (IS). The aim of this study was to determine the frequency and factors affecting inflammatory phenotype variability in IS. METHODS: Retrospective observational study that included 61 asthmatic patients who underwent at least two IS tests over a period of 5 years. They were classified according to their baseline inflammatory phenotype and subsequently grouped according to phenotype variability (persistent eosinophilic, persistent non-eosinophilic and intermittent eosinophilic). Demographic, clinical and functional data and factors potentially influencing IS variability were collected in all cases. RESULTS: Of the 61 patients, 31 (50.8%) had a change with respect to baseline inflammatory phenotype. Of these, 16 (51.6%) were eosinophilic, 5 (16.1%) neutrophilic, 1 (3.2%) mixed and 9 (29.1%) paucigranulocytic. According to phenotype variability, 18 patients (29.5%) were classified as persistent eosinophilic, 17 (27.9%) non-persistent eosinophilic, and 26 (42.6%) intermittent eosinophilic. Smoking and recent asthma exacerbation were significantly associated with increased risk of variability of the IS inflammatory phenotype (OR=6.44; p=.013; 95% CI=1.49-27.80 and OR=5.84; p=.022; 95% CI=1.29-26.37, respectively). CONCLUSION: Half of asthma patients, predominantly those with eosinophilic phenotype, present a change in IS inflammatory phenotype. This variability is associated with smoking and recent asthma exacerbation. Data suggest these factors can modify the classification of IS inflammatory phenotype in clinical practice.

Exhaled nitric oxide fraction as an add-on to ACQ-7 for not well controlled asthma detection.

BACKGROUND: The measurement of fractional nitric oxide concentration in exhaled breath (FeNO), a noninvasive indicator of airway inflammation, remains controversial as a tool to assess asthma control. Guidelines currently limit asthma control assessment to symptom and spirometry based appraisals such as the Asthma Control Questionnaire-7 (ACQ-7). We aimed at determining whether adding FeNO to ACQ-7 improves current asthma clinical control assessment, through enhanced detection of not well controlled asthma. METHODS: Asthmatic subjects, classified as not well controlled as per ACQ-7 on regular clinical practice, were included in a prospective, multicenter fashion, and had their maintenance treatment adjusted on visit 1. On follow-up (visit 2) four weeks later, the subjects were reevaluated as controlled or not well controlled using ACQ-7 versus a combination of FeNO and ACQ-7. RESULTS: Out of 381 subjects enrolled, 225 (59.1%) had not well controlled asthma on visit 2 as determined by ACQ-7, and 264 (69.3%) as per combined FeNO and ACQ-7. The combination of FeNO to ACQ-7 increased by 14.8% the detection of not well controlled asthma following maintenance therapy adjustment. CONCLUSIONS: The addition of FeNO to ACQ-7 increased the detectability of not well controlled asthma upon adjustment of maintenance therapy. Adding a measure of airway inflammation to usual symptom and spirometry based scores increases the efficacy of current asthma clinical control assessment.

Flow cytometry analysis of leukocytes in induced sputum from asthmatic patients.

Inflammatory cell counts in induced sputum from asthmatic patients partially correlate with respiratory physiology data. To identify and quantify these inflammatory components, microscopy has been useful but it is not without its limitations. Flow cytometry could be an alternative but still has underlying methodological difficulties. While passing airways, leukocytes undergo morphologic cellular changes that alter their conventional phenotype. To demonstrate the usefulness of cytometry in accurately identifying cellular profiles in induced sputum of asthmatic and chronic cough patients, we introduced a new panel of monoclonal antibodies against specific subset markers. To identify neutrophils, sputum cells were stained with CD45 and CD66b. To identify eosinophils, sputum cells were stained with anti-CD45 and anti-CD125. We co-stained CD45, CD14 and CD66b to identify macrophages as CD45+CD14+CD66b- cells. Comparable results of trypan blue exclusion and annexin V-FITC suggested that cytometry manipulation did not decrease cellular viability. Range values were similar in microscopy neutrophils (median 19.9%, range 1.7-90.1%) and CD45+CD66b+ neutrophils (median 31% range 0.9-89%). After gating out CD45- non-leukocyte events, CD45+ and SSC dot-plots defined three patterns of leukocyte distribution. The eosinophil range in microscopic examination was 0-71.3% (median 2.85%) whereas CD45+CD125+ cell range in cytometry was 0-29% (median 3.7%). Since no exclusive markers were found on airways macrophages, we co-stained CD45, CD14 and CD66b to identify macrophages as CD45+CD14+CD66b- cells. Microscopy showed that macrophage and CD45+CD14+CD66b- cell counts were comparable (median 52.3 and range 6.7-94.8 vs median 61 and range 10.5-97.7 respectively). Correlations between neutrophils, eosinophils and macrophages in microscopic examination and flow cytometry were strong (R=0.725, 0.747 and 0.532, respectively p<0.001). This study validates effectiveness of combining specific antibodies and cytometry to quantify inflammatory leukocytes in induced sputum. Multiple markers at a single cell level will deepen our knowledge concerning the phenotype of airway leukocytes.

Noninvasive home mechanical ventilation in elderly patients.

STUDY OBJECTIVE: To determine the short- and long-term benefits of noninvasive home mechanical ventilation (NIHMV) in patients aged 65 and older who were eligible for this treatment. DESIGN AND SETTING: This retrospective, comparative, longitudinal study was carried out in a tertiary care hospital in Barcelona (Spain). PATIENTS AND METHODS: The study included all patients in whom NIHMV with a nasal mask was established in the period from 1998 to 2001. Patients were divided into 3 groups according to age: group 1 (n = 10) > or =75; group 2 (n = 40) 65-74, and group 3 (n = 41) <65 years old. Clinical characteristics, pulmonary function results, and arterial blood gas findings were assessed in all patients before starting ventilation and after 6 months. MEASUREMENTS AND RESULTS: Statistically significant improvements in PaO(2) (13.4, 10, and 15.3 mm Hg for groups 1-3) and PaCO(2) (-17.6, -9.6 and -12.8 mm Hg for groups 1-3) were found at 6 months (p < 0.001 in all cases). There were no significant differences between the groups in blood gas parameters and treatment compliance. The incidence of related adverse events was not statistically different between the study groups (40%, 35% and 32% for groups 1-3; p = 0.859). CONCLUSIONS: NIHMV is effective in all patients for whom it is indicated, regardless of their age.

[Effect of changes in airway pressure and the inspiratory volume on the fluid filtration rate and pulmonary artery pressure in isolated rabbit lungs perfused with blood and acellular solution]. / Efecto de los cambios de presión de via aérea, volumen inspiratorio y fenoterol sobre la tasa de filtración de líquidos y la presión de arteria pulmonar en pulmones de conejos aislados y perfundidos con sangre y con solución acelular.

It has been reported that ventilation with large tidal volumes causes pulmonary edema in rats by the stimulation and release of proinflammatory mediators. Our objective was to determine the level at which volutrauma induced by changes in Airway Pressure (PAW) and Inspiratory Volume (VI) produce significant changes on the Fluid Filtration Rate (FFR) and Pulmonary Artery Pressure (PAP) in lungs perfused with blood (cellular groups) or with a buffer-albumin solution (acellular groups), with a Positive End Expiratory Pressure (PEEP) 0 or 2 cmH2O and to study the effect of a vasodilator with antiinflammatory properties (fenoterol) in blood-perfused groups. Three experimental groups were used: the cellular groups studied the effect of increased PAW and IV in isolated lungs perfused with blood and PEEP 0 and 2; the acellular groups studied the increased PAW and IV in isolated lungs perfused with a buffer-albumin solution and PEEP 0 and 2; The fenoterol group studied the effect of increased PAW and IV in isolated lungs perfused with blood + fenoterol and PEEP 2. The results show that an increase of FFR is produced earlier in acellular groups than in cellular ones and that the damage in cellular groups is microscopically and macroscopically inferior when compared to acellular groups. Fenoterol did not inhibit edema formation, and that PEEP 2, both in the cellular and the acellular groups, has a protective effect. We propose the possible existence of mediators with protective effects against the formation of pulmonary edema in the blood. These data suggest that volutrauma induced pulmonary edema has a predominantly traumatic origin when the lungs are perfused with blood.

Efecto de los cambios de presión de vía aérea, volumen inspiratorio y fenoterol sobre la tasa de filtración de líquidos y la presión de arteria pulmonar en pulmones de conejos aislados y perfundidos con sangre y con solución acelular / Effect of changes in airway pressure and the inspiratory volume on the fluid filtration rate and pulmonary artery pressure in isolated rabbit lungs perfused with blood and acellular solution

Es bien conocido que el uso de la ventilación mecánica con altos volúmenes causa edema pulmonar y que uno de los mecanismos propuestos es la estimulación y aumento de mediadores proinflamatorios. Por este motivo, se realizó un estudio con el objeto de, a través de la creación de volutrauma con aumentos graduales de la Presión de Vía Aérea (PVA) y Volumen Inspiratorio (VI), conocer a que nivel se producen cambios significativos sobre la Tasa de Filtración de Líquidos (TFL) y Presión de Arteria Pulmonar (PAP), mostrar la diferencia entre los pulmones perfundidos con sangre o con solución acelular, con Presión Positiva al final de la Espiración (PEEP) 0 y 2 cmH2O y por último determinar el efecto del uso de un vasodilatador con efecto antiinflamatorio (fenoterol). Se utilizaron 3 grupos experimentales: en los grupos celulares se estudió el efecto de los aumentos de PVA y VI en pulmones aislados y perfundidos con sangre utilizando PEEP 0 y PEEP 2. En los grupos acelulares se estudiaron los aumentos de PVA y VI en pulmones aislados y perfundidos con una solución buffer-albúmina utilizando PEEP 0 y PEEP 2. En el grupo fenoterol se estudió el efecto de los aumentos de PVA y VI en pulmones aislados y perfundidos con sangre y con fenoterol utilizando un PEEP de 2. Los resultados obtenidos nos señalan: a) el aumento de la TFL se produce más tempranamente en los grupos acelulares que en los celulares; b) en los grupos celulares tanto macroscópica como microscópicamente el daño pulmonar fue menor que en los grupos acelulares; c) el PEEP 2 tuvo un efecto protector tanto en los grupos celulares como acelulares; d) el fenoterol acelera el efecto del volutrauma en los grupos celulares con PEEP 2. Estos resultados permiten concluir la posible existencia de mediadores con efecto protector que retardan la formación del edema pulmonar por volutrauma en los pulmones perfundidos con sangre, los cuales pueden ser inhibidos mediante el uso de fenoterol. Se sugiere que el volutrauma...

[Effect of using several levels of positive end-expiratory pressure over barotrauma's induced lung injury in a model of isolated and perfused rabbit lungs]. / Estudio del efecto de las variaciones de la Presión Positiva Espiratoria Final en el daño pulmonar inducido por barotrauma en un modelo de pulmones de conejo aislados y perfundidos.

The use of Positive end-expiratory pressure (PEEP) as a strategy of mechanical ventilation offers its advantages, such as improved oxygenation, without causing alveolar overstretching and barotrauma. We aim to investigate the effect of several levels of PEEP on barotrauma and, whether an optimal level of PEEP exists. Forty-eight New Zealand rabbits (2.5-3.5 kg) were divided into four groups with PEEP settings of 0, 4, 8 and 12 cmH2O, at increasing levels of inspiratory volume (IV). This was done in blood perfused rabbit lungs and in lungs perfused with a Buffer-Albumin Solution. We observed that lungs ventilated with PEEP 0 cmH2O suffered pulmonary rupture at high IV (300cc), with significant increases of Pap (Pulmonary artery pressure) and FFR (Fluid filtration rate). Lungs ventilated with PEEP 8 and 12 suffered pulmonary rupture at lower IV (200cc and 150cc vs. 300cc respectively) On the other hand, lungs ventilated with PEEP 4 cmH2O reached the highest IV (400cc), in addition, they showed the lowest elevations of Pap and FFR. The acellular lungs ventilated with PEEP 4, 8 and 12 showed pulmonary rupture at lower IV when compared with cellular ones (300cc vs. 400cc: 100cc vs. 200cc and 100cc vs. 150cc respectively). We concluded that an optimal PEEP exists, which protects against barotrauma, however, excess of PEEP could enhance its development. The blood could contain some mediators which attenuate the damage induced by barotrauma.

Estudio del efecto de las variaciones de la presión positiva espiratoria Final en el daño pulmonar inducido por barotrauma en un modelo de pulmones de conejo aislados y perfundidos / Effect of using several levels of positive end-expiratory pressure over barotrauma's induced lung injury in a model of isolated and perfused rabbit lungs

El uso de Presión Positiva Espiratoria Final (PPEF) como estrategia de ventilación mecánica es beneficioso, permite una mejor oxigenación, sin ocasionar estiramiento alveolar y barotrauma El objetivo de este trabajo es estudiar el efecto del uso de varios niveles de PPEF sobre el barotrauma y determinar si existe un nivel de PPEF óptimo protector. Cuarenta y ocho conejos New Zeland se dividieron en cuatro grupos con PPEF establecidos en 0, 4, 8 y 12 cmH2O, a niveles crecientes de volumen inspiratorio (VI). Se utilizó un modelo de pulmones de conejo aislados y perfundidos con sangre (PC) o Solución Buffer-Albúmina (PA). Las preparaciones celulares con PPEF 0 cmH2O sufrieron ruptura a VI elevados (300cc), observándose incrementos significativos de la Pap (Presión de arteria pulmonar) y de la TFL (Tasa de filtración de líquidos). Las preparaciones con PPEF 8 y 12 cmH2O sufrieron ruptura a más bajos VI (200cc y 150cc vs. 300cc respectivamente). Las preparaciones celulares con PPEF 4 cmH2O alcanzaron el VI más elevado (400cc) con el menor incremento de Pap y TFL. Las preparaciones acelulares con PPEF 4, 8 y 12 sufrieron ruptura pulmonar a menores VI en comparación con las celulares (300cc vs. 400cc; 100cc vs. 200cc y 100cc vs. 150cc respectivamente), desarrollaron mayor edema con Pap más baja. Se pudo concluir que existe una PPEF óptima que protege contra el barotrauma, excesos de PPEF, pueden, por el contrario, acelerar el desarrollo del mismo. En la sangre podría existir algún mediador que atenúa el daño producto del barotrauma

Comparative study of two different modes of noninvasive home mechanical ventilation in chronic respiratory failure.

STUDY OBJECTIVE: Two modes of noninvasive home mechanical ventilation (NIHMV) with volumetric ventilators were compared in patients with chronic respiratory failure. DESIGN: Retrospective, parallel-group, comparative study. SETTING: Third-level teaching Hospital in Barcelona (Spain). PATIENTS AND METHODS: We studied 110 patients with chronic hypercapnic respiratory failure secondary to neuromuscular disease, kyphoscoliosis or post-tuberculosis sequelae, starting NIHMV with volumetric ventilators. The assist/control (A/C) ventilation mode was used in 45 patients and the control (C) mode in 65 patients. Clinical characteristics, pulmonary function results and arterial blood gas findings were assessed in each patient before establishing ventilation and at 6 and 12 months after. The patient's satisfaction with ventilation, the time required for adaptation, and compliance with the prescription were also assessed. MEASUREMENTS AND RESULTS: Significant improvements in PaO(2) and PaCO(2) (P<0.001) were found at 6 and 12 months with both modes of mechanical ventilation. There were no significant differences between the two modes for pulmonary function or blood gas parameters with the exception of maximum inspiratory pressure (MIP) in patients receiving the C mode, which was significantly different as compared to the baseline value after 12 months of use (mean+/-sd: 36.6+/-14.8 and 44.7+/-24.2 cmH(2)O, respectively; P=0.010). No significant differences were found in adaptation, compliance with ventilation or patient satisfaction between the two modes studied. CONCLUSIONS: According to several factors analysed, results with the A/C or C mode used with volumetric ventilators appear to be comparable in patients with chronic respiratory disease receiving NIHMV. Choice of mode will depend on the acquired experience of the prescribing physicians in each centre.

Norepinephrine increases alveolar fluid reabsorption and Na,K-ATPase activity.

The purpose of this study was to determine whether alpha-adrenergic receptor agonists have a role in alveolar fluid reabsorption, via Na,K-ATPase, in the alveolar epithelium. Alveolar fluid reabsorption increased approximately twofold with increasing concentrations of norepinephrine (NE) as compared with control rats. Treatment with the nonselective alpha-adrenergic receptor agonist, octopamine, and the specific alpha(1) agonist, phenylephrine, increased alveolar fluid reabsorption by 54 and 40%, respectively, as compared with control. The specific alpha(1)-adrenergic receptor antagonist, prazosin, inhibited the stimulatory effects of NE by approximately 30%, whereas alpha(2)-adrenergic antagonist, yohimbine, did not prevent the stimulatory effects of NE. The administration of ouabain, Na,K-ATPase inhibitor, prevented the NE-mediated increase in alveolar fluid reabsorption. In parallel with these changes, NE increased Na,K-ATPase activity and protein abundance in alveolar epithelial type II cells via the alpha(1)- and beta-adrenergic receptor. We report here that NE increased alveolar fluid reabsorption via the activation of both alpha(1)- and beta-adrenergic receptors, but not alpha(2)-adrenergic receptors. These effects are due to increased activity and abundance of the Na,K-ATPase in the basolateral membrane of ATII cells.

The indirect effect of Tityus discrepans on rabbit pulmonary vasculature.

Serum (IS) was obtained 0.5, 2, 4 or 6 h after inoculating s.c. six rabbits (approximately 2 kg) in each time period with 1 mg/kg of Tityus discrepans (Td) venom; the control was serum obtained from four rabbits 4 h after injecting them 1 ml s.c. of 0.9% NaCl. IS produced a transient (<25 min) rise in pulmonary artery pressure of isolated and perfused rabbit lungs, other lung parameters were not altered. We found that both scorpion venom and IS produced a approximately 50% transient increase of transendothelial electric resistance in cultured tissue human umbilical cord vein. Neither venom nor IS changed the transepithelial electrical resistance of tissue cultured human airway epithelia. The experiments suggest that humoral factors contained in the inoculated serum modify vascular endothelium in a much more effective manner than the venom by itself. These experiments also make it unlikely that vascular endothelium is the source of the humoral factors contained in inflammatory serum.