Antoni Xaubet

Role of bronchoalveolar lavage in the diagnosis of fat embolism syndrome

Fat embolism syndrome (FES) is a serious clinical disorder occurring in trauma patients. The diagnosis of fat embolism syndrome may be difficult to establish clinically. We therefore wanted to investigate the usefulness of bronchoalveolar lavage (BAL) in the diagnostic evaluation of fat embolism syndrome. We analysed the presence of fat droplets in BAL cells in 32 trauma patients (7 with full diagnostic criteria of fat embolism syndrome, 17 with incomplete diagnostic criteria, and 8 with no diagnostic criteria at the time of bronchoscopy), 9 nontrauma patients with acute respiratory failure and radiographic pulmonary infiltrates, and a control group composed of 10 individuals. An increased percentage of oil red O positive alveolar macrophages (cut-off point > 3%) in BAL was found in 6 out of 7 patients with definite clinical criteria of fat embolism syndrome, and in 6 out of 20 trauma patients without the clinical diagnosis of fat embolism syndrome. In two patients with fat embolism syndrome, sequential BAL showed that the percentage of positive macrophages decreased when the clinical manifestations disappeared. An increased number of BAL macrophages with fat droplets was also observed in two trauma patients without evidence of fat embolism syndrome after long-bone surgical intervention. By contrast, all non-trauma patients had a percentage of positive cells lower than 3%. Our findings suggest that BAL oil red O positive macrophages are frequently observed in trauma patients irrespective of the presence of fat embolism syndrome. Conceivably, a high number of oil red O positive macrophages could reflect clinically silent fat embolization.

Aetiology and prognostic factors of patients with AIDS presenting life-threatening acute respiratory failure

Respiratory failure is a significant contributor to morbidity and mortality in patients with the acquired immune deficiency syndrome (AIDS). We performed a study to investigate the aetiology, prognostic factors, and short- and long-term outcome of AIDS patients with life-threatening respiratory failure and pulmonary infiltrates. Forty-two AIDS patients (29 of whom required mechanical ventilation), admitted to a Respiratory Intensive Care Unit (ICU) from 1985 to 1992 because of severe respiratory failure (arterial oxygen tension/fractional inspiratory oxygen (Pa,O2/FI,O2) ratio at hospital admission 19 +/- 14 kPa (mean +/- SD)) and diffuse pulmonary infiltrates, were studied for evaluation of the aetiology and outcome. Necropsy studies were performed in 14 out of 23 (61%) patients who died. Pneumocystis carinii was the most common aetiology of pulmonary infiltrates (28 patients (67%)). Overall, 19 patients survived (45%) and 23 (55%) died. A multivariate analysis of prognostic factors influencing the outcome of the whole population showed that the presence of P. carinii pneumonia and the requirement for mechanical ventilation (MV) were the major determinants of outcome for this type of patient. The median survival time after ICU discharge for P. carinii pneumonia patients was lower (49 days) when compared to that of the remaining patients (154 days). Median survival time after ICU discharge for patients needing MV (112 days) did not differ from that observed in patients not requiring artificial ventilatory support (154 days). Although the ICU survival rate in this study was reasonable, 55% for the whole population, and 36% for P. carinii pneumonia patients, the poor outcome after ICU discharge, in particular for P. carinii pneumonia patients, deserves the reassessment of ICU admission criteria for this type of AIDS population.

Angiotensinogen gene G-6A polymorphism influences idiopathic pulmonary fibrosis disease progression

Angiotensin II is a growth factor that plays a key role in the physiopathology of idiopathic pulmonary fibrosis (IPF). A nucleotide substitution of an adenine instead of a guanine (G-6A) in the proximal promoter region of angiotensinogen (AGT), the precursor of angiotensin II, has been associated with an increased gene transcription rate. In order to investigate whether the G-6A polymorphism of the AGT gene is associated with IPF development, severity and progression, the present study utilised a case–control study design and genotyped G-6A in 219 patients with IPF and 224 control subjects. The distribution of G-6A genotypes and alleles did not significantly differ between cases and controls. The G-6A polymorphism of the AGT gene was not associated with disease severity at diagnosis. The presence of the A allele was strongly associated with increased alveolar arterial oxygen tension difference during follow-up, after controlling for the confounding factors. Higher alveolar arterial oxygen tension changes over time were observed in patients with the AA genotype (0.37±0.7 mmHg (0.049±0.093 kPa) per month) compared to GA genotype (0.12±1 mmHg (0.016±0.133 kPa) per month) and GG genotype (0.2±0.6 mmHg (0.027±0.080 kPa) per month). G-6A polymorphism of the angiotensinogen gene is associated with idiopathic pulmonary fibrosis progression but not with disease predisposition. This polymorphism could have a predictive significance in idiopathic pulmonary fibrosis patients.

Chacinero's lung - hypersensitivity pneumonitis due to dry sausage dust.

OBJECTIVE Hypersensitivity pneumonitis (HP) comprises a large group of diseases that occur secondary to inhalation of a variety of antigens. This report describes a little-known cause of HP, previously unreported in the English literature. METHODS Five patients (three women) with a mean age of 41 years who fulfilled the criteria for HP due to exposure to dry sausage dust were studied. The clinical findings, immunologic testing, results of the specific inhalation challenge, and follow-up are described. RESULTS Three patients developed an acute form of disease and two patients a subacute form. A diffuse micronodular centrolobular pattern was seen on high-resolution computer tomography scanning of four patients. A restrictive pattern was identified on pulmonary function testing of four patients and decreased lung diffusion of carbon monoxide (DLCO) among three. In bronchoalveolar lavage specimens from three patients, lymphocytosis was 17%, 40%, and 40%, with a CD4/CD8 ratio of <0.6. Specific immunoglobin G (IgG) antibodies to Penicillium frequentans and Aspergillus fumigatus were positive for three patients. Performed on three patients, the specific inhalation challenge was positive for dry sausage dust extract in two cases and Penicillium frequentans in the third. Resolution of clinical, radiologic, spirometry, and DLCO alterations occurred among the three patients who avoided exposure following the diagnosis. CONCLUSIONS A short patient series affected by a little-known cause of occupational HP is described. Penicillium frequentans may be the causative agent in some cases, but other fungi were found that could also be implicated in the etiology of this disease.

Lung fibrotic tenascin-C upregulation is associated with other extracellular matrix proteins and induced by TGFβ1

BackgroundIdiopathic pulmonary fibrosis (IPF) is a progressive parenchymal lung disease of unknown aetiology and poor prognosis, characterized by altered tissue repair and fibrosis. The extracellular matrix (ECM) is a critical component in regulating cellular homeostasis and appropriate wound healing. The aim of our study was to determine the expression profile of highlighted ECM proteins in IPF lungs.MethodsECM gene and protein expression was analyzed by cDNA microarrays, rt-PCR, immunohistochemistry and western-blot in lungs from idiopathic pulmonary fibrosis (IPF), hypersensitivity pneumonitis (HP), categorized as chronic (cHP) and subacute (saHP), and healthy lung tissue. Primary fibroblast cultures from normal subjects and fibrotic patients were studied to evaluate tenascin-C (TNC) synthesis.ResultsA total of 20 ECM proteins were upregulated and 6 proteins downregulated in IPF. TNC was almost undetected in normal lungs and significantly upregulated in fibrotic lungs (IPF and cHP) compared to saHP. Furthermore, it was located specifically in the fibroblastic foci areas of the fibrotic lung with a subepithelial gradient pattern. TNC levels were correlated with fibroblastic foci content in cHP lungs. Versican and fibronectin glycoproteins were associated with TNC, mainly in fibroblastic foci of fibrotic lungs. Fibroblasts from IPF patients constitutively synthesized higher levels of TNC than normal fibroblasts. TNC and α-sma was induced by TGF-β1 in both fibrotic and normal fibroblasts. TNC treatment of normal and fibrotic fibroblasts induced a non-significant increased α-sma mRNA.ConclusionsThe difference in ECM glycoprotein content in interstitial lung diseases could contribute to the development of lung fibrosis. The increase of TNC in interstitial areas of fibrotic activity could play a key role in the altered wound healing.

Punción transbronquial aspirativa en el estudio de las adenopatías mediastínicas: rentabilidad y coste-beneficio

Objetivo Existe controversia sobre el papel de las diferentes tecnicas diagnosticas en la estadificacion del mediastino en pacientes con sospecha de cancer de pulmon. El objetivo del estudio ha sido analizar la rentabilidad diagnostica y el coste-beneficio de la puncion transbronquial aspirativa (PTA) en la estadificacion mediastinica del cancer de pulmon, en pacientes evaluados en un hospital de tercer nivel. Pacientes y metodos Se ha realizado un estudio observacional retrospectivo, en el que se han analizado los resultados de las PTA practicadas a pacientes con sospecha de cancer de pulmon y adenopatias mediastinicas patologicas. Tambien se ha evaluado el coste-beneficio de la aplicacion sistematica de esta tecnica. Resultados Se evaluo a 194 pacientes (un 85% varones y un 15% mujeres), en 157 de los cuales (81%) se confirmo el diagnostico de cancer de pulmon. La muestra citologica que se obtuvo de la PTA fue adecuada en 147 de los 194 casos (76%). Cuando se analizaron las muestras adecuadas, la sensibilidad de la PTA fue del 88%, la especificidad del 100%, el valor predictivo positivo del 100%, el valor predictivo negativo del 64% y el valor global del 90%. En 44 de los 127 casos (34%) con cancer de pulmon no microcitico localizado se evito la realizacion de una mediastinoscopia, lo que represento un ahorro economico estimado de 119.456 €. Conclusiones La PTA es una tecnica con una elevada rentabilidad diagnostica que puede evitar la realizacion de una mediastinoscopia en un porcentaje significativo de pacientes, con las consiguientes implicaciones terapeuticas y economicas que ello conlleva.

Modelos experimentales para el estudio de la fibrosis pulmonar: utilidad práctica actual y futura

Las enfermedades pulmonares intersticiales difusas son un grupo de enfermedades respiratorias con multiples incognitas por resolver. En los ultimos anos se ha asistido a un gran avance en la clasificacion para el diagnostico correcto de cada una de ellas, con lo que se han sentado las bases indispensables para el estudio del proceso fisiopatologico en cada entidad. Sin embargo, resultan desconocidos tanto la causa desencadenante como los mecanismos exactos que llevan a la alteracion irreversible del parenquima. Dentro de las enfermedades pulmonares intersticiales difusas, la mas frecuente y de peor pronostico es la fibrosis pulmonar idiopatica. Los tratamientos actuales son empiricos, con respuesta aleatoria, e incapaces de mejorar la supervivencia. Por este motivo la mayoria de los estudios basicos se han centrado en buscar respuestas sobre su fisiopatologia y un abordaje terapeutico efectivo. El objetivo de esta revision es dar a conocer los estudios experimentales que han empezado a abrir caminos hacia la comprension del complejo proceso fibrotico.

[Experimental models for the study of pulmonary fibrosis: current usefulness and future promise].

Diffuse interstitial lung diseases form a group of respiratory diseases about which many questions remain to be answered. In recent years there have been major advances in the correct diagnostic classification of each disease, and therefore, the essential foundations have been laid for investigation of their pathophysiology. However, both the triggers and the precise mechanisms that lead to irreversible changes in the lung parenchyma remain to be identified. Idiopathic pulmonary fibrosis is the most common diffuse interstitial lung disease and has the worst prognosis. Current treatments are empirical and the response is random; furthermore, they do not improve survival. Consequently, most basic research has focused on the pathophysiology of the disease and on identifying an effective therapeutic approach. The aim of this review is to describe the experimental studies that have begun to open the way towards an understanding of the complex process of fibrosis.

Neumonía intersticial descamativa y bronquiolitis respiratoria asociada a enfermedad pulmonar intersticial: datos del registro español

Dentro de las neumopatias intersticiales idiopaticas, la bronquiolitis respiratoria asociada a enfermedad pulmonar intersticial (BR-EPI) y la neumonia intersticial descamativa (NID) forman un subgrupo de enfermedades raras que comparten una relacion clara con el habito tabaquico. Se han publicado pocas series con un numero importante de pacientes. En este trabajo se describen las caracteristicas de 19 casos (12 con NID y 7 con BR-EPI) recogidos en nuestro pais. Se detallan las caracteristicas clinicas, radiologicas y evolutivas, incluidos los tratamientos empleados y sus resultados. Excepto 2 pacientes con NID, todos eran o habian sido fumadores. Tos y disnea fueron los sintomas de inicio mas frecuentes, sin diferencias entre las 2 enfermedades. La alteracion radiologica predominante en la NID fue el patron en vidrio deslustrado, y en la BR-EPI, la presencia de nodulos pulmonares. La mayor parte de los pacientes recibieron tratamiento con esteroides. El pronostico en general fue bueno, y fallecio unicamente un paciente con NID.

Neumonía intersticial no específica: Características clínicas y epidemiológicas

BACKGROUND AND OBJECTIVES: Patients diagnosed with non-specific interstitial pneumonia (NSIP) in 2 hospitals in Barcelona, Spain, were studied to investigate the factors that could contribute to the etiology of disease. PATIENTS AND METHOD: The consensus diagnostic criteria established by the American Thoracic Society/European Respiratory Society were followed. The study included 16 patients, 10 men (65%) and 6 women (35%), all diagnosed with NSIP by open lung biopsy. Patients were questioned on pathological history, occupational or environmental exposure, medicinal drug use, contact with birds, and relationship with smoking. In addition, were recorded symptoms and physical signs, laboratory and respiratory function results, chest X-ray and computerized tomography scan features, fiberbronchoscopy findings and open lung biopsy findings. RESULTS: Eleven patients (69%) -10 men (100%) and one woman (12%) -were smokers: 4 were active and 7 former smokers; 8 (80%) patients had fibrotic NSIP and three (50%) had cellular NSIP. Nine (56%) patients had a medication history, and 5 received chronic non-steroideal anti-inflammatory drug treatment. Occupational exposure to bleach, detergents, and ammonia or chloride products was documented in 6 cases. Three patients had contact with manufactured plastic products and isocyanate inhalation. CONCLUSIONS: Smoking and medication use were prevalent in NSIP patients. Ibuprofen and celecoxib clearly provoked symptoms in one NSIP patient. Further studies are required to clarify the role of detergents, isocyanates and other occupation-related substances as triggering factors.