Neumonitis por hipersensibilidad. Estudio diagnóstico menos invasivo / Hypersensitivity Pneumonitis. Towards a Less Invasive Diagnostic Procedure

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Sequential broncho-alveolar lavages reflect distinct pulmonary compartments: clinical and research implications in lung transplantation.

BACKGROUND: Bronchoalveolar lavage (BAL) has proven to be very useful to monitor the lung allograft after transplantation. In addition to allowing detection of infections, multiple BAL analytes have been proposed as potential biomarkers of lung allograft rejection or dysfunction. However, BAL collection is not well standardized and differences in BAL collection represent an important source of variation. We hypothesized that there are systematic differences between sequential BALs that are relevant to BAL analysis. METHODS: As part of 126 consecutive bronchoscopies in lung transplant recipients, two sequential BALs (BAL1 and BAL2) were performed in one location during each bronchoscopy by instilling and suctioning 50 ml of normal saline twice into separate containers. Cell concentration, viability and differentials, Surfactant Protein-D (SP-D), Club Cell Secretory Protein (CCSP), and levels of CXCL10, IL-10, CCL2, CCL5, VEGF-C, RAGE, CXCL9, CXCL1, IL-17A, IL-21, PDGF, and GCSF were compared between BAL1 and BAL2. RESULTS: Total cell concentration did not differ between BAL1 and BAL2; however, compared to BAL2, BAL1 had more dead cells, epithelial cells, neutrophils, and higher concentrations of airway epithelium-derived CCSP and inflammatory markers. BAL2 had a higher concentration of SP-D compared to BAL1. CONCLUSION: In this study performed in lung transplant recipients, we show that sequential BALs represent different lung compartments and have distinct compositions. BAL1 represents the airway compartment with more epithelial cells, neutrophils, and epithelium-derived CCSP. Conversely, BAL2 samples preferentially the distal bronchoalveolar space with greater cell viability and higher SP-D. Our findings illustrate how the method of BAL collection can influence analyte concentrations and further emphasize the need for a standardized approach in translational research involving BAL samples.

Rituximab for auto-immune alveolar proteinosis, a real life cohort study.

BACKGROUND: Whole lung lavage is the current standard therapy for pulmonary alveolar proteinosis (PAP) that is characterized by the alveolar accumulation of surfactant. Rituximab showed promising results in auto-immune PAP (aPAP) related to anti-GM-CSF antibody. METHODS: We aimed to assess efficacy of rituximab in aPAP in real life and all patients with aPAP in France that received rituximab were retrospectively analyzed. RESULTS: Thirteen patients were included. No patients showed improvement 6 months after treatment, but, 4 patients (30%) presented a significant decrease of alveolar-arterial difference in oxygen after 1 year. One patient received lung transplantation and one patient was lost of follow-up within one year. Although a spontaneous improvement cannot be excluded in these 4 patients, improvement was more frequent in patients naïve to prior specific therapy and with higher level of anti-GM-CSF antibodies evaluated by ELISA. No serious adverse event was evidenced. CONCLUSIONS: These data do not support rituximab as a second line therapy for patients with refractory aPAP.

Neurosarcoidosis en el área sanitaria de Pontevedra-Salnés / Neurosarcoidosis in the Pontevedra-Salnés health district

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Silicoproteinosis pulmonar. Un caso con supervivencia prolongada / Pulmonary silicoproteinosis. A case of prolonged survival

La silicoproteinosis pulmonar es una forma muy rara de la silicosis, que puede desarrollarse con un período de latencia entre pocos meses y 5 años de la primera exposición a sílice y cursa, invariablemente, con un rápido deterioro de la función pulmonar, sin respuesta eficaz a tratamiento alguno. Por su rareza y por su excepcional evolución, comunicamos el caso de una mujer de 55 años, diagnosticada en nuestro hospital de silicoproteinosis, que mejoró al retirar la exposición laboral al polvo de sílice y que permanece estable, sin empeoramiento radiológico ni de la función pulmonar 4 años después del diagnóstico de la enfermedad. En nuestro conocimiento, se trata del primer caso de silicoproteinosis que cursa con una buena evolución(AU)

Alveolar silicoproteinosis is a very rare form of silicosis that can develop after a latency period of between a few months and 5 years after the first exposure to silica, and courses invariably, with rapid deterioration of lung function, without an effective response to treatment. Because of its rarity and its unique outcome, the case is presented of a 55 year old woman, diagnosed with alveolar silicoproteinosis in our hospital, who improved by removing the occupational exposure to silica dust and remains stable with no radiological or lung function worsening four years after diagnosis of the disease. To our knowledge, this is the first case of alveolar silicoproteinosis that had a good outcome(AU)

Identificación fenotípica y molecular de Coccidioides posadasii en una paciente examinada para un trasplante bipulmonar / Phenotypic and molecular identification of Coccidioides posadasii in a patient evaluated for bilateral lung transplantation

Antecedentes. La coccidioidomicosis es una infección micótica endémica debida a Coccidioides immitis y Coccidioides posadasii. Su presencia en receptores de un trasplante puede revestir especial gravedad, en particular en pacientes con una infección activa o previa por Coccidioides. En este grupo de pacientes se han descrito casos letales de la infección. Objetivos. Describimos un caso grave de neumonía debida a C. posadassi en una mujer blanca de 29 años de edad, que fue ingresada en el hospital como parte de la valoración de un trasplante bipulmonar. La paciente había nacido y residía en Catamarca, Argentina. La metodología molecular contribuyó a la identificación de la especie. Métodos. Para establecer el diagnóstico de la infección e identificar C. posadasii, se efectuaron una exploración clínica, pruebas de laboratorio y exámenes microbiológicos. Resultados. A partir del cultivo del líquido de lavado broncoalveolar se aisló el hongo. La caracterización fenotípica, la reacción en cadena de la polimerasa específica y la inoculación experimental a un animal demostraron la presencia de C. posadasii. La paciente respondió al tratamiento con anfotericina B desoxicolato. El trasplante de pulmón se difirió. Conclusiones. La RCP específica puede ser una importante alternativa para la correcta identificación de C. immitis o C. posadasii en los laboratorios con medios implementados de biología molecular. El caso descrito destaca la necesidad de que, en las unidades de trasplante de órganos, se efectúe una valoración sistemática de los pacientes que viven en áreas endémicas de coccidioidomicosis(AU)

Background. Coccidioidomycosis is an endemic fungal infection caused by Coccidioides immitis and Coccidioides posadasii. It can be particularly severe in transplant recipients that have a current or a previous coccidioidal infection. Fatal case of coccidioidomycosis has been described in this group of patients. Aims. We report a severe case of pneumonia caused by C. posadassi in a 29 year-old white woman that had been admitted to hospital as part of the evaluation for bilateral lung transplantation. The patient was a native and resident of Catamarca, Argentina. Molecular methodologies contributed to the species identification. Methods. Clinical, laboratory records and microbiological tests were carried out to diagnose the infection and to identify C. posadasii. Results. A fungus was isolated from BAL culture. Phenotypic characterization, specific PCR and experimental animal inoculation demonstrated the presence of C. posadasii. The patient responded well to amphotericin B deoxycholate. Lung transplantation was postponed. Conclusions. Specific PCR can be an important alternative for the correct identification of C. immitis or C. posadasii in laboratories with implemented molecular biology tools. This case emphasizes the need for a systematic assessment in organ transplant units of patients inhabiting endemic areas of coccidioidomycosis(AU)

Neumonía eosinófila crónica: a propósito de un caso / Chronic eosinophilic pneumonia: presentation of a case

La neumonía eosinófila crónica es una entidad poco frecuente de etiología desconocida. Hasta 1969 Carrington y colaboradores no la definen como una entidad propia separándola del grupo de enfermedades que asocian patología pulmonar y eosinofilia. Se describe un caso de una mujer joven que presentó un cuadro de tos crónica seguida de fiebre. Las pruebas complementarias demostraron eosinofilia periférica y en el lavado broncoalveolar 60% de eosinófilos. Las radiografías de tórax mostraron infiltración bilateral en lóbulos superiores. El tratamiento con corticoides mejoró el cuadro, permaneciendo la paciente asintomática hasta la actualidad (AU)

Chronic eosinophilic pneumonia is a rare condition of unknown origin. It was not until 1969 when Carrington et al defined it as a disease separate from the group of diseases associated with lung disease and eosinophilia. We describe a case of a young woman who presented with a chronic cough followed by a fever. Additional tests showed peripheral eosinophilia in bronchoalveolar lavage with 60% eosinophils. Chest x-rays showed bilateral infiltration in the upper lobes. Corticosteroid therapy improved the picture, the patient still remains asymptomatic (AU)

Diagnósticos y procedimientos en 500 pacientes consecutivos con sospecha clínica de enfermedad pulmonar intersticial / Diagnoses and diagnostic procedures in 500 consecutive patients with clinical suspicion of interstitial lung disease

Objetivo: Determinar las tasas de diagnósticos alcanzados con el seguimiento de las directrices actuales y los procedimientos que deben utilizarse para establecer el diagnóstico definitivo mediante la aplicación del nuevo protocolo en la evaluación de los pacientes con sospecha de enfermedad pulmonar intersticial (EPI). Pacientes y métodos: Durante un período de 10 años se evaluó, mediante un único protocolo diagnóstico, a 500 pacientes consecutivos atendidos en una consulta ambulatoria de EPI que presentaban las características de esta enfermedad. Los resultados se introdujeron en una base de datos específica y los diagnósticos de neumonía intersticial idiopática (NII) se establecieron siguiendo los criterios del reciente Consenso. Resultados: Se estableció un diagnóstico definitivo en 427 pacientes (85%), en 125 de ellos sin procedimientos invasivos y en 302 con procedimientos invasivos. En 73 casos (14,6%) no se alcanzó un diagnóstico definitivo y en estos pacientes se estableció el diagnóstico de neumonía intersticial no clasificable. La NII constituyó el grupo predominante, con 193 casos (39%). Las entidades específicas principales fueron: sarcoidosis (n = 93; 19%), neumonía intersticial usual (n = 84; 17%) y neumonitis por hipersensibilidad (n = 75; 15%). En 30 pacientes (6%) se estableció el diagnóstico de una enfermedad distinta a la EPI (falsa neumonía intersticial). Se realizó un total de 433 procedimientos invasivos en 332 pacientes (66%): biopsia transbronquial en 252 (rendimiento diagnóstico directo: 38% y rendimiento diagnóstico cuando se utilizó para excluir otros diagnósticos específicos: 50%); lavado broncoalveolar en 260 (rendimiento diagnóstico: 5%), y biopsia pulmonar quirúrgica en 141 (rendimiento diagnóstico: 93%). Por lo tanto, siguiendo el protocolo diagnóstico actual, se estableció un diagnóstico definitivo en el 85% de los pacientes; de ellos, en el 25% el diagnóstico se estableció únicamente en función de los datos clínicos y de los criterios de imagen, mientras que en el 60% se realizó con procedimientos invasivos. En 141 pacientes (28%) fue necesaria la biopsia pulmonar quirúrgica para establecer el diagnóstico. Conclusiones: La tasa de diagnósticos es elevada cuando se utiliza el protocolo de estudio recomendado. La cuarta parte de los diagnósticos se efectúa mediante criterios clínicos como procedimiento único; sin embargo, otra cuarta parte de los diagnósticos requiere la realización de una biopsia pulmonar quirúrgica

Objective: To determine the diagnostic yield achieved with the application of current recommendations for evaluating patients with suspected interstitial lung disease (ILD) and the procedures that must be applied to reach a definitive diagnosis. Patients and methods: Over a 10-year period, 500 consecutive patients attending an ILD outpatient clinic who showed features of diffuse lung involvement were assessed with a single diagnostic protocol. Results were introduced in a dedicated database and diagnoses for idiopathic interstitial pneumonia were established according to a recent consensus classification. Results: A definitive diagnosis was reached in 427 (85%) patients: in 125 without invasive procedures and in 302 with invasive procedures. In 73 (14.6%) cases a definitive diagnosis was not reached, and patients were placed in the group of unclassifiable interstitial pneumonia. Idiopathic interstitial pneumonia was the predominant group with 193 (39%) patients. The main specific entities included sarcoidosis with 93 (19%) patients, usual interstitial pneumonia with 84 (17%) patients, and hypersensitivity pneumonitis with 75 (15%) patients. Thirty (6%) patients were diagnosed with an illness other than ILD (false ILD). In 332 patients, we performed a total of 433 invasive procedures: transbronchial biopsy in 252 (direct diagnostic yield, 38%, or if used also to exclude other specific diagnosis, 50%), bronchoalveolar lavage in 260 (yield, 5%), and open lung biopsy in 141 (yield, 93%). Hence, following the current diagnostic approach, a definitive diagnosis was established for 85% of patients, for 25% solely on clinical grounds and imaging criteria and for 60% on the basis of invasive procedures. Diagnosis by open lung biopsy was still required for 141 (28%) patients. Conclusions: The diagnostic yield was high when the recommended study protocol was followed. A quarter of the diagnoses were reached with clinical criteria alone, but another quarter could only be made after open lung biopsy

Thin-layer preparations of dithiothreitol-treated bronchial washing specimens.

OBJECTIVE: To evaluate the combined effect of dithiothreitol (DTT) treatment and ThinPrep (TP) (Cytyc Corp, Boxborough, Massachusetts, U.S.A.) processing on bronchial washing specimens. STUDY DESIGN: A total of 431 bronchial washing specimens were initially treated with 0.05% DTT in a 30% methanol solution. After centrifugation, 1 TP slide and 2-4 conventional cytospin or smear preparations (CPs) were prepared. The reports of both preparations were compared in all cases. All 48 abnormal cases and 52 consecutive negative cases were also compared for cellular composition, distribution of the cells, ease of interpretation and overall preparation quality. Screening time was recorded for 20 of the cases. RESULTS: The diagnostic accuracy of one TP slide appeared comparable to that of 2-4 CPs. The TP slide was assessed to be equal or superior in overall quality to CP in 85% of 100 cases of paired specimens. The cleaner background and smaller cellular area of TP slides significantly reduced the screening time. Mucolysis and specimen homogenization were not always optimal, occasionally resulting in uneven subsampling and poorly cellular TPs. However, in general, TP slides were considered superior to CPs in overall quality. CONCLUSION: Improvement in specimen quality and reduced screening time have to be balanced against the high cost of consumables with the TP technique.

Use of bronchoalveolar lavage in humans--past necessity and future imperative.

Limited bronchoalveolar lavage (BAL) as an extension of fiberoptic bronchoscopy has permitted the recovery of airway-alveolar space cells and soluble substances in the extracellular lining fluid that have been used diagnostically and as research specimens in patients with a variety of lung diseases and in normal subjects for the study of lung host defenses. During the past three decades, use of BAL specimens has stimulated immunologic and cellular research of pulmonary diseases, which has provided significant insight into local host immunity, inflammation, fibrogenesis, asthma mechanisms, and infections. From this research new methods of antifibrotic therapy of interstitial pulmonary fibrosis, for example, have followed. Moreover, BAL applications have greatly enhanced professional interest in the field of pulmonary medicine. This review attempts to analyze the history and impact of BAL, appraise its current status, and assess its future usefulness. Understanding the immunopathogenesis of many lung diseases is predicated on obtaining in situ specimens from affected lung tissue and airways. BAL provides a direct sample that can be compared with an endobronchial or transbronchial biopsy tissue specimen and with cellular and immunologic components in the vascular circulation. Thus, the recovery of BAL fluid and its components involved directly with a disease process or continguous with interstitial tissue permits a much more detailed assessment of new cellular mediators and cytokines participating in the pathologic process. Furthermore, subjecting BAL cells to microarrays of DNA to discern what genes, are activated will be one step closer to identifying intracellular processes involved or deranged. Identification of causative factors may solve questions of causation, so that preventive strategies or definitive therapy can be used.

Tuberculosis endobronquial: experiencia en el Hospital Santa Clara de Bogotá 1980-1990

Se estudiaron los pacientes con lesiones endobronquiales por broncofibroscopia en el período de 1980-1990 en el servicio de Broncoscopia en el Hospiatl Santa Clara de Bogotá, a quienes se les practicó estudio directo con ZN y cultivo en medio de Ogawa-Kudoh de lavado y cepillado bronquial. Además se tomaron biopsias de las lesiones visualizadas durante el procedimiento, enviándose a cultivo para BK e histopatología. Presentamos 84 pacientes con diagnóstico de tuberculosis endobronquial, en quienes las baciloscopias fueron siempre negativas. Se les practicó broncofibroscopia con diagnósticos provisionales de tuberculosis, cáncer broncogénico, neumonía de resolución lenta, sarcoidosis, EPID y bronquiectasias. Durante el procedimiento se observaron cambios que en nuestra experiencia son eventualmente característicos y elporcentaje de acierto fue de 100 por ciento.