María Jesús Cruz

Chronic hypersensitivity pneumonitis in patients diagnosed with idiopathic pulmonary fibrosis: a prospective case-cohort study

BACKGROUND The clinical features of idiopathic pulmonary fibrosis (IPF) and chronic hypersensitivity pneumonitis can be indistinguishable; the need to eliminate occult environmental factors known to cause pulmonary fibrosis in patients suspected to have IPF during diagnostic evaluation is evident. We aimed to investigate occult, putative causes in the environments of patients diagnosed with IPF using tests beyond those conventionally used. METHODS In this case-cohort study, 60 consecutive patients diagnosed with IPF on the basis of the 2000 American Thoracic Society (ATS) and the European Respiratory Society (ERS) criteria were prospectively followed up every 4 months for 6 years between Jan 1, 2004, and Dec 31, 2009. At each visit a uniformly applied questionnaire was administered to these 60 patients to identify occult antigen exposure known to cause hypersensitivity pneumonitis. Patients underwent specific IgG determination, bronchoalveolar lavage, bronchial challenge testing with suspected antigens, and re-review of histopathological features in existing and subsequently obtained surgical lung biopsy samples and from lung explants. Specimens obtained from suspected sources from the patients environment were subjected to cultures in microbiology laboratory. These clinical data and discussions among pulmonologists and radiologists familiar with IPF were used to confirm the diagnosis in accordance with 2011 ATS, ERS, Japanese Respiratory Society, and Latin American Thoracic Association guidelines; 46 of the 60 patients had IPF according to the 2011 guidelines, and our analyses in this study were focused on these 46 patients. FINDINGS 20 of the 46 (43%, 95% CI 29-58) patients with IPF according to 2011 guidelines had a subsequent diagnosis of chronic hypersensitivity pneumonitis: nine patients had positive bronchial challenge testing (eight of whom were also IgG positive and six of these patients also had surgical lung biopsy showing a pattern consistent with chronic hypersensitivity pneumonitis); seven were IgG positive plus had histopathology on surgical lung biopsy that was consistent with hypersensitivity pneumonitis; one was IgG positive plus had greater than 20% lymphocytes in bronchoalveolar lavage fluid; and three had findings on surgical lung biopsy that were consistent with subacute hypersensitivity pneumonitis (and IgG positive). Altogether, 29 of 46 patients diagnosed with IPF who had met the 2011 criteria had lung tissue available for histopathology (surgical lung biopsy in 28 patients and explanted lung in two patients, one of whom also had surgical biopsy) during the study period, and 16 of the 20 patients with chronic hypersensitivity pneumonitis had histopathological features on surgical lung biopsy that were consistent with this diagnosis. 26 of the 46 patients remained with a diagnosis of IPF. INTERPRETATION Almost half of patients diagnosed with IPF on the basis of 2011 criteria were subsequently diagnosed with chronic hypersensitivity pneumonitis, and most of these cases were attributed to exposure of occult avian antigens from commonly used feather bedding. Our results reflect findings in one centre with recognised expertise in chronic hypersensitivity pneumonitis, and further research and studies at other centres are warranted. FUNDING Fondo de Investigaciones Sanitarias; Fundació Privada Cellex; SEPAR 2010.

Evolución de la hiperrespuesta bronquial en pacientes con asma ocupacional por exposición a sales de persulfato

Objetivo: Las sales de persulfato son uno de los agentes m?s frecuentemente implicados en el origen del asma ocupacional (AO). El objetivo de este estudio ha sido establecer la evoluci?n de la hiperrespuesta bronquial y de las pruebas inmunol?gicas en pacientes con AO por persulfatos en funci?n de que persista o no la exposici?n a dichas sales. Pacientes y m?todos: Se estudi? a 10 pacientes con AO por exposici?n a sales de persulfato, diagnosticados con prueba de provocaci?n bronquial espec?fica, en los que como m?nimo hab?an transcurrido 3 a?os tras el diagn?stico. En todos los casos se realizaron un exhaustivo interrogatorio cl?nico y laboral, espirometr?a forzada y prueba de provocaci?n bronquial inespec?fica con metacolina, se determinaron los valores de inmunoglobulina E total y se practicaron pruebas cut?neas con las distintas sales de persulfato. Resultados: En el momento del control evolutivo, 7 pacientes hab?an abandonado la exposici?n a persulfatos. De los pacientes con hiperrespuesta bronquial positiva que hab?an abandonado el trabajo, se observ? una mejor?a significativa de ?sta en 3 de ellos. Este hecho no se observ? en ninguno de los pacientes que siguieron expuestos. La prueba cut?nea espec?fica se negativiz? en 3 pacientes que no estaban expuestos en el momento del control evolutivo. Desde el punto de vista cl?nico, la mayor?a de los pacientes continuaron presentando s?ntomas, aunque ?stos hab?an mejorado, excepto en un caso en que, a pesar de evitar la exposici?n, empeoraron. Conclusiones: Aunque pueden persistir los s?ntomas de asma y la hiperrespuesta bronquial positiva, la evoluci?n de los pacientes con AO por persulfato parece ser favorable si se evita la exposici?n. Esta respuesta no parece diferir de la comunicada en otros casos de AO.

α-Synuclein Levels in Blood Plasma from LRRK2 Mutation Carriers

The diagnosis of Parkinson’s disease (PD) remains primarily a clinical issue, based mainly on phenotypic patterns. The identification of biomarkers capable of permitting the preclinical detection of PD is critically needed. α-Synuclein is a key protein in PD, with missense and multiplication mutations in the gene encoding α-synuclein (SNCA) having been reported in familial cases of PD, and accumulation of the protein identified in Lewy bodies (LBs) and Lewy neurites (LNs) in affected brain regions. With the objective of validating the use of α-synuclein as a clinical or progressive biomarker in an accessible tissue, we used an enzyme-linked immunosorbent assay (ELISA) to measure α-synuclein levels in the peripheral blood plasma of idiopathic PD and LRRK2 mutation carrier patients and compared our findings with healthy control subjects. Compared to healthy controls, we found a significant decrease in plasma total α-synuclein levels in idiopathic PD (iPD) patients (n = 134, p = 0.010). However, the reduction was less significant in patients who were LRRK2 mutation carriers (n = 32, p = 0.133). This lack of significance could be due to the small number of individuals employed in this group. No predictive value of total α-synuclein in the diagnosis of PD was found in a receiver operating characteristic (ROC) curve analysis. Although this is a pilot study requiring corroboration on a larger cohort of patients, our results highlight the possible use of plasma α-synuclein as a biomarker for PD.

Course of Bronchial Hyperresponsiveness in Patients With Occupational Asthma Caused by Exposure to Persulfate Salts

OBJECTIVE Persulfate salts are among the most frequently implicated causes of occupational asthma. The aim of this study was to describe the course of bronchial hyperresponsiveness and immunologic test results in patients with occupational asthma due to persulfate salts. PATIENTS AND METHODS Ten patients with occupational asthma due to persulfate salts were studied. Diagnosis was based on specific bronchial challenge tests performed at least 3 years before enrollment. An exhaustive medical and work history was taken during interviews with all patients, and all underwent spirometry and nonspecific bronchial challenge testing. Total immunoglobulin E levels were determined and skin prick tests to several persulfate salts were performed. RESULTS At the time of evaluation, 7 patients had avoided workplace exposure to persulfate salts. The bronchial hyperresponsiveness of 3 of those 7 patients had improved significantly. No improvement was observed in patients who continued to be exposed. Specific skin prick tests became negative in 3 patients who were no longer exposed at the time of the follow-up evaluation. Most of the patients continued to report symptoms, although improvements were noted. One patient, however, reported worsening of symptoms in spite of avoidance of exposure. CONCLUSIONS Although asthma symptoms and bronchial hyperresponsiveness may persist for patients with occupational asthma due to persulfate salts, their condition seems to improve if they avoid exposure. This course does not seem to differ from that reported for other cases of occupational asthma.

Occupational asthma caused by chromium and nickel

We report the case of a 40-year-old woman who developed occupational asthma following exposure to chromium and nickel in the nickel-plating section of a metalworks company. Skin prick tests for specific antibodies proved positive for nickel chloride at a concentration of 1 mg/mL and negative for potassium dichromate. The specific bronchial provocation test confirmed the diagnosis of occupational asthma due to exposure to chromium and nickel. The patient presented a late positive reaction to nickel chloride (0.1 mg/mL) and an immediate positive reaction to a 10 mg/mL solution of potassium dichromate. These results indicate a dual response to nickel and chromium in this patient.

Neumonitis por hipersensibilidad en los yeseros de la construcción (espartosis): estudio de 20 casos

FUNDAMENTO Y OBJETIVO: La espartosis es un tipo de neumonitis por hipersensibilidad que afecta, con cierta frecuencia, a los trabajadores de la construccion que manejan fibras de esparto como material de soporte de las placas de yeso. Aun se discute cual es el agente concreto que causa la enfermedad. Los objetivos del estudio fueron: a) demostrar el posible papel etiologico de los hongos que colonizan las fibras de esparto y el del propio esparto en la etiologia de esta enfermedad, y b) describir las caracteristicas clinicas de esta enfermedad en una serie amplia de pacientes. PACIENTES Y METODO: Se estudio a 20 pacientes diagnosticados de neumonitis por hipersensibili- dad causada por la exposicion a esparto. Se realizaron cultivos micologicos de las muestras de esparto proporcionadas por cada paciente. Para determinar los anticuerpos IgG especificos y para realizar pruebas cutaneas especificas y pruebas especificas de provocacion bronquial, se utilizaron extractos antigenicos de los hongos obtenidos en el cultivo y/o el propio esparto no contaminado. RESULTADOS: Los hongos aislados con mayor frecuencia en las muestras de esparto causal fueron Aspergillus sp. (60%) y Mucor sp. (47%). La determinacion de los anticuerpos IgG especificos y las pruebas especificas de provocacion bronquial demostraron antigenicidad no solo para As- pergillus sp., sino tambien para el esparto no contaminado por hongos y para otros hongos como Penicillium sp. o Mucor sp. Estos resultados fueron utiles para establecer una nueva aproximacion diagnostica a esta enfermedad. CONCLUSIONES: Aspergillus fumigatus es conocido como un agente causal de la neumonitis por hipersensibilidad producida por exposicion a esparto. Sin embargo, otras fuentes antigenicas, como Penicillium frequentans y otros hongos, asi como las propias fibras de esparto, parecen tener un papel en la genesis de esta enfermedad. Palabras clave: Neumonitis por hipersensibilidad. Espartosis. Esparto.

Prevalence and Distribution of Asbestos Lung Residue in a Spanish Urban Population

Abstract Introduction The purpose of the present study is to analyse the prevalence and distribution of asbestos lung residue in the Barcelona urban population. Material and methods Lung autopsy samples were obtained from 35 individuals who had lived in Barcelona. The close family was interviewed in order to rule out asbestos exposure. Samples were obtained from three areas of the right lung during the autopsy: upper lobe apex, lower lobe apex, and lower lobe base. The samples were treated to remove organic material. The inorganic residue was analysed using a light microscope. The results were expressed as asbestos bodies (AB) per gram of dry tissue. Levels greater than 1000AB/g of dry tissue were considered as potentially causing disease. Results AB were detected in 29(83%) of the subjects, of which 86% had levels less than 300AB/g. Only one individual (3%) had values greater than 1000AB/g dry tissue. The asbestos residue was higher in the lower lung lobe in 17 individuals (48%) than in the rest, although no significant differences were seen as regards AB residue in the three lung areas studied. Conclusions The results of this study show that the urban population of Barcelona has asbestos levels in the lung that vary between 0 and 300AB/g dry tissue. No differences in the asbestos residues were detected in the lung areas studied in this population.

Incidencia y características de las agudizaciones asmáticas en Barcelona (ASMAB II)

INTRODUCTION A study has been made on the incidence and clinical characteristics of asthma exacerbations (AE) seen in hospital emergency departments (HED) and domiciliary services (DS) in Barcelona. PATIENTS AND METHODS AEs were identified over a 56 day period during the months of October and November 2003 and the patients seen in university hospitals were interviewed. RESULTS A total of 262 AE were identified, 188 in hospital emergency departments and 82 in domiciliary, which was a mean of 4.6 AE/day, giving an incidence of 0.37 AA/10(5) inhabitants. This incidence was no different from that obtained in the same months in 2002 (P>0.05). The mean age (+/-standard deviation) of the 143 cases of AE seen in university hospitals was 41+/-17 years; 87/143 (60%) were women and 57/138 (41%), smokers. In 36/61 (59%) the AE started in the home; in 88/132 (61%) it began 24 hours before arriving at the hospital centre. In 78/123 cases (63%) slow onset of nasal catarrh was noted before the AE and a viral infection was suspected. Inhaled corticoids were given to 45/112 patients (40%), and only one added oral corticoids 12 hours before admission. The AE were mild in 38/75 cases (51%), moderate in 28/75 (37%), severe in 8/75 (11%) and almost fatal in one patient (1.3%). Around 10% (13/137) of patients (10%) were re-admitted. CONCLUSIONS The daily incidence of AE is 0.37/10(5) inhabitants. More than half of the exacerbations started after nasal catarrh and 11% of the AE were severe.

Assessment of soy aeroallergen levels in different work environments

Background Airborne soybean hull proteins are known causes of asthma epidemics around harbours and soy processing plants. Soy flour dust proteins may cause occupational allergy in food and feed industries.

Asma ocupacional inducida por cromo y níquel

Se describe el caso de una paciente de 40 anos que desarrollo asma ocupacional tras la exposicion a cromo y a niquel mientras realizaba recubrimientos de niquel en una empresa metalurgica en la seccion de niquelado. Las pruebas cutaneas especificas resultaron positivas a cloruro de niquel a una concentracion de 1 mg/ml y negativas a dicromato potasico. La prueba de provocacion bronquial especifica confirmo el diagnostico de asma ocupacional debida a la exposicion a cromo y a niquel, presentando la paciente una respuesta positiva tardia a una concentracion de 0,1 mg/ml de cloruro de niquel, y una respuesta positiva precoz con una solucion de 10 mg/ml de dicromato potasico. Estos resultados indican una doble sensibilizacion a niquel y cromo es esta paciente.