Maria-Jesus Cruz

Validation of specific inhalation challenge for the diagnosis of occupational asthma due to persulphate salts

Background: The significant value of tests used to certify the diagnosis of occupational asthma due to persulphate salts remains uncertain. Aims: To validate the specific inhalation challenge (SIC) test for the diagnosis of occupational asthma. Methods: Eight patients with occupational asthma due to persulphate salts, eight patients with bronchial asthma who were never exposed to persulphate salts, and ten healthy subjects were studied. Clinical history taking, spirometry, bronchial challenge with methacholine, skin prick testing to common inhalant allergens and persulphate salts, total IgE levels, and SIC to potassium persulphate were carried out in all subjects. The SIC used increasing concentrations of potassium persulphate (5, 10, 15, and 30 g) mixed with 150 g of lactose. Patients tipped the mixture from one tray to another at a distance of 30 cm from the face for 10 minutes in a challenge booth. Results: The SIC was positive in all subjects with persulphate induced asthma and in one patient with bronchial asthma who had never been exposed to persulphate salts. Sensitivity was 100% (95% CI 67.6 to 100) and specificity was 87.5% (95% CI 52.9–97.8) when patients with occupational asthma due to persulphate salts were compared with those with bronchial asthma never exposed to persulphate salts. Conclusions: SIC to persulphate salts performed according to the protocol described appears to be useful for the diagnosis of occupational asthma secondary to inhalation of this substance.

Impact Of Age on pH, 8-Isoprostane, and Nitrogen Oxides in Exhaled Breath Condensate

BACKGROUND Few studies have addressed the effects of aging on levels of inflammatory markers in exhaled breath condensate (EBC). The aim of this study was to determine whether there are significant age-associated differences in pH, 8-isoprostane, and nitrogen oxide values in EBC from a population of healthy adults. MATERIAL AND METHODS EBC samples were obtained from 75 healthy volunteers aged 18 to 80 years and stratified into five groups according to age (n = 15): 18 to 29, 30 to 39 years, 40 to 49 years, 50 to 59 years, and 60 to 80 years. The following were measured in the samples collected: pH before and after deaeration, nitrite, nitrate, and 8-isoprostane. Differences between the groups were assessed by the Kruskal-Wallis test. RESULTS Significant differences in deaerated pH (p < 0.0001) were found in the group of individuals 60 to 80 years of age as compared to the remaining groups. Significant differences were also found in 8-isoprostane levels between the younger and older groups (18 to 29 years and 30 to 39 years of age; p = 0.006 and p = 0.034, respectively). There were no significant differences in nitrite or nitrate values between younger and older individuals. CONCLUSION The results of this study indicate that pH and 8-isoprostane levels in EBC show a relationship with age. Thus, values obtained in studies with control groups may require adjustment for these factors.

Diagnostic yield of specific inhalation challenge in hypersensitivity pneumonitis

Reliable methods are needed to diagnose hypersensitivity pneumonitis. The aim of the study was to establish the diagnostic yield of specific inhalation challenge (SIC) in patients with hypersensitivity pneumonitis. All patients with suspected hypersensitivity pneumonitis in whom SIC was performed (n=113) were included. SIC was considered positive when patients showed a decrease of >15% in forced vital capacity (FVC) or >20% in diffusing capacity of the lung for carbon dioxide, or a decrease of 10% to 15% in FVC accompanied by a temperature increase of 0.5°C within 24 h of inhalation of the antigen. SIC was positive to the agents tested in 68 patients: 64 received a diagnosis of hypersensitivity pneumonitis and SIC results were considered false-positive in the remaining four patients. In the SIC-negative group (n=45), 24 patients received a diagnosis of hypersensitivity pneumonitis and SIC results were considered false-negative, and 21 patients were diagnosed with other respiratory diseases. The sensitivity and specificity of the test were 72.7% and 84%, respectively. Having hypersensitivity pneumonitis caused by an antigen other than birds or fungi predicted a false-negative result (p=0.001). In hypersensitivity pneumonitis, positive SIC testing virtually confirms the diagnosis, whereas negative testing does not rule it out, especially when the antigenic sources are not birds or fungi. Specific inhalation challenge can be very useful for establishing the diagnosis of hypersensitivity pneumonitis http://ow.ly/zxszi

Effects of salbutamol on exhaled breath condensate biomarkers in acute lung injury: prospective analysis

IntroductionThe benefits of β-adrenergic stimulation have been described in acute lung injury (ALI), but there is still no evidence of its anti-inflammatory effect in these patients. Biomarkers in exhaled breath condensate (EBC) were used to study the effects of salbutamol on lung inflammation in mechanically ventilated patients with ALI.MethodsEBC was collected before and 30 minutes after administration of inhaled salbutamol (800 μg). The following parameters were measured in the samples: volume obtained, conductivity, pH after helium deaeration, and concentration of nitrites, nitrates and 8-isoprostane. The leukotriene B4 concentration was measured after sample lyophilization and reconstitution. Results are expressed as the median (interquartile range).ResultsEBC was obtained from six ALI patients, with a median age of 56 (46 to 76) years. At the time of EBC collection, the Lung Injury Score was 3 (2.3 to 3.1) and the PaO2/FIO2 ratio was 133 (96 to 211) mmHg. A significant increase in deaerated EBC pH was observed after salbutamol administration (7.66 (7.58 to 7.75) versus 7.83 (7.67 to 7.91), P = 0.028). Trends toward decreased nitrosative species (18.81 (13.33 to 49.44) μM versus 21.21 (8.07 to 29.83) μM, P = 0.173) and decreased 8-isoprostane concentration (11.64 (7.17 to 17.13) pg/ml versus 6.55 (4.03 to 9.99) pg/ml, P = 0.068) were detected. No changes in leukotriene B4 concentration were found (1.58 (0.47 to 3.57) pg/ml versus 2.06 (1.01 to 3.01) pg/ml, P = 0.753).ConclusionEBC analysis is a noninvasive technique that can be used to monitor ventilated patients. In EBC from a small cohort of patients with ALI, inhaled salbutamol significantly decreased airspace acidosis, a marker of inflammation, and was associated with a trend toward decreased markers of nitrosative and oxidative stress.

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.

Ammonium persulfate can initiate an asthmatic response in mice.

Background Persulfate salts are the main cause of occupational asthma (OA) in hairdressers. The aim of this study was to verify whether ammonium persulfate ((NH4)2S2O8, AP) is capable of triggering an asthma-like response in mice. Methods BALB/c mice were dermally treated on days 1 and 8, with dimethylsulfoxide (DMSO), 1% AP or 5% AP (20 μl/ear). On day 15, the auricular lymph nodes were removed and an in vitro lymphocyte proliferation test (LPT) was performed. AP was tested for its ability to elicit an asthmatic response using a locally developed mouse model of chemical-induced asthma. On days 1 and 8, BALB/c mice received 20 μl AP (5%) or DMSO on each ear. On day 15, they received an intranasal instillation of AP (1%) or saline. Afterwards, ventilatory, inflammatory and immunological parameters were assessed. Results The LPT showed that in vitro stimulation of lymphocytes with AP leads to specific proliferation of lymphocytes from AP-sensitised mice. In vivo, AP induced, in AP-sensitised mice only, an ‘early’ ventilatory response (increased Penh (enhanced pause)) immediately after challenge, and airway hyper-reactivity to methacholine 22 h later. Pulmonary inflammation was mainly characterised by neutrophils (10–15%). AP-sensitised mice showed an increase in total number of T helper (Th) and B lymphocytes together with an increased in vitro secretion of interleukin-4 (IL-4), IL-10 and IL-13 and an increase in total serum immunoglobulin E. Conclusions In a mouse model, it was confirmed that dermal sensitisation to AP can lead to asthma-like responses after a single administration via the airway.

Tasa y características de las agudizaciones asmáticas (ASMAB I)

Objetivo El presente estudio examina la incidencia y las caracteristicas clinicas de los episodios de agudizacion asmatica (AA) atendidos en los servicios de urgencias (SU) de la ciudad de Barcelona (estudio ASMAB-I). Pacientes y metodos Se estudiaron los episodios de AA atendidos en los SU hospitalarios y en el SU domiciliario (061) durante 129 dias, correspondientes a una poblacion mayor de 14 anos de 1.203.598 habitantes. Resultados Se identificaron 831 episodios de AA, de los que 523 fueron atendidos en 3 hospitales universitarios, 113 en 2 hospitales de segundo nivel y otros 195 (de los que 20 se remitieron a hospitales) en los SU domiciliarios. La frecuentacion media fue de 6,4 episodios/dia, con una incidencia de AA de 0,53/105 habitantes/dia (intervalo de confianza del 95%, 0,46-0,56) y de 8,2/105 pacientes asmaticos (intervalo de confianza del 95%, 6,89-8,41). De los 276 episodios atendidos de lunes a jueves en los servicios de los hospitales universitarios, 66 pacientes (24%) reconocieron un inicio agudo y 14 (5%) un inicio subito. Unicamente 85 pacientes (31%) tomaban de modo regular corticoides inhalados y solo 33 (12%) anadieron corticoi-des orales en las 12 h previas a su llegada a urgencias. Un 16% de los episodios se calificaron de graves y un 3% de casi fatales. Un total de 82 pacientes (30%) fueron finalmente hospitalizados; ingresaron el 12% de las AA leves, el 39% de las AA moderadas, el 62% de las A A graves y el 100% de las casi fatales. El indice de comorbilidad de Charlson fue mayor en los pacientes hospitalizados (p Conclusiones La tasa de A A establecida puede ser un indicador util del grado de control del asma y servir para confirmar futuros aumentos de AA permanentes o puntuales. El inicio rapido (agudo o subito) es frecuente. Muchos pacientes no reciben un tratamiento adecuado antes de la hospitalizacion. La agudizacion grave es frecuente en nuestro medio. El ingreso esta relacionado con la gravedad y la comorbilidad. Los readmitidos han recibido al alta menos antibioticos y bromuro de ipratropio.

Detection of specific antibodies to pigeon serum and bloom antigens by enzyme linked immunosorbent assay in pigeon breeder's disease

BACKGROUND Pigeon breeders disease is an extrinsic allergic alveolitis in the lungs of sensitised people, caused by hypersensitivity reactions to inhaled pigeon antigens. Antigens from different sources of the animal are used for diagnostic purposes, with serum being the most widely used. Bloom is rarely used; very little is known of its antigenicity and diagnostic performance, particularly when used with the enzyme linked immunosorbent assay (ELISA) method, which is the most popular test as it permits measurement of the antibody response. METHODS To (a) standardise an ELISA for the measurement of specific IgG against pigeon serum and pigeon bloom extract; (b) to establish reference values for specific IgG in 73 non-exposed controls, (c) to show the presence of specific IgG against pigeon serum and bloom in serum samples of 17 patients with bird fanciers lung and 11 asymptomatic fanciers, and (d) to study the similarity of the two antigen sources by cross reactivity experiments. RESULTS Reference values of specific IgG were defined with the 97.5 percentile (367.9 U/ml for pigeon serum and 953.7 U/ml for pigeon bloom extract). Of symptomatic patients 100% had values higher than the cut off for both antigens. In asymptomatic fanciers values were higher than the cut off for pigeon serum in 45% and bloom extract in 54%. Cross reactivity experiments showed that the two antigens differed in antigenic content although some components may be common to both. CONCLUSION The ELISA methods used proved to be useful tools for evaluating specific IgG antibody responses against both antigens. The diagnostic performance of both ELISA methods performed with these antigen sources was similar, showing very high sensitivity but moderate specificity. Although some antigenic similarity was found between pigeon serum and bloom extract, cross reactivity studies showed that various antigens seemed to be specific to the bloom extract. However, the antigens responsible for pigeon breeders disease seem to be present in both antigenic sources.

Bronchial inflammation and hyperresponsiveness in well controlled asthma

Little research has been devoted to the characteristics of bronchial inflammation in patients with stable, well controlled asthma.

An Amplified ELISA Inhibition Method for the Measurement of Airborne Soybean Allergens

Background: Measurement of the soybean aeroallergen in Barcelona and other cities where soybean is unloaded is of increasing importance in controlling population exposure and evaluating the influence of such exposure on the persistence of asthma symtpoms. Objective: The aims of the study were: (1) to standardize an amplified ELISA inhibition method for the quantification of soybean aeroallergen and (2) to compare this method to a previously described RAST inhibition method. Methods and Results: An amplified competitive ELISA inhibition method with a biotin-streptavidin system was carried out using a pool of sera from soybean-sensitized patients. The results were expressed as U/ml using a low-molecular-mass soybean allergen as reference standard. Reproducibility was calculated by statistically comparing the slope of the regression lines of the standard curve of 4 consecutive assays and by determining the coefficient of variation (CV) of the percent inhibition data for each point of several independent standard curves, each from the same assay (intra-assay) and also from a separate assay (inter-assay). No significant differences in the slopes were obtained by analysis of covariance (ANCOVA) F = 1.04. The CV between assays varied between 4 and 22% (for the assay range used in the reference standard) and was greater than the CV within assays (5–10%). Only values with a CV(%) smaller than 20% were considered acceptable. 78.5% of the samples satisfied this criterion. The RAST inhibition and ELISA inhibition methods were compared by difference plots from the values of 338 air filter eluates. The intraclass correlation coefficient was 0.456 (p < 0.001). After the results of both methods were classified as lower and higher than 165 U/m3, the kappa index was 0.46 (p < 0.001). Conclusions: The data obtained in the present study are comparable to those reported from other similar immunoassays. Moreover, despite the difficulty in comparing air-sampling values from different laboratories, the kappa index may be taken to represent fairly good agreement beyond chance between both methods. All these data demonstrate that the present immunoassay is useful for measuring airborne soybean aeroallergens and can also be applied to evaluate the relationship between exposure and the development of asthma symptoms.