Possible role of molds as secondary etiologic agents of the asthma epidemics in Barcelona, Spain.
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Allergens↗
Biomedical subjects
R Codina
Publications and source records attributed to R Codina.
Neoallergens in heated soybean hull.
BACKGROUND: During the process of harvest, transport and storage, microbial and mold contamination can raise the temperature of soybeans to 75 degreesC or higher. The purposes of this study were (1) to evaluate the allergenicity of fresh and stored soybean hulls and (2) to ascertain whether heat alters the allergenicity of stored soybean hulls. METHODS: Allergen extracts were prepared from (1) stored soybean hulls, (2) fresh soybean hulls and (3) stored soybean hulls heated to 37 degreesC (E1), 55 degreesC (E2) and 80 degreesC (E3) or kept at room temperature (E4) for 16 h. Individual serum from 68 soybean asthmatic (SA) subjects, 30 nonallergic subjects and two serum pools made from 4 SA sera and 4 sera from asthmatics not sensitive to soybean were studied. All sera and serum pools were assayed for content of specific IgE (radioallergosorbent test) and IgG4 (ELISA). The following additional studies were done for extracts E1-E4: (1) SDS-PAGE, (2) SDS-PAGE/Western blot for specific IgE and IgG4 using both serum pools, and (3) study of the effects of heat on inhibiting activity of the extracts prepared from stored soybean hulls using the pool of SA sera. RESULTS: Test results demonstrated a reduced binding of specific IgE and IgG4 to fresh soybean hull extract compared to stored soybean hull extract, and an increased binding for heated extracts (E1-E3) compared to unheated ones (E4). Moreover, there was an increase in potency for IgE and IgG4 bindings for the heated (E1-E3) compared to unheated (E4) extract, as measured by the amount of protein to produce 50% inhibition. Several protein bands with a molecular weight (MW) higher than 20 kD were absent from the SDS-PAGE for E3 but were present in E1, E2 and E4, and a new protein band (MW 15.3 kD) appeared for E3 only. Two new protein bands, with MWs of 15.3 and 10 kD, which bind specific IgE, were present on Western blot and one of the 3 main soybean hull allergens, probably Gly m 2, disappeared in E3. IgG4 Western blot showed similar results, but only the 10 kD protein band was present. CONCLUSION: The results demonstrate that soybean hull allergenicity is affected by heat, and suggest that the heat generated during storage and transport of soybeans could generate 2 new allergen determinants or increases in epitope exposure as a result of conformational changes. The significance of these new IgE and IgG4 binding proteins has yet to be determined.
Allergens↗
Purification and characterization of a soybean hull allergen responsible for the Barcelona asthma outbreaks. II. Purification and sequencing of the Gly m 2 allergen.
BACKGROUND: A low MW allergen from soybean hull, Gly m 1, with two isoallergens, Gly m 1 A and Gly m 1 B, was associated with the asthma outbreaks that occurred in Cartagena, Spain. Using sera of asthmatic epidemic patients (AEP) from Barcelona, three main soybean hull allergens, two of them with MWs and pIs identical to those reported for Gly m 1 A and Gly m 1 B, were identified. OBJECTIVE: The purpose of this study was to purify and to study the N-terminal amino acid sequence of the third allergen, which has a MW of 8 kDa. METHOD: The purification procedure combined the double dialysis method and preparative isoelectofocusing (IEF). Specific IgE determination to the fractions obtained demonstrated three peaks, one of them corresponding to the 8 kDa allergen. The pooled fractions containing this allergen were studied by sodium dodecylsulfate-polyacrylamide gel electrophoresis (SDS-PAGE), SDS-PAGE/Western blot and IEF/Western blot. Only a band with a MW of 8 kDa and a pI of 6 was obtained. Its allergenic activity was measured and it was demonstrated that the allergenicity of soybean hull correlates with the presence of the 8 kDa allergen. The N-terminal amino acid sequence of the first 20 amino acids, which was registered at the PIR Data Submission as the N-terminal partial sequence of Gly m 2, was determined according the Edman degradation method. RESULTS: Gly m 2 N-terminal amino acid sequence lacks homology with that reported for the allergen Gly m 1 but has a homology of 71% with a storage protein from cotyledon of Vigna radiata (cow pea) and 64% with a "disease response protein' from Pisum sativum (green pea). These results suggest that Gly m 2 in soybeans could protect against diseases which affect soybean plants. CONCLUSION: This study demonstrates the existence of another soybean hull allergen, Gly m 2, partially responsible for the soybean asthma outbreaks that occurred in Barcelona, Spain.
Allergens↗
Mite allergens did not cause asthma epidemics in Barcelona, Spain.
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Adult↗
IgG subclass deficiencies associated with bronchiectasis.
Only a small number of patients with IgG subclass deficiencies (IgGSD) have been observed to have bronchiectasis. Moreover, in the series of patients with bronchiectasis, IgGSD have not been found at any frequency, and the etiology of bronchiectasis remains unclear in 29 to 49% of cases. Serum concentrations of total IgG, IgA, and IgG subclasses as well as pulmonary function were measured in 65 patients (aged: 10 to 74 yr) with bronchiectasis of unknown etiology. An ELISA test was performed to quantify subclasses 1 through 4 using subclass-specific antihuman monoclonal antibodies. IgG subclass estimation in a healthy population with age-stratified normal ranges was derived from 100 adults, 37 children aged between 10 and 12 yr, and 27 adolescents aged between 13 and 16 yr. Serum concentrations of specific IgG antibodies to Haemophilus influenzae type b capsular polysaccharide (Hib-PRP) were also assayed by an ELISA test in 19 of the patients (10 with IgGSD and nine with non-IgGSD) and in 58 healthy individuals before and 3 wk after immunization with Hib-PRP conjugated to meningococcal outer membrane protein complex (OMPC). Thirty-one patients (48%) had low serum concentrations of one or more IgG subclasses (19 IgG2 deficiencies, 2 IgG3 deficiencies, 3 IgG4 deficiencies, and 7 combined subclass deficiencies). All patients showed increased levels of total IgG, IgG1, and IgA, but this rise was significantly higher in patients without IgGSD. Patients with IgGSD showed impaired antibody response to Hib-PRP compared with patients with non-IgGSD and the control group. IgGSD, particularly IgG2 deficiency, are not an unusual cause of bronchiectasis. Therefore, serum levels of IgG subclasses must be assayed whenever other causes of bronchiectasis have been ruled out.
Adolescent↗
[IgG subclasses in patients with symptomatic IgA deficiency].
BACKGROUND: Patients with IgA deficiency may be asymptomatic or may present recurrent infections mainly respiratory. A possible explanation for this variety of symptoms may be the association with a deficiency of IgG subclasses. METHODS: Twenty-five patients with a symptomatic IgA deficiency with a mean age of 18 +/- 12 years were studied. The quantification of the IgG subclasses was performed by ELISA test with antisubclass specific monoclonal murine antibodies. Serum from 100 healthy adults was collected to determine normal values of the IgG subclasses. RESULTS: Twenty-five (48%) had a deficiency of associated IgG subclasses (6 IgG2 deficiency, 1 IgG3, 3 IgG4 and 2 combined deficiency). The patient with a deficiency of associated IgG subclasses had more recurrent respiratory infections (chi 2, p < 0.03) and pneumonias (chi 2, p < 0.04). This group also had a greater FEV1 alteration (Student-t test, p < 0.04). CONCLUSIONS: Patients with symptomatic IgA deficiency frequently present IgG subclass deficiency and are more likely to have recurrent respiratory infections and greater changes in pulmonary function.
Adolescent↗
Diagnosis of soybean-induced asthma.
BACKGROUND: The role of soybean dust as a causal agent of asthma has been clearly established since the Barcelona asthma epidemics in the 1980s. The large number of patients who were first seen with asthma symptoms during those epidemics provided an excellent opportunity to study the possibilities of different diagnostic tests. OBJECTIVE: This study was designed to evaluate the usefulness of the skin test and amplified ELISA technique for quantifying specific IgE in the diagnosis of soybean asthma. PATIENTS AND RESULTS: Ninety epidemic asthmatic patients and 95 nonepidemic asthmatic patients were studied 2 years after the last epidemic. Results of prick tests and ELISAs for specific IgE with hull and dust extracts showed a significant difference between the two groups of patients (p < 0.001). Sensitivity and specificity of glycerinated prick test with hull extract in epidemic asthmatic patients were 57.7% and 95.3%, respectively, and ELISA values were 56.6% and 93.7%, respectively. Similar results were obtained with dust extracts. CONCLUSION: Glycerinated skin prick tests and ELISAs with soybean hull and dust extracts have proved effective in the diagnosis of soybean asthma, even 2 years after the epidemics. Taking into account the sensitivity (90.5%) and specificity (93.7%) of ELISA test results for epidemic asthmatic patients found when the epidemic occurred, data from this study suggest that both tests may be very useful for the diagnosis of soybean dust-induced asthma.
Asthma↗
Clinical and functional characteristics of patients two years after being affected by the soybean asthma epidemic in Barcelona.
BACKGROUND: Patients affected during the asthma outbreaks caused by soybean dust inhalation in Barcelona presented with sudden onset of severe asthma followed by the rapid relief of symptoms after treatment. Two years after the epidemics ended, a case-control study was conducted in which the clinical, functional, and immunological characteristics of these asthma patients (a randomised sample of asthmatic patients admitted as emergency cases on epidemic days, n = 213) were compared with those of a control group (a random sample of asthmatic patients admitted as emergency cases for attacks of asthma on non-epidemic days, n = 170). METHODS: The study included the administration of the ATS-DLD78 standardised respiratory questionnaire, the measurement of atopy, and performance of spirometric tests and a methacholine inhalation test. RESULTS: Patients with epidemic asthma reported fewer symptoms of asthma, had attended emergency departments less frequently during the previous year for acute attacks of asthma, were taking fewer inhaled corticosteroids at the time of the study, and attended medical follow up less frequently than did the patients with non-epidemic asthma. However, the cases and controls showed no differences in ventilatory capacity or reactivity to the methacholine bronchoprovocation test. CONCLUSIONS: Two years after the end of the soybean epidemics, people affected by epidemic asthma had a favourable prognosis. This finding contrasts with a higher risk of life threatening asthma and death during the epidemics. This paradox could be the result of a complex interaction between host and conditions of exposure.
Asthma↗
Preventing asthma epidemics due to soybeans by dust-control measures.
BACKGROUND: The inhalation of soybean dust released during the unloading of soybeans into a silo caused outbreaks of asthma in Barcelona, Spain. This study was designed to determine morbidity due to asthma and serum IgE reactivity before and after the installation of filters in the silo. METHODS: We measured soybean-allergen concentrations in 136 samples of air collected for 9 months before and 24 months after the installation of filters. We compared the number of days on which there was an unexpected increase in emergency room visits for asthma, the number of days on which the number of emergency room visits for asthma in one four-hour period was so high that it was unlikely to be due to chance, and the mean daily number of emergency room and intensive care unit admissions for asthma for a total of 60 months before and after filter installation. Serum IgE antibodies against soybean allergens were measured in 38 patients before and after filter installation. RESULTS: The concentration of airborne soybean allergens on days when soybeans were unloaded decreased from 324 to 25 U per cubic meter after the installation of filters (P < 0.001). The number of days on which there was an unusually large number of visits to the hospital for asthma and the number of days on which asthma was epidemic both decreased significantly (both P < 0.001), from 29 to 6 and from 18 to 0, respectively. The mean daily number of emergency room and intensive care unit admissions for asthma on days when soybeans were unloaded decreased from 8.3 to 5.4 and from 0.26 to 0.01, respectively (both P < 0.001). The mean serum IgE antibody concentrations in the 38 patients studied decreased from 2 Pharmacia reference units per milliliter to 1 (P < 0.001). CONCLUSIONS: Installing filters on silos to prevent airborne dissemination of allergenic soybean dust eliminates outbreaks of asthma caused by inhalation of the dust, thus supporting the idea that the avoidance of allergens helps prevent asthma.
Adolescent↗
[Normal values of the immunoglobulin G subclasses in an adult population. Importance in a study of their deficiency].
BACKGROUND: Quantification of the IgG subclasses (IgGS) requires highly sensitive and specific techniques since their molecular structure is more than 95% homologous. At present, ELISA and RIA are the most appropriate techniques; although the variability of these techniques and the possible ethnic differences in serum levels of IgGS oblige each laboratory to establish its own reference values in a normal population, a condition necessary for defining IgGS deficits. METHODS: In the present study the normal serum values of IgGS in 100 healthy individuals were established. Serum quantification of the IgGS was performed by optimization of the indirect ELISA technique using AcMo and OMS reference standards H00-03 for the 4 subclasses, calibrated vs the OMS WHO 67/97 pattern. RESULTS: Normal values observed for IgG1 were 2.61-10.81 g/l; IgG2, 1.12-4.08 g/l; IgG3, 0.22-2.88 g/l; and IgG4, 0.05-1.56 g/l obtained as of the mean +/- 2 SD for IgG1 and as of the extent of the values of the remaining 3 subclasses by following a non-normal distribution. The sensitivity of the technique was 0.05 g/l with mean intra and inter analysis coefficients of 3.5% and 10.7% respectively. The correlation between total IgG and the sum of the 4 subclasses showed a r = 0.894 (p less than 0.01). CONCLUSIONS: The ELISA technique using AcMo and OMS reference standards is an adequate method for the quantification of the IgG subclasses. However, given the variability of this technique and in order to avoid error, strict working conditions, such as the use of control sera at 2 concentration levels, should be observed for the 4 IgGS in each of the analytic series and each series should also be duplicated.
Adult↗
Risk factors of soybean epidemic asthma. The role of smoking and atopy.
Epidemics of emergency room admissions for asthma occurring in Barcelona during the period 1981 to 1987 were caused by inhalation of soybean dust. To investigate the risk factors that determined why some asthma patients became reactive to soybean and were consequently affected by the asthma epidemics of Barcelona but others did not do so, a case-control study was conducted during 1989, 2 yr after the cessation of asthma epidemics. Patients with asthma admitted in emergency room services during epidemic asthma days (n = 169) were compared with asthma patients admitted in the same services during nonepidemic days and who were never admitted during the epidemics (n = 147). Risk factors other than soybean exposure, namely skin reactivity against at least one common allergen (odds ratio [OR] 3.0, 1.7 to 5.3), age over 64 yr (OR 2.8, 1.4 to 6.0), cigarette smoking at the time of the epidemics (OR 2.3, 1.2 to 2.4), past smoking (OR 1.8, 0.9 to 3.7), and total immunoglobulin E (IgE) higher than 100 IU/ml (OR 1.7, 1.0 to 3.0), were found independently related to epidemic asthma. The role of smoking was especially important for those who had a positive skin reaction and were exposed to soybean dust (OR 7.9, 1.8 to 36.0). In this group, a dose-response pattern with pack-years was observed (p less than 0.01). The present findings suggest a multifactorial process for epidemic asthma, in which atopy and cigarette smoking played an important synergistic role. This has a preventive potential for IgE-related asthma.
Asthma↗
[Evaluation and significance of circulating immunocomplexes and their correlation with other immunologic parameters in connective tissue diseases].
The presence of circulating immunocomplexes (CIC) was evaluated in several collagen diseases and in a control group of 100 healthy individuals. Three methods were used for their detection: binding to C1q in solid phase, binding to conglutinin in solid phase, and measurement of the serum capacity to solubilize an experimental immunocomplex. In the group of patients with systemic lupus erythematosus (SLE) significant differences were found for the three techniques (p less than 0.001) and also for activity (p less than 0.001). The most sensitive method was binding to C1q. The sensitivity of the three techniques for CIC was very low in the group of patients with systemic sclerosis, and the highest rate of positive results was found with binding to C1q (10%). In the group with hypersensitivity vasculitis and polyarteritis nodosa CIC were found in 71% of cases, more than one method being positive in 50%. The highest sensitivity was obtained with the conglutinin method (48%). In patients with temporal arteritis, significant differences were only found for conglutinin binding method (p less than 0.001), with low rates of positivity.
Adolescent↗
Mollusk shell hypersensitivity pneumonitis.
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Alveolitis, Extrinsic Allergic↗
Partial characterization of the silk allergens in mulberry silk extract.
Although there have been reports of allergic reactions such as asthma and hypersensitivity pneumonitis to silk allergens (especially in oriental countries), these allergens have not been characterized. We report an in vivo and in vitro study of subjects allergic to silk, as well as a partial characterization of the allergens involved. Forty-one subjects with a clinical history of silk allergy who had asthma, allergic rhinitis or both, and who had a positive intradermal skin test to mulberry silk extract, were evaluated in the study. Four asthmatic subjects with negative skin tests and RASTs to mulberry silk extract were used as controls. RAST specific lgE was present in 37/41 (90%) subjects. SDS-PAGE of mulberry silk extract demonstrated 13 protein bands of less than 21-95 kD. lgE which bound to protein bands was present in 13/32 (41%) sera, twelve of which bound to a single protein with a molecular weight between 35.1 and 50 kD. A pool made with the four control sera did not react with any protein band. The patients allergic to silk showed evidence of sensitivity to mulberry silk extract, both in vivo and in vitro, but sera from 19/32 (59%) subjects did not have antibodies reactive with the mulberry silk extract immunoblot protein bands. The low avidity of the lgE may be responsible for this discrepancy between in vivo and in vitro results.
Adolescent↗