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Exposure to hexahydrophthalic and methylhexahydrophthalic anhydrides--dose-response for sensitization and airway effects.

OBJECTIVES: This study clarified the exposure-response relationships for the organic acid anhydrides (OAA) hexahydrophthalic (HHPA) and methylhexahydrophthalic (MHHPA) anhydrides and the development of specific immunoglobulin (IG) E and G antibodies and work-related symptoms. METHODS: In an epoxy resin-using factory, air levels of OAA were determined by gas chromatography-mass spectrometry. Occupational, smoking, and medical histories (questionnaire) were obtained for 154 exposed workers and 57 referents. Work-related symptoms of the eyes and airways were recorded, and OAA metabolites were analyzed in urine. A skin-prick test with common allergens and conjugates of OAA were performed. Specific IgE (radioallergosorbent test) and IgG (enzyme-linked immumosorbent assay) antibodies were determined in serum, and spirometry was performed. RESULTS: Air levels of the OAA were low (HHPA < 1 to 94, MHHPA < 3 to 77 microg/m3) and associated with the concentrations of the OAA metabolites in urine. Furthermore, for the exposed workers, there were high prevalences of sensitization (IgE 22%, IgG 21%), which correlated with the exposure. Neither atopy nor smoking increased this risk significantly. Furthermore, work-related symptoms were more prevalent among the exposed workers than among the referents (eyes 23% versus 14%, nose 28% versus 16%, nose bleeding 8% versus 0%, lower airways 10% versus 4%), and they were related to the exposure (adjusted prevalence odds ratios (POR) in the highest group 7.7, 3.6 and 17, respectively) and the IgE levels (POR 4.9, 3.1 and 5.6, respectively). CONCLUSIONS: In spite of the very low OAA levels in the air and metabolites in the urine, there were high and exposure-related risks of specific IgE and IgG sensitization and of work-related symptoms for the eyes, nose (especially bleeding), and lower airways.

Adult↗

Insomnia and cow's milk allergy in infants.

A group of eight infants (six boys and two girls, 7 to 46 weeks of age) is reported, in whom a causal relationship between cow's milk allergy and chronic sleeplessness was suspected. They were referred because of waking and crying episodes that had occurred since the early days of life during sleep hours. During an average night, they slept about 4.5 hours and woke their parents about five times. They cried a lot during the day and were described as fussy. Two infants had been treated with phenothiazine without improvement. No cause for chronic insomnia was found during a standard medical and psychologic workup. An all-night polygraphic recording confirmed the disrupted sleep pattern of these infants, as compared with that of normal infants, and excluded further causes of arousals. Due to a clinical suspicion of atopy, the infants were further subjected to a series of allergy tests. IgE levels were shown to be elevated in each child, and radioallergosorbent tests were positive for cow's milk protein. The infants were than fed exclusively with a hydrolyzed milk protein mixture for 4 weeks. Sleep normalized within 2 weeks in every infant: night sleep increased to a median of 10 hours, and the awakenings only occurred occasionally. In four infants less than 6 months of age, cow's milk was reintroduced in the diet, and within 1 week all four became severely sleepless. Cow's milk was again excluded from the diet and the babies' sleep behaviors were again normalized. It is concluded that, when no evident cause for sleeplessness can be found in an infant, the possibility of milk allergy should be given serious consideration.

Animals↗

Clinical evaluation of histamine release test: a novel method for identifying allergens from the whole blood of allergic patients.

Identification of allergens is necessary for proper treatment of allergic diseases. We have so far mainly used two types of allergen identifying tests, one type based on the quantification of specific serum IgE (e.g. radioallergosorbent test (RAST)), the other on allergen challenging (e.g. prick test, provocation test) for an estimation of immediate allergic reaction. However, with the former test, a high level of serum specific IgE does not necessarily indicate evidence of allergy; the latter type causes itching on the challenged focus and may, in some cases, cause anaphylaxis. The histamine release test using the glass-fiber method (HRT) is based on the measurement of an immediate allergic reaction but can be performed safely in vitro. In this investigation, we measured the reaction of samples taken against 10 allergens simultaneously using HRT with a small amount of peripheral whole blood. HRT showed a high correlation and concordance with the CAP-RAST system. HRT also had a significant correlation with the nasal provocation test, and had good specificity and positive predictive value. With these advantages, HRT is considered to be clinically useful and especially suitable for screening of allergens because of its high specificity and positive predictive value, and also because of its safety and ease of performance.

Adolescent↗

Studies on Alternaria allergens. II. Measurement of the relative potency of commercial Alternaria extracts by the direct RAST and by RAST inhibition.

The relative potency of 12 commercial Alternaria extracts was analyzed by end-point skin test titrations and compared to in vitro measurements of potency, including (1) the radioallergosorbent test (RAST) inhibition procedure; (2) the direct RAST procedure; and (3) the protein nitrogen unit (PNU) content. Potencies determined by skin testing 10 sensitive patients were strongly correlated among the various patients. Measurements of potency by both RAST inhibition and direct RAST assay were strongly correlated to potency as measured by skin testing. In contrast, neither the weight:volume nor the PNU content bore any relationship to allergenic potency as measured by skin testing or by either of the RAST procedures. Extracts differed by as much as 3,000-fold in allergen content by skin testing. Moreover, the extracts appeared to contain different allergenic determinants when tested by RAST inhibition. RAST inhibition offered several technical advantages over the direct RAST procedure, in that only one solid-phase RAST reagent was required, slopes of dose-response curves could be more easily compared, and a greater discrimination in allergenic potencies among extracts could be made. The RAST appears to offer an excellent method for measuring the potency of allergy extracts, pending the isolation and characterization of actual allergens.

Allergens↗

Discontinuation of bee venom immunotherapy in children and adolescents.

Sixty-six patients with a history of systemic allergy reactions to bee stings, positive skin prick test to less than or equal to 100 micrograms/ml bee venom, and positive radioallergosorbent test (RAST) results were given venom immunotherapy. IgE and IgG antibodies to bee venom were measured by RAST and enzyme-linked immunosorbent test (ELISA), respectively. IgE and IgG anti-bee venom levels rose initially, but subsequently fell during immunotherapy. In 31 patients in whom specific IgE fell to low (less than 6% counts bound) or unmeasurable levels, immunotherapy was discontinued, and sting challenge was carried out 1 to 3 years later. All patients tolerated sting challenge well. The specific IgE and IgG antibody levels did not change significantly after treatment was stopped. Our data suggest that hyposensitization treatment can be stopped when specific IgE serum concentrations have fallen to low or unmeasurable levels and specific IgG antibody values are maintained, and that in a considerable number of patients venom immunotherapy has a lasting therapeutic and immunologic effect.

Adolescent↗

Detection of blocking antibodies after hyposensitization.

We have studied two techniques and developed another to detect blocking antibodies in allergic asthmatic children who have been exposed to seven months of hyposensitization to house dust. These techniques were: RAST Neutralization test (RAST-N), RAST Interference test (RAST-I) and RAST Previous Adsorption test (RAST-PA). We have also determined the specific IgE values, by radioallergosorbent test (RAST), before and after the treatment and have not found a significant decrease in these levels. The percentages of positive development of blocking antibodies obtained were: 28% by RAST-N, 80% by RAST-I and 28% by RAST-PA. Thus, RAST Interference test seems to be more sensitive concerning the qualitative determination of blocking antibodies.

Antibodies↗

Immunologic contact urticaria due to airborne methylhexahydrophthalic and methyltetrahydrophthalic anhydrides.

Acid anhydrides are low-molecular-weight chemicals known to cause respiratory irritancy and allergy. Skin allergy has on rare occasions been reported. 2 workers contracted hives and itching on uncovered skin after 2 months exposure to methyltetrahydrophthalic anhydride (MTHPA) and methylhexahydrophthalic anhydride (MHHPA), to which they had airborne exposure. Later, the patients also developed conjunctivitis, rhinitis, sore throat, cough or asthma. In addition to MTHPA, 1 worker was also exposed to unsaturated polyester resin (UP). Both patients' immediate allergy to MTHPA and MHHPA was verified by positive prick tests to MTHPA and MHHPA, conjugated with human serum albumin (HSA), and positive radioallergosorbent tests (RASTs) to these anhydrides. On prick testing, both patients also reacted to a phthalic anhydride (PA)-HSA-conjugate and 1 of the patients to UP-HSA-conjugate. Specific immediate allergy to UP was shown by RAST. RAST inhibition with MTHPA, MHHPA and UP-resin conjugates confirmed IgE-mediated allergy and cross-reactivity between anhydrides. Our patients had developed airborne contact urticaria caused by phthalic anhydrides, in addition to respiratory allergy. Phthalic anhydride contained in the UP resin was possibly responsible for the immediate reaction of the skin.

Adult↗

Severe cow's milk induced colitis in an exclusively breast-fed neonate. Case report and clinical review of cow's milk allergy.

Cow's milk induced eosinophilic colitis presenting in the first week of life has been reported, but is very rare. The authors describe a 4-day-old female infant who presented with profuse rectal bleeding resulting in a hematocrit fall from 38% to 30% within 8 hr after hospital admission. Sigmoidoscopy revealed colonic mucosa that was red, edematous, and friable, with punctate hemorrhages. Rectal biopsy showed marked eosinophilic infiltration with multifocal hemorrhage. Further history indicated that while the infant had been exclusively breast-fed since birth, the nursing mother had been drinking 4-5 glasses of cow's milk per day since delivery. Prick puncture skin testing of the infant was positive for cow's milk protein. A serum radioallergosorbent test (RAST) for cow's milk protein was positive. The infant's serum IgE was 1.5 IU/ml. Rectal bleeding resolved when the patient was given a casein hydrolysate formula (Nutramigen, Mead Johnson Nutrition, Evansville, IN), and endoscopy one week later showed improvement, with only scattered areas of erythema, and no friability. We conclude that since the infant was exclusively breast-fed, the milk protein must have passed into the breast milk antigenically intact. Prenatal sensitization probably occurred. Cow's milk induced allergic colitis should be considered in the differential diagnosis of colitis in breast-fed neonates.

Adult↗

Specific sensitization to the common housefly (Musca domestica) not related to insect panallergy.

BACKGROUND: Allergy to houseflies is rare. We report a case of respiratory allergy from occupational exposure to houseflies in a farmer. CASE REPORT: A 30 year-old female farmer with a long-standing history of grass pollen allergy observed for 2 years rhino-conjunctivitis and mild asthma when entering livestock stables and barns. Allergy retesting revealed sensitization to various pollens but not to animal danders. Houseflies (Musca domestica) occurring on the farm in great quantity were suspected by the farmer herself as the causative agent. RESULTS: Skin prick testing with housefly was positive in the patient and negative in four controls. Experimental radioallergosorbant test was class 3 positive. Sensitization to house dust mite, storage mites and cockroach was not detectable. Western blots with housefly extracts revealed immunoglobulin E (IgE)-binding to bands of 70, 50, and approximately 16 kDa. Tropomyosin in the housefly extract (35 kDa) was recognized by a tropomyosin reference serum but not by the patient. In enzyme-linked immunosorbent assay (ELISA) inhibition assays using housefly as the solid phase, IgE-binding of the patient was inhibited by 75% by M. domestica and by 44% by the closely related lesser housefly (Fannia canicularis), but not by extracts from blowfly (Lucilia spp.), fruit fly (Drosophila spp.), horsefly (Haematopota pluvialis) and mosquito (Culex pipiens). The IgE-binding of the tropomyosin control serum was inhibited by 60-80% by all species. CONCLUSIONS: In accordance with previous reports, this case demonstrates that respiratory sensitization to insects may be highly specific. According to ELISA inhibition, cross-sensitization in the present case was restricted to species of the family of true flies (Muscidae).

Adult↗

23. Clinical laboratory assessment of IgE-dependent hypersensitivity.

This chapter reviews clinical and laboratory analyses that aid in the diagnosis and management of human allergic (IgE-dependent) diseases. The diagnostic algorithm for immediate-type hypersensitivity begins with a thorough clinical history and physical examination. Once signs and symptoms compatible with an allergic disorder have been identified, a skin test and/or blood test for allergen-specific IgE antibodies may serve as primary confirmation to strengthen the diagnosis. Puncture and intradermal skin testing provide a biologically relevant immediate-type hypersensitivity response in the skin, with resultant wheal and flare reactions within 15 minutes of allergen application. Bleeding, dermatographism, and antihistamines may confound the quality of the skin test. Allergen-specific IgE antibody may also be detected in the blood using a radioallergosorbent test (RAST). Nonisotopic "second-generation" RAST-type assays have evolved to provide more quantitative, sensitive, precise IgE antibody results. In vivo provocation tests may serve as secondary confirmatory tests when the clinical history is discordant with a primary IgE antibody test result. The multiallergen screen is a qualitative RAST-type assay that detects specific IgE antibody to approximately 15 allergens that evoke a large majority of aeroallergen or food-related allergic disorders. Other useful serological assays performed in the diagnostic allergy laboratory include total serum IgE, Hymenoptera venom-specific IgG antibody, IgG precipitins for organic dusts, mast cell tryptases, and the venom RAST inhibition test. Above all, in vivo or laboratory confirmatory test results that are inconsistent with the clinical history should be repeated as for any laboratory assessment.

Algorithms↗

Latex allergy and occupational asthma in health care workers: adverse outcomes.

The prevalence of natural rubber latex (NRL) allergy has been estimated to be 5-18% in health care workers, and latex exposure has been one of the leading causes of occupational asthma in the last several years. We present the cases of two nurses who developed sensitivity to NRL, both with dermatologic symptoms and respiratory symptoms that included asthma. They were referred to the University of Maryland for evaluation of their allergies, then for occupational and environmental consults. The patients' allergy to NRL was confirmed on the basis of clinical history, a positive skin test to latex, and the presence of latex-specific immunoglobulin E (IgE) serology by radioallergosorbent test (RAST). Both patients worked in the same community hospital for approximately 20 years; one was an endoscopy nurse and the other worked in the emergency department. Following the diagnosis of allergy to latex, both patients avoided direct skin contact with latex, but they continued to work in the same respective environments, where powdered latex gloves and other potentially sensitizing chemicals were used. Instead of improving, the clinical condition of the patients worsened and they remained symptomatic, even after they were removed from their workplace. Their airways reacted to low levels of a variety of sensitizers and irritants in the environment, and they became depressed. Both nurses were referred for vocational rehabilitation.

Asthma↗

Incidence of IgG short-term sensitizing antibodies in an allergic population.

Heat-stable, immunoglobulin G, short-term sensitizing antibodies (IgG S-T S) were sought in serum from 149 allergic patients who had strongly positive immediate skin tests to inhalant allergens. The sera were tested by passive cutaneous anaphylaxis (PCA) in monkeys. No IgG S-T S antibodies were demonstrated in 169 tests with a variety of allergens. Antibody with the characteristics of IgE was demonstrated in 47% of monkey PCA tests and, in an additional 34% of sera. IgE antibody to the same allergen was demonstrated by radioallergosorbent testing (RAST).

Adolescent↗

Allergy to a product(s) of ethylene oxide gas: demonstration of IgE and IgG antibodies and hapten specificity.

Patient D.H., on chronic hemodialysis, developed severe allergic reactions after exposure to articles such as plastic tubing and hemodialysis supplies which had undergone cold sterilization with ethylene oxide (EO) gas. It was shown that human serum albumin (HSA) exposed to EO (EO-HSA) in the usual sterilization procedure selectively elicited positive skin tests and in vitro histamine release. It is now demonstrated that D.H. serum reacts selectively in a radioallergosorbent test (RAST) which utilizes discs coated with HSA and exposed to EO gas. In addition, D.H. serum contained IgG antibodies reactive with EO-HSA. This antibody activity was not detected in the sera of 27 normal subjects and 25 chronic hemodialysis patients. EO-HSA and ragweed RAST inhibition tests with a number of proteins in native form and after exposure to EO demonstrated the EO hapten specificity of the IgE antibody.

Antibodies, Anti-Idiotypic↗

Anaphylaxis to wine.

Anaphylaxis following the ingestion of wine was found in a non-atopic woman. The reaction occurred within 15 min of wine ingestion but did not follow other alcoholic beverages. An immediate skin test response to the offending wine was found but specific IgE levels could not be measured by radioallergosorbent testing.

Adult↗

Occupational asthma due to freeze-dried raspberry.

OBJECTIVE: To investigate the possibility that inhalation of raspberry powder at work can cause occupational asthma. METHODS: We report the case of a 35-year-old, nonsmoking woman who complained of hay fever symptoms, wheezing, and shortness of breath two or three times a month exclusively in association with coating chewing gum with raspberry powder. Prick test extracts with the five types of fruit powder were produced. Peak expiratory flow rate monitoring five times daily was performed for an 8-week period while the patient was at work. Specific IgE and histamine release tests for raspberry powder were performed. Breathing zone dust measurements were taken. RESULTS: Baseline lung function and histamine provocation test results were normal. During the 8-week monitoring period, 5 episodes of reduced peak expiratory flow rate were demonstrated. Each period was directly related to working with raspberry powder. A 9-mm prick test result positive for raspberry powder was seen (histamine control, 9 mm). In addition, the result of a radioallergosorbent test for raspberry was positive (0.84 kUA/L). The result of a histamine release test with raspberry powder from work was negative. Breathing zone total dust measurement was 5.9 mg/m3. CONCLUSIONS: To our knowledge, this is the first description of occupational asthma due to the inhalation of raspberry powder. The symptoms of the patient described herein disappeared after she was moved to another part of the factory. Hygienic improvements were performed at the workplace to reduce the sensitization risk of other workers.

Adult↗

Safety of Hymenoptera venom rush immunotherapy.

We studied 97 consecutive patients who had received Hymenoptera venom rush immunotherapy in our department. There were 53 males and 44 females, whose mean age was 46 years (8-74 years). Most study patients had experienced severe anaphylaxis induced by a Hymenoptera sting: the reaction was Müller stage IV in 48 patients. Skin tests were positive for Vespula venom in 85 cases, Polistes venom in 23, and bee venom in 23. Radioallergosorbent test values exceeded 0.70 kIU/l in 60 cases. Immunotherapy was performed with Vespula venom alone in 73 cases, bee venom alone in five cases, and both Vespula and bee venom in 19 cases. A cutaneous reaction was seen at the injection site in most patients. Four patients also had skin manifestations in areas remote from the injection site. Blood pressure elevation was seen in 11 patients, moderate hypotension in two, rhinitis in one, asthenia or headache in seven, visual disorders and vertigo in two, and transient dyspnea in two. Our protocol has proved very safe, epinephrine never being required in the 97 reported cases.

Adolescent↗

Increased risk of obstructive pulmonary disease in tunnel workers.

BACKGROUND: Tunnel workers are exposed to gases and particles from blasting and diesel exhausts. The aim of this study was to assess the occurrence of respiratory symptoms and airflow limitation in tunnel workers and to relate these findings to years of exposure. METHODS: Two hundred and twelve tunnel workers and a reference group of 205 other heavy construction workers participated in a cross sectional investigation. Exposure measurements were carried out to demonstrate the difference in exposure between the two occupational groups. Spirometric tests and a questionnaire on respiratory symptoms and smoking habits were applied. Atopy was determined by a multiple radioallergosorbent test (RAST). Radiological signs of silicosis were evaluated. Respiratory symptoms and lung function were studied in relation to years of exposure and adjusted for smoking habits and atopy. RESULTS: Compared with the reference subjects the tunnel workers had a significant decrease in forced vital capacity (FVC) % predicted and forced expiratory volume in one second (FEV(1)) % predicted when related to years of exposure. Adjusted FEV(1) decreased by 17 ml for each year of tunnel work exposure compared with 0.5 ml in outdoor heavy construction workers. The tunnel workers also reported significantly higher occurrence of respiratory symptoms. The prevalence of chronic obstructive pulmonary disease (COPD) was 14% in the tunnel workers compared with 8% in the reference subjects. CONCLUSION: Exposure to dust and gases from diesel exhaust, blasting, drilling and rock transport in tunnel work enhances the risk for accelerated decline in FEV(1), respiratory symptoms, and COPD in tunnel workers compared with other heavy construction workers.

Adult↗

[Radioimmunologic determination of total IgE and allergen-specific IgE-antibodies in diffuse neurodermitis].

Total IgE levels in sera of 165 patients with atopic dermatitis and 79 patients with dermatoses as well as normal control patients were determined by radioimmunoassay (Phadebas, Pharmacia). Although the mean value for patients with atopic dermatitis was found far above the mean value for normal controls, 38% of patients showed total IgE serum levels within the normal range. Highest IgE serum levels were observed in patients with the generalized form of the disease and in patients with asthma and allergic rhinitis. No direct correlation however, to severity of disease could be found. In a series of 50 patients prick tests were compared to total IgE serum levels and to levels of allergen specific antibodies determined by radioallergosorbent-test (RAST). Extracts of grass pollens and of animal dandruff were used. There was complete agreement between results of skin testing and RAST in at least 80%. While cross reactions were common with grass pollen extracts in RAST, there was no cross-over with animal dandruff. No correlation was found between titer of allergen specific antibody and severity of skin lesions. IgE specific antibody could be detected in 48% of patients with normal total IgE serum levels and in 82% of patients with elevated values.

Allergens↗