Formaldehyde is a low molecular weight chemical and can elicit acute and chronic health related problems. Most of the inhaled formaldehyde is retained in the upper respiratory tract due to its extraordinary solubility. Therefore, cases of formaldehyde-induced occupational asthma are sporadic despite its widespread use in industrial processes. We herein report upon a case of occupational asthma due to formaldehyde, which was confirmed by workplace challenge including working environmental assessments, and by formaldehyde inhalation challenge using a specially designed closed-circuit apparatus. To investigate the possible involvement of an IgE-mediated mechanism, both in vitro and in vivo tests were done. IgE antibody specific for formaldehyde-human serum albumin conjugate (F-HSA) was not detected by ELISA, and no specific cutaneous reactivity to F-HSA was noted by either skin prick or intradermal test. The patient was diagnosed with formaldehyde-induced occupational asthma not associated with an IgE mediated mechanism.
Adult ; Antibodies/blood ; Asthma/*chemically induced ; Case Report ; Formaldehyde/*adverse effects/immunology ; Human ; Male ; Occupational Diseases/*chemically induced

Isocyanates are the most significant cause of occupational asthma in our country. To evaluate the prevalence of work-related respiratory symptoms and immunologic sensitization to it, we performed a questionnaire survey, allergy skin test, radioallergosorbent test (RAST) to toluene diisocyanate (TDI)-human serum albumin (HSA) conjugate and methacholine bronchial challenge test on 23 isocyanate-exposed employees and 9 unexposed controls working in a zipper factory. Six employees (26.1%) complained of work-related respiratory symptoms and three symptomatic workers showed significant bronchoconstrictions on TDI-bronchoprovocation test. Three (13%) asymptomatic workers had high specific IgE antibodies to TDI-HSA and none of the TDI-sensitive asthmatic workers had specific IgE antibody. One of the TDI-sensitive asthmatic workers showed a negative result on the initial methacholine bronchial challenge test, but bronchial hyperresponsiveness developed after the TDI challenge. It was suggested that TDI-sensitive asthma was noted in three (13%) of 23 exposed workers and that asymptomatic workers could have high specific IgE antibody. Measurement of the changes in bronchial hyperresponsiveness after the TDI challenge could be helpful to diagnose TDI-sensitive asthma.
Adult ; Asthma/*chemically induced/diagnosis ; Bronchial Provocation Tests ; Humans ; Immunoglobulin E/analysis ; Occupational Diseases/*chemically induced/diagnosis ; Occupational Exposure ; Serum Albumin/immunology ; Toluene 2,4-Diisocyanate/*adverse effects/immunology

Reactive dyes have been widely used in recent years. This paper reports nine cases of immediate type occupational asthma to reactive dyes in one dye industry. All patients had had asthmatic symptoms, four had had rhinitis and they had worked for 6 to 25 months. Skin prick tests with reactive dyes were positive and bronchoprovocation tests also produced immediate or dual types of bronchoconstriction. We used the radioallergosorbent test (RAST) technique with nitrocellulose filter paper as a solid phase to detect specific IgE to four reactive dye-human serum albumin conjugates. High specific IgE binding was found in eight asthmatic workers compared with 13 negative controls. The RAST inhibition test revealed that there was no immunological cross-reactivity between 4 reactive dyes. These results suggested that the mechanism of their asthmatic symptoms was immunological, mostly an IgE-mediate reaction.
Adult ; Asthma/chemically induced/*immunology ; Dyes/*adverse effects ; Human ; Immunoglobulin E/*analysis ; Male ; Middle Age ; Occupational Diseases/chemically induced/*immunology ; Support, Non-U.S. Gov't

Reactive dyes have been widely used in recent years. This paper reports nine cases of immediate type occupational asthma to reactive dyes in one dye industry. All patients had had asthmatic symptoms, four had had rhinitis and they had worked for 6 to 25 months. Skin prick tests with reactive dyes were positive and bronchoprovocation tests also produced immediate or dual types of bronchoconstriction. We used the radioallergosorbent test (RAST) technique with nitrocellulose filter paper as a solid phase to detect specific IgE to four reactive dye-human serum albumin conjugates. High specific IgE binding was found in eight asthmatic workers compared with 13 negative controls. The RAST inhibition test revealed that there was no immunological cross-reactivity between 4 reactive dyes. These results suggested that the mechanism of their asthmatic symptoms was immunological, mostly an IgE-mediate reaction.
Adult ; Asthma/chemically induced/*immunology ; Dyes/*adverse effects ; Human ; Immunoglobulin E/*analysis ; Male ; Middle Age ; Occupational Diseases/chemically induced/*immunology ; Support, Non-U.S. Gov't

The prevalence studies on specific IgE to toluene diisocyanate (TDI)-human serum albumin (HSA) conjugate in TDI-induced asthma have shown variable results. In this study, we attempted to compare specific IgE bindings to TDI-HSA conjugate and its specificity using 3 different conjugates. Sera were collected from 20 TDI-induced asthma and 10 controls. Specific IgE were measured by ELISA using three TDI-HSA conjugates; two from Carnegie Mellon (CM; 98 and 99 CM conjugates) and one from Ajou University. To evaluate specificity and cross-reactivity, ELISA inhibition tests were applied. Positive and negative predictive values between Ajou conjugate and 98 CM conjugate were 75% and 100%. Those between Ajou and 99 CM were 100% and 93.8%. One patient showed an isolated positive response to the Ajou with negative responses to the other two conjugates. ELISA inhibition test using this patient's serum revealed the significant inhibitions by the Ajou and minimal inhibitions by the others. On the other hand, another patient showed an isolated positive response to 99 CM with negative responses to the others, and ELISA inhibition test showed significant inhibition by 99 CM with minimal inhibitions by the others. These results suggest that specific IgE bindings to a new antigenic determinant of TDI-HSA conjugate can be heterogeneous and differ from one individual to another.
Asthma/immunology ; Asthma/chemically induced* ; Enzyme-Linked Immunosorbent Assay ; Human ; IgE/biosynthesis* ; Serum Albumin/immunology* ; Toluene 2,4-Diisocyanate/immunology* ; Toluene 2,4-Diisocyanate/adverse effects

Isocyanate is the most prevalent agent in occupational asthma(OA) in Korea. We analyzed 43 toluene diisocyanate(TDI) induced OA patients of whom 81% were found to be spray painters. The bronchial sensitivity of all subjects was confirmed by TDI-bronchial challenge test. Serum-specific IgE antibodies to isocyanate-human serum albumin(HSA) conjugate were detected by RAST technique(Pharmacia, Sweden). Bronchial challenge test results revealed 21(57%) early, 5 late only, 4 dual, and 12 atypical responders(5 prolonged immediate, 6 square-shaped, 1 progressive). Four(9%) subjects had negative results on the methacholine bronchial challenge test. High levels of serum specific IgE antibody to isocyanate-HSA were found in 17(40%) patients. The prevalence of a specific IgE antibody was not associated with a type of TDI-bronchial challenge test response, smoking and atopic status, presence of rhino-sinusitis and systemic symptoms, or a degree of airway hyperresponsiveness to methacholine(p> 0.05). The period of latency, ranging from 3 to 132 months, was significantly longer in high specific IgE responders (p< 0.05). These data suggest that 40% of isocyanate-induced occupational asthma patients had high specific IgE antibody to isocyanate-HSA conjugate. The presence of specific IgE antibody does not seem to correlate with clinical parameters.
Allergens/adverse effects/*immunology ; Asthma/chemically induced/*immunology ; Female ; Human ; Immunoglobulin E/blood/*immunology ; Male ; Occupational Exposure/*adverse effects ; Toluene 2,4-Diisocyanate/adverse effects/*immunology

During the course of establishing an animal model of chronic asthma, we tried to elucidate the time sequence of airway hyperresponsiveness (AHR), airway inflammation, airway remodeling, and associated cytokines. Seven-week-old female BALB/c mice were studied as a chronic asthma model using ovalbumin (OVA). After sensitization, mice were exposed twice weekly to aerosolized OVA, and were divided into three groups depending on the duration of 4 weeks, 8 weeks, and 12 weeks. At each time point, airway responsiveness, inflammatory cells, cytokines in bronchoalveolar lavage fluids (BALF), serum OVA-specific IgE, IgG1, IgG2a, and histological examination were carried out. AHR to methacholine, increased levels of OVA-specific IgG1 and IgG2a, and goblet cell hyperplasia were continuously sustained at each time point of weeks. In contrast, we observed a time-dependent decrease in serum OVA-specific IgE, BALF eosinophils, BALF cytokines such as IL-13, transforming growth factor-beta1, and a time-dependent increase in BALF promatrix metalloproteinase-9 and peribronchial fibrosis. In this OVA-induced chronic asthma model, we observed airway remodelings as well as various cytokines and inflammatory cells being involved in different time-dependent manners. However, increased airway fibrosis did not directly correlate with a further increase in airway hyperresponsiveness.
Time Factors ; Pneumonia/chemically induced/*immunology ; Ovalbumin ; Mice, Inbred BALB C ; Mice ; Lung/drug effects/*immunology ; Female ; *Disease Models, Animal ; Cytokines/*immunology ; Chronic Disease ; Asthma/chemically induced/*immunology ; Animals

Allergic airway diseases are related to exposure to atmospheric pollutants, which have been suggested to be one factor in the increasing prevalence of asthma. Little is known about the effect of ozone and diesel exhaust particulates (DEP) on the development or aggravation of asthma. We have used a mouse asthma model to determine the effect of ozone and DEP on airway hyperresponsiveness and inflammation. Methacholine enhanced pause (P(enh)) was measured. Levels of IL-4 and IFN-gamma were quantified in bronchoalveolar lavage fluids by enzyme immunoassays. The OVA-sensitized-challenged and ozone and DEP exposure group had higher P(enh) than the OVA-sensitized-challenged group and the OVA-sensitized-challenged and DEP exposure group, and the OVA-sensitized-challenged and ozone exposure group. Levels of IFN-gamma were decreased in the OVA-sensitized-challenged and DEP exposure group and the OVA-sensitized-challenged and ozone and DEP exposure group compared to the OVA-sensitized-challenged and ozone exposure group. Levels of IL-4 were increased in the OVA-sensitized-challenged and ozone exposure group and the OVA-sensitized-challenged and DEP exposure group, and the OVA-sensitized-challenged and ozone and DEP exposure group compared to OVA-sensitized-challenged group. Co-exposure of ozone and DEP has additive effect on airway hyperresponsiveness by modulation of IL-4 and IFN-gamma suggesting that DEP amplify Th2 immune response.
Air Pollutants, Environmental/toxicity ; Animals ; Asthma/*chemically induced/*immunology ; Disease Models, Animal ; Drug Combinations ; Drug Synergism ; Female ; Hypersensitivity/complications/*etiology/*immunology ; Interferon Type II/immunology ; Interleukin-4/immunology ; Mice ; Mice, Inbred BALB C ; Ovalbumin ; Ozone/*toxicity ; Pneumonia/*chemically induced/complications/*immunology ; Research Support, Non-U.S. Gov't ; Respiratory Hypersensitivity/chemically induced/complications/immunology ; Vehicle Emissions/*toxicity

PURPOSE: Cockroach (CR) is an important inhalant allergen and can induce allergic asthma. However, the mechanism by which CR induces airway allergic inflammation and the role of endotoxin in CR extract are not clearly understood in regards to the development of airway inflammation. In this study, we evaluated whether endotoxin is essential to the development of CR induced airway allergic inflammation in mice. MATERIALS AND METHODS: Airway allergic inflammation was induced by intranasal administration of either CR extract, CR with additional endotoxin, or endotoxin depleted CR extract, respectively, in BALB/c wild type mice. CR induced inflammation was also evaluated with toll like receptor-4 (TLR-4) mutant (C3H/HeJ) and wild type (C3H/HeN) mice. RESULTS: Intranasal administration of CR extracts significantly induced airway hyperresponsiveness (AHR), eosinophilic and neutrophilic airway inflammation, as well as goblet cell hyperplasia in a dose-dependent manner. The addition of endotoxin along with CR allergen attenuated eosinophilic inflammation, interleukin (IL)-13 level, and goblet cell hyperplasia of respiratory epithelium; however, it did not affect the development of AHR. Endotoxin depletion in CR extract did not attenuate eosinophilic inflammation and lymphocytosis in BAL fluid, AHR and IL-13 expression in the lungs compared to CR alone. The attenuation of AHR, eosinophilic inflammation, and goblet cell hyperplasia induced by CR extract alone was not different between TLR-4 mutant and the wild type mice. In addition, heat inactivated CR extract administration induced attenuated AHR and eosinophilic inflammation. CONCLUSION: Endotoxin in CR extracts may not be essential to the development of airway inflammation.
Allergens/*immunology ; Animals ; Asthma/*chemically induced/*immunology/metabolism ; Cockroaches/*immunology ; Endotoxins/*immunology ; Enzyme-Linked Immunosorbent Assay ; Female ; Inflammation/*chemically induced/*immunology/metabolism ; Interferon-gamma/metabolism ; Interleukin-13/metabolism ; Interleukin-5/metabolism ; Mice ; Mice, Inbred BALB C ; Respiratory Hypersensitivity/chemically induced/*immunology

OBJECTIVEInhaled glucocorticosteroids (ICS) remains the first line controller medication for chronic airway inflammation in asthma till now. If the impact of allergen could not be eliminated, how would the improvement of airway inflammation be achieved with inhaled glucocorticosteroids therapy? What was its effect on airway remodeling? In this study, an animal model of asthma was established and the effects of budesonide on airway allergic inflammation and extracellular matrix (ECM) deposition in sensitized guinea pigs with repeated exposure to allergen were investigated.

METHODSThirty-two male Hartley guinea pigs were randomly divided into four groups with 8 in each group: (A) Group of repeated exposure to ovalbumin (OVA), (B) Group of repeated exposure to OVA plus budesonide (BUD) intervention, (C) Group of stopping repeated exposure to OVA plus stopping BUD intervention, (D) Control group. At 24 h after the last OVA challenge (8 weeks after the first OVA challenge), bronchoalveolar lavage fluid (BALF) was collected from each animal. Total and differential leukocyte counts in BALF was performed on cell suspension smear stained with May-Grünwald-Giemsa (MGG) method. The upper lobe of right lung was removed and regularly fixed, then paraffin embedded lung tissues sections were prepared. The count of eosinophils infiltrated in the airway wall was performed on H&E stained lung tissue sections with LEICA Q500IW computerized image analysis system. Fibronectin and collagen type III (Col-III) deposited in the airway wall were detected by immunohistochemical staining on the paraffin embedded lung tissues sections. The intensity of positive reaction of fibronectin or Col-III deposited in the airway wall was analyzed with LEICA Q500IW computerized image analysis system.

RESULTSThe count of eosinophils in BALF (x 10(5)/ml) of group A and B were higher than that of group C and D (35.70 +/- 25.22, 11.49 +/- 5.51 vs. 1.00 +/- 0.90, 1.02 +/- 0.78, P < 0.01), the difference between group A and B, group B and C was significant. The count of eosinophils infiltrated at each level of airway wall in group A and B were higher than that of group C and D (large airway: 6.95 +/- 2.28, 1.54 +/- 1.09 vs. 0.76 +/- 0.45, 0.88 +/- 0.25; medial airway: 9.22 +/- 3.89, 3.99 +/- 2.3 vs. 1.25 +/- 1.20, 0.64 +/- 0.36; small airway: 11.56 +/- 4.02, 2.67 +/- 1.15 vs. 1.32 +/- 0.83, 0.43 +/- 0.24, P < 0.01), the difference between group A and B, group B and C was significant. The gray values of fibronectin deposited in medial and small airway of group A and B were lower than those of group C and D (medial airway 122 +/- 22, 174 +/- 23 vs. 219 +/- 34, 229 +/- 20; small airway 135 +/- 29, 165 +/- 41 vs. 236 +/- 20, 220 +/- 16, P < 0.05), the difference between group A and B, group B and C was significant. The gray values of Col-III deposited in medial and small airway of group A and B were lower than those of group C and D (medial airway 153 +/- 21, 174 +/- 22 vs. 189 +/- 14, 200 +/- 18; small airway 133 +/- 23, 176 +/- 20 vs. 191 +/- 14, 198 +/- 20, P < 0.05), the difference between group A and B was significant.

CONCLUSIONInhaled budesonide could partially inhibit allergic inflammation and ECM deposition in airway wall in guinea pig chronic asthma model with repeated exposure to allergen. Early inhaled budesonide combined with avoidance of OVA exposure could completely inhibit allergic inflammation and ECM deposition. These results suggest that the inhibitory effect on airway allergic inflammation and airway remodeling of inhaled glucocorticosteroids would be limited when the allergen factor could not be avoided.

Administration, Inhalation ; Airway Remodeling ; drug effects ; immunology ; Allergens ; administration & dosage ; immunology ; Animals ; Asthma ; chemically induced ; drug therapy ; immunology ; Bronchitis, Chronic ; chemically induced ; drug therapy ; immunology ; Bronchoalveolar Lavage Fluid ; immunology ; Budesonide ; administration & dosage ; pharmacology ; Collagen Type III ; metabolism ; Disease Models, Animal ; Eosinophils ; immunology ; Extracellular Matrix ; immunology ; Fibronectins ; metabolism ; Glucocorticoids ; administration & dosage ; pharmacology ; Guinea Pigs ; Immunohistochemistry ; Lung ; drug effects ; immunology ; Male ; Ovalbumin ; administration & dosage ; immunology