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In the literature, bronchial allergen challenge is usually reported to result in an increase in histamine-induced airway responsiveness (AR). The present study investigated the relation between baseline AR and allergen-induced changes in AR. The effect of allergen challenge on AR was investigated in 21 atopic asthmatic patients. Allergen challenge resulted in a significant decrease in PC20 histamine after 24 h. When the group was divided into three subgroups according to baseline PC20 histamine, a significant decrease in PC20 histamine was found only in patients with relatively high baseline PC20 histamine (groups 1 and 2). A significant inverse correlation was found between baseline PC20 and allergen-induced PC20 histamine. The effect of repeated allergen challenge on AR was studied in eight patients. The first allergen challenge resulted in a significant decrease in PC20 histamine; no further decrease in mean PC20 histamine was seen after the second allergen challenge. These results suggest that allergen-induced changes in AR occur mainly in patients with relatively high baseline PC20 values. Once an increase in AR is induced, further allergen challenge does not always result in further increase in AR.

Increased airway hyperresponsiveness is thought to be one of the phenomena underlying nocturnal airway obstruction in asthma. To investigate the mechanisms that influence and modulate this phenomenon, we compared circadian variations in airway responsiveness with AMP and propranolol with the circadian variation in airway responsiveness to methacholine. Inhalation provocation tests were performed at 16.00 and 04.00 h in 16 nonsmoking atopic asthmatic subjects (18 to 42 yr of age), prospectively assigned to Group 1 (mean circadian peak expiratory flow rate [PEFR] variation greater-than-or-equal-to 15%) and Group 2 (

Skin reactivity (intracutaneous test) to histamine and allergens was studied cross-sectionally in a Dutch asthmatic patient population from childhood to old age (4-75 years). It was found that the histamine skin reactivity rose significantly (p less than 0.05) during childhood, was significantly higher in the 10-15-year age group, and was constant between 20 and 75 years of age. The mean wheal index (histamine ratio) of all allergens was constant during childhood, and decreased after the age of 25 for grass pollen and house-dust mite and after the age of 15 for the other allergens. The prevalence of a positive skin test decreased with age, except for grass pollen. During childhood the indoor allergens, cat dander and house-dust mite, were the most important, while after the age of 15 sensitivity to an outdoor allergen, grass pollen, increased markedly. At all ages house-dust mite was the most important allergen. After the age of 25 the prevalence of every allergen declines. The prevalence of a positive skin test to Cladosporium was unexpectedly high in childhood (10-40%). It can be concluded that the prevalence of a positive skin test declines with age, except for grass pollen. The degree of sensitization in asthmatics peaked in the age groups between 20 and 40 and sensitivity to indoor allergens developed earlier than sensitivity to outdoor allergens.

Bronchial hyperresponsiveness (BHR) to methacholine and adenosine 5'-monophosphate (AMP) was studied in 15 allergic asthmatic patients before and 3 and 24 h after allergen challenge with house dust mite (HDM). Subjects attended the clinic on 3 consecutive days. On the first day a control solution was inhaled, and methacholine or AMP challenge was performed 3 h later. The next day HDM was inhaled, and 3 and 24 h later methacholine or AMP challenge was performed again. There were no significant difference in FEV1 baseline value between any of the study days. PD20 HDM, percentage decrease in FEV1, and AUC for both the EAR and LAR were not significantly different in the methacholine and AMP studies. After HDM challenge, PC20 methacholine decreased significantly from a geometric mean (+/- SEM) starting value of 1.39 +/- 0.63 mg/ml to 0.30 +/- 0.78 mg/ml (p less than 0.001) at 3 h and to 0.22 +/- 0.75 mg/ml (p less than 0.001) at 24 h. The magnitude of the decrease in PC20 methacholine at 3 h correlated with the severity of the late asthmatic reaction (LAR) as measured by the percentage fall in FEV1 and area under the curve (AUC) (r = -0.60 and r = 0.55; p less than 0.05). A significant decrease was observed in the PC20 AMP at 3 h, from a geometric mean value of 12.2 +/- 0.96 mg/ml after challenge with the control solution to 4.47 +/- 0.99 mg/ml (p less than 0.05) after HDM challenge.(ABSTRACT TRUNCATED AT 250 WORDS)

Background: Despite increasing evidence implicating fungal proteases in the virulence of pulmonary fungal diseases, routine fungal culture media do not favor protease production. Hence, filtrates that serve as the source of antigen for serologic determinations are poor in proteases, and consequently, the immunologic significance of these enzymes is unknown. Methods: A clinical isolate of Aspergillus fumigatus was cultured on collagen medium, resulting in excretion of high levels of fungal proteases in the culture filtrate. This was compared with standard culture filtrates by diverse analytic techniques including immunoblotting with sera of patients with pulmonary aspergilloma (PA) and allergic bronchopulmonary aspergillosis (ABPA). Results: Protein profiles of collagen medium filtrate showed several (glyco)proteins not found in conventional culture filtrates, including a prominent 32 kd glycoprotein, which coisolated in gel filtration and ion-exchange chromatography with elastase activity, as well as 67 kd and 94 kd (glyco)proteins. Intense IgG binding was seen with the 32 kd glycoprotein when ABPA and PA sera were used. The 94 kd protein showed intense binding with PA sera but not with ABPA sera, whereas for the 67 kd glycoprotein the reverse tended to be the case. Conclusion: Fungal culture on collagen media results in the production of filtrates with high protease activity, containing unique (glyco)proteins of which at least one (32 kd) is closely associated with fungal elastase activity. These constituents are immunologically relevant, eliciting IgG production in patients with PA and ABPA, suggesting production of these (glyco)proteins during disease in vivo. The use of collagen media filtrates may enhance our serodiagnostic capacity in patients with fungal pulmonary diseases.

Standardized extracts of Phleum pratensis (grass) and Dermatophagoides pteronyssinus (house-dust mite) were used as test allergens for multiple regression in order to determine optimum concentrations and cutoff values with regard to diagnostic capacity and safety. If a RAST value of class 1 or more was taken as an indication of sensitization, it was found that the optimum concentrations for the detection of sensitization are in the range 10-100 BU/ml and 1500-10,000 BU/ml for intracutaneous tests (ICT) and skin prick tests (SPT), respectively. The skin test results were expressed as histamine ratios. Using allergen concentrations of 30 and 3,000 BU/ml, we found cutoff values of 0.87 and 0.53 and predictive values of 87.1% and 79.1% for ICT and SPT, respectively. The maximum wheal size (mean wheal size + 2 SD) to be expected in 95% of the population was 26.6 mm (ICT) and 10.9 mm (SPT), sizes regarded as safe by most clinicians. In conclusion, by using this method with a limited number of patients, one can probably improve the diagnostic precision and safety of the skin test. In the second part of this study, these hypotheses were prospectively tested in a multicenter study.

An otherwise healthy 44-yr-old man experienced a serious attack of bronchial obstruction after working with resins and hardeners, releasing fumes of a mixture of an alipathic and a cycloaliphatic diamine hardener. Eight hours after deliberate challenge with the hardener a large increase of airway resistance was found. Seventy-two hours after challenge, eosinophilia in the bronchoalveolar lavage (BAL) fluid together with a decrease of peripheral eosinophils was seen. After cessation of contact with this hardener, no more acute episodes occurred, although maintenance treatment with a topical corticosteroid and a beta 2-agonist remained necessary. A BAL performed 1 yr later showed a normal cell distribution. The results suggest that these aliphatic and cycloaliphatic diamine hardeners may be occupational hazards. Eosinophil inflammation may play a causal role.

Bronchoalveolar lavage was performed in a patient during an acute stage of allergic bronchopulmonary aspergillosis (ABPA) and repeated 17 mo later during a remission stage and cessation of corticosteroid therapy. Measurement of protein concentrations (albumin, IgG, IgA, and IgM) by laser nephelometry and crossed immunoelectrophoresis indicates that transudation of proteins occurs from the circulation into the lung compartment during the acute stage of ABPA. Furthermore, comparing total Ig concentrations and titers of ELISA IgG, IgA, and IgM antibodies against Aspergillus fumigatus with the corresponding values of serum measurements indicates a preferential local production of IgA antibodies and IgM to a lesser extent. No indications were found for a local production of either IgG, total IgE, or IgE against A. fumigatus. During remission of the ABPA, titers of antibodies in the bronchoalveolar fluid (BAF) decreased to normal levels except IgA against A. fumigatus that remained elevated. The elevated titers of IgA in the BAF and IgE antibodies in the serum against A. fumigatus together with the elevated numbers of granulocytes in the BAF during the remission stage indicate that the immunologic situation is not yet normalized.

Following the manifestation of humidifier fever in a number of workers in a carpet yarn texturing plant, a comparative study was begun of a group of workers exposed to fungi from the air-conditioning system and a control group not so exposed. For both group of workers anamnestic data were collected, intracutaneous skin tests were performed, certain lung function parameters were determined, and the presence of antibodies to a number of antigens from the system was tested for. It was found that the group of exposed workers had a significantly higher rate of positive intracutaneous skin test than non-exposed workers. Additionally, their serology was more often positive. Both positive skin test and positive serology were more frequent in non-smokers than in smokers. A positive immediate skin reaction among exposed workers was found to correlate with an FEF25-75 reduction during the working week. A positive delayed skin reaction among exposed workers correlated with a lower FVC prior to the start of the working week than recorded for non-exposed workers. A positive serology in exposed workers did not correlate with a difference in lung function compared with non-exposed workers, nor was there a correlation with a change in lung function in the course of the working week. When humidifier fever is diagnosed, steps should be taken to reduce exposure. It would also appear desirable to keep exposed workers under medical observation and to monitor the subsequent development of their lung function.

Both short-term and long-term effects of the beta-sympathomimetic drugs isoprenaline and terbutaline on the urinary excretion of histamine and its two main metabolites were evaluated in patients with systemic mastocytosis. In a short-term study isoprenaline and terbutaline were given intravenously during five hours to three and two patients, respectively. Compared with placebo infusion Nt-methylhistamine excretion fell during terbutaline administration, whereas during isoprenaline no changes were observed. In a long-term study three patients received a treatment with orally administered terbutaline for 24 days. In one patient a slight reduction of the excretion of the histamine metabolites was found. In another patient the excretion of histamine and its metabolites decreased especially during the eight days observation period after the end of the treatment. In this study we saw occasionally large and rapid changes occurring simultaneously in all three urinary parameters of histamine release. In conclusion, terbutaline can reduce histamine release in systemic mastocytosis. However, because of the small symptomatic and biochemical effects found in our patients, the clinical significance of beta-sympathomimetic drug treatment in this disease has yet to be established.

Precipitating antibodies and positive skin tests to antigens from a contaminated humidification system in a synthetic carpet yarn plant were tested in a group of exposed (n = 66) and non-exposed (n = 45) workers. The first investigation was carried out in 1979 shortly before hygienic actions to reduce exposure had been taken. In 1981 and 1985 they were repeated. The significant difference between the positive skin reactions and of positive serology (4 or more lines), observed in 1979 between the exposed and non-exposed population, was not found in 1981 and 1985. In 1979 the differences were the most pronounced in the non-smoking individuals. However, even in that category the significant difference disappeared in 1981 and 1985. A positive skin test in 1979 did not increase the chance of having a positive skin test during repeat investigations. In serology this was only the case when the positive criterion was lowered to three or more lines. This study demonstrates that, in the absence of a quantitative analysis of airborne antigens, skin tests and serology may be helpful in obtaining an estimation of antigenic contamination of the air and subsequent sensitization on a group level. However, these tests are less appropriate when used in an individual health surveillance program at this type of nonspecific antigen exposure.

Eosinophils from normal nonatopic healthy volunteers (195 +/- 106 cells per microliter) were isolated by centrifugation over a discontinuous Percoll gradient, under isotonic conditions, with a recovery of 46.5 +/- 26.2% from whole blood (n = 21; mean +/- SD). More than 90% of the eosinophils (purity greater than 93%) with a density between 1.095 to 1.105 gm/ml were defined normodense. Less than 10% of the eosinophils had a density less than 1.095 gm/ml and were defined hypodense. Isolation of eosinophils of patients with atopic asthma revealed a cell population with 65% to 70% hypodense cells that was independent of the total eosinophilic cell count. In vitro activation of normodense eosinophils, measured by an increase in superoxide production, induced quantities of hypodense eosinophils in the range found in patients with asthma. The amount of hypodense eosinophils induced by different stimuli was in the same order as the increase in superoxide production (antibiotic calcium ionophore A23187 greater than serum-treated zymosan greater than platelet-activating factor greater than N-formyl-methionyl-leucyl phenylalanine). During the stimulation of the normodense cells, no secretion of eosinophilic peroxidase or arylsulfatase B could be measured, even though hypodense eosinophils were produced. Enzymatic activity of arylsulfatase B within the eosinophils remained the same, before and after stimulation. The enzymatic activity of eosinophilic peroxidase in normodense eosinophils (16.6 +/- 9.7 micrograms/10(6) cells) did not change in the normodense fraction but was increased in the induced hypodense cells (34.0 +/- 8.4 micrograms/10(6) cells; n = 7; mean +/- SD; p less than 0.01) after stimulation.(ABSTRACT TRUNCATED AT 250 WORDS)

In order to investigate the role of histamine in the late asthmatic reaction (LAR) following house-dust mite (HDM) inhalation, we studied, with hourly intervals, urinary N tau-methylhistamine (an important metabolite of histamine) in 14 allergic asthmatic patients before and after broncho provocation with HDM. Four patients showed an early asthmatic reaction (EAR), while 10 patients developed a LAR as well. In the hour following the EAR a significant increase in urinary N tau-methylhistamine was observed as compared to the control day (0.01 less than p less than 0.05). During the LAR no increase of this metabolite was detected in the urine of the patients. Additionally, histamine was measured in broncho alveolar lavage fluid (BAF) obtained from 6 patients during the HDM-provoked LAR and compared to histamine levels in BAF from patients without a LAR, following broncho provocation. In the LAR group higher histamine levels were found than in the other patient and control groups. For the whole patient group no correlation was found between the degree of bronchial obstruction during the LAR and the BAF histamine values. No difference was found in N tau-methylhistamine in BAF between patients with LAR and controls. Thus histamine metabolite studies in the urine failed to provide evidence of involvement of histamine in the LAR, while further data are needed to interpret the results of local sampling in the lung.

The phenotypic cellular profile of bronchial lavage (BL) and bronchoalveolar lavage (BAL) was studied in 7 single early (SR) and 10 dual asthmatic responders (DR). Lavage was performed, after previously having determined bronchial hyperresponsiveness to histamine and the response to house dust mite (HDM) challenge. The recovered lavage fluid was separated in two fractions, BL and BAL. Total fluid recovery and cell number from the BL and BAL were comparable in both patient groups. Differential cell counting and immunocytochemistry were performed. DR had a significantly higher number of eosinophils and EG2+ cells in BL but not in their BAL. No differences could be found in CD4+, CD8+, and HLA-DR+ cells. A strong correlation was found between eosinophils in the BL+ and EG2+ cells in the BL (r = 0.79, p