Mean IgE Levels Research Articles

Total serum IgE levels in a large cohort of patients with severe or difficult-to-treat asthma

Limited data are available on levels of IgE in large cohorts of patients with severe or difficult-to-treat asthma. To examine IgE levels and disease in patients from The Epidemiology and Natural History of Asthma: Outcomes and Treatment Regimens (TENOR) study. From January 2001 to October 2001, 4,923 patients were screened for inclusion in the study. Of these, 4,756 patients 6 years or older with severe or difficult-to-treat asthma were enrolled and completed a baseline study visit. Total serum IgE levels were measured at the baseline visit and are summarized by geometric means. The mean total IgE level of the population is 106.6 IU/mL (95% confidence interval, 101.5-112.0 IU/mL). Children (6-12 years old) and adolescents (13-17 years old) have higher mean IgE levels than adults (> or =18 years old) (P < .001). Males have a higher mean IgE level than females (P < .001). IgE levels are higher among nonwhite patients than white patients (P < .001). Current smokers have higher IgE levels than past smokers or never smokers (P < .001). Among children, patients with severe asthma have a higher mean IgE level (280.2 IU/mL) than patients with moderate (145.8 IU/mL) or mild (137.8 IU/mL) asthma (P < .001). Among adults, patients with childhood-onset asthma have higher IgE levels (124.3 IU/mL [n = 1,348]) than patients with adult-onset asthma (65.7 IU/mL [n = 1,956]) (P < .001). In patients with severe or difficult-to-treat asthma from the TENOR study, higher total IgE levels were observed in males, children, smokers, nonwhite racial/ethnic groups, and adults with childhood-onset disease. In addition, IgE levels are associated with asthma severity among younger patients.

Declining cell-mediated immunity and increased chronic disease burden

The effects of chronic disease have been proposed as an explanation for conflicting results in studies of age effects on cell-mediated immunity. To examine the hypothesis that declining cell-mediated immunity is more closely linked to chronic disease burden than to chronological age. Fifty-eight elderly individuals were tested for delayed-type hypersensitivity (DTH) responses to Candida and tetanus antigens. Disease burden was quantified using the Cumulative Illness Rating Scale (CIRS). Higher CIRS scores reflect greater disease burden. Mean DTH response by age group (<71, 71-78, and >78 years) was compared with mean DTH response by CIRS score (<11, 11-15, >15). Total serum IgE levels were measured and similarly stratified by age and CIRS score. Mean Candida DTH responsiveness declined progressively with increasing disease burden (increasing CIRS score). Mean DTH responses were 7.78, 3.05, and 0.0 mm for CIRS scores less than 11, 11 to 15, and greater than 15, respectively. Candida DTH responses showed no progressive decline with advancing age. Mean DTH responses were 4.7, 3.5, and 5.0 mm in participants younger than 71, 71 to 78, and older than 78 years, respectively. Total serum IgE levels increased with advancing age. Mean total IgE levels were 182, 249, and 342 IU/mL in participants younger than 71, 71 to 78, and older than 78 years, respectively. No correlation was observed between mean total IgE levels and CIRS scores. An inverse relationship between Candida DTH response and CIRS score suggests that increased chronic disease burden is associated with diminished cell-mediated immune response. Advancing age did not predict a diminished DTH response in our patients. No relationship was observed between chronic disease burden and total serum IgE level.

Evaluation of the relationship between cockroach sensitivity and house-dust-mite sensitivity in Turkish asthmatic patients

Exposure to cockroach has been identified as an important source of indoor allergens in patients with asthma and allergic rhinitis. We evaluated the relationship between cockroach sensitivity and other allergens in patients with asthma. A total of 114 patients, defined asthma according to GINA, were enrolled in this study. A questionnaire including age, sex, duration of asthma, history of cockroach presence at home, and total IgE, blood eosinophil count, pulmonary function tests, standard skin prick test additional cockroach and shrimp allergen were performed. There were 84 (73.7%) female and 30 (26.3%) male patients with a mean age of 38.1+10.1 years. The average duration of asthma was 7.7+7.2 years. Sixty five (57%) patients were determined atopic and 49 (43%) nonatopic. Pollen allergen was the most common allergen in 59 (51.8%) patients with asthma, and second common allergen was mite allergen in 43 (37.7%) patients. Cockroach sensitivity were detected in 23 (20.2%) of 114 all asthmatics and 23 (35%) of atopic asthmatics. High rates of house-dust-mite allergy (73.9%) was determined in patients with cockroach sensitivity (P<0.05), while we found no relationship with other allergens. There was no difference for cockroach sensitivity between rural and urban population. Cockroach sensitivity was more common in mild bronchial asthmatics and a female predominance was observed. In addition, there was no association between shrimp and cockroach sensitivity. As a result, a high rate of cockroach sensitivity alone or with mite sensitivity was seen in patients with bronchial asthma in Turkish population. Because of cross-reactivity between mites and cockroach, cockroach sensitivity should be investigated in patients with house-dust-mite allergy. In addition, a high rate of cockroach sensitivity, in terms of IgE sensitization, may be important for the development of new sensitizations.

Dose effects of respiratory neoantigen exposure on primary allergic sensitization

Background Respiratory allergen dose effects on the human immune response are incompletely understood. We prospectively examined the effect of respiratory antigen dose exposure on the rate of primary allergic sensitization to a neoantigen, keyhole limpet hemocyanin, using a unique model of human nasal allergic sensitization. Methods Fifty-one atopic human volunteers were consecutively assigned to 1 of 4 groups completing a 4-week nasal sensitization protocol. Group protocols varied only in initial antigen dose exposure. Intranasal doses of 0.1, 10, 1000, or 100,000 μg keyhole limpet hemocyanin with adjuvant intranasal diesel exhaust particles were administered in the research laboratory. Antigen-specific IgE, IgG, and IgG4 were measured in nasal lavage samples at completion of the protocol. Results Allergic sensitization rates for the 0.1, 10, 1000, and 100,000 μg dose groups were 0%, 100%, 57%, and 11% respectively (p= 0.0003). Mean IgE levels for the 10 μg, 1000 μg, and 100,000 μg doses were 29.2, 11.5, and 1.2 U/ml, respectively (Kruskal-Wallis test, overall p= 0.001; 10 μg vs. 1000 μg p= 0.05; 1000 μg vs. 100,000 μg p= 0.034). All subjects produced antigen-specific IgG. Conclusions Respiratory antigen dose at the time of first exposure influences the mucosal immune response in antigen naïve humans. The risk of primary allergic sensitization may paradoxically be decreased by initial high levels of respiratory antigen exposure through the induction of a modified, non-allergic immune response. Clinical Pharmacology & Therapeutics (2005) 77, P3–P3; doi: 10.1016/j.clpt.2004.11.013

Altered Calcium-Induced Exocytosis in Neutrophils from Allergic Patients

We have investigated the exocytotic characteristics of neutrophils from allergic patients and healthy volunteers employing the whole cell membrane capacitance (Cm) measurement. The mean serum IgE level from allergic patients (423.75 ± 12.75 IU/ml) determined by chemiluminescence immunoassay was much higher than that of healthy volunteers (28.47 ± 16.68 IU/ml). Intracellular dialysis of buffered Ca²⁺ and GTPγS triggered biphasic exocytosis. The total capacitance increment displayed a steep dependence on pipette free Ca²⁺ concentration ([Ca²⁺]_p), with maximal stimulation achieved at 10 µM. A significant decrease in the total capacitance increment was observed in the allergic group at [Ca²⁺]_p >10 µM. Moreover, at submaximal stimulatory [Ca²⁺]_p of 1 µM, the maximal rate of exocytosis in allergic patients (V_max = 20.75 ± 6.19 fF/s) was much faster than that of the healthy control group (V_max = 7.97 ± 2.49 fF/s). On the other hand, the Ca²⁺-independent exocytosis stimulated by GTPγS displayed no significant difference in either the total membrane capacitance increments or the maximal rate of exocytosis. The results suggest that hypersecretion of neutrophils in allergic diseases may involve the development of abnormal Ca²⁺-dependent exocytosis.

Declining cell-mediated immunity is associated with increased chronic disease burden

Rationale We used delayed type hypersensitivity (DTH) skin testing to examine the hypothesis that declining cell-mediated immunity is more closely linked to chronic disease burden than to chronological age. Methods 58 elderly subjects were tested for delayed type hypersensitivity (DTH) response to Candida antigen. Each subjects' disease burden was quantified using the Cumulative Illness Ratings Scale (CIRS). Higher CIRS score reflects greater disease burden. Mean DTH response by age group (<71 yo, 71-78 yo, and >79 yo) was compared with mean DTH response by CIRS score (<11, 11-15, >15). Total serum IgE levels were measured and similarly stratified by age and CIRS score. Results Mean Candida DTH responsiveness declined progressively with increasing disease burden (increasing CIRS score). Mean DTH responses were 7.4 mm, 3.4 mm, and 0.0 mm for CIRS groups <11, 11-15, and >15 respectively. Interestingly, Candida DTH response showed no progressive decline with advancing age. Mean DTH responses were 5.2 mm, 3.5 mm, and 5.0 mm in subjects <71 yo, 71-78 yo, and >79 yo respectively. Total serum IgE levels increased with advancing age. Mean total IgE levels were 183, 249, and 342 in subjects >71 yo, 71-78 yo, and >79 yo respectively. No correlation was observed between mean total IgE levels and CIRS score. Conclusions We note an inverse relationship between Candida DTH response and CIRS score, suggesting that increased chronic disease burden is associated with diminished cell-mediated immune response. Surprisingly, advancing age did not predict a diminished DTH response in our subjects. No relationship was observed between disease burden and total serum IgE.

Clinical significance antigen-specific IgG 4 for the diagnosis of food allergy in atopic dermatitis : The comparison of serum antigen-specific IgE and IgG4 levels with the results of DBPCFC for milk and egg white

Rationale Allergen-specific IgG 4 has been known to have protective effects for allergy provocation as a blocking antibody. The clinical significance of food-specific IgG4 for food allergy provocation was investigated. Methods A total of 68 atopic dermatitis patients were involved. The serum levels of food-specific IgE and IgG4 were measured by Pharmacia UniCAP and using allergy protein chip of Food BioTech APC. Double-blind placebo-controlled food challenges (DPBCFC) for milk and egg white were performed. The results of DBPCFC were compared the serum levels of allergen-specific IgE and IgG4. Results The mean serum milk-specific IgE level of atopic dermatitis patients with milk allergy was lower than the level of those without milk allergy. Moreover, mean serum milk-specific IgG4 levels were also significantly low in atopic dermatitis patients with milk allergy than in those without milk allergy. The results showed also similar pattern in egg white. Conclusions The measurement of serum allergen-specific-IgG4 levels as well as IgE may be necessary for the diagnosis of food allergy.

Omalizumab rapidly decreases nasal allergic response and FcεRI on basophils

Background Omalizumab is a monoclonal anti-IgE antibody that is effective for the treatment of allergic respiratory disorders; however, its onset of action is unknown. Objective This study was designed to determine the onset of action of omalizumab through the use of a challenge model to determine time-dependent inhibition of ragweed-induced changes in nasal volume as well as correlate the kinetics of omalizumab-induced decreases in serum free IgE and FcεRI receptors on basophils. Methods We conducted a 6-week, randomized, double-blind, placebo-controlled study of 24 rhinitic patients with ragweed allergy. After PD 30 ragweed nasal allergen challenge, patients received either omalizumab, ∼0.016 mg/kg per IgE (IU/mL), or placebo at days 0 and 28 and were rechallenged with ragweed PD 30 dose biweekly. FcεRI expression on blood basophils was determined by flow cytometry at baseline and 7, 14, 28, and 42 days after treatment. IgE levels were measured at baseline and on days 3, 28, and 42. Results Mean IgE levels decreased by 96% ( P < .001) from baseline within 3 days in the omalizumab group. Baseline 30% ragweed-induced nasal volume response was decreased to 20.4% at 7 to 14 days ( P < .001) and 12.2% at 35 to 42 days ( P < .001) for the omalizumab group. There was a median decrease in basophil FcεRI expression of 73% ( P < .001) in the omalizumab group, with maximum inhibition occurring within 14 days of treatment. No significant changes in IgE levels, nasal allergen challenge responses, or basophil FcεRI expression were observed throughout the study in the placebo group. Conclusions Our study showed that the onset of action by omalizumab in blunting ragweed-induced nasal responses is within 2 weeks, and this response was associated with 2 putative mechanisms of action: decreased serum free IgE and decreased FcεRI receptor expression on immune effector cells.

Dermatitis atópica: características alergológicas y asociación a patología respiratoria

BackgroundAtopic dermatitis (AD) is a chronic inflammatory skin disease that frequently precedes the development of asthma or other respiratory allergies. The aim of this study was to review allergen sensitization, type of feeding in infancy, and development of asthma or rhinitis in a group of patients with AD MethodologyOne hundred children with AD were selected. All patients underwent skin prick and patch tests to foodstuffs and inhalant allergens, total and specific IgE determination, and oral challenge tests ResultsThe study included 57 boys and 43 girls. The mean age at consultation was 3.77 ± 2.81 years and mean age at onset of of AD was 1.09 ± 1.69 years. Twenty-eight percent of the children were exclusively sensitized to food allergens, 20 % to inhalant allergens and 22 % to both food and inhalant allergens. Mean serum IgE levels were higher in children sensitized to Dermatophagoides pteronyssinus (DPT) (346.86 ± 430.43 U/ml) than in non-sensitized children (78.24 ± 132.93 U/m) (p < 0.001). Total IgE levels were also higher in patients with respiratory symptoms (283.77 ± 336.53 U/ml) than in children without respiratory disease (124.62 ± 285.21 U/ml) (p = 0.021). Thirty-five percent of the children developed some kind of respiratory allergic disease (asthma and/or rhinitis) in a mean interval of 2.55 years after the onset of dermatitis. Of the children sensitized to inhalant allergens (DPT), 55.26 % developed respiratory symptoms compared with 22.58 % of the non-sensitized children (p < 0.001). The odds ratio of developing respiratory allergy if the patient showed sensitization to DPT was 4.235 (95 % CI 1.768-0.147, p = 0.002) ConclusionsChildren with AD that develops in the first year of life, associated with high IgE levels and early sensitization, independently of the kind of feeding, develop respiratory allergic disease more frequently than children without these factors

Regulation of TH1/TH2 Cytokine Production by Chungsim-Yeunja-Tang in Patients with Cerebral Infarction

Chungsim-Yeunja-Tang is a prescription for the Taeumin cerebral infarction (CI) patients according to Sasang constitutional philosophy. Taeumin patients with CI were treated with CY-Tang during the acute stage. Clinical signs of CI disappeared markedly in about 2 weeks after oral administration of CY-Tang in all patients. The mean interleukin (IL)-2 plasma levels were slightly lower in the patients with CI than in the normal groups, whereas the mean TNF-α, IL-4, IL-6, and IgE levels were significantly higher in the patients with CI. There were no significant differences in interferon-γ (IFN-γ) levels between the groups. Serum IFN-γ and IL-2 levels derived from T helper (Th) 1 cells were significantly elevated in the patients with CI by CY-Tang administration. Significant reduced plasma levels of IL-4 and IL-6 derived from Th2 cells and IgE were observed in the patients treated with CY-Tang. Plasma levels of TNF-α derived from Th1 significantly increased in the patients treated with CY-Tang. During the period of CY-Tang administration, there were no other adverse effects. The data indicate that CY-Tang has a good CI treatment effect, and that its action may be due to the regulation of cytokine production.

Yangkyuk-Sanhwa-Tang induces changes in serum cytokines and improves outcome in focal stroke patients

Yangkyuk-Sanhwa-Tang (YS-Tang), a specific prescription composed of nine herbal mixtures, has been developed as a formula for the Soyangin cerebral infarction (CI) patients according to Sasang constitutional philosophy. However, the mechanisms by which this formula affects CI remain unknown. This study revealed changes in cytokine production in the acute stage of Soyangin constitution CI patients after YS-Tang administration. Clinical signs (vertigo, headache and slurred speech) of CI disappeared significantly in about 2 weeks after oral administration of YS-Tang ( P<.05). The mean interleukin (IL)-2 plasma levels were lower by 15% in the patients with CI than in the normal groups, whereas the mean TNF-α, IL-4, IL-6 and IgE levels were significantly higher in the patients ( P<.01). There were no significant differences in interferon-γ (IFN-γ) levels between the groups. Serum IFN-γ and IL-2 levels were elevated significantly ( P<.01) in the patients with CI by YS-Tang administration. Significant reduced plasma levels ( P<.01) of TNF-α, IL-4, IL-6 and IgE were observed in the patients treated with YS-Tang. During the period of YS-Tang administration, there were no other adverse effects. The data indicate that YS-Tang has an enhancing effect on antiinflammatory cytokines and an inhibitory effect on inflammatory cytokines. These results may implicate a good CI treatment effect of YS-tang and that its action may be due to regulation of cytokine production.

Serum immunoglobulins and immunoglobulin G subclasses with recurrent wheezing.

In this study serum immunoglobulins (Ig) and IgG subclasses were measured in 42 patients (ranging 9 month-6 year) with recurrent wheezing and in 37 healthy children determined the relationship between serum Igs and recurrent wheezing. Patients were divided into two groups according to the age [9 month-2 year (n: 15), and 2-6 year (n: 27)]. In the patients placed in 9-24 month age group, serum IgG4 level was found to be lower than controls (p < 0.05). But there was not a significant difference in mean serum concentrations of total IgG, IgA, IgM, IgE, IgG1, IgG2 and IgG3 subclasses between the groups (P > 0.05). In the 25 month-6 year age group the mean IgE level was increased compared to the control while IgG3 and IgG4 levels were decreased (p < 0.05). On the other hand, in the 9-24 month age group there was no significant difference between the patients and controls for IgG subclasses deficiency (P > 0.05). However, significant difference in IgG subclasses deficiency was present between the patients and controls in the 25 month-6 year group (P < 0.001). In conclusion, our findings suggest that wheezing in childhood may be associated with low IgG3 and/or IgG4, and in older children high IgE level may be a part of pathogenetic mechanism in patients with recurrent wheezing.

Asthma and airway hyper-responsiveness in adults who required hospital admission for bronchiolitis in early childhood

Viral respiratory infections in infancy may contribute to the development of airway hyper-responsiveness (AHR) in childhood but their effects on respiratory function at the adult age are still uncertain. A group of 42 subjects aged 17–35 with a pediatrician-made diagnosis of severe bronchiolitis in infancy (Br) were compared for the presence of asthma and AHR to a control group (C) paired for age and gender, without evidence of lower respiratory disease in infancy. All had a respiratory and environmental questionnaire, allergy skin prick tests, blood eosinophil count, total serum IgE determination and measurements of expiratory flows and airway response to methacholine. In Br and C groups, respectively, 38 and 12% of subjects had a physician-made diagnosis of asthma, 26 and 7% used bronchodilators and 12 and 0% an inhaled corticosteroid; 71 and 67%, respectively, were atopic, 50 and 24% were smokers and 43 and 17% had a first-degree relative with asthma. Mean baseline FEV1and FEV1/FVC ratio were lower in the Br than in the C group, with 94/103% (P=0·002) and 80/87 (P<0·0001) of the predicted value, respectively. Geometric mean PC20methacholine was significantly lower in the Br than in the C group 3·9/20·3 mg ml−1(P<0·0001). Mean blood eosinophil count and serum IgE levels were similar in both groups (P>0·05).In conclusion, asthma and AHR were found more frequently in young adults with a past history of bronchiolitis, suggesting that this type of respiratory infection may contribute to altered pulmonary function in adulthood, although it may also represent an early manifestation of asthma. The influence of potential confounding factors, such as familial predisposition and exposure to cigarette smoke on the development of asthma and AHR in the Br group, cannot be excluded.

Regulatory Effect of Cytokine Production in Patients with Cerebral Infarction by Yulda-Hanso-Tang

Yulda-Hanso-Tang (YH-Tang) is a prescription for the Taeumin cerebral infarction (CI) patients according to Sasang constitution philosophy. Taeumin patients with CI were treated with YH-Tang during the acute stage. Clinical signs of CI disappeared markedly in about 2 weeks after oral administration of YH-Tang in all patients. The mean interleukin (IL)-2 serum levels were lower in the patients with CI than in the normal groups, whereas the mean IL-4, 1L-6 and IgE levels were significantly higher in the patients. There were no significant differences in interferon-y (IFN-γ) levels between the groups. Serum IFN-γ and IL-2 levels derived from T helper (Th)1 cells elevated significantly in the patients with CI by YH-Tang administration. Significant reduced serum levels of IL-4 and IL-6 derived from Th2 cells and IgE were observed in the patients treated with YH-Tang. During the period of YH-Tang administration, there were no other adverse effects. The data indicate that YH-Tang has a good CI treatment effect, and that its action may be due to regulation of cytokine production.

Hydroxychloroquine improves airflow and lowers circulating IgE levels in subjects with moderate symptomatic asthma

Background Although antiinflammatory therapy is accepted as the cornerstone of asthma treatment, available systemic immunosuppressive agents are not widely used because of justified concerns over potential toxicity. Hydroxychloroquine (HCQ) is a well-tolerated, safe immunomodulating drug, with proven efficacy in rheumatic diseases and known actions that suggest potential utility in the treatment of asthma. Objective: We sought to assess the effectiveness of HCQ in subjects with moderate symptomatic asthma. Methods: Symptomatic asthmatic subjects receiving stable doses of at least 6 puffs of inhaled corticosteroid per day with daily need for β 2-adrenergic agonists were studied. After baseline run-in, these subjects were randomized to 30 weeks of HCQ ( n = 8) or placebo ( n = 9). Objective measures included change from baseline mean FEV 1, morning and evening peak flows, β 2-agonist use, IgE level, and need for rescue cortico-steroids. Subjective symptom scores from bidaily diaries were also obtained. Results: In the treatment group, mean FEV 1 at the last 2 visits on therapy increased by 10.8% ( P < .05), morning peak flows rose 16.2% ( P < .03), evening peak flows rose 14.2% ( P < .04), and β 2-agonist use fell 18.6% ( P < .03). Mean IgE level declined 48% from 240 to 125 IU/mL ( P < .05). In the placebo group no significant change in these parameters occurred. Comparison of changes in these objective measures between the treatment and placebo groups failed to reach significance in the small population studied. Corticosteroid rescue interventions were required in 4 patients receiving placebo and 2 receiving HCQ. HCQ was well tolerated without notable side effects. Conclusions: Although the size of our sample population precludes definitive conclusions, these findings extend previous open-label observations. The late improvement in the HCQ group is consistent with its known slow onset of action. Further studies are warranted to confirm the antiasthmatic and antiallergic effects of HCQ and to investigate its potential as a disease-modifying agent. (J Allergy Clin Immunol 1998;102:198-203).

Allergic and immunologic profile of symptomatic Persian Gulf War veterans.

Persian Gulf War veterans have been enrolled in the Veterans Administration Persian Gulf Health Registry for evaluation of unexplained symptoms and illnesses. The allergy and immunology division at the West Los Angeles Veterans Administration Medical Center evaluated 20 consecutive symptomatic Persian Gulf War veterans. The purpose of this study was to examine the immunologic profiles of symptomatic Persian Gulf War Veterans. A detailed history was obtained that included duties/responsibilities, length of time in the Persian Gulf, location, and exposures during the Gulf War. A complete physical examination was performed, with extensive laboratory testing and immediate and delayed hypersensitivity skin testing. Data from these Persian Gulf War Veterans were compared with a control population consisting of 44 non-Persian Gulf War veterans enrolled in our allergy and immunology clinic. Presenting allergic symptoms, presence of atopy, and total serum IgE levels were compared. Persian Gulf study patients and registry patients had a broad spectrum of nonspecific symptoms as compared with allergy clinic control patients who had dermatologic and respiratory symptoms. Persian Gulf study patients with allergy symptoms had a higher mean IgE level (88.7 IU/mL) than Persian Gulf study patients without allergy symptoms (47.5 IU/mL). Persian Gulf study patients with positive skin tests had a higher mean IgE level (161.5 IU/mL) than Persian Gulf study patients with negative skin tests (22.3 IU/mL). Laboratory data showed no significant immune abnormalities. Our study showed that 20 Persian Gulf veterans with a multitude of nonspecific symptoms had no immune abnormality. Mean IgE levels and eosinophil counts correlated with atopic state and reported allergy symptoms.

Persistence of atopic effects on airway calibre and bronchial responsiveness in older adults.

the relationships between atopy and chronic airflow obstruction and bronchial hyperresponsiveness in adults are unclear. We measured airways calibre (FEV1), bronchial responsiveness, eosinophil count and total serum IgE in a random population sample of adults aged 45 years or older. Caucasian adults (n = 783) were selected from the practice lists of local general practitioners using random number tables. Responders to a postal questionnaire were invited to attend for venous blood sampling and methacholine challenge (Newcastle dosimeter method). the questionnaire response rate was 92.3% (723 subjects); 62.5% of subjects invited to attend did so. Attenders were slightly younger than the whole study population, but otherwise representative. Methacholine challenge was completed by 208 subjects. Geometric mean IgE level was higher in current smokers; both IgE and eosinophils were raised in subjects reporting asthma. Multiple regression showed a negative independent relationship between age- and sex-standardized eosinophils and baseline FEV1 and a positive relationship between standardized IgE score and level of bronchial responsiveness. Separate analysis of subjects aged <65 and > or =65 years showed that these relationships were only significant in older subjects. airways calibre and level of bronchial responsiveness are associated with measures of atopy in older adults. Atopy should not be overlooked as a factor in elderly patients with asthma or chronic airflow obstruction.

A placebo-controlled multicenter study of auranofin in the treatment of patients with corticosteroid-dependent asthma

BACKGROUND: Previous clinical studies have demonstrated that injectable gold salts and the oral gold compound, auranofin, possess significant steroid-sparing effects in the treatment of asthma. OBJECTIVES: The objectives of this investigation were to determine whether auranofin could reduce oral corticosteroid requirements and to evaluate the safety of auranofin in the treatment of chronic corticosteroid-dependent asthma. METHODS: Patients with asthma were eligible if they required at least 10 mg of prednisone per day for control and prevention of asthma exacerbations. Two hundred seventy-nine patients with chronic corticosteroid-dependent asthma (requiring ≥ 10 mg/day) were randomized to receive auranofin, 3 mg twice daily, or placebo during an 8-month clinical trial, which was divided into three phases including: a 4-week baseline period (phase I), a 6-month double-blind treatment and steroid reduction period (phase II), and a 4-week posttreatment observation period during which steroid and auranofin doses or placebo doses were maintained at levels achieved by the end of phase II (phase III). The primary efficacy variable was “therapeutic success” or reduction of daily corticosteroid use by 50% or more. RESULTS: The proportion of patients in the auranofin group achieving therapeutic success (41%) was significantly higher than that in the placebo group (27%) ( p = 0.01). This effect was greatest in patients requiring 10 to 19 mg of oral prednisone per day at baseline ( p < 0.001). In all treated patients, including those who did and did not complete the trial, significant reduction (≥50% of baseline) in oral corticosteroid dosage was achieved in the auranofin group (60%) compared with the placebo group (32%) ( p < 0.001). There were no significant differences between treatment groups in symptoms, concomitant medication use, or lung function. Mean serum total IgE levels decreased significantly from baseline in the auranofin group (-44.63 IU/ml) compared with the placebo group ( p = 0.001). Gastrointestinal and cutaneous adverse events were greater in the auranofin group. CONCLUSIONS: Auranofin demonstrated a steroid-sparing effect without concomitant worsening of symptoms or lung function and appeared to be more effective in patients dependent on 10 to 19 mg of prednisone per day. Therefore this study has demonstrated that auranofin is useful as a steroid-sparing agent in the treatment of chronic corticosteroid-dependent asthma. (J A LLERGY C LIN I MMUNOL 1996;98:317-24.)

Investigations on plasma levels of mast cell mediators in acute atopic dermatitis

Skin mast cells have been proposed to be involved in the pathogenesis of acute and chronic phases of atopic dermatitis (AD). The aim of the present study was to investigate the significance of different mast cell mediators during acute exacerbation of this frequent skin disease. Plasma levels from 19 patients with AD were screened for elevation of the mast cell-specific protease tryptase, the biogene amine histamine, and the arachidonic acid metabolite prostaglandin D 2. None of the patients showed elevated plasma levels of these three mediators, whereas the mean serum IgE level was strongly elevated. We conclude that the investigated mediators are either only active on the cutaneous level or that other mediators are responsible for the development of the acute eczematous and pruritic skin reactions. Alternatively, the assays could have been insufficiently sensitive since some studies have demonstrated increased plasma histamine levels, e.g. after food challenge of such patients.

Serum total IgE levels in a representative sample of a Greek population

The distribution of IgE in a large randomly stratified Greek population sample was determined in 1187 subjects (793 men and 394 women) aged between 20 and 60 years. Skin prick testing was performed and serum total IgE expressed in iu/ml was measured by Phadebas PRIST: the data are presented as the geometric mean. Subjects were classified as atopic (257 men, 118 women) and nonatopic (536 men, 276 women) according to the results of skin testing with various aeroallergens. At any age, atopic males (120.5 vs 38 iu/ml) and females (99.8 vs 29.3 iu/ml) had higher mean IgE levels, as compared to nonatopic subjects (P < 0.0001). In our adult nonatopic sample, IgE levels did not differ with age (P > 0.05). At any age, nonatopic males had higher (38 iu/ml) mean IgE levels than nonatopic females (29.3 iu/ml) (P < 0.05). The comparison of normal IgE values (nonatopic subjects) from this study with those reported by other investigators revealed that Greek adult males and females had higher IgE levels than populations from other nations. Our results represent the first report on reference values regarding serum total IgE in Greek adults.