Showing papers in "The Journal of Allergy and Clinical Immunology in 1997"

Relationship between food-specific IgE concentrations and the risk of positive food challenges in children and adolescents

Abstract: Background: The double-blind, placebo-controlled food challenge (DBPCFC) is the "gold standard" for diagnosis of food hypersensitivity. Skin prick tests and RASTs are sensitive indicators of food-specific IgE antibodies but poor predictors of clinical reactivity. Previous studies suggested that high concentrations of food-specific IgE antibody were predictive of food-induced clinical symptoms. Because the CAP System FEIA (Pharmacia Diagnostics, Uppsala, Sweden) provides a quantitative assessment of allergen-specific IgE antibody, this study was undertaken to determine the potential utility of the CAP System FEIA in diagnosis of IgE-mediated food hypersensitivity. Methods: Sera from 196 patients with food allergy were analyzed for specific IgE antibodies to egg, milk, peanut, soy, wheat, and fish by CAP System FEIA. Sera were randomly selected from 300 stored samples of children and adolescents who had been evaluated by history, skin prick tests, and DBPCFCs. The study population was highly atopic; all patients had atopic dermatitis, and approximately 50% had asthma and allergic rhinitis at the time of initial evaluation. The performance characteristics of the CAP System FEIA were compared with those of skin prick tests and the outcome of DBPCFCs or "convincing" histories of anaphylactic reactions. Results: The prevalence of specific food allergies in the study population varied from 22% for wheat to 73% for egg. Allergy to egg, milk, peanut, and soy accounted for 87% of confirmed reactions. The performance characteristics of skin prick tests and CAP System FEIA (egg, milk, peanut, fish) were comparable, with excellent sensitivity and negative predictive accuracy but poor specificity and positive predictive accuracy. The performance characteristics of the CAP System FEIA for soy and wheat were poor. For egg, milk, peanut, and fish allergy, diagnostic levels of IgE, which could predict clinical reactivity in this population with greater than 95% certainty, were identified: egg, 6 kilounits of allergen-specific IgE per liter (kU A /L); milk, 32 kU A /L; peanut, 15 kU A /L; and fish, 20 kU A /L. Conclusions: When compared with the outcome of DBPCFCs, results of CAP System FEIA are generally comparable to those of skin prick tests in predicting symptomatic food hypersensitivity. Furthermore, by measuring the concentrations of food-specific IgE antibodies with the CAP System FEIA, it is possible to identify a subset of patients who are highly likely (>95%) to experience clinical reactions to egg, milk, peanut, or fish. This could eliminate the need to perform DBPCFCs in a significant number of patients suspected of having IgE-mediated food allergy. (J Allergy Clin Immunol 1997;100:444-51.)

Probiotics: A novel approach in the management of food allergy ☆ ☆☆ ★ ★★

Abstract: Background: The gastrointestinal microflora is an important constituent of the gut mucosal defense barrier. We have previously shown that a human intestinal floral strain, Lactobacillus GG (ATCC 53103), promotes local antigen-specific immune responses (particularly in the IgA class), prevents permeability defects, and confers controlled antigen absorption. Objective: The aim of this study was to evaluate the clinical and immunologic effects of cow's milk elimination without ( n = 14) and with ( n = 13) the addition of Lactobacillus GG (5 × 10 8 colony-forming units/gm formula) in an extensively hydrolyzed whey formula in infants with atopic eczema and cow's milk allergy. The second part of the study involved 10 breast-fed infants who had atopic eczema and cow's milk allergy. In this group Lactobacillus GG was given to nursing mothers. Methods: The severity of atopic eczema was assessed by clinical scoring. The concentrations of fecal α 1 -antitrypsin, tumor necrosis factor-α, and eosinophil cationic protein were determined as markers of intestinal inflammation before and after dietary intervention. Results: The clinical score of atopic dermatitis improved significantly during the 1-month study period in infants treated with the extensively hydrolyzed whey formula fortified with Lactobacillus GG. The concentration of α 1 -antitrypsin decreased significantly in this group ( p = 0.03) but not in the group receiving the whey formula without Lactobacillus GG ( p = 0.68). In parallel, the median (lower quartile to upper quartile) concentration of fecal tumor necrosis factor-α decreased significantly in this group, from 709 pg/gm (91 to 1131 pg/gm) to 34 pg/gm (19 to 103 pg/gm) ( p = 0.003), but not in those receiving the extensively hydrolyzed whey formula only ( p = 0.38). The concentration of fecal eosinophil cationic protein remained unaltered during therapy. Conclusion: These results suggest that probiotic bacteria may promote endogenous barrier mechanisms in patients with atopic dermatitis and food allergy, and by alleviating intestinal inflammation, may act as a useful tool in the treatment of food allergy. (J Allergy Clin Immunol 1997;99:179-85.)

Indoor allergens and asthma : Report of the third international workshop

Abstract: In parallel with changes in lifestyle over the last 50 years (sedentary living in warm houses with extensive furnishing and low ventilation rates), there has been a progressive increase in the prevalence and morbidity of asthma in many parts of the world. The increase has been in perennial rather than seasonal asthma, and a large proportion of the patients are sensitized to one or more of the allergens found predominantly inside houses, that is, indoor allergens. The Third International Workshop on Indoor Allergens and Asthma was designed to discuss recent progress in basic and clinical research in this area, to formulate recommendations for allergen-specific management of asthma, and to consider future research directions. As with the two previous workshops, discussion topics included biology; allergen immunochemistry; molecular biology and immune response; epidemiology of asthma; and the role of allergen avoidance, a, 2 Because of dramatic progress in recent years, the Third International Workshop was expanded to cover not only house dust mite allergens but also allergens from cat, dog, and cockroach, for which immunochemical and epidemiologic data are available. Over the past 5 years there have been significant advances in several areas of research on indoor allergens, including: (1) cloning and expression of recombinant allergens, 3-7 (2) analysis of T-cell responses to indoor allergens, derivation of T-cell clones, and analysis of T-cell epitope specificity and cytokine profiles, s, 9 (3) investigation of the dose-response relationship between exposure to mite, cat, and cockroach allergens and sensitization, 1°-13 and (4) epidemiologic studies on indoor allergens as risk factors for the symptoms of asthma and bronchial hyperreactivity (BHR)? 4-17 Better definition of the allergens has made it possible to analyze their structure and biologic function and to define epitopes recognized by antibodies or T cells. Information obtained from those studies has provided exciting possibilities for developing new vaccines for safe and effective immunotherapy. 9, 18. 19 Studies of T-cell responses to dust mites have confirmed the dominance of T-helper cell (Tin) responses in allergic individuals.

Indoor allergen exposure is a risk factor for sensitization during the first three years of life.

Abstract: Background: The purpose of the study was to investigate the influence of environmental allergen exposure on allergic sensitization in infancy and early childhood. Methods: A cohort of 1314 newborns was recruited and followed up prospectively at the ages 12, 24, and 36 months. The levels of major mite (Der p 1 and Der f 1) and cat (Fel d 1) allergens were determined from domestic carpet dust samples by sandwich ELISA. Specific serum IgE antibodies to mite and cat allergens were determined by CAP fluoroimmunoassay (Pharmacia). Logistic regression was used to assess the effects of allergen exposure, age, family history, and cord blood IgE simultaneously on the risk of sensitization. Results: Children, who had been found to be sensitized at least once during the first 3 years of life, were found to be exposed to significantly higher house dust mite (median, 868 ng/gm vs 210 ng/gm; p =0.001) and cat (median, 150 ng/gm vs 64 ng/gm; p =0.011) allergen concentrations in domestic carpet dust compared with the group without sensitization. In homes with low (≤25th percentile) dust concentrations, the risk of sensitization to mite (1.6%) and cat (2.0%) is low, compared with 6.5% for mite and 6.3% for cat if the domestic exposure is above the 75th percentile. The dose-response relationships between allergen levels and sensitization indicate that the increase in sensitization risk at low allergen levels is more pronounced in cat allergy ( p =0.002) than in mite allergy ( p =0.026). In the group with a positive family history, lower mite and cat allergen concentrations are needed to achieve specific sensitization compared with the group with a negative family history. Conclusion: Our data indicate that avoidance measures in the domestic environment aimed at the primary prevention of allergen-driven sensitization should be introduced at the earliest possible stage, if possible during infancy. (J Allergy Clin Immunol 1997;99:763–9.)

Immunotherapy with a standardized Dermatophagoides pteronyssinus extract. VI. Specific immunotherapy prevents the onset of new sensitizations in children.

Abstract: Background: The natural history of allergic sensitization is complex and poorly understood. A prospective nonrandomized study was carried out in a population of asthmatic children younger than 6 years of age whose only allergic sensitivity was to house dust mites (HDMs). Objectives: The study was designed to determine whether specific immunotherapy (SIT) with standardized allergen extracts could prevent the development of new sensitizations over a 3-year follow-up survey. Methods: We studied 22 children monosensitized to HDM who were receiving SIT with standardized allergen extracts and 22 other age-matched control subjects who were monosensitized to HDM. The initial investigation included a full clinical history, skin tests with a panel of standardized allergens, and the measurement of allergen-specific IgE, depending on the results of skin tests. Children were followed up on an annual basis for 3 years, and the development of new sensitizations in each group was recorded. Results: Ten of 22 children monosensitized to HDM who were receiving SIT did not have new sensitivities compared with zero of 22 children in the control group ( p = 0.001, chi square test). Conclusions: This study suggests that SIT in children monosensitized to HDM alters the natural course of allergy in preventing the development of new sensitizations. (J Allergy Clin Immunol 1997;99:450-3.)

Treatment of anaphylactic sensitivity to peanuts by immunotherapy with injections of aqueous peanut extract

Abstract: Background: Immediate hypersensitivity to peanuts is a frequent cause of anaphylactic reactions and deaths in children and adults Currently, preventive treatment consists of avoidance, which is difficult because of the widespread and often disguised use of peanuts in the food industry Methos: Twelve patients with immediate hypersensitivity to ingestion of peanuts were recruited Half were treated with injections of peanut extract: a maintenance level of tolerance was first achieved by a rush protocol, then maintained with weekly injections for at least 1 year The other six were untreated control subjects All patients underwent double-blind, placebo-controlled, oral peanut challenges initially, after approximately 6 weeks, and after 1 year Results: All treated patients achieved the maintenance dose of 05 ml of 1:100 wt/vol peanut extract by the rush injection protocol All experienced increased tolerance to double-blind, placebo-controlled peanut challenge and decreased sensitivity on titrated skin prick testing with peanut extract, whereas the threshold to oral peanut challenge and cutaneous reactivity to peanut extract were unchanged in the untreated control subjects Systemic reactions were common in the treated group both during rush immunotherapy and with maintenance injections Only three patients remained tolerant of the full maintenance dose The increased tolerance to oral peanut challenge was maintained in the three subjects who received full maintenance doses, but there was partial ( n =2) or complete ( n =1) loss of protection in the patients who required dose reduction because of systemic reactions Conclusions: Injections of peanut extract increase the tolerance of patients with peanut allergy to oral ingestion of peanuts Injections result in repeated systemic reactions in most patients, even during maintenance injections For clinical application of this method of treatment, a modified peanut extract is needed

Inflammation of small airways in asthma

Abstract: This study was designed to examine the inflammatory process in the central and peripheral airways of surgically resected lungs from asthmatic and nonasthmatic subjects. Lung specimens were inflated with cryoprotective, rapidly frozen, and systematically sampled. Cryosections prepared from frozen tissue blocks were fixed in acetone/methanol and immunostained with monoclonal antibodies by using the alkaline phosphatase-anti-alkaline phosphatase technique to detect CD3 (T cells), major basic protein (total eosinophils), EG2 (activated eosinophils), anti-tryptase (mast cells), anti-elastase (neutrophils), and CD68 (macrophages). All airways from patients with asthma demonstrated a significant increase in the numbers of T cells and total and activated eosinophils compared with airways from nonasthmatic subjects (p < 0.001). In the patients with asthma, the numbers of activated eosinophils but not T cells were significantly greater in airways with an internal perimeter less than 2 mm compared with those with an internal perimeter greater than 2 mm (p < 0.05). There were also significantly higher numbers of major basic protein-positive eosinophils, when expressed as a fraction of the alveolar wall tissue, in patients with asthma compared with control subjects (p < 0.05). In asthmatic airways with an internal perimeter of more than 2 mm, there was a greater number of activated eosinophils in the tissue between the epithelium and the smooth muscle compared with the tissue between the smooth muscle layer and lung parenchyma (p < 0.05). In contrast, there was a greater number of total eosinophils in the outer airway layer compared with the inner airway layer (p < 0.05). These results show that there is a similar but more severe inflammatory process present in the peripheral compared with the central airways of patients with asthma, which is consistent with the fact that the smaller airways are a major site of obstruction in asthma.

Nasal obstruction as a risk factor for sleep-disordered breathing

Abstract: Nasal obstruction frequently has been associated with sleep-disordered breathing as a potential etiologic factor. Nasal obstruction results in pathologic changes in airflow velocity and resistance. Experimentally produced nasal obstruction increases resistance and leads to sleep-disordered breathing events, including apnea, hypopnea, and snoring. Clinical research examining the correlation between nasal obstruction and sleep-disordered breathing is limited, especially in regard to patients with conditions that increase nasal resistance, such as rhinitis and sinusitis. To further identify risk factors for sleep-disordered breathing, the role of chronic and acute nasal congestion was investigated in a population-based sample. Data on nasal congestion history and sleep problems were obtained by questionnaire (n = 4927) and by objective inlaboratory measurement (n = 911). Participants who often or almost always experienced nighttime symptoms of rhinitis (5 or more nights a month) were significantly (p < 0.0001) more likely to report habitual snoring (3 to 7 nights a week), chronic excessive daytime sleepiness, or chronic nonrestorative sleep than were those who rarely or never had symptoms. Habitual snorers had significantly (p < 0.02) lower air flow than nonsnorers, although a linear relation between decreased airflow and sleep-disordered breathing severity did not exist. Participants who reported nasal congestion due to allergy were 1.8 times more likely to have moderate to severe sleep-disordered breathing than were those without nasal congestion due to allergy. Men and women with nasal obstruction, especially chronic nighttime symptoms of rhinitis, are significantly more likely to be habitual snorers, and a proportion also may have frequent episodes of apnea and hypopnea, indicative of severe sleep-disordered breathing. Because allergic rhinitis is a common cause of nasal obstruction and it is a modifiable risk factor, further study of this association is warranted.

Sinusitis: Bench to bedside: Current findings, future directions

Abstract: Sinusitis, an inflammatory disease of the sinus, is one of the most commonly reported diseases in the United States, affecting an estimated 14% of the population. The prevalence of sinusitis is rising. Between 1990 and 1992, persons with sinusitis reported approximately 73 million restricted activity days—an increase from the 50 million restricted activity days reported between 1986 and 1988. Because critical questions remain unanswered about its cause, pathophysiology, and optimal treatment, sinusitis continues to generate significant health care costs and affects the quality of life of a large segment of the U.S. population. To identify critical directions for research on sinus disease, the American Academy of Allergy, Asthma and Immunology and the American Academy of Otolaryngology-Head and Neck Surgery Foundation, Inc., convened a meeting in January 1996 in collaboration with the National Institutes of Allergy and Infectious Disease. This document summarizes the proceedings of that meeting and presents what is intended to be the background for future investigation of the many unanswered questions related to sinusitis.

Antigen receptor engagement delivers a stop signal to migrating T lymphocytes.

Abstract: We investigated the role of the T cell antigen receptor (TcR) in control of T cell migration in an in vitro system. We used T cells from transgenic mice bearing a TcR for the lysozyme peptide 48–62 bound to I-Ak (3A9). T cells from the 3A9 TcR transgenic mice crawled on purified intercellular adhesion molecule-1 substrates, but strikingly, stopped upon interaction with the physiological ligand, i.e., the mouse I-Ak with covalently attached hen egg white lysozyme peptide residues 48–62 complex. TcR-triggered stopping was reversible by treatment with adhesion-strengthening phorbol esters. The microtubule organizing center of stopped cells was positioned adjacent to the site of stable cell anchorage. Direct conversion of lymphocyte function associated-1 to the high-affinity conformation with antibodies also stopped T cells in a similar manner to antigen. Thus, physiological TcR engagement triggers a stop signal through lymphocyte function associated-1. We propose that the stop signal is an early and essential event in T cell activation that also will play an important role in control of T cell migration. Antigen-specific T cells are enriched in the draining lymph nodes and antigen-containing tissue sites during an immune response (1–4). The mechanism of this enrichment is not known, but it has been proposed that extended interaction of antigen-specific T lymphocytes with antigen-presenting cells (APC) may account for this effect (5). Consistent with this proposal, the T cell must interact with the APC for several hours to initiate cytokine production and to enter the cell cycle (6–8). However, this requirement to remain in contact with the APC is contrary to the natural tendency of lymphocytes to actively crawl through lymphoid and nonlymphoid tissues (9–12). Thus, antigen-specific mechanisms to suppress locomotion and ensure extended contact of T cells and APC should exist. Here, we tested the hypothesis that antigen receptor engagement can alter T lymphocyte migration on a model cell surface containing purified adhesion molecules without and with purified antigenic major histocompatibility complex (MHC)-peptide complexes. Our results demonstrate that T cell antigen receptor (TcR) engagement by physiological ligands generates a long-lived stop signal. This result is discussed in terms of an integrated model for T cell migration and activation.

Elevated expression of messenger ribonucleic acid encoding IL-13 in the bronchial mucosa of atopic and nonatopic subjects with asthma

Abstract: Local secretion of cytokines by T cells within the bronchial mucosa, with consequent selective eosinophil influx, has been implicated in the pathogenesis of bronchial asthma. The cytokine IL-13 exhibits activities (selective eosinophil vascular adhesion by very late antigen-4/vascular cell adhesion molecule-1 interaction and promotion of IgE synthesis and "T112-type" T cell responses) that may be relevant to this process. We hypothesized that, compared with conditions in control subjects, elevated expression of messenger ribonucleic acid (mRNA) encoding IL-13 is a feature of the bronchial mucosa of both atopic (positive skin prick test result to at least one of a range of common aeroallergens) and nonatopic (negative skin prick test results and serum total IgE concentrations within the normal range) subjects with asthma. With use of a semiquantitative reverse transcriptase-polymerase chain reaction technique, we measured the quantities (relative to beta-actin) of IL-13 mRNA in bronchial mucosal biopsy specimens from atopic and nonatopic subjects with asthma and atopic and nonatopic control subjects. Biopsy specimens from the subjects with asthma, whether the subjects were atopic or nonatopic, had statistically equivalent quantities of IL-13 mRNA relative to beta-actin, and these quantities were significantly elevated compared with those in specimens from both the atopic and nonatopic control subjects (p < or = 0.02 in each case), in which the quantities of IL-13 mRNA relative to beta-actin were also statistically equivalent. The quantities of IL-13 mRNA reflected the numbers of EG2+ eosinophils per unit area of submucosa in the biopsy specimens as determined by immunohistochemistry, which were statistically equivalent in the atopic and nonatopic subjects with asthma and significantly elevated as compared with those in both the atopic and nonatopic control subjects without asthma (p < or = 0.007 in each case). Taking the subjects with asthma as a group, no correlations were observed between the quantities of IL-13 mRNA (relative to beta-actin) and several measures of disease severity. These data are consistent with the hypothesis that IL-13 plays a role in the pathogenesis of both atopic and nonatopic asthma, at least partly through promoting recruitment of eosinophils to the bronchial mucosa, although other factors may be more important in regulating the severity of the disease.

IL-5 synthesis is upregulated in human nasal polyp tissue

Abstract: Background: In most nasal polyps, tissue eosinophilia is a striking finding, the pathologic mechanism of which is not understood Objective: This study was performed to investigate a possibly distinct cytokine and chemokine pattern that could explain the characteristic tissue eosinophilia in nasal polyps Methods: Polyps from 23 patients and turbinate tissue from 18 control subjects were investigated The cytokine protein content (IL-1β, IL-3, IL-4, IL-5, IL-6, IL-8, IL-10, tumor necrosis factor-α, granulocyte-macrophage colony-stimulating factor, IL-1RA, RANTES, GRO-α) of tissue homogenates was measured by ELISA Immunohistochemistry was performed in selected samples to detect IL-5 + , major basic protein-positive, and EG2 + cells Results: IL-5 was detectable in only one sample of tissue from 18 control subjects but was found in 18 of 23 nasal polyps Immunohistochemistry revealed an abundant number of IL-5 + cells, of which 695% could be identified as eosinophils by morphology IL-6, IL-8, IL-10, tumor necrosis factor-α, GRO-α, and RANTES were detected in all specimens, without significant differences between groups ( p ≥005), whereas significantly higher concentrations of IL-1β and IL-1RA were found in turbinate mucosa ( p ≤005) IL-3 was not detectable; granulocyte-macrophage colony-stimulating factor could only occasionally be found Conclusion: This study indicates that IL-5 plays a key role in the pathophysiology of cosinophilic nasal polyps and may be produced by eosinophils

Allergic rhinitis and asthma: How important is the link?

Abstract: Dysfunction of the upper and lower airways frequently coexist, and they appear to share key elements of pathogenesis. Data from epidemiologic studies indicate that nasal symptoms are experienced by as many as 78% of patients with asthma and that asthma is experienced by as many as 38% of patients with allergic rhinitis. Studies also have identified a temporal relation between the onset of rhinitis and asthma, with rhinitis frequently preceding the development of asthma. Patients with allergic rhinitis and no clinical evidence of asthma commonly exhibit nonspecific bronchial hyperresponsiveness. The observation that management of allergic rhinitis also relieves symptoms of asthma has heightened interest in the link between these diseases. Intranasal corticosteroids can prevent increases in nonspecific bronchial reactivity and asthma symptoms associated with seasonal pollen exposure. Similarly, among patients with perennial rhinitis, daily asthma symptoms, exercise-induced bronchospasm, and bronchial responsiveness to methacholine are reduced after administration of intranasal corticosteroids. Antihistamines, with or without decongestants, reduce seasonal rhinitis symptoms, asthma symptoms, and objective measurements of pulmonary function among patients with rhinitis and asthma. The mechanisms that connect upper and lower airway dysfunction are under investigation. They include a nasal-bronchial reflex, mouth breathing caused by nasal obstruction, and pulmonary aspiration of nasal contents. Nasal allergen challenge results in increases in lower airway reactivity within 30 minutes, suggesting a neural reflex. Improvements in asthma associated with increased nasal breathing may be the result of superior humidification, warming of inspired air, and decreased inhalation of airborne allergens. Postnasal drainage of inflammatory cells during sleep also may affect lower airway responsiveness. A link between allergic rhinitis and asthma is evident from epidemiologic, pathophysiologic, and clinical studies. Future research, however, is needed to determine whether nasal therapy can alter the natural history of asthma. (J Allergy Clin Immunol 1997; 99:S781-6.)

Use of an anti-IgE humanized monoclonal antibody in ragweed-induced allergic rhinitis

Abstract: Background: Increased serum levels of antigen-specific IgE are often associated with allergic respiratory disorders. RhuMAb-E25, a recombinant humanized monoclonal antibody, decreases free serum IgE by forming biologically inactive immune complexes with free IgE. Objective: We hypothesized that rhuMAb-E25 would decrease total serum IgE and reduce symptoms. Methods: Two hundred forty subjects were enrolled into five groups to determine the safety, tolerance, and efficacy of repeated administration of rhuMAb-E25 in adults with ragweed-induced allergic rhinitis and to explore the pharmacodynamic relationship of rhuMAb-E25 and IgE. One hundred eighty-one subjects received an initial intravenous loading dose (day 0, 1 month before ragweed season), followed by administration of rhuMAb-E25 (in mg/kg body weight) of 0.15 mg/kg subcutaneously, 0.15 mg/kg intravenously, or 0.5 mg/kg intravenously on days 7, 14, 28, 42, 56, 70, and 84. A subcutaneous placebo group and an intravenous placebo group were included. The total evaluation time included the 84-day treatment period, followed by a 42-day observation period. Results: Adverse events were mild, and no differences were observed in the rates between the three active and two placebo treatment groups. Ragweed-specific IgE levels correlated with symptom scores. RhuMAb-E25 decreased serum free IgE levels in a dose- and baseline IgE–dependent fashion. However, only 11 subjects had IgE levels that were suppressed to undetectable levels (≤24 ng/ml), a sample too small to demonstrate significant differences and clinical efficacy. Thus the case for efficacy was not proven. Nonetheless, the study confirms that it is safe to repeatedly administer rhuMAb-E25 over a period of months. Conclusions: Because rhuMAb-E25 decreased serum free IgE in a dose-dependent fashion and because symptom scores correlated with antigen-specific IgE levels, the results suggest that if given in adequate doses, rhuMAb-E25 should be an effective therapy for allergic diseases. (J Allergy Clin Immunol 1997;100:110-21.)

An evaluation of the sensitivity of subjects with peanut allergy to very low doses of peanut protein: A randomized, double-blind, placebo-controlled food challenge study

Abstract: Background: The minimum dose of food protein to which subjects with food allergy have reacted in double-blind, placebo-controlled food challenges is between 50 and 100 mg. However, subjects with peanut allergy often report severe reactions after minimal contact with peanuts, even through intact skin. Objective: We sought to determine whether adults previously proven by challenge to be allergic to peanut react to very low doses of peanut protein. Methods: We used a randomized, double-blind, placebo-controlled food challenge of 14 subjects allergic to peanuts with doses of peanut ranging from 10 μg to 50 mg, administered in the form of a commercially available peanut flour. Results: One subject had a systemic reaction to 5 mg of peanut protein, and two subjects had mild objective reactions to 2 mg and 50 mg of peanut protein, respectively. Five subjects had mild subjective reactions (1 to 5 mg and 4 to 50 mg). All subjects with convincing objective reactions had short-lived subjective reactions to preceding doses, as low as 100 μg in two cases. Five subjects did not react to any dose up to 50 mg. Conclusion: Even in a group of well-characterized, highly sensitive subjects with peanut allergy, the threshold dose of peanut protein varies. As little as 100 μg of peanut protein provokes symptoms in some subjects with peanut allergy. (J Allergy Clin Immunol 1997;100:596-600.)

Sensitization to hen's egg at the age of twelve months is predictive for allergic sensitization to common indoor and outdoor allergens at the age of three years

Abstract: Background: Specific predictors for atopic sensitization in early infancy are prerequisites for preventive intervention studies. Objective: To identify predictors of allergic sensitization to common aeroallergens in infancy, 1314 children in five German cities were followed up from birth (1990) to the age of 3 years. Methods: BLOOD samples were taken from cord blood and at follow-up visits at the ages of 1, 2, and 3 years. Total serum IgE and specific IgE antibodies to common food and inhalant allergens were determined. Results: Among our study population, risk factors for sensitization to indoor and/or outdoor allergens at the age of 3 years were a positive family history, the presence of hen's egg–specific IgE antibodies (G0.35 kU/L), and increased log[total IgE] levels at the age of 12 months. Elevated cord blood IgE was not associated with sensitization to inhalant allergens at the age of 3 years. Egg-specific IgE greater than 2 kU/L in combination with a positive family history of atopy was a highly specific (specificity, 99%) and predictive (positive predictive value, 78%) marker for sensitization to inhalant allergens at 3 years of age. Conclusions: Hen's egg–specific IgE at the age of 12 months is a valuable marker for subsequent allergic sensitization to allergens that cause asthma, allergic rhinitis, and atopic dermatitis. (J Allergy Clin Immunol 1997;99:613-7.)

The distribution of total and specific serum IgE in the European Community Respiratory Health Survey

Abstract: Background: Variations in the prevalence of atopy could provide important clues to the etiology of atopy and asthma. Although estimates of prevalence are available from different studies, a lack of standardization makes comparisons difficult. Objective: This study was conducted to estimate the variation of geometric mean levels of serum IgE and the prevalence of specific IgE to common allergens between populations as part of the European Community Respiratory Health Survey (ECRHS), a multicenter survey of asthma and risk factors for asthma. Methods: Random samples of subjects living in 37 centers in 16 countries who had answered a questionnaire about their respiratory symptoms were invited for further assessment including total serum IgE and the presence of specific IgE against house dust mite (Dermatophagoides pteronyssinus) , timothy grass, cat, Cladosporium herbarum, and a local allergen. Sera were tested from 13,883 persons. Results: The estimated prevalence of atopy, defined as the presence of at least one positive specific IgE, ranged from 16% in Albacete (Spain) to 45% in Christchurch (New Zealand). The geometric mean total serum IgE varied from 13 kU/L in Reykjavik (Iceland) to 62 kU/L in Bordeaux (France). There was no relation between the geometric mean total serum IgE in a center and the prevalence of atopy. Conclusions: There are substantial variations in the prevalence of atopy and the level of serum IgE. These variations are independent of each other and likely to be largely environmental in origin. (J Allergy Clin Immunol 1997;99:314-22.)

A cost of illness study of allergic rhinitis in the United States

Abstract: Background: Allergic rhinitis is a common condition, but the burden of this condition on the national economy is not well understood. Objective: The purpose of this study was to estimate the national direct and indirect costs of allergic rhinitis. Methods: Data from the National Medical Expenditure Survey were used to provide estimatesof resource utilization, medical expenditures, and lost productivity. With the complex survey design, variance estimates were used to construct confidence intervals for cost estimates of resource utilization and lost productivity. Results: It is estimated that approximately 39 million persons in the United States experiencedallergic rhinitis in 1987. However, only 12.3% (4.8 million) sought medical treatment for allergic rhinitis. The total estimated cost of the condition, in 1994 dollars, was $1.23 billion (95% confidence interval, $846 million to $1.62 billion). Direct medical expenses accounted for 94% of total costs. Allergic rhinitis resulted in approximately 811,000 missed workdays, 824,000 missed school days, and 4,230,000 reduced activity days. Conclusion: Allergic rhinitis clearly creates a burden in terms of the number of persons affected, total expenditures, and lost productivity. It also appears that a relatively large proportion of persons with allergic rhinitis were not seeking medical treatment.

Poor Biologic Activity of Cross-Reactive IgE Directed to Carbohydrate Determinants of Glycoproteins

Abstract: Background: In our outpatient population, approximately one third of patients sensitized to grass pollen were found to have significant serum levels of anti-peanut IgE in the RAST, without positive peanut skin prick test (SPT) response and without peanut-related allergic symptoms. It was suggested earlier that poor biologic activity of IgE antibodies directed to cross-reactive carbohydrate determinants (CCD) of glycoproteins might explain these discrepancies. Objective: In this study we investigated the biologic activity of IgE directed to CCD. Methods: Sera of 32 patients allergic to grass pollen with significant levels of anti-peanut IgE, a negative response on peanut SPT, and no symptoms of peanut allergy were tested for the presence of anti-CCD IgE. Eleven of these patients with greater than 3.0 IU/ml anti-peanut IgE (patients 1 to 11) were selected together with four control patients allergic to peanut, on the basis of a positive response on peanut SPT and a history of peanut allergy (patients 12 to 15). Inhibition of the peanut RAST was performed by using proteinase K–treated grass pollen extract as a CCD source. Basophil histamine release assays (BHRAs) were performed with peanut extract and the isolated peanut major allergens Ara h 1 and Ara h 2. In addition, intracutaneous tests with peanut extract were performed. Results: In 29 (91%) of 32 patients with discrepant peanut RAST and SPT responses, anti-CCD IgE (≥0.1 IU/ml) was detected. In patients 1 to 11 almost complete inhibition of the peanut RAST with CCD was found (94.3% ± 5.5%; mean ± SD). In contrast, in the patients allergic to peanut only partial inhibition (59%) was found in one subject ( p = 0.002, Mann-Whitney test). In the BHRAs and the intracutaneous tests of patients with discrepant peanut RAST and SPT results, reactivity was found only at high concentrations of peanut allergens. When related to specific IgE levels, reactivity to peanut allergens in the BHRAs of these patients was found to be at least a factor of 1000 less when compared with reactivity to control inhalant allergens. Conclusion: We conclude that cross-reactive IgE directed to carbohydrate determinants of glycoproteins, as found in grass pollen–sensitized patients, has poor biologic activity. It can therefore cause positive RAST results without apparent clinical significance. (J Allergy Clin Immunol 1997;100:327-34.)

Prevalence of allergic rhinitis in the United States

Abstract: The study objective was to examine the current national prevalence of allergic rhinitis by gender, age, geographic region, population density (urban/rural), and household income. A self-administered questionnaire was sent to 15,000 households representative of the U.S. population in respect to these factors. The household member who knew the most about the family's health status and health history in the previous 12 months was asked to estimate the number of days during which household members had experienced sneezing, runny nose, stuffy nose or head, itchy eyes, or watery eyes. They were also asked about physician diagnosis of hay fever, rhinitis, persistent stuffy nose or head, or allergies involving the eyes, nose, or throat. The 9946 households responding (66.3%) represented 22,285 persons, 8394 of whom had experienced the symptoms described. In a follow-up questionnaire sent to a balanced sample of 1450 responders (>90% white, slightly more females than males), subjects were asked to indicate which of the following best described their symptoms: a common cold; a seasonal allergy (i.e., hay fever); an allergy I have all the time; an allergy only when exposed to triggers (i.e., dust, pollution); or sinus problems. Of the 1065 subjects (73.4%) responding, 31.5% reported ≥7 days of nasal/ocular symptoms, and 17.7% reported ≥31 days of symptoms. Physician-diagnosed hay fever was reported by 8.2% and allergic rhinitis (seasonal plus perennial) by 14.2%. Prevalence was highest among those age 18 to 34 years and 35 to 49 years, decreasing after age 50 years. No major trends were evident with regard to other variables studied. Extrapolation based on 1993 census data suggests that at least 35.9 million persons have symptoms associated with allergic rhinitis and up to 79.5 million persons experience ≥7 days of nasal/ocular symptoms yearly.

Allergenic activity of heated and ovomucoid-depleted egg white.

Abstract: Background: No egg white products have been clearly proven to be hypoallergenic. The role of egg white proteins in allergic reactions to eggs is still debatable. Objective: This study was designed to determine the importance of ovomucoid, an egg white protein, in the development of allergies to egg white. Methods: We performed a double-blind, placebo-controlled food challenge in subjects with high levels of IgE antibodies for egg white to compare the allergenicities of heated and ovomucoid-depleted egg white, freeze-dried egg white, and heated egg white. Levels of IgE antibodies for egg white, ovomucoid, ovalbumin, ovotransferrin, and lysozyme were measured in serum by RAST. Results: Twenty-one of 38 subjects with positive challenge responses to freeze-dried egg white had negative challenge responses to heated egg white, whereas 16 of 17 subjects (94.1%) with positive responses to heated egg white did not respond to the heated and ovomucoid-depleted egg white challenge. The subjects with positive challenge responses to freeze-dried egg white tended to have higher IgE antibody values to ovomucoid than those with negative responses. IgE antibody levels to ovomucoid were significantly higher in subjects with positive responses to a challenge with heated egg white than in those with no response. There were no significant differences in the levels of IgE antibodies to the other proteins, except ovomucoid, in the negative-response and positive-response groups in challenge tests with freeze-dried and heated egg white. Conclusion: The heated and ovomucoid-depleted egg white preparation was less allergenic than heated or freeze-dried preparations. Ovomucoid has a more important role in the pathogenesis of allergic reactions to egg white than other proteins in egg white. (J Allergy Clin Immunol 1997;100:171-6.)

Pathogenesis of allergic rhinitis

Abstract: Allergic rhinitis is an increasing problem for which new and exciting therapies are being developed. These can be understood through an appreciation of the newer concepts of pathogenesis of allergic rhinitis. Allergen induces Th2 lymphocyte proliferation in persons with allergies with the release of their characteristic combination of cytokines including IL-3, IL-4, IL-5, IL-9, IL-10, and IL-13. These substances promote IgE and mast cell production. Mucosal mast cells that produce IL-4, IL-5, IL-6, and tryptase proliferate in the allergic epithelium. Inflammatory mediators and cytokines upregulate endothelial cell adhesion markers, such as vascular cell adhesion molecule-1. Chemoattractants, including eotaxin, IL-5, and RANTES, lead to characteristic infiltration by eosinophils, basophils, Th2 lymphocytes, and mast cells in chronic allergic rhinitis. As our understanding of the basic pathophysiologic features of allergic rhinitis continues to increase, the development of new diagnostic and treatment strategies may allow more effective modulation of the immune system, the atopic disease process, and the associated morbidity. (J Allergy Clin Immunol 1997;99:S763-72.)

Nasal nitric oxide is increased in patients with asthma and allergic rhinitis and may be modulated by nasal glucocorticoids

Abstract: Nitric oxide (NO) is produced in large amounts in the noses of normal individuals. We have measured NO by chemiluminescence in the noses and exhaled air of subjects with symptomatic allergic rhinitis, some of whom had concomitant asthma, during the pollen season and compared this with values measured in normal subjects and in patients treated with nasal and/or inhaled glucocorticoids. We found that nasal levels of NO were significantly ( p n =12) compared with normal individuals (996±39 ppb, n =46) or subjects treated with nasal steroids (681±34 ppb, n =10), whereas exhaled NO in patients with untreated rhinitis was similar to that in normal subjects (10±2 ppb vs 7±0.6 ppb, respectively). In five subjects who were nasally challenged with allergen, there was a significant decrease in nasal NO 1 hour after challenge, and this was significantly correlated with increased rhinitis symptoms. In patients with rhinitis and concomitant asthma, nasal NO was also significantly elevated (1441±76 ppb, n =16) but not when they were treated with nasal or inhaled steroids; whereas exhaled NO was elevated in untreated patients and in patients treated with nasal, but not inhaled, steroids. Our data suggest that the increase in exhaled NO in patients with allergic rhinitis is likely to be due to increased local production, caused by long-term exposure to allergen, which is suppressed by locally administered steroids. Measurement of nasal NO may be useful to study the inflammatory response in rhinitis and its response to antiinflammatory treatments.

Measuring airway inflammation in asthma: eosinophils and eosinophilic cationic protein in induced sputum compared with peripheral blood.

Abstract: Background: Airway eosinophilic inflammation is a characteristic feature of asthma. This can be assessed directly by measurement of eosinophils and eosinophilic cationic protein (ECP) in sputum or indirectly by measurement of the same markers in blood. We investigated the performance of these markers of airway eosinophilic inflammation in a population of patients with asthma compared with control subjects and the extent to which the markers differed. Methods: In a cross-sectional study, subject characteristics were documented on day 1 and induced sputum and blood samples were obtained on day 2. Nineteen patients with asthma and 20 control subjects (10 heathy subjects and 10 smokers with nonobstructive bronchitis) were consecutively enrolled in the study. Sputum (selected from saliva) and blood samples were processed by persons blind to the clinical details. Results are presented as median values (minimum-maximum); differences were measured by Mann-Whitney U test. The accuracy of the tests (sensitivity and specificity) was measured by plotting the data in receiver-operating characteristic (ROC) curves and comparing the areas under the curve for each marker. Results: Patients with asthma in comparison with control subjects had a higher proportion of sputum eosinophils (5.2% [0.2% to 93%] vs 0.3% [0% to 1.7%], p 6 /L [144.0 to 1520.0 × 10 6 /L] vs 155.0 × 10 6 /L [34.0 to 426.0 × 10 6 /L], p = 0.003), and higher levels of ECP in sputum (1040.0 μg/L [76.8 to 32,000.0 μg/L] vs 455.3 μg/L [54.4 to 1280.0 μg/L], p = 0.001) but not in serum (25.0 μg/L [5.6 to 52.4 μg/L] vs 16.5 μg/L [3.3 to 36.0 μg/L], p = 0.08). Markers of airway inflammation in induced sputum and blood samples were correlated with clinical and physiologic variables. The area under the ROC curve showed that eosinophils in sputum (0.90) are significantly more accurate markers than blood eosinophils (0.72) and serum ECP (0.67) ( p = 0.02). Although the area under the ROC curve for sputum ECP was greater than those for blood eosinophils and serum ECP, the differences could have occurred by chance ( p ≥ 0.1). Conclusion: We conclude that the proportion of eosinophils in sputum is a more accurate marker of asthmatic airway inflammation than the proportions of blood eosinophils or serum ECP. (J Allergy Clin Immunol 1997;99:539-44.)

Increases in IL-12 messenger RNA+ cells accompany inhibition of allergen-induced late skin responses after successful grass pollen immunotherapy

Abstract: IL-12, a novel cytokine produced by tissue macrophages and B lymphocytes, stimulates proliferation of T h 1 -type T lymphocytes. We recently showed that in patients with summer hay fever, immunotherapy was effective and was associated with inhibition of allergen-induced late skin responses and increases in local interferon-γ messenger RNA-positive cells. In this study 10 patients were reassessed after 4 years of immunotherapy and compared with 10 untreated patients with hay fever. Intradermal grass pollen challenge was performed, the late response was measured, and biopsies were performed at 24 hours. In situ hybridization of biopsy sections was performed by using a riboprobe coding for IL-12 mRNA. When immunotherapy and control subjects were compared, there was a marked reduction in the size of the late skin response ( p = 0.0001). Significant increases in allergen-induced IL-12 mRNA+ cells in cutaneous biopsy specimens occurred only in the immunotherapy-treated group (all 10 patients, p = 0.002). At allergen-challenged sites, IL-12+ cells correlated positively with interferon-γ+ cells ( r = 0.64, p r = -0.67, p < 0.05). The principal cell source (55% to 80%) of IL-12 message was the tissue macrophage (CD68+ cells). We suggest that IL-12 may promote T h 1 responses and inhibit late-phase responses after successful immunotherapy. (J Allergy Clin Immunol 1997;99:254-60.)

Assessment of autoimmunity in patients with chronic urticaria

Abstract: Background: The etiology of chronic urticaria is unknown, and an exogenous allergen cannot be identified as the cause in the vast majority of subjects. Thus the concept has evolved that it might be autoimmune. Objective: We have prospectively assessed sera obtained from 50 consecutive patients with chronic urticaria for the presence of autoantibodies that could be pathogenic. Methods: We tested sera for their ability to release histamine from human basophils and to activate rat basophil leukemia cells that were transfected with the α subunit of the IgE receptor. We also tested selected sera for anti-IgE antibodies and for IgG anti-FcϵRIα by Western blot. Results: Sera from 38 of 50 patients with chronic urticaria released β-hexosaminidase from transfected rat basophil leukemia cells, whereas only one of 20 control sera did so ( p p Conclusion: A large fraction of patients with chronic urticaria have antibody directed to FcϵRIα that is functional (60%). A smaller number have IgG anti-IgE (10%). A third group may also have circulating factors capable of activating basophils or mast cells of which the identity is unknown. Thus chronic urticaria may be autoimmune in origin. (J Allergy Clin Immunol 1997;99:461-5.)

Overview of comorbid associations of allergic rhinitis

Abstract: Allergic rhinitis affects approximately 20% of the U.S. population. An association between allergic rhinitis and conditions including asthma, sinusitis, otitis media, nasal polyposis, respiratory infections, and even orthodontic malocclusions has been observed. Clinical research has identified shared pathogenic mechanisms, epidemiologic correlations, and findings from allergy testing to indicate that these conditions represent long-term physical consequences in allergic individuals. The positive response of patients afflicted with these conditions to antiallergic treatment further enhances the association between allergic rhinitis and other airway diseases. The use of nasal corticosteroids in patients with rhinitis and asthma reduces not only rhinitis symptoms but also asthma symptoms and airway reactivity to methacholine challenge. Similarly, antihistamines, with or without decongestants, result in improvement of objective measurements of pulmonary function. In the treatment of acute sinusitis, the combination of an intranasal corticosteroid and an antibiotic provides greater benefit than an antibiotic alone. Treatment strategies for allergic rhinitis should be directed at controlling the symptoms of allergic rhinitis and reducing the development of physical complications in susceptible persons. Three techniques for the treatment of allergic rhinitis are used, including avoidance of offending allergens, selection of appropriate pharmaceuticals, and allergy immunotherapy. Appropriate treatment may spare some patients of related airway diseases and may also reduce the overall cost of care. The broadened scope of allergic rhinitis and increased prevalence of IgE-mediated diseases have heightened awareness regarding the profound consequences of allergic rhinitis and the importance of effective treatment.

Human CD4+ T cell clones produce and release nerve growth factor and express high-affinity nerve growth factor receptors

Abstract: Background: Increasing evidence shows that nerve growth factor (NGF) plays a role in the complex and fascinating linkage between the nervous and the immune systems due to its ability to modulate functions of several inflammatory cells. Objective: To investigate NGF receptor expression and NGF production and release by human CD4+ cells clones, which have primary relevance in modulating inflammatory events through their different subsets of functional phenotypes. Methods: The expression of NGF and a transmembrane tyrosine kinase (TrkA) was evaluated by immunohistochemistry and flow cytometry analysis in five T H 0 , six T H 1 , and five T H 2 cell clones derived from human circulating mononuclear blood cells. Moreover, the amount of NGF protein was assessed by measuring the NGF levels in culture supernatants of the T cell clones before stimulation and 48 hours after phytohemagglutinin (PHA) activation by use of an immunoenzymatic assay. Results: Our data have shown that in unstimulated conditions, human CD4+ T cell clones express both immunoreactivity for NGF and the TrkA NGF receptor irrespective of their cytokine profile. Moreover, T H 1 and T H 2 clones, but not T H 0 clones, secrete NGF in basal conditions. PHA activation induces NGF secretion in T H 0 clones and a significant increase of NGF levels in T H 2 ( p < 0.05), but not in T H 1 culture supernatants. Conclusions: Results obtained represent the first evidence of TrkA expression and NGF production and release in human CD4+ cell clones and suggest a possible functional role of NGF in modulating the immune and inflammatory network. (J Allergy Clin Immunol 1997;100:408-14.)