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Background: Investigations at the Danish Anesthesia Allergy Centre have included testing for allergy to chlorhexidine since 1999., Objective: To investigate whether measurement of IgE and histamine release confirm an IgE-mediated mechanism for chlorhexidine allergy., Methods: Twenty-two patients with clinical history suggestive of chlorhexidine allergy were included. Skin tests with chlorhexidine and tryptase measurements were performed during initial investigations. Sera were analyzed retrospectively for IgE and histamine release (passive sensitization) to chlorhexidine., Results: Twelve patients were skin test positive and 10 were skin test negative. Of the skin test-positive patients, 11 of 12 had IgE to chlorhexidine and 7 of 11 had a positive histamine release test. None of the skin test-negative patients had specific IgE or positive histamine release to chlorhexidine. Skin test-positive patients had higher median age (64 vs 49 y) and were mainly male (11/12 vs 6/10). In both groups, 8 patients had hypotension, but bronchospasm mainly appeared in skin test-negative patients (1/12 vs 6/10). Reactions occurred more often during urologic surgery in skin test-positive patients (5/12 vs 0/10). Baseline tryptase was higher in skin test-positive patients (median, 11.5 vs 3.7 microg/L), and 6 of 7 patients had elevated IgE to chlorhexidine in serum at the time of reaction., Conclusion: This study confirms that chlorhexidine allergy is IgE-mediated and that measurement of specific IgE and histamine release are good adjuncts to skin testing in patients with clinical history suggesting chlorhexidine allergy., Clinical Implications: IgE and histamine release can be used to support the diagnosis of allergy to chlorhexidine.

Background: Contradictory results have been found when analyzing the IgE cross-reactivity among pyroglyphid mites and storage mites, as well as the role of these as true sensitizing agents., Objective: We sought to study the prevalence of sensitization to Glycyphagus domesticus in patients naturally exposed to this mite together with the more ubiquitous Dermatophagoides pteronyssinus and the IgE cross-reactivity between them., Methods: Mite species present in house dust samples of consecutive patients with mite allergy from Huelva (southwest Spain) were determined by means of light microscopy. Clinical sensitization was assessed by using skin prick and conjunctival provocation tests. Cross-reactivity at the IgE level was studied by using serum IgE determination and inhibition of RAST, IgE immunoblotting, and mite group 2 immunoassays., Results: After D pteronyssinus, which is present in about 95% of house dust samples, G domesticus was the most important mite and present in about 50% of the samples. Tyrophagus putrescentiae and Lepidoglyphus destructor were detected in third and fourth place, respectively. About half of the patients with G domesticus at home were sensitized to this mite. A low IgE cross-reactivity was observed between D pteronyssinus and G domesticus, but an important IgE cross-reactivity was detected among glycyphagid mites at the level of group 2 allergens., Conclusion: Glycyphagid mites can act as primary sensitizing agents independently of pyroglyphid mites in a subset of patients naturally exposed to them., Clinical Implications: The inclusion of glycyphagid mite extracts in the diagnostic battery in areas with adequate mite growing conditions is important to ensure proper diagnosis.

Background: There is evidence that CD4(+)CD25(high) T-regulatory cells are important for establishing tolerance to allergens, but information in children is limited., Objective: To test the hypothesis that greater numbers and function of CD4(+)CD25(high) T cells are associated with a reduced risk of childhood allergies and wheezing., Methods: A cohort of 151 six-year-old children from atopic families was analyzed for peripheral blood CD4(+)CD25(high) and CD4(+)CD25(int) T cells by flow cytometry and for clinical and immunologic correlates of atopy. The associations between these variables were assessed by regression analysis., Results: Factors positively associated with % CD4(+)CD25(high)/CD4 T cells were male sex, number of positive allergen-specific IgE tests, total IgE, season, and 1-month average total pollen count preceding blood draw. The percentage of CD4(+)CD25(high)/total CD4 T cells did not correlate with induced cytokine production, and correlated negatively with suppressive capacity of CD4(+)CD25(+) T cells (r = -0.45; P = .034). The percentage of CD4(+)CD25(int)/CD4 T cells was 54% higher in pollen-sensitized children compared with nonsensitized children in spring (P = .023 for interaction), and correlated positively with IL-5, IL-10, and IL-13 (P < or = .001 for all)., Conclusion: Our findings suggest that blood CD4(+)CD25(high) cells are a mixture of activated and regulatory T cells, and that these cells could be seasonally regulated by environmental factors such as pollen exposure., Clinical Implications: Seasonal increases in CD4CD25(high) expression in children with allergy may represent systemic immune activation caused by pollen exposures.

Background: Epidemiologic data on allergic rhinitis and asthma are frequently based on self-reported symptoms., Objective: This cross-sectional study examined the relationship between self-reported symptoms and histories of allergic rhinitis or asthma and a marker of allergic sensitization, allergen-specific IgE., Methods: We surveyed 702 pregnant women in Michigan. Blood samples were analyzed for specific IgE to 9 allergens: dust mites (Dermatophagoides farinae and Dermatophagoides pteronyssinus), cat, dog, cockroach, ragweed, timothy grass, egg, and Alternaria alternata. Seratopy was defined as a specific IgE greater than or equal to 0.35 kU/L to any allergen., Results: Seroatopy was found in 66.7% of those with hay fever symptoms, 68.3% with a physician's diagnosis of asthma, and 72.1% of those with both conditions. These results differed significantly from asymptomatic subjects, where 49.8% of patients without hay fever and 50.4% without asthma were seroatopic. Race and education did not modify the relationships. Symptoms related to specific exposures were modest predictors of positive specific IgE to related allergens (positive predictive values from 26.5% to 50.3%)., Conclusion: Self-reported symptoms of allergic rhinitis or asthma were significantly associated with allergic sensitization, but the odds ratios were of relatively low magnitude for this historical information to be considered evidence of current allergic sensitization. A 66% to 68% probability existed that those with symptoms of allergic rhinitis or asthma would have a positive specific IgE test., Clinical Implications: Self-reported histories of hay fever or asthma alone are only modest predictors of allergic sensitization. When knowledge of allergic sensitization is important, information beyond self-reported symptoms is necessary.

Background: Staphylococcus aureus-secreted enterotoxins (SEs) may be involved in the pathophysiology of atopic diseases., Objective: We investigated the role of SEs in allergic diseases during early childhood (using the mixture of SE-specific IgEs [SE-mix] as a marker)., Methods: Children (N = 510) were followed from birth to age 5 years (repeated questionnaires, IgE to inhalant and food allergens, lung function [spirometry, plethysmography], airway reactivity [dry air challenge]). We measured SE-mix specific IgE (SE-A, SE-C, toxic shock syndrome toxin 1) by using fluorescence immunoassay., Results: We found no association between rhinitis and SE-mix sensitization. Children with eczema were more frequently SE-mix-sensitized than children without (17.4% vs 8.3%; P = .02). SE-mix sensitization rate increased significantly with increasing eczema severity (no eczema, mild, moderate/severe: 8.3%, 14.8%, 42.9%; P = .003) and remained independently associated with eczema in a multivariate model adjusting for total IgE (adjusted odds ratio, 2.19; 95% CI, 1.05-4.56; P = .04). SE-mix sensitization was associated with current wheeze in the univariate but not the multivariate model. Among wheeze phenotypes, persistent wheezers were most commonly sensitized to SE-mix (never, transient, late-onset, persistent: 8.5%, 3.8%, 7.7%, 17.6%; P = .05). Among wheezers, those SE-mix-sensitized had significantly higher airway reactivity compared with those nonsensitized (mean FEV(1) change, mL [95% CI]: -59 [-121, 3] vs 19 [-10.2, 48.9]; P = .04), with little difference after adjusting for atopy., Conclusion: We found differences in SE-mix IgE antibodies between healthy 5-year-old children and children with eczema and wheeze. The proportion of patients sensitized to SE-mix increases with increasing disease severity., Clinical Implications: Staphylococcal enterotoxins are potential modifiers of childhood wheeze and eczema.

Background: Allergens from cat are among the most potent elicitors of allergic disease. Four cat allergens have been identified; however, evidence indicates the existence of additional allergens., Objective: In this study, we evaluated IgE sensitization to IgA from cat., Methods: Sera from cat-sensitized patients (n = 81) were analyzed for IgE antibodies to purified cat IgA in the Pharmacia CAP System. Indirect ELISA was performed with cat IgA, cat IgM, and deglycosylated cat IgA. Competitive inhibition ELISA was performed with cat IgA, cat IgM, calf intestine alkaline phosphatase (CIP), and cat serum albumin on solid phase bound cat IgA. IgE reactivity was also evaluated on membrane blotted cat IgA., Results: Thirty-eight percent (31/81) of the cat-sensitized sera were ImmunoCAP-positive to cat IgA. Indirect ELISA demonstrated a high correlation between IgE reactivity to cat IgA and cat IgM (r = 0.94; P < .001). Very low responses were observed to deglycosylated IgA. Strong inhibition of cat IgA was observed in all sera after preincubation with cat IgA and cat IgM. Inhibition was also observed in most sera after preincubation with CIP. Immunoblotting demonstrated that the IgE reactivity was mainly directed to the heavy chain of IgA., Conclusion: This study has revealed a new allergen, cat IgA, containing a novel group of cross-reactive epitopes depending on carbohydrates also present on IgM and partially on CIP., Clinical Implications: This new group of cross-reactive carbohydrate IgE epitopes should be taken into consideration when diagnosing patients with suspected animal allergy.

Background: Eosinophilic esophagitis (EE) is a gastrointestinal disorder that is increasingly diagnosed in pediatric patients., Objective: We aimed to define, in pediatric patients with EE, their demographic and atopic characteristics, the histopathology of all segments of the gastrointestinal tract, and the effect of therapeutic interventions on the natural history., Methods: We conducted a retrospective analysis of a database of pediatric patients with EE followed over a period of 8 years., Results: In 89 pediatric patients with EE, male sex (78.6%), white race (94.4%), young age at diagnosis, mean +/- SD, 6.2 +/- 4.8 years, and atopy with sensitization to environmental and food allergens in 79% and 75%, respectively, were prevalent. Patients had EE of the proximal and distal esophagus, and 77% had in addition either mucosal eosinophilia or noneosinophilic histopathology in the stomach, duodenum, and colon. EE was chronic, with a duration of mean +/- SD, 0.91 +/- 0.84 years, until first resolution, and was recurrent; of 66% of the patients who had resolution, 79% later relapsed., Conclusion: Eosinophilic esophagitis in the pediatric population is a chronic and relapsing condition, associated with atopy and sometimes with subsequent histopathology in segments of the gastrointestinal tract other than the esophagus., Clinical Implications: Physicians evaluating pediatric patients with chronic gastrointestinal symptoms should consider the diagnosis of EE, particularly in young white male patients with atopy. Once diagnosed and treated, the physicians should follow the patients over a period of several years because the course of the disease is protracted, other gastrointestinal segments may be affected, and relapses are common.

Background: Children with severe asthma have persistent symptoms despite treatment with inhaled corticosteroids (ICSs). The differentiating features of severe asthma in children are poorly defined., Objective: To identify features of severe versus mild-to-moderate asthma in school-age children using noninvasive assessments of lung function, atopy, and airway inflammation., Methods: A total of 75 children (median age, 10 years) with asthma underwent baseline characterization including spirometry and lung volume testing, methacholine bronchoprovocation, allergy evaluation, and offline measurement of exhaled nitric oxide (F(ENO)). Twenty-eight were followed longitudinally over 6 months. Participants were assigned to the severe asthma subgroup if they required high-dose ICS plus 2 or more minor criteria., Results: Children with severe versus mild-to-moderate asthma had more symptoms, greater airway obstruction, more gas trapping, and increased bronchial responsiveness to methacholine. Subjects with severe asthma also had higher concentrations of F(ENO) and significantly greater sensitization to aeroallergens. With long-term study, both the reduction in FEV(1) and increase in F(ENO) persisted in the severe versus mild-to-moderate group. Furthermore, despite adjustments in ICS doses, the frequency of exacerbations was significantly higher in subjects with severe (83%) versus mild-to-moderate asthma (43%)., Conclusion: Severe asthma in childhood is characterized by poor symptom control despite high-dose ICS treatment and can be differentiated from mild-to-moderate asthma by measurement of lung function and F(ENO)., Clinical Implications: Clinicians should suspect severe asthma in children with poor response to ICS, airway obstruction, and high F(ENO).

Background: Farmers' children have a reduced prevalence of allergic disorders. The specific protective environmental factors responsible are not yet identified., Objective: We sought to determine whether farmers' children in the rural county of Shropshire, England, have a reduced risk of atopy and, if so, to identify the factors responsible., Methods: The Study of Asthma and Allergy in Shropshire was a 2-stage cross-sectional study. In stage 1 a questionnaire to elicit allergic status, diet, and farming exposure was completed by the parents of 4767 children. In stage 2 a stratified subsample of 879 children underwent skin prick testing and measurement of domestic endotoxin., Results: Compared with rural nonfarming children, farmers' children had significantly less current asthma symptoms (adjusted odds ratio (OR), 0.67; 95% CI, 0.49-0.91; P = .01) and current seasonal allergic rhinitis (adjusted OR, 0.50; 95% CI, 0.33-0.77; P = .002) but not current eczema symptoms (adjusted OR, 0.91; 95% CI, 0.68-1.21; P = .53) or atopy (adjusted OR, 0.68; 95% CI, 0.40-1.16; P = .15). In contrast, current unpasteurized milk consumption was associated with significantly less current eczema symptoms (adjusted OR, 0.59; 95% CI, 0.40-0.87; P = .008) and a greater reduction in atopy (adjusted OR, 0.24; 95% CI, 0.10-0.53; P = .001). The effect was seen in all children, independent of farming status. Unpasteurized milk consumption was associated with a 59% reduction in total IgE levels (P < .001) and higher production of whole blood stimulated IFN-gamma (P = .02)., Conclusion: Unpasteurized milk consumption was the exposure mediating the protective effect on skin prick test positivity. The effect was independent of farming status and present with consumption of infrequent amounts of unpasteurized milk., Clinical Implications: Unpasteurized milk might be a modifiable influence on allergic sensitization in children.

Background: Exhaled nitric oxide (eNO) levels are increased in airway inflammatory disorders, such as asthma., Objective: We sought to determine whether eNO could serve as a noninvasive marker of allergic airway inflammation for an epidemiologic study in schoolchildren., Methods: Two hundred seventy-eight schoolchildren aged 10 to 12 years answered a modified American Thoracic Society questionnaire, and eNO levels and pulmonary function were measured. In 246 subjects serum nonspecific IgE levels and levels of IgE specific to house dust mite, cat, cedar, and mold were also measured. Correlation analysis was used to examine eNO levels, nonspecific IgE levels, antigen-specific IgE levels, and pulmonary function. In addition, we compared these variables between subjects with (recurrent wheezers) and without (nonwheezers) recurrent wheeze. Finally, multiple logistic regression analysis was used to find possible predictors for recurrent wheezers., Results: eNO showed significant positive correlations with nonspecific IgE (r=0.62, P <.001) and mite-specific IgE (r=0.74, P <.001) and weak positive correlations with specific IgE to cat and cedar. Only eNO showed a weak but significant inverse correlation with pulmonary function (%FEV(1), P=.035; FEV(1)/forced vital capacity, P=.018). eNO, nonspecific IgE, and mite-specific IgE levels in recurrent wheezers were greater (P <.001), and %FEV(1) was less (P=.06) when compared with values seen in nonwheezers. Finally, eNO was determined by means of multiple logistic regression analysis to be the best predictor for recurrent wheezers compared with other variables (odds ratio, 11.2; 95% CI, 1.33-94.0)., Conclusion: eNO can be used in epidemiologic studies as a noninvasive marker of allergic airway inflammation in schoolchildren.

Background: Asthma is an increasing public health concern that disproportionally affects children. In 1998, the Centers for Disease Control identified children aged 0 to 4 years as the "driving force" behind climbing rates of asthma-related emergency department visits and hospitalizations. Despite the significant asthma burden in preschool children, few studies characterize this population., Objective: This study identifies and characterizes children at risk for asthma who are enrolled in a local Head Start program., Methods: Caregivers of 368 children aged 3 to 5 years who were identified by using an asthma survey were recruited. Data were collected on demographics, health care use and access, medication use, symptoms, and trigger exposure. Exposure to tobacco smoke was determined by urinary cotinine and allergen sensitization by skin prick test., Results: At baseline, 64% of the children had more than 1 emergency department visit for asthma in their lifetime, whereas 31% had more than 1 visit in the previous 6 months. Caretakers reported smoking in 37% of households with cotinine exceeding 20 ng/mg in 27% of the sample. Twenty-one percent reported symptoms consistent with intermittent asthma, and 79% reported symptoms consistent with persistent asthma. Forty-five percent of the children reported nighttime symptoms more than 1 night per week. Seventy-one percent had positive test results for more than 1 allergen, and 42% had positive test results for more than 3 allergens. Only 32% of children with persistent asthma had both rescue and controller medications., Conclusion: Children with asthma enrolled in a Head Start program have significant environmental tobacco smoke exposure, are highly atopic and symptomatic, and do not receive appropriate medication treatment. Overall, children in the study had poor asthma control. This high-risk group could benefit from case management programs.

The importance of fungal allergen products in the practice of clinical allergy is frequently underestimated. A wide variety of fungal species have been demonstrated to elicit allergic symptoms and to sensitize patients. The quality of fungal allergen preparations might have a significant effect on the specificity and sensitivity of diagnostic tests. Varying degrees of cross-reactivity have been shown among fungal genera, and the clinical relevance of this cross-reactivity has been neither fully appreciated nor applied to clinical practice. In addition, an increasing number of potentially new fungal allergen sources for which commercial extracts are not available are being identified. Manufacturers of allergen products have the formidable task of providing quality fungal allergen extracts that are routinely used for specific allergy diagnosis and treatment in the clinic. Currently there are no standardized fungal allergen products available in the United States because of inherent difficulties with manufacturing and standardizing fungal extracts. Without intervention, progress will not be forthcoming.

Background: Recent epidemiologic evidence has challenged the paradigm suggesting a direct causal relationship between allergic sensitization and asthma., Objective: We sought to investigate the role of a familial predisposition for asthma in the development of atopy in children., Methods: Subjects were participants in the Tucson Children's Respiratory Study. Skin tests to aeroallergens were performed in parents and in children at ages 6, 11, and 16 years. Parents were considered asthmatic if they reported physician-confirmed asthma. Parents were divided into 4 phenotypes on the basis of skin sensitization (Skt+ or Skt-) and asthma status (As+ or As-): Skt-/As-, Skt-/As+, Skt+/As-, and Skt+/As+., Results: Children's allergic sensitization differed among parental phenotypes at all ages (P <.0001). Children in the Skt+/As- and Skt+/As+ groups were significantly more likely to be allergic than children in the Skt-/As- group at all ages. Among children with allergic parents, those with at least one parent with asthma were significantly more likely to have positive skin test responses than those with nonasthmatic parents at age 6 years (52.4% vs 37.4%, P <.005) and 11 years (70.1% vs 55.6%, P <.005) but not at age 16 years (82.3% vs 75.1%, P =.180). Results were independent of wheezing in the child and of the characteristics of atopy in parents. The Skt-/As+ group had too few subjects for meaningful comparisons., Conclusion: Among children of atopic parents, parental asthma is a risk factor for allergic sensitization in early childhood. The strong association between allergic sensitization and asthma is at least in part explained by an increased susceptibility to allergen sensitization in subjects predisposed to asthma.

Background: Objective lung function measurements are routinely used to diagnose and manage asthma, but their utility for young children has not been defined., Objective: Bronchodilator responses were measured by means of impulse oscillometry (IOS) and compared with conventional spirometry to determine the value of lung function measures in 4-year-old asthma-prone children., Methods: The study participants were in the Childhood Asthma Prevention Study (National Institute of Health/National Institute of Allergy and Infectious Diseases) and at risk for asthma. At age 4 years, concurrent asthma was determined by using a previously validated modified American Thoracic Society questionnaire. Children performed IOS and spirometry before and after albuterol administration and underwent skin prick testing to 13 common allergens to assess atopy. IOS measures were as follows: airways resistance at 5 Hz and 10 Hz, airways reactance at 5 Hz and 10 Hz, and resonant frequency., Results: Asthmatic patients versus nonasthmatic patients significantly differed in their IOS-assessed bronchodilator responses through Delta resistance at 5 Hz (medians, 27% vs 17%; P =.02) and Delta resistance at 10 Hz (24% vs 16%; P =.03). Because atopic children who have frequent wheezing are at risk for persistent asthma, the data were analyzed in regard to atopic patients with or without asthma. IOS strongly distinguished atopic asthmatic children through Delta resistance at 5 Hz (36% vs 13%, P =.007), Delta resistance at 10 Hz (25% vs 11%, P =.02), and Delta reactance at 10 Hz (47% vs 12%, P =.03). Conventional spirometry did not establish similar statistically significant findings., Conclusion: IOS bronchodilator responses are remarkably abnormal in 4-year-old children, who are most likely to have persistent asthma. IOS is a useful diagnostic tool in early asthma development and might be a helpful objective outcome measure of early interventions.

Background: Recent investigations suggest a common genetic rather than environmental cause to explain the association between IgE-mediated atopic allergies and depression., Objective: Taking into account psychosocial confounding factors, we investigated separately and at the epidemiologic level the effects of maternal, paternal, and sibling atopy on the cumulative incidence of a child's depression., Methods: We used an unselected, genetically homogenous, general population birth cohort of 12,058 live-born children in Finland. The 31-year prospective follow-up included questionnaire information on atopic disorders of the cohort members' parents and siblings. The probands' own atopic conditions were evaluated by means of skin prick tests, and information on lifetime depression diagnoses was gleaned from postal questionnaires and national hospital discharge registers. Potential confounders were mother's parity, father's social class, maternal smoking during pregnancy, proband's regular daily smoking, and proband's dwelling place. Total variable information was available from 4068 cohort members., Results: Among female probands, the presence of atopy in parents was the strongest predictor for lifetime depression (P <.001), and sibling atopy and parental atopy were the strongest predictors for hospital-treated depression (P =.018 and P =.036, respectively). After controlling for confounders, it was noticed that maternal atopy increased a female proband's risk of lifetime depression up to 1.9-fold (odds ratio, 1.9; 95% CI, 1.1-3.0). The corresponding risk increased over 4-fold if parental-maternal atopy was combined with proband's own atopy., Conclusions: Our findings suggest that maternal inheritance could be a significant causative factor in the association between atopy and depression of female probands.

Background: The skin prick test is used to examine specific IgE-mediated allergic responses. Generally, results accord well with anamnestic information on atopy. Several genetic factors probably affect the strength of allergen-mediated skin test reactions., Objective: We sought to investigate skin test findings in a population-based sample of adult asthmatic patients and control subjects and to establish whether the IL1A genotype affects allergy testing., Methods: We analyzed the single G-to-T base exchange polymorphism in exon 5 at +4845 of the gene encoding IL-1alpha (IL1A) in adult asthmatic patients (n = 245) and nonasthmatic control subjects (n = 405). The data were assessed for correlation with data on the skin test responses of these subjects to 22 common allergens., Results: The IL1A genotype distribution and allele frequencies proved similar in patients and control subjects. Surprisingly, the IL1A genotype distribution was markedly different in control subjects with positive (ie, >/=1 positive reaction) and negative skin test responses (P =.006). This difference was caused by an increase in the frequency of the rarer allele 2 in control subjects with negative skin test responses (P =.004)., Conclusion: Our study demonstrates that the IL1 gene complex is involved in the regulation of IgE-mediated atopic reactions. The results suggest that skin test responses to specific allergens are differently regulated in nonasthmatic and asthmatic subjects. Because of the potential role of the IL1A genotype as a confounding factor in skin prick testing, these results require special attention and should be further evaluated in other clinical settings.

Background: Individuals with pollen allergy often have IgE against plant-derived foods. This can be due to cross-reactive IgE against Bet v 1 and homologues, profilins, and/or cross-reactive carbohydrate determinants., Objective: The aim of this study was to correlate sensitization to Bet v 1 and profilin with individual recognition patterns to plant foods and clinical relevance., Methods: Fifty-two patients with pollen allergy and IgE against at least one plant-derived food were included in the study. Adverse reactions to plant-derived foods were documented by using standardized interviews. Skin prick tests were performed for pollen (grass, birch, and mugwort) and 14 plant-derived foods. In addition, recombinant (r) Bet v 1 and rBet v 2 (profilin) were tested intracutaneously. Specific IgE against the abovementioned allergens were determined by means of RAST. Cross-reactivity was studied by means of RAST inhibition., Results: Eighty-five percent of patients were sensitized to Bet v 1, and 71% were sensitized to profilin. Profilin was associated with a higher number of positive RAST results to plant-derived foods than Bet v 1. In contrast, Bet v 1 was associated with more positive skin prick test responses and more food-related symptoms. Sensitization to Bet v 1 was associated with IgE against apple, hazelnut, and peach, whereas sensitization to profilin was associated with positive RAST results to all investigated plant-derived foods except apple, peach, and melon., Conclusions: IgE antibodies against Bet v 1 have a more limited spectrum of cross-reactivity than those against profilin, but they frequently give rise to clinically relevant cross-reactivities to food. In analogy to anticarbohydrate IgE, cross-reactive IgE against food profilins have no or very limited clinical relevance.

Background: The hygiene hypothesis proposes that declining exposure to infections is implicated in the rising trend of allergy and asthma., Objective: We sought to test this hypothesis by examining the relationship of hay fever, asthma, and atopic sensitization with markers of infection in a large general population sample of the United States., Methods: We analyzed the data of 33,994 US residents recorded in a public database of a nationally representative cross-sectional survey (Third National Health and Nutrition Examination Survey, 1988-1994). The variables examined were sociodemographic information, lifetime diagnosis and age at first diagnosis of hay fever or asthma, current skin sensitization to 9 airborne allergens and peanut, and current serology for Toxoplasma gondii, herpes simplex viruses type 1 and 2, and hepatitis A, B, and C viruses., Results: Hay fever (adjusted odds ratio, 0.27; 95% CI, 0.18-0.41; P <.001) and asthma (adjusted odds ratio, 0.45; 95% CI, 0.31-0.66; P <.001) were less frequent in subjects seropositive for hepatitis A virus (HAV), T gondii, and herpes simplex virus 1 versus seronegative subjects after adjusting for age, sex, race, urban residence, census region, family size, income, and education. Skin sensitization to peanut and to all the airborne allergens examined, except for cockroach, was less frequent among HAV-seropositive versus HAV-seronegative subjects younger than 40 years of age. The prevalence of hay fever and asthma diagnosed at or before 18 years of age in HAV-seronegative subjects increased progressively from 2.7% (95% CI, 0.7%-4.7%) and 0.4% (95% CI, 0.1%-1.6%), respectively, in cohorts born before 1920 to 8.5% (95% CI, 7.3%-9.7%) and 5.8% (95% CI, 4.8%-6.8%), respectively, in cohorts born in the 1960s, whereas they remained constant at around 2% in all cohorts of HAV-seropositive subjects., Conclusion: In the United States serologic evidence of acquisition of certain infections, mainly food-borne and orofecal infection, is associated with a lower probability of having hay fever and asthma. Third National Health and Nutrition Examination Survey data support the hypothesis that hygiene is a major factor contributing to the increase in hay fever, asthma, and atopic sensitization in westernized countries.

The accurate diagnosis of hypersensitivity to natural rubber latex is the initial step in the effective management of individuals with latex allergy and in ensuring the quality of epidemiologic studies. The diagnostic algorithm used in the evaluation of an individual with suspected latex allergy begins with a comprehensive clinical history during which risk factors (atopy, food allergies, hand dermatitis) and temporal relationships between symptoms and natural rubber product exposure are identified. If type IV hypersensitivity is suspected because of the delayed nature (hours to days) and confinement of symptoms to the skin-latex product contact areas, patch testing can be conducted to confirm the presence of activated T cells with specificity for rubber chemicals. If type I hypersensitivity is suspected because of ocular, upper and lower airway, and/or systemic symptoms that have rapid onset (minutes) after a definable latex exposure, a confirmatory skin or blood test for IgE antibody may be conducted to verify a state of sensitization within the individual. The definitive diagnosis would then be made only after consideration of the individual's clinical history and confirmatory in vivo and/or in vitro laboratory test results. If discordance remains between highly convincing latex-associated symptoms as identified in the history and repetitively negative confirmatory IgE antibody test results, then one of several types of in vivo provocation tests may be performed for adjudication. This overview examines the current state of the art in both in vivo and in vitro diagnostic methods for latex-specific IgE antibody detection in skin and blood. The performance, advantages, and limitations of each diagnostic method are compared.

Archaeologists have found that latex items were used as early as 1600 BC, but it took until approximately 1900 AD before surgical gloves were commonly used. Descriptions of apparent allergic reactions to natural rubber appeared in the medical literature in 1927, and irritant and delayed-contact reactions were reported in 1933. Although irritant and delayed-contact reactions to rubber products were increasingly recognized, immediate-type allergic reactions were not reported again until 1979. However, after 1980, increasing numbers of contact urticarial reactions to latex were reported, and investigations suggested that many of these reactions were IgE-mediated. In 1984, the first anaphylactic reactions caused by latex surgical gloves were reported, followed in 1991 by the first report of a fatal anaphylactic reaction to latex. Increasing recognition of latex allergy led to divergent paths of investigation. Critical early questions were whether the observed reactions were truly IgE-mediated, and if they were IgE-mediated, what was the source of the allergen? If the allergen was present in latex products, where did it come from? Was it present in raw latex or was it added during processing? As knowledge about the allergens improved, efforts were made to develop and test materials for skin testing and for allergen-specific IgE assays. Now more than 10 unique proteins are recognized as major latex allergens. Although much has been learned about latex allergy, important unanswered questions remain, including the sources of latex exposure that led to sensitization, why latex allergy increased dramatically during the 1980s, and the prevalence of latex allergy in diverse populations. This review concentrates on the history of latex use in medicine and the dramatic emergence of immediate-type latex allergy.

Background: Traditionally, the diagnosis of type I allergies is based on clinical data, skin test results, and laboratory test results with allergen extracts. During the past few years, several attempts have been made to refine diagnostic assays in clinical allergy by introducing recombinant allergens and novel markers of IgE-dependent cell activation., Objectives: We have identified the ectoenzyme CD203c as a novel basophil antigen that is upregulated on IgE receptor cross-linkage. In this study we applied CD203c and a panel of recombinant allergens to establish a novel basophil test that allows for a reliable quantification of IgE-dependent responses at the effector cell level., Methods: Patients allergic to birch (Bet v 1, n = 15; Bet v 2, n = 8) and grass (Phl p 1, n = 15; Phl p 2, n = 10; Phl p 5, n = 14) pollen allergens, as well as 10 nonallergic donors, were examined. Basophils were exposed to various concentrations of recombinant allergens for 15 minutes and then examined for expression of CD203c by means of flow cytometry. CD203c upregulation was correlated with the increase in CD63., Results: Exposure to recombinant allergens resulted in a dose-dependent increase in expression of CD203c on peripheral blood basophils in sensitized individuals, whereas no increase was seen in healthy control subjects. The effects of the recombinant allergens on CD203c expression were also time dependent. There was a good correlation between allergen-induced upregulation of CD203c and upregulation of CD63 (R = 0.76)., Conclusion: Flow cytometric quantitation of CD203c on blood basophils exposed to recombinant allergens is a useful approach to determine the allergic state in sensitized individuals and represents a basis for a sensitive novel allergy test.

Background: The relationship between early allergen exposure, sensitization, and development of atopic disease remains controversial. In 1993, extremely high levels of birch pollen were recorded in Stockholm, Sweden, creating the unique opportunity to study children with different exposures during infancy., Objective: We sought to assess the influence of early high-dose exposure to an inhalant allergen (birch pollen) on sensitization and development of atopic disease in children., Methods: A total of 583 children with atopic heredity born in Stockholm in February through April 1992, 1993, or 1994 were investigated at age 4.5 to 5 years. The children were examined and underwent skin prick testing with inhalant and food allergens. IgE antibodies (RAST) against birch pollen and recombinant birch pollen allergen (rBet v 1) were analyzed in serum., Results: The children born in 1993 (high-dose exposure at 0-3 months) were more often sensitized (ie, positive skin prick test response) to birch pollen than the children born in 1994 (low-dose exposure; 17.8% and 8.8%, respectively; odds ratio [OR], 2.4; 95% CI, 1.2-4.6). A tendency in the same direction was seen for children born in 1992 (high-dose exposure at 12-15 months; OR, 1.7; 95% CI, 0.9-3.2). The results were supported by the RAST analyses. The prevalence of bronchial asthma, allergic rhinoconjunctivitis, and atopic dermatitis did not differ between the birth-year groups. However, the prevalence of pollen- and animal dander-induced allergic asthma was increased in the children born in 1993 (OR, 2.6; 95% CI, 1.2-5.6). An interaction between early high-dose exposure to birch pollen and cat in the household was suggested for sensitization to cat (P =.06)., Conclusion: Exposure to high levels of birch pollen in infancy increases the risk of sensitization to the same allergen, as well as the risk of allergic asthma.

Whether gene expression is useful in discriminating different atopic phenotypes is unclear. The aim of the study was to evaluate a gene-expression score for the diagnosis of atopy and asthma and to assess disease activity as a guide for therapeutic decisions. Purified mRNA from PBMCs of 18 atopic asthmatic subjects, 8 atopic nonasthmatic subjects, and 14 healthy control subjects was hybridized to cDNA membranes. A composite atopy gene expression (CAGE) score was determined by using 10 genes dysregulated in atopic individuals according to a specific algorithm. The CAGE score was better than total IgE in differentiating atopic from nonatopic subjects (sensitivity, 96%; specificity, 92%). Correlation between the CAGE score and total IgE (P <.001) was found, and there was a trend for correlation with asthma severity (P =.051). The CAGE score was able to quantify phenotype-specific alteration in gene expression of atopic individuals. The CAGE score might be used as a diagnostic tool or to monitor the effects and side effects of therapy.

Background: In Atlanta, as in other major urban areas of the United States, asthma is a leading cause of school absenteeism, emergency department use, and hospitalization. Recent guidelines for asthma management recommend reducing exposure to relevant allergens, but neither the feasibility nor the efficacy of this form of treatment has been established for children living in poverty., Objective: We sought to investigate allergen avoidance as a treatment for asthma among inner-city children., Methods: One hundred four children with asthma living in the city of Atlanta were enrolled into a controlled trial of avoidance without being skin tested. The children were randomized to an active avoidance group, a placebo avoidance group, and a second control group for which no house visits occurred until the end of the first year. Avoidance included bed and pillow covers, hot washing of bedding, and cockroach bait. Eighty-five children completed the study, and the outcome was measured as unscheduled clinic visits, emergency department visits, and hospitalization for asthma, as well as changes in mite and cockroach allergen levels., Results: There was a significant decrease in acute visits for asthma among children whose homes were visited (P < .001). However, there was no significant difference between the active and placebo homes either in the effect on asthma visits or in allergen concentrations. When the children with mite allergy were considered separately, there was a significant correlation between decreased mite allergen and change in acute visits (P < .01). The avoidance measures for cockroach allergen appeared to be ineffective, and the changes observed did not correlate with changes in visits., Conclusions: Applying allergen avoidance as a treatment for asthma among children living in poverty is difficult because of multiple sensitivities and problems applying the protocols in this environment. The current results demonstrate that home visiting positively influences the management of asthma among families living in poverty. Furthermore, the results for children with mite allergy strongly suggest that decreasing relevant allergen exposure should be an objective of treatment in this population.

Background: A variety of definitions of asthma and atopy traits have been used in genetic studies. The variables used may be correlated, increasing the likelihood of type I error., Objective: We sought to clarify and quantify phenotypes that may be characterized by related traits. Principal components and factor analysis were applied to the correlation matrix of asthma and atopy traits before linkage analysis., Methods: Factor analysis was performed on 468 Hispanic and non-Hispanic white children enrolled in the Tucson Children's Respiratory Study, with complete information on 24 items, including skin test response to 7 allergens, total serum IgE levels, presence or absence of asthma attacks, wheezing episodes, hay fever, and cough. Factor score coefficients were then applied to all siblings (n = 877), and quantitative factor scores were derived. Single-point and multipoint nonparametric sib-pair analyses were performed to assess linkage to markers on chromosome 5q31-33. Analyses were also performed for individual items., Results: Two main factors were identified: Factor I had high loadings on atopic items, including skin test responses, IgE, and hay fever, and Factor II had high loadings that included asthma diagnosis, wheezing, cough, and Alternaria species skin test response. Factors I and II were correlated at an r value of 0.19. For the quantitative factor scores, significant single-point linkage (P < .0001) was demonstrated only for atopic Factor I, and a peak multipoint LOD score of 2.7 was seen for marker D5S479. Multipoint LOD scores for individual items were 1.1 or less., Conclusion: These analyses suggest evidence for a locus or loci mapping to chromosome 5q31-33 associated with this composite atopic phenotype.

Background: Prediction of adult asthma is important, and early prevention strategies should be targeted at those most at risk. Identifying high-risk children at an early age, however, is currently difficult., Objective: We sought to determine those factors present in early life that predict an increased risk of adult asthma., Methods: A prospective cohort study of subjects at risk of asthma and atopy was undertaken in Poole, England. One hundred babies of atopic parents were recruited at birth. During the first 5 years of life, subjects were recalled annually, all respiratory events were reported, and skin prick tests and total serum IgE measurements were performed. At 11 and 22 years, bronchial hyperresponsiveness was also measured. Seventy-three subjects were followed up at 5 years, 67 at 11 years, and 63 at 22 years., Results: Twenty-three (37%) adult subjects reported wheezing within the previous 12 months. Fifteen (25%) of these subjects showed signs of bronchial hyperresponsiveness and were regarded as asthmatic. Wheezing before the age of 2 years occurred in 28% and was not significantly related to adult asthma (odds ratio, 0.3; 95% CI, 0.03-1.7; P = .19). A positive skin prick test response to hen's egg, cow's milk, or both in the first year was independently predictive of adult asthma (odds ratio, 10.7; 95% CI, 2.1-55.1; P = .001; sensitivity, 57%; specificity, 89%)., Conclusion: Prediction of adult asthma remains difficult. In this study of subjects at risk of atopy, skin sensitivity to hen's egg or cow's milk in the first year was predictive of adult asthma.

Background: Asthma is increasing in prevalence and severity in Africa. Previous studies have suggested that the prevalence of atopy in West Africa was low., Objective: We sought to investigate the risk factors for asthma in Ghanaian school children., Methods: Fifty children (age range, 9-16 years) with a physician diagnosis of asthma and asthma symptoms within the previous 12 months and 50 age- and sex-matched healthy control subjects were randomly selected and evaluated by means of questionnaire, skin testing, total and specific IgE measurements, and allergen level measurements from bed dust samples (mite, cat, dog, and cockroach)., Results: Asthmatic children were exposed to higher levels of mite allergens than were control children (geometric mean, 19 microg/g [95% CI, 13.6-26.5] vs. 11.2 microg/g [7.4-15.7]; P <.05). Cat and dog allergen levels were low. There was a marked dissociation between skin test responses and the presence of specific IgE to cat and dog (CAP method). However, 84% of subjects with positive cat dander-specific IgE levels in cat CAP tests and negative skin test responses did not have Fel d 1-specific IgE (chimeric ELISA). In the univariate analysis significant associations with the patient group were found for sensitization to mite (odds ratio [OR], 9.3; 95% CI, 3.7-23.4) and cockroach (OR, 3.9; 95% CI, 1.3-11.6), inner-city residence (OR, 3.5; 95% CI, 1.4-8.9), asthma in family member (OR, 3.5; 95% CI, 1.4-9.0), low (<5) position in sibship (OR, 3.6; 95% CI, 1.2-11), presence of smoker in home (OR, 3.7; 95% CI, 1.2-11.9), small household size (OR, 0.57; 95% CI, 0.35-0.93), and use of electricity as domestic fuel (OR, 0.34; 95% CI, 0.12-0.97). In the multivariate analysis sensitization to mites remained the strongest risk factor associated with the asthmatic group (OR, 10.4; 95% CI, 3.5-30.9). The other significant associations were inner-city residence (OR, 4.8; 95% CI, 1.5-5.2), sensitization to cockroach (OR, 4.9; 95% CI, 1.3-18.6), and position in sibship of less than 5 (OR, 6.3; 95% CI, 1.3-29.4)., Conclusion: Sensitization to dust mite and cockroach allergens, inner-city residence, and low position in sibship were independent risk factors for asthma in Ghanaian children.

Background: In our 1976 controlled venom immuno rapy trial, 33% of 182 patients with a history of systemic reactions to insect stings were excluded because of negative venom skin test responses. There have been reports of patients with negative skin test responses who have had severe reactions to subsequent stings., Objective: Our aim is to increase awareness about the patient with a negative skin test response and insect sting allergy and to determine the frequency and significance of negative skin test responses in patients with a history of systemic reactions to insect stings., Methods: We prospectively examined the prevalence of negative venom skin test responses in patients with a history of systemic reactions to stings. In patients who gave informed consent, we analyzed the outcome of retesting and sting challenge., Results: Of 307 patients with positive histories screened for our sting challenge study, 208 (68%) had positive venom skin test responses (up to 1 microg/mL concentration), and 99 (32%) had negative venom skin test responses. In 36 (36%) of the 99 patients with negative skin test responses, the venom RAST result was a low positive (1-3 ng/mL), or repeat venom skin test responses were positive; another 7 (7%) patients had high venom-specific IgE antibody levels (4-243 ng/mL). Notably, 56 (57%) of 99 patients with positive histories and negative skin test responses had negative RAST results. In patients with positive skin test responses, sting challenges were performed in 141 of 196 patients, with 30 systemic reactions. Sting challenges were performed on 37 of 43 patients with negative skin test responses and positive venom-specific IgE and in 14 of 56 patients with negative skin test responses and negative RAST results. There were 11 patients with negative skin test responses who had systemic reactions to the challenge sting: 2 had negative RAST results, and 9 had positive RAST results at 1 ng/mL. The frequency of systemic reaction was 21% in patients with positive skin test responses and 22% in patients with negative skin test responses (24% in those with positive RAST results and 14% in those with negative RAST results)., Conclusions: Venom skin test responses can be negative in patients who will subsequently experience another systemic sting reaction. Venom skin test responses are negative in many patients with a history of systemic allergic reactions to insect stings and may be associated with positive serologic test responses for venom-specific IgE antibodies (sometimes strongly positive results). Venom skin test responses should be repeated when negative, along with a serologic IgE antivenom test. Better diagnostic skin test reagents are urgently needed.

Background: Exhaled nitric oxide (ENO) has been proposed as a noninvasive marker of airway inflammation in asthma., Objective: We investigated the relationships among ENO, eosinophilic airway inflammation as measured by induced sputum, and physiologic parameters of disease severity (spirometry and methacholine PC(20)). We also examined the effect of corticosteroid treatment and atopy on ENO levels and eosinophil counts in induced sputum., Methods: Measurements were taken on one day in 22 healthy nonatopic subjects, 28 healthy atopic subjects, 38 asthmatic subjects not taking inhaled steroids, 35 asthmatic subjects taking inhaled steroids, and 8 subjects with eosinophilic bronchitis without asthma., Results: ENO levels showed significant but weak correlations with eosinophil differential counts in the steroid-naive asthmatic and healthy atopic groups (r (s) < 0.05). ENO levels were significantly lower in the asthmatic subjects taking steroids compared with the asthmatic subjects not taking steroids, despite there being no difference in the sputum cell counts, and a tendency to increased airflow limitation. ENO levels and sputum eosinophil counts were equally good at differentiating from steroid-naive asthmatic subjects. ENO levels were consistently raised in subjects with eosinophilic bronchitis without asthma. Atopy had no effect on ENO levels in the healthy subjects., Conclusion: We conclude that ENO is likely to have limited utility as a surrogate clinical measurement for either the presence or severity of eosinophilic airway inflammation, except in steroid-naive subjects.

Background: Epicutaneous application of aeroallergens induces a positive atopy patch test (APT) response in about 50% of patients with atopic eczema (AE) and sensitization for these allergens., Objective: To elucidate the mechanisms determining the outcome of the APT, the following questions were addressed. Are there differences in clinical features between patients with AE who have positive versus negative APT responses? Is a macroscopically negative APT response also histologically negative, and if so, are there differences in clinically noninvolved skin between the two groups regarding (1) the sensitivity toward an irritant, (2) the composition of cellular infiltrate, (3) the presence of aeroallergen-specific T cells, and (4) the number of IgE(+) cells?, Methods: Punch biopsy specimens from both house dust mite patch tested and the clinically noninvolved skin of patients with AE who have positive APT responses (n = 10) and negative APT responses (n = 10) and those from the normal skin of atopic individuals without AE (n = 10) and nonatopic volunteers (n = 10) were analyzed by using immunohistochemistry with mAbs against eosinophil cationic protein, IgE, the high-affinity receptor for IgE, and CD3 and CD25 mAbs. Furthermore, T-cell lines were propagated from noninvolved skin of all patient and control groups. The T-cell lines were tested for house dust mite specificity., Results: Negative APT sites were immunohistochemically similar to clinically noninvolved AE skin. There were no significant differences between patients with AE who had positive and negative APT results regarding either clinical features, the composition of cellular infiltrate, or the presence of allergen-specific T cells in clinically noninvolved skin. However, differences were observed regarding the presence of IgE on epidermal CD1a(+) cells., Conclusion: Our results indicate that a positive APT reaction requires the presence of epidermal IgE(+) CD1a(+) cells in clinically noninvolved skin, but that also other, as yet unknown, discriminatory factors are involved.

Background: Chronic rhinosinusitis (CRS) occurs frequently in patients with atopy, but little is known of the prognosis after surgery and of factors that may predict a poor outcome., Objective: Our purpose was to assess the long-term prognosis in atopic patients with CRS who undergo surgery and whether certain immune markers could predict a worse prognosis in this setting., Methods: Fifteen patients with diffuse involvement of the sinuses on computed tomographic (CT) scan but without nasal polyposis underwent ethmoidectomy with middle meatotomy for CRS when it was clinically indicated. All patients had a biopsy of the inferior turbinate and of the most inflamed areas of the maxillary and ethmoid sinuses at the time of surgery. Follow-up was performed by video endoscopy and by assessment of 2 chronic sinusitis questionnaires at 0, 6, and 24 months postoperatively. The number of lymphocyte subsets (CD3, CD4, CD8), mast cells and eosinophils, and cells expressing IL-4 and IL-5 messenger RNA (mRNA) in all 3 biopsy sites at the time of surgery were compared with the clinical response after surgery., Results: Seven patients had persistent improvement after surgery, with a decrease in pain, rhinorrhea, or nasal obstruction and a decrease in the need for medication. Eight patients were unchanged or worsened after surgery with disabling rhinorrhea and repeated sinusitis. We found no difference in the number of inflammatory cells, lymphocyte subsets, or IL-4 mRNA-positive cells in the sinus mucosa between responders and nonresponders. However, an increased number of cells expressing IL-5 mRNA was found in the ethmoid sinus at the time of surgery in patients who did not respond to the surgical intervention (P =.007)., Conclusion: More than 50% of patients with perennial rhinitis and CRS do not improve after surgery, a response that may be predicted by more cells expressing IL-5 mRNA in the ethmoid sinuses. The increased number of cells expressing IL-5 mRNA may have the potential to be used as a marker for prediction of the response to surgery. The worsening of symptoms in some patients with CRS after sinus surgery could be a result of the disturbance of the anatomy of the sinuses and exposure to the environmental allergens.

Background: It has been proposed that Trichophyton infection is associated with atopy and allergy., Objectives: Our purpose was (1) to confirm whether atopy predisposes to chronic dermatophytosis and (2) to investigate whether Trichophyton infection induces atopic disease., Methods: Patients attending dermatology clinics and suspected of having dermatomycosis underwent in a prospective manner fungal culture and Trichophyton and inhalant skin tests, and blood serum was collected for total IgE and Trichophyton radioallergosorbent testing. Personal and family history of atopic diseases was also investigated., Results: According to mycologic culture, atopic history, and inhalant skin test results, patients were classified into 4 groups: (1) atopy plus mycosis (n = 28), (2) atopy (n = 26), (3) mycosis (n = 35), and (4) no atopy, no mycosis (n = 33). Patients with active mycosis (groups 1 and 3) demonstrated significantly increased positivity of Trichophyton skin tests compared with patients without fungal infection (groups 2 and 4), regardless of their atopic status, whereas atopic patients (those in groups 1 and 2) had significantly increased levels of total serum IgE compared with nonatopic subjects. Trichophytosis was not more prevalent in atopic than in nonatopic subjects, and atopic diseases were not more frequent in culture-positive than in culture-negative patients., Conclusions: Our results indicate that Trichophyton -specific IgE is observed in patients with trichophytosis regardless of atopy.

Background: Cupressaceae pollen allergy is a worldwide pollinosis, but its in vitro diagnosis is notoriously difficult. The Basotest is a newly available in vitro test for the detection of allergen-specific IgE based on the level of cellular activation of basophils by using flow cytometry., Objectives: The Basotest was compared with the measurement of cypress pollen-specific IgE in highly selected patients., Methods: We analyzed 34 patients allergic to cypress pollen selected on the basis of a suggestive clinical history and positive skin test and nasal challenge responses to cypress pollen extract. We also analyzed 8 patients with positive skin test responses to cypress pollen extract who did not present symptoms during the pollen season (intermediate group) and 33 control subjects. Sensitivity, specificity, and efficiency of the Basotest and serum-specific IgE levels measured by using the CAP System were determined in patients allergic to cypress pollen. Histamine release was studied in a selected group of patients., Results: The Basotest was more sensitive (91.2%) than the CAP System (76%) for the in vitro diagnosis of cypress pollen allergy. A dose-response curve was observed in basophils obtained from patients allergic to cypress pollen. There were no false-positive results with either test (specificity 100%). The results of the Basotest or those of the CAP System did not correlate with the patients' in vivo threshold sensitivity assessed by skin tests and nasal challenge., Conclusions: The Basotest was found to be an effective diagnostic test in patients allergic to cypress pollen.

Background: The major allergen of birch pollen, Bet v 1, is present in structurally slightly different isoforms. It has been postulated that certain isoforms show a distinct ability to bind birch pollen-specific IgE, although the T-cell response remains similar., Objective: We verified the hypothesis of a distinct allergenicity but similar T-cell immunogenicity of 2 isoforms in birch pollen-allergic subjects by in vivo tests and an in vitro assay for T-cell stimulation., Methods: Forty-eight birch pollen-allergic, 11 grass pollen-allergic, and 10 nonatopic control individuals were tested with 10-fold increasing concentrations (0.01 to 10.0 microg/mL) of recombinant (r) Bet v 1a and rBet v 1d by skin prick test (SPT), intradermal test (IDT), and conjunctival provocation test (CPT). An allergen-specific proliferation assay was performed on 21 patients with the 2 recombinant and the natural birch pollen allergens., Results: In each test system only birch pollen-allergic subjects but no controls reacted to the recombinant allergens. A positive in vivo response to 10 microg/mL of rBet v 1a was observed in 21 of 48 by SPT, in 48 of 48 by IDT, and in 33 of 48 by CPT. In contrast, the IDT response to 10 microg/mL of rBet v 1d was reduced by a factor of 100 because it was equivalent to the response to 0.1 microg/mL of rBet v 1a. rBet v 1d failed to elicit a positive reaction in SPT and CPT. The proliferative response of T cells was similar for both recombinant isoforms because 8 of 21 individuals reacted to rBet v 1a and 6 of 21 to rBet v 1d. Only 1 subject had a positive reaction to rBet v 1d alone., Conclusion: The natural isoforms rBet v 1a and rBet v 1d differ in their ability to bind IgE but are similar in their immunogenicity for T cells. Thus rBet v 1d might be a promising candidate for use in immunotherapy of birch pollen-allergic individuals.

Background: Maculopapular and urticarial rashes are nonimmediate manifestations common during aminopenicillin (AP) treatment, and the former often represent cell-mediated hypersensitivity., Objectives: We sought to determine the significance and incidence of skin test reactions to APs in adults reporting adverse reactions during therapy with these beta-lactams and, particularly, to evaluate the potential of patch tests, delayed-reading skin tests, and challenges in the diagnosis of nonimmediate reactions., Methods: We used skin tests with penicilloylpolylysine, minor determinant mixture, benzylpenicillin, ampicillin, and amoxicillin, as well as patch tests with the last 3 drugs. We also performed in vitro assays for specific IgE and challenges with the suspect penicillin in subjects with nonimmediate reactions., Results: Among the 144 patients reporting nonimmediate manifestations (mostly maculopapular rashes), delayed hypersensitivity was diagnosed in 62 on the basis of positive patch test and/or delayed intradermal test results and responses to challenges; negative reactions to challenges allowed us to reasonably exclude the possibility of allergy in 66 subjects, and the challenge confirmed that 1 patient had linear IgA bullous dermatosis. Definitive diagnoses could not be provided for the remaining 15 subjects, who had negative allergologic test results, because they did not consent to challenges. In 40 of 49 immediate reactors, a diagnosis of IgE-mediated hypersensitivity was made., Conclusions: Both patch and intradermal tests are useful in evaluating nonimmediate reactions to APs. Positive patch test and delayed intradermal responses together indicate delayed hypersensitivity. Intradermal testing appears to be more sensitive than patch testing, but the pattern of positive delayed intradermal test responses and negative patch test responses needs further investigation because of false-positive cases.

Background: Venom immunotherapy (VIT) protects most patients allergic to Hymenoptera stings while booster injections are continued. Few data on long-term protection after discontinuation of treatment are available., Objective: We sought to investigate protection from re-stings over a prolonged period after stopping VIT., Methods: Re-sting data were obtained from 200 of 322 patients in whom VIT had been stopped between 1988 and 1992 after a duration of at least 3 years. The 25 (12.5%) patients who again developed systemic allergic reactions were compared with 50 matched patients without re-sting reactions. Clinical data and diagnostic parameters (i.e., skin sensitivity and specific IgE and IgG) were studied., Results: Of the 25 patients who had re-sting reactions, 19 had been treated with bee venom (relapse rate, 15.8%), and six had been treated with Vespula venom (relapse rate, 7.5%). About half of the re-sting reactions occurred on the first resting after stopping VIT. Most of these reactions were mild, whereas the majority of reactions occurring after repeated re-stings were severe. When re-sting reactions were related to the total re-stings per year, an accumulation of sting reactions was observed in years 3 to 5 after stopping VIT. Patients with re-sting reactions had been receiving VIT for a significantly shorter duration (43.35 months) than those with continued protection (54.65 months) (p < 0.01). Of the diagnostic parameters, only a negative intracutaneous skin test at 10(-3) gm/L predicted long-term protection reliably., Conclusion: Venom immunotherapy of 3 to 5 years duration induces long-term protection in most patients. In rare occasions severe re-sting reactions may, however, occur, especially after repeated re-stings.

Background: Our studies of discontinuing venom immunotherapy after at least 5 years have led to the conclusion that the residual risk of a systemic reaction to a sting was in the range of 5% to 10% in adults, and no severe or life-threatening reaction occurred with 270 challenge stings in 74 patients after 1 to 5 years without venom immunotherapy., Objective: The objective of this study was to extend our observation of patients who discontinue venom immunotherapy over 5 to 10 years and to determine which patients are at higher risk for a reaction., Methods: Patients who discontinued venom immunotherapy were surveyed for 3 consecutive years to determine the frequency of systemic reactions to field stings and the fate of venom sensitivity. The evaluation included the 74 patients previously studied (group 1) and 51 additional patients followed after stopping therapy in our clinical center (group 2)., Results: Of the original 74 patients, 11 had field stings again after 3 to 7 years without venom immunotherapy, with one systemic reaction (dyspnea). Of the 51 patients in the other group, 15 were stung, of whom four (26%) had systemic reactions, including respiratory symptoms requiring epinephrine. Review of group 1 and group 2 revealed that half of the patients who had systemic reactions to a sting after stopping venom immunotherapy had a history of a systemic reaction occurring during venom immunotherapy (to an injection or a sting). Systemic reactions occurred in three patients who had negative skin test reactions; all three had very low but detectable venom-specific serum IgE antibody levels as determined by RAST and had a history of systemic reactions during venom immunotherapy. Greater severity of the pretreatment reaction was not associated with higher frequency of reaction to stings after stopping therapy but was associated with greater severity if a reaction did occur., Conclusions: Venom immunotherapy (yellow jacket/mixed vespid) in adults can be discontinued after 5 to 6 years with a 5% to 10% residual risk of a systemic reaction. Risk factors may include history of a systemic reaction during venom immunotherapy, persistent strongly positive skin test sensitivity, and the severity of the pretreatment reaction.

Background: Rosaceae fruit allergy is frequently associated with birch pollinosis in Central and Northern Europe and with grass pollen allergy in Central Spain. The main cross-reactive structures involved for birch pollinosis are Bet v 1 and profilin, and for grass pollinosis they are profilin and carbohydrate determinants. Rosaceae fruit allergy can occasionally be observed in patients without pollinosis., Objective: We investigated the clinical presentation and the allergens involved in allergy to Rosaceae fruit without pollinosis., Methods: Eleven patients from Central Spain allergic to apples, peaches, and/or pears but not to pollens were compared with 22 control subjects with combined grass pollen and fruit allergy. Skin prick tests and RASTs to apple, peach, and pear were performed. Cross-allergenicity was studied by RAST inhibition. Bet v 1 was tested with an indirect RAST, and profilin was tested in skin prick tests, histamine release, and RAST., Results: Rosaceae fruit allergy without pollinosis is severe with 82% of patients reporting systemic symptoms, mainly anaphylaxis (73%), whereas oral symptoms are less frequent (64%). Anaphylactic shock was observed in 36% of patients. The fruit allergens involved showed cross-reactivity among Rosaceae species but were not related to profilin or Bet v 1. Ninety-one percent of patients with combined grass pollinosis and fruit allergy reported oral allergy, 45% reported systemic symptoms, 18% reported anaphylaxis, and 9% reported anaphylactic shock., Conclusion: Allergy to Rosaceae fruits in patients without a related pollen allergy is a severe clinical entity. Profilin- and Bet v 1-related structures are not involved in Rosaceae fruit allergy without pollinosis.

Objective: The existence of Platanus pollinosis is not generally accepted despite the production of very large quantities of airborne Platanus pollen in many cities of the United States and Europe. The aim of this study was to investigate if Platanus pollen really contributes to the symptoms of the patients with pollinosis in the Madrid area., Methods: We carried out systematic skin prick testing with Platanus pollen extract on 47 patients seen in our allergy center with spring-summer pollinosis symptoms. Each patient maintained symptom score diaries before, during, and after the Platanus pollination season. The average symptom scores were calculated and compared with the Platanus pollen counts. Measurements of specific IgE by ELISA and immunoblotting also were performed in each patient., Results: The Platanus skin tests were positive in 33 of the 39 patients first seen with seasonal symptoms during Platanus pollen season and only in three of the eight patients without symptoms during Platanus exposure (Fisher's exact test; p < 0.05). Twenty-two of the 33 Platanus-positive skin test patients also had a positive ELISA result. Furthermore, the average 24-hour rhinitis symptom scores of the 39 patients first seen with seasonal symptoms during March through April showed significant correlation with Platanus pollen counts (r(s) = 0.57, p < 0.05). The immunoblot results suggest that a 17 kd pollen protein could be a major allergen in patients with Platanus pollinosis., Conclusions: Platanus pollen is an important cause of pollinosis in Madrid. A protein with a molecular weight of 17 kd appeared to be its major allergen.