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Low doses of animal antigen attenuates the late asthmatic reaction.

Five subjects with a history of asthma after exposure to cat or dog underwent a trial of low-dose antigen injection followed by bronchoprovocation with the relevant antigen. The neutralization dose of antigen was determined by serial and point dilution skin testing. In a crossover protocol, patients received this antigen or placebo injections. They then underwent bronchoprovocation with the same antigen. The results of the early and late reaction to bronchoprovocation were compared, with each patient serving as her own control. As measured by the number of breath units to lower the FEV1 by 20%, placebo group tolerated only 6.9 +/- 2 breath units, whereas the neutralization group tolerated 29 +/- 3 breath units (p less than 0.05). The maximum decline in FEV1 during the late reaction was 27 +/- 13% after injection of placebo and 12 +/- 12% after injection of antigen (p less than 0.05). In this model of antigen-induced asthma, injection of low doses of allergen immediately preceding bronchoprovocation blunted the immediate and delayed asthmatic reaction.

Adolescent↗

Ménière's syndrome and allergy.

The role of allergic and autoimmune factors in both the production and amplification of symptoms of Ménière's disease has yet to be clearly defined. Reasons to suspect an allergic factor influencing Ménière's disease include a relationship with symptoms to seasons or a suspect food, a known history of allergy in a Ménière's patient, bilaterality of symptoms, and refractoriness to the usual medical and surgical treatments. The majority of patients tested in this study were found to have rather low levels of sensitivity to inhalant allergens as measured by SET, and to have food reactions to very common "hidden" foods that are frequently ingested in the diet. By proper recognition and treatment of the underlying allergic factors affecting Ménière's disease, significant clinical improvement may be obtained even in longstanding or refractory cases.

Adult↗

In vivo diagnostic testing and immunotherapy for allergy. Report I, Part I, of the allergy panel. Council on Scientific Affairs.

The diagnosis and treatment of allergic disease constitute a particularly difficult and complex field in medicine, a field that has been complicated further by the promulgation and the use of unproved procedures and/or the inappropriate use of proved procedures. This report is the first in a series of reports prepared by a multidisciplinary panel appointed by the Council on Scientific Affairs of the American Medical Association. It discusses the necessity for proper clinical trials to generate reproducible results under similar conditions to adequately prove the validity of various diagnostic and therapeutic procedures. In vivo immunologic tests have been shown to be reliable and valid diagnostic tools and include skin tests with standardized allergenic extracts by prick, puncture, and intradermal techniques, skin end-point titration, and patch testing for contact allergic dermatitis. Other clinically useful physiologic tests include the exercise tolerance test, methacholine and/or histamine inhalation challenge test, and other inhalation tests utilizing either nasal or bronchial delivery. Oral challenge testing has also been utilized and includes open, single-blind, or double-blind techniques, depending on the requirements of the patient being studied. The second article is a continuation of the first report, and describes other challenge tests and unproved procedures. The third report of this series evaluates in vitro tests for allergy.

Bronchial Provocation Tests↗

Diagnosis and immunotherapy of mould allergy. II. Reproducibility and relationship between skin sensitivity estimated by end-point titration and histamine equivalent reaction using skin prick test and intradermal test.

To determine reproducibility and the optimal way of expressing skin sensitivity, simultaneous skin prick tests (SPT) and intradermal tests (ICT) were performed on 25 mould-allergic patients. The patients had a well-documented history of allergy to Cladosporium and Alternaria and were tested with partially purified standardized extracts of these two mould species. Skin prick tests were carried out on the volar side of the forearm and intradermal tests on the backs of the patients. The skin tests were performed as titration using quadruplicate determinations of 10-fold allergen dilutions. The area of the skin reactions measured by planimetry were plotted in a log-log system as a function of the allergen concentration. The reproducibility (SD/mean area X 100%) of the ICTs was significantly higher than that of the SPTs (17% versus 29%). A very low reproducibility was found with wheal areas less than 5 mm2. The dose response curve of the SPT wheal area was steeper than that obtained with ICT, both concerning ICT wheal and flare. Increasing the allergen concentration with a factor 10 resulted in a doubling of the wheal area in SPT, in contrast to a factor 1.7 using ICT. The coefficient of correlation using linear regression on the dose response curve was always higher than 0.9 with SPT and ICT wheal, but significantly lower with ICT flare. Skin sensitivity was estimated as end-point and histamine equivalent reaction. No significant correlation between SPT and ICT end-point titration was found contrary to the histamine equivalent reaction.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Determinants of airway responses to cat allergen: comparison of environmental challenge to quantitative nasal and bronchial allergen challenge.

BACKGROUND: Why allergic subjects may have asthma or rhinitis off allergen exposure remains unclear. OBJECTIVE: This study was carried out to compare airway responses during environmental allergen challenge (EAC) with quantitative allergen provocation challenges of the upper and lower airways. METHODS: Thirteen subjects with allergy to cats underwent EAC to cats. Lower airway responses during EAC were compared with bronchoprovocation with allergen. Nasal mucosal challenge with allergen-soaked disks were compared with EAC nasal responses. Nonspecific bronchial reactivity was assessed with methacholine; allergen sensitivity was assessed by skin prick tests, RAST, and end-point skin titration. RESULTS: During EAC, the maximal fall in FEV1 ranged from 6% to 57% (median, 18%) and correlated closely with allergen bronchoprovocation PD20 (Spearman's correlation coefficient [Rs] = -0.85, p < 0.0002). EAC asthmatic responses and allergen bronchoprovocation correlated with methacholine PD20 (Rs = -0.85, p = 0.0002 and Rs = 0.83, p = 0.0004, respectively). Nasal provocation and EAC nasal responses correlated with each other but not with lower airway responses. On the basis of EAC and allergen bronchoprovocation responses, seven participants with asthma were identified. This group was significantly more sensitive to inhaled methacholine but was similar to the nonasthmatic group in IgE-mediated sensitivity and nasal responses. CONCLUSIONS: The lower respiratory tract is less responsive to allergic and nonallergic stimuli in persons with allergic rhinitis. In persons with asthma during EAC, the response to nebulized cat allergen is also abnormal and correlates closely with their abnormal responsiveness to nonimmunologic stimuli.

Administration, Inhalation↗

New in vitro method for detecting asthma allergen. Counting reactive basophils after addition of allergen.

Changes in the morphology and number of basophils were examined after the addition in vitro of house dust extract in cells from seventy-seven patients with bronchial asthma. Morphological changes (reactive basophils) showed a close relation to the end-point titrations of antigen in skin tests, RAST score and bronchial provocation tests, but changes in number of basophils did not. With a RAST score of 2 or greater the change in reactive basophils varied from 40 to 80% (mean 58.1%), which was much greater than seen in persons with no RAST, score 0. Patients with positive bronchial inhalation tests, showed 40 to 80% (mean 57.8%) reactive basophils, whereas persons with a negative bronchial challenge test showed a range of reactive basophils from 0 to 50% (mean 28.9%). The difference in percentage of reactive basophils between the positive and negative groups of persons tested by bronchial inhalation was statistically significant.

Allergens↗

Efficiency of different skin prick testing methods in the diagnosis of allergy to dog.

The study of 202 asthmatic children shows that prick testing with standardized dog allergen extract is very useful in the diagnosis of allergy to dog dander. A good correlation was demonstrated with clinical history, RAST and the provocation tests. The use of the histamine control system improves the specificity of the prick test when compared with the simple measuring of the mean wheal diameter. End-point titration of the skin prick reactivity did not further improve the specificity when compared with the histamine control system.

Adolescent↗

Fel d 1 peptides: effect on skin tests and cytokine synthesis in cat-allergic human subjects.

We tested peptide immunotherapy in cat-allergic humans, using a formation of two synthetic peptides, IPC-1 and IPC-2, each of which is 27 amino acids long and contains T cell-reactive regions of Fel d 1, the major cat allergen. In this exploratory, randomized, double-blind, parallel-group study, 42 subjects received s.c. injections of treatment peptides 250 micrograms or placebo weekly for four consecutive weeks. Changes in immediate- and late-phase skin test reactivity, and in antigen-driven cytokine synthesis were assessed. Epicutaneous (end-point titration) and intradermal tests were performed with cat extract (ALK SQ Cat Hair) containing Fel d 1, before the first injection, then 2, 6 and 24 weeks after the fourth and last injection of peptides or placebo. IL-4, IL-10 and IFN-gamma expression by circulating peripheral blood mononuclear cells (PBMC) in response to cat extract was measured using short-term bulk culture of PBMC and short-term limiting dilution analysis. Subjects who received peptide immunotherapy did not tolerate significantly more cat extract containing Fel d 1 in the skin tests 2, 6 or 24 weeks after the last injection than they did at baseline, and their late-phase responses did not decrease significantly compared to baseline. Substantial IL-4, IL-10 and IFN-gamma responses were observed following primary culture of cat antigen-stimulated PBMC; however, the intensity of cytokine synthesis and the IFN-gamma: IL-4 ratio were unchanged in peptide- and placebo-treated groups 6 and 24 weeks after the last injection. A few hours after the injections, subjects receiving peptides reported more allergic rhinitis and asthma symptoms and more pruritus than those receiving placebo. We conclude that under the conditions tested, peptide immunotherapy did not reduce immediate- or late-phase skin reactivity to cat extract containing Fel d 1 or modify cat antigen-specific cytokine production significantly.

Adult↗

Effect of iodoxamide ethyl on allergy skin tests.

Lodoxamide ethyl is a new cromolyn-like drug which prevents antigen-induced mediator release from mast cells and antigen-induced bronchoconstriction in sensitive animals and man. The purpose of this study was to determine the effect of a single administration of lodoxamide ethyl on allergy skin tests. The effect of this drug on allergy skin testing was studied in a double-blind design on ten adult subjects allergic to ragweed. Serial end-point titrations with short ragweed extract and with histamine were performed after a placebo and 1- and 3-mg capsules of lodoxamide ethyl. The immediate wheal-and-flare responses as well as the late allergic reaction were recorded. No statistically significant difference was found between lodoxamide ethyl and placebo in the suppression of the allergen-induced immediate wheal-and-flare response or the late allergic reaction. Furthermore, 1 and 3 mg of oral lodoxamide ethyl did not inhibit the histamine-induced cutaneous reactions.

Amino Acids↗

Prediction of airway responsiveness to allergen from skin sensitivity to allergen and airway responsiveness to histamine.

Previous data have indicated that airway responsiveness to allergen, expressed as the provocation concentration causing a 20% FEV1 fall (PC20), was dependent on nonallergic airway responsiveness (histamine PC20) and sensitivity to allergen (skin sensitivity or end-point titration). From retrospective data in 24 subjects, we developed a formula to predict allergen PC20 and examined its accuracy prospectively in 26 new subjects undergoing allergen inhalation test with doubling allergen concentrations. Allergen PC20 (APC20) was predicted from histamine PC20 (HPC20) and skin sensitivity (SS) by the formula: Log10 (APC20) = 0.69 Log10 (HPC20 X SS) + 0.11 (r = 0.85). Allergen PC20 was accurately predicted in 6, and overestimated or underestimated by 1 doubling concentration in 11, by 2 concentrations in 6, by 3 concentrations in 3, and by greater than 3 concentrations in none. From the total of 50 subjects, a new relationship was developed: Log10 (APC10) = 0.68 log10 (HPC20 X SS) (r = 0.82) from which 46 of 50 (92%) of allergen PC20 values fall within 2 doubling concentrations of the regression line (and all within 3). Early airway responsiveness to a given allergen can be predicted within a +/- 8-fold range, which is better than some investigator's test reproducibility of +/- 1 log (10-fold). Allergen inhalation tests to determine early asthmatic responsiveness to different IgE-mediated allergens can probably be replaced by the simpler and safer determinations of allergen sensitivity (SS, RAST) and histamine or methacholine airway responsiveness.

Allergens↗

The atopic dog model: report of an attempt to establish a colony.

In an attempt to establish a colony of atopic dogs as a research resource, dogs with seasonal dermatitis - a reported manifestation of naturally occurring allergy in that species - were identified, acquired, and inbred. Progeny were studied during their first 2 years of life to determine if the trait could be genetically transmitted and to investigate the hypothesis that this spontaneously occurring dermatitis correlates with positive laboratory measurements for specific IgE to airborne allergens. (Serial immunoglobulin levels, including total IgE, end-point titration of histamine, and results of fecal examinations for identification of parasites were also investigated and are to be the subject of a separate publication.) Only a weak correlation between positive direct skin test results and the appearance of seasonal dermatitis was found in initial studies. Neither the results of testing by passive cutaneous anaphylaxis nor radioallergosorbent procedures correlated with positive clinical findings. Independently conducted clinical examinations and direct skin testing using selected antigens, as well as additional bronchial challenges of representative animals from the colony, also failed to furnish evidence of atopy in the dogs. Therefore, the goal of establishing an inbred line of atopic animals was not accomplished within the allotted 2-year period. Also, the data did not show a positive correlation between the seasonal dermatitis and measurements for specific IgE to airborne allergens.

Animals↗

Comparison of modified PhadezymRAST, ImmunoCAP, and serial dilution titration skin testing by receiver operating curve analysis.

Improved technology in in vitro tests for allergen-specific immunoglobulin E has led to increased efficiency and faster turnaround times. ImmunoCAP (Pharmacia Diagnostics, Clayton, N.C.) is an in vitro-specific immunoglobulin E test that uses a three-dimensional cellulose solid allergen phase, which allows quick results in 6 hours. In comparison, modified Phadezym-RAST (Pharmacia Diagnostics) uses a two-dimensional solid phase, and results take 3 days to obtain. This study compares the sensitivity and specificity of CAP with that of modified RAST in the detection of specific immunoglobulin E, and it assesses the correlation of the individual class scores of CAP and modified RAST with end points obtained from skin-dilutional end-point titration. The reproducibility of CAP was also assessed. Patients evaluated at the University of Chicago Allergy Clinic who had a history and physical examination consistent with immunoglobulin E-mediated allergy and in whom skin testing was clinically indicated as part of their allergy management, were asked to donate some blood for simultaneous in vitro testing by PhadezymRAST and ImmunoCAP. Testing was performed in batches. Random samples from the CAP batches were chosen for duplicate runs under conditions blinded to the technician. Receiver operating curve analysis was used for comparison of the sensitivity and specificity of RAST vs. that of CAP. We used Pearson product-moment correlation coefficients to compare the correlation of RAST and CAP classes with the end points from skin testing. Our results indicate that the sensitivity and specificity of RAST and CAP are similar, that the classes of these two tests correlate well with the end points from skin testing, and that duplicate samples of CAP also correlate well.

Adolescent↗

Local allergen challenge and bronchoalveolar lavage of allergic asthmatic lungs. Description of the model and local airway inflammation.

The local mechanisms that result in the cellular inflammation and bronchial airway hyperreactivity that characterize allergic bronchial asthma are poorly defined. In order to study these processes, we developed a method for local allergen challenge using a fiberoptic bronchoscope and direct observation and bronchoalveolar lavage (BAL) to assess the airway responses to allergen. In these studies, 11 allergic asthmatics (all of whom had previously demonstrated a late-phase asthmatic response to aeroallergen challenge) and 6 healthy, asymptomatic subjects volunteered to undergo bronchoalveolar lavage after local airway challenge via a bronchoscope wedged into subsegmental airways. These studies revealed that asthmatic airways respond to allergen with an immediate pallor followed by reactive hyperemia, edema, and bronchial narrowing. This site and a control site were relavaged at 48 or 96 h after the immediate response. Neutrophils and eosinophils increased significantly at 48 h after challenge, as did helper T-lymphocytes. Characteristically, at 96 h, neutrophil counts returned to normal values, whereas eosinophiles and helper T-cells remained elevated. Peroxidase-staining cells were also elevated at 48 h after local allergen challenge. Electron microscopy revealed degranulation of mast cells and eosinophils, both immediately and later (48 and 96 h) after local allergen challenge. Macrophages were highly activated and had phagocytized, partially intact granules from both eosinophils and mast cells. There was a significant correlation (p less than 0.001) between the concentration of allergen required to produce a visible airway response and a positive end-point skin titration in the asthmatic subjects.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗

Skin prick reaction and nasal provocation response in diagnosis of nasal allergy to the house dust mite.

BACKGROUND: The allergen skin test is commonly used to ensure the diagnosis of allergic rhinitis even though positive results do not necessarily indicate that rhinitis is of allergic origin. OBJECTIVE: To determine the association between skin prick reactions and nasal provocation responses to Dermatophagoides pteronyssinus (Der p) allergen extract. METHODS: Twenty-six patients with perennial rhinitis and 25 controls underwent skin prick and nasal provocation tests to standardized Der p allergen extract. With the use of allergen extract titration delivered by a metered dose pump, nasal stuffiness, itching, and sneezing were noted, the amount of secretions measured, and nasal airway resistance was recorded by active anterior rhinomanometry. RESULTS: The majority of the patients with rhinitis (20/26), but none of the controls, exhibited strong skin test positivity (4+) to Der p allergen extract. In addition, the majority of the patients with 4+ skin reactions (16/20) had moderate to severe rhinitis. Significantly increased nasal reactivity to the allergen was also observed among those with 4+ skin test positivity. The controls exhibited nasal provocation responses only with significantly higher end-point doses of the allergen extract regardless of the skin test results. CONCLUSION: Only 4+ skin test positivity was closely associated with increased nasal reactivity to Der p allergen among the patients with perennial rhinitis. The nasal provocation technique would be a useful adjunct testing to ensure the diagnosis of nasal allergy to the Der p mite, particularly among those patients with rhinitis with only mild to moderate skin test positivity.

Adolescent↗

A multidot immunobinding assay for the serodiagnosis of tuberculosis. Comparison with an enzyme-linked immunosorbent assay.

A simple dot immunobinding (dot blot) assay procedure has been developed for the detection of antibodies directed against a soluble mycobacterial antigen preparation. This technique was compared with the widely used ELISA, in a study of samples from tuberculous patients. Dot blots were read on a densitometer. The correlation between both assays was excellent (r = 0.91; P less than 0.001); 90% of sera from tuberculous patients were detected using both techniques and a serial two-fold dilution method. Assessments of the end-points of titration curves by reflectometry and simple visual interpretation gave similar results. The dot blot assay is easier to perform and appears to be a practical alternative to ELISA for the detection of anti-mycobacterial antibodies in tuberculous patients.

Adult↗

Nasal provocation with histamine in allergic rhinitis patients: clinical significance and reproducibility.

In a selected group of rhinitis patients (n = 12) with an IgE-mediated allergy to house dust mites, the nasal response to insufflation of histamine chloride appeared to be related to symptom scores obtained from the patients. In contrast to the sum of the nasal airway resistances (NAR) induced by all doses of histamine, the total amount of secretion and total number of sneezes could be predicted from clinical scores. The reproducibility of the nasal provocation test was tested by comparison of the test results in two sessions with a 1-week interval. The correlation between both sessions was highest with respect to nasal secretion (r = 0.87; P less than 0.001) and the number of sneezes (r = 0.76; P = 0.004). The correlation coefficient was 0.71 (P = 0.01) when the nasal airway resistance was used in the assessment of nasal response. A good reproducibility of the nasal provocation test was also obtained using an end-point titration method and determining the concentration required to produce 0.5 ml secretion and/or five sneezes as the end-point (r = 0.76; P = 0.004). The concentration required to double nasal airway resistance yielded a correlation coefficient of 0.56 (P = 0.052). We conclude that the clinical significance of nasal provocation with histamine increases when, besides nasal airway resistance, the amount of secretion and the number of sneezes is used in the assessment of the nasal response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗

Allergenic differences between the domestic mites Blomia tropicalis and Dermatophagoides pteronyssinus.

BACKGROUND: House dust mite allergens are the most important indoor allergens associated with asthma and rhinitis in Singapore and the tropics. Recent data to suggest that besides the Dermatophagoides spp., the domestic mite Blomia tropicalis (Bt) is also an important source of allergens in these regions. OBJECTIVE: To evaluate the degree of allergenic cross-reactivity between Bt and D. pteronyssinus (Dp). METHODS: Cross-reactivity between extracts of Bt and Dp was evaluated by fluorescent allergosorbent (FAST) inhibition studies and cross enzyme immunoelectrophoresis. Additionally, the major Dp allergens - Der p 1, Der p 2 and Der p 5, were also compared with the Bt extract by dot blot inhibition. Skin prick and intradermal end-point titration were then carried out to compare the homologous allergens of the mite species, Blo t 5 and Der p 5. RESULTS: FAST inhibition studies showed low to moderate cross-reactivity between the two dust mite extracts (maximum cross-inhibition, 60%). Native allergens studied by cross enzyme immunoelectrophoresis using mite allergic sera also showed similar results but with at least four cross-reactive IgE binding antigens. Dot blot inhibition studies using allergens of Dp, Der p 1, Der p 2, and Der p 5, showed little cross-reactivity between these allergens with components of the crude Bt extracts. Further, evaluation of a recombinant allergen of Bt, Blo t 5, showed low levels of cross-reactivity even with its homologous Dp counterpart, Der p 5. CONCLUSION: These results provide evidence that Bt allergens are distinct and have relatively low to moderate cross-reactivity with Dermatophagoides spp. allergens. Bt allergens should therefore be included in the diagnostic panel for the evaluation of allergic disorders in the tropics, and the development of new diagnostic and therapeutic strategies should include allergens of Bt.

Allergens↗