Immunotherapy decreases skin sensitivity to ragweed extract: demonstration by midpoint skin test titration.
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Humans↗
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Allergy skin tests and immunotherapy: comparison of methods in common use.
Scratch, prick, single dilution intradermal, and skin endpoint titration skin testing techniques are compared and contrasted. The use of these skin testing methods for safely initiating and advancing allergy immunotherapy treatment is discussed. Concepts of low-dose, symptom-relieving dose, and maximally-tolerated dose immunotherapy are described, and common factors in all allergy techniques are stressed.
Humans↗
Studies on Alternaria allergens. II. Measurement of the relative potency of commercial Alternaria extracts by the direct RAST and by RAST inhibition.
The relative potency of 12 commercial Alternaria extracts was analyzed by end-point skin test titrations and compared to in vitro measurements of potency, including (1) the radioallergosorbent test (RAST) inhibition procedure; (2) the direct RAST procedure; and (3) the protein nitrogen unit (PNU) content. Potencies determined by skin testing 10 sensitive patients were strongly correlated among the various patients. Measurements of potency by both RAST inhibition and direct RAST assay were strongly correlated to potency as measured by skin testing. In contrast, neither the weight:volume nor the PNU content bore any relationship to allergenic potency as measured by skin testing or by either of the RAST procedures. Extracts differed by as much as 3,000-fold in allergen content by skin testing. Moreover, the extracts appeared to contain different allergenic determinants when tested by RAST inhibition. RAST inhibition offered several technical advantages over the direct RAST procedure, in that only one solid-phase RAST reagent was required, slopes of dose-response curves could be more easily compared, and a greater discrimination in allergenic potencies among extracts could be made. The RAST appears to offer an excellent method for measuring the potency of allergy extracts, pending the isolation and characterization of actual allergens.
Allergens↗
Skin endpoint titration. Still the standard?
Skin endpoint titration, being both quantitative and calibrated in accordance with the patient's own reactivity, may still be considered the most sophisticated means of identifying an allergenic offender. Other forms of skin testing, simpler to perform, are rapidly becoming more uniform and quantitative. Laboratory tests provide more specific information and improved convenience. All occupy important positions in allergy diagnosis.
History, 20th Century↗
Blending skin endpoint titration and in vitro methods in clinical practice.
The definitive diagnosis of allergy involves proving the presence of allergen-specific IgE. This had traditionally been done by skin testing, the most precise method being skin endpoint titration. In vitro diagnostic methods offer advantages over skin tests and have become increasingly popular with both patients and physicians. However, thorough knowledge of skin testing techniques and interpretation of results is necessary for the physician using in vitro test methods and also allows moving back and forth between the two modalities in the preparation of antigen treatment sets and adjustment of immunotherapy dosage.
Antibody Specificity↗
Experience with RAST-based immunotherapy.
During its 80 year history, allergen immunotherapy has been used essentially as Noon and other early investigators described it. Immunotherapy is practiced mainly as an art based on uncontrolled clinical observations of individual patients treated in private practice. Dosing schedules and skin test interpretations are based primarily on the biases of the treating physicians. In an effort to improve the results obtained from immunotherapy, different approaches have evolved. Serial dilution skin endpoint titration (SET), practiced mostly by otolaryngologists, became popularized in the 1960s out of the need to optimize immunotherapy dosing regimens. SET can be viewed as a forward step in the direction of more aggressive yet safe initial immunotherapy doses. With the discovery of IgE in 1966 as the prime carrier of reaginic hypersensitivity in humans came the availability of a remarkable set of in vitro assays for the measurement of total and allergen-specific IgE reactivity. The radioallergosorbent test (RAST), which has been shown to correlate reliably with the major variants of the atopic state, was modified in 1977 in such a way as to enhance the sensitivity of the assay with minimal alteration of specificity. The modified RAST (MRT) has been carefully investigated and has shown reliable concordance with the major parameters of clinical allergy. Since its development only 14 years ago, the MRT has become a dependable adjunct for the determination of initial and in many cases final immunotherapy doses. An important contribution of RAST-based immunotherapy is that only patients with quantifiable serum titers of allergen-specific IgE qualify as candidates for immunotherapy. The fact that fewer allergens are used for treatment at higher initial doses and that potential reactors are identified before starting therapy are yet other advantages of RAST-based immunotherapy. The use of RAST as a method of allergen standardization only reinforces its value in patient management.
Allergens↗
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↗
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↗
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↗
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↗
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↗