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Showing papers in "The Journal of Allergy and Clinical Immunology in 1979"


Journal ArticleDOI
TL;DR: This case study represents a previously undescribed late food hypersensitivity, induced only by strenuous exercise, that illustrates classical epidemiologic analysis, improves medical advice for the allergic and athletically inclined, and raises new questions in the areas of allergy and immunology.
Abstract: The syndrome of immediate type I food hypersensitivity, mediated by tissue-bound IgE antibody and mast cell histamine release, is well recorded in the medical literature. This case study represents a previously undescribed late food hypersensitivity, induced only by strenuous exercise. Identification of this new syndrome illustrates classical epidemiologic analysis, improves medical advice for the allergic and athletically inclined, and raises new questions in the areas of allergy and immunology.

328 citations


Journal ArticleDOI
TL;DR: In 10 of these 11 allergic children, complement-fixing antibodies to viruses (parainfluenza, RSV, CMV) increased in the same blood samples in which immunologic allergic sensitization was first evidenced, which suggests that certain viruses may contribute to the allergy sensitization process.
Abstract: Children born into allergic families, with two allergic parents, are at high risk of developing allergy within the first 5 years of life. In order to observe possible external factors in the sensitization process, a prospective study of 13 such children was done, in which serial clinical and immunologic observations were made at 3- to 6-month intervals over a period of 1 to 4 yr. Eleven of these children are now clinically allergic; 5 have asthma. Immunologic evidence for allergic sensitization was observed in these 11 children by RAST, antigen-induced leukocyte histamine release, lymphoblastogenesis, and rise in serum IgE. Upper respiratory infections (URI) occurred in these 11 allergic children 1 to 2 months prior to the onset of allergic sensitization. In 10 of these 11 URI children, complement-fixing antibodies to viruses (parainfluenza, RSV, CMV) increased in the same blood samples in which immunologic allergic sensitization was first evidenced. This coincidence suggests that certain viruses may contribute to the allergic sensitization process.

286 citations


Journal ArticleDOI
TL;DR: The nasal and respiratory symptoms observed after oral challenge to aspirin (ASA), tartrazine, and other nonsteroidal anti-inflammatory substances are best described as idiosyncratic reactions as mentioned in this paper.
Abstract: The nasal and respiratory symptoms observed after oral challenge to aspirin (ASA), tartrazine, and other nonsteroidal anti-inflammatory substances are best described as idiosyncratic reactions. A positive response to oral challenge, defined as a 20% fall in forced expiratory volume in 1 sec (FEV1) from baseline for up to 4 hr, occurred in 44 of 230 patients with ASA, 11 of 277 with tartrazine, 2 of 93 with sodium salicylate, and 2 of 69 with acetaminophen. No one had a positive response to tartrazine, sodium salicylate, or acetaminophen who was not also positive to ASA. The dose of ASA causing a positive response was less than 5 grains in 95% of the patients. Of 50 patients with a suspicious history studied in detail, 96% of those with ASA idiosyncrasy had sinusitis and 71% had nasal polyps. Methacholine challenges and random circulating and sputum eosinophils did not differentiate patients with a negative challenge from those with a positive challenge. However, patients with a positive history and positive challenge had significantly more random nasal eosinophils than those with negative aspirin challenges. The term "aspirin triad" has outlived its usefulness since ASA idiosyncrasy can exist in patients lacking certain components of the triad. ASA idiosyncrasy is unsuspected in many patients and possibly overdiagnosed in others.

208 citations


Journal ArticleDOI
TL;DR: The findings suggest nonspecific bronchial hyperreactivity is likely to be the consequence rather than the predisposing factor in occupational asthma, and Methacholine inhalation test is a simple, safe, and useful procedure in the initial assessment of patients suspected to have occupational asthma.
Abstract: The provocative concentration (PC 20 mg/ml) of methacholine required to produce a fall in the baseline FEV 1 by 20% was determined in 86 patients with occupational asthma due to exposure to western red cedar, California redwood, grain dust, or isocyanates. Fifty-seven patients were assessed at the time of diagnosis when they were symptomatic. Twenty-nine patients were studied after they had been removed from exposure for a period from 2 mo to 4 yr and were asymptomatic. Nine of the 57 patients with symptomatic asthma had repeat methacholine inhalation tests after removal from exposure. The results were compared with 33 normal healthy subjects, 30 patients with nonoccupational asthma, and 17 patients with nonindustrial chronic bronchitis. Patients with symptomatic occupational asthma had marked increase in bronchial reactivity similar to those with nonoccupational asthma. The degree of hyperreactivity decreased after removal from exposure and increased following re-exposure to the offending agents. There was little overlap in the range of PC 20 in the asthmatic compared with the nonasthmatic groups. These findings suggest nonspecific bronchial hyperreactivity is likely to be the consequence rather than the predisposing factor in occupational asthma. Methacholine inhalation test is a simple, safe, and useful procedure in the initial assessment of patients suspected to have occupational asthma before institution of time-consuming specific bronchial provocation test.

189 citations


Journal ArticleDOI
TL;DR: Recommendations are derived from experience with the evaluation of over 500 patients and the therapy of over 300 adults and children, and a degree of controversy persists in this field, and additional data must be gathered before a fully defined position can be established.
Abstract: There has been significant recent progress in the diagnosis and treatment of patients with Hymenoptera sensitivity.‘-” Many problems remain, and, indeed, the introduction of new information has raised additional questions. Treatment is highly efficacious but expensive, of long duration, and has an unknown degree of long-term side effects. The question of whom to treat, therefore, becomes critical. With the commercial availability of venoms for immunotherapy, the practicing allergist will need to make a series of difficult decisions. With this in mind, it seems appropriate to present our clinical and laboratory experience during the last five years and to summarize our suggestions concerning the management of patients with an allergy to insect stings. Our recommendations are derived from experience with the evaluation of over 500 patients and the therapy, including inhospital sting, of over 300 adults and children. A degree of controversy persists in this field, and additional data must be gathered before a fully defined position can be established. We have tried to make what follows as precise a statement of what is and is not known as is currently possible. Whole body extract therapy In the first volume of the

185 citations


Journal ArticleDOI
TL;DR: Binding studies using (−) [ 3 H] dihydroalprenolol (DHA) were performed on lymphocytes of 10 control subjects and 11 stable asthmatic patients, finding specific DHA binding was generally lower at all DHA concentrations in asthmatics.
Abstract: In order to assess the status of beta adrenergic receptors in bronchial asthma, binding studies using (−) [ 3 H] dihydroalprenolol (DHA) were performed on lymphocytes of 10 control subjects and 11 stable asthmatic patients. Specific DHA binding was generally lower at all DHA concentrations in asthmatics. At 12 nM DHA concentration, specific DHA binding was 391 ± 40 fM/mg protein in controls and 263 ± 35 fM/mg protein for asthmatic subjects (p

160 citations


Journal ArticleDOI
TL;DR: The findings confirm that ASA intolerance is relatively common but suggest on the other hand that reactions to dyes and preservatives are uncommon cause of clinically significant bronchoconstriction in moderately severe perennial asthmatics.
Abstract: Forty-five patients with moderately severe perennial bronchial asthma were challenged by ingestion of: acetylsalicylic acid (ASA); 4 azo dyes (tartrazine, sunset yellow, amaranth, and ponceau); 3 non-azo dyes (erythrosine, brilliant blue, and indigotin); sodium benzoate (NaB): parahydroxybenzoic acid (OHBA); butylated hydroxyanisole (BHA); and butylated hydroxytoluene (BHT). A fall in forced expiratory volume in one second (FEV 1 ) greater than 25% from baseline was considered positive. Seven patients who gave an unequivocal history of aspirin intolerance were not challenged with ASA; an additional 13 had positive open challenges to ASA, giving an apparent incidence of aspirin sensitivity of 2045. The presence of nasal polyps, sinusitis, or the regular use of corticosteroids, either singly or in combination, was not associated with an increased incidence of reactions to ASA. Significant bronchoconstriction to open challenges with agents other than ASA was less frequent. Positive open challenges to all substances except aspirin were followed by double-blind challenges which were positive in only 3 instances: 1 each with erythrosine, ponceau, and NaBOHBA. Our findings confirm that ASA intolerance is relatively common but suggest on the other hand that reactions to dyes and preservatives are an uncommon cause of clinically significant bronchoconstriction in moderately severe perennial asthmatics.

153 citations


Journal Article
TL;DR: In this article, the authors studied 64 sting-allergic patients treated with one of three regimens of insect-venom immunotherapy: slow, rush, or a step-function regimen.
Abstract: We studied 64 sting-allergic patients treated with one of three regimens of insect-venom immunotherapy: slow, rush, or a step-function regimen. All regimens had a top dose of 100 micrograms and a similar cumulative dose. Efficacy was 100% in all regimens. Fifty percent of the patients had at least one large local reaction at a rate of 9.6 reactions/100 injections. Sixteen percent had systemic symptoms at 1.6 reactions/100 injections. Reaction rates did not differ among the groups, but the slow regimen involved twice as many injections as the rush regimen, and thus caused twice the number of reactions. The rush regimen caused a greater and more rapid rise in anti-venom IgG than did the slow regimen, with no difference in IgE levels. We conclude that although equally effective, the rush regimen of venom immunotherapy is associated with a greater immune response and fewer adverse reactions that the slow regimen.

152 citations


Journal ArticleDOI
TL;DR: It is concluded that the methacholine test may prove useful as a sign of perennial rhinitis and also for the objective evaluation of medication, but further studies are warranted.
Abstract: The aim of this study was to develop a test for the measurement of nasal reactivity. Different concentrations of methacholine were sprayed intranasally, and the nasal secretion and blockage were measured in normal subjects. The simple collection and measurement of secretion was found to be a valuable parameter of mucosal reactivity, while measurement of nasal airway resistance was unreliable, due in part to the presence of secretion in the nasal cavity. The methacholine test had a fairly good reproducibility when the amount of secretion was used as the only parameter. It caused a significantly stronger reaction in women than in men. Patients with perennial rhinitis had a more vigorous response than the controls. It is concluded that the methacholine test may prove useful as a sign of perennial rhinitis and also for the objective evaluation of medication, but further studies are warranted.

143 citations


Journal ArticleDOI
TL;DR: Changes in lung mechanics and blood gas tensions seen during exercise-induced asthma are similar to those observed in patients with asthma provoked by other stimuli.
Abstract: It is 15 yr since Jones et al.’ first described the effects of isoproterenol on the postexercise increase in airway resistance in patients with asthma. Studies of the incidence, severity, and reproducibility of exercise-induced asthma (EIA) have established that in 70% to 75% of patients with clinically recognized asthma, the postexercise fall in peak expiratory flow rate (PEFR) or forced expiratory volume in 1 set (FEV,) exceeds 10% of the preexercise value.2. I’ Changes in lung mechanics and blood gas tensions seen during EIA are similar to those observed in patients with asthma provoked by other stimuli.“. Irk II Consequently EIA has been used as a model for the investigation of drugs used in treatment of asthmatics. During the past 10 yr many studies have been carried out to determine the effect of a wide variety of pharmacologic agents on EIA. The drug groups studied include

139 citations


Journal ArticleDOI
TL;DR: The dose-response curves and thus the degree of bronchial sensitivity were determined in 19 subjects in a randomized 4-way crossover study and the short-term reproducibility for both methods was good.
Abstract: Methacholine sensitivity has become a valuable and widely used technique for studying the irritability of the airways. Asthmatics are lOOto l,OOO-fold more sensitive than normal subjects to various mediators such as methacholine (P-acetyl methacholine).‘-” This degree of sensitivity has been used to define asthma and also as a genetic marker.l The methacholine responsiveness may be determined by 1 of 2 methods: (1) by determining dose-response curves to increasing concentrations of methacholine while keeping the number of breaths and the volume of methacholine inhaled constant” and (2) by determining dose-response curves by keeping the concentration constant while increasing the number of inhalations of methacholine.” The first method is currently being used more widely and has been recommended by the American Academy of Allergy to provide a standard and uniform method. It is described in detail elsewhere.” The second method has been used since 1962 and has been the basis for a number of short-term and long-term studies. We have recently compared both of these methods to determine the short-term reliability of each method. The dose-response curves and thus the degree of bronchial sensitivity were determined in 19 subjects in a randomized 4-way crossover study. Each subject was challenged twice by each method at 1-wk intervals. The short-term reproducibility for both methods was good (r = 0.934 and 0.942). The correlation between methods was also significant (r =0.953). The various pulmonary function parameters that can be evaluated during an inhalation challenge are numerous and include the FVC, FEV,, SG,,,, FEF,,-,,, PEFR, flow volume loops, etc. The easiest and the most widely used currently is the FEV,, which is the minimum requirement for comparison of responses as recommended by the Standardization Committee, j

Journal ArticleDOI
TL;DR: The results indicate that cockroach antigen causes antigen-specific IgE-mediated bronchial asthma and peripheral eosinophilia in specifically sensitized asthmatic subjects.
Abstract: To assess the etiologic role of cockroach antigen in bronchial asthma, 46 asthmatic subjects were studied using in vitro assays for total and cockroach-specific IgE antibodies (IgEcr) and the responsiveness of the skin and bronchial tree to the antigen challenge in vivo. Asthmatic subjects were divided into skin test-positive (PCR) and skin test-negative (NCR) groups according to immediate skin response to cockroach antigen. The 28 in the PCR group showed high total IgE (1,901 ng/ml) and a high cockroach-specific IgE antibody level (329%) in the serum compared to the 10 in the NCR group (IgE: 915 ng/ml, IgEcr: 84%) (p < 0.001). Bronchial challenge with the antigen revealed immediate asthmatic reaction (3033) and late asthmatic reaction (1633) in the PCR asthmatics, whereas the NCR asthmatics showed neither immediate asthmatic reaction (213 showed questionable decrease in FEV1) nor late asthmatic reaction (p < 0.001). A marked increase in peripheral eosinophils (758% vs 121%) was noted following antigen inhalation in the skin test-positive asthmatics (p < 0.025). The results indicate that cockroach antigen causes antigen-specific IgE-mediated bronchial asthma and peripheral eosinophilia in specifically sensitized asthmatic subjects.

Journal ArticleDOI
TL;DR: The close correlation between the level of bronchial responsiveness to histamine and exercise supports the view that release of endogenous chemical mediators is an important determinant of exercise-induced asthma.
Abstract: Bronchial responsiveness to inhaled histamine and exercise was measured in 19 asthmatics. Histamine aerosol was inhaled to determine the provocative concentration producing a 20% fall in forced expired volume in one second (FEV 1 ) (PC 20 ). Exercise was performed on a treadmill and a cycle ergometer; following each procedure the percent fall in the FEV 1 (ΔFEV 1 ) and the exercise lability (percent rise in FEV 1 plus percent fall in FEV 1 ) were calculated. ΔFEV 1 and exercise lability after both forms of exercise were similar. PC 20 correlated with ΔFEV 1 and exercise lability in both forms of exercise; however, the correlation with exercise lability was better. PC 20 was more sensitive in demonstrating bronchial hyperresponsiveness. The close correlation between the level of bronchial responsiveness to histamine and exercise supports the view that release of endogenous chemical mediators is an important determinant of exercise-induced asthma. The treadmill exercise and cycle ergometry protocols were equally effective in producing exercise-induced asthma.

Journal ArticleDOI
TL;DR: Peyton A. Eggleston, M.D., Richard R. Rosenthal, and Joseph J. Trautlein are the co-chairs of the Study Group on Exercise Challenge, Bronchoprovocation Committee.
Abstract: Peyton A. Eggleston, M.D., Richard R. Rosenthal, M.D., Chairmen, Sandra A. Anderson, Ph.D., Ross Anderton, M.D., C. Warren Bierman, M.D., Eugene R. Bleecker, M.D., Hyman Chai, M.D., Gerd J. A. Cropp, M.D., Ph.D., Jerry D. Johnson, Ph.D., Peter Konig, M.D., John Morse, M.D., Laurie J. Smith, M.D., Richard J. Summers, M.D., and Joseph J. Trautlein, M.D. Study Group on Exercise Challenge, Bronchoprovocation Committee. American Academy of Allergy

Journal ArticleDOI
TL;DR: Prick test reactivity to 14 common local allergens correlated with the presence of allergy symptoms and mean total serum IgE (PRIST) levels were significantly higher than normal.
Abstract: The relationship between prick and intradermal skin test reactivity and serum levels of total and specific IgE was evaluated in 311 subjects selected from a general population. Test results were related to the historical allergy status of the subjects. Prick test reactivity to 14 common local allergens correlated with the presence of allergy symptoms. Similarly, mean total serum IgE (PRIST) levels were significantly higher (p

Journal ArticleDOI
TL;DR: Skin testing as part of a progressive challenge protocol is a useful approach to the management of alleged local anesthetic hypersensitivity and may suggest the possibility of true immediate hypersensitivity to the agent tested.
Abstract: We have studied the utility of skin testing and progressive challenge to detect local anesthetic hypersensitivity in patients with histories of reactions to local anesthetics. The likelihood of previous immediate hypersensitivity reactions was determined by history in 90 referrals. Fourteen had histories compatible with immediate hypersensitivity reactions, 24 did not, and the history was uncertain in 52. Of the 14, 12 were negative to lidocaine skin test and challenge, although 5 gave histories of immediate hypersensitivity reactions to it. The other 76 patients also underwent skin testing and progressive challenge. No skin tests were positive with 1:100 local anesthetics but 10 patients had positive intradermal skin tests to undiluted 1% local anesthetics. Proof of false positivity was confirmed in 4 of 10 cases by uneventful challenge to the local anesthetic giving the positive skin test. At least 1 local anesthetic was cleared for use in each of the 90 patients. Skin testing as part of a progressive challenge protocol is a useful approach to the management of alleged local anesthetic hypersensitivity. True immediate hypersensitivity reactions to local anesthetics are rare. Positive skin tests to dilutions of 1:100 local anesthetics are also rare and may suggest the possibility of true immediate hypersensitivity to the agent tested.

Journal ArticleDOI
TL;DR: Patients who suffered a reaction to the administration of muscle relaxant during induction of general anesthesia were explored using skin tests, leukocyte histamine release, lymphocyte transformation test, and the Prausnitz-Küstner test, suggesting possible specific serum IgE antibodies to muscle relaxants.
Abstract: Eleven patients who suffered a reaction to the administration of muscle relaxants during induction of general anesthesia were explored using skin tests, leukocyte histamine release, lymphocyte transformation test, and the Prausnitz-Kustner test (P-K). Fifteen normal subjects served as controls. Patients who suffered a reaction showed considerable cutaneous hypersensitivity to muscle relaxants. Leukocyte histamine release was positive in three cases and the P-K test was positive in one case. These findings suggest possible specific serum IgE antibodies to muscle relaxants. However, reliable discrimination between immunological and idiosyncratic pharmacological mechanism is difficult to obtain.

Journal ArticleDOI
TL;DR: Two protein fractions of rice, grain, glutelin and globulin, were prepared by dilute alkali and salt extraction and found to be reactive with specific IgE antibody, and G1-1 and G-2 revealed lymphocyte-stimulating activity.
Abstract: Two protein fractions of rice, grain, glutelin and globulin, were prepared by dilute alkali and salt extraction, respectively The globulin fraction was separated into G1-1, G1-2, and G1-3 fractions by Sephadex G-200 column chromatography The allergenic activities and lymphocyte-stimulating properties of these fractions were investigated by the radioallergosorbent test (RAST) with sera from 6 individuals who showed immediate skin reaction to soluble rice extract and by 3H-thymidine incorporation tests with 5 subjects with indurated skin reaction of delayed onset All fractions were found to be reactive with specific IgE antibody, and G1-1 and G-2 revealed lymphocyte-stimulating activity RAST inhibition revealed considerable cross-reactivity of IgE antibody with the glutelin and globulin fractions When the glutelin and globulin fractions were heated at 60 degrees C for 1 hr, 100 degrees C for 2 min, or 100 degrees C for 10 min, RAST activities were reduced to 40%-70% of native On the other hand, lymphocyte-stimulating activities of the globulin fraction heated at 60 degrees C for 1 hr or 100 degrees C for 2 min were enhanced up to 6 times of native activities, while those of identically treated glutelin fractions remained unchanged

Journal ArticleDOI
TL;DR: Mattress dust collected at monthly intervals for 2 1/2 yr was examined for mites and both Dermatophagoides pteronyssinus and D. farinae were found.
Abstract: Mattress dust collected at monthly intervals for 2 1/2 yr was examined for mites. Both Dermatophagoides pteronyssinus and D. farinae were found. There was a significant association between the presence of live mites and the relative humidity (RH): Live mites were seen only when the RH had been greater than or equal to 50% for at least part of every day during the month of collection. There was a seasonal variation in that live mites were found only in the warmer months and not in the winter. However, the peak in the mite population was consistent neither for month nor for numbers: In 1977 a slight peak in mite numbers occurred in October, while in 1978 the peak was higher and occurred in July. Use of data from previously published studies to preduct mite levels may therefore be misleading.

Journal ArticleDOI
TL;DR: The vulnerability of the hypoxic myocardium to the effects of isoproterenol suggests that careful cardiac monitoring is essential in the management of patients receiving this medication for treatment of respiratory failure secondary to severe asthma.
Abstract: We recently utilized continuous infusion intravenous isoproterenol in the treatment of respiratory failure in an 18-yr-old steroid-dependent asthmatic female. Aminophylline, hydrocortisone, aerosolized isoetharine, and oxygen were also administrered. The patient responded to this therapy, with PaCO2 falling from 70 torr to 33 torr in 18 hr. The maximum isoproterenol dosage administered was 0.32 microgram/kg/min. Thirty-six hours following the institution of therapy, while the isoproterenol was being tapered, the patient experienced an increase in respiratory distress followed by cardiac arrest. Postmortem examination revealed multiple small areas of myocardial necrosis. These findings, unusual in asthma, probably were related to the effects of isoproterenol or the combination of isoproterenol and aminophylline on the stressed myocardium. The vulnerability of the hypoxic myocardium to the effects of isoproterenol suggests that careful cardiac monitoring is essential in the management of patients receiving this medication for treatment of respiratory failure secondary to severe asthma.

Journal ArticleDOI
TL;DR: Although satisfactory long-term clinical results were achieved for most patients, the frequency of systemic reactions during the rush immunization caused this form of treatment to be abandoned in favor of a once-weekly outpatient injection program.
Abstract: The clinical and immunological effects of honeybee venom (HBV) immunotherapy were studied in 20 HBV-sensitive patients. Patients were treated once monthly in a hospital setting by "rush" immunotherapy; we aimed for a maximum single dose of 200 μg. One patient withdrew shortly after beginning therapy. Eleven patients required epinephrine during treatment for reversal of anaphylaxis. Patients who tolerated maximum doses were readmitted one month later for deliberate honeybee sting challenges. Stings were tolerated by 11 of 19 patients; 5 of the remaining 8 required epinephrine therapy. Twelve of 16 patients achieved long-term protection as determined by deliberate stings; 4 of 16 achieved partial protection. Three additional patients, who were treatment failures, were switched to weekly immunotherapy. IgE antibodies to HBV and phospholipase A (PLA) rose shortly after immunotherapy was begun and in many patients remained elevated above baseline values. Serum IgG antibodies to PLA rose steadily during therapy; there was no absolute level of IgG antibody which was protective for all patients. Although satisfactory long-term clinical results were achieved for most patients, the frequency of systemic reactions during the rush immunization caused us to abandon this form of treatment in favor of a once-weekly outpatient injection program.

Journal ArticleDOI
TL;DR: This response may require quantitative assessment because of the poor correlation that exists between historical and laboratory evidence for exercise-induced bronchospasm (EIB), and it can be used to provoke airway obstruction in patients with suspected, but unconfirmed asthma.
Abstract: Patients with asthma frequently develop acute, reversible, and usually self-terminating airway obstruction after or near the end of strenuous muscle exercise.‘. 2 This response may require quantitative assessment because of the poor correlation that exists between historical and laboratory evidence for exercise-induced bronchospasm (EIB),:’ and it can be used to provoke airway obstruction in patients with suspected, but unconfirmed asthma. During the past few years a number of tests have been developed for the assessment of EIB. The increased utilization of such procedures makes standardization of the methods timely and necessary so that safe and adequate techniques are used and so that results obtained in different laboratories can be compared.

Journal ArticleDOI
TL;DR: TDI reactors gave decreased lymphocyte cAMP dose response slopes to stimulation with isoproterenol, prostaglandin E1, and TDI, which suggests that impairment of adrenergic receptors may play an important role in TDI reactivity.
Abstract: Workers with "sensitivity" to toluene diisocyanate (TDI) studied in depth in an attempt to determine mechanisms of bronchial hyperreactivity. Tests included provocative inhalation challenge (PIC) with TDI and methacholine challenge. Blood samples obtained prior to and at various times after PIC were used to measure complement and split products of complement and plasma histamine levels and to determine dose-response slopes of lymphocyte cyclic adenosine monophosphate (cAMP) following stimulation with agonists. TDI-reactive individuals were all reactive to methacholine and responded to PIC with TDI by immediate, delayed, or dual bronchospastic reactions. No change in plasma histamine, total complement levels, or split products of complement were measurable. TDI reactors gave decreased lymphocyte cAMP dose response slopes to stimulation with isoproterenol, prostaglandin E1, and TDI, which suggests that impairment of adrenergic receptors may play an important role in TDI reactivity.

Journal ArticleDOI
TL;DR: Although histamine levels, complement activity, and fibrin split products changed in a substantial number of patients undergoing RCM infusions, these changes did not correlate with immediate generalized reactions or with the previously described clinical parameters.
Abstract: To further an understanding of the effects of radiographic contrast media (RCM) infusions, 43 patients underwent clinical evaluation, including allergy history and skin testing, at least 48 hr before receiving a bolus of Renografin-60 (meglumine diatrizoate [52] and sodium diatrizoate [8]) for intravenous pyelography. Venous plasma samples were obtained serially before and at 2, 4, 10, 30, and 60 min after the infusion. Each sample was assayed for histamine by isotopic enzyme assay, for complement by total hemolytic activity, and for fibrin split products by radioimmunoassay. Immediate generalized reactions occurred in 6 of the patients. Each of the 43 patients had a change in at least 1 of the mediators measured. Plasma histamine rose in 40% of the patients (mean, 3.1 ± 1.62 ng/ml). Plasma complement hemolytic activity decreased in 63% (mean, 29 ± 19%). Fibrin split products were detected in 41%. In comparing the 6 patients who experienced reactions to the 37 who did not, there were no statistically significant differences in rise in plasma histamine, decrease in complement activity, presence of fibrin split products, personal history of allergy, prior exposure or reaction to RCM, skin tests to RCM, and histamine or saline. Although histamine levels, complement activity, and fibrin split products changed in a substantial number of patients undergoing RCM infusions, these changes did not correlate with immediate generalized reactions or with the previously described clinical parameters. It is probable that other modulating factors play significant roles in determining whether or not a reaction occurs.

Journal ArticleDOI
TL;DR: Both airway hyperpermeability and hyperreactivity to inhaled histamine were observed following specific antigen challenge in this animal model, consistent with the hypothesis that airway mucosal hyper permeability induced by an allergic reaction is one of the factors contributing to airwayhyperreactivity by increasing flows of inhaled bronchoactive agents to effector sites in the airway wall.
Abstract: In four Ascaris-sensitive rhesus monkeys, we measured the fractional absorption of 3 H-histamine ( 3 HH) and airway response, as pulmonary resistance (R 1 ), to standard histamine aerosols containing tracer amounts of 3 HH for control runs (Run 1) and runs after Ascaris antigen challenge (Run 2). The mean rate of accumulation of radioactivity in the plasma volume as a function of delivered dose during histamine exposure (2 min) was fivefold greater for Run 2 (0.047% delivered dose/min) as compared with Run 1 (0.009% delivered dose/min). Whereas histamine inhalation led to insignificant (less than 25%) increases in R L over control in Run 1, R L increased by 247% over control after histamine inhalation in Run 2. Thus, both airway hyperpermeability and hyperreactivity to inhaled histamine were observed following specific antigen challenge in this animal model. These data are consistent with the hypothesis that airway mucosal hyperpermeability induced by an allergic reaction is one of the factors contributing to airway hyperreactivity by increasing flows of inhaled bronchoactive agents to effector sites in the airway wall.

Journal ArticleDOI
TL;DR: Results suggest that corticosteroids induce a prominent decrease in leukocyte histamine due to a depletion of basophils without a decrease in histamine content per basophil, and that skin tissue histamine stores remain unchanged by such treatment.
Abstract: The comparative effect in 11 atopic subjects of a single intravenous injection of methylprednisolone on sequential studies of blood eosinophils, basophils, leukocyte sensitivity to antigen for histamine release, leukocyte histamine content, and skin histamine was examined. No significant changes occurred in any parameter after placebo treatment. In contrast, 4 hr after intravenous treatment with steroid there were significant decreases in mean eosinophil counts (-95%), basophil counts (-72%), and histamine content of 1 X 10(7) leukocyte samples (-62%). Temporal changes in the latter paralleled alterations in circulating basophil levels. No significant changes occured in the antigen histamine release sensitivity, or the total skin histamine. Studies over a longer period after steroids in 4 subjects showed eosinophil and basophil levels at a nadir at 8 hr, remaining suppressed for 24 hr, and returned to pretreatment levels by 72 hr. Results suggest that corticosteroids induce a prominent decrease in leukocyte histamine due to a depletion of basophils without a decrease in histamine content per basophil, and that skin tissue histamine stores remain unchanged by such treatment.

Journal ArticleDOI
TL;DR: Clinical, physiological, and immunological studies of the supervisor of a meat tenderizer factory who developed asthma after long-term contact with papain dust revealed the presence of a dual type I and III hypersensitivity.
Abstract: Increasing reports of respiratory disease associated with exposure to papain prompted clinical, physiological, and immunological studies of the supervisor of a meat tenderizer factory who developed asthma after long-term contact with papain dust. His symptoms were worse at work and better on weekends and vacations. Bronchial inhalation challenges produced both immediate and late asthma to papain but not to the other ingredients in the food product. Immunological studies revealed the presence of specific IgE antibodies by direct and passive transfer skin tests and the radioallergosorbent test, and specific precipitating antibodies by immunodiffusion tests. These findings are indicative of a dual type I and III hypersensitivity. Papain acting as an allergen in an occupational setting is a risk factor for eliciting asthma even in a nontropic individual.

Journal ArticleDOI
TL;DR: It is suggested that exercise-induced asthma is dependent on two factors: a stimulus generated during exercise and a response from abnormal bronchi, and the bronchial response may be a limiting factor in asthmatics with less responsive airways.
Abstract: The airway responses to methacholine and to exercise challenges were compared in 45 young adults with asthma. The spirometric response to five minutes of treadmill exercise was first documented. On a separate day methacholine dose-response relationships were determined. All asthmatics had an abnormal response to methacholine, and 36 had an abnormal response to exercise. Methacholine sensitivity and exercise-induced asthma were significantly related (r = 0.69, p

Journal ArticleDOI
TL;DR: Data indicate that human and GP peripheral lung tissues respond to H1, but not H2, stimulation with the generation of PGF2 alpha and PGE; these parenchymal responses are specific and may not be attributed to muscle contraction; and stimulation of muscle contraction in human airway preparations results in the selectivegeneration of PGE while GP airways produce both PGE and P GF2 alpha.
Abstract: Anaphylaxis of human lung is accompanied by the synthesis of prostaglandins (PG), including PGF 2α and PGE. In an analysis of the tissue source of these prostaglandins, parenchymal preparations of both human and guinea pig (GP) lungs were compared. Peripheral, relatively airway-free preparations of human lung generate PGF 2α and PGE in response to histamine and 2-methylhistamine, an H 1 agonist, but not to dimaprit, an H 2 agonist. GP parenchymal preparations respond in a similar fashion. Stimulation of these same preparations with KCl or carbachol caused no increase in the synthesis of either PG. In human airway preparations all three agonists (histamine, KCl, and carbachol) caused the selective generation of PGE. However, stimulation of GP airway preparations with the agonists caused the production of both PGE and PGF 2α . These data indicate that (1) human and GP peripheral lung tissues respond to H 1 , but not H 2 , stimulation with the generation of PGF 2α and PGE; (2) these parenchymal responses are specific and may not be attributed to muscle contraction; and (3) stimulation of muscle contraction in human airway preparations results in the selective generation of PGE while GP airways produce both PGE and PGF 2α .

Journal ArticleDOI
TL;DR: In this paper, terbutaline was inhaled in one, two, or four inhations at 1 min intervals from a freon-propelled, metered-dose aerosol.
Abstract: Sixteen patients with bronchial asthma participated in three studies of inhaled terbutaline. Onset of action, duration, and peak effects were compared for a dose of 0.5 mg given in one, two, or four inhalations at 1 min intervals from a freon-propelled, metered-dose aerosol. There was no significant difference in the response between the schedules. Dose-response curves were compared for terbutaline from a metered-dose aerosol, and pressure nebulized with and without intermittent positive pressure breathing (IPPB). There was no difference between the response with IPPB and simple nebulization. Improvement continued to the total dose administered of 9.0 mg. For a given bronchial response, six to eight times as much terbutaline was required by pressure nebulization as from the metered-dose aerosol.