Showing papers in "The Journal of Allergy and Clinical Immunology in 1986"

The eosinophil and the pathophysiology of asthma

Abstract: Eosinophilia of lung and blood associated with injury to the mucociliary escalator and excessive shedding of bronchial epithelium are hallmarks of both allergic and nonallergic asthma. In vitro, the eosinophil granule major basic protein (MBP) is toxic to helminths and to mammalian cells, including human respiratory epithelium. The MBP-mediated damage to the respiratory epithelium consists of desquamation and frank destruction of ciliated cells. Increased sputum MBP concentration is a good marker for asthma, and patients treated for acute asthma have high levels of MBP in their sputa, which decrease after treatment. Peak sputum MBP levels approximate concentrations toxic to respiratory epithelium in vitro. In the lungs of patients who had died of asthma, MBP has been localized outside of the eosinophil in association with damage to the epithelium. Overall, these and other findings suggest the hypothesis that the eosinophil mediates damage to the respiratory epithelium and is the prime effector cell in the pathophysiology of asthma.

Adjuvant activity of diesel-exhaust particulates for the production of IgE antibody in mice.

Abstract: The prevalence rate of allergic rhinitis caused by pollen has strikingly increased in Japan in the last three decades. The number of diesel cars in use has also rapidly increased in the country. This fact urged us to study the effects of particulates emitted from diesel cars on the production of IgE antibody. The primary IgE antibody responses in mice immunized with intraperitoneal injection of ovalbumin (OA) mixed with diesel-exhaust particulates (DEP) were higher than those in the animals immunized with OA alone. This effect of DEP on the production of IgE antibody in mice was also demonstrated when mice were immunized with repeated injections of dinitrophenylated-OA. In addition, persistent IgE-antibody response to major allergen of Japanese cedar pollen (JCPA), a most common pollen causing allergic rhinitis in Japan, was observed in mice immunized with JCPA mixed with DEP but not in the animals immunized with JCPA alone. The results do indicate that the adjuvant activity of DEP can not be excluded as a possible cause of the associated change in the number of diesel cars and allergic rhinitis caused by pollen in Japan.

The impact of health education on frequency and cost of health care use by low income children with asthma.

Abstract: A sample of 310 low income urban children with asthma from 290 families was randomized into a control group and an experimental group that received health education to improve asthma management at home. No significant decreases in subsequent health care use were observed when the experimental group was compared to the control group without regard to previous hospitalization. When the comparison was restricted to children who had been hospitalized during the preceding year, however, the experimental group was found to have decreased its use of the emergency room significantly more than the control group (p less than 0.05) and to have experienced a significantly greater reduction in the mean number of hospitalizations (p less than 0.05) during the year of follow-up. The program reduced health care costs for children with one or more hospitalizations, saving $11.22 for every $1.00 spent to deliver health education.

Biphasic and protracted anaphylaxis

Abstract: We performed a prospective study of anaphylaxis in 25 consecutive patients. Three distinct clinical patterns were observed: uniphasic, biphasic, and protracted anaphylaxis. Thirteen patients (52%) experienced a single episode. Biphasic anaphylaxis occurred in five patients (20%), two episodes of hypotension or laryngeal edema separated by asymptomatic intervals of 1 to 8 hours. Initial therapy included large doses of glucocorticoids in three of the five patients. Seven patients (28%) suffered hypotension, lower respiratory obstruction, or laryngeal obstruction that persisted 5 to 32 hours despite vigorous therapy that included systemic glucocorticoids. Recurrent or prolonged reactions were 2.8-fold more likely if the onset was 30 or more minutes after exposure to the stimulus or if the offending agent had been administered by mouth ( p

Maternal smoking influences cord serum IgE and IgD levels and increases the risk for subsequent infant allergy

Abstract: The effects of parental smoking on IgE and IgD levels in cord serum and subsequent infant allergy were investigated in an unselected series of 186 European newborn infants. Maternal smoking caused a significant rise in both IgE ( p p p p = 0.005, respectively). Furthermore, newborn infants of nonallergic parents had a more than threefold ( p p = 0.005) higher risk of developing definite or probable atopic disease before 18 months of age if the mother smoked than if she did not. Paternal smoking did not influence, in whatever the subgroup, cord IgE or subsequent infant allergy but increased cord IgD ( p p

Compliance of patients with asthma with an experimental aerosolized medication: implications for controlled clinical trials.

Abstract: A Nebulizer Chronolog, a portable device that houses a standard nebulizer canister, was used in a unique method to measure compliance with aerosolized medication. Each actuation is tabulated to within 4 minutes of the actual time of usage and can subsequently be displayed in a day-hour-minute format. Of the 19 patients studied for 12 weeks with a cromolyn-like agent, appropriate usage four times a day ranged from 4.3% to 94.8%. Underusage exceeded overusage and ranged from 5.2% to 95% of the study days. Younger subjects and male subjects were less likely to use the aerosol appropriately. Patients failed to write the truth in their diaries with overreporting of appropriate usage more than 50% of the times. Lack of compliance with aerosolized medication represents an important medical issue for the physicians caring for patients with asthma. The Nebulizer Chronolog elicits new insight into the disparity between reported and observed compliance.

The origin of airway hyperresponsiveness

Abstract: Consideration of the origin of airway hyperresponsiveness appears central to understanding the origin of asthma. Subjects with and without asthma differ both in the ease with which airway narrowing is produced by inhalation of histamine or methacholine and in the ability to demonstrate a maximal response to these agents. The latter appears, on present evidence, to be due to an added mechanism in asthma rather than the absence of a potent inhibitory process. Airway hyperresponsiveness is probably acquired during life as a result of airway reactions to various stimuli, although genetic factors such as atopy are likely to predispose the person to develop hyperresponsiveness. Environmental stimuli include inhaled allergens, chemical sensitizers, airway infections, immunization, and ozone. Allergen-induced airway hyperresponsiveness occurs in association with late-phase asthmatic responses. This and ozone-induced hyperresponsiveness have been demonstrated to be associated with release of chemical mediators and the cellular phase of inflammation. Their effect does not appear to be accounted for by increase in airway epithelial permeability, decrease in airway caliber, reflex bronchoconstriction, or beta-adrenoceptor blockade. The mechanism(s) responsible for the induced hyperresponsiveness are unknown but may involve airway epithelial damage, edema in and around the airway walls, stimulation of the noncholinergic excitatory or inhibition of the nonadrenergic inhibitory systems, or a change in function of airway smooth muscle. Airway hyperresponsiveness can be transient or persistent. Transient increases in responsiveness are almost certainly associated with mediator release and inflammation. It is not known whether persistent hyperresponsiveness is due to the same process, fired, for example, by leaky mediator-releasing cells and/or to some persisting change in neurogenic or smooth muscle function.

The effect of cigarette smoke from the mother on bronchial responsiveness and severity of symptoms in children with asthma.

Abstract: The effect of parental smoking was assessed in 94 consecutively observed children, aged 7 to 17 years, who had a history of asthmatic wheezing. The 24 children whose mothers smoked, when they were compared with children whose mothers did not smoke, had 47% more symptoms, a 13% lower mean FEV1 percent, a 23% lower mean FEF25-75%, and fourfold greater responsiveness to aerosolized histamine. A dose response was evident. There was a highly significant correlation between the results of the tests and the number of cigarettes the mother smoked while she was in the house. The differences between the children of smoking and nonsmoking mothers were greater in older than in younger subjects. The smoking habits of the father were not correlated with the severity of the child's asthma.

Airborne allergens associated with asthma: Particle sizes carrying dust mite and rat allergens measured with a cascade impactor

Abstract: Patients with asthma may develop acute symptoms after exposure to domestic or laboratory animal allergens; however, they are usually not aware of a direct relationship between their acute attacks and exposure to pollen or dust mite allergens. The present experiments were designed to study whether the differences in symptoms could be explained by differences in the number or size of particles carrying airborne allergens. Airborne particles were collected with a filter or on the stages of a cascade impactor, and allergens were measured by use of inhibition radioimmunoassays. In rat rooms and during disturbance of rat litter, a large proportion of rat urinary allergen (45.9%) was collected on the second stage of the impactor (mean size approximately 7 microns diameter). When sampled 15 to 35 minutes after disturbance, 16% of these medium-sized particles were still airborne. By contrast, during disturbance of house dust, a significantly larger proportion of dust mite, antigen P1 (80.6 +/- 11.8%; p less than 0.001) was collected on the first stage of the impactor, and in keeping with the apparent size of these particles (diameter greater than 10 microns), very little of this allergen (less than 4%) was still airborne when sampled 15 to 35 minutes after disturbance. With nebulized diluted rat urine, approximately 75% of the allergen was collected on the fourth and final stages of the cascade impactor in keeping with the expected size, 0.5 to 3 microns in diameter. These results demonstrate that natural exposure to both allergens is strikingly different from the conditions used for bronchial provocation.(ABSTRACT TRUNCATED AT 250 WORDS)

Seasonal asthma in northern California: allergic causes and efficacy of immunotherapy.

Abstract: Inland areas of northern California have an intense grass pollination in the spring of each year. This is accompanied by a stirking rise in the incidence of asthma. We documented this relationship and designed a trial to test the efficacy of immunotherapy for grass-pollen asthma. Aeroallergen counts were performed on the roof of the allergy clinic of David Grant Medical Center from January 1981 to December 1984 by a gravity collector. These counts were compared to counts done on a Rotorod at a nearby hospital from July 1982 to September 1984. Climatologic factors were also tabulated. Visits for asthma and rhinitis to our emergency room and asthma admissions to our hospital were counted for the 4-year period. A randomized, double-blinded, placebo-controlled trial of immunotherapy with grass-pollen extract was performed from November 1984 to June 1985. Two groups of clinically and immunologically well-matched subjects were started on an accelerated preseasonal trial of immunotherapy. One group received a standardized grass extract, and the other group did not. Both groups received other extracts of aeroallergens to which they were skin test positive that occur locally in the spring and summer. This was done because of our dissatisfaction with a histamine placebo used in a previous pilot study. Symptom medication scores (SMS) and immunologic parameters were followed. For the 4-year period, grass-pollen count (GPC) correlated strongly with asthma emergency room visits (r = 0.90; p p p p p = 0.11. RGGI sIgE did not rise significantly in the grass-treated group but did in the placebo-treated group. RGGI sIgG rose in both groups, although to significantly higher levels in the grass-treated group, p p

Morbidity in asthma in relation to the menstrual cycle

Abstract: After observing three cases of severe recurrent exacerbations of asthma in relation to menstruation, we conducted a survey among women with asthma inquiring about the relationship of asthma symptoms to the menstrual cycle. Of 57 women with asthma, 19 (33%) had significant worsening (p = 0.006) of total pulmonary symptom scores during either the premenstrual period, the menstrual period, or both with maximum increase in dyspnea, wheezing, and chest tightness during the premenstrual period (p = 0.002). The other 38 (66%) women noted no such changes in their asthma. Logistic regression analysis comparing women with and without worsening of their asthma around menstruation revealed that the former group reported significantly more severe wheezing in general (p less than 0.05) and also more severe pulmonary symptoms during the premenstrual period (p less than 0.05). Of the women whose asthma was affected by menses, 13 (68%) had been hospitalized for asthma but only 10 (26%) of the women who were unaffected (p = 0.002). Both dysmenorrhea scores and premenstrual syndrome scores correlated significantly with baseline pulmonary symptom scores in the premenstrual asthma group. It appears that asthma morbidity is affected by the menstrual cycle in a subgroup of women with asthma.

Placebo-controlled double-blind food challenge in asthma

Abstract: To determine the prevalence of food allergy as a cause of exacerbation of asthma, we studied 300 consecutive patients with asthma (7 months to 80 years of age) who attended a respiratory clinic. Each patient was screened for possible food allergy by means of a questionnaire and by skin prick tests with the six food allergens most common in our area. Patients with either a suggestive history and/or a positive prick test and/or RAST underwent double-blind food challenge with lyophilized food in capsules or food mixed in a broth to disguise its taste. Pulmonary function tests and symptoms were followed for 8 hours after each challenge. Of the 300 patients screened, only 25 had either a history or skin prick tests or RAST responses suggestive of food allergy. Twenty patients had interpretable food challenges. In these 20 patients, food challenge caused asthma in six and caused other symptoms (atopic dermatitis and gastrointestinal symptoms) in five. On rechallenge after pretreatment with disodium cromoglycate (300 mg 30 minutes before the food challenge), the asthmatic response was blocked in four of five subjects. The patients with asthma with food allergy were generally young, had a current or past history of atopic dermatitis, and high total serum IgE levels. Our findings confirm that food allergy can elicit asthma, but its incidence is low, even in the population attending a specialty clinic. Food elimination diets should not be prescribed for all patients reporting an adverse reaction to foods or having a positive skin prick test and/or RAST with food allergens. In patients with asthma caused by food allergy, disodium cromoglycate may be used to complement elimination diets.

Cow's milk allergy in breast-fed infants: The role of allergen and maternal secretory IgA antibody

Abstract: The protective effect of breast-feeding in allergy prophylaxis remains controversial despite many epidemiologic studies. One reason for confusion could be heterogeneity of breast milk with regard to its protective capacity. To clarify this issue, we studied 57 mother-infant pairs where breast-feeding was the sole source of infant nutrition. Family history and infant symptom scores suggestive of allergic disease were noted. The presence and quantity in breast milk of a prominent food allergen (β-lactoglobulin), total IgA, and IgA antibodies to whole cow's milk and casein were measured serially. Eleven infants had symptom scores highly suggestive of allergic disease. The breast milk from mothers of these 11 infants was found to have lower total IgA ( p p p

Immunotherapy with partially purified and standardized animal dander extracts: I. Clinical results from a double-blind study on patients with animal dander asthma

Abstract: Forty-one patients (21 adults and 20 children) with cat dander- or dog dander-induced asthma were selected for immunotherapy with standardized and partially purified cat- or dog-dander extracts by use of a double-blind protocol. Based on sex, age, clinical history, results of bronchial challenge, and crossed radioimmunoelectrophoresis studies, the patients were stratified in matched pairs, and the treatment alternatives were distributed randomly among the pairs. Twenty-two patients treated with allergen (15 with cat allergen and seven with dog allergen) and 17 patients receiving placebo therapy completed the first year of treatment. In the cat allergentreated group, the bronchial sensitivity toward cat and histamine decreased ( p p

Outcome of pregnancy in women requiring corticosteroids for severe asthma.

Abstract: We report on the outcome of 56 pregnancies in 51 women with severe asthma requiring prednisone and/or beclomethasone dipropionate. There were no malformations, neonatal deaths, or maternal deaths. The overall incidence of premature (

Neutrophil granules in health and disease

Abstract: The granules of the neutrophil, in addition to contributing to its distinctive morphologic appearance, are critical to its unique functions. Specific granules appear necessary for neutrophil recruitment to sites of inflammation, for upregulation of receptors important in the control of chemotaxis and the respiratory burst, for disaggregation, for bactericidal activity, and for chemoattractant generation. The azurophilic granules supply enzymes for digestive and bactericidal functions and supply MPO to the MPO-halide-hydrogen peroxide bactericidal system. Azurophilic granule contents also regulate inflammation by degrading inflammatory products. Both granules may play a role in intracellular calcium regulation. In addition to these activities that protect the host from infection, granules also, under certain circumstances, contribute to disease processes. For these reasons, greater knowledge about granule contents, control of degranulation, inactivation of toxic granule contents and products, and the role of granules in neutrophil membrane events and function has widespread implications for treatment of patients with neutrophil dysfunction syndromes and patients with multiple other systemic diseases.

Hyperosmolarity as the stimulus to asthma induced by hyperventilation

Abstract: Hyperosmolarity of the epithelial fluid of the large airways caused by evaporative water loss (wloss) has been proposed as the stimulus to exercise-induced asthma. The aim of this study was to compare the wloss during hyperpnea with a theoretical wloss from a known hypertonic stimulus in order to determine whether comparable volumes of wloss will induce the same response. Since wloss also occurs during isocapnic hyperventilation (ISH), we decided to compare the airway response to ISH with the response obtained after inhaling 4.5% NaCl aerosol. Changes in FEV1 were measured in 17 subjects with asthma in response to increasing rates of ventilation (ISH) and increasing doses of 4.5% NaCl aerosol. For ISH, wloss was calculated at 29 mg/L of expired air and for 4.5% NaCl, at 4.0 ml/l ml of aerosol inhaled, as this is the volume of water that will bring the periciliary fluid to normal tonicity. Two dose-response curves were drawn for each subject. These curves were similar both in position (PD20) and in shape (i.e., the slope of the curve as estimated by the ratio of wloss for maximum recorded percent fall in FEV1 [PDmax] to PD20). There was no significant difference in the PD20 (ISH, 10.3 ml, 95% confidence limits 7.5 and 13.9; 4.5% NaCl, 12.3 ml, 95% confidence limits 8.9 and 17.1) or between the ratio of log PDmax:log PD20 (ISH, 1.19 +/- 1 SD, 0.14; 4.5% NaCl, 1.17 +/- 1 SD, 1.17; p = not significant). These findings support the concept that airway hyperosmolarity may be the mechanism for ISH and exercise-induced asthma.

Studies of the cellular infiltrate of chronic idiopathic urticaria: Prominence of T-lymphocytes, monocytes, and mast cells

Abstract: We have used a panel of monoclonal antibodies and enzyme histochemistry in order to characterize further the perivascular mononuclear cell infiltrate found in chronic idiopathic urticaria. Biotinylated anti-mouse immunoglobulin was exposed to avidin-biotin-peroxidase-labeled complex followed by peroxidase development in order to detect binding of monoclonal antibodies. The mean percent staining obtained for 12 patients with chronic urticaria was 47% T-lymphocytes, 22% monocytes (14% by α-naphthyl acid esterase), and 11% mast cells. B-lymphocytes were not detectable, and approximately 20% of cells could not be identified. Although patients varied greatly in the ratio of Leu 3a positive helper-inducer T cells to T8 positive cytotoxic-suppressor cells, the average of all patients was not significantly different from the T4T8 ratio in plasma. Our results suggest that the infiltrate resembles that observed in cellular immune reactions (although no antigen has been identified) and that interaction of T-lymphocytes and/or monocytes with mast cells to cause mediator release appears likely.

A study of the human immune response to Lolium perenne (Rye) pollen and its components, Lol p I and Lol p II (Rye I and Rye II): I. Prevalence of reactivity to the allergens and correlations among skin test, IgE antibody, and IgG antibody data

Abstract: In a stratified random sample of 320 white adults, the prevalence of puncture skin test positivity (ST +) to Lolium perenne (rye grass)-pollen extract (LPE) was 16%. Fifteen percent of all subjects (or 84% of subjects classified LPE IgE antibody positive [Ab +]) was classified IgE Ab + to highly purified Lol p I (Rye I), and 4% of all subjects (or 26% of subjects classified LPE IgE Ab +) was classified IgE Ab + to highly purified Lol p II (Rye II). These data and similar results obtained in an allergy-enriched group of 361 subjects are consistent with previous studies that Lol I is a major allergen and Lol II is a minor allergen of LPE. Whether we studied LPE, Lol I, or Lol II, responder subjects were younger than nonresponder subjects and more male than female subjects were responders. We then investigated the quantitative interrelationships among ST, IgE, and IgG Ab responsiveness to LPE, Lol I, and Lol II in the allergy-enriched group. For each allergen, log-log correlations were strong and significant for ST versus IgE Ab and for IgE Ab versus IgG Ab. All subjects IgE Ab + to Lol I or Lol II were IgG Ab + to that allergen, supporting other evidence for a commonality in the genetic control influencing the production of IgE and IgG Abs to a given allergen. Log-log correlations among ST end points, IgE Ab levels, or IgG Ab levels were strong for LPE versus either Lol I or Lol II but weak between Lol I and Lol II, consistent with the reported lack of cross-reactivity between Lol I and Lol II. Despite these findings, almost all Lol II + subjects were Lol I + by ST (98%), IgE Ab (91%), and IgG Ab (83%), suggesting that the Ia-restricted immune recognition of both these molecules is at least in part under a common genetic control.

Clinical characteristics of cold-induced systemic reactions in acquired cold urticaria syndromes: recommendations for prevention of this complication and a proposal for a diagnostic classification of cold urticaria.

Abstract: The acquired cold urticaria (ACU) syndromes consists of nonfamilial heterogeneous disorders characterized by urticaria, angioedema, and occasionally symptoms of hypotension after cold exposure. In a study of 50 consecutive patients with ACU syndromes, it was observed that 70% experienced cold-induced systemic reactions, most frequently with aquatic activities. Patients with ACU syndromes were categorized by their response to an experimental cold-stimulation time test (CSTT) i.e., minimum time threshold of cold stimulation required to induce a coalescent wheal. One subpopulation of patients with ACU syndromes with positive CSTTs of 3 minutes or less experienced the highest incidence (68%; 13/19) of severe systemic reactions with hypotensive symptoms after natural cold exposure. However, 32% of patients with ACU syndromes (6/19) who experienced cold-induced systemic reactions with hypotension had a negative CSTT or a positive test of greater than 3 minutes. These observations indicate that all patients with ACU with active histories of cold urticaria are at risk to develop systemic reactions to cold and should therefore refrain from participating in aquatic activities. In addition, high-risk patients should receive prophylactic medications (i.e., cyproheptadine or doxepin) that are effective in suppressing this disorder. A diagnostic classification of cold urticaria is presented. This classification permits a more specific definition of the various cold urticaria disorders that comprise the ACU syndromes.

The mast cell as a primary effector cell in the pathogenesis of asthma.

Abstract: Holgate, S T Hardy, C Robinson, C Agius, R M Howarth, P H Review United states The Journal of allergy and clinical immunology J Allergy Clin Immunol. 1986 Feb;77(2):274-82.

Segregation analysis of bronchial response to methacholine inhalation challenge in families with and without asthma

Abstract: A segregation analysis was performed on the bronchial response to a standardized methacholine inhalation challenge obtained from members of 83 families that were part of a Natural History of Asthma study population. Each bronchial response was expressed as the area under the best fitting parabolic dose-response curve. Standard methods of statistical analysis demonstrated that age, sex, and recent respiratory infection had a significant effect on the bronchial response to methacholine inhalation. Segregation analysis indicated that, although a familial component exists in the transmission of bronchial response to methacholine, the bimodal distribution of the bronchial response is not due to segregation at a single autosomal locus.

Dose of cat (Felis domesticus) allergen 1 (Fel d 1) that induces asthma

Abstract: In 10 patients with cat asthma and hay fever, we quantified the doses of cat allergen (expressed as cat allergen 1 [Cat-1] in log Food and Drug Administration [FDA] units) inspired from the ambient air of a room containing living cats required to induce a 20% drop in FEV 1 These doses were compared with the doses required to cause the same change in FEV 1 when the patients were subjected to bronchial challenge with aerosols of cat hair and dander extract in the conventional manner Patients highly sensitive to cat extract by skin, leukocyte histamine release, and bronchoprovocation tests and with measurable levels of antic at IgE by RAST were exposed for up to 2 hours in a room occupied full-time by two cats At the same time, room air was sampled by a Durham gravity sampler, by an Andersen sampler, and by lapel fiberglass filters When hair and dander particles trapped on greased slides by gravity and Andersen samplers were stained, sized, and counted, squamous cell fragments in the p 1 , when air sampling was stopped, the lapel filters had trapped a total of −186 to p 1 in the conventional bronchoprovocation tests

Effectiveness of dietary manipulation in the prevention of food allergy in infants

Abstract: The desire to alter the natural incidence of atopic illness has piqued physicians' imaginations for decades. Specifically, the phenotypic expression of IgE-mediated disorders, which appears regulated by multiple genetic (factors and modulated by environmental experiences (allergen exposure, infecton, and smoking), has been a target for preventive medicine since the 1920s when dietary intervention was espoused in infancy. To be successful, such intervention must overcome many patient factors that in concert markedly increase the risk for development of atopic disease (Table XII). During the past 60 years, much controversy has emerged from multiple clinical studies designed to evaluate the effect of dietary and other environmental exclusions on the subsequent manifestation of atopy. One may conservatively conclude, from critical evaluation of these conflicting studies, that sole breast feeding for about 6 months combined with delayed introduction of solid foods for at least 6 months may reduce atopic dermatitis and food allergy in early infancy. A randomized, prospective study of allergy prophylaxis during infancy is mandatory to determine definitely the benefits and feasibility of such a regimen and its long-term effects on the development of atopy. From our recent findings, which demonstrate the development of atopy in infants entered in a strict prophylactic protocol, it becomes apparent that monumental obstacles confront preventive efforts to overcome the strength of the allergic constitution. In the very near future, results from our prospective study of prenatally randomized allergy prophylaxis should be available for critical scutiny of the effectiveness and feasibility of allergy prevention during infancy.

Immunoregulatory disorders associated with hereditary angioedema. I. Clinical manifestations of autoimmune disease.

Abstract: Occasional reports have appeared linking hereditary angioedema (HAE) with autoimmune diseases. We have systematically evaluated 157 patients for manifestations of autoimmunity. Nineteen of these patients (12%) had clinical immunoregulatory diseases including glomerulonephritis (five patients), Sjogren's syndrome (three), inflammatory bowel disease (three), thyroiditis (two), systemic lupus erythematosus (one), drug-induced lupus (one), rheumatoid arthritis (one), juvenile rheumatoid arthritis with IgA deficiency (one), incipient pernicious anemia (one), and sicca syndrome (one). All eight patients with HAE who developed an autoimmune disease with a known human histocompatibility antigen association developed a disease associated with their histocompatibility antigen haplotype (p = 0.014). Although only four patients developed Sjogren's syndrome or sicca syndrome, an additional nine manifested part of the sicca complex. We also found patients with HAE with features suggestive of an immune-based abnormality. These features included idiopathic pancreatitis (three patients), Raynaud's disease (two), partial lipodystrophy (one), chronic chorioretinitis (one), and alopecia universalis (one).

Recurrent Sinopulmonary Infection and Impaired Antibody Response to Bacterial Capsular Polysaccharide Antigen in Children with Selective IgG-Subclass Deficiency

Abstract: We studied 20 children with recurrent sinopulmonary infections and serum IgG levels within the normal range, who had selective IgG-subclass deficiency. Twelve of the children were IgG2 deficient, five were IgG3 deficient, and three were deficient in both IgG2 and IgG3. IgA deficiency was present in 3 of the 20 patients. In the children with IgG2 deficiency, serum antibody concentrations to the capsular polysaccharide of Hemophilus influenzae type B (Hib) were significantly lower than those in age-matched controls, both before and after immunization with the Hib capsular polysaccharide antigen, which elicits antibody predominantly of the IgG2 subclass. In contrast, their serum antibody titers to the tetanus and diphtheria toxoid protein antigens, which elicit antibody predominantly of the IgG1 subclass, were normal in comparison with those of age-matched controls. These results suggest that impairment of the antibody response to specific microbial antigens predisposes patients with selective IgG-s...

Hypothalamic-pituitary-adrenal axis suppression after short-term, high-dose glucocorticoid therapy in children with asthma

Abstract: Short-term, high-dose oral glucocorticoid therapy is often required for control of acute asthma episodes in children. To evaluate possible hypothalamic-pituitary-adrenal (HPA) axis suppression after such therapy, we studied 11 children with just asymptomatic asthma before and at 3 and 10 days after completion of a five-day course of prednisone (up to 2 mg/kg/day in divided doses, maximum dose = 60 mg/day). HPA axis responsiveness was tested by measuring plasma corticosteroid levels before and after insulin-induced hypoglycemia. When these levels were compared to pretreatment levels, there was a statistically significant blunting of the peak corticosteroid responses to hypoglycemia 3 days after completion of the course of prednisone (p less than 0.001). However, corticosteroid responses were normal in all children 10 days after completion of the course of prednisone. We concluded that a single course of short-term, high-dose glucocorticoid therapy in children with asymptomatic asthma produces only transient (less than 10 days) HPA axis suppression.

Direct in vivo evidence for mast cell degranulation during allergen-induced reactions in man.

Abstract: There is little or no direct in vivo evidence in man to support the involvement of mast cell-mediator release in the pathogenesis of immediate allergic reactions. We have performed a within-subject controlled study to determine the changes that occur in nasal mast cells during allergen-induced rhinitis. Twelve subjects with asymptomatic rhinitis were studied. Nasal biopsy specimens were obtained from each subject after a control solution (isotonic saline, 0.9% w/v) had been nebulized into one nostril and allergen solution (freeze-dried allergen extract reconstituted with isotonic saline) into the other. The tissues obtained were fixed in Carnoy's solution and stained with the alpha-naphthol AS-D chloroacetate esterase reaction (N AS-D CA ER). Mast cells were counted under light microscopy in the epithelium and lamina propria, and the integrity of each cell was assessed. No significant differences were found in the number of epithelial or lamina propria mast cells in biopsy specimens obtained after saline or allergen administration. However, the number of degranulated mast cells after allergen provocation (89%) was significantly greater than after instillation of control solution (15%) (p = 0.003). Changes of mast cell degranulation after allergen provocation were confirmed by electron microscopy. In six nonatopic, control subjects without rhinitis, there was no significant difference between the percentages of degranulated mast cells after allergen provocation (25.8%) and instillation of saline (24.3%). This study provides direct in vivo evidence for allergen-induced mast cell activation in man.