Alpha-1 antitrypsin levels and prevalence of Pi variant phenotypes in asthmatic children

A total of 151 children with severe atopic bronchial asthma were screened for AAT levels by the STIC and RID methods. They were also phenotyped by the method of acid starch electrophoresis and crossed immunoelectrophoresis. The results were compared with those in a like control age group of children without known pulmonary problems. Both groups revealed similar incidences of AAT deficiency and 3% phenotype Z variants. The children with steroid-dependent severe asthma had a greater proportion of Z heterozygote variants than the non-steroid-dependent asthmatic and control population.     

Effect of an inhaled corticosteroid on methacholine airway reactivity

Methacholine airway reactivity was studied in seven asthmatic patients before and at the end of 4 mo of beclomethasone dipropionate therapy, as well as in a control group. There was no statistically significant change in reactivity in either group, suggesting that a change in airway cholinergic receptor activity is not part of the mechanism of action of corticosteroids in asthma.     

Hypersensitivity to procarbazine associated with angioedema, urticaria, and low serum complement activity.

Hypersensitivity to procarbazine associated with urticaria, angioedema, and painful joint swelling was found in a 20-year-old student being treated for Hodgkin's disease. A marked fall in complement component activity occurred simultaneously with the development of symtoms. It is suggested that generation of products of complement component activation could be important in the pathogenesis of hypersensitivity to some drugs.     

Estimation of serum IgE by an enzyme-linked immunosorbent assay (ELISA)

A reliable and relatively simple method for the estimation of serum IgE is presented. It is a modification of radioimmune inhibition methods in which the marker is an enzyme, alkaline phosphatase, not radioactivity. The method does not require radioactivity or expensive equipment, and the reagents are stable for long periods of time. As presented it has a minimum sensitivity of about 10 ng. per milliliter. The reproducibility of the method is ±3 per cent and for correlation with radioimmunoassay ? = 0.97.     

Comparison of aerosolized atropine sulfate and SCH 1000 on exercise-induced bronchospasm in children.

The new anticholinergic compound Sch 1000 (ipratropium bromide) has been reported to be an effective bronchodilator without significant atropine-like side effects. We evaluated the effectiveness of different doses of nebulized Sch 1000 (40 microgram and 80 microgram) aerosolized atropine sulfate (1 mg) and placebo in the prevention of exercise-induced bronchospasm (EIB) in 20 children with atopic bronchial asthma. A random, crossover double-blind protocol was used. Standard exercise on a cycloergometer was used to induce EIB. Pulmonary function was determined before and after drug administration and exercise. Following no treatment or placebo, exercise resulted in average reductions of 33% to 43% in plethysmographic specific airway conductance (SGaw), of 20% to 25% in forced expiratory volume in 1 sec (FEV1), and of 25% to 32% in maximal midexpiratory flow rate. Exercise following no treatment or placebo resulted in average increases of 23% to 30% in thoracic gas volume (Vtg). Prior to exercise atropine and either dose of Sch 1000 caused significant increases in SGaw (48% to 59%). After pretreatment with Sch 1000 or atropine, exercise caused SGaw to fall to values that were not significantly different from pretreatment medication values, but were significantly higher than values following exercise without pretreatment or after pretreatment with placebo. No significant differences were noted between the effects of atropine and Sch 1000 on EIB. We conclude that at the doses used atropine and Sch 1000 cause equivalent degrees of bronchodilation but neither drug specifically inhibits EIB.     

Presidential address. The advancement of the knowledge and practice of allergy.

State and local allergy societies have appeared in response to pressures created by progressive specialization, increase in knowledge, and need for cost control within the field of allergy and clinical immunology. They provide a mechanism whereby allergists and immunologists with many different interests and functions can work in an integrated and cooperative manner to provide, in a cost-effective fashion, adequate patient care, teaching, and research in allergy and immunology for the geographic area. Maximum effectiveness requires close liaison with medical schools, state medical societies, national allergy organizations, and the local chapter of the Asthma and Allergy Foundation of America. Their structure should permit frequent close communication between members in various fields of allergy and clinical immunology, and the organization of committees that can accomplish the hard work of ensuring care for the disadvantaged patient, time and money for research, cost control, identification and rehabilitation of the poorly functioning allergists, continuing education for physician and patient, and all of the other tasks that make the practice of allergy and clinical immunology such a wonderful and absorbing way of life.     

Bronchodilator characteristics of nebulized metaproterenol sulfate, isoetharine, and atropine in chronic asthma

A randomized double-blind comparison of aerosolized META, ISO, ATR, and PI solutions delivered by motorized mist nebulizer was conducted in subjects with known reversible airway obstruction. Vital signs and spirometric parameters were monitored sequentially during each of four 6 hr test periods. Abstention from all medication was required for at least 12 hr before each test period. Baseline percent predicted FEV₁ and FEF_25–75 among subjects for all test periods were statistically similar. Compared to the other agents tested META treatment (15 mg) resulted in significantly improved global response and higher mean percent increases in FEV₁ and FEF_25–75 over the entire test period as well as at individual measurement points up to 4 hr for FEV₁ and 5 hr for FEF_25–75. Peak FEV₁ and FEF_25–75 values with META treatment were noted at 30 min and persisted above baseline during the entire 6 hr. ATR (2 mg) treatment resulted in later onset of bronchodilatory effect and, as with ISO (125 μg), more rapid diminution in measured response. Administration of saline alone resulted in a net 9% increase in FEV₁ and 11 % in FEF_25–75 over the entire test period. Clinically insignificant tremor was noted in 41 % of META-treated subjects. Delivery of META by a motorized mist nebulizer provides safe, effective bronchodilation and META is superior to the other agents tested in terms of onset of action, peak reversal of airway obstruction, and duration of effect.     

SECA, a new mediator of the human eosinophil response.

Spontaneous eosinophilic chemotactic activity (SECA) present in human sera can mediate the directed movement of normal human eosinophils. Our data utilize normal peripheral blood eosinophils obtained from subjects with 500 eosinophils/m3 or less. SECA is defined as that chemotactic activity for eosinophils present in serum that has been heat-inactivated immediately after collection. It was demonstrated in patients with severe chronic eczema with eosinophilia (20 to 30%); mixed collagen vascular disease with vasculitis; clinical serum sickness; acute glomerulonephritis, and chronic membranoproliferative glomerulonephritis. Control sera were obtained from normal, healthy individuals. The data indicated: (1) that SECA in patient sera was significantly higher than in control sera; (2) when activated by endotoxin, no additional chemotactic activity was generated from patient sera over that spontaneously present--by contrast, addition of endotoxin to control sera did result in increased chemotactic activity; (3) sera from patients with extrinsic bronchial asthma had no SECA.     

Diagnosis of IgE-mediated reactions to food antigens by radioimmunoassay

The radioallergosorbent test (RAST) was performed on sera from 127 pediatric age patients, who reported the occurrence of more than one episode of immediate hypersensitivity type symptoms (urticaria, angioedema, anaphylaxis, asthma, allergic rhinitis, and atopic eczema) or other acute manifestations upon the gastrointestinal tract after the ingestion of one or more foods. Fourteen different foods, as well as two purified cow's milk fractions, were studied by radioimmunoassay. Specific IgE antibodies to the clinically suspected food allergen were demonstrated in 59 per cent of all reported untoward reactions. A questionable result was obtained in an additional 12 per cent. A positive RAST to at least one food allergen was found in 75 per cent of the patients studied. This technique appears to be a promising and useful adjunct in the diagnosis of IgE-mediated food hypersensitivity.     

Specific IgE antibodies in atopic eczema

Radioallergosorbent tests (RAST'S) with 35 antigens and total serum IgE levels were performed on sera from 25 patients with atopic eczema, ranging from mild to very severe, who had been evaluated clinically and, when possible, skin-tested to inhalant allergens. IgE levels varied from 95 to 112,000 I.U., with a geometric mean of 2,200 I.U. Individual patients' sera gave an average of 8.4 positive RAST's to 14 inhalant allergens with a range of from 1 to 14 positive tests. The correlation of RAST with skin tests averaged 55 per cent with no difference observed with either the scratch or the prick methods. The degree of correlation was not related to severity of eczema. In eczema patients the great majority of noncorrelating tests were RAST positive and skin-test negative, unlike the noncorrelating tests found in children with asthma and allergic rhinitis, where there are more positive skin tests with negative RAST. The 25 sera were tested by RAST with 18 food antigens and the various sera gave from 1 to 18 positive tests, with an average of 9.7. IgE antibodies reacting with at least one of the DPT antigens were found in 10 of the 25 sera. Sera from 4 of the patients studied contained IgE antibodies that combined with all 35 antigens studied. Control RAST's with these sera were negative. This study shows that much of the elevation of serum IgE observed in atopic eczema represents specific IgE antibodies that can combine with common antigens with relatively high affinity.     

Defective T cell function in atopic dermatitis

The cellular immune system of 37 patients with atopic dermatitis (AD) was assessed by measuring peripheral blood T and B cells and the in vitro lymphocyte response to graded doses of phytohemagglutinin (PHA) (background and 6 concentrations of PHA from 100 to 1.6 mug). These were then correlated with clinical severity, ecosinophil counts, and serum IgE levels. The IgE levels (1,482 IU +/- 252 SEM), eosinophil counts (977 +/- 143), and absolute number of B cells (958 +/- 123) were significantly (p less than 0.05) higher than in age-matched controls (70 IU +/- 28, 182 +/- 79, and 480 +/- 60, respectively), and each significantly (p less than 0.05) correlated with the clinical severity. By contrast, percent B lymphocytes (20 +/- 1), percent (51 +/- 2) and total (2,357 +/- 217) T cells did not differ from controls. Eleven patients had low percent T cells (less than 40%); clinical and laboratory evaluation in these patients did not differ from the remaining 26. Lymphocytes from AD patients had higher background deoxyribonucleic acid (DNA) synthesis than controls (suggestive of increased number of B cells) and significantly depressed responses at the low PHA concentrations (6.3, 3.1, and 1.6 mug), which significantly correlated (p less than 0.05) inversely with IgE levels. These studies suggest a subtle defect in T lymphocyte function leading to increased B cells and increased IgE production.     

Partial characterization of in vivo chemotactic activity: Comparison to human C5a

Spontaneous eosinophil chemotactic activity (SECA) can mediate the directed movement of human eosinophils and neutrophils.¹ Preliminary characterization of SECA has been carried out. SECA is nondialyzable and heat-stable (56 °C, 30 min). Chromatography on Sephadex G-75 demonstrated that SECA had elutional and functional properties similar to C5a (prepared from endotoxin-activated normal sera). Polyacrylamide gel electrophoresis (PAGE) with the use of 15% bisacrylamide gels of lyophilized, chemotactically active column fractions demonstrated a single protein band of identical electrophoretic mobility from either SECA or C5a preparations. Enzymatic hydrolysis with carboxypeptidase B, a known inhibitor of CSa activity, significantly decreased chemotactic activities of C5a and SECA. The addition of purified anti-C5 to either SECA or C5a significantly inhibited chemotactic activity. SECA is naturally occurring chemotactic activity identical to human C5a. Thus C5a may be an important source of in vivo chemotactic activity in various inflammatory disorders.     

Intact humoral and cell-mediated immunity in chronic marijuana smoking.

The immune system of 12 healthy chronic marijuana-smoking adults was evaluated while they smoked marijuana daily for 64 consecutive days under controlled hospitalized conditions. Studies included enumeration of B and T cell subpopulations, lymphocyte proliferative responses to PHA and to allogeneic cells, and serum immunoglobulin levels. Percent B cells, initially low in 2 patients, became normal. Baseline total B cells, determined either by surface immunoglobulins (338 cells/mm3 +/- 60 SEM) or complement receptors (162 cells/mms +/- 27) were significantly (p less than 0.05) less than control but increased to normal (485 +/- 97 and 239 +/- 47) over time. Percent T cells, initially low (less than 40%) in 4 patients, became normal. Baseline T cells (951 cells/mm3 +/- 70 SEM), significantly lower than controls (2,010 +/- 210, p less than 0.05), increased to normal by day 63 (1,875 +/- 281). In vitro lymphocyte response to graded doses of PHA and to allogeneic cells was normal initially and did not change over time. Serum IgG (1,064 +/- 33), IgA (166 +/- 13), and IgM (96 +/- 6) were normal. Serum IgE levels increased in 4 subjects without evidence of allergy. Short-term chronic marijuana use does not have a substantial adverse effect on B or T cells of young healthy adults.     

Dose-response effects of albuterol aerosol compared with isoproterenol and placebo aerosols: response to albuterol, isoproterenol, and placebo aerosols.

Albuterol aerosol was an effective bronchodilator as reflected by indices of pulmonary function obtained from spirometry and flow volume curves; Compared with isoproterenol, there were minimal side effects even at the highest doses, and bronchodilation lasted significantly longer. In addition albuterol was successfully used by a patient with idiopathic hypertrophic subaortic stenosis who was unable to tolerate isoproterenol, as well as by some patients with idiosyncratic responses to isoproterenol; A few patients appeared to derive little benefit from either albuterol or isoproterenol.     

IgE levels in sera of cancer patients.

Immunoglobulin E (IgE) was measured in the sera of 18 healthy adult volunteer donors, 67 adults with various types of solid neoplasms, and 17 adults with clinical allergy by means of a double-antibody radioimmunoassay. There was no siginificant difference in the geometric mean serum IgE level between all cancer subjects and the healthy control subjects except that cancer and noncancer patients who had definite clinical allergies showed an increased mean IgE level. Similarly, there was no significant difference in the mean IgE level of any of the six cancer subgroups studied when compared to the control mean. Thus, there was no evidence reflected in serum levels that IgE plays a role in the immunopathology of the cancer population tested.     

An action of disodium cromoglycate: inhibition of cyclic 3',5'-AMP phosphodiesterase.

Disodium cromoglycate (DSCG) prevents allergic asthma by inhibiting the release of chemical mediators of immediate-type allergic reactions. The mechanism of this action is unclear and prompted us to examine the effect of DSCG on cyclic adenosine 3',5'-monophosphate (cAMP), the implicated regulator of IgE-mediated reactions. We used the peripheral blood lymphocyte as a model to mirror the biochemical events occurring in the allergic shock organs. Isolated peripheral blood lymphocytes from perennial allergic asthmatic children receiving only DSCG had significantly (p less than 0.005) lower phosphodiesterase (PDE) activity (mean 1.05 +/- 0.17 SE per 10(6) cells) than normal individuals (2.93 +/- 0.14) and allergic children receiving methylxanthines (4.08 +/- 0.28) or no medications (3.58 +/- 0.2). DSCG (10 mug/ml) significantly lowered PDE activity in normal lymphocytes (p less than 0.005) in a beef heart extract (p less than 0.001), and 100 mug/ml lowered PDE activity in fetal rabbit lung homogenates (p less than 0.001). DSCG (10 mug/ml) significantly elevated (p less than 0.01) cAMP concentration in normal human lymphocytes (118 +/- 38 vs 30 +/- 10 picomoles cAMP/10(6) lymphocytes). Thus, DSCG appears to inhibit chemical mediator release by increasing intracellular cAMP through the inhibition of cAMP PDE.     

Quantitative requirements for C3 to induce Forssman systemic shock and cutaneous hemorrhagic vasculitis in guinea pigs

The requirements of complement (C) to induce systemic and cutaneous Forssman reactions were studied in inbred DHC-BA and Hartley strain guinea pigs. After intravenous injection of Forssman antibody, fatal systemic shock was associated with a marked drop in CH₅₀, C4, and C3 and a lesser decrease in C5 hemolytic activity. Platelet counts and leukocyte counts dropped as well. With the use of the purified low molecular weight factor from cobra venom (CVF) to deplete C3, guinea pigs with less than 1% intravascular C3 were protected from lethal shock. Approximately 1% to 3% C3 activity is required for Forssman cutaneous vasculitis. These results confirm earlier studies that classical complement pathway activation occurs in Forssman shock and demonstrate the exquisite biologic efficiency of C3 in provoking the shock syndrome.