Lymphocytes with immunoglobulin E Fc receptors in patients with atopic disorders.

Lymphocytes from normal nonallergic donors and patients with atopic disorders were analyzed for subpopulations bearing Fc receptors for immunoglobulin (Ig)E (Fc(epsilon)) and IgG (Fc(gamma)), surface IgM (sIgM) and IgD (sIgD), and for T cells forming spontaneous rosettes with sheep erythrocytes (E). The patients were divided into three groups according to serum IgE concentrations and systemic corticosteroid treatment. Group I consisted of 12 atopic patients with either normal or moderately increased IgE levels up to 4,000 U/ml. Four patients of group II and three of group III had 10,500-31,000 U/ml and severe atopic dermatitis. Patients of group III, but not I and II, were receiving corticosteroids systemically. The percentage (mean +/-SD) and total number of Fc(epsilon) (+) lymphocytes were 1.2+/-0.5%, 41+/-24/mm(3) in 12 normals; 1.6+/-0.9%, 59+/-43/mm(3) in patients of group I: 7.0+/-2.0%, 187+/-67/mm(3) in group II; and 0.3+/-0.1%, 13+/-5/mm(3) in patients of group III. The increase in group II and decrease in group III of Fc(epsilon) (+) cells were statistically significantly different from the normal persons and patients of group I. In contrast, the patients did not differ significantly from the donors in sIgM(+), sIgD(+), Fc(gamma) (+), and E(+) cell populations. As shown by depletion of sIg(+) cells in four patients with atopic disorders, the great majority of the Fc(epsilon) (+) lymphocytes were B cells. However, two patients with elevated Fc(epsilon) (+) cell numbers had small numbers of mixed E- and Fc(epsilon)-rosetting cells, presumably T cells. Two patients of group II were examined during an acute herpes simplex infection. Both showed an congruent with80% decrease of Fc(epsilon) (+) cells at that time. No apparent correlation between numbers of Fc(epsilon) (+) cells and IgE level existed in patients of group I. Injection of an IgE myeloma protein into two monkeys did not significantly change their percentages of Fc(epsilon) (+) lymphocytes. The data indicate that Fc(epsilon) (+) lymphocytes are increased in patients with markedly elevated serum IgE and severe atopic disease, suggesting that these cells may be involved in the regulation and(or) synthesis of IgE antibody formation.

Immunoglobulin E-rheumatoid factor in the serum of patients with rheumatoid arthritis, asthma, and other diseases.

A solid-phase radioimmunoassay was developed to detect immunoglobulin (Ig)E antibodies that bound to human IgG. IgE-rheumatoid factor activity was found in the serum of 18 of 20 patients with seropositive rheumatoid arthritis, 1 of 4 patients with seronegative rheumatoid arthritis, 3 of 32 patients with seronegative rheumatoid arthritis, 3 of 32 patients with asthma, and in 1 patient with hypocomplementemic vasculitis and iodide sensitivity. Immunopathologic implications of IgE-rheumatoid factor are discussed.

Provoking factors in bronchial asthma.

Asthmatic patients were identified as having asthma on the basis of lung function studies (76%), objective physical findings of asthma (11%), or a strong history of asthma (13%). Each of the 234 patients so identified was assigned to an asthma subgroup determined by careful clinical assessment of the major provoking factor or factors for his asthmatic episodes; minor provoking factors were also identified. Only 20% of the patients had asthmatic episodes provoked by a single factor. Most asthmatics had at least one major and one or more minor provoking factor(s). Reagin-mediated mechanisms constituted the major provoking factor in 25% of patients and were a minor provoking factor in an additional 20% of the patients. Thus, in only 45% of the patients, were reaginic mechanisms responsible for some part of their asthmatic episodes.

Precipitating factors in asthma. Aspirin, sulfites, and other drugs and chemicals.

Several types of reactions to drugs and chemicals may precipitate or perpetuate asthmatic relapse. This review focuses on reactions to aspirin and sulfites. Approximately 40 percent of patients with rhinosinusitis, nasal polyps, and asthma and 5 to 10 percent of all asthmatic patients are sensitive to aspirin and aspirin-like nonsteroidal anti-inflammatory drugs at some time in their course. A prudent recommendation to all asthmatics is to substitute acetaminophen for aspirin. When aspirin/aspirin-like drug is essential for treatment of cardiovascular or musculoskeletal disorder, desensitization by cautious oral challenges with graded doses of aspirin can be accomplished. Treatment of the respiratory disorder per se by desensitization followed by daily therapeutic aspirin remains investigational. Sulfur dioxide and sulfites, commonly used as sanitizers and preservatives of foods and pharmaceuticals, may precipitate acute asthma in 5 percent or more of asthmatic patients. When the history suggests sulfite sensitivity, challenges can be used to confirm sensitivity and the patient counseled in avoidance of these chemicals.

Allergic bronchopulmonary candidiasis.

A patient had an illness consistent with allergic bronchopulmonary candidiasis. She had asthma, fleeting pulmonary infiltrate, immediate skin reactivity and precipitating antibody against Candida albicans, elevated total serum IgE concentration, elevated IgE and IgG antibody activity against C albicans, and two positive sputum cultures for C albicans. Serial serologic studies showed a significant decrease of serum IgE levels and IgE antibody activity after corticosteroid treatment.

Persistent asthma: patient characteristics, courses of asthma, and utility of salmeterol.

Applications of National Asthma and Education and Prevention Program (NAEPP) guidelines for the diagnosis and management of asthma may reduce the morbidity of this disorder. Medical records and questionnaires from a series of 177 outer-city adolescents and adults with persistent asthma were audited according to NAEPP guidelines and for utility of salmeterol (Serevent). Allergic sensitivity and exposure to indoor allergens house-dust mite (66% of patients), fungi (42%), cat (20%) and/or dog (14%) were of dominant importance to persistent asthma. Patients who continued salmeterol over 1 year had reduced severity of disease, improved forced expiratory flow at 25%-75% of vital capacity, and reduced usage of systemic, but not inhaled, corticosteroid.

In vitro cyclic nucleotide responsiveness of leukocytes and platelets in patients suffering from atopic dermatitis.

Peripheral blood leukocytes from patients with severe atopic dermatitis (serum IgE levels between 1,560 and 28,000 U/ml) showed a significantly weaker increase in intracellular cAMP after stimulation with epinephrine (10(-5)-10(-3) M) than leukocytes from normals. At the same time stimulation with methylcholine (10(-10)-(10(-4) M) induced a significantly higher increase in intracellular levels of cGMP in the atopic group compared to normals. The immunomodulating agent levamisole induced a slight increase in cAMP and cGMP response both in leukocytes from atopic patients and in normals. Platelet cAMP concentrations were lowered by epinephrine stimulation both in atopics and controls. There was no effect of methylcholine upon platelet cyclic nucleotide levels in the dose range examined. The data support the concept that abnormal cyclic nucleotide responsiveness--not only as beta-adrenergic blockade but also as cholinergic hyperreactivity--may plays a role in the pathogenesis of atopic dermatitis.

Aspirin-sensitive asthma: tolerance to aspirin after positive oral aspirin challenges.

Two aspirin-sensitive asthmatic patients underwent oral aspirin challenges for investigative purposes. Folowoing the expected respiratory reaction to aspirin, the patients became refractory to the further adverse effects of aspirin. Additionally they began taking 325 mg aspirin per day, and after 6 and 8 mo aspirin dosage was increased to 650 mg per day. We have noted an improvement in their rhinitis and asthma during this open drug trial. Furthermore, maintenance systemic corticosteroids have been reduced in one patient and discontinued in the other without a decline in lung function values. If these intitial observations are found in a larger number of aspirin-sensitive asthmatic patients, changes in our understanding of the pathogenesis of rhinosinusitis-asthma-aspirin syndrome would follow, and treatment for such asthmatic patients might be improved.

Radiographic contrast media studies in high-risk patients.

Patients with prior anaphylactoid reactions (AR) to radiographic contrast media (RCM) are at increased risk for another reaction upon repeat exposure to RCM. One hundred one patients, who had prior AR to RCM, who gave informed consent, and who had an essential need for a repeat RCM study, were pretreated with prednisone, 50 mg orally every 6 hours for 3 doses ending one hour prior to RCM study, and diphenhydramine, 50 mg intramuscularly, one hour prior to RCM study. The repeat RCM study was then carried out using standard procedures with resuscitation equipment readily available. Ninety-six patients had no reaction. Five of the 101 (4.95%) developed AR. These AR consisted only of mild urticaria or pruritus. No significant or life-threatening reactions occurred. Pretreatment decreases the risk in this population of patients and is recommended as standard prophylaxis for patients requiring RCM who have had a previous AR.

Purification and characterization of two functionally distinct forms of C1 inhibitor from a patient with angioedema.

A minority of patients with hereditary angioedema (HAE) have normal concentrations of a dysfunctional C1 inhibitor protein (C1INH) in their plasmas. We purified C1INH from the plasmas of one such patient before and during treatment with the anabolic steroid stanozolol. Both the pretreatment plasma and plasma obtained during stanozolol treatment contained varying amounts of two extremely similar C1INH proteins that were functionally distinct. The pretreatment plasma contained primarily (94%) dysfunctional C1INH that did not inactivate or complex with either purified C1s, activated Hageman factor, or kallikrein and small amounts (6%) of functionally normal C1INH. Stanozolol treatment increased the plasma concentrations of both of these proteins as well as the proportion (23%) of functional C1INH in the plasma. The purified dysfunctional and functional C1INHs had identical or nearly identical molecular sizes, charges, amino acid compositions, and amino sugar contents, and could not be distinguished physicochemically from each other or from normal C1INH. From these studies of purified C1INH proteins we concluded that HAE associated with dysfunctional C1INH is due to a defect at the structural locus for one C1INH gene and that both the dysfunctional C1INH gene and the normal C1INH gene products are present in the plasma of the affected subject. Treatment with stanozolol comparably increased the synthesis of both C1INH proteins. The disproportionate rise in the level of the normal C1INH protein is consistent with the view that it is more rapidly catabolized as a consequence of its interaction with the proteases it inactivates.

In vitro releasability of histamine and serotonin: studies of atopic patients.

Sixteen atopic patients with anaphylaxis to food, eczema, asthma and/or rhinitis were investigated for in vitro reactivity of their leukocytes and platelets to various stimuli. Leukocytes from two patients with anaphylaxis to foods had very high spontaneous release of histamine. Compared to non-atopic volunteers without respiratory disease, leukocytes from the other atopic patients showed increased histamine release after stimulation with methacholine in concentrations between 10(-2) and 10(-6) M. Histamine release induced by anti-IgE or anti-kappa chain serum was slightly decreased in atopics compared to controls, and was significantly decreased at low concentrations of anti-IgE (p less than 0.05). There was no significant difference of means for histamine release induced by the calcium ionophore A-23815. The uptake of 3H serotonin from platelet-rich plasma of atopic patients appeared to occur more slowly than in non-atopics. Serotonin release from washed platelets after stimulation with aggregated IgG was significantly lower in the atopic group (p less than 0.01). There was no significant difference in serotonin release induced by thrombin, epinephrine, ionophore or methacholine. Alterations in releasability of mediator containing cells to immunologic and non-immunologic stimuli may play a role in the expression of atopic disease.

Potassium iodide sensitivity in four patients with hypocomplementemic vasculitis.

During metabolism studies of radiolabeled proteins in 126 participants four patients were suspected of being sensitive to potassium iodide (Kl) because they repeatedly developed urticaria and other symptoms after Kl administration. Two of the four patients suspected of Kl sensitivity and 10 control patients were orally challenged with Kl to document and characterize Kl sensitivity and to evaluate the possible association(s) of Kl sensitivity with urticaria, hypocomplementemia, and vasculitis. The Kl challenges in the two sensitive patients precipitated urticaria, angioedema, polymyalgias, conjunctivitis, and coryza. One of these two patients also developed a severe systemic illness characterized by fever, headache, peritonitis, episcleritis, and pneumonitis. The four sensitive patients were strikingly similar in that they exhibited hypocomplementemia and dermal vasculitis associated with chronic urticaria or systemic lupus erythematosus, suggesting that other patients with similar clinical features may be sensitive to Kl and that Kl may precipitate severe systemic illness in them.

Montelukast is only partially effective in inhibiting aspirin responses in aspirin-sensitive asthmatics.

BACKGROUND: Leukotrienes have been implicated as major mediators of ASA-induced respiratory reactions. In several prior studies, pretreatment of ASA-sensitive respiratory disease (ASRD) patients with leukotriene modifiers have sometimes allowed subjects to tolerate previously established provoking doses of oral ASA or inhalation ASA-lysine, without respiratory reactions. OBJECTIVE: The purpose of this study was to examine whether ASA-provoked respiratory reactions would be blocked or attenuated by pretreatment with a cystLT1 receptor antagonist, montelukast, particularly if ASA doses were increased above their threshold doses. METHODS: Baseline ASA oral challenges were performed. Eight to 12 days later, following pretreatment with montelukast 10 mg daily, threshold and then escalating doses of ASA were used during repeat oral ASA challenges. The differences in responses between baseline and montelukast protected ASA oral challenges were then compared. RESULTS: Nine of 10 patients, despite pretreatment with montelukast, experienced at least naso-ocular reactions during their second oral ASA challenges. In four of nine patients, asthmatic reactions also occurred. In comparing baseline and montelukast protected ASA challenges, there were no statistically significant differences in their responses. CONCLUSIONS: Pretreatment with montelukast allowed only one patient to proceed through all challenge doses of ASA without any reactions. The remaining nine patients enjoyed only partial protection from respiratory reactions. Montelukast pretreatment was generally not effective in altering upper airway reactions and only partly effective in altering lower airway reactions.

Long-term effects of aspirin desensitization--treatment for aspirin-sensitive rhinosinusitis-asthma.

One hundred seven known aspirin (ASA)-sensitive patients with rhinosinusitis-asthma were studied from 1975 to 1988. Forty-two of the patients avoided ASA and served as the control group. Thirty-five patients were desensitized to ASA and treated with daily ASA treatment (Rx) for as long as 8 years (mean, 3.75 years) to May 1988 and were designated the continuous group. Thirty patients, initially desensitized to ASA and treated with daily ASA, who stopped Rx permanently after a mean duration of 2 years, were designated the discontinued group. Retrospective analyses of baselines revealed that both continuous and discontinued groups during ASA Rx demonstrated statistically significant reduction in number of hospitalizations per year, emergency room visits per year, outpatient visits per year, upper respiratory infections-sinusitis-antibiotics per year, need for nasal polypectomies and additional sinus operations, and improvement in sense of smell compared to the control group. Simultaneously, the ASA-Rx groups were able to significantly reduce systemic corticosteroid dosage, corticosteroid bursts per year, and, in the continuous group only, significantly reduce inhaled corticosteroids. All three groups maintained control of respiratory symptoms. ASA desensitization followed by long-term daily ASA Rx appears to improve ASA-sensitive rhinosinusitis-asthma and concomitantly allows reduction of systemic corticosteroids.

Safety and possible efficacy of fiberoptic bronchoscopy with lavage in the management of refractory asthma with mucous impaction.

Mucous impaction may be suspected in asthmatic exacerbation when, despite aggressive medical management, patients continue to produce sputum containing mucous plugs and exhibit prominent rhonchi and/or wheezes on chest auscultation. Spirometric measurements in this setting corroborate lack of improvement and reveal significant impairment in indices that may reflect small airways function (FEF25-75). We hypothesized that clearance of inspissated secretions by fiberoptic bronchoscopy with lavage (FOBwL) may promote or hasten the clinical improvement of such patients. Fifty-one therapeutic FOBwL were accomplished in 19 patients during 20 episodes of stabilized yet refractory asthma with mucous impaction. No significant complications were encountered. After FOBwL, spirometric measurements of FEV1, FEF25-75, and FVC increased significantly (P less than .01, paired t test), and correlated with relief of dyspnea and mobilization of secretions with cough. FOBwL can be safely performed in stabilized, refractory asthma, and with apparent efficacy. Further investigation is needed to document the therapeutic utility of FOBwL in refractory asthma.

Prevalence of cross-sensitivity with acetaminophen in aspirin-sensitive asthmatic subjects.

OBJECTIVE: Cross-sensitivity between aspirin and acetaminophen in aspirin-sensitive asthmatic patients has been reported with frequencies ranging from 0% to 29%. The relationship is dose-dependent for acetaminophen challenges, ranging between 300 and 100 mg. METHODS: To determine the prevalence of cross-sensitivity to high-dose acetaminophen, we performed single-blind acetaminophen oral challenges with 1000 mg and 1500 mg in 50 aspirin-sensitive asthmatic patients and in 20 non-aspirin-sensitive asthmatic control subjects. RESULTS: Overall, 17 of 50 (34%) of aspirin-sensitive asthmatic patients reacted to acetaminophen in doses of 1000 to 1500 mg (95% confidence interval: 20% to 49%). By contrast, none of the 20 non-aspirin-sensitive asthmatic patients reacted to acetaminophen (95% confidence interval: 0% to 14%). This difference was highly significant (p = 0.0013), supporting the hypothesis that cross-sensitivity between aspirin and acetaminophen is unique in aspirin-sensitive asthmatic patients. CONCLUSION: Although high-dose ( > 1000 mg) acetaminophen cross-reactions with aspirin were significant with respect to frequency (34%), such reactions included easily reversed bronchospasm in only 22%, and were generally mild. We recommended that high doses of acetaminophen (1000 mg or greater) should be avoided in aspirin-sensitive asthmatic patients.