Antibody production following immunization with diphtheria and tetanus toxoids in children receiving chemotherapy during remission of malignant disease.

Twenty-seven children with various childhood malignancies who were in clinical remission and receiving maintenance chemotherapy were given diphtheria-pertussis-tetanus (DPT) immunizations. Antidiphtheria and antitetanus titers were drawn before and 1 month after immunization. Only one child had no antibody response to either antigen. Two other children failed to develop any detectable antitetanus antibody titer but did mount a normal antibody response to inactivated diphtheria antigen. In fact, most children made good antibody responses to both immunizing antigens, irrespective of the nature of their disease or of the treatment given. These results show that children receiving long-term chemotherapy should not be denied the protection afforded by immunization with nonliving vaccines.

Flunisolide aerosol for treatment of severe, chronic asthma in steroid-independent children.

The efficacy and safety of flunisolide aerosol were studied in 46 steroid-independent children with asthma inadequately controlled by nonsteroid drugs. This was a double-blind, placebo-controlled, parallel study lasting eight weeks. Patients were randomly assigned either flunisolide by inhalation, 0.5 mg twice a day, or placebo. Effectiveness was evaluated daily by symptom scores, by Wright peak flow measurements twice daily, and weekly by spirometry and physical examination. Adrenal function and throat cultures for Candida were evaluated before and after the test-drug treatment period. Flunisolide was administered to 25 patients and 21 received placebo. Most symptom scores were statistically significantly better in flunisolide-treated than in placebo-treated patients; these included severity of wheezing (P = .01), chest tightness (P = .01) and shortness of breath (P = .02), and frequency (P = .001) and severity of asthma attacks (P = .03). In addition, placebo-treated patients used significantly more bronchodilators than flunisolide-treated patients. In the final therapeutic effectiveness evaluation, 72% of flunisolide-treated patients received very good or good ratings, whereas only 29% of placebo-treated patients received these ratings (P = .005). No patient developed thrush, evidence of adrenal suppression, or other severe adverse reaction. Flunisolide aerosol was shown to be effective and safe in controlling asthma in children who were candidates for oral steroid therapy.

A 1-week dose-ranging study of inhaled salmeterol in patients with asthma.

STUDY OBJECTIVE: A dose-ranging study was conducted to evaluate the efficacy and safety of a new long-acting, selective beta 2-adrenoceptor agonist, salmeterol. DESIGN: Adolescents and adults (N = 160) with mild-to-moderate asthma received salmeterol (10.5, 21, 42, or 84 micrograms) or placebo by metered-dose inhaler twice daily for 1 week. Twelve-hour serial spirometry measurements were performed on the first and last days of treatment, and patients recorded their peak expiratory flow (PEF) twice daily on diary cards. RESULTS: On day 1, salmeterol produced greater bronchodilation than placebo (p = 0.001), and both the 42-micrograms and 84-micrograms doses of salmeterol were significantly more effective in improving FEV1 responses than the two lower doses of salmeterol (p < 0.05). After 1 week of treatment, all but the 21-micrograms dose of salmeterol remained statistically superior to placebo (p < 0.01), but significant differences between salmeterol doses were no longer evident, despite an apparent dose-response effect. Only the 42-micrograms and 84-micrograms doses of salmeterol sustained bronchodilation for 12 h in the majority of patients at both treatment days. The degree of improvement in morning and evening PEF was also found to be dose related. There was no significant difference among treatment groups in the overall incidence of adverse events; however, pharmacologically predictable events (eg, tremor) occurred significantly more often with salmeterol, 84 micrograms. CONCLUSIONS: Salmeterol, 42 micrograms, was similar in efficacy to 84 micrograms but was associated with a lower incidence of adverse events. Salmeterol, 42 micrograms twice daily, is a safe and effective dosage for patients with mild-to-moderate asthma who are persistently symptomatic and require maintenance bronchodilator therapy.

Serum immunoglobulin E and incidence of allergy in group of enuretic children.

Serum immunoglobulin E levels were determined in 34 enuretic children and 20 age-matched controls. No differences were detected. Additionally, the incidence of allergic disorders in these enuretic children was no different from the general population.

Histamine levels and nasal cytology in children with chronic otitis media and rhinitis.

OBJECTIVE: Nasal and middle ear diseases are frequent health problems for young children. In some of these patients, allergic reactions may be contributing factors. The objective of this study was to determine whether the histamine level in nasal mucosal scrapings may be used as a marker for this subset of children. METHODS: A total of 50 children, aged 2 through 7 years, was categorized into five groups of ten subjects as: normal, allergic rhinitis, nonallergic rhinitis, allergic with otitis media and nonallergic with otitis media by history, physical examination, allergy skin testing, nasal cytology, and tympanometry. Nasal mucosal scrapings were obtained using the Rhino-probe technique. Eosinophils, basophilic cells, neutrophils, and bacteria in nasal cytograms were quantified. Histamine levels were measured by radioimmunoassay, the values normalized to the total protein content assayed by enzyme-linked immunoassay, and expressed in pcg/micrograms of total protein. RESULTS: The mean histamine level for each group was: normal = 0.20, allergic rhinitis = 10.14, nonallergic rhinitis = 0.13, allergic with otitis media = 5.34, nonallergic with otitis media = 0.24 pcg/micrograms of total protein. Mean levels of histamine were statistically significantly higher in the allergic groups than in the nonallergic and normal groups (P < .05). Allergic groups had significantly more eosinophils and basophilic cells in the nasal cytograms than the nonallergic groups. By contrast, the cytograms of children with nonallergic rhinitis and nonallergic otitis had significantly more neutrophils than the normal and allergic groups. CONCLUSION: We conclude that measuring histamine in nasal mucosal scrapings could be useful in the evaluation of young children with rhinitis and otitis and in determining which patients may have allergic disease.

The safety of egg-containing vaccines for egg-allergic patients.

Forty-two patients with a history of egg sensitivity were evaluated for receiving avian-grown vaccines. After giving a history and undergoing physical examination, each patient was skin-tested with egg antigens and six egg-propagated vaccines, given an oral egg challenge, and finally, when possible, given a vaccine challenge. Thirty-seven of the 42 patients (88%) were ultimately given one or more of the vaccines with no reactions or only minimal ones to both egg protein and vaccine; they had mild reactions consisting of pruritus, headache, and apprehension. Immunization was withheld from three patients who had a history of severe reactions after egg ingestion and strongly positive skin reactivity to both egg and vaccine. A history of egg intolerance should not, by itself, disqualify a patient from receiving one of these vaccines. However, a history of exquisite sensitivity to egg protein indicates that a severe vaccine reaction is likely. An intradermal skin test utilizing 0.02 ml of a 1:100 dilution of the vaccine and resulting in a wheal of greater than 5 mm was found to be the test that most reliably predicted those patients who should not receive the vaccine.

Flunisolide aerosol in treatment of steroid-dependent asthma in children.

The efficacy of flunisolide aerosol in permitting the reduction of oral steroid dosage without deterioration of asthma was studied in 34 children requiring at least 10 mg prednisone g.o.d. This was a double-blind, placebo-controlled, parallel study lasting 14 weeks. Progress was evaluated daily by symptom scores, bronchodilator use and Wright Peak Flow measurement and every two weeks by spirometry and physical examination. Adrenal function and throat culture for Candida were evaluated before and after the study period. Similar reduction in mean prednisone dosage was achieved in flunisolide and placebo patients. However, flunisolide patients improved and placebo patients deteriorated clinically. These changes were gradual and frequently not detected at bi-weekly evaluation. No patient developed thrush, adrenal suppression or other adverse reaction. Flunisolide aerosol was shown to be safe, acceptable and effective in permitting reduction of oral steroid dosage without increase in symptoms.

Therapeutic efficacy and equivalence of tablet and syrup formulations of procaterol hydrochloride in childhood asthma.

It has been reported that albuterol syrup produces more improvement in pulmonary function and greater increases in heart rate than an equal dose of albuterol tablets in asthmatic children. Consequently, tablet and syrup formulations of a new beta 2-adrenergic drug, procaterol hydrochloride, were tested for efficacy and equivalence. The two formulations were compared after the first dose and after 1 week of double-blind treatment in 11 children. Statistical analyses indicated that there were few significant differences in the bronchodilating efficacy of the tablet and syrup formulations. Improvement in pulmonary function began within one-half hour postdose and continued until four to six hours postdose. Increases in heart rate were small. Adverse effects were similar for the two formulations. Five patients showed minimal electrocardiogram changes. Tremor, reported by four patients, was the only other adverse effect. In conclusion, the tablet and syrup formulations of procaterol hydrochloride were equivalent in bronchodilating efficacy and safety in childhood asthma.

Atopy and IgE in a pediatric allergy practice.

In children under six years of age referred to a pediatric allergy practice the usefulness of serum IgE assay was evaluated in relation to age, symptoms, nasal eosinophilia, skin tests and family history. In more than 60% of the children the initial symptom, usually rhinorrhea, had occurred before one year of age. In infancy the diagnosis was more difficult, gastrointestinal complaints were more frequent and nasal eosinophilia less frequent than in the older children. Many infants had positive skin tests to foods and to environmental allergens. There was a significant correlation between elevated serum IgE level and age, nasaeosinophilia, the number of positive skin tests and the probability of immunotherapy being prescribed. Although no clear diagnostic level is seen, an IgE level above 100 micron/ml at any age and an IgE level above 20 micron/ml in infants strongly suggest the possibility of atopic disease. However, a low IgE level does not exclude atopic disease.

Subjective and objective assessments in patients with seasonal allergic rhinitis: effects of therapy with mometasone furoate nasal spray.

BACKGROUND: Efficacy of topical nasal steroid therapy for allergic rhinitis is usually evaluated by patient and clinician assessments of subjective symptom changes in diaries and at clinical interviews. OBJECTIVE: We sought to complement the subjective measures with objective measures of nasal cytology, biochemistry, and function. METHODS: In this double-blind, randomized study patients with seasonal allergic rhinitis (SAR) 12 years of age or older received 200 microg mometasone furoate nasal spray (n = 80) or placebo spray (n = 41) once daily for 2 weeks. Subjective assessments by clinician and patient comprised symptom/sign scores and overall therapeutic response evaluations. Objective measures included nasal cytology, nasal biochemistry, nasal airway resistance (NAR), mucociliary clearance, and olfactory functions. RESULTS: Mometasone furoate produced a significantly greater decrease than placebo in subjective measures of SAR for total symptom score (-46% vs -30%, p < 0.05), total nasal score (-47% vs -30%, p < 0.024), individual nasal symptom scores, and overall therapeutic response. The objective measures of eosinophil, basophil, and neutrophil counts and mucociliary clearance were significantly better in mometasone furoate- than in placebo-treated patients. Similarly, within-treatment statistically significant improvements were produced by mometasone furoate but not by placebo sprays for levels of eosinophilic cationic protein, tryptase and albumin, NAR, and odor identification. Significant positive correlations were found between NAR and nasal stuffiness and between eosinophils, basophils, and neutrophils and both eosinophilic cationic protein and albumin. CONCLUSION: Subjective measures of SAR were significantly improved in the mometasone furoate group by comparison with placebo-treated patients. Objective assessments supported the subjective findings because within-treatment measures were frequently significantly improved after mometasone furoate treatment but not after placebo treatment.

Clinical, rhinomanometric, and cytologic evaluation of seasonal allergic rhinitis treated with beclomethasone dipropionate as aqueous nasal spray or pressurized aerosol.

The currently available beclomethasone dipropionate (BDP) metered-dose nasal aerosol spray is considered uncomfortable by some patients because of the force of delivery. It was compared for efficacy and acceptability in a double-blind study with a new aqueous suspension BDP spray for the treatment of seasonal allergic rhinitis in 44 symptomatic patients aged 12 to 43 years. After 7 days of baseline evaluation, every patient was given both an aerosol canister and an aqueous spray bottle each containing either BDP, 42 mcg per spray, or placebo (P). For 15 days the patient sprayed each nostril twice a day with one spray of suspension (BDP or P) followed 5 minutes later by one spray of aerosol (P or BDP). Patients were evaluated before the study medications were started (day 1) and on days 4, 8, and 15 for nasal and eye symptoms. Nasal cytologic specimens were examined on days 1 and 15, and rhinomanometry was performed on days 1, 8, and 15 of the study. Topical BDP by both methods of delivery was rapidly effective in decreasing mean nasal obstruction, rhinorrhea, sneezing, and itching symptoms as well as mean eye symptoms with no statistically significant differences between them. Nasal airflow increased with both treatments; rhinomanometry significantly correlated with subjective nasal obstruction scores. Of 34 patients with nasal eosinophils, 74% had fewer eosinophils after treatment. Most patients (84%) preferred the aqueous spray over the pressurized aerosol.

Bitolterol and albuterol metered-dose aerosols: comparison of two long-acting beta 2-adrenergic bronchodilators for treatment of asthma.

In this double-blind, parallel, single-dose study, bitolterol mesylate aerosol (three sprays, 1.11 mg) and albuterol aerosol (two sprays, 180 mcg) were compared for efficacy of bronchodilation in 120 adolescent and young adult patients with moderate to severe asthma. All patients required regular medications for asthma control. None was steroid dependent. Both medications gave effective bronchodilation within 5 min with maximum effect at 30 to 60 min. Mean percent increase in forced expiratory volume in 1 sec (FEV1) over baseline was higher for bitolterol than for albuterol at all test times up to 8 hr after a dose at which time 20% mean percent increase of FEV1 over baseline was still present in the bitolterol-treated patients. With albuterol mean percent increase in FEV1 fell to 15% over baseline at 5 hr after a dose. Differences in FEV1 increase between the two treatment groups were statistically significant at 4 to 8 hr after a dose. Patients with baseline FEV1 less than 50% of predicted normal had a response to bitolterol that was higher than that observed with albuterol treatment (p less than 0.1). Mean maximum percent increase in FEV1 and median duration of bronchodilation were greater with bitolterol than with albuterol, but the differences were not statistically significant. Both bitolterol aerosol and albuterol aerosol were demonstrated to be safe, effective, and long-acting bronchodilating agents. Both bitolterol and albuterol administered by aerosol had a rapid onset, and the maximum degree of bronchodilation was comparable. However, at the doses studied, bitolterol produced significantly higher increase in FEV1 over baseline at longer times after medication than did albuterol.

Inhaled albuterol powder for the treatment of asthma--a dose-response study.

Many patients are unable to obtain optimal benefit from inhaled bronchodilators as delivered by metered-dose aerosol spray because of difficulty in synchronizing release of medication with the start of inspiration. The Rotahaler is a flow-activated device that avoids this problem since the act of inspiration itself delivers medication to the lungs. In this randomized, double-blind, crossover study, each of 20 male patients with moderate to severe asthma, ages 12 to 23 yr, received a single treatment with 100, 200, or 400 mcg of albuterol powder or placebo by Rotahaler on 4 study days separated by 2 to 10 days. All patients stopped theophylline and inhaled beta-agonists as needed 24 and 12 hr, respectively, before study days. All patients emptied the Rotahaler with a single inhalation. Pulmonary functions were followed for 8 hr after medication. Statistical analyses of FEV1, FEF25-75, and FVC revealed that all doses of albuterol powder were superior to placebo within 5 min with a log dose-response trend for both degree and duration of bronchodilation.

Assessment of the correlation of rhinometry with the symptoms and signs of allergic rhinitis in children.

The measurement of nasal patency by anterior rhinometry is a potentially useful tool in evaluating patients with various forms of rhinitis. This study measured both nasal air flow by anterior rhinometry and symptom/sign scores in 49 children with perennial allergic rhinitis. We found that anterior rhinometry in children is (1) a simple, rapid procedure, (2) well accepted by the pediatric patient, and (3) a valid technique for objectively assessing and quantifying the somewhat subjective parameters that physicians traditionally follow for allergic rhinitis.

Steady-state evaluation of twice-a-day dosing of a new sustained-release theophylline preparation for young children.

We studied the absorption properties of a new sustained-release theophylline, Theo-Dur Sprinkle (TS), to see if this formulation when given on a b.i.d. basis results in acceptable steady-state theophylline levels in children with asthma. Twelve patients (ages 5-8 years), after multiple TS dosing, had serum theophylline levels determined over a 10-hr period after a morning TS dose. Fluctuations in serum theophylline concentrations were acceptable with the observed mean percent peak-to-trough fluctuation [(peak-trough/trough) x 100] being 53%. Patients required higher than usually recommended theophylline doses to obtain therapeutic levels, suggesting incomplete absorption of TS; this was documented with one patient using a 100% bioavailable theophylline product as a comparison.

Effect of dosing schedule on efficacy of beclomethasone dipropionate aerosol in chronic asthma.

Fifty-two children 6 to 12 yr of age and 37 young adults 13 to 38 yr of age with moderate to severe extrinsic asthma requiring daily bronchodilators and who had been taking beclomethasone dipropionate (BDP) for at least 3 months were evaluated. All patients received their regular daily medications and BDP, 2 inhalations 4 times a day (q.i.d.) (total dose, 336 micrograms/day), for 2 wk; they were then randomized to receive either BDP or placebo aerosol, 4 inhalations twice a day (b.i.d.), with the same total dose/day as well as their regular medications, for 8 wk. Placebo patients deteriorated significantly by comparison with BDP patients in respiratory symptoms and pulmonary functions. More placebo than BDP patients ended participation in the study prematurely because of increasingly severe symptoms. In the 89 study patients, there were no significant differences in respiratory symptoms or pulmonary function measurements between the b.i.d. and q.i.d. dosage regimens in either pediatric or adult age groups. There were no significant changes in mean morning cortisol levels from baseline measurements to the end of the study period; at that time, all patients had a normal ACTH stimulation test. We conclude that BDP (336 micrograms/day) is as effective and safe for control of asthma symptoms with b.i.d. as with q.i.d. dosage schedules in pediatric and young adult patients.

Nasal cytology in patients with allergic rhinitis: effects of intranasal fluticasone propionate.

BACKGROUND: Nasal cytograms of patients with allergic rhinitis contain increased numbers of eosinophils and basophilic cells. Neutrophils are also more numerous in cytograms of allergic persons. Topical intranasal corticosteroid therapy for allergic rhinitis has been shown to decrease the numbers of some inflammatory cell types. Fluticasone propionate aqueous nasal spray, a potent synthetic corticosteroid preparation, is effective therapy for seasonal and perennial allergic rhinitis. METHODS: Nasal mucosal scrapings were obtained with a Rhinoprobe (Apotex Scientific, Inc. Arlington, Texas) before and after therapy with fluticasone propionate aqueous nasal spray at several doses in patients with either seasonal allergic rhinitis (2 to 4 weeks' therapy) or perennial allergic rhinitis (24 weeks' therapy). More than 1000 paired nasal cytograms obtained from patients participating in five multicenter studies were evaluated. RESULTS: The percentage of patients with nasal eosinophils (p < 0.01, most studies) and basophilic cells (p < 0.05, most studies) decreased significantly after treatment with fluticasone propionate compared with placebo-treated patients. Similar findings were observed with beclomethasone dipropionate in one study. The number of neutrophils remained relatively unchanged after treatment with the intranasal corticosteroids or placebo. CONCLUSIONS: These findings suggest that the therapeutic benefits of topical intranasal fluticasone propionate and beclomethasone dipropionate for the therapy of seasonal and perennial allergic rhinitis are reflected by the decrease in inflammatory cells in the nasal mucosa.

Terbutaline sulfate and isoproterenol sulfate (metered dose aerosols) in the treatment of asthma.

A double-blind randomized study of 50 patients was conducted to evaluate the efficacy and safety of terbutaline sulfate aerosol and isoproterenol sulfate aerosol in the treatment of patients with moderate to severe asthma. The patients were randomized to receive either terbutaline or isoproterenol (two sprays, four times a day) for 14 weeks with office evaluations at three week intervals. On that day pulmonary function studies as well as electrocardiographs (EKG), blood chemistry analysis and urinalysis were performed before, and pulmonary function studies and EKG at intervals for four hours after, study medications were taken. Terbutaline sulfate was shown to have a much more sustained effect and a larger "area under the curve" than isoproterenol, but the magnitude of the peak effect was similar. There was no statistically significant difference in pulmonary function responsiveness throughout the duration of this study with either medication. Few patients experienced serious adverse reactions and no EKG changes were noted.

Concomitant bitolterol mesylate aerosol and theophylline for asthma therapy, with 24 hr electrocardiographic monitoring.

A higher incidence of fatal asthma after increased use of combined inhaled beta 2-agonists and theophylline has been attributed to additive cardiac toxicity of these agents. This study had three major objectives: first, to evaluate the efficacy and safety of a new long-acting beta 2-agonist, bitolterol mesylate, given as metered-dose aerosol in a regular "round-the-clock" asthma medication regimen; second, to compare the efficacy and safety of bitolterol with those of sustained-release theophylline alone and of the combination of bitolterol and theophylline; third, to use 24 hr Holter monitoring to evaluate cardiac toxicity of the three medication regimens. This was a 6 wk double-blind study of regular, daily medication in 36 young non-steroid-dependent and 37 older steroid-dependent stable asthmatic patients. All patients had two 24 hr Holter ECG monitorings during the 2 wk baseline period when all patients received theophylline only and four further 24 hr Holter monitorings during the double-blind period. All Holter recordings from the study groups showed no significant abnormalities in any treatment group. Pulmonary function studies were performed on 4 study days in the 6 wk double-blind period. The largest increase in bronchodilator effect was obtained with combined medication and the smallest with theophylline alone. Mean duration of action was markedly longer in the combined treatment group (greater than 7 hr) than with bitolterol mesylate aerosol or theophylline alone (greater than 5 and greater than 4 hr, respectively) in the non-steroid-dependent patients. Degree of bronchodilation and duration of action was less in the steroid-dependent patients in all treatment groups. There is no evidence from cardiac monitoring that therapeutic doses of bitolterol mesylate or theophylline alone or in combination have cardiotoxic effects.