Dietary manipulations in infants and their mothers and the natural course of atopic disease.
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Allergens↗
Biomedical subjects
R S Zeiger
Publications and source records attributed to R S Zeiger.
Reduction of environmental tobacco smoke exposure among asthmatic children: a controlled trial.
STUDY OBJECTIVE: This randomized clinical trial tested a behavioral medicine program designed to reduce asthmatic children's exposure to environmental tobacco smoke (ETS) in the home. DESIGN: Families were randomly assigned to an experimental preventive medicine counseling group, a monitoring control group, or a usual treatment control group. Families were measured six times over 1 year. PARTICIPANTS: Ninety-one families were recruited from four allergy clinics. INTERVENTION: The experimental group received a 6-month series of counseling sessions designed to decrease ETS exposure. This group also monitored smoking, exposure, and children's asthma symptoms. The monitoring group did not receive counseling and the usual treatment control group received outcome measures only. MEASUREMENTS AND RESULTS: Parents reported the daily number of cigarettes children were exposed to during the week preceding interviews. A nicotine air monitor and construct validity analysis confirmed the validity of exposure reports. Exposure to the parent's cigarettes in the home decreased for all groups. The experimental group attained a 79 percent decrease in children's ETS exposure, compared with 42 percent for the monitoring control and 34 percent for the usual treatment control group. Repeated-measures analysis of variance resulted in a significant (F([10,350] = 1.92, p < 0.05) group by time effect. At the final 12-month visit, the experimental/counseling group sustained a 51% decrease in children's exposure to cigarettes in the home from all smokers, while the monitoring control group showed an 18% decrease and the usual treatment control group a 15% decrease from pre-intervention [corrected]. CONCLUSION: A behavioral medicine program was successful in reducing exposure to ETS in the home for these asthmatic children.
Adolescent↗
Development of nasal basophilic cells and nasal eosinophils from age 4 months through 4 years in children of atopic parents.
BACKGROUND: The importance of the inflammatory response in allergic disease has warranted investigation of two of the more integral cells in the pathogenesis of allergic rhinitis, namely, nasal basophilic cells (NBCs) and nasal eosinophils (NEs). In the present study the natural history of NBCs and NEs was studied from birth through 4 years of age in infants of atopic parents to better understand their relationship to the development of various atopic disorders. METHODS: During a prospective, randomized, controlled trial of the effect of maternal and infant food avoidance on the development of atopic disorders in 288 infants of atopic parents, NBCs and NEs were determined semiquantitatively on Wright-Geimsa stained nasal mucosal scrapings and related to each other and to various atopic parameters. RESULTS: In these infants who are at high risk NBCs developed in both those becoming atopic and those remaining nonatopic, but they occurred with increased frequency and quantity in those children in whom most allergic disorders and food or inhalant sensitization developed. NEs, rare at 4 months in all infants, increased in atopic children from 1 to 4 years, and remained infrequent and nominal in nonatopic children. Levels of NBCs and NEs (1) correlated with each other strongly, directly, and with increasing magnitude in children from ages 4 months to 4 years and (2) correlated with log serum IgE levels weakly and moderately in children from ages 2 to 4 years. Stepwise linear regression analyses revealed that allergic rhinitis accounted for most of the variance seen in the level of NBCs and NEs during early childhood, reaching 50% by age 4 years. Asthma, atopic dermatitis, food allergy, food and inhalant sensitization, serum IgE level, and IgG beta-lactoglobulin level accounted for a small proportion of the variance in NBCs and NEs from ages 4 months to 4 years. CONCLUSIONS: These findings help to elucidate the natural history of NBCs and NEs in infants at risk for atopic disorders and document the temporal association of these cells with the development of atopic disease, principally allergic rhinitis.
Basophils↗
Prospects for ancillary treatment of sinusitis in the 1990s.
The basis for ancillary therapy of sinusitis derives from anecdotal accounts and personal beliefs rather than definitive data. The recent appreciation that noninfectious inflammatory causes predispose to infectious sinusitis has stimulated renewed interest in developing and documenting efficacious ancillary therapies that could supplement or abrogate antibiotic use. Ancillary therapies of sinusitis could be directed toward (1) preventing viral upper respiratory tract infections (immunizations, virucidal-impregnated tissues, and proper hand-washing techniques); (2) blocking rhinoviral replication and suppressing mediator release with supraphysiologic nasal hyperthermia, although contradictory studies exist with regard to efficacy; (3) promoting sinus and nasal ventilation with both topical and oral alpha-agonists and exercise; (4) improving mucociliary clearance by reducing mucus viscosity and elasticity with saline solution irrigation, mucoregulators (N-acetylcysteine, S-carboxymethylcysteine, and iodinated glycerol), and ciliary stimulants (adenosine triphosphate); and (5) suppressing/modulating cellular inflammation (eosinophilic, basophilic, and neutrophilic) with topical nasal corticosteroid sprays and mediator antagonists. Recommendations are forwarded for future investigations of promising nonantibiotic ancillary therapies of chronic sinusitis.
Adrenergic alpha-Agonists↗
The impact of status asthmaticus practice guidelines on patient outcome and physician behavior.
This study assesses the effects of a status asthmaticus guideline on patient outcome and pediatrician behavior in a staff model health maintenance organization (HMO). The guidelines were drafted by an asthma specialist in the HMO and then discussed with key clinical personnel. A preprinted protocol order form was developed to help implement the guideline into clinical practice. The medical records of pediatric patients admitted to the hospital with status asthmaticus before (N = 67) and after (N = 59) guideline development and implementation were reviewed. This study demonstrates that locally developed, treatment-specific guidelines based on scientific evidence and combined with a staff consensus process and a user-friendly protocol form can influence physician behavior and patient outcome positively.
Adolescent↗
Increased transient tachypnea of the newborn in infants of asthmatic mothers.
OBJECTIVE: To compare the incidence of transient tachypnea of the newborn (TTN) in infants of asthmatic vs nonasthmatic mothers. RESEARCH DESIGN: Case-control analysis. SETTING: Group model health maintenance organization. PATIENTS: A volunteer sample of 294 pregnant asthmatic women and 294 pregnant nonasthmatic women with normal pulmonary function test results, matched on the basis of age and smoking status. All subjects entered the study before their third trimester of pregnancy. Subjects with multiple gestations and abortions (less than 20 weeks' gestation) were excluded. INTERVENTION: Asthma was treated in the allergy department. Routine obstetric, neonatal, and pediatric care was provided to all patients by staff physicians. MEASUREMENTS/RESULTS: Transient tachypnea occurred in 11 infants (3.7%) of asthmatic women and in one control infant (0.3%). There were no significant differences between asthmatic and matched control subjects in previously defined TTN risk factors, such as the occurrence of longer labors, failure to progress, cesarean sections, premature births, male sex, Apgar scores of less than 7 at 1 minute, or birth weight greater than 4 kg. Although infants of asthmatic mothers were more likely to exhibit wheezing by age 15 months compared with control infants (12.0% vs 3.2%), none of the infants with TTN manifested wheezing by age 15 months. No relationships could be identified in the asthmatic cohort between the occurrence of TTN and asthma severity or medication use (during the pregnancy in general or during labor and delivery in particular). CONCLUSION: Although the mechanism is uncertain, maternal asthma appears to increase the risk of infant TTN.
Adult↗
Facilitated referral to asthma specialist reduces relapses in asthma emergency room visits.
Facilitated asthma-specialist care delivered by allergists was compared to generalist care on the rate of relapse of asthma emergency room (ER) visits and hospitalizations and on asthma control in a prospective, controlled study of San Diego Kaiser Health Plan members with asthma. Subjects with asthma between the ages of 6 and 59 years presenting for acute ER care for asthma were systematically assigned by alternating, consecutively, the day of their ER visit to receive either (1) facilitated referral to an asthma specialist within the allergy department and concomitant comprehensive ongoing asthma care (intervention group, n = 149) or (2) continued outpatient management from generalist physicians (control group, n = 160). The course of their asthma was evaluated blindly during the subsequent 6 months by review of medical records, initial and follow-up questionnaires, and spirometry. Compared to the control group, the intervention group noted (1) a 75% reduction in the number of, and percent of, subjects with asthma awakenings per night (p less than or equal to 0.0001), (2) an almost 50% reduction in asthma ER relapses (p = 0.017) resulting from a reduction in the frequency of multiple relapse (p = 0.005), and (3) a greater use of inhaled corticosteroids (p less than 0.00001) and cromolyn (p = 0.002). Thus, facilitated referral of subjects with asthma to specialists in asthma therapy after acute ER therapy appears to reduce asthma ER relapses and to improve asthma outcome.
Adult↗
Intrauterine growth is related to gestational pulmonary function in pregnant asthmatic women. Kaiser-Permanente Asthma and Pregnancy Study Group.
Asthmatic mothers have been reported to deliver infants of lower mean birth weight than nonasthmatic mothers. This study examined the relationship between intrauterine growth and serial gestational spirometry in 352 pregnant asthmatic women who were prospectively treated and observed during pregnancy. A small (r = 0.11) but significant (p less than 0.04) direct correlation was demonstrated between infant birth weight and individual mean percent predicted FEV1 during pregnancy. In addition, lower maternal mean FEV1 during pregnancy was associated with increased incidences of birth weight in the lower quartile of the infant population (p = 0.002) and ponderal indices less than 2.2 (suggestive of asymmetric intrauterine growth retardation) (p less than 0.05), but not with increased incidences of preterm (less than 38 weeks) or low birth weight (less than 2,500 g) infants. Although lower mean birth weight occurred in infants of smoking compared with nonsmoking asthmatic mothers (p less than 0.02), the relationships of lower FEV1 to birth weight in the lower quartile of the population (odds ratio 3.0, p = 0.002) and ponderal indices less than 2.2 (odds ratio 2.8, p less than 0.05) were shown by multivariate analysis to be above and beyond the influence of smoking and also independent of the effects of age, parity, acute asthmatic episodes, and asthma medications. These data support the hypothesis that lower maternal gestational FEV1 during pregnancy is related to intrauterine growth retardation and suggest that the goals of gestational asthma therapy should include optimization of pulmonary function in addition to achievement of symptomatic control.
Asthma↗
Treatment of asthma and allergic rhinitis during pregnancy.
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Asthma↗
Prevention of food allergy in infancy.
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Food Hypersensitivity↗
Effect of combined maternal and infant food-allergen avoidance on development of atopy in early infancy: a randomized study.
The effect of maternal and infant avoidance of allergenic foods on food allergy was examined in a prenatally randomized, controlled trial of infants of atopic parents. The diet of the prophylactic-treated group (N = 103) included (1) maternal avoidance of cow's milk, egg, and peanut during the third trimester of pregnancy and lactation and (2) infant use of casein hydrolysate (Nutramigen) for supplementation or weaning, and avoidance of solid foods for 6 months; cow's milk, corn, soy, citrus, and wheat, for 12 months; and egg, peanut, and fish, for 24 months. In the control group (N = 185), mothers had unrestricted diets, and infants followed American Academy of Pediatrics feeding guidelines. The cumulative prevalence of atopy was lower at 12 months in the prophylactic-treated (16.2%) compared to the control (27.1%) group (p = 0.039), resulting from reduced food-associated atopic dermatitis, urticaria and/or gastrointestinal disease by 12 months (5.1% versus 16.4%; p = 0.007), and any positive food skin test by 24 months (16.5% versus 29.4%; p = 0.019), caused primarily by fewer positive milk skin tests (1% versus 12.4%; p = 0.001). The prevalences of allergic rhinitis, asthma, and inhalant skin tests were unaffected. Serum IgE levels in the prophylactic-treated group were marginally lower only at 4 months. Thus, reduced exposure of infants to allergenic foods appeared to reduce food sensitization and allergy primarily during the first year of life.
Adult↗
Double-blind, placebo-controlled food challenge (DBPCFC) as an office procedure: a manual.
There is now enough experience with the use of double-blind, placebo-controlled, food challenge (DBPCFC) to recommend its use as an office procedure for most patients complaining of adverse reactions to foods. This manual discusses the practical methods required for the allergist to undertake DBPCFC in the office. Thorough histories supplemented by food allergen skin testing are used to design a DBPCFC that carefully attempts to reproduce the history of food-induced symptoms described by the patient. Precautions that must be taken are delineated before challenge, as is treatment that may be required if a reaction occurs. For those foods to which challenges are positive, longitudinal evaluation with repeated challenge at appropriate intervals help to determine whether or not the problem will resolve over a period of time.
Allergens↗
IgG-, IgA-, and IgE-induced release of leukotriene C4 by monocytes isolated from patients with atopic dermatitis.
Purified peripheral blood monocytes isolated from patients with atopic dermatitis (AD) and from nonallergic normal donors were compared for their abilities to release leukotriene C4 (LTC4), leukotriene B4 (LTB4) and beta-glucuronidase in response to challenge with aggregated immunoglobulins or anti-immunoglobulins. The relationship between mediator release and the number of monocytes that formed rosettes with immunoglobulin-coated indicator cells was examined. Patients with AD had twice as many IgA- and three times as many IgE-rosetting monocytes as normal donors (48 +/- 12% versus 27 +/- 10% and 40 +/- 15% versus 14 +/- 3%, respectively), and yet the amounts of IgA- and IgE-induced LTC4 released were similar for both groups. This apparent discrepancy did not result from a decreased capacity for arachidonate metabolism via the C5-lipoxygenase pathway, since stimulation of monocytes from patients and normal donors with the calcium ionophore A23187 induced similar amounts of LTC4 and LTB4 release (LTC4, 3.0 +/- 1.7 versus 3.0 +/- 1.0 ng/10(6) cells; LTB4, 5.3 +/- 0.7 versus 5.2 +/- 0.5 ng/10(6) cells, respectively). In addition, aggregated IgG-induced LTC4 release by monocytes of both groups was similar, concomitant with an equivalent number of IgG-rosetting cells. Determination of cytophilically bound IgG and IgE by flow cytometry demonstrated that monocytes from atopic patients had more IgG bound than monocytes from normal donors. Similar amounts of IgE were detected on most monocytes from both groups, despite the higher serum IgE levels of patients. However, approximately 3% to 8% of monocytes from atopic but not normal donors stained brightly for IgE, suggesting that relatively large amounts of cytophilic IgE were bound to a small percentage of the patients' monocytes. Challenge of monocytes with anti-IgE or anti-IgG induced release of similar amounts of LTC4 for both groups, despite the presence of more cytophilic IgG on monocytes from atopic donors. These data indicate that monocytes from patients with AD release LTC4 and LTB4 in response to challenge with aggregated IgE or anti-IgE, as well as aggregated IgG, IgA, and anti-IgG. However, under our in vitro conditions, stimulation of patients' monocytes with aggregated IgA or IgE was not associated with increased mediator release, despite higher percentages of IgA- and IgE-rosetting cells compared to normal donors.
Antigens, Differentiation↗
The safety of inhaled beta-agonist bronchodilators during pregnancy.
To assess the safety of inhaled beta-agonist bronchodilators during pregnancy, perinatal outcomes in 259 prospectively managed women with asthma using these medications during pregnancy were compared to perinatal outcomes in 101 concurrently followed pregnant subjects with asthma not using inhaled bronchodilators and to perinatal outcomes in 295 concurrently followed pregnant control subjects without asthma. No significant differences between women with asthma using inhaled bronchodilators and subjects not receiving inhaled bronchodilators were found in the following parameters: perinatal mortality, congenital malformations, preterm births, low birth weight infants, mean birth weight, small for gestational age or low ponderal index infants, Apgar scores, labor/delivery complications, or postpartum bleeding. Increased incidences of maternal chronic and pregnancy-induced hypertension and transient tachypnea of the neonate were observed in the pregnancies of subjects with asthma using regular inhaled bronchodilators compared to control subjects, but a logistic regression analysis within the sample of subjects with asthma did not significantly associate the use of inhaled bronchodilators with these outcomes. In the light of the known substantial perinatal risks of severe, uncontrolled asthma and the relatively sparse evidence of human gestational safety for alternative asthma medications, these data support the use of inhaled beta-agonist bronchodilators as part of the management of asthma during pregnancy.
Administration, Inhalation↗
A multicenter evaluation of the clinical benefits of cromolyn sodium aerosol by metered-dose inhaler in the treatment of asthma.
The efficacy and safety of cromolyn sodium by metered-dose inhaler (MDI) (1 mg per actuation) was evaluated with a double-blind, placebo-controlled, parallel-study design. Subjects with asthma, aged 8 to 58 years, whose asthma was well controlled taking cromolyn sodium capsules by Spinhaler turboinhaler, plus beta 2-agonists, entered the study after being maintained with cromolyn sodium capsules for a minimum of 4 weeks. The investigation began with a 2-week control interval with cromolyn sodium capsules followed by a 4-week single-blind period with placebo capsules. Subjects whose asthma significantly worsened while they were receiving placebo therapy were then randomized to a 10-week double-blind phase in which they received either active cromolyn sodium or placebo by MDI. Efficacy variables included diary data, physician evaluation, and spirometry. Comparisons were made between baseline period scores and each assessment variable over time. Of 155 subjects entered, 93 qualified for the double-blind, randomized phase. Eighty-three subjects completed the study and were analyzed. At baseline there existed no significant differences between the active-treatment and placebo-treatment groups. Significant differences (p less than 0.05) in favor of the cromolyn sodium-treatment group, however, were noted at all time points for daily diary symptoms (cough, breathlessness, and overall asthma severity), physician's assessments at each clinic visit, physician's and patient's overall final assessments, FEV1 at each clinic visit, and FVC and peak expiratory flow rate at the final visit. Concomitant bronchodilator medication use was less in the cromolyn sodium-treatment group. Cromolyn sodium by MDI is highly effective for (1) controlling asthmatic symptoms, (2) improving lung functions, and (3) decreasing the need for concomitant bronchodilators.
Administration, Inhalation↗
The course of asthma during pregnancy, post partum, and with successive pregnancies: a prospective analysis.
We studied 366 pregnancies in 330 prospectively managed women with asthma to determine the effect of pregnancy on asthma. Asthma activity was assessed by (1) daily symptom and medication diaries and (2) monthly auscultation and spirometry during pregnancy and for 3 months post partum. At 3 months post partum, subjects were asked to assess the overall course of their asthma during pregnancy compared to the usual course for them, and the course of their asthma during the 3 months post partum compared to the asthma during pregnancy. Asthma worsened during pregnancy in 35% of the women, improved in 28%, and was unchanged in 33%. Based on diary-card analysis, asthma was significantly less frequent and less severe during the last 4 weeks of pregnancy than during any other gestational interval. In women whose asthma improved during pregnancy, diary-card analysis revealed a gradual improvement with progressive pregnancy, whereas in women whose asthma worsened during pregnancy, there was an increase in asthma symptoms during 29 to 36 weeks gestation. During labor and delivery, asthma symptoms occurred in 10% of women with approximately equal proportions of these women receiving either no treatment or inhaled bronchodilators; only two subjects required intravenous aminophylline. During the 3 months post partum, asthma reverted toward its prepregnancy course in 73% of women. In 34 subjects prospectively studied for two successive pregnancies, there existed a significant concordance between the asthma course during the first and second pregnancies. The mechanistic and clinical implications of these findings are discussed.
Asthma↗
Challenges in the prevention of allergic disease in infancy.
The prevention of atopic disease, though admirable, remains a difficult endeavor. One must overcome inherent and natural forces constantly working to sensitize humans to produce IgE antibodies. These multiple risk factors for developing allergies (Table 1) act in concert to oppose preventive efforts. IgE mediated disorders potentially could be prevented by selectively interfering with the major genetic, cellular, and environmental factors that determine the ultimate phenotypic expression of atopy. Present efforts to prevent allergic disease remain relegated to manipulating the environment by reducing the allergenic load. Unfortunately, however, there has yet to exist a definitive, prospective study that conclusively documents and defines optimal or proven effective dietary and environmental regimens that prevent allergic disease. Until such studies emerge, physicians interested in prevention should be cognizant of the data derived from the limited published reports of dietary and environmental prevention efforts in order to appreciate current espoused recommendations. In addition to developing effective and proven prevention regimens, other issues deserving scrutiny include the following: 1) recognition of those groups (individuals) most at risk, amenable, and/or responsive to preventive efforts; 2) determination of the cost-effectiveness of such endeavors; and 3) identification of interfering variables, ie, noncompliance to recommendations.
Allergens↗
Effectiveness of dietary manipulation in the prevention of food allergy in infants.
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, infection, 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 scrutiny of the effectiveness and feasibility of allergy prevention during infancy.
Breast Feeding↗