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Background: Tracking longitudinal measurements of growth and decline in lung function in patients with persistent childhood asthma may reveal links between asthma and subsequent chronic airflow obstruction., Methods: We classified children with asthma according to four characteristic patterns of lung-function growth and decline on the basis of graphs showing forced expiratory volume in 1 second (FEV1), representing spirometric measurements performed from childhood into adulthood. Risk factors associated with abnormal patterns were also examined. To define normal values, we used FEV1 values from participants in the National Health and Nutrition Examination Survey who did not have asthma., Results: Of the 684 study participants, 170 (25%) had a normal pattern of lung-function growth without early decline, and 514 (75%) had abnormal patterns: 176 (26%) had reduced growth and an early decline, 160 (23%) had reduced growth only, and 178 (26%) had normal growth and an early decline. Lower baseline values for FEV1, smaller bronchodilator response, airway hyperresponsiveness at baseline, and male sex were associated with reduced growth (P<0.001 for all comparisons). At the last spirometric measurement (mean [±SD] age, 26.0±1.8 years), 73 participants (11%) met Global Initiative for Chronic Obstructive Lung Disease spirometric criteria for lung-function impairment that was consistent with chronic obstructive pulmonary disease (COPD); these participants were more likely to have a reduced pattern of growth than a normal pattern (18% vs. 3%, P<0.001)., Conclusions: Childhood impairment of lung function and male sex were the most significant predictors of abnormal longitudinal patterns of lung-function growth and decline. Children with persistent asthma and reduced growth of lung function are at increased risk for fixed airflow obstruction and possibly COPD in early adulthood. (Funded by the Parker B. Francis Foundation and others; ClinicalTrials.gov number, NCT00000575.).

Asthma is the most common chronic lower respiratory disease in childhood throughout the world. Several guidelines and/or consensus documents are available to support medical decisions on pediatric asthma. Although there is no doubt that the use of common systematic approaches for management can considerably improve outcomes, dissemination and implementation of these are still major challenges. Consequently, the International Collaboration in Asthma, Allergy and Immunology (iCAALL), recently formed by the EAACI, AAAAI, ACAAI, and WAO, has decided to propose an International Consensus on (ICON) Pediatric Asthma. The purpose of this document is to highlight the key messages that are common to many of the existing guidelines, while critically reviewing and commenting on any differences, thus providing a concise reference. The principles of pediatric asthma management are generally accepted. Overall, the treatment goal is disease control. To achieve this, patients and their parents should be educated to optimally manage the disease, in collaboration with healthcare professionals. Identification and avoidance of triggers is also of significant importance. Assessment and monitoring should be performed regularly to re-evaluate and fine-tune treatment. Pharmacotherapy is the cornerstone of treatment. The optimal use of medication can, in most cases, help patients control symptoms and reduce the risk for future morbidity. The management of exacerbations is a major consideration, independent of chronic treatment. There is a trend toward considering phenotype-specific treatment choices; however, this goal has not yet been achieved., (© 2012 John Wiley & Sons A/S.)

Background: While the ingestion of small amounts of an offending food can elicit adverse reactions in individuals with IgE-mediated food allergies, little information is known regarding these threshold doses for specific allergenic foods. While low-dose challenge trials have been conducted on an appreciable number of allergic individuals, a variety of different clinical protocols were used making the estimation of the threshold dose very difficult., Objective: A roundtable conference was convened to develop a consensus clinical protocol for low-dose challenge trials for the estimation of threshold doses for specific allergenic foods., Methods: In May 2002, 20 clinical allergists and other interested parties were invited to participate in a roundtable conference to develop consensus of the key elements of a clinical protocol for low-dose challenge trials., Results: A consensus protocol was developed. Patients with convincing histories of food allergies and supporting diagnostic evidence including past challenge trials or high CAP-RAST scores can be enrolled in low-dose challenge trials. Care must be taken with younger patients to assure that they have not outgrown their food allergy. An approach was developed for the medication status of patients entering such trials. Challenge materials must be standardized, for example, partially defatted peanut flour composed of equal amounts of the three major varieties of peanuts (Florunner, Virginia, Spanish). Challenge materials must be appropriately blinded with sensory evaluation used to confirm the adequacy of blinding. A double-blind, placebo-controlled design should be used for low-dose challenge trials. Low-dose challenge trials would begin at doses of 10 microg of the allergenic food and would continue with doses of 100 microg and 1 mg followed by specific higher doses up to 100 mg depending upon the expert judgement of the physician; even higher doses might be applied to assure that the patient is indeed reactive to the particular food. A 30-min time interval would be used between doses, and reactive doses would be expressed as both discrete and cumulative doses. The goal of each challenge would be to develop objective symptoms; trials should not be discontinued on the basis of subjective symptoms only. Statistically, a minimum of 29 patients would be enrolled in low-dose challenge trials for each allergenic food because 0 reactors out of 29 patients at a particular dose allow the conclusion that there is 95% certainty that 90% of allergic individuals will not react to that dose., Conclusion: A consensus protocol was developed. Using this protocol, it will be possible to estimate threshold doses for allergenic foods, the lowest amount that elicits mild, objective symptoms in highly sensitive individuals.

The purpose of this study was to evaluate mental and psychomotor development in infants of mothers whose asthma was actively managed during pregnancy and to compare the results with those froms infants of non-asthmatic mothers. Bayley Scales were assessed at age 15 +/- 3 months in 379 infants of asthmatic mothers and 376 control infants. Relationships were assessed between developmental indices and asthma severity, socioeconomic status, and infant prematurity. No significant differences in developmental indices were observed between infants of asthmatic mothers and control infants. No relationships were identified between developmental indices and maternal asthma severity. In the infants of both asthmatic and control mothers, a lower mean psychomotor developmental index was associated with birth weight < 2,500 g, and a lower mental developmental index with lower socioeconomic status. Hence, infants of asthmatic mothers whose asthma has been actively managed during pregnancy have developmental outcomes at 15 months of age that are similar to those of control infants.

Atopic disorders, which afflict millions of Americans and hundreds of millions worldwide, are at epidemic levels with concomitant increases in morbidity and mortality. Environmental and lifestyle changes over the past three to five decades are proposed causes for this pandemic and as such present major burdens to reverse. The scope of allergy practice bridges directly on this challenge. Allergy as a specialty is a major leader in developing effective strategies to confront this epidemic. Allergists have made major contributions to the understanding of the risk factors, immunology, pathophysiology, immunomodulation, and prevention of atopic and immunologic disorders. Allergist epidemiologists and clinicians have helped develop and implement national and international guidelines in the recognition, management, and prevention of asthma and rhinitis. Allergist clinical researchers are active in (1) outcomes research that demonstrates convincingly the value of allergy as a specialty in asthma, allergic rhinitis, anaphylaxis, drug and food allergy, and other atopic disorders, (2) National Institutes of Health clinical trials that will form the basis for the future treatment of asthma and allergic disease, and (3) pharmaceutical trials that evaluate new, effective, and safe medication to treat atopic disease. Allergist educators, comprising academic and practicing allergists, supported by allied health professionals, national associations, and affiliated lay organizations, provide comprehensive education to fellows, residents, colleague physicians, media, the public, and patients. Documentation of the value of allergists in improving patient-centered and societal outcomes in their core domain, allergy, is the appropriate final topic contribution in the important series "New millennium: The conquest of allergy."

The relationship between increased airway responsiveness and asthma severity in children is unclear. The Childhood Asthma Management Program (CAMP) with 1,041 children with mild to moderate asthma offers an opportunity to relate the concentration of methacholine that causes a 20% fall in FEV(1) (PC(20)) to level of lung function, occurrence of respiratory symptoms, duration of disease, and assessment of severity by clinical staff. Decreasing PC(20) was found to be associated with lower levels of lung function (prebronchodilator percent predicted FEV(1): r = 0.29, beta = 3.5, p < 0.001), the occurrence of chronic asthma symptoms, persistent wheezing (odds ratio [OR] = 1.66, p < 0.001), subjective clinical staff assessment of asthma severity (p < 0.001), and longer duration of asthma (r = -0.11, beta = -0.20, p < 0.002). These data provide evidence that the degree of airway responsiveness is linked to disease severity in children with mild to moderate asthma.

During the past several years, immunoassays for specific IgE antibodies have been refined to permit reporting results in mass units. Thus quantitative immunoassays for IgE antibodies may be an adjunct to skin tests. In cases of food allergy among children with atopic dermatitis, cutoff values for IgE antibody concentrations to egg, milk, peanut, and fish have been derived to provide 95% positive and 90% negative predictive values. Food-specific IgE antibody determinations can also be used to predict which food allergies are resolving spontaneously. Elevated egg-specific IgE antibody levels in infancy are associated with significantly increased risk for development of inhalant allergies later in childhood. In cases of inhalant allergy, specific IgE antibody levels correlate closely with results of inhalation challenge studies in cat-sensitive persons. Also, mite-specific IgE antibody levels correlate significantly with the mite allergen contents of reservoir dust in the homes of mite-sensitive persons. Immunoassays for quantitation of specific IgE antibodies may be used to document allergen sensitization over time and to evaluate the risk of reaction on allergen exposure. However, immunoassays and skin tests are not entirely interchangeable, and neither will replace the other in appropriate circumstances.

Food allergy occurs in approximately 4% to 6% of children, has increased in prevalence during the past decade, and thus represents a major burden to our young. The natural history of food allergy documents that allergies to cow's milk, egg, and soy frequently remit whereas allergies to peanut, nuts, and fish typically persist to adulthood, although exceptions exist. Food allergen avoidance subsequent to sensitization and manifestation of symptoms appears to hasten tolerance; however, the immunologic mechanism responsible for tolerance to one food group and not another is poorly understood. Identification and characterization of allergens and determination of B- and T-cell epitopes has provided an opportunity to better define these mechanisms. Identifying and developing effective strategies to prevent food and other allergic diseases represents a high priority for medicine at this time because of the unbridled increase in the prevalence and morbidity attributed to them. Immunologic engineering holds the greatest promise for allergy prevention in the not too distant future, but environmental strategies that promote food avoidance provide an avenue for prevention at present. Such efforts rely actively on reducing the food allergenic load and exposure of atopy-prone infants and children.

Objectives: To determine the prevalence of soy allergy in IgE-associated cow's milk allergy (CMA)., Study Design: Children <3.5 years with documented IgE-associated CMA (n = 93) were evaluated for soy allergy by double-blind, placebo-controlled food challenge, open challenge, or convincing previous history of an anaphylactic reaction to soy. Children tolerant to soy at entry received soy formula and were followed up for 1 year., Results: Of this IgE-associated CMA cohort (ages 3 to 41 months), 14% (95% CI = 7. 7%-22.7%) were determined to have soy allergy, 12 definitely at entry and 1 possibly after 1 year of soy ingestion. The latter child experienced severe failure to thrive at enrollment and exhibited improved growth while receiving soy during follow-up but was diagnosed with eosinophilic esophagitis at study completion. Improved growth (P <.05) occurred in the non-soy-allergic cohort ingesting soy formula (579 31 mL/d) during the year of follow-up., Conclusions: Soy allergy occurs in only a small minority of young children with IgE-associated CMA. As such, soy formula may provide a safe and growth-promoting alternative for the majority of children with IgE-associated CMA shown to be soy tolerant at the time of introduction of soy formula.

Background: Many factors, including heredity, atopic status, and environment, have been implicated in the determination of asthma severity. Relatively little is known about the degree to which asthma duration influences asthma severity., Objective: The Childhood Asthma Management Program (CAMP), consisting of 1041 children (age 8. 9 +/- 2.1 years at enrollment) with mild-to-moderate asthma, offers an opportunity to examine the relationship between asthma duration and asthma severity., Methods: By using the extensive CAMP baseline cross-sectional data on asthma duration, spirometry, bronchial responsiveness, symptomatology, and markers of atopy, univariate and multivariate regression models were used to evaluate whether asthma duration is associated with asthma severity., Results: Duration of asthma in the study cohort from time of diagnosis until randomization into CAMP ranged from 0.3 to 12.1 years (mean, 5.0; SD, 2.7; median, 4.8). Asthma duration is associated in univariate analyses both with lower levels of several lung functions (P <.001), including methacholine bronchial reactivity (natural log [ln] FEV1 PC20, mg/mL; r = -0.112), prebronchodilator and postbronchodilator percent predicted FEV1 (r = -0.176 and r = -0.130, respectively), and prebronchodilator and postbronchodilator FEV1 /forced vital capacity (FVC) (%) (r = -0.237 and r = -0.211, respectively), as well as higher levels of symptoms (symptom score: r = 0.147, P <. 001) and borderline greater use of albuterol for symptoms (r = 0.058, P =.064) during a 28-day screening period before randomization. Simple linear regression detected the following differences in lung functions per year of asthma duration: ln FEV1 PC20, -0.050 mg/mL/y; prebronchodilator FEV1, -0.907 percent predicted/y; and prebronchodilator FEV1 /FVC, -0.729 percent predicted/y. After controlling for potential explanatory variables (atopy, inflammatory markers, household Der p 1 levels, anti-inflammatory medication use, and clinical center), regression models revealed that the duration of asthma remained significantly and independently associated with ln FEV1 PC20 (P =.004), prebronchodilator percent predicted FEV1 (P =.043), and prebronchodilator and postbronchodilator FEV1 /FVC (%) (P <.001), as well as being positively associated with mean daily symptom score (P <.001) and albuterol use for symptoms (P =.003) during a 28-day screening period. Duration was also found to be significantly associated with physician/nurse assessment of asthma severity and other historical measures of medication use., Conclusions: These data demonstrate that asthma duration is associated with lower lung function, greater methacholine responsiveness, more asthma symptomatology, and greater use of as-needed albuterol, which are all measures of asthma severity. As such, early diagnosis and intervention may be necessary to ameliorate these adverse effects of persistent asthma.

Objectives: Specific recommendations for administering the influenza vaccine to patients with egg allergy are based on limited scientific data. The objectives of this investigation were to determine the safety of a 2-dose administration of an influenza vaccine to patients with egg allergy and to evaluate the usefulness of skin testing with the influenza vaccine before administration., Study Design: In this multicenter clinical trial, clinical histories of egg allergy were confirmed by skin testing with egg and, if possible, by oral challenges with egg. Subjects with egg allergy received the vaccine in 2 doses, 30 minutes apart; the first dose was one tenth and the second dose nine tenths of the recommended dose as determined by age. Subjects without egg allergy were recruited as control subjects and received 1 age-determined dose of the vaccine. Skin prick tests with the influenza vaccine were performed on all subjects., Results: From 1994 to 1997, 83 subjects with egg allergy and 124 control subjects were evaluated. The content of ovalbumin/ovomucoid was 0.1, 1.2, and 0.02 micrograms/mL, respectively in the 1994-95, 1995-96, and 1996-97 influenza vaccines. Results of vaccine skin prick tests were positive in 4 subjects with egg allergy and in 1 control subject. All patients with egg allergy tolerated the vaccination protocol without any significant allergic reactions., Conclusions: These results demonstrate that patients with egg allergy, even those with significant allergic reactions after egg ingestion, can safely receive an influenza vaccine in a 2-dose protocol when the vaccine preparation contains no more than 1.2 micrograms/mL egg protein.

Experimental research in humans and animals points to the importance of adverse respiratory effects from short-term particle exposures and to the importance of proinflammatory effects of air pollutants, particularly O(subscript)3. However, particle averaging time has not been subjected to direct scientific evaluation, and there is a lack of epidemiological research examining both this issue and whether modification of air pollutant effects occurs with differences in asthma severity and anti-inflammatory medication use. The present study examined the relationship of adverse asthma symptoms (bothersome or interfered with daily activities or sleep) to O(3) and particles (less than or equal to)10 micrometer (PM10) in a Southern California community in the air inversion zone (1200-2100 ft) with high O(3) and low PM (R = 0.3). A panel of 25 asthmatics 9-17 years of age were followed daily, August through October 1995 (n = 1,759 person-days excluding one subject without symptoms). Exposures included stationary outdoor hourly PM10 (highest 24-hr mean, 54 microgram/m(3), versus median of 1-hr maximums, 56 microgram/m(3) and O(3) (mean of 1-hr maximums, 90 ppb, 5 days (greater than or equal to)120 ppb). Longitudinal regression analyses utilized the generalized estimating equations (GEE) model controlling for autocorrelation, day of week, outdoor fungi, and weather. Asthma symptoms were significantly associated with both outdoor O(3) and PM(10) in single pollutant- and co-regressions, with 1-hr and 8-hr maximum PM(10) having larger effects than the 24-hr mean. Subgroup analyses showed effects of current day PM(10) maximums were strongest in 10 more frequently symptomatic (MS) children: the odds ratios (ORs) for adverse symptoms from 90th percentile increases were 2.24 [95% confidence interval (CI), 1.46-3.46] for 1-hr PM10 (47 microgram/m(3); 1.82 (CI, 1.18-2.81) for 8-hr PM10 (36 microgram/m(3); and 1.50 (CI, 0.80-2.80) for 24-hr PM10 (25 microgram/m(3). Subgroup analyses also showed the effect of current day O(subscript)3 was strongest in 14 less frequently symptomatic (LS) children: the ORs were 2.15 (CI, 1.04-4.44) for 1-hr O(3) (58 ppb) and 1.92 (CI, 0.97-3.80) for 8-hr O(3) (46 ppb). Effects of 24-hr PM10 were seen in both groups, particularly with 5-day moving averages (ORs were 1.95 for MS and 4. 03 for LS; p(less than or equal to)0.05). The largest effects were in 7 LS children not on anti-inflammatory medications [5-day, 8-hr PM10, 9.66 (CI, 2.80-33.21); current day, 1-hr O(3), 4.14 (CI, 1.71-11.85)]. Results suggest that examination of short-term particle excursions, medication use, and symptom severity in longitudinal studies of asthma yields sensitive measures of adverse respiratory effects of air pollution.

Background: Although no asthma or allergy medications can be considered proven safe for use during pregnancy, these medications are often used to prevent the potential direct and indirect consequences of uncontrolled asthma or allergy., Objective: The safety of asthma medications, antihistamines, and decongestants was assessed in a prospectively monitored cohort of 824 pregnant women with and 678 pregnant women without asthma., Methods: Medications used since conception were recorded on each subject's initial visit (< 28 weeks' gestation). Thereafter, diary cards for medications were completed by the patient through the time of delivery. Perinatal outcomes were compared in exposed versus unexposed individuals. A multivariate analysis accounted for the potential effects of age, parity, smoking, race, weight gain during pregnancy, maternal pulmonary function, acute asthmatic episodes, and multiple medication exposure., Results: No significant relationships were identified between major congenital malformations and first trimester or any exposure to beta-agonists, theophylline, cromolyn, corticosteroids, antihistamines, or decongestants. In the multivariate analyses, oral corticosteroids were independently associated with preeclampsia (odds ratio = 2.0, p = 0.027), but no other independent associations were observed between asthma or allergy medications and adverse perinatal outcomes., Conclusion: Use of most common asthma and allergy medications during pregnancy was not associated with increased perinatal risks. Maternal use of oral corticosteroids was independently associated with the occurrence of preeclampsia in this study, although the mechanism of this association is not clear. However, because prior observations suggest that severe asthma may be associated with maternal and/or fetal mortality, risk-benefit considerations still favor the use of oral corticosteroids when indicated for the treatment of asthma during pregnancy.

Rhinitis is extremely common during pregnancy, and asthma is one of the most common potentially serious medical problems to complicate pregnancy. Cutaneous allergy (urticaria/angioedema and eczema) also may occur during pregnancy. All of these entities may worsen with pregnancy in some patients and appear to improve in others. Uncontrolled asthma may directly threaten the fetus, and morbidity from the other illnesses may indirectly affect pregnancy through an effect on eating, sleeping, or emotional well-being. Appropriate diagnosis, avoiding triggering factors when possible; appropriate use of pharmacotherapy; and, when indicated, allergen immunotherapy usually allow these chronic conditions to be controlled during pregnancy so as to optimize both the health of the mother and that of her baby.

The relationship between day-to-day changes in asthma severity and combined exposures to community air pollutants and aeroallergens remains to be clearly defined. We examined the effects of outdoor air pollutants, fungi, and pollen on asthma. Twenty-two asthmatics ages 9-46 years were followed for 8 weeks (9 May-3 July 1994) in a semirural Southern California community around the air inversion base elevation (1,200 ft). Daily diary responses included asthma symptom severity (6 levels), morning and evening peak expiratory flow rates (PEFR), and as-needed beta-agonist inhaler use. Exposures included 24-hr outdoor concentrations of fungi, pollen, and particulate matter with a diameter < 10 microns (PM10; maximum = 51 micrograms/m3) and 12-hour day-time personal ozone (O3) measurements (90th percentile = 38 ppb). Random effects longitudinal regression models controlled for autocorrelation and weather. Higher temperatures were strongly protective, probably due to air conditioning use and diminished indoor allergens during hot, dry periods. Controlling for weather, total fungal spore concentrations were associated with all outcomes: per minimum to 90th percentile increase of nearly 4,000 spores/m3, asthma symptom scores increased 0.36 (95% CI, 0.16-0.56), inhaler use increased 0.33 puffs (95% CI, -0.02-0.69), and evening PEFR decreased 12.1 l/min (95% CI, -1.8-22.3). These associations were greatly enhanced by examining certain fungal types (e.g., Alternaria, basidiospores, and hyphal fragments) and stratifying on 16 asthmatics allergic to tested deuteromycete fungi. There were no significant associations to low levels of pollen or O3, but inhaler use was associated with PM10 (0.15 inhaler puffs/10 micrograms/m3; p < 0.02). These findings suggest that exposure to fungal spores can adversely effect the daily respiratory status of some asthmatics.

Epidemiologic investigations of ambient ozone (O3) effects on daily asthma status have not used personal O3 exposures and have often lacked well-characterized allergen exposures. To address this, we studied 12 asthmatic subjects aged 9 to 16 yr, who recorded daily asthma symptoms (functional levels 0 to 5) and as-needed inhaler use during September and October 1993 in San Diego, California, Outdoor aeroallergens, O3, and fine particle concentrations were measured at a central outdoor site, and personal 12-h daytime exposures to O3 were measured daily. Personal O3 differed greatly between subjects and was 27% of mean outdoor O3. In random-effects autoregression models controlling for weekend days and fungal spores, personal O3 was associated with asthma severity: for a 90th percentile increase in O3 (25 ppb), symptom scores increased by 25% (95% CI: 0 to 49%) and inhaler use increased by 26% (95% CI: 3 to 48%) over their averages. Outdoor 12-h O3, but not 1-h maximum O3, was associated with inhaler use (p < 0.03). Fungal spores were significantly associated with symptoms (scores increased by 0.1 to 0.3/1,000 spores/m3) and inhaler use (0.1 to 0.4 puffs/1,000 spores/m3) across speciated groups. Pollen and fine particles (low levels) were not associated with any outcomes. These findings illustrate that the epidemiologic importance of O3 and allergenic cofactors can be underestimated by failure to account for personal O3 and fungal exposures.

Background: The natural history of allergic disease and its potential for prevention merit close examination because of the explosive worldwide increase in the prevalence and morbidity of atopic disorders. This study examines the development of atopy at age 7 years in 165 children in a high-risk cohort, previously reported from birth to age 4 years., Methods: In this prospective, randomized, controlled study of food allergen avoidance in infancy, the prophylactic-treated group consisted of infants whose mothers avoided cow's milk, egg, and peanut during the last trimester of pregnancy and lactation and who, themselves, avoided cow's milk until age 1 year (casein hydrolysate supplementation before age 1), egg until age 2 years, and peanut and fish until age 3 years. The control group consisted of maternal/infant pairs who followed standard feeding practices., Results: Despite a significant reduction in food allergy and milk sensitization before age 2 years, none of the following differed between the groups at age 7 years: food allergy, atopic dermatitis, allergic rhinitis, asthma, any atopic disease, lung function, food or aeroallergen sensitization, serum IgE level, or presence of nasal eosinophils or nasal basophilic cells. Children with food allergy by 4 years evidenced higher 7-year (current) prevalences of allergic rhinitis and asthma (p < 0.01). Atopic diseases/parameters at age 7 years were shown, by multivariate analysis (p < 0.05), to be associated with several genetic and environmental risk factors (male gender, maternal nonwhite ethnicity and asthma, and household smoking), as well as predictive atopic markers during infancy (elevated serum IgE level; egg, cow's milk, and peanut sensitization; and nasal eosinophils and nasal basophilic cells)., Conclusions: These findings help to: (1) elucidate the natural history of atopic disease in high-risk children; (2) document the progression of allergy from atopic dermatitis, food allergy, and food sensitization to respiratory allergy and aeroallergen sensitization despite food allergy prevention in infancy; (3) identify allergy predictive markers; and (4) expand our appreciation of the interactions of genetic and environmental factors in the development of atopy.

Prior studies have found an increased incidence of adverse perinatal outcomes of pregnancies in asthmatic mothers, but these studies have been poorly controlled for asthma therapy and other confounding factors. The purpose of this study was to assess perinatal outcomes in actively managed pregnant asthmatic women as compared with matched nonasthmatic controls. Using an inception cohort design, we studied a volunteer sample of 486 pregnant (< 28 wk) women with documented asthma and 486 pregnant nonasthmatic controls with normal pulmonary function. Cases and controls were matched for age, smoking status, parity, and year of delivery. Asthma was managed with step therapy to prevent acute asthmatic episodes and asthma symptoms that interfered with sleep or normal activity. Chronic hypertension was significantly more common (p = 0.007) in asthmatic subjects (3.7%) than in matched controls (1.0%). However, no significant differences in incidences of preeclampsia, perinatal mortality, preterm births, low-birth-weight infants, intrauterine growth retardation, or congenital malformations were observed in the pregnancies of the asthmatic women as compared with the matched controls. Trends were observed toward relationships between more severe asthma requiring emergency therapy or corticosteroids and increased incidences of preeclampsia and low-birth-weight infants, but these associations were not statistically significant. These data suggest that the overall perinatal prognosis for women with actively managed asthma during pregnancy is comparable to that for the nonasthmatic population.

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.

This study sought to identify clinical and laboratory characteristics associated with the development of osteoporosis in 44 corticosteroid (CS)-treated asthmatic patients. Percentage predicted bone density was inversely correlated with both the duration of CS therapy (r = -.39, p = 0.009) and 24-hour urine calcium excretion (chi 2 = 5.2, p = 0.022). Bone density was not related to prednisone equivalent dose, alternate day versus daily therapy or serum cortisol levels. These data suggest that (1) long duration of CS therapy and increased urine calcium may identify patients at increased risk of developing CS-induced osteoporosis, and (2) urinary loss of calcium may be of particular importance in the pathogenesis of this condition.

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.

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.

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.

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.

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.

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.

The ability of human peripheral blood mononuclear cells to synthesize IgE in vitro in response to pokeweed mitogen (PWM) is controversial. To determine whether the conflicting results obtained by different laboratories could be due to inherent qualitative differences in the anti-IgE antibodies used to measure low concentrations of IgE in culture supernatants, we compared the specificities of anti-IgE reagents prepared by various methods. Immunoadsorbent-purified antibodies were isolated from a goat antiserum to the lambda, IgE myeloma protein PS and a rabbit antiserum to the kappa, IgE protein Bed in three ways: 1) antibodies to IgE PS (anti-PS) were isolated from the goat antiserum by affinity chromatography with PS coupled to Sepharose 4B; these antibodies consisted of anti-epsilon chain-specific and anti-idiotypic antibodies to protein PS; 2) antibodies specific for the epsilon-chain (anti-epsilon) were purified by affinity chromatography with IgE myeloma proteins that were not used for immunization; and 3) antibodies to idiotypic determinants of proteins PS (anti-id PS) and Bed (anti-id Bed) were isolated on affinity columns with the respective myeloma proteins after absorption of the epsilon-chain-specific antibodies. These three types of antibodies were then used in a solid phase radioimmunosorbent test to quantitate the amount of "IgE" synthesized by peripheral blood mononuclear cells from nonatopic and atopic donors cultured for 7 days in the presence and absence of PWM. ANTI-PS antibodies detected a PWM-induced "IgE formation" in cell culture supernatants of both non-atopic and atopic donors. (ABSTRACT TRUNCATED AT 250 WORDS)

Peripheral blood T lymphocytes from nonatopic control donors, asymptomatic atopic donors, and patients with moderate to severe atopic dermatitis were analyzed for Fc receptors for IgE (T epsilon cells) and IgG (T gamma cells) by rosette assays and were characterized with monoclonal antibodies. The T cells were reacted first with monoclonal antibodies, followed by fluoresceinated F(ab')2 goat antimouse Ig; they were then rosetted, and subsequently the rosetting cells were examined for immunofluorescence. Seven nonatopic control donors had less than 0.1% T epsilon cells and a mean +/- SD of 10.5% +/- 4.1 T gamma cells. Seven asymptomatic atopic donors with low IgE levels (2 to 233 IU/ml) varied from less than 0.1 to 1.3% T epsilon cells and 7.2% +/- 3.7 T gamma cells. Six of seven patients with moderate to severe atopic dermatitis and IgE levels of 1339 to 24,261 IU/ml had less than 0.1% T epsilon cells and significantly fewer T gamma cells (3.1% +/- 2.7, p less than 0.01) than the nonatopic control donors and the atopic donors in remission. Both T epsilon and T gamma cells reacted with the pan-T cell antibody Lyt-3 (anti-sheep red cell receptor) but not with antibodies OKT3, OKT4, or OKT6. Subpopulations of both T epsilon and T gamma cells reacted with antibodies OKT8 and the antimonocyte antibody OKM1. The OKM1+ cells did not appear to be monocytes, however, because the T cells did not react with another antimonocyte antibody, BRL.2, and were negative for nonspecific esterase activity. (ABSTRACT TRUNCATED AT 250 WORDS)

The role of particle-bound complement proteins in the induction of noncytotoxic enzyme release from human granulocytes was investigated with the use of sera genetically deficient in complement and highly purified complement components. Release of histaminase, one of two important histamine catabolizing enzymes, and beta-glucuronidase from polymorphonuclear leukocytes was solely dependent on particle-bound C3b (the larger cleavage product of the third component of complement) when fluid-phase complement was excluded. The extent of enzyme release was a function of particle-bound C3b input, was reduced by exposing the particles to C3b inactivator, and was blocked by fluid-phase C3b. Phagocytosis of the C3b-coated particles was not required for enzyme release from neutrophils. In contrast, phagocytosis of "opsonized" particles was required for noncytotoxic release of histaminase and arylsulfatase from eosinophils; other proteins, as well as C3b, were able to opsonize particles for induction of enzyme release from eosinophils. These studies suggest a dual role for complement (particularly C3) in modulating vascular permeability phenomena, i.e., release of vasoactive mediators by the action of C3a and C5a, and release of the corresponding enzymes that inactivate the mediators by C3b.

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.

Thin-layer radiochromatographic methods for the measurement of histaminase and histidine decarboxylase activities have been developed. The assays are specific for the respective enzymes, are sensitive and reproducible, and can be performed using commercially available substrates. The histaminase assay permits determination of enzyme activity from 2.5 mul of pregnancy sera, 1-2 X 10(6) human granulocytes, and microgram quantities of partially purified human placenta histaminase with an error of less than 5 per cent. The histidine decarboxylase assay permits measurement of nanogram quantities of newly formed histamine from as few as 2 X 10(4) rat peritoneal mast cells or rat basophilic leukemia cells with an error of less than 5 per cent.

In order to determine the types of respiratory responses observed during aspirin-induced reactions, 50 consecutive asthmatic patients with a history of aspirin sensitivity underwent prospective oral aspirin challenges between 1979 and 1981. Oral aspirin challenges produced 36 asthmatic responses (33 combined with rhinitis and three purely asthmatic) and six acute rhinoconjunctivitis responses (three combined with mild asthma and three purely rhinoconjunctivitis) but failed to stimulate any reaction in eight patients. The results produced by these challenges were then compared with results recorded during additional aspirin challenges in 28 of these patients, performed after the index challenge in 1979-1981 in 26 patients and in the case of two patients before 1979. The type of respiratory response to aspirin varied significantly in 11 (39%) of the 28 patients and included disappearance of aspirin reactivity in four patients.

Peripheral blood monocytes, defined as latex bead-ingesting mononuclear cells, from 15 healthy nonallergic donors and 22 patients with allergic disorders were analyzed for Fc receptors for IgE (Fc epsilon) by a rosette assay employing ox erythrocytes coated with IgE. The patients were divided into 3 groups. Group I: 12 patients with mild to moderate atopic disease and serum IgE levels up to 2300 IU/ml. Group II: 6 patients with severe generalized atopic dermatitis, allergic rhinitis, and asthma, of which 5 had IgE serum levels of 8000 to 77,500 IU/ml. Group III: 4 severely atopic patients with IgE levels greater than 10,000 IU/ml and receiving oral corticosteroids. The numbers of monocytes were similar in healthy donors and patients. In contrast, severely atopic patients (Group II) had significantly more (p less than 0.01) Fc epsilon + monocytes (107 +/- 42/mm3) than healthy donors (20 +/- 14/mm3) or patients of Group I (31 +/- 14/mm3). Patients of Group III had significantly fewer (p less than 0.05) Fc epsilon + monocytes (12 +/- 16/mm3) than controls and patients of Groups I and II. We conclude that patients with severe allergic disorders have a significant increase of peripheral blood monocytes with Fc receptors for IgE, which suggests that these cells may participate in the pathophysiology of atopic disease.

A delayed cutaneous response to cold, characterized by areas of erythematous, edematous deep swelling at 9 to 18 hr after experimental ice challenge, was recognized in a 10-yr-old boy and several members of his family. Biopsy of the cold-induced lesion showed edema and an infiltrate of mononuclear cells; mast cells were normal, and immunoglobulins, complement factors, and fibrin were not detected by immunofluorescence techniques. Local cold challenge did not release histamine or induce alterations in the complement system or the enzymes, histaminase, and histamine methyl transferase. The delayed cutaneous response to cold could not be passively transferred with serum or tissue extracts to monkey skin. Family studies suggested an autosomal-dominant mode of inheritance.

Sixteen severe, corticosteroid-dependent yet resistant outpatient asthmatics were treated with troleandomycin (TAO), a macrolide antibiotic, in an attempt to both induce a clinical remission and reduce methylprednisolone requirements. Within the first 2 wk of initiating TAO therapy, 50% of the patients experienced a greater than 20% increase in forced expiratory volume in 1 sec (FEV1) and 80% noted a greater than 20% increase in forced vital capacity between 25% and 75% (FVC 25%-75%). Maximal increases in FEV1 and FVC 25%-75% were noted in all patients within the first 6 wk on TAO and methylprednisolone. There was a concomitant clinical improvement in all patients. Corticosteroid-induced side effects, gastrointestinal tract discomfort, and elevated serum glutamic pyruvic transaminase (SGPT) were common yet generally transient during TAO and methylprednisolone therapy. After a 4- to 18-mo follow-up 15/16 patients were well-controlled on TAO and methylprednisolone. Methylprednisolone requirements were reduced at least four- to fivefold in most patients during TAO therapy. Normal morning serum cortisol levels were documented after varying intervals in most patients when both TAO (250 mg) and methylprednisolone (4 to 16 mg) could be reduced to alternate-day administration. Only one patient was forced to discontinue therapy due to side effects. The present study extends the effectiveness of TAO therapy to ambulatory asthmatics, establishes a clinical strategy that maximizes benefit/risk factors, and provides practical guidelines for the long-term use of TAO and methylprednisolone.

Nineteen aspirin sensitive adult patients were identified who experienced naso-ocular responses without associated bronchospasm during standardized oral aspirin challenge. These 19 patients exhibited the characteristics of the aspirin triad except asthma. These included hypertrophic rhinitis with or without associated nasal polyps, abnormal sinus roentgenograms, nasal eosinophilia, aspirin-provoked responses of the upper airway identical to those observed in aspirin-sensitive asthmatics, capacity of the upper airway to be desensitized to aspirin, and cross-reactivity and/or cross-desensitization of the upper airway to indomethacin. Of the 17 patients who were treated with daily aspirin after desensitization, 77% experienced improvement in their nasal symptoms.

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.