Peanut oral immunotherapy in a pediatric allergy clinic: Patient factors associated with clinical outcomes.

BACKGROUND: Additional information is needed to inform optimal patient selection, expected outcomes, and treatment end points for clinical peanut oral immunotherapy (OIT). OBJECTIVE: To provide insight into the optimal patient selection, expected outcomes, and treatment end points for clinical peanut oral immunotherapy by analyzing a real-world peanut OIT cohort. METHODS: Records were reviewed for 174 children undergoing peanut OIT at a pediatric allergy clinic. Patient age, peanut skin prick test results, and peanut-specific immunoglobulin E (sIgE) results, with inclusion of additional foods in OIT, were analyzed for correlations with OIT outcomes. RESULTS: To date, 144 patients have achieved maintenance dosing, 50 of whom transitioned to ad lib twice-weekly peanut ingestion. A total of 30 discontinued OIT. In addition, 47 patients who underwent multifood OIT had no significant difference in reactions (FDR-adjusted P = .48) or time-to-reach maintenance (FDR-adjusted P = .48) compared with those on peanut OIT alone. Age at initiation inversely correlated with achievement of maintenance: 92% of patients 0.5 to less than 5 years, 81% of those 5 to less than 11 years, and 70% of those 11 to less than 18 years reached and continued maintenance (P = .01). Baseline peanut-sIgE level positively correlated with number of reactions during updosing (P < .001) and maintenance (P = .005), though it was not significantly different in patients achieving successful maintenance vs those who discontinued OIT (P = .09). Furthermore, 66% of patients experienced greater than or equal to 1 adverse reaction during OIT. Of those on ad lib peanut ingestion, 2 reported mild reactions after lapses in peanut consumption. CONCLUSION: Clinical peanut OIT has similar outcomes to research protocols. OIT can be successful in older children and those with high peanut-sIgE levels, though these factors affect outcomes. Clinical and laboratory criteria can guide successful transition to intermittent ad lib peanut consumption.

Oral immunotherapy for multiple foods in a pediatric allergy clinic setting.

BACKGROUND: The increasing incidence of pediatric food allergy results in significant health care burden and family stress. Oral immunotherapy (OIT) can induce tolerance to peanut, milk, and egg. OIT for other foods, particularly multiple foods simultaneously, has not been thoroughly studied. OBJECTIVE: To summarize our experience with OIT for multiple foods in a pediatric allergy clinic setting. METHODS: Medical records were reviewed for patients undergoing OIT for multiple foods. Methods and outcomes of OIT were summarized. Outcomes were analyzed for correlation with baseline food allergen skin prick tests (SPTs) and specific IgE (sIgE) test results. RESULTS: Forty-five patients aged 1.5 to 18 years undertook OIT for up to 12 foods, including peanut, tree nuts, seeds, legumes, and egg. At the time of review, 35 patients were receiving daily maintenance dosing, 4 had completed OIT and were continuing to eat their foods 3 times weekly, and 6 had stopped OIT because of anxiety, inconvenience, or allergy symptoms. A total of 49% of patients had reactions during the up-dosing process, mostly oral itching (33%), perioral hives (40%), and abdominal pain (35%). There was no correlation of baseline skin prick test (SPT) and sIgE test results with reaction threshold for baseline food challenge, lowest dose causing reactions during up-dosing, or time to reach maintenance. Higher baseline sIgE level but not baseline SPT result was associated with an increased number of allergic reactions during OIT. Baseline SPT correlated with stopping OIT. CONCLUSION: A similar approach to that used for peanut OIT can be taken for nonpeanut foods and for multiple foods simultaneously. High baseline allergy test results are not a contraindication to OIT.

Allergen sensitization profiles in a population-based cohort of children hospitalized for asthma.

RATIONALE: Allergen sensitization is associated with asthma morbidity. A better understanding of allergen sensitization patterns among children hospitalized for asthma could help clinicians tailor care more effectively. To our knowledge, however, sensitization profiles among children hospitalized for asthma are unknown. OBJECTIVES: We sought to describe allergen sensitization profiles and the distribution of self-reported in-home exposures among children hospitalized for asthma. We also sought to assess how sensitization profiles varied by sociodemographic and clinical factors. METHODS: This population-based cohort study includes data for 478 children, aged 4-16 years, hospitalized for an asthma exacerbation. Predictors included child age, race, sex, insurance status, reported income, salivary cotinine, exposure to traffic-related air pollution, asthma and atopic history, and season of admission. Outcomes included serum IgE specific to Alternaria alternata/A. tenuis, Aspergillus fumigatus, American cockroach, mouse epithelium, dust mite (Dermatophagoides pteronyssinus and farinae), cat dander, and dog dander (deemed sensitive if IgE ≥ 0.35). Self-reported adverse exposures included mold/mildew, water leaks, cockroaches, rodents, and cracks or holes in the walls or ceiling. Presence of carpeting and furry pets was also assessed. MEASUREMENTS AND MAIN RESULTS: More than 50% of included patients were sensitized to each of Alternaria, Aspergillus, dust mite, cat dander, and dog dander; 28% were sensitized to cockroach and 18% to mouse. Roughly 68% were sensitized to three or more allergens with evidence of clustering. African American children, compared with white children, were more likely to be sensitized to Alternaria, Aspergillus, cockroach, and dust mite (all P<0.01). White children were more likely to be sensitized to mouse, cat, and dog (all P<0.01). Lower income was associated with cockroach sensitization whereas higher income was associated with dog and cat sensitization (all P<0.01). Atopic history was associated with sensitization to three or more allergens (P<0.01). Although 42% reported exposure to at least one adverse in-home exposure (and 72% to carpet, 51% to furry pets), only weak relationships were seen between reported exposures and sensitizations. CONCLUSIONS: Most children admitted to the hospital for asthma exacerbations are sensitized to multiple indoor allergens. Atopy on the inpatient unit serves as a potential target for improvement in chronic asthma management.

New developments in the treatment of pediatric allergic rhinitis and conjunctivitis.

The primary care physician is the first line of treatment for allergic rhinitis, which affects approximately one-fourth of children in the United States. There is an increasing trend toward self-management by patients or parents due to high-deductible insurance plans and the over-the-counter availability of allergy medications. The primary care physician can offer guidance on appropriate selection of medications and potential adverse effects. Vitamin D deficiency has been proposed as a potential contributing factor in patients with allergic diseases, and studies are underway to determine whether supplementation with vitamin D is helpful for these conditions. Sublingual immunotherapy has recently received US Food and Drug Administration approval for grass and ragweed allergens; many children will be interested in this alternative to allergy shots. The relative advantages and disadvantages of sublingual vs subcutaneous immunotherapy are discussed.

Myxomycete (slime mold) spores: unrecognized aeroallergens?

BACKGROUND: Myxomycete spores are present in the outdoor air but have not been studied for allergenicity. OBJECTIVE: To determine whether patients with seasonal allergic rhinitis (SAR) symptoms are sensitized to myxomycete spores. METHODS: Myxomycete specimens were collected in the field. Nine species of myxomycetes were collected and identified: Arcyria cinerea, Ceratiomyxa fruticulosa, Fuligo septica, Hemitrichia clavata, Lycogala epidendrum, Metatrichia vesparium, Stemonitis nigrescens, Tubifera ferruginosa, and Trichea favoginea. Allergen extracts were made for each species. Protein content of each extract was measured by bicinchoninic acid assay. Protein electrophoresis was performed. Subjects with a history of SAR symptoms were enrolled, and allergy skin prick testing was performed with each extract. RESULTS: Protein content of the extracts ranged from 1.05 to 5.8 mg/mL. Protein bands were seen at 10 to 250 kD. Allergy prick testing was performed in 69 subjects; 42% of subjects had positive prick test results for at least 1 myxomycete extract, with 9% to 22% reacting to each extract. Five of the 12 subjects who tested negative for all allergens on the standard aeroallergen panel had positive prick test results for myxomycetes. CONCLUSION: Forty-two percent of subjects with SAR were sensitized to myxomycete spores. A significant subset of subjects who had SAR symptoms and otherwise negative skin test results showed sensitization to myxomycetes. These spores are present in the outdoor air during the summer and autumn and might be significant aeroallergens.

Environmental exposures, nitric oxide synthase genes, and exhaled nitric oxide in asthmatic children.

Exhaled nitric oxide (FeNO), a measure of airway inflammation, is being explored as a tool to guide asthma management in children. Investigators have identified associations of genetic polymorphisms in nitric oxide synthase genes (NOS1 and NOS3) with FeNO levels; however, none have explored whether these polymorphisms modify the relationship of environmental exposures with FeNO. The objective of this project was to evaluate the association of NOS polymorphisms and environmental exposures with FeNO levels among children with asthma. We conducted a 12-month prospective cohort study of 225 tobacco-smoke exposed children (6-12 years) with doctor-diagnosed asthma. We assessed environmental exposures (tobacco, indoor allergens, & airborne particulates), polymorphisms in NOS1 (an intronic AAT tandem repeat) and NOS3 (G894T), and FeNO levels. There was no association of NOS1 or NOS3 polymorphisms with FeNO levels. There were no significant interactions of environmental exposures and the NOS1 polymorphism with FeNO levels. In contrast, there was an interaction of the NOS3 polymorphism and airborne nicotine concentration with FeNO levels (P = 0.01). Among GG genotype individuals, nicotine exposure did not affect FeNO levels; however, among individuals with at least one T allele, higher nicotine exposure was associated with lower FeNO levels (approximately 5 ppb decrease from the lowest to the highest quartile). We conclude that genetic differences may explain some of the conflicting results in studies of the effects of tobacco smoke exposure on FeNO levels and may make FeNO interpretation difficult for a subset of children with asthma.

Seasonal variation and environmental predictors of exhaled nitric oxide in children with asthma.

The fraction of exhaled nitric oxide (FeNO), a measure of airway inflammation, shows promise as a noninvasive tool to guide asthma management, but there is a paucity of longitudinal data about seasonal variation and environmental predictors of FeNO in children. The objective of this project was to evaluate how environmental factors affect FeNO concentrations over a 12-month study period among children with doctor diagnosed asthma. We conducted a prospective cohort study of 225 tobacco-smoke exposed children age 6-12 years with doctor-diagnosed asthma including measures of FeNO, medication use, settled indoor allergens (dust mite, cat, dog, and cockroach), and tobacco smoke exposure. Baseline geometric mean FeNO was 12.4 ppb (range 1.9-60.9 ppb). In multivariable analyses, higher baseline FeNO levels, atopy, and fall season were associated with increased FeNO levels, measured 6 and 12 months after study initiation, whereas inhaled steroid use, summer season, and increasing nicotine exposure were associated with lower FeNO levels. In secondary analyses of allergen sensitization, only sensitization to dust mite and cat were associated with increased FeNO levels. Our data demonstrate that FeNO levels over a year long period reflected baseline FeNO levels, allergen sensitization, season, and inhaled steroid use in children with asthma. These results indicate that FeNO levels are responsive to common environmental triggers as well as therapy for asthma in children. Clinicians and researchers may need to consider an individual's baseline FeNO levels to manage children with asthma.

Relationship of outdoor air quality to pediatric asthma exacerbations.

BACKGROUND: Although exposure to outdoor air pollutants has been shown to be associated with exacerbations of asthma, there are relatively few admissions for asthma to Cincinnati Children's Hospital, Cincinnati, OH during the summer months when air quality tends to be worst. OBJECTIVE: The objective of this study was to determine the relationship of outdoor air quality parameters to asthma exacerbations in children. METHODS: The number of emergency room visits and hospitalizations for asthma were determined by review of emergency department logs and the hospital computer database. Outdoor air concentrations of ozone, particulates of < 10 microm diameter (PM-10), pollens, and fungal spores were obtained from the Hamilton County Department of Environmental Services. Multiple regression analysis was performed, looking for relationships between the daily number of asthma visits and the air quality data for the same day and for 1 through 5 days before the visits. RESULTS: A significant association was found between the number of asthma visits and the daily pollen count (P = 0.014, SE = 0.001). The effect was stronger for visits 1, 2, and 3 days after the pollen count (P < 0.001 for pollen count lagged 3 days). High PM-10 counts were synergistic with the pollen count as a predictor of asthma visits. There was no association between asthma visits and the ozone concentration or fungal spore count. CONCLUSIONS: Exacerbations of asthma severe enough to require visits to the hospital were associated with elevated concentrations of airborne pollens and particulates, with a significant delayed effect. Ozone, in the concentrations measured here, was not a risk factor for severe asthma exacerbations in children.