Environmental Interventions for Preventing Atopic Diseases.

PURPOSE OF REVIEW: In this review, we detail the exposome (consisting of environmental factors such as diet, microbial colonization, allergens, pollutants, and stressors), mechanistic and clinical research supporting its influence on atopic disease, and potentiation from climate change. We highlight contemporary environmental interventions and available evidence substantiating their roles in atopic disease prevention, from observational cohorts to randomized controlled trials, when available. RECENT FINDINGS: Early introduction to allergenic foods is an effective primary prevention strategy to reduce food allergy. Diverse dietary intake also appears to be a promising strategy for allergic disease prevention, but additional study is necessary. Air pollution and tobacco smoke are highly associated with allergic disease, among other medical comorbidities, paving the way for campaigns and legislation to reduce these exposures. There is no clear evidence that oral vitamin D supplementation, prebiotic or probiotic supplementation, daily emollient application, and antiviral prophylaxis are effective in preventing atopic disease, but these interventions require further study. While some environmental interventions have a well-defined role in the prevention of atopic disease, additional study of many remaining interventions is necessary to enhance our understanding of their role in disease prevention. Alignment of research findings from randomized controlled trials with public policy is essential to develop meaningful public health outcomes and prevent allergic disease on the population level.

The Role of IgA in the Manifestation and Prevention of Allergic Immune Responses.

PURPOSE OF REVIEW: Immunoglobulin A (IgA) mediates immune exclusion of antigens in the gut. Notably, IgA plays also a role in the prevention of IgE-mediated allergies and induction of immune tolerance. The present review addresses the role of IgA in the manifestation of IgE-mediated allergies, including allergen-specific immunotherapy (AIT), the regulation of IgA production, and the mechanism of IgA in immune cell activation. RECENT FINDINGS: The majority of studies report an association of IgA with the induction of immune tolerance in IgE-mediated allergies. However, reports on the involvement of humoral and mucosal IgA, IgA subtypes, monomeric and polymeric IgA, and the mechanism of IgA-mediated immune cell activation are confounding. Effects by IgA are likely mediated by alteration of microbiota, IgE-blocking capacity, or activation of inhibitory signaling pathways. However, the precise mechanism of IgA-regulation, the contribution of serum and/or mucosal IgA, and IgA1/2 subtypes, on the manifestation of IgE-mediated allergies, and the underlying immune modulatory mechanism are still elusive.

Mediterranean-Type Diets as a Protective Factor for Asthma and Atopy.

We are currently riding the second wave of the allergy epidemic, which is ongoing in affluent societies, but now also affecting developing countries. This increase in the prevalence of atopy/asthma in the Western world has coincided with a rapid improvement in living conditions and radical changes in lifestyle, suggesting that this upward trend in allergic manifestations may be associated with cultural and environmental factors. Diet is a prominent environmental exposure that has undergone major changes, with a substantial increase in the consumption of processed foods, all across the globe. On this basis, the potential effects of dietary habits on atopy and asthma have been researched rigorously, but even with a considerable body of evidence, clear associations are far from established. Many factors converge to obscure the potential relationship, including methodological, pathophysiological and cultural differences. To date, the most commonly researched, and highly promising, candidate for exerting a protective effect is the so-called Mediterranean diet (MedDi). This dietary pattern has been the subject of investigation since the mid twentieth century, and the evidence regarding its beneficial health effects is overwhelming, although data on a correlation between MedDi and the incidence and severity of asthma and atopy are inconclusive. As the prevalence of asthma appears to be lower in some Mediterranean populations, it can be speculated that the MedDi dietary pattern could indeed have a place in a preventive strategy for asthma/atopy. This is a review of the current evidence of the associations between the constituents of the MedDi and asthma/atopy, with emphasis on the pathophysiological links between MedDi and disease outcomes and the research pitfalls and methodological caveats which may hinder identification of causality. MedDi, as a dietary pattern, rather than short-term supplementation or excessive focus on single nutrient effects, may be a rational option for preventive intervention against atopy and asthma.

Atopy risk among school-aged children in relation to early exposures to a farm environment: A systematic review.

BACKGROUND AND OBJECTIVES: Childhood atopy is a complex condition with both a genetic and an environmental component. This systematic review will explore the current understanding of the importance of early life exposures to a farm in the development of atopy measured by objective markers of skin prick testing, and specific IgE measurements in school age children. METHODS: A systematic review was performed. RESULTS: Among 7285 references identified, 14 studies met the inclusion criteria (13 cross-sectional studies and 1 case-control study). The results were fairly consistent in that early farm-related exposures can protect children from becoming atopic at school age. In general, there was heterogeneity in the assessment of outcomes and exposures. CONCLUSIONS: Early-life farm exposures are associated with a protective effect on childhood atopy as assessed by objective markers. Future work should focus on understanding specific farm exposures that may important in these associations between atopy and farm exposures in children.

Fel d1 Blocking Antibodies: A Novel Method to Reduce IgE-Mediated Allergy to Cats.

Fel d1 is an important allergen produced by cats that causes IgE reactions in up to 95% of cat-allergic adults. Immunotherapy to reduce human allergy to cats has demonstrated that people have the capacity to produce allergen-specific neutralizing antibodies that block IgE-mediated allergic responses. We wished to determine if "blocking" antibodies could be used to reduce the IgE binding ability of cat allergens prior to their exposure to humans. Here, we describe the characterization of Fel d1-specific antibodies. We demonstrated the efficacy of a rabbit polyclonal and an allergen-specific chicken IgY to bind to Fel d1 in cat saliva and block Fel d1-IgE binding and IgE-mediated basophil degranulation. Fel d1 blocking antibodies offer a new and exciting approach to the neutralization of cat allergens.

Preventing Atopic Diseases During Childhood - Early Exposure Matters.

Atopic diseases in childhood are a major burden worldwide and there is still a lack of knowledge about treatable causes. In industrialized countries such as Germany, almost every second child is sensitized to at least one common allergen. Recent studies show that although the predisposition to allergies is inherited, the adaptive immune system of neonates and infants follows a developmental trajectory and whether an allergy actually occurs depends also on timing of allergen exposure including diet as well as environmental factors. New recommendations are far from being rigid of allergen avoidance; it is rather moving toward conditions that stand for more biodiversity. The observation that introduction of peanuts or eggs early in life significantly reduced the development of a later allergy will change our recommendations for the introduction of complementary foods. This is consistent with the hygiene hypothesis that early provocation shapes the developing immune system so that it reacts appropriately. Therefore, promoting the development of tolerance is at the heart of sensible allergy prevention - and this begins with the last trimester of pregnancy. In light of this concept, actual recommendations are discussed.

Sargassum horneri as a Functional Food Ameliorated IgE/BSA-Induced Mast Cell Activation and Passive Cutaneous Anaphylaxis in Mice.

Sargassum horneri (S. horneri), an edible brown alga, has been proposed as a functional food with an improvement effect on abnormal skin immune responses. The present study investigates the anti-allergic effect of an ethanol extract from S. horneri (SHE) on immunoglobulin E (IgE)/bovine serum albumin (BSA)-mediated activation in bone marrow-derived cultured-mast cells (BMCMCs) and passive cutaneous anaphylaxis (PCA) reaction in mice. SHE markedly and dose-dependently suppressed the degranulation of BMCMCs by reducing the ß-hexosaminidase and histamine release without cytotoxicity. In addition, SHE significantly decreased the FcεRI expression on the surface of BMCMCs and its IgE binding. Moreover, SHE reduced the mRNA expression and the production of allergic cytokines; interleukin (IL)-1ß, IL-4, IL-5, IL-6, IL-10, IL-13; interferon (IFN)-γ and/or tumor necrosis factor (TNF)-α; and a chemokine, thymus and activation-regulated chemokine (TARC), by suppressing the activation of Src-family kinases and nuclear factor (NF)-κB signaling. In further study, the application of SHE reduced the PCA reaction in an IgE/BSA-induced type I allergic mice model. Taken together, we suggest that SHE has an anti-allergic effect in type I allergic responses.

Do Human Milk Oligosaccharides Protect Against Infant Atopic Disorders and Food Allergy?

Atopic disorders (AD), often coexistent with food allergy (FA), start developing in early life and have lifelong health consequences. Breastfeeding is thought to be protective against AD and FA, but the data are controversial, and mechanisms are not well understood. Human milk oligosaccharides (HMOs) are complex carbohydrates that are abundant in human milk. These are thought to contribute to the development of the infant immune system by (i) promoting healthy microbiome, (ii) inhibiting pathogen binding to gut mucosa and (iii) modulating the immune system. Differences in microbiome composition between allergic and healthy infants have been observed, regardless of breastfeeding history. To date, limited studies have examined the preventive effects of HMOs on AD and FA in infants and current data relies on observation studies as trials of varying HMO intake through randomising individuals to breastfeeding are unethical. There is evidence for beneficial effects of breastfeeding on lowering the risks of FA, eczema and asthma but there are inconsistencies amongst studies in the duration of breastfeeding, diagnostic criteria for AD and the age at which the outcome was assessed. Furthermore, current analytical methods primarily used today only allow detection of 16-20 major HMOs while more than 100 types have been identified. More large-scale longitudinal studies are required to investigate the role of HMO composition and the impact of changes over the lactation period in preventing AD and FA later in life.

Preventing immediate-onset food allergy in infants, children and adults: Systematic review protocol.

BACKGROUND: More than 17 million people across Europe have allergies to food and the burden of food allergies is increasing. In 2014, the European Academy of Allergy and Clinical Immunology (EAACI) published guidelines for preventing food allergy. Important research has been published since then and it is essential to ensure the guidelines reflect the latest evidence. A systematic review will be undertaken to help prepare new guidelines due to be published in 2020. METHODS: Eleven bibliographic databases will be searched from inception to 31 October 2019 for randomized controlled trials about any intervention designed to prevent the development of new cases of immediate-type/IgE-mediated food allergy in infants, children and adults. There are few randomized controlled trials about the impact of breastfeeding on food allergy so prospective cohort studies about breastfeeding with at least 1000 participants at general risk or 200 at high risk of food allergy will also be eligible. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach will be used to assess the certainty of the evidence and tabulate summary data. The risk of bias in individual trials will be assessed using the Cochrane risk of bias tool. All data extraction and quality appraisal will be undertaken independently by two reviewers in partnership with a taskforce of EAACI members. CONCLUSIONS: Preventing food allergy has the potential to improve personal well-being and reduce societal healthcare costs. It is important that forthcoming European guidelines take the latest research into account. Past reviews have tended to focus on single interventions or combined food allergy with other outcomes, making it difficult to draw robust conclusions about potential impacts for policy and practice.

Reduction in mouse allergen exposure is associated with greater lung function growth.

BACKGROUND: Current childhood asthma therapies have little effect on lung function trajectory. OBJECTIVE: We sought to determine whether mouse allergen exposure reduction is associated with lung function growth in mouse-sensitized/exposed asthmatic children. METHODS: Three hundred fifty mouse-sensitized/exposed asthmatic children (5-17 years old) were enrolled in a 1-year randomized trial of integrated pest management plus education versus education alone. Prebronchodilator/postbronchodilator spirometry was performed at baseline and 6 and 12 months, and bedroom floor mouse allergen levels were measured every 3 months. Mouse allergen reduction was defined as a 75% or greater decrease in mouse allergen levels from baseline. Treatment groups were combined for analyses because there were no differences in outcomes between groups. Changes in lung function over time were modeled, adjusting for age, sex, race, atopy, group, and bronchodilator reversibility and including an interaction term (allergen reduction*time). RESULTS: The study population was predominantly black (79.4%) and low income (66.3% [<$30,000]). At baseline, the median mouse allergen level was 5.7 µg/g (interquartile range, 1.5-22.8 µg/g), and the mean (SD) prebronchodilator FEV1/forced vital capacity ratio was 80.2% (9.0%). Ninety-two (26.3%) participants had 75% or greater reduction in mouse allergen levels. For a 10-year-old black boy, 75% or greater allergen reduction was associated with an increase in prebronchodilator FEV1 of 238 mL/y (95% CI, 177-299 mL/y), whereas less than 75% allergen reduction was associated with an increase in prebronchodilator FEV1 of 131 mL/y (95% CI, 97-166 mL/y). Estimated differences in prebronchodilator and postbronchodilator FEV1 growth were as follows: 107 mL/y (95% CI, 37-177 mL/y; Pint = .003) and 48 mL/y (95% CI, -17 to 113 mL/y; Pint = .15), respectively. Estimated differences in prebronchodilator and postbronchodilator forced expiratory flow at 25% to 75% of vital capacity growth were as follows: 182 mL/y (95% CI, 61-304 mL/y; Pint = .003) and 181 mL/y (95% CI, 48-314 mL/y; Pint = .008), respectively. CONCLUSION: Mouse allergen reduction is associated with greater increases in prebronchodilator FEV1 and prebronchodilator/postbronchodilator forced expiratory flow at 25% to 75% of vital capacity over 1 year among sensitized/exposed asthmatic children.

Systematic review and meta-analysis on the use of probiotic supplementation in pregnant mother, breastfeeding mother and infant for the prevention of atopic dermatitis in children.

Probiotic supplementation may decrease the risk of allergic disease; however, there are differences between studies, such as the type of probiotic, the route or the duration of supplementation. Therefore, determining the most effective probiotic strain/s, route of administration and duration for clinical recommendation has been difficult. An electronic systematic literature search was undertaken between using Ovid MEDLINE, Embase, PubMed and Cochrane. Risk ratio (RR) and 95% confidence interval (CI) are presented for the studies. PEDro scale and Newcastle-Ottawa Scale were used to assess the quality of the included studies. A total of 21 studies met the inclusion criteria. Strain-specific sub-meta-analyses indicated that single strains are not as effective as probiotic mixtures and administration to a combination of pregnant mothers, breastfeeding mothers and infants had a reduced risk in the onset of atopic dermatitis in children. Our systematic review and meta-analysis showed that a mixture of probiotic supplementation given to the mother in pregnancy and continuing while breastfeeding and also to the infant in children classified as high-risk for atopic dermatitis and non-high-risk groups is the most efficacious in reducing the risk of incidence of atopic dermatitis in children.

Adjuvant Allergen Fusion Proteins as Novel Tools for the Treatment of Type I Allergies.

While acute allergic symptoms can be managed by emergency medication, to date, allergen-specific immunotherapy (SIT) with allergen extracts is the only available curative treatment option. However, the risk of anaphylactic reactions, long treatment duration, varying extract quality, and underrepresentation of certain allergens currently prevent many patients from successfully undergoing SIT. Novel strategies are needed to enhance efficacy, safety, and convenience of allergy treatment. Fusion proteins combining allergen and adjuvant into a single molecule can efficiently induce immune responses by targeting the allergen to the relevant immune cells in vivo. Simultaneous co-delivery of both antigen and adjuvant to the same cell in a fixed molecular ratio triggers the uptake and presentation of the conjugated allergen in the context of the adjuvant-induced immune cell activation. This review summarizes the published strategies to improve the treatment of type I allergies using fusion proteins consisting of allergen (peptides) and either (1) immune-activating bacterial (flagellin, MPLA, S-layer, cholera-, and tetanus toxin), (2) viral (PreS, VP-1, TAT), or (3) fungal (FIP-fve) components, (4) immune-activating DNA motifs, (5) forced delivery of allergens to the MHC-II loading pathway, and (6) killing of immune cells expressing allergen-specific IgE by fusion of the allergen to diphtheria toxin.

The Humoral Immune Response to BCG Vaccination.

Bacillus Calmette Guérin (BCG) is the only currently available vaccine against tuberculosis (TB), but it confers incomplete and variable protection against pulmonary TB in humans and bovine TB (bTB) in cattle. Insights into the immune response induced by BCG offer an underexploited opportunity to gain knowledge that may inform the design of a more efficacious vaccine, which is urgently needed to control these major global epidemics. Humoral immunity in TB and bTB has been neglected, but recent studies supporting a role for antibodies in protection against TB has driven a growing interest in determining their relevance to vaccine development. In this manuscript we review what is known about the humoral immune response to BCG vaccination and re-vaccination across species, including evidence for the induction of specific B cells and antibodies; and how these may relate to protection from TB or bTB. We discuss potential explanations for often conflicting findings and consider how factors such as BCG strain, manufacturing methodology and route of administration influence the humoral response. As novel vaccination strategies include BCG prime-boost regimens, the literature regarding off-target immunomodulatory effects of BCG vaccination on non-specific humoral immunity is also reviewed. Overall, reported outcomes to date are inconsistent, but indicate that humoral responses are heterogeneous and may play different roles in different species, populations, or individual hosts. Further study is warranted to determine whether a new TB vaccine could benefit from the targeting of humoral as well as cell-mediated immunity.

Novel Strategy for the Prevention of Recurrent Hypersensitivity Reactions to Radiocontrast Media Based on Skin Testing.

BACKGROUND: Hypersensitivity reactions to iodinated contrast media (ICM) is a persistent clinical issue with increased use of computed tomography. With the evidence indicating underlying allergic mechanisms, there have been studies regarding the skin tests using ICM. OBJECTIVE: This study aimed to evaluate the intradermal skin test (IDT) as a tool for preventing recurrent hypersensitivity reactions to ICM in patients with prior reactions to a known culprit agent. METHODS: Sixty-nine patients who had experienced immediate hypersensitivity reactions to ICM were included in the study. All patients underwent IDT with 7 different ICMs, including the causative ICM. We analyzed clinical data from 38 patients who were reexposed to ICMs, grouped by the IDT results to their original culprit ICM. RESULTS: Thirty-eight patients showed positive IDT results to the culprit ICM (CULPRIT+), whereas 31 patients showed negative results (CULPRIT-). Sixteen patients from the CULPRIT+ group and 22 from the CULPRIT- group were subsequently exposed to an ICM. In the CULPRIT+ group, 4 of the 5 patients who were subsequently exposed to an IDT-positive ICM reexperienced hypersensitivity reactions. When patients were exposed to IDT-negative ICM as an alternative, hypersensitivity reactions were not observed. In the CULPRIT- group, IDT-positive ICMs did not provoke hypersensitivity reactions whereas 2 patients using IDT-negative ICMs experienced hypersensitivity reactions. CONCLUSIONS: When the IDT results are positive for the culprit ICM, additional IDTs with other ICMs are needed to select a safe alternative. If the IDT results are negative against the culprit ICM, further IDTs might not play a role in selecting a safe alternative.

Complementary feeding and food allergy, atopic dermatitis/eczema, asthma, and allergic rhinitis: a systematic review.

BACKGROUND: Nutrition during infancy and toddlerhood may influence health and disease prevention across the life span. Complementary feeding (CF) starts when human milk or infant formula is complemented by other foods and beverages, beginning during infancy and continuing to age 24 mo. OBJECTIVES: The aim of this study was to describe systematic reviews conducted for the USDA and the Department of Health and Human Services Pregnancy and Birth to 24 Months Project to answer the following question: What is the relationship between the timing of the introduction of complementary foods and beverages (CFBs), or types and amounts of CFBs consumed, and the development of food allergy, atopic dermatitis/eczema, asthma, and allergic rhinitis? METHODS: The literature was searched using 4 databases (CINAHL, Cochrane, Embase, PubMed) to identify articles published from January 1980 to February 2017 that met predetermined inclusion criteria. For each study, data were extracted and risk of bias was assessed. The evidence was qualitatively synthesized to develop a conclusion statement, and the strength of the evidence was graded. RESULTS: Thirty-one included articles addressed the timing of CFB introduction, and 47 articles addressed the types and amounts of CFBs consumed. CONCLUSIONS: Moderate evidence suggests that there is no relationship between the age at which CF first begins and the risk of developing food allergy, atopic dermatitis/eczema, or childhood asthma. Limited to strong evidence, depending on the specific food, suggests that introducing allergenic foods in the first year of life (after 4 mo) does not increase the risk of food allergy and atopic dermatitis/eczema but may prevent peanut and egg allergy. There is not enough evidence to determine a relationship between diet diversity or dietary patterns and atopic disease. Research is needed to address gaps and limitations in the evidence on CF and atopic disease, including research that uses valid and reliable diagnostic measures and accounts for key confounders and potential reverse causality.

Preventive Effect of Changing Contrast Media in Patients With A Prior Mild Immediate Hypersensitivity Reaction to Gadolinium-Based Contrast Agent.

OBJECTIVES: Currently, the prevention of recurrent immediate hypersensitivity reactions (HSRs) to contrast media (CM) requests premedication and changing the culprit contrast agent. However, strategies for the prevention of immediate HSRs to gadolinium-based magnetic resonance contrast agents (GBCAs) have not yet been established. This study aimed to evaluate the effectiveness of changing the contrast agent and single-dose premedication for HSR recurrence prevention in patients with a history of mild immediate HSR to GBCA. MATERIALS AND METHODS: The outcomes of patients with mild immediate HSR to GBCA who subsequently underwent enhanced magnetic resonance imaging between October 2012 and July 2017 were analyzed. The institutional CM monitoring system was retrospectively reviewed, and data on the application of premedication and choice of CM were obtained. Gadolinium-based magnetic resonance contrast agents were classified into 3 classes according to their molecular structure (macrocyclic ionic, macrocyclic nonionic, and linear ionic). Intravenous chlorpheniramine 4 mg, 30 minutes before the GBCA administration, or intravenous methylprednisolone sodium succinate 40 mg plus chlorpheniramine 4 mg, 1 hour before the GBCA administration, was administrated as premedication regimen. Recurrence rates of immediate HSR were compared according to prevention strategies. RESULTS: A total of 185 patients with a history of mild immediate HSR to GBCA were re-exposed to GBCA 397 times during the study period. The overall recurrence rate was 19.6% (78/397). Changing the culprit GBCA significantly reduced the recurrence rate, compared with reusing the culprit GBCA (6.9%, 9/130 and 25.8%, 69/267; P < 0.001). The recurrence rate was lowest when the GBCA was changed to a different molecular structure class from the culprit agent, followed by changing to CM with the same molecular structure and reusing the culprit GBCA (6.2%, 7/113 vs 11.8%, 2/17 vs 25.8%, 69/267; P < 0.001 with χ test for trend). Single-dose premedication demonstrated no significant prophylactic effect on recurrence (20.4%, 17/98 vs 17.3%, 61/299 with and without premedication, respectively; P = 0.509). Premedication in addition to changing CM also showed no additional prophylactic effect (7.2%, 7/97 and 6.1%, 2/33, respectively; P = 0.821). CONCLUSIONS: Changing the CM from the culprit agent could reduce the chance of HSR recurrence in patients with prior mild immediate HSR to GBCA, especially when the CM was changed to one of a different molecular structure class. However, single-dose premedication administration did not show significant HSR recurrence rate difference.

The Effects of Early Nutritional Interventions on the Development of Atopic Disease in Infants and Children: The Role of Maternal Dietary Restriction, Breastfeeding, Hydrolyzed Formulas, and Timing of Introduction of Allergenic Complementary Foods.

This clinical report updates and replaces a 2008 clinical report from the American Academy of Pediatrics, which addressed the roles of maternal and early infant diet on the prevention of atopic disease, including atopic dermatitis, asthma, and food allergy. As with the previous report, the available data still limit the ability to draw firm conclusions about various aspects of atopy prevention through early dietary interventions. Current evidence does not support a role for maternal dietary restrictions during pregnancy or lactation. Although there is evidence that exclusive breastfeeding for 3 to 4 months decreases the incidence of eczema in the first 2 years of life, there are no short- or long-term advantages for exclusive breastfeeding beyond 3 to 4 months for prevention of atopic disease. The evidence now suggests that any duration of breastfeeding ≥3 to 4 months is protective against wheezing in the first 2 years of life, and some evidence suggests that longer duration of any breastfeeding protects against asthma even after 5 years of age. No conclusions can be made about the role of breastfeeding in either preventing or delaying the onset of specific food allergies. There is a lack of evidence that partially or extensively hydrolyzed formula prevents atopic disease. There is no evidence that delaying the introduction of allergenic foods, including peanuts, eggs, and fish, beyond 4 to 6 months prevents atopic disease. There is now evidence that early introduction of peanuts may prevent peanut allergy.

Characteristics of inner-city children with life-threatening asthma.

BACKGROUND: Intensive care unit (ICU) admission is a risk factor for fatal asthma. Little is known about risk factors for pediatric ICU admissions for asthma. OBJECTIVE: To examine characteristics of underserved minority children with prior ICU admissions for asthma. METHODS: Baseline survey data, salivary cotinine levels, and allergen specific IgE serologic test results were obtained from children with uncontrolled asthma enrolled in a randomized clinical trial of a behavioral education environmental control intervention. Characteristics of children with and without prior ICU admission were compared using χ2 and t tests. Logistic regression assessed significance of higher odds of prior ICU admission comparing factor-level categories. RESULTS: Patients included 222 primarily African American (93.7%), male (56%), Medicaid-insured (92.8%) children with a mean (SD) age of 6.4 (2.7) years with uncontrolled asthma. Most (57.9%) had detectable cotinine levels, 82.6% were sensitized to more than 1 environmental allergen, and 27.9% had prior ICU admissions. Prior ICU patients were more likely to be very poor (<$10,000 per year) and sensitized to more than 1 allergen tested (most importantly mouse) (P < .05). Allergen sensitization in the groups did not differ for cockroach, cat, dog, Alternaria, Aspergillus, dust mite, grass, or tree. Although more ICU patients received combination controller therapy, they also overused albuterol. Only 27.4% of ICU patients received specialty care in the previous 2 years, which was not significantly different from non-ICU patients. CONCLUSION: Children with high mortality risk, including history of ICU admission, were twice as likely to live in extreme poverty, have atopy (particularly mouse allergen), use combination controller therapy, and overuse albuterol. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01981564.