Manoj R. Warrier

The Prevalence, Severity, and Distribution of Childhood Food Allergy in the United States

OBJECTIVE: The goal of this study was to better estimate the prevalence and severity of childhood food allergy in the United States. METHODS: A randomized, cross-sectional survey was administered electronically to a representative sample of US households with children from June 2009 to February 2010. Eligible participants included adults (aged 18 years or older) able to complete the survey in Spanish or English who resided in a household with at least 1 child younger than 18 years. Data were adjusted using both base and poststratification weights to account for potential biases from sampling design and nonresponse. Data were analyzed as weighted proportions to estimate prevalence and severity of food allergy. Multiple logistic regression models were constructed to identify characteristics significantly associated with outcomes. RESULTS: Data were collected for 40 104 children; incomplete responses for 1624 children were excluded, which yielded a final sample of 38 480. Food allergy prevalence was 8.0% (95% confidence interval [CI]: 7.6–8.3). Among children with food allergy, 38.7% had a history of severe reactions, and 30.4% had multiple food allergies. Prevalence according to allergen among food-allergic children was highest for peanut (25.2% [95% CI: 23.3–27.1]), followed by milk (21.1% [95% CI: 19.4–22.8]) and shellfish (17.2% [95% CI: 15.6–18.9]). Odds of food allergy were significantly associated with race, age, income, and geographic region. Disparities in food allergy diagnosis according to race and income were observed. CONCLUSIONS: Findings suggest that the prevalence and severity of childhood food allergy is greater than previously reported. Data suggest that disparities exist in the clinical diagnosis of disease.

Fresh frozen plasma in the treatment of resistant angiotensin-converting enzyme inhibitor angioedema

BACKGROUND Angioedema, particularly of the head and neck, is a well-recognized adverse effect of angiotensin-converting enzyme (ACE) inhibitors. Most cases respond to conventional therapy, including antihistamines and corticosteroids. Severe episodes may require epinephrine and intubation. OBJECTIVE To report the case of a patient with ACE inhibitor-induced angioedema treated with fresh frozen plasma (FFP). METHODS The patient is a 43-year-old, white woman who first received the ACE inhibitor ramipril in March 2002. After 3 weeks, she developed angioedema of her lips and fingers, which resolved with antihistamines, corticosteroids, and one dose of epinephrine. A low dose of ramipril was restarted 4 days later, which was increased throughout 4 days. In late August 2002, she developed severe upper lip and tongue edema recalcitrant to conventional therapy. Her C1 esterase inhibitor level was normal. RESULTS After 4 days of treatment with antihistamines, corticosteroids, epinephrine, antileukotrienes, cyclosporine, and intravenous immunoglobulins, the patients tongue swelling continued to recur and became more severe. Two units of intravenous FFP was given, with rapid improvement and no further recurrence of tongue swelling. CONCLUSIONS In our patient, FFP was highly successful in the treatment of resistant, life-threatening angioedema due to an ACE inhibitor. The benefit of FFP in this setting might be due to the effect of kininase II in breaking down accumulated bradykinin.

IL-4 alpha chain receptor (IL-4Rα) polymorphisms in allergic bronchopulmonary sspergillosis

BackgroundAllergic bronchopulmonary aspergillosis occurs in 7–10% of cystic fibrosis (CF) and 1–2% of asthmatic patients. HLA-DR restriction and increased sensitivity to IL-4 stimulation have been proposed as risk factors in these populations.ObjectiveWe examined for the presence of IL-4 receptor alpha chain (IL-4Rα) single nucleotide polymorphisms (SNPs) in ABPA and whether these accounted for increased sensitivity to IL-4 stimulation.MethodsOne extracellular (ile75val) and four cytoplasmic IL-4Rα SNPs were analyzed in 40 CF and 22 asthmatic patients and in 56 non-ABPA CF and asthmatic patients. Sensitivity to IL-4 stimulation was measured by induction of CD23 expression on B cells.ResultsIL-4Rα SNPs were observed in 95% of ABPA patients. The predominant IL-4Rα SNP was the extracellular IL-4Rα SNP, ile75val, observed in 80% of ABPA patients.ConclusionThe presence of IL-4Rα SNPs, principally ile75val, appears to be a genetic risk for the development of ABPA.

Geographic Variability of Childhood Food Allergy in the United States

Objective The aim of this study was to describe the distribution of childhood food allergy in the United States. Methods A randomized survey was administered electronically from June 2009 to February 2010 to adults in US households with at least 1 child younger than 18 years. Data were analyzed as weighted proportions to estimate prevalence and severity of food allergy by geographic location. Multiple logistic regression models were constructed to estimate the association between geographic location and food allergy. Results Data were analyzed for 38 465 children. Increasing population density corresponded with increasing prevalence, from 6.2% in rural areas (95% confidence interval [CI] = 5.6-6.8) to 9.8% in urban centers (95% CI = 8.6-11.0). Odds of food allergy were graded, with odds in urban versus rural areas highest (odds ratio [OR] = 1.7, 95% CI = 1.5-2.0), followed by metropolitan versus rural areas (OR = 1.4, 95% CI = 1.2-1.5), and so on. Significance remained after adjusting for race/ethnicity, gender, age, household income, and latitude. Conclusions An association between urban/rural status and food allergy prevalence was observed.

Matrix metalloproteinase 8 contributes to solubilization of IL-13 receptor α2 in vivo

BACKGROUND IL-13 receptor alpha2 (IL-13R alpha 2) is a high-affinity receptor for IL-13, a central mediator of allergic asthma. It acts predominantly as a decoy receptor but can also contribute to IL-13 responses under certain conditions. IL-13R alpha 2 exists in soluble and membrane forms, which can both bind IL-13 and modulate its activity. Yet the proteolytic processes that contribute to the generation of soluble IL-13R alpha 2 are largely unknown. OBJECTIVE We sought to investigate the role of matrix metalloproteinases (MMPs) in the generation of soluble IL-13R alpha 2. METHODS Acellular cleavage assays by MMPs were performed by using glutathione-S-transferase fusion proteins of murine or human IL-13R alpha 2. IL-13R alpha 2 stable-transfected cells were used for analysis of surface expression and release of soluble IL-13R alpha 2. Wild-type and MMP-8-deficient mice were used for analysis of allergen-induced airway hyperresponsiveness and solubilization of IL-13R alpha 2. RESULTS Among several MMPs tested, only MMP-8 cleaved IL-13R alpha 2. Treatment of transfected human or murine cells expressing high levels of surface IL-13R alpha 2 with MMP-8 resulted in release of soluble IL-13R alpha 2 into the supernatants, with a concomitant decrease in surface IL-13R alpha 2 levels. The IL-13R alpha 2 solubilized by MMP-8 retained IL-13 binding activity. In an asthma model MMP-8-deficient mice displayed increased airway hyperresponsiveness and decreased soluble IL-13R alpha 2 protein levels in bronchoalveolar lavage fluid compared with those seen in wild-type mice after house dust mite challenge. CONCLUSION MMP-8 cleaves IL-13R alpha 2 in vitro and contributes to the solubilization of IL-13R alpha 2 in vivo.

Parent report of physician diagnosis in pediatric food allergy

BACKGROUND Childhood food allergy is a serious health problem. However, little is known about the frequency and manner in which it is currently diagnosed. OBJECTIVE To describe parent report of physician practices in the diagnosis of pediatric food allergy. METHODS Data from children with food allergy were identified for analysis from a representative survey administered in US households with children from June 2009 to February 2010. Analyses were performed at the level of the allergy. Demographic characteristics, symptom prevalence, and diagnostic methods were calculated as weighted proportions. Adjusted models were estimated to examine the association of reaction history and allergenic food with odds of physician diagnosis and testing. RESULTS Food allergies (n = 3,218) to 9 common allergens were reported among 2,355 children in a sample of 38,480. We found that 70.4% of reported food allergy was diagnosed by a physician. Among physician-diagnosed food allergy, 32.6% was not evaluated with diagnostic testing, 47.3% was assessed with a skin prick test, 39.9% with a serum specific IgE test, and 20.2% with an oral food challenge. Odds of physician diagnosis and testing were significantly higher for severe versus mild/moderate food allergy. Urticaria and angioedema were not reported as symptoms in 40.7% and 34.6% of severe food allergies, respectively. CONCLUSION Thirty percent of parent-reported food allergies in this study were not diagnosed by a physician. One in 5 physician-diagnosed allergies was evaluated with oral food challenge. Understanding parent report of practices in food allergy provides insight into ways in which to streamline the diagnosis and management of care.

The epidemiology of milk allergy in US children

BACKGROUND Milk is one of the most common food allergies in US children, yet little is known about its distribution and diagnosis. OBJECTIVE To better understand current pediatric milk allergy distribution and diagnosis trends in the United States. METHODS A randomized, cross-sectional survey was administered to parents belonging to a representative sample of US households with children from June 2009 to February 2010. Data from 38,480 parents regarding demographic characteristics, allergic symptoms associated with food ingestion, and methods used to diagnose food allergy were collected and analyzed as weighted proportions. Adjusted models were estimated to examine association of these aspects with odds of milk allergy. RESULTS Of the 3,218 children identified with food allergy, 657 (19.9%) were reported to have milk allergy. Asian (odds ratio [OR], 0.5) and black (OR, 0.4) children were half as likely as white children to develop milk allergy. The highest percentage of milk-allergic children (23.8%) were aged 6 to 10 years, and the lowest percentage of milk-allergic children (15.0%) were aged 11 to 15 years. Nearly one-third (31.4%) of children with milk allergy had a history of severe reactions. Compared with children with other food allergies, children with milk allergy had a higher odds of having physician-diagnosed allergy (OR, 1.7) and were twice as likely (OR, 2.1) to outgrow their milk allergy. CONCLUSION Childhood milk allergy, which accounts for one-fifth of US food allergies, is less prevalent among Asian and black children than white children. Although less than half of children with milk allergy received confirmatory testing, it is the most commonly diagnosed food allergy.

A brief intervention to improve food allergy knowledge among US pediatricians: lessons learned

Objective:  To evaluate a brief educational tool for pediatricians developed to address known gaps in food allergy knowledge.

A curious case of cough

http://dx.doi.org/10.1016/j.anai.2014.11.013 1081-1206/ 2015 American College of Allergy, A A 41-year-old woman presented to a private practice allergy/ exposure is perhaps most likely. The patient had not yet tried a nasal immunology office with 1 year of persistent cough. The cough was often productive of yellow sputum in the morning and clear sputum throughout the day. At other times, the cough was dry and associated with wheezing, but she denied any shortness of breath. The coughwoke her up from sleep most nights and was worse with exertion. In addition, the patient had symptoms for the past 5 years of perennial clear rhinorrhea, postnasal drip, nasal pruritus, and sneezingwith occasional ocular pruritus and erythemawithout any significant nasal congestion or obstruction. She did not have cough before the onset 1 year ago. There was no seasonal variation of her symptoms. She had tried over-the-counter antihistamines, which partially controlled her symptoms. She had also tried a combination inhaled corticosteroid and long-acting b-agonist (ICS-LABA), with no improvement of her cough. She had not tried nasal sprays or nasal irrigation. She had recently seen an otolaryngologist and had unremarkable rhinolaryngoscopy findings. She had not required any antibiotics during the last year. She had 2 dogs and 1 cat, which all slept in her bed. She smoked cigarettes socially. She had no recent changes in the home or work environment. In a patient with persistent dry cough associated with wheeze, nocturnal awakenings, and exertion, asthma or bronchospasm is initially considered. Typically, asthma symptoms improve with appropriate therapy, such as inhaled corticosteroids or b-agonists. However, other factors may be at play, such as adherence, administration technique, environmental exposures, and comorbid conditions. In such a patient, asthma is the first condition considered, with pulmonary function tests (PFTs) performed and then a trial of a shortacting b-agonist alone or with an ICS, depending on results of the workup and clinical picture. This patient’s rhinoconjunctivitis symptoms were likely contributing to the cough and represent an allergic or nonallergic origin. However, with nasal pruritus and sneezing and a partial response to oral antihistamines, allergy to a perennial

Increased sensitivity to IL-4 in cystic fibrosis patients with allergic bronchopulmonary aspergillosis

BACKGROUND Allergic bronchopulmonary aspergillosis (ABPA) is characterized by a heightened Th2 CD4+ T-cell response to Aspergillus fumigatus allergens and a hyper-immunoglobulin (Ig)E state compared with cystic fibrosis patients without ABPA. We hypothesize that one reason for this response is increased sensitivity to interleukin (IL)-4 in ABPA resulting in increased expression of CD23 and CD86 and leading to a positive amplification mechanism that increases Th2 CD4+ T cell responses. METHODS Peripheral blood mononuclear cells (PBMC) were isolated from seven ABPA CF and 19 non-ABPA CF patients and 16 nonatopic controls and stimulated with rIL-4 (range 0.1-10 ng/ml) and rIL-13 (range 1-10 ng/ml) for 48 h. The number of CD23 molecules and percentages of CD23+ B cells were quantified by flow cytometry. Both phorbol 12-myristate 13-acetate (PMA)/ionomycin (IO) and antigen stimulated, toxoid and Asp f2/f3/f4, PBMC were examined for cytoplasmic cytokine synthesis enumerated by cytokine staining using flow cytometry to measure Th2 and Th1 CD3+ T cells. RESULTS The numbers of CD23 molecules on B-cells were significantly elevated at time 0 in ABPA CF patients compared with both non-ABPA CF patients and nonatopic controls. Following IL-4 stimulation in vitro, the numbers and percentages of CD23 expression on B cells were significantly up-regulated in ABPA CF patients compared with non-ABPA CF patients and controls. The IL-13 stimulation up-regulated CD23 expression; however, there was no significant difference in ABPA CF patients compared with non-ABPA CF patients and controls. The percentages of interferon (IFN)-gamma+ CD3+T cells following PMA/IO stimulation were significantly decreased in both ABPA and non-ABPA CF patients compared with controls. There were no significant differences of IL-4+ and IL-13+ CD3+ T cells between ABPA and non-ABPA CF patients. When tetanus toxoid stimulated T cells were examined, both ABPA and non-ABPA CF patients had significantly decreased IFN-gamma+ CD3+ T cells compared with controls. In Asp f2/f3/f4 stimulated T cells, ABPA CF patients had significantly increased IL-4+ CD3+ T cells compared with non-ABPA CF patients and controls. CONCLUSIONS ABPA CF patients have increased sensitivity to IL-4 but not to IL-13 up-regulation of CD23 molecules compared with non-ABPA CF patients. There were decreased percentages of IFN-gamma+ and IL-2+ Th1 T cells in CF patients compared with nonatopic controls but similar percentages of IL-4+ Th2 T cells in all three groups. However, ABPA CF patients had increased frequency of Aspergillus-stimulated Th2 T cells. This indicated that there is skewing of Th2 T cells in ABPA CF patients. Thus, in CF ABPA patients there is increased Th2 T cells and increased sensitivity to IL-4.