click on the links to learn more about a few of Dr. Anjuli’s publications

fOOD ALLERGY

  • Safety and feasibility of oral immunotherapy to multiple allergens for food allergy

    Allergy Asthma Clin Immunol. 2014 Jan 15;10(1):1.

    Background: Thirty percent of children with food allergy are allergic to more than one food. Previous studies on oral immunotherapy (OIT) for food allergy have focused on the administration of a single allergen at the time. This study aimed at evaluating the safety of a modified OIT protocol using multiple foods at one time.

    Methods: Participants underwent double-blind placebo-controlled food challenges (DBPCFC) up to a cumulative dose of 182 mg of food protein to peanut followed by other nuts, sesame, dairy or egg. Those meeting inclusion criteria for peanut only were started on single-allergen OIT while those with additional allergies had up to 5 foods included in their OIT mix. Reactions during dose escalations and home dosing were recorded in a symptom diary.

    Results: Forty participants met inclusion criteria on peanut DBPCFC. Of these, 15 were mono-allergic to peanut and 25 had additional food allergies. Rates of reaction per dose did not differ significantly between the two groups (median of 3.3% and 3.7% in multi and single OIT group, respectively; p = .31). In both groups, most reactions were mild but two severe reactions requiring epinephrine occurred in each group. Dose escalations progressed similarly in both groups although, per protocol design, those on multiple food took longer to reach equivalent doses per food (median +4 mo.; p < .0001).

    Conclusions: Preliminary data show oral immunotherapy using multiple food allergens simultaneously to be feasible and relatively safe when performed in a hospital setting with trained personnel. Additional, larger, randomized studies are required to continue to test safety and efficacy of multi-OIT.

  • Multiple-allergen oral immunotherapy improves quality of life in caregivers of food-allergic pediatric subjects

    Allergy Asthma Clin Immunol. 2014 May 12;10(1):25.

    Background: Food allergy (FA) negatively affects quality of life in caregivers of food-allergic children, imposing a psychosocial and economic burden. Oral immunotherapy (OIT) is a promising investigational therapy for FA. However, OIT can be a source of anxiety as it carries risk for allergic reactions. The effect of OIT with multiple food allergens (mOIT) on FA-specific health-related quality of life (HRQL) has never been studied in participants with multiple, severe food allergies. This study is the first to investigate the effects of mOIT on FA-related HRQL in caregivers of pediatric subjects.

    Methods: Caregiver HRQL was assessed using a validated Food Allergy Quality of Life - Parental Burden (FAQL-PB) Questionnaire (J Allergy Clin Immunol 114(5):1159-1163, 2004). Parents of participants in two single-center Phase I clinical trials receiving mOIT (n = 29) or rush mOIT with anti-IgE (omalizumab) pre-treatment (n = 11) completed the FAQL-PB prior to study intervention and at 2 follow-up time-points (6 months and 18 months). Parents of subjects not receiving OIT (control group, n = 10) completed the FAQL-PB for the same time-points.

    Results: HRQL improved with clinical (change < -0.5) and statistical (p < 0.05) significance in the mOIT group (baseline mean 3.9, 95% CI 3.4-4.4; 6-month follow-up mean 2.5, 95% CI 2.0-3.0; 18-month follow-up mean 1.8, 95% CI 1.4-2.1) and rush mOIT group (baseline mean 3.9, 95% CI 3.1-4.7; 6-month follow-up mean 1.7, 95% CI 0.9-2.6; 18-month follow-up mean 1.3, 95% CI 0.3-2.4). HRQL scores did not significantly change in the control group (n = 10).

    Conclusion: Multi-allergen OIT with or without omalizumab leads to improvement in caregiver HRQL, suggesting that mOIT can help relieve the psychosocial and economic burden FA imposes on caregivers of food-allergic children.

  • Phase 1 results of safety and tolerability in a rush oral immunotherapy protocol to multiple foods using Omalizumab

    Allergy Asthma Clin Immunol. 2014 Feb 20;10(1):7.

    Background: Up to 30% of patients with food allergies have clinical reactivity to more than one food allergen. Although there is currently no cure, oral immunotherapy (OIT) is under investigation. Pilot data have shown that omalizumab may hasten the ability to tolerate over 4 g of food allergen protein.

    Objective: To evaluate the safety and dose tolerability of a Phase 1 Single Site OIT protocol using omalizumab to allow for a faster and safe desensitization to multiple foods simultaneously.

    Methods: Participants with multiple food allergies received OIT for up to 5 allergens simultaneously with omalizumab (rush mOIT). Omalizumab was administered for 8 weeks prior to and 8 weeks following the initiation of a rush mOIT schedule. Home reactions were recorded with diaries.

    Results: Twenty-five (25) participants were enrolled in the protocol (median age 7 years). For each included food, participants had failed an initial double-blind placebo-controlled food challenge at a protein dose of 100 mg or less. After pre-treatment with omalizumab, 19 participants tolerated all 6 steps of the initial escalation day (up to 1250 mg of combined food proteins), requiring minimal or no rescue therapy. The remaining 6 were started on their highest tolerated dose as their initial daily home doses. Participants reported 401 reactions per 7,530 home doses (5.3%) with a median of 3.2 reactions per 100 doses. Ninety-four percent (94%) of reactions were mild. There was one severe reaction. Participants reached their maintenance dose of 4,000 mg protein per allergen at a median of 18 weeks.

    Conclusion: These phase 1 data demonstrate that rush OIT to multiple foods with 16 weeks of treatment with omalizumab could allow for a fast desensitization in subjects with multiple food allergies. Phase 2 randomized controlled trials are needed to better define safety and efficacy parameters of multi OIT experimental treatments with and without omalizumab.

aSTHMA

  • The role of leukotrienes in airway remodeling

    Curr. Molec. Med. 2009 April; 9(3):383-91.

    Asthma is an inflammatory disorder of the airways that has been typified by its bronchospastic component. New attention has been directed to the long-term changes in asthmatic airways as indicated by the accelerated rate of lung function decline occurring in these patients despite therapy with inhaled corticosteroids. These structural changes in the airway wall, termed airway remodeling, are now thought to be a key component in the pathophysiology of asthma. Airway remodeling is characterized by thickening of the lamina reticularis with deposition of collagen and other extracellular matrix proteins leading to subepithelial fibrosis and increased airway goblet cells causing mucus hypersecretion. Of note, there is myofibroblast proliferation and increased airway smooth muscle mass caused by both hyperplasia and hypertrophy of smooth muscle cells. While an important role for cysteinyl leukotrienes (CysLTs) in the pathogenesis of airway inflammation and bronchoconstriction in asthma has been well-established, the specific role of CysLTs in airway remodeling is less clear. This aim of this review is to summarize the data from mouse models of asthma as well as limited human studies that demonstrate a key role for CysLTs in allergen-induced mucus hypersecretion, thickening of the lamina reticularis, and subepithelial fibrosis in the lungs. We will also focus on the interaction between CysLTs and cytokines/growth factors that mediate these changes in epithelial cells, smooth muscle cells, vasculature, and other structural components of the lungs in patients with asthma.

  • Review of article: Early Rattles, Purrs and Whistles as Predictors of Later Wheeze.

    Pediatrics 2008; 122: S212-S213.

    PURPOSE OF THE STUDY. To determine how different respiratory sounds in 2-year-olds (whistles, purrs, and rattles) characterized as wheeze by parents predicted wheeze and asthma diagnosis at 5 years of age. A better understanding of parental descriptions of respiratory symptoms may lead to a more accurate diagnosis of asthma.

    STUDY POPULATION. The study subjects were children followed at 2 time points: at ages 2 and 5 years. They were recruited randomly before birth irrespective of history of parental asthma and allergy.

    METHODS. Two thousand pregnant women were recruited randomly at 12 weeks’ gestation, initially as part of a longitudinal birth cohort designed to relate dietary exposure in early life to asthma outcomes in childhood. Parents filled out questionnaires by mail regarding respiratory symptoms when their children were aged 2 and 5 years. Questions included, “Has your child ever suffered from asthma?” and “Has this been diagnosed by a doctor?” Current wheeze was defined as wheezing that has occurred over the last 12 months. If present, parents were asked to categorize the wheeze by sound, describing it as a whistle, rattle, purr, or other sound. If “other sound” was designated, the subjects were excluded from the analysis.

    RESULTS. A total of 210 children wheezed as determined by the questionnaire at 2 years of age, and 77% (162) of the parents of these children also returned a questionnaire when the child was 5 years old. Wheeze persisted in 62 of these subjects. At 5 years of age, children with “whistle” at age 2 were more likely to have current wheeze (73% [11 of 15]) with physician-confirmed asthma (67% [10 of 15]). They were also more likely to be on asthma treatment (40% [6 of 15]). This was compared with “rattle,” which only translated to a 34% (33 of 97) incidence of current wheeze at age 5 and 42% (43 of 97) with physician-confirmed asthma, with 11% (11 of 97) on asthma therapy. A description of “purr” at age 2 had similar outcomes to that of rattle. Children with whistle at 2 years of age were more likely to have mothers with asthma, whereas children with rattle and purr were more likely to be exposed to environmental tobacco smoke.

    CONCLUSIONS. Parents often interpret any respiratory sound as “wheeze.” When respiratory sounds are further characterized as whistle, rattle, or purr, a parent using the terminology “whistle” to describe his or her child's wheeze was a good predictor of persisting symptoms and was associated with future asthma treatment. Use of terms “rattle” and “purr” did not predict future wheeze particularly well.

    REVIEWER COMMENTS. In pediatric medicine, physicians must rely on parents for the history. For children with respiratory symptoms, parents often do not understand or know what “wheeze” means. Having parents use terms such as whistle, rattle, or purr to characterize the noise they hear may help physicians make a diagnosis of asthma, especially if the term whistle is used.

iNFECTIOUS DISEASE/IMMUNOLOGY

  • Association of thymectomy with infection following congenital heart surgery

    World J Pediatr Congenit Heart Surg. 2011 Jul 1;2(3):351-8.

    Background: Congenital absence of the thymus can lead to profound immunodeficiency, suggesting that thymic function during fetal development is essential to normal lymphocyte development. How vital the thymus after birth is to human immune competence and regulation is not known. Routine thymectomy, especially at an early age, may influence immunity, and therefore the risk of infection, autoimmunity, or malignancy.

    Methods: A retrospective review of cardiac surgery patients followed at Seattle Children's Hospital was performed. The primary outcome was rate of serious infections requiring hospitalization. Secondary analyses included age, type of infection, cardiac diagnosis, surgical procedure, and comorbidities.

    Results: Patients fell into 2 groups: 60 with complete thymectomy and 35 with partial or no thymectomy. There was no statistical difference between groups in the overall prevalence of serious infections (16.7% vs 17.2%, P = 1.0). There was a nonsignificant trend toward reduced time between surgery and onset of first infection in patients in the total thymectomy group versus those without thymectomy (1.7 years vs 4.6 years, P = .07). Total thymectomy before 6 months of age also tended to increase infection rate, but the effect was not significant (0.09/year vs 0.02, P = .14). Gastroesophageal reflux in patients with total thymectomy increased the risk of infection (P = .013), suggesting a cumulative effect.

    Conclusions: Though infections occurred frequently in the childhood cardiac surgery population, total thymectomy was not associated with increased risk of serious infection. Comorbid conditions may be more important contributing factors increasing the risk of infection in this complex and vulnerable population.

  • Bacterial Biofilms

    Pediatric Asthma, Allergy, and Immunology 2007; 20(3): 191-195.

    Bacteria can exist in two different forms: a free floating or planktonic form, or a biofilm form. Biofilms are bacteria organized in structured communities enmeshed in an exopolysaccharide matrix and adherent to inert or living surfaces. Bacteria in biofilms have distinct properties from planktonic bacteria, most importantly being their resistance to antimicrobials, which is a multifactorial process. Biofilms have been implicated in several infections, including chronic rhinosinusitis, although there is a paucity of large-scale studies to demonstrate the true role of biofilms in this disease. More studies are needed to understand the nature of biofilms on a cellular and molecular level which may help us with potential targeted therapy.