Canadian Society of Allergy and Clinical Immunology annual scientific meeting 2016

© The Author(s) 2017. This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/ publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated. Allergic Rhinitis/Asthma


Background:
The efficacy and safety profile of 300IR 5-grass pollen sublingual tablet administered daily pre-and co-seasonally has been demonstrated in subjects with grass pollen-induced allergic rhinoconjunctivitis (ARC). Using data from 7 clinical trials (one pediatric) of the development program, we present the results in 1388 polysensitized subjects. Methods: At enrollment, subjects with medically confirmed grass pollen-induced ARC underwent skin testing to 5-grass mix or timothy and a panel of geographically relevant aeroallergens. Those testing positive to 5 grass/timothy and at least one other allergen were considered polysensitized. The Combined Score (scale 0-3) equally weighing symptom and rescue medication scores was analyzed using an ANCOVA for the single or first pollen period of 4 studies. Adverse events (AEs) pooled from all studies were analyzed descriptively. Results: 1201 (64%) of 1878 adults (300IR = 663, placebo = 538) and 187 (60%) of 312 pediatric subjects (300IR = 92, placebo = 95) were polysensitized. Significant differences from placebo in the mean Combined Score were observed in both actively treated adult (−0.14, relative difference: −26.2%) and pediatric (−0.24, relative difference: −36.3%) subsets. As per overall population, application-site reactions such as oral pruritus (adults: 24.9%, pediatrics: 19.6%), throat irritation (adults: 20.8%, pediatrics: 13.0%) and mouth edema (adults: 9.0%, pediatrics: 9.8%) were the most commonly reported AEs. Three serious drug-related AEs occurred in actively treated adults: hypersensitivity (one polysensitized subject), angioedema and diarrhea (two monosensitized subjects) and resolved.
Background: The IDEAL study described the proportion of severe asthma patients eligible for anti IL-5 and/or anti-IgE directed treatments according to clinical trial or licensed indications. This study presents the results of the Canadian subjects to assess the local generalizability of the results compared to the overall cohort. Methods: IDEAL was a cross-sectional, single-visit, non-drug interventional study conducted in 6 countries. It included subjects aged ≥12 years with severe asthma defined according to the ATS/ ERS guidelines by treatment with high-dose ICS plus an additional controller(s) for ≥12 months; this post hoc analysis presents result for the Canadian cohort. Assessments included blood sample, spirometry, and symptom/burden of illness questionnaires. Mepolizumab, omalizumab and reslizumab treatment eligibilities were based on licensed indications or on clinical trial when indications were not available. Results: 190 Canadian subjects were enrolled, of which 166 met analysis criteria. After exclusion of subjects currently treated with omalizumab, 88 subjects were included (mean age = 52.8 years [SD 15.95]; 49% female). 15 subjects (17.0% [95% Exact CI 9.9, 26.6]) were eligible for mepolizumab and 15 (17.0% [9.9, 26.6]) were eligible for omalizumab by Canadian label criteria, whereas 6 subjects (6.8% [2.5, 14.3]) were eligible for reslizumab. Among the 15 mepolizumab eligible subjects, 3 (20.0% [4.3, 48.1]) were also eligible for omalizumab and 2 (13.3% [1.7, 40.5]) for reslizumab. Conclusions: In this Canada-based severe asthma population defined by high-dose ICS use plus additional controller(s) not currently taking omalizumab, a similar proportions of patients (~17%) were either mepolizumab-eligible (i.e., uncontrolled with eosinophilic inflammation) or omalizumab-eligible (i.e., with an allergic phenotype). In those mepolizumab eligible subjects, ~20% may be eligible for omalizumab, confirming the limited treatment options in this defined uncontrolled severe asthma population with an eosinophilic phenotype. These subgroup results were in general consistent with those for the overall IDEAL cohort Funded by GSK; 201722.

A10
Investigating systemic immune responses in the pathophysiology of allergic rhinitis under the nasal allergen challenge model Young Woong Kim 1,2,3 , Casey P. Shannon 3 , Amrit Singh 1,2,3 , Anne K. Ellis 4,5 , Helen Neighbour 6,7 , Mark Larché 6,7 , Scott J. Tebbutt 1,2,3,8 Background: Antibiotic exposure during infancy has been linked to asthma, but few studies have evaluated prenatal antibiotic exposure. Antibiotics can have long-term health effects through induced dysbiosis of the gut microbiota and associated disruption of immune development. We investigated the association between maternal antibiotic use in pregnancy and childhood asthma, accounting for antibiotic type and trimester of exposure. Methods: Using Manitoba's health administrative data housed at the Manitoba Centre for Health Policy, we created a provincial birth cohort of mother-child dyads comprising all children born between 1996 and 2012. In utero antibiotic exposure was determined from maternal prescription records and child asthma was defined as: any hospitalization for asthma or ≥2 physician diagnoses of asthma or ≥2 prescriptions for asthma medications within a 1 year period after age 5. Associations were determined using Cox regression and expressed as hazard ratios (HR) and 95% confidence intervals (CI). Results: In our study population of 213,661 children, 12% had asthma and 37% were exposed to antibiotics in utero. Prenatal exposure to antibiotics was positively associated with asthma (crude HR 1.30; 95% CI 1.27-1.33). This association persisted after controlling for sex, location of residence, gestational age, and number of siblings, but was attenuated after adjusting for healthcare utilization. Associations were similar regardless of the trimester of exposure. When classified by antibiotic type, associations were observed for penicillins, macrolides, and sulphonamides and trimethoprim, but not for other beta-lactams or tetracyclines. Ongoing analyses will account for additional covariates, number of antibiotic exposures and postnatal antibiotic use. Conclusion: We found that antibiotic use during any trimester of pregnancy was associated with a modest increase in asthma risk among offspring. Healthcare utilization patterns appear to be an important confounder of this association.
Background: Obesity has been linked with poor asthma control and decreased response to inhaled corticosteroids (ICS). However, other studies have refuted these claims. Objective: To determine if weight status has a dose-response relationship with time to first exacerbation among children with asthma. Methods: A historical cohort study was conducted from a clinical database that was linked to health and drug administrative databases. The cohort consisted of children aged 2-18 years with specialist-confirmed asthma, who consulted with the Asthma Centre (AC) of the Montreal Children's Hospital between April 1st, 2000 and September 31st, 2007 in Quebec, Canada. We included children initiating higher-dose ICS monotherapy (MT) or ICS combination therapy (CT) at the clinic index date. We excluded children with: bronchopulmonary dysplasia, cystic fibrosis, or no public drug insurance coverage. The cohort end date was the date of first exacerbation, end of health insurance coverage, or end of 1-year follow-up, whichever occurred first. Sex-specific BMI for age percentiles were calculated using the WHO growth charts. Exacerbation was defined as an emergency department visit, hospital admission, or use of oral corticosteroids for asthma. A Cox model was used to assess the dose response between weight status, i.e. using BMI percentile categories, on the hazard of first exacerbation. Conclusions: This study is the first to demonstrate the dose-response relationship between weight status and exacerbation-free time in pediatric asthma.

Background:
The Kingston Allergy Birth Cohort (KABC) was initiated to study the developmental origins of allergic disease. Kingston General Hospital serves a population with notable diversity in exposures relevant to the emerging concept of the exposome. The exposome concept organizes exposures across the life course into three domains; "general external" (population level; SES, rural/urban residency), "specific external" (individual level; cigarette smoke, breastfeeding, mold/ dampness), and "internal" (respiratory health, gestational age). The objective of this study was to establish a profile of the KABC cohort using the exposome framework and examine parentally reported respiratory symptoms to age 2. Methods: We determined the effects of the general external domain (urban/rural residence, SES) on specific external exposures by Fisher's exact test or Chi squared test, and adjusted the resulting p values for multiple testing. Multivariate Cox proportional hazard models were used to determine associations between prenatal/postnatal factors and respiratory symptoms. Results: Rural KABC participants were significantly less likely to report living within 100 m of major roads, construction and parking lots. However, they were significantly more likely to use wood for heat, have a furry pet inside the home, and to live near a farm. Lowest-tertile SES participants were significantly less likely to live near a farm and to use wood heating, but more likely to live in older homes, in proximity to major roads and parking lots, and to use air fresheners. Significant associations emerged between parental reports of wheeze/cough without a cold and SES, prenatal smoke exposure and mold/dampness. Respiratory symptoms were negatively associated with increasing gestational age and breastfeeding for at least the first six months of life. Conclusions: The KABC is a unique cohort with diversity that can be leveraged for exposomics-based studies. This study demonstrated the impacts of all three domains of the exposome on the respiratory health of KABC children. Background: Across the development program, treatment with 5-grass pollen sublingual tablet has a well established safety profile in subjects with grass pollen-induced allergic rhinoconjunctivitis (ARC). Here we present the safety data of the product over the pre-and coseasonal treatment periods from a pooled analysis. Methods: Subjects with medically confirmed grass pollen-induced ARC were enrolled in one of 8 double-blind studies. They received a 5-grass or placebo tablet daily 2 or 4 months pre-and co-seasonally (5 single season studies and over 3 years in a long-term study) or outside the pollen season (Phase I studies). Adverse events (AEs) from the first preco-seasonal treatment period (pool from all studies) and from 3 consecutive treatment periods (long-term study) were analyzed descriptively. Results: The analysis included 2512 subjects (2200 adults and 312 pediatric subjects) of which 1514 received the active treatment and 998 the placebo. Drug-related AEs were reported by 58% of actively treated subjects and 20% of placebo-recipients. Events were mostly consistent with application-site reactions (e.g., oral pruritus, throat irritation, mouth edema). The majority of these events occurred within the first week of treatment initiation, most on the first day. In the longterm study, drug-related AE incidences in actively treated adults in the respective 2-and 4-month groups were 61 and 71% in Year 1, 54 and 59% in Year 2, and 40 and 45% in Year 3. Three serious treatmentrelated AEs (hypersensitivity, angioedema and diarrhea) were reported in Year 1 in adults, none in pediatrics.

Conclusion:
The 5-grass pollen sublingual tablet showed a favorable safety profile in grass pollen allergic subjects. Adverse events were reported with decreasing incidences over consecutive seasons. Background: Group 2 innate lymphoid cells (ILC2s) produce IL-5 and IL-13, drive Th2 inflammation, and are increased in the peripheral blood of individuals with allergic rhinitis (AR) after allergen challenge, and during pollen season. However, the identification of ILC2s in nasal samples has not been carefully examined. In participants with birch pollen-induced AR, we quantified the frequency of both nasal and peripheral ILC2s before and after a nasal allergen challenge (NAC). Methods: 11 individuals with birch pollen-induced AR and 8 non-allergic individuals were recruited. Each participant underwent a NAC with birch pollen extract (ALK-Abello, Mississauga). Nasal lavage (NL) and peripheral blood were collected at baseline (before challenge) and 4 h post-challenge. NL samples were treated with dithiothreitol and peripheral blood mononuclear cells (PBMCs) were isolated and cryo-preserved. Fresh NL samples and thawed PBMCs were stained with fixable viability dye (PBMCs only), lineage (Lin) surface markers, CD45, CD294 (CRTH2), and CD127 (IL-7Rα) antibodies. Stained cells were acquired using a 4-colour Beckman Coulter Cytomics FACSCanto 500 flow cytometer and an 8-colour FACSAria III cell sorter. Data was analyzed using FlowJo software. GraphPad Prism 6 was used for statistical analysis. Results: A trend was observed suggesting an increase in the frequency of both nasal ILC2s (defined as Lin CD45 + CRTH2 + IL-7Rα+) (p = 0.08) and nasal non-ILC2s (including ILC1s and ILC3s; defined as Lin CD45 + CRTH2-IL-7Rα +) (p = 0.06) in participants with birch pollen-induced AR following a NAC. This trend was absent for both cell subsets in peripheral blood.

Conclusions:
In NL samples, we demonstrated a trend suggesting an increase in both nasal ILC2s and nasal non-ILC2s after allergen challenge. However, the frequency of peripheral ILC2s remained unchanged, contrasting with previous literature. This suggests that Allergy Asthma Clin Immunol 2017, 13(Suppl Background: Western red cedar asthma is the most common form of occupational asthma in the Pacific Northwest region of North America and affects 4.0-13.5% of the exposed population. It has been shown that individuals with western red cedar asthma are sensitive to plicatic acid (PA), which is a low molecular weight molecule found in the wood. In this study, peripheral whole blood gene expression was used as a source to identify biomarker panels which distinguish asthmatic individuals who are sensitive to PA (PA-positive) from asthmatic individuals who are not sensitive to PA (PA-negative). Methods: Peripheral whole blood samples were collected using PAXgene Blood RNA tubes from 10 PA-positive subjects and 8 PA-negative subjects. Gene expression was profiled using a custom NanoString nCounter Elements assay. Sparse partial least squares discriminant analysis (sPLS-DA) was used to identify potential biomarker panels that distinguish the PA-positive subjects from the PA-negative subjects. Results: Using sPLS-DA followed by a leave-one-out cross-validation, a 14-gene panel was shown to distinguish PA-positive subjects from PA-negative subjects at an AUC (area under the receiver operating characteristic [ROC] curve) of 0.82. The top 3 tissues related to these 14 genes are Myeloid CD33+ (FDR = 4.62 × 10 −7 ), Monocyte CD14+ (FDR = 2.39 × 10 −5 ) and γδ T cells (FDR = 5.02 × 10 −4 ). Conclusions: Peripheral blood can potentially be used as an easily obtainable biospecimen to diagnose western red cedar asthma. Further validation of the biomarker panel is required and is currently underway.
Background: Idiopathic anaphylaxis (IA) is a generalized systemic reaction to unknown triggering factors. We classify IA as frequent (six or more episodes in the past year) or infrequent (less than six episodes in the past year). The treatment of IA with frequent recurrence can be challenging. To our knowledge, we present the first case of successful treatment of IA with colchicine. Case presentation: A 52-year-old female is known to have IA for 25 years, with frequent recurrence of symptoms, which required multiple courses of systemic corticosteroids in the past. She was admitted with an acute episode of IA that manifested by urticarial rash, facial angioedema, acute cough, abdominal discomfort, and hypotension.
She is found to have active painful mouth ulcers on admission that she reports have been recurrent for more than 5 years. Other past medical history includes hypothyroidism for 25 years due to Hashimoto thyroiditis. Her regular medications included cetirizine, and thyroid hormone replacement. Thyroperoxidase antibody and total IgE were found to be elevated at 345 and 992 IU/mL respectively, and the total serum tryptase was normal. She was discharged on oral colchicine 0.5 mg twice daily, and oral prednisone 1 mg/kg once daily. She discontinued prednisone after 10 days. During a course of 42 months of follow up, she tolerated colchicine well, and reported good compliance with it. This patient has had no recurrence of mouth ulcers or anaphylaxis symptoms since commencing colchicine. Discussion: Colchicine was prescribed for this patient to prevent recurrent mouth ulcers. The improvement of her recurrent IA was a positive side effect to the drug. More studies are needed to determine colchicine's benefit for IA.

Conclusion:
We have concluded that colchicine may be helpful in the treatment of IA.
Background: Epidemiological studies, clinical trials and clinical practice often rely on "physician-diagnosis" of asthma to draw conclusions from data and direct treatment. We present a case that illustrates the limitations of this dogma and the need to use objective clinical measurements to improve clinical outcomes. Case presentation: A 31 year-old female non-smoker presented with asthma and recurrent bronchitis since childhood. Asthma had been diagnosed by specialists based on symptoms of intermittent wheezing, chest tightness and cough. These symptoms continued into adulthood with significant limitation in her work. She had been prescribed regular inhaled corticosteroids, long-acting beta-agonists and multiple courses of antibiotics and prednisone. A negative methacholine challenge suggested her symptoms were unlikely to represent variable airflow obstruction. Absence of eosinophils on quantitative sputum cytometry suggested that she did not have steroid-responsive airway disease. Persistent sputum neutrophilia and a high lipid index in sputum macrophages led to investigations identifying gastroesophageal reflux, a tracheal diverticulum and mild bronchomalacia as other possible contributors to her symptoms. Discussion: We present a case of persistent respiratory symptoms treated as asthma, with inhaled and oral corticosteroids used over many years. In addition to other investigations, sputum analysis helped identify bacterial bronchitis and silent aspiration as a more likely explanation of her symptoms. Although difficult to prove, a small tracheal diverticulum may also have contributed. High doses of corticosteroids seem to have been not only unnecessary, but may have exacerbated infective bronchitis. Discontinuation of inhaled corticosteroids and beta-agonists, and the use of anti-reflux therapies now maintain her symptom-free. Conclusion: This case illustrates the utility of clinical measurements of airway hyper-responsiveness and cellular bronchitis in the investigation and management of airway symptoms. They are particularly helpful in the evaluation of patients with complex airway diseases and the prevention of over-treatment of patients with mild airway disease.
Background: Mast cells are well known for their role in allergic reactions. When activated, they release multiple mediators of inflammation, a process termed degranulation. This process is thought to cause signs and symptoms such as flushing, urticaria, gastrointestinal symptoms and anaphylaxis. Mastocytosis is defined by abnormal mast cell proliferation and accumulation in various tissues. This is a case of mastocytosis presenting with recurrent anaphylaxis and pruritic skin lesions, which highlights the importance of early recognition and treatment of the disease. Case presentation: A 58 year old male was referred to the allergy clinic after experiencing an episode consistent with idiopathic anaphylaxis. His past medical history was significant for a 5-year history of skin lesion; previously diagnosed as a dermatitis, prior anaphylaxis from shellfish and chronic gastrointestinal symptoms. His physical exam revealed hypergimented skin lesions with central telangiectasia typical of urticaria pigmentosa. Darier's sign, urtication of the skin when lesions are stroked, was positive. Tryptase levels were elevated on three separate occasions. Skin biopsies showed numerous abnormal mast cells and telangiectasia macularis eruptiva perstans. A bone marrow biopsy revealed diffuse spindle-shaped mast cells. DNA testing expressed a KIT Asp816Val mutation, a proto-oncogene that entails mast cell hyperplasia. A diagnosis of indolent systemic mastocytosis was made. The patient currently takes anti-histamines and the pruritus has resolved. He has not experienced further episodes of anaphylaxis. Discussion: Diagnosis and treatment of mastocytosis decreases health care utilization and costs. Visits to health care professionals for episodes of idiopathic anaphylaxis can be avoided when the disease is adequately controlled. Conclusion: Clinicians should be aware of presenting symptoms of mastocytosis and refer to allergy and immunology when concern of mastocytosis exists.
Consent to publish: Consent to publish was obtained. Background: Chlorhexidine is a widely used topical antiseptic which can be found in an increasing number of commercially available products. It is also impregnated in certain medical materials including central venous catheters, pleural tunneled catheters, and Foley catheters. Adverse reactions to chlorhexidine include delayed-hypersensitivity reactions as well as increasing reports of immediate IgE-mediated reactions [1,2]. Case presentation: A 68 year-old male with past medical history of primary biliary cirrhosis, metastatic cholangiocarcinoma with previous Whipple surgery, and anastomotic biliary strictures, presented with severe peri-operative anaphylaxis during a planned revision hepatojejunostomy. After induction with midazolam, propofol, rocuronium, lidocaine, ampicillin, ceftriaxone, and fentanyl he developed generalized urticaria, mild airway edema without bronchospasm, and severe hypotension requiring epinephrine and vasopressors. His surgery was aborted. He had no previous history of drug allergies or food allergies and had undergone multiple previous surgeries without incident. Following this episode, skin prick testing to penicillin and graded challenges to ceftriaxone and amoxicillin were performed and were negative. Local anesthetic testing was also negative. Unfortunately, repeat surgery without antibiotics and using different induction agents resulted in recurrent severe peri-operative anaphylaxis with refractory hypotension immediately following insertion of a central venous catheter impregnated with chlorhexidine. Induction medications included propofol, fentanyl, succinylcholine, desflurane, glycopyrrolate, and lidocaine. Tryptase drawn in the operating room was 40.4 µg/L and later the same day was 6.8 µg/L. Skin prick testing and intradermal testing was performed to all medications he received peri-operatively and to common induction agents including succinylcholine, cistracurium, rocuronium, fentanyl, midazolam, propofol, and lidocaine according to concentrations previously published [3]. All were negative except for skin prick testing to chlorhexidine gluconate 2% which was positive with a 7 mm wheal and 10 mm flare. The patient returned to the operating room three weeks later and had a successful surgery with the avoidance of all chlorhexidine products. Conclusion: Peri-operative anaphylaxis is a challenging and potentially life-threatening clinical problem which demands a thorough evaluation of all possible culprit medications including topical antiseptics such as chlorhexidine.
Consent to publish: Consent to publish was obtained. Background: Hypereosinophilic Syndrome (HES) represents a constellation of disorders characterized by increased production of eosinophils, both in tissues and peripherally. In this case report, we highlight the importance of early and aggressive treatment of acute eosinophilic necrotic myocarditis with corticosteroids in order to mitigate the potential for fatal consequences. Case description: A previously completely healthy, athletic 14 year old female was admitted to the pediatric intensive care unit with a three day history of general malaise, chest pain and shortness of breath. Echocardiogram revealed severe hypertrophic cardiomyopathy with pericardial effusions and severely reduced ejection fraction. Despite treatment she continued to decompensate, such that by 72 h she had a near-fatal cardiac arrest, was intubated and put on extracorporeal membrane oxygenation (ECMO). She was placed at the top of the cardiac transplant list (1A). Cardiac biopsy performed during septostomy revealed severe extensive myocytic necrosis with eosinophilic infiltration. A decision was made to trial her on methylprednisolone 25 mg/ kg (1000 mg) for three days, followed by a slow oral taper. Within hours she exhibited improvement and by day three was extubated, off ECMO and ambulating. She was discharged home the subsequent week with completely normal cardiac function. Her serum eosinophil count, which had peaked at 12.10, was 0.18 at discharge (normal < 0.50 × 10 3 cells/mcl). Discussion: This case highlights the importance of early and aggressive treatment with corticosteroids in patients with cardiac involvement secondary to hypereosinophilia. Current literature has no established benchmark for corticosteroids dosing in acute myocardial necrosis secondary to hypereosinophilia, especially in the pediatric population. We have found that a dose of 25 mg/kg/day for three days with subsequent taper resulted in dramatic and rapid clinical improvement. This patient went from ECMO and the cardiac transplant list to being clinically asymptomatic and home within one week.
Consent to publish: Consent to publish was obtained. Background: Fixed drug eruption (FDE) is a distinctive type of delayed drug hypersensitivity reaction that presents with circumscribed skin lesions recurring at the same location upon exposure to the culprit drug. Appropriate testing to confirm diagnosis is still debated, and evaluation of reactivity to others agents with similar chemical structure is poorly documented. We present a rare case of FDE to amoxicillin reproducible with a graded drug provocation test (DPT) in which we also assed cross-reactivity with other beta-lactams. Methods: Investigation was first performed by skin prick tests with penicilloyl-polylysine (PPL), benzylpenicillin (BP) and amoxicillin, and intradermal tests with PPL and BP. Subsequently, the patient underwent successive DPT to amoxicillin, penicillin V potassium and cefprozil in the allergy outpatient clinic with an interval of 4-6 weeks between each test. If negative, each DPT was followed by a four-day home DPT. Finally, patch testing with penicillin V potassium and amoxicillin was performed. Results: We report a case of a 4-year-old boy who presented with a clinical picture compatible with FDE with well-demarcated oval lesions on the base of the neck, the manubrium, and the inner thigh the second day of amoxicillin treatment for an otitis media. Prick and intradermal skin testing were all negative with a positive histamine control. Amoxicillin DPT (45 mg/kg) showed a delayed positive response 4 h after exposure with a recurrence of the lesions at the same initial sites. The lesions resolved within two days with topical corticosteroid treatment. Subsequent DPT with penicillin V (25 mg/kg) and cefprozil (15 mg/kg) were negative. Finally, extra and intralesional patch testing were negative. Conclusions: We describe the first pediatric case of a selective FDE to amoxicillin tolerating penicillin V potassium and cephalosporins with identical lateral chains. Moreover, our case strengthens the idea that DPT is the most reliable test for FDE diagnosis.

Consent to publish:
The authors consent to publish this abstract in the AACI Journal. Written informed consent for publication was obtained from the patient.
Background: Omalizumab is a humanized recombinant monoclonal antibody approved for treatment of moderate to severe allergic asthma. Adverse reactions include localized skin reactions most commonly; however, anaphylaxis is reported in the literature. Case presentation: LM is a 45-year-old female with severe allergic asthma. She has required frequent hospitalizations and courses of steroids. LM has CT findings and spirometry concerning for asthma-COPD overlap syndrome (ACOS) with triggers of cigarette smoke, mould and cat dander at home. Prescribed respiratory medications include: tiotropium bromide, mometasone furoate/formoterol fumarate, montelukast, fluticasone furoate, and salbutamol. Ipratropium bromide is used during exacerbations. LM was prescribed omalizumab due to suboptimal ACOS control and a serum IgE level of 260. LM had recently finished a steroid taper and experienced dry cough, but returned to her baseline respiratory status before initiating omalizumab. Thirty minutes after receiving omalizumab LM experienced mild, transient pruritus in bilateral hands that resolved spontaneously. She then had acute dyspnea, wheezing and mild abdominal pain. There was no urticaria, angioedema, or hypotension, and her initial oxygen saturation was 99% on room air. She received IM epinephrine, salbutamol, cetirizine and prednisone and was transferred to the emergency department. In triage she was hypoexemic and treated for an asthma exacerbation under the care of internal medicine. Discussion: Given the concerning history of anaphylaxis a tryptase level was ordered and treatment of an asthma exacerbation was continued. LM improved to her baseline the next morning and was subsequently discharged with no rebound anaphylaxis. The episode is challenging as history is concerning for anaphylaxis, but tryptase was low and several asthma triggers were present. Conclusion: The case illustrates the challenge of assessing a potential adverse reaction to omalizumab in a severe asthmatic patient. The role of subsequent skin prick testing and a future challenge to omalizumab remains unclear.
Background: Chronic granulomatous disease (CGD) is a rare primary immunodeficiency characterized by recurrent life-threating bacterial and fungal infections and granuloma formation. CGD is caused by defects in NADPH oxidase, which results in the inability of phagocytes (neutrophils, monocytes and macrophages) to destroy certain microbes. Hematopoietic stem cell transplantation (HSCT) is the only established curative therapy for CGD. Case presentation: A 23 year old male with a history of X-linked CGD underwent a reduced-intensity matched unrelated donor peripheral blood stem cell transplant in July 2015. In February 2016, he was admitted to hospital for nutritional support secondary to odynophagia and anorexia. An upper endoscopy revealed ulcers in his esophagus and he was initially treated with IV acyclovir until biopsies came back negative for HSV/CMV. Pathology report showed a pattern of widespread inflammatory changes. He was then started on mesalamine. Nitroblue tetrazolium (NBT) testing showed no evidence of CGD and a peripheral blood chimerism study (VNTR) showed 100% donor alleles. It was then thought he might have graft-versus-host disease (GvHD) and he was treated with IV steroids. The patient subsequently had several episodes of lower GI bleeding. A colonoscopy demonstrated patchy severe active colitis with ulceration and one granuloma. CMV, acid-fast bacilli and Epstein Barr virus testing was negative. Flow cytometry revealed CD4 15%, CD8 16%, CD56 59% and CD19 1%. He was started on IVIG at immunomodulatory dosing, his MMF was discontinued, and prednisone and tacrolimus doses were adjusted. Repeat colonoscopy one month later showed very severe disease with no improvement. Discussion: This patient with chronic granulomatous disease presented with a new-onset gastrointestinal inflammation and ulceration. This was initially suggestive of a diagnosis of CGD colitis, a common GI manifestation of x-linked CGD. After allelic testing, GvHD was then suspected due to the widespread inflammation, and plethora of phagocytes and lymphocytes within the gastrointestinal lining. However, since this patient has presented with esophageal and colonic involvement, is post-HSCT, and allelic testing demonstrates entirely donor alleles, the possibility of Crohn's disease secondary to HSCT cannot be ruled out. This case would be one of the first documented reports of colitis secondary to HSCT in a patient treated to cure CGD, but the possibility of an infectious etiology cannot be excluded. Conclusion: A broad differential diagnosis is required for colitis presenting after HSCT and in a patient with pre-existing CGD. This case delineates the need for interdisciplinary care and describes a severe case of colitis after HSCT. Consent to publish: Consent to publish was obtained. Background: Hereditary Angioedema (HAE) is a rare, potentially life threatening disease of intermittent soft tissue and mucous membrane swelling caused by low levels of C1-esterase inhibitor (C1-INH), a complement protein that regulates bradykinin production. C1-INH is an acute phase reactant, but the implications of this on the interpretation of the C1-INH assay are not known. Case presentation: A 3-year-old girl whose father has HAE was referred for assessment. History revealed no angioedema attacks. Blood work showed low C1-INH functional level at 0.26 U (normal 0.7-1.3 U) and low complement C4 at 0.07 (normal 0.15-0.47), consistent with the diagnosis. The investigations were repeated upon assessment by a pediatric allergist as two abnormal values are required to confirm the diagnosis. The second C1-INH functional level was in the normal range at 0.76 U. The patient did have an upper respiratory tract infection at the time the sample was drawn. She went on to have a mild attack of angioedema involving a finger and a third C1-INH functional level, when well, was again low at 0.36 U with undetectable C4. Functional C1-INH was measured using Siemens Chromogenic assay. Discussion: This is the first reported case of increased C1-INH level during viral illness, suggesting its role as an acute phase reactant. This has impact on how clinicians test patients for HAE, as blood work drawn during a viral infection may produce falsely normal or elevated C1-INH levels. Given the autosomal dominant nature of this disease, many family members get tested and missed diagnosis may occur. Further research needs to assess a larger population of patients to determine C1-INH role as an acute phase reactant. Conclusion: Low level of C1-INH is required for the diagnosis of Hereditary Angioedema. If it is an acute phase reactant, testing during a time of illness may result in falsely elevated levels and the diagnosis of HAE may be missed.

Consent to publish:
Consent to publish this case report was obtained from the patient and her father. Background: Adult-onset, acquired immunodeficiency due to antiinterferon gamma (IFN-ϒ) antibody was first described in 2004 and is seen only in the East Asian population. Autoantibody against IFN-ϒ lead to defective cell-mediated immunity, making individuals susceptible to disseminated non-tuberculous mycobacterial (NTM) infections and other opportunistic infections that are recalcitrant to standard antimicrobial treatment. Lung, lymph node, skin, soft tissue and bone are the tissues most affected with NTM. Rituximab, an anti-B cell therapy, has shown promise in eliminating this autoantibody. Case presentation: A 60-year-old previously healthy Vietnamese man presented with weight loss, non-productive cough, shortness of breath, fatigue, bony pain, hypercalcemia and multiple subcutaneous lesions and draining sinuses. Mycobacterium avium grew in sputum and he was treated for pulmonary MAC, but his condition continued to deteriorate. Imaging showed lesions in lung, spine, ribs, skull, pelvis, both humeri and diffuse lymphadenopathy. Biopsy of rib, lymph node and lung lesion revealed non-necrotizing granulomas negative for malignancy or acid fast bacilli. CD4 count was 264 cells/mm 3 , IgG 26.3 g/L, IgA 4.73 g/L (polyclonal increases), bone marrow reactive, and HIV status negative. Serum contained neutralizing anti-interferon IFN-ϒ antibodies (NIH-S.Holland). The patient was initiated on rituximab as per lymphoma protocol along with continued antimicrobial therapy. Follow-up after 1 cycle/4 courses of Rituximab revealed weight gain, increased energy, absence of bone pain, and resolution of subcutaneous nodules and sinuses. 8 months later, he demonstrated worsening bony lesions and hypercalcemia that stabilized with a further 3 doses of rituximab given 4 weeks apart.

A37 Disseminated Mycobacterium avian complex (MAC) infection secondary to neutralizing anti-interferon gamma antibody in a Vietnamese man
Discussion: This is the first Canadian case report of this disease. Given the large Asian population in this country it is an important entity for clinicians to be aware of. Like other published cases in Asia and the USA, our patient improved significantly with the use of adjunct Rituximab but repeated courses are likely required to maintain suppression of anti-IFNɣ antibodies. Without such antibody suppressive therapy, the results using anti-tuberculous therapies alone are very poor. Conclusion: Cell-mediated immunodeficiency due to neutralizing interferon-gamma autoantibodies presents in East Asian adults, predisposing them to disseminated NTM infections. Rituximab, a B-cell depleting treatment, shows promise as an adjunct to antimicrobial therapy. Consent to publish: Consent to publish this case report was obtained from the patient. We describe a patient with recurrent Neisseria meningitides bacteremia and a persistently low CH50 suggesting a deficiency in a terminal complement protein.

Case presentation:
A 56 year old caucasian female with past history of severe Neisseria meningitides meningitis and bacteremia at age 42 years of age, presented with a 2 day history of feeling unwell with vomiting and loose stools. On presentation she was found to have a purpuric rash similar to that that occurred with her previous Neisserial meningitis. She was afebrile and looked well, with no meningismus, but was hypotensive. Although initially suspected to have leukocytoclastic vasculitis, blood cultures grew Neisseria meningitides. Immunodeficiency work-up was initiated due to the recurrence of meningococcus infection, demonstrating CH50 < 10 U/mL three days post-presentation. Repeat CH50 after 19 days was unchanged. Individual terminal complement levels are pending. She had not been vaccinated after her initial meningococcal infection. Discussion: This case allows a review of the approach to a patient with recurrent Neisseria meningitides infection, and the characteristics of the CH50 test. Terminal compliment deficiency would explain the presentation of our patient with multiple meningococcal infections. We are currently awaiting the results of confirmatory testing for the exact complement protein implicated by obtaining levels from a specialized lab in the United States. This case is unique in that patients with terminal complement deficiency typically present earlier in life than our patient. Conclusion: This is a case of likely terminal complement deficiency presenting with recurrent Neisseria meningitides infection later in life than typically seen. Confirmation of this diagnosis is pending. Consent to publish: Consent to publish has been obtained from patient presented. Background: Most allergic reactions to nuts occur with small quantities. We report a case where a large amount of nut ingestion was required in order to trigger an allergic reaction. Case history: A 14 year old male ingested 160 g (approximately 100) pistachios over 30-60 min. 60 min later, he developed periorbital angioedema, sore throat and difficulty talking. He was nauseated. He was taken to the nearest hospital and he received an antihistamine and oral prednisone. He did not receive epinephrine. His angioedema resolved over several days. An epicutaneous test was positive to fresh pistachio (8 mm wheal). The patient did not wish to carry an epinephrine auto-injector, as he did not believe he was allergic. A food challenge was offered and accepted. A graded oral challenge to pistachios was performed (1/4, ½, 1, 2, 4, 8, 16 and 32 nuts). Fifteen minutes after ingesting 32 pistachios (22.5 g) he developed perioral redness. His blood pressure was normal. 30 min later, there was a blotchy rash on his torso. He complained about feeling tired and a lump in his throat. He was given epinephrine, 0.3 mg intramuscularly, cetirizine and prednisone. His symptoms rapidly improved. He was observed for 2 more hours. No other symptoms developed. Discussion: This case illustrates the importance of recognizing that threshold doses for allergic reactions can vary widely between patients. It also brings up other questions. Should he strictly avoid pistachio? Does he need to carry an epinephrine auto injector? Will the threshold for allergic reactions stay at this level or decrease with further exposures? Consent to publish: Consent to publish was obtained. Background: Food allergies and anaphylaxis have no cure and are on the rise. Epinephrine is the primary recommended treatment for anaphylaxis. Children with life threatening food allergies live with the constant threat of a fatal reaction, and caregivers must be prepared to treat with an epinephrine auto-injector (EAI). Morbidity and mortality are associated with a delay or lack of epinephrine use. Despite this, use of epinephrine for anaphylaxis is still underutilized. Methods: A consent form and short questionnaire were distributed to caregivers of children under the age of 12 diagnosed with a food allergy, prescribed an EAI and who experienced an anaphylactic reaction within the last 2 years. In-depth, informal, semi-structured interviews were audio-recorded and transcribed verbatim. Nvivo software was used and interpretive phenomenological analysis was performed. Results: Ten caregivers participated (5 females) 32-46 years (mean age 41 years). Children ranged from 3 to 10 years, all with multiple food allergies. Every child regularly carried an EAI, and had experienced between 2 and 7 anaphylactic reactions. Epinephrine treatment from caregivers ranged from 1 to 6 times. Six main themes emerged: life challenges, isolation, anxiety, hesitation, guilt, and influence of health care. Caregivers explained the multiple life challenges and feelings of isolation. During reactions, caregivers felt anxiety and hesitation that lead to subsequent guilt. They were often unsure if it was anaphylaxis, and waited for the situation to spontaneously improve. Interestingly, many mentioned that handling reactions correctly gave them confidence to treat subsequent reactions, which was often influenced by what they had learned from healthcare professionals. Conclusion: Despite the anxiety of experiencing a child's reaction, handling reactions correctly provided participants with confidence to treat subsequent reactions. Witnessing the rapid effects of epinephrine and receiving positive support from health care providers further facilitated their ability to quickly react to anaphylaxis. Background: Studies suggest that there are a growing number of patients who self-perceive food allergy [1][2][3][4][5]. There is considerable public misconception on food allergy prevalence, definition and management [6]. There is a need for accessible, evidence-based information on food allergies. This study will provide content for a mobile app to engage/educate the public. Methods: A convenience sample of family physicians completed a questionnaire on demographics, allergy complaints/referrals, patient signs/symptoms, public perceptions, and attitudes on mobile application use for patients concerned about allergic disease. We have completed one focus group of adolescents ages 10-17; two additional adolescent and three parent groups are planned. Open-ended questions explored trusted health information sources, information to be included in a mobile app, and features that would facilitate use and trustworthiness. Discussions were recorded and transcribed. Comparative methods will be used to categorize emerging themes. Results: 17 family physicians completed the questionnaire. 71% (n = 12) reported allergy as a common presentation. 71% (n = 12) responded patients 'often' present without signs/symptoms of true allergy. The most common presenting signs/symptoms included: eczema, urticaria, nasal congestion, wheeze, anaphylaxis, family history and parental concern. All felt that patients have a poor understanding of food allergy. 100% (n = 17) felt patients would benefit from a mobile app and would recommend this. 95% (n = 16) felt this would reduce allergy referrals. Adolescents from our initial focus group supported this. They recommended this content: (1) allergy definition/ distinction from 'intolerance' , (2) true allergy signs/symptoms, (3) forms of allergy testing, and (4) treatment of true allergy. They felt an app developed by Allergy physicians and institutions would be trusted. They suggested easy-to-navigate interfaces, bright colours and animated characters to increase engagement. Conclusions: These results support development of a mobile app to educate/engage the growing number of patients concerned about allergy, and support family physician counselling. Content encompassing several domains was recommended. Physician and institution development would improve user trust.

Background:
The past decade has seen a shift in paradigm towards oral introduction as a mean for tolerance. Many patients that react to oral food challenges (OFC) do so at a high threshold, and could benefit from daily introduction of foods without the need for formal oral immunotherapy (OIT). We hypothesized that introduction of peanuts in the diet of peanut-allergic patients with a high reactivity threshold would be safe and would promote tolerance. Methods: Starting in 2015, patients with high reaction thresholds to peanuts on OFC at our center were invited to introduce low doses of peanuts (at least one peanut) at home on a daily basis and were followed every 3 months to assess tolerance and to increase daily dosages. A high reaction threshold was defined as a non-systemic reaction over 1 peanut (240 mg of peanut protein) or a systemic reaction over 5 peanuts (1200 mg of peanut protein). OFCs performed between 2012 and 2016 were examined to determine the rate of such high threshold reactors in our population. Previous high threshold reactors were invited to repeat OFCs to act as a reference cohort and to assess natural evolution. Results: We introduced peanuts in the diet of 14 patients with high threshold reactions. The only adverse events reported were mild oral pruritus or abdominal pain, which could be prevented with oral antihistamines. The rate of peanut OFC reactions since January 2012 was 14.2% (49/346). Of these patients, 71.4% (35/49) reacted to high amounts of peanuts. Conclusion: In patients with high threshold reactivity, daily low amounts of peanuts can be introduced safely. This approach can be easily applied in general practice without needing the complex infrastructure of OIT protocols. Longer follow up of patients and of reference cohorts are needed to measure long-term outcomes.

Likelihood of sensitization to alternate ingredients in patients evaluated for chocolate allergy
Hani Hadi 1 , Charles Barnes 1 , Jay Portnoy 1 , Vincent Stagg 2 1 Division of Allergy and Immunology, Department of Pediatrics, Children's Mercy Hospital, University of Missouri, Kansas City, MO, USA, 2 Health Background: Delayed introduction of peanut has been shown to increase the risk of peanut allergy among children at high risk of peanut allergy, including children with egg allergy. We evaluated the association between sensitization (a positive skin prick test) to other highly-allergenic foods and delayed introduction of peanut in children without sensitization to peanut in an unselected Canadian cohort. Methods: Caregivers of participants in the Canadian Healthy Infant Longitudinal Development (CHILD) Study prospectively reported their child's age of dietary introduction to peanut in the first 3 years of life and frequency of peanut consumption at age 3 years. At ages 1 and 3 years, the children underwent skin prick testing for sensitization to peanut and other food allergens and assessment by a pediatric allergist or trained researcher for food allergies. We evaluated delayed peanut introduction among children who were sensitized to other highly allergenic foods, such as milk and egg, but not sensitized to peanut. Results: Among children with negative skin prick tests to peanut at age 1 year, some children were sensitized to egg (5.52%) and milk (1.37%). Children who were not sensitized to peanut at age 1 year were more likely to have delayed the introduction of peanut until after age 18 months if they were sensitized to egg (OR 1.52, 95% CI 1.04-2.21). They were also still more likely to be avoiding peanut at age 3 years if they were sensitized to egg at ages 1 year (OR 2.45, 95% CI 1.66-3.62) or 3 years (OR 2.60, 95% CI 1.27-5.33), even if they had never had a reaction to peanut (OR 2.14, 95% CI 1.25-3.67). Conclusion: Avoidance of peanut in egg-sensitized children without sensitization to peanut may reflect caregiver concern about introducing highly allergenic foods. Improved knowledge translation is needed to personalize food-allergen avoidance recommendations for children.
Background: Interleukin-13 (IL-13) is a central effector cytokine in asthma and promotes eosinophilic inflammation, airway hyperresponsiveness, mucus secretion, epithelial damage and fibrotic changes in the airways. Many of the IL-13 effects in the lung are through its interactions with the airway epithelium. IL-13 stimulates bronchial epithelial cells to release eotaxin-3 (CCL26) through the activation of signal transducer and activator of transcription 6 (STAT6). CCL26 is a potent chemoattractant for eosinophils, a hallmark of asthma. The effects of bacterial infections on airway eosinophilia are incompletely understood. There is evidence that microbial products through Toll Like Receptors (TLRs) activation affect the release of eosinophil chemotactic factors. Here we studied the effects of TLR4 activation on IL-13-induced CCL26 induction in airway epithelial cells. Methods: We used LPS (TLR-4 ligand) to mimic the effects of bacterial insult on the airway epithelium. The human bronchial epithelial cell line BEAS-2B was stimulated with LPS (10 μg/ml) alone or in combination with IL-13 (20 ng/ml) for 24 h. RNA was extracted and CCL26 mRNA measured using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR). STAT6 phosphorylation was measured by western blot. Results: BEAS-2B cell activation with IL-13 strongly induced CCL26 mRNA expression (16.48 ± 6.05 fold over unstimulated cells, n = 7, p < 0.05). Simultaneous treatment of the cells with LPS inhibited IL-13-induced CCL26 expression (n = 7, p < 0.02). IL-13 induced STAT6 phosphorylation in BEAS-2B cells, which peaked at 30 min. This phosphorylation was attenuated when cells were activated by IL-13 in the presence of LPS. Conclusion: LPS, a TLR4 ligand, attenuates the effects of IL-13 on CCL26 expression in airways epithelial cells. This effect may be dependent on LPS preventing STAT6 activation by IL-13. Background: Food allergy includes immune sensitization towards one or more food proteins, such as beta-lactoglobulin (βLG) that is a major allergen in cow's milk. Milk contains several regulatory molecules, such as TGF-β, Vitamin-A, and microbiota that can enhance oral tolerance. Soluble toll-like receptor 2 (sTLR2) that acts as a decoy receptor is found in breast milk, but its exact role in oral tolerance is not well studied. Having shown previously that TLR2 activation can lead to tolerance disruption toward ovalbumin but not milk, we hypothesise that it could be due to sTLR2 in milk. This work aims to understand the impact of sTLR2 and other regulatory molecules in milk on the development of oral tolerance towards potential allergens. Methods: Murine models of oral tolerance to cow's milk, βLG, and ovalbumin were established. Oral tolerance was assessed in wild-type and TLR2-deficient mice through analysis of antigen-specific antibody responses after a systemic antigen challenge. The bioactivity of milk and recombinant sTLR2 in blocking the effects of a TLR2 activator (PAM3 CSK4) were assessed in vivo and in vitro. The development of antigen-specific Tregs and tolerogenic dendritic cells were also assessed. sTLR2 levels in commercial milk products were analysed by ELISA and bioassay. Results: Oral administration of skim-milk, βLG, and ovalbumin was sufficient to enhance the development of tolerance, independent of TLR2. Tolerized mice produced less allergen-specific IgE. Soluble TLR2 was detected in cow's milk and in commercial baby formulas, which was sufficient to block the bioactivity of PAM3 CSK4 in vitro similar to recombinant sTLR2. Furthermore, cow's milk feeding was also able to enhance the development of ovalbumin-specific Treg cells and tolerogenic-dendritic cells in the mesenteric lymph node of mice.

Conclusion:
Our results confirm an important role for milk-regulatory molecules, including sTLR2, in the development of oral tolerance, which could inform both allergy prevention and treatment strategies.
Background: Phthalates, a plasticizer used in many common commercial products, are ubiquitous environmental contaminants and epidemiological studies suggest that phthalate exposure is associated with development or worsening of airway diseases. Dibutylphthalate (DBP) is a type of phthalate found in high concentrations in indoor air and appears to have a high inflammatory potential. Increasing interest is focused on altered innate immune responses that may increase the risk of allergic asthma. The activation of receptors on innate immune cells trigger the production of cytokines that influence adaptive immune responses. We aimed to understand how phthalate alters the systemic innate immune response by analyzing the co-exposure of DBP and toll-like receptor ligands in whole peripheral blood in vitro. These findings will inform our upcoming double-blinded, randomized controlled, crossover study in which an in vivo model will be employed. Methods: Peripheral blood was exposed to DBP for 20 h followed by LPS challenge for 4 h. The cellular fraction was analyzed by flow cytometry to study surface markers such as CD16, CD24, CD9 and CD14 on neutrophils, eosinophils, lymphocytes and monocytes, respectively. The supernatant was used to detect cytokine expression by ELISA. Statistical significance was assessed by repeated measures one-way ANOVA with Dunnett's correction. Results: The median fluorescence intensity (MFI) of CD14 decreased significantly when stimulation with DBP + LPS (72 ± 10) was compared to the unstimulated control (258 ± 6, p < 0.001) and DBP only (160 ± 12, p < 0.01). MFI of CD24 increased when the co-exposure condition (333 ± 229) was compared to DBP only (237 ± 168, p < 0.01). TNFa expression following co-exposure (723 ± 88 pg/ml) increased compared to stimulation with LPS only (640 ± 95 pg/ml, p = 0.03). Conclusions: Stimulation of peripheral blood with DBP and LPS alters the innate immune cellular and humoral response in vitro; next stage of our project will assess other relevant ligands (R848, PMA/ Ionomycin).

Background:
The T-cell receptor (TCR) genes (alpha, beta, delta, and gamma) are comprised of numerous, discontinuous coding segments that somatically rearrange to produce heterodimeric cell surface T-cell receptors, either alpha/beta (90-95% of T cells) or gamma/delta (5-10% of T cells). Distributive differences in both TCR sequence and genomic rearrangement fragment sizes can be detected by molecular techniques and is useful to determine if a population of T cells in conditions such as hyper-eosinophilic syndromes shows monoclonal or polyclonal features. Objectives: To observe the association between TCR gene rearrangements and peripheral blood eosinophilia. Methods: As part of a comprehensive immune-cytogenetic and hematology evaluation of patients with respiratory symptoms and leucocyte disorders (n = 48) in a newly established joint respirology-haemoncology clinic at the Firestone Institute for Respiratory Health, TCR gene rearrangements in peripheral blood was examined by PCR in 23 patients. Results: 7 of the 23 patients (30%) were detected to have TCR-γ gene rearrangement. There was no difference in the proportion of patients with peripheral blood eosinophilia (>1500/µL) in those with the rearrangement (4/7) and those in whom the rearrangement was not detected (12/16). However, we observed that 4 of the 7 patients with the TCR rearrangements (3 with eosinophilia) had solid tumors of kidney, lung, colon or breast (with three of them developing the tumors after the rearrangement was detected). In one patient, the TCR gene rearrangement disappeared after the tumor was removed. Conclusion: We suggest a careful evaluation of TCR gene arrangements associated with peripheral blood eosinophilia as a potential marker of solid organ tumors.
Background: As there are limited publications on real-life use omalizumab in chronic idiopathic urticaria (CIU) in Canada, there is a need to generate data to inform us of patient characteristics and use of omalizumab. The study aims to describe patient demographics and treatment patterns of patients prescribed omalizumab in a real-world Canadian setting. Methods: Following regulatory approval, a nationwide patient support program (PSP) was made available to all Canadian patients prescribed omalizumab. Baseline demographics and treatment information were collected for patients who provided consent, enrolled between August 26 2014 and April 21 2016; additional patient reported information was collected as of November 2015. Results: The cohort included 1391 patients enrolled in the PSP who received at least one dose of omalizumab (71% women; average age: 46). Most patients (73%) were prescribed OMA 300 mg q4wks while 15% were prescribed 150 mg q4wks; 12% of patients were treated with other dosing regimens. Treatment history was reported by 191 patients; 70% reported being treated with ≥1 H1-antihistamine while 35% received montelukast. Prednisone was used in 24% of patients; use of cyclosporine was uncommon. Data on angioedema was available for 130 patients; 65% reported having a history of angioedema, 26% had not experienced angioedema, while 8% did not know. ER visits in the last year were reported by 137 patients; 55% reported not having visited the ER while the rest had been at least once. Average omalizumab treatment persistency is 13 months. Conclusion: In a real-life world Canadian setting, omalizumab is prescribed to a population comparable to that of the Phase 3 clinical program. Treatment history and healthcare resource use were likely underestimated as data were patient reported and collected as of November 2015. There remains a need to further collect and disseminate real-world data to understand the effectiveness of omalizumab in a real-world setting. Background: A self-reported history of penicillin allergy often results in the use of less effective and more expensive antibiotics. This practice also subjects patients to the complications of broader spectrum antibiotics and longer hospital stays. Phase 1 of our study aims to identify the barriers to referral amongst anesthesiologists. Methods: A qualitative survey was completed by anesthesiology staff and senior residents. We questioned the perceived barriers to referral, if they thought a referral would be of benefit, and how a history of penicillin allergy alters their preoperative management. Results: 15 responses were collected. 66.7% of respondents have never referred patients for a drug allergy evaluation, however 80% of anesthesiologists felt a referral would be beneficial. Barriers to referral included the potential for delay to surgery (33.3%) and the lack of an affiliated allergist to expedite a consult (33.3%). 86.6% of anesthesiologists change their preoperative antibiotic to vancomycin or clindamycin, while 13.3% rarely substitute an alternative for cefazolin. Conclusion: While a large percentage of anesthesiologists believe a referral to an allergist for drug allergy testing is beneficial, only 33.3% have completed a referral in the past due to a host of systemic barriers. Phase 2 will work with anesthesiologists, surgeons and infectious disease at St. Joseph's Health Centre to identify and refer all pre-operative patients with a penicillin allergy. Primary objectives include decreased costs of pre-operative antibiotics. Secondary objectives include the incidence of iatrogenic infections and length of stay. Background: Dendritic cells (DC) are important in innate and adaptive immune responses. Available data on cord blood (CB) DC phenotype with respect to allergic disease development are scarce. In this pilot study, we compared conventional and plasmacytoid CB DC cell surface receptor expression in CHILD cohort subjects with and without signs of atopy at 1 year of age. We hypothesized differential receptor expression profiles between atopic and non-atopic infants.
Methods: CB mononuclear cells from a randomly chosen subset of subjects participating in the CHILD Study were used to phenotype conventional (cDC) and plasmacytoid (pDC) CB DC compartments. Expression of toll-like receptors (TLR), epithelial derived cytokine receptors, costimulatory molecules and high affinity IgE receptors were measured by means of flow cytometry. Expression of CB DC receptors was compared between subjects with and without signs of atopy [positive skin prick test or physician diagnosed atopic dermatitis (AD)] at 1 year of age. Results: TLR-9 expression on pDC was significantly lower (p < 0.05) in subjects with AD compared to infants without signs of atopy. In contrast, TLR-5 on cDC was higher in subjects with AD. FcεRI expression on pDC was significantly higher in subjects with a positive skin prick test (p < 0.01) or AD (p < 0.001) compared to subjects without atopy. There was a significantly higher expression of IL-33 receptor (ST-2) on pDCs from subjects with AD (p < 0.01) with a similar trend seen for cDC. Conclusion: Lower pDC TLR-9 expression may indicate a weakened Th1 immune response, whereas increased expression of TLR-5, FcεRI, and ST-2 receptors suggest early biases favouring Th2 responses. These preliminary results indicate that specific CB DC phenotypes are associated with atopic development in the first year of life, and point to potential changes in innate and adaptive immunity which may preexist in utero in infants at risk of an allergic disease trajectory. Background: One treatment modality for Eosinophilic Esophagitis (EoE) involves the removal of offending dietary antigens. The traditional six-food-elimination diet has long been considered a standard treatment. However, this approach has shown suboptimal effectiveness (72%) despite it being very restrictive, and can negatively affect patients' quality of life [1]. In 2012, Kagalwalla described an initial series of 17 patients who underwent cow's milk elimination (CME) with 65% achieving clinical and histological remission (<15 mean peak eosinophils per high power field (eos/hpf )) [2]. This outcome has been further supported by a 2015 study showing 64% (n = 20) of patients achieving remission on a CME diet [3]. Objective: To describe the clinical and histological response of study subjects who have undergone a CME diet as a primary intervention. Methods: This study was approved by The University of British Columbia/Children's and Women's Health Centre of British Columbia Research Ethics Board. A retrospective chart review was performed on EoE Registry patients that were followed in a multidisciplinary EoE Clinic at BC Children's Hospital (BCCH), or seen in GI clinic. Data on follow up endoscopy and biopsy counts, symptoms as assessed at follow up visits and skin prick test results were collected to measure the effectiveness of a CME diet. Results: Among 125 reviewed charts, 31 (25%) patients followed a CME diet. The majority (90%) of patients had high symptomatic improvement. Histologically, nearly three quarters (74%) of patients on a CME diet had decreased eosinophil counts after the intervention. For both responders and non-responders, the mean average peak eosinophil count decreased by 26 (Pre-treatment mean counts: 47.3 eos/hpf vs Post-treatment mean counts: 21.7 eos/hpf ). Histologic remission (<15 eos/hpf ) was achieved in 58% (18/31), with 16% (5/31) obtaining complete remission (0 eos/hpf ). Patients who followed CME to a strict degree (i.e. reading labels and looking for hidden sources of milk protein) had a (63%, 14/22) chance of remission, compared to (44%, 4/9) who avoided only obvious sources of dairy (milk, cheese, yogurt, and creamy items). No differences in remission rates were seen with strict diets when compared with less strict diets (p = 0.39). There was no differential response to CME for those with atopy versus those without (p = 0.48). Skin prick testing to milk was not predictive of response to CME amongst the 14 patients who underwent testing.