Proceedings of the Canadian society of allergy and clinical immunology annual scientific meeting 2015

Table of contents A1 Role of fibrocytes in allergic rhinitis Marie-Ève Côté, Marie-Ève Boulay, Sophie Plante, Jamila Chakir, Louis-Philippe Boulet A2 Patterns of aeroallergens sensitization in Northern Alberta Hanan Ahmed, Maria-Beatriz Ospina, Kyriaki Sideri, Harissios Vliagoftis A3 Addressing acceptable risk for adolescents with Food-Induced Anaphylaxis (FIA) Sara F. Johnson, Roberta L. Woodgate A4 Outcomes of matched related and unrelated bone marrow transplantation after reduced-toxicity conditioning for children suffering from Chronic Granulomatous Disease Guilhem Cros, Pierre Teira, Sonia Cellot, Henrique Bittencourt, Helene Decaluwe, Marie France Vachon, Michel Duval, Elie Haddad A5 Outcomes of patients with severe combined immunodeficiency (SCID) prior to and after initiation of newborn screening for SCID in Ontario Vy H.D. Kim, Anne Pham-Huy, Eyal Grunebaum A6 Detection of regulatory B cells in the airways of subjects with asthma John-Paul Oliveria, Stephanie Phan, Mark W. Tenn, Damian Tworek, Steven G. Smith, Adrian J. Baatjes, Caitlin D. Obminski, Caroline E. Munoz, Tara X. Scime, Roma Sehmi, Gail M Gauvreau A7 Characterization of IgE-expressing B cells in the airways and peripheral blood of allergic asthmatic subjects John-Paul Oliveria, Stephanie Phan, Mark W. Tenn, Brittany M Salter, Steven G Smith, Caitlin D Obminski, Caroline E Munoz, Abbey Schlatman, Tara X Scime, Rick Watson, Roma Sehmi, Gail M Gauvreau A8 Pregnancy: could it be a risk factor for primary immunodeficient patients Roya Sherkat, Razieh Khoshnevisan, Saba Sheikhbahaei A9 Clinical experience with Octagam: a Canadian retrospective chart review Stephen Betschel, Richard Warrington, Robert Schellenberg A10 Kounis syndrome secondary to contrast media with inferior ST elevations and bilateral ischemic stroke Michael N Fein, Jean-Philippe Pelletier A11 Honey bee venom immunotherapy ineffective in bumble bee-induced anaphylaxis: case report and review of literature Manstein Kan, Robert Schellenberg A12 Delayed immune reconstitution occurring after multiple immune complications of hematological stem cell transplantation for a leaky SCID Roxane Labrosse, Guilhem Cros, Pierre Teira, Henrique Bittencourt, Helene Decaluwe, Michel Duval, Elie Haddad A13 Comparison of Three Case Reports of Acquired Angioedema: presentation, management and outcome Raymond Mak, James Loh, Amin Kanani A14 Sitagliptin-associated angioedema not related to concurrent use of ARB or ACE inhibitor Dominik A. Nowak, Paul K. Keith A15 Sneddon-Wilkinson subcorneal pustular dermatosis associated with an IgA monoclonal gammopathy Daniel Pannozzo, Dominik A. Nowak, Hermenio C. Lima A16 Omalizumab can be effective in patients with allergic bronchopulmonary aspergillosis Diana Pham, Hoang Pham, Gonzalo G. Alvarez, Istvan T. Bencze, Krishna B. Sharma, Mark Smith, Shawn Aaron, Jennifer Block, Tara Keays, Judith Leech, David Schneidermen, Jodi Cameron, Jennifer Forgie, Alicia Ring, John W. O’Quinn, Stephanie Santucci, William H. Yang A17 Efficacious use of omalizumab in the treatment of cystic fibrosis Diana Pham, Hoang Pham, Ena Gaudet, Shawn Aaron, Stephanie Santucci, William H. Yang A18 HAE with normal C1-INH with inconsistent response to C1 esterase inhibitor infusion but reliably responsive to icatibant Hoang Pham, Stephanie Santucci, William H. Yang A19 Anaphylaxis reaction to lactase enzyme Mathew R. Voisin, Rozita Borici-Mazi A20 Risk of solid tumor malignancies in patients with primary immune deficiency Kateryna Vostretsova, Donald F. Stark A21 Is it time to adopt the chromogenic assay for measuring C1 esterase inhibitor function in patients with HAE Type 2? Elizabeth Yeboah, Paul K. Keith A22 Emergency department visits for anaphylaxis and allergic reactions Michelle Martin-Rhee, Cheryl Gula, Clare Cheng, Geoff Paltser A23 START: Susceptibility To food Allergies in a Registry of Twins Alizée Dery, Ann Clarke, Kari Nadeau, Laurie Harada, Kimberley Weatherall, Celia Greenwood, Denise Daley, Yuka Asai, Moshe Ben-Shoshan A24 Qualifying the diagnostic approach employed by allergists when managing patients with self-diagnosed non-celiac gluten sensitivity (NCGS) Lee Horgan, Teresa Pun A25 Retrospective analysis on the agreement between skin prick test and serum food specific IgE antibody in adults with suspected food allergy Ling Ling, Maria B. Ospina, Kyriaki Sideri, Harissios Vliagoftis A26 Staple food hypersensitivity from infancy to adolescence: a report from the BAMSE cohort Jennifer L.P. Protudjer, Mirja Vetander, Marianne van Hage, Ola Olén, Magnus Wickman, Anna Bergström A27 Evaluating the impact of supervised epinephrine autoinjector administration during food challenges on perceived parent confidence Timothy Teoh, Christopher Mill, Tiffany Wong, Ingrid Baerg, Angela Alexander, Kyla J. Hildebrand, John Dean, Boris Kuzeljevic, Edmond S. Chan A28 Local immunoglobulin production to Aspergillus fumigatus cystic fibrosis Jonathan Argeny, Mia Gona-Hoepler, Petra Fucik, Edith Nachbaur, Saskia Gruber, Reto Crameri, Andreas Glaser, Zsolt Szépfalusi, Claudio Rhyner, Thomas Eiwegger A29 Extract consumption with skin prick test (SPT) devices Greg. Plunkett, Brad Mire A30 Evaluation of our cases with nonsteroidal anti-inflammatory drug reactions Mehtap Yazicioglu, Ceren Can, Gokce Ciplak A31 Reasons for referral and final diagnoses in a tertiary care pediatric allergy clinic Victoria E. Cook, Kyla J. Hildebrand, Elodie Portales-Casamar, Christopher Mill, Edmond S. Chan A32 Internist referral practices for inpatients with self-reported penicillin allergies at a tertiary care teaching hospital Michael N Fein, Emil P Nashi A33 Assessing the risk of reactions in children with a negative oral challenge after a subsequent use of amoxicillin Sofianne Gabrielli, Christopher Mill, Marie-Noel Primeau, Christine Lejtenyi, Elena Netchiporouk, Alizee Dery, Greg Shand, Moshe Ben-Shoshan A34 Validity of self-reported penicillin allergies Erica Hoe, Joel Liem A35 Effectiveness of allergy-test directed elimination diets in eosinophilic esophagitis Jason K. Ko, David J.T. Huang, Jorge A. Mazza A36 Allergy testing and dietary management in pediatric eosinophilic esophagitis (EoE): A retrospective review of a tertiary Canadian centre’s experience Mary McHenry, Anthony Otley,Wade Watson A37 Visualizing the impact of atopic and allergic skin disease Dominik A. Nowak, John N. Kraft A38 Cystic fibrosis with and without nasal polyposis in pediatric patients: a cross-sectional comparative study Mihaela Paina, Ahmed A. Darwish Hassan, Delia Heroux, Lynn Crawford, Gail Gauvreau, Judah Denburg, Linda Pedder, Paul K. Keith A39 Evaluation of macrolide antibiotic hypersensitivity: the role of oral challenges in children Bahar Torabi, Marie-Noel Primeau, Christine Lejtenyi, Elaine Medoff, Jennifer Mill, Moshe Ben-Shoshan A40 Venom allergy testing: is a graded approach necessary? Jaclyn A. Quirt, Xia Wen, Jonathan Kim, Angel Jimenez Herrero, Harold L. Kim A41 The role of oral challenges in evaluating cephalosporin hypersensitivity reactions in children Magdalena J. Grzyb, Marie-Noël Primeau, Christine Lejtenyi, Elaine Medoff, Jennifer Mill, Moshe Ben-Shoshan A42 Breastfeeding and infant wheeze, atopy and atopic dermatitis: findings from the Canadian Healthy Infant Longitudinal Development Study Meghan B. Azad, Zihang Lu, Allan B. Becker, Padmaja Subbarao, Piushkumar J. Mandhane, Stuart E. Turvey, Malcolm R. Sears, the CHILD Study Investigators A43 IL33 DNA methylation in bronchial epithelial cells is associated to asthma Anne-Marie Boucher-Lafleur, Valérie Gagné-Ouellet, Éric Jacques, Sophie Plante, Jamila Chakir, Catherine Laprise A44 NRF2 mediates the antioxidant response to organic dust-induced oxidative stress in bronchial epithelial cells Michael Chen, Toby McGovern, Mikael Adner, James G. Martin A45 The effects of perinatal distress, immune biomarkers and mother-infant interaction quality on childhood atopic dermatitis (rash) at 18 months Nela Cosic, Henry Ntanda, Gerald Giesbrecht, Anita Kozyrskyj, Nicole Letourneau A46 Examining the immunological mechanisms associated with cow’s milk allergy Bassel Dawod, Jean Marshall A47 Tryptase levels in children presenting with anaphylaxis to the Montréal Children’s Hospital Sarah De Schryver, Michelle Halbrich, Ann Clarke, Sebastian La Vieille, Harley Eisman, Reza Alizadehfar, Lawrence Joseph, Judy Morris, Moshe Ben-Shoshan A48 Secondhand tobacco smoke exposure in infancy and the development of food hypersensitivity from childhood to adolescence Laura Y. Feldman, Jesse D. Thacher, Inger Kull, Erik Melén, Göran Pershagen, Magnus Wickman, Jennifer L. P. Protudjer, Anna Bergström A49 Combined exposure to diesel exhaust and allergen enhances allergic inflammation in the bronchial submucosa of atopic subjects Ali Hosseini, Tillie L. Hackett, Jeremy Hirota, Kelly McNagny, Susan Wilson, Chris Carlsten A50 Comparison of skin-prick test measurements by an automated system against the manual method Saiful Huq, Rishma Chooniedass, Brenda Gerwing, Henry Huang, Diana Lefebvre, Allan Becker A51 The accurate identification and quantification of urinary biomarkers of asthma and COPD through the use of novel DIL- LC-MS/MS methods Mona M. Khamis, Hanan Awad, Kevin Allen, Darryl J. Adamko, Anas El-Aneed A52 Systemic immune pathways associated with the mechanism of Cat-Synthetic Peptide Immuno-Regulatory Epitopes, a novel immunotherapy, in whole blood of cat-allergic people Young Woong Kim, Daniel R. Gliddon, Casey P. Shannon, Amrit Singh, Pascal L. C. Hickey, Anne K. Ellis, Helen Neighbour, Mark Larche, Scott J. Tebbutt A53 Reducing the health disparities: online support for children with asthma and allergies from low-income families Erika Ladouceur, Miriam Stewart, Josh Evans, Jeff Masuda, Nicole Letourneau, Teresa To, Malcolm King A54 Epigenetic association of PSORS1C1 and asthma in the Saguenay-Lac-Saint-Jean asthma study Miriam Larouche, Liming Liang, Catherine Laprise A55 IL-33 induces cytokine and chemokine production in human mast cells Stephanie A. Legere, Ian D. Haidl, Jean-Francois Legaré, Jean S. Marshall A56 Reference ranges for lung clearance index from infancy to adolescence for Canadian population Zihang Lu, Malcolm Sears, Theo J. Moraes, Felix Ratjen, Per Gustafsson, Wendy Lou, Padmaja Subbarao A57 Kingston Allergy Birth Cohort: cohort profile and mother/child characteristics to age 2 Michelle L. North, Elizabeth Lee, Vanessa Omana, Jenny Thiele, Jeff Brook, Anne K. Ellis A58 Cow’s milk protein specific IgE, IgA and IgG4 as a predictor of outcome in oral immunotherapy Tanvir Rahman, Duncan Lejtenyi, Sarah De Schryver, Ryan Fiter, Ciriaco Piccirillo, Moshe Ben-Shoshan, Bruce Mazer A59 Age of peanut introduction and development of reactions and sensitization to peanut Elinor Simons, Allan B. Becker, Rishma Chooniedass, Kyla Hildebrand, Edmond S. Chan, Stuart Turvey, Padmaja Subbarao, Malcolm Sears A60 Multi-omic blood biomarker signatures of the late phase asthmatic response Amrit Singh, Casey P. Shannon, Young Woong Kim, Mari DeMarco, Kim-Anh Le Cao, Gail M. Gauvreau, J. Mark FitzGerald, Louis-Philippe Boulet, Paul M. O’Byrne, Scott J. Tebbutt A61 Early life gut microbial alterations in children diagnosed with asthma by three years of age Leah T. Stiemsma, Marie-Claire Arrieta, Jasmine Cheng, Pedro A. Dimitriu, Lisa Thorson, Sophie Yurist, Boris Kuzeljevic, Diana L. Lefebvre, Padmaja Subbarao, Piush Mandhane, Allan Becker, Malcolm R. Sears, Kelly M. McNagny, Tobias Kollmann, the CHILD Study Investigators, William W. Mohn, B. Brett Finlay, Stuart E. Turvey A62 The relationship between food sensitization and atopic dermatitis at age 1 year in a Canadian birth cohort Maxwell M. Tran, Diana L. Lefebvre, Chinthanie F. Ramasundarahettige, Allan B. Becker, Wei Hao Dai, Padmaja Subbarao, Piush J. Mandhane, Stuart E. Turvey, Malcolm R. Sears A63 Allergen inhalation enhances Toll-like receptor-induced thymic stromal lymphopoietin receptor expression by hematopoietic progenitor cells in mild asthmatics Damian Tworek, Delia Heroux, Seamus N. O’Byrne, Paul M. O’Byrne, Judah A. Denburg A64 The Allergic Rhinitis Clinical Investigator Collaborative – replicated eosinophilia on repeated cumulative allergen challenges in nasal lavage samples Laura Walsh, Mena Soliman, Jenny Thiele, Lisa M. Steacy, Daniel E. Adams, Anne K. Ellis A65 The CHILD Study: optimizing subject retention in pediatric longitudinal cohort research Linda Warner, Mary Ann Mauro, Robby Mamonluk, Stuart E. Turvey A66 Differential expression of C3a and C5a in allergic asthma ChenXi Yang, Amrit Singh, Casey P. Shannon, Young Woong Kim, Ed M. Conway, Scott J. Tebbutt


Outcomes of patients with severe combined immunodeficiency (SCID) prior to and after initiation of newborn screening for SCID in Ontario
Vy H.D. Kim 1 , Anne Pham-Huy 2 , Eyal Grunebaum 1 1 Background: IgE is critical for allergen-mediated inflammation. IgE is expressed by memory B cells (MBC) and plasmablast (PPC) intermediates, which differentiate into IgE-producing plasma cells (PC). Allergen exposure has been shown to increase IgE levels in the airways of allergic asthmatics; however, B cell subsets expressing and producing IgE in the airways has yet to be studied. Methods: Allergic asthmatics (AA), allergic non-asthmatics (ANA) and healthy controls (HC) were recruited to donate blood and sputum samples. Peripheral blood mononuclear cells (PBMCs) were separated using density gradient centrifugation, and stained with CD19, CD27, CD38, CD45, CD138, IgG and IgE antibodies with appropriate isotype controls. Sputum was induced by inhalation of 3, 4 and 5 % hypertonic saline, and sputum cells were isolated and stained with CD19, CD45, IgE and IgG. Cells were acquired using a Becton-Dickinson LSRII flow cytometer, analyzed using FlowJo and data were expressed as mean ± SEM. Lymphocytes were defined as SSC low CD45+, and B cells were defined as SSC low CD45+CD19+. GraphPad Prism was used to perform one-way ANOVAs and Tukey post hoc analyses. Results: Circulating levels of B cells and IgE-expressing B cell subsets, including MBCs (CD27+CD38−), PPCs (CD27+CD38+) and PCs (CD38+CD138+) were similar in percentages and absolute numbers between AA, ANA and NC. In contrast, the level of IgE-expressing B  0.00013 ± 0.00005 0.00018 ± 0.00007 0.00004 ± 0.00003 In Canada intravenous immune globulin (IVIg) products are licensed for eight disease indications. Although individual IVIg products are not approved for the same indications, Canadian hospitals stock a mix of IVIgs leading to their generic use. IVIG products are used for antibody replacement therapy and in many autoimmune diseases. First approved in Germany in 1995, Octagam ® products have been in clinical use for over 20 years in 80 countries. In Canada, Octagam ® 10 % has been available since 2013. Here we report the routine clinical use of Octagam ® 10 % across three Canadian institutions, and compare its use to other IVIg products licensed in Canada. A total of 135 patients were treated with Octagam ® 10 % for 28 different conditions represented by five distinct indication groups: immunology (43 %), hematology (28 %), neurology (17 %), rheumatology (5 %), and infectious disease (3 %). Ontario Regional Blood Coordinating Network (ORBCoN) recently published an audit of the routine clinical use of IVIg products across Ontario [1]. The audit included 2246 patients over a 3-month period representing 120 indications. The audit captured labeled versus unlabeled utilization. Labeled indications referred to those that were approved for use by Health Canada for at least one IVIg product. The off-label utilization was categorized as off-label and potentially indicated, or off-label and not indicated. Applying the same criteria set forth in the ORBCoN audit, each of the indications identified in this study were similarly classified (Fig. 1).
The results of this retrospective chart review indicate that Octagam ® 10 % is prescribed to Canadian patients similar to other IVIg products, with 85 % of the utilization deemed appropriate based on current IVIg Table 3 Comparing the percentages and absolute numbers of IgE-expressing B cells in the airways and blood of allergic asthmatics, allergic non-asthmatics and healthy controls * p < 0.05 compared across subject groups

Subset of cells Asthmatics blood (n = 11)
Allergic nonasthmatics blood (n = 11) Healthy controls blood (n = 7) Background: Kounis syndrome is a rare but increasingly recognized clinical entity whereby anaphylactic or anaphylactoid reactions provoke coronary artery spasm that may lead to acute myocardial infarction. The pathogenesis is thought to be secondary to mast cell activation-degranulation [1]. A "Kounis-like" syndrome has been described in two patients with mast cell activation disorders presenting with neurologic symptoms yet no evidence of stroke on extensive imaging [2]. Case presentation: A 62-year-old male with a history of dyslipidemia and hypothyroidism presented with a three-day history of nausea, vomiting, fevers, and abdominal pain. There were no complaints of chest pain or shortness of breath. On exam he was vitally well but had significant left lower quadrant tenderness. His initial blood work revealed a leukocytosis of 12.3 × 10^9/L, a C-reactive protein of 78 mg/L, and a lactate of 0.9 mmol/L. During an abdominal computerized tomography (CT) scan with contrast, a code blue was called when the patient became hypotensive, cyanotic, and lost consciousness. He was intubated and an electrocardiogram (ECG) revealed ST elevations in leads II, III, and aVF. A new urticarial rash was now present on his abdomen. He was treated with intravenous fluids, steroids, and anti-histamines with rapid recovery of his blood pressure. Twenty minutes later a repeat ECG showed resolution of the ST elevations; however the troponin level did rise to 4.43 μg/L. Off sedation, the patient had decreased level of consciousness. A head CT revealed multiple hypo-densities in both cerebral hemispheres consistent with cortical and subcortical infarctions in the middle cerebral artery territories, thought to be secondary to hypoperfusion and cerebral vasospasm. Conclusion: Kounis syndrome has been associated with a wide range of medical conditions, drugs, and environmental exposures. We describe the first case of Kounis syndrome secondary to contrast media with evidence of coronary vasospasm and bilateral ischemic stroke. Consent: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Background: Bumble bee allergy is an uncommon cause of Hymenoptera venom allergy. Studies have suggested a variable degree of immunological cross reactivity between bumble bee and honeybee venoms [1]. Bumble bee venom is not available for skin testing in Canada.Treating bumble bee allergic patients with honeybee venom immunotherapy has been described in the literature [2]. We present a case of unsuccessful honey bee immunotherapy in a patient with a previous anaphylactic reaction to eastern North American bumble bee, Bombus impatiens. Case presentation: A 32 year old laboratory worker with bumble bees had a number of stings over years without reaction. In 2009 he had three stings within a few months and developed hypotension, generalized urticaria and wheezing immediately after the third sting. Serum IgE levels were markedly elevated for both honey bee and bumble bee and he was commenced on honey bee immunotherapy at another centre, being maintained on 100 mcg monthly injections for 5 years with total compliance. He was not stung over this period. On subsequent evaluation he was negative to intradermal testing (0.02 mL) with honey bee venom at 1 mcg/mL. A sting challenge to western bumble bee (Bombus occidentalis) was done and the patient developed immediate anaphylaxis symptoms and required treatment with epinephrine and antihistamine. Conclusions: Without access to IgE testing to specific antigens contained in various Apidae species, cross-reactivity canntot be determined. Immunotheapy with honey bee venom did not protect our patient with bumble bee allergy. Bumble bee venom immunotherapy has been reported in Europe but European species vary significantly from North American species. Our experience suggest significant similarity in allergen content between eastern and western bumble bee venoms. With incresing use of bumble bees in agriculture, allergic reactions to stings may become more prevalent and access to venoms for testing and immunotherapy more important. Consent: Written informed consent was obtained from the patient for publication of this case report and any accompanying images.  Case report: We report a 7-year-old patient with persistant and refractory auto-immune complications post-hematological stem cell transplantation (HSCT). He was diagnosed at 3 years of age with a leaky SCID (homozygous mutations of RAG1) after several auto-immune complications and repeated infections. He underwent a mismatched umbilical cord blood transplantation (5/6) at 40 months with a conditioning regimen of Busulfan, Cyclophosphamide and rabbit ATG. His hematological reconstitution was good and he was platelet transfusion-free by day 59 post-HSCT. Chimerism stayed 100 % donor from day 100 post-HSCT. He presented severe acute and chronic GvHD adequately controlled with heavy immunosuppression until 2 years post HSCT. Two and half years post-HSCT, he presented with profound peripheral pancytopenia. As this pancytopenia was resistant to Prednisone, immunoglobulins and rituximab, he received two injections of Alemtuzumab. While red and white blood cells recovered completely, he presented a persistant and refractory immune thrombopenia (ITP) despite treatment with prednisone, sirolimus, Rituximab, and two courses of bortezomib.
A splenectomy was performed with transient efficacy, and romiplostim was added to his treatment shortly after. Concurrently, our patient had very poor immune reconstitution. His CD4+T lymphocytes stayed inferior to 200/µl and the emigrant thymic naive T cells (CD45RA+CD31+/CD4 cells) were nonexistent. As the thymic function seemed to be absent, thymic transplantation was discussed. However, with the combination of splenectomy and romiplostim as platelet-enhancing therapies, we were able to progressively wean prednisone therapy down to a minimal dose of 0.3 mg/kg/day with subsequent restoration of thymic function, as shown by uptrending of CD4+ T lymphocytes and emigrant thymic naive T cells, with latest values of 561/µl and 38 % respectively. Consent: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Background: There are limited reports linking the dipeptidyl peptidase-IV (DPP-IV) inhibitor sitagliptin with upper airway angioedema. Most reports thus far suggest an interaction with the concurrent use of an angiotensin II receptor blocker (ARB) or an angiotensin-convertingenzyme (ACE) inhibitor. The proposed mechanism is shared inhibition of the bradykinin degradation pathway by ACE or DPP-IV inhibitor, or increased effect of bradykinin while on ARB. Case: In March 2015, a 100 pack year former smoker was referred to our Adverse Reactions Clinic for recurrent episodes of lip, tongue, and throat swelling. These episodes occurred 3-4 times a month for several years, with numerous emergency department visits. Our patient had been on prednisone 5 mg daily for several years to manage these episodes, increasing to 40 mg during an exacerbation. They previously had angioedema while taking an ACE inhibitor and possibly following aspirin. They also had seasonal allergies, a rash with amoxicillin, and GI upset with glyburide. They managed their diabetes with insulin. Their other medications included sitagliptin/metformin (Janumet ® ), atorvastatin, hydrochlorothiazide, furosemide, diltiazem, cetirizine, domperidone, ezetimibe, levothyroxine, pantoprazole, ranitidine, vitamin D, ferrous fumarate, B12 injections, docusate, and the following as needed: epinephrine autoinjector, nitroglycerin, senekot. Course: We advised our patient to discontinue sitagliptin and take metformin alone. They have had no further emergency department visits for angioedema. Discussion: Sitagliptin, like ACE inhibitors but not to the same extent, may prevent the breakdown of bradykinin. ACE inhibitors are also much more likely to cause swelling than ARBs. Although ARBs do not inhibit the breakdown of bradykinin, they block bradykinin two receptors and make more available to cause swelling. It is thus possible that sitagliptin played a role in this patient's recurrent episodes of angioedema, especially given the onset of the symptoms after the initiation of the drug ten years ago, the disappearance of symptoms with its discontinuation, and the similar previous problems with ACE inhibitors. Our patient had Allergy Asthma Clin Immunol 2016, 12(Suppl Background: Subcorneal pustular dermatosis (SCPD) is a rare benign chronic inflammatory skin disorder of unknown etiology. First described by Sneddon and Wilkinson in 1956, it is characterized by a relapsing course of symmetric subcorneal sterile pustules involving the flexures, proximal limbs, and trunk. SCPD is often associated with a benign monoclonal IgA gammopathy, which can either precede or follow diagnosis. [1]. Case: A 56-year old Caucasian female presented to our outpatient immunology-dermatology clinic with a seven-year relapsing history of a mildly pruritic and irritating pustular skin eruption under the arms, breasts, and around the groin. Physical examination showed several pea-sized flaccid pustules on an erythematous base in the axillae, groin, and submammary regions (Fig. 2). The patient was otherwise well with no signs of systemic disease.

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Investigations: Routine blood work including a complete blood count and liver function tests were normal. Serum protein electrophoresis showed an abnormal IgA monoclonal gammopathy lambda type with a value of 4.63 g/l (normal 0.7-3.52 g/l). Histopathology showed a sterile subcorneal pustule with inflammatory infiltrate of lymphocytes and neutrophils with the absence of acantholysis. Her previous treatments included topical corticosteroids and antibiotics as well as oral cephalexin and itraconazole, all with poor response. Discussion: The main differential diagnosis of SCPD includes pustular psoriasis, pemphigus foliaceus, IgA pemphigus, impetigo, dermatitis herpetiformis, and acute generalized exanthematous pustulosis. Our patient had been previously treated with antibiotic and antifungal agents with poor response for an infectious cause of the disease. Clinicians may consider an inflammatory disease in their differential when presented with a pustular eruption in the interigenous areas. Consent: Written informed consent was obtained from the patient for publication of this case report and any accompanying images.
Background: Allergic bronchopulmonary aspergillosis (ABPA) is a challenging respiratory disease with significant morbidity and mortality. Among patients with severe asthma, 10 % have ABPA. Typically they have a decline in lung function, positive skin prick reaction to Aspergillus, elevated IgE levels, increased Aspergillus fumigatus specific IgE antibody and central bronchiectasis. Patients often exhibit refractory symptoms despite conventional asthma therapy. Longterm use of high dose inhaled and oral corticosteroids may lead to serious adverse effects such as immunosuppression, adrenal insufficiency, metabolic syndrome, hypokalemia, glaucoma, cataracts, peptic ulcers, osteoporosis, avascular necrosis, and psychiatric disturbances. Antifungals have many drug interactions and may require therapeutic monitoring. Some studies seem to suggest that omalizumab may be a better therapeutic option as there is some evidence demonstrating efficacy in ABPA and fewer adverse effects than long-term corticosteroids.
Methods: A retrospective chart review was performed for ABPA patients receiving omalizumab between 2007 and 2015 at our tertiary care Allergy and Asthma Clinic and The Ottawa Hospital Chest Clinic. Data was collected on demographics, total IgE, aspergillus specific skin testing, the use of inhaled and oral corticosteroids, quality of life (QoL) questionnaires, and number of asthma exacerbations/hospitalizations. Results: A total of ten patients were evaluated (59.7 ± 13.9 years, 7 females and 3 males). Compared to their baseline, the average dose of inhaled corticosteroids dropped by 24 % at month 16 and out of the three patients who were dependent on oral corticosteroids, there was an 89 % decrease in prednisone use by month 16. QoL scores improved in relation to baseline. Nine of the subjects that reported exacerbations 12 months prior to treatment and none reported exacerbations once they started omalizumab. Conclusion: Our retrospective study provides evidence to support the fact that omalizumab may be an effective low-risk treatment for patients with ABPA. Further prospective studies are required to confirm this finding. Consent: Written informed consent was obtained from the patient for publication of this case report and any accompanying images. Background: Lactose intolerance affects approximately 20 % of Canadians and roughly 70 % of the world's population, leading to symptoms of flatulence and bloating after the ingestion of lactosecontaining foods. Lactose intolerance develops primarily due to the absence of the enzyme lactase and can occur in childhood or adulthood. Treatment involves ingestion of commercially-available lactase enzyme preparations often produced by Aspergillus bacteria [1,2]. Although anaphylactic reactions involving IgE mediated hypersensitivity have been reported for a number of foods, this case report represents the first documented evidence of anaphylaxis after exposure to supplemental lactase enzyme preparation. Case report: A 38 year old white female teacher presented with a history of adult-onset lactose intolerance and a suspected allergy to lactase tablets after an episode of bilateral orbital swelling, shortness of breath, and throat constriction that responded to diphenhydramine. The patient's past medical history included oral allergy syndrome and medication-controlled asthma. She handled lactase tablets for years due to her children being lactose intolerant but only recently began using the tablets herself. Physical examination was benign, and skin prick testing to a slurry of the lactase tablet revealed a strongly positive reaction wheal size of 10 mm and flare of 60 mm with normal controls (Fig. 3). The patient required cetirizine treatment in clinic. Skin testing was performed with individual ingredients of the lactase tablet provided by the manufacturer and Aspergillus niger, a common bacteria used in lactase preparations. Only concentrated lactase enzyme elicited a positive response. Avoidance of lactase tablets was advised and the patient was educated in the use of injectable epinephrine. Conclusion: This is the first documented case report of an anaphylactic reaction to lactase enzyme. The patient experienced systemic symptoms including shortness of breath and orbital swelling, reinforcing the importance of education and avoidance of triggers in these rare circumstances. Disclosures: None. Background: Primary immune deficiency (PID) is a major risk factor for the development of malignancy in both the pediatric and adult patient population. It is a major cause of morbidity and mortality, coming second only after infection as the leading cause of death. To date, lymphoreticular malignancies are cited as the most common type of malignancy known to affect people with PID. Little is known about the risk of solid tumor malignancies in this population. Methods: A literature review and a retrospective chart review of 400 adult patients at a local private practice was undertaken. Patients were selected if they both met a diagnosis of primary immune deficiency and solid tumor malignancy. Solid tumor malignancy was defined as a malignancy that was neither lymphoma nor leukemia. Results: Two patients met the criteria of PID and solid tumor malignancy. The first was a male with X-linked agammaglobulinemia (XLA) who developed colorectal cancer and the other patient was a female with Common Variable Immune Deficiency (CVID) who was diagnosed with pancreatic cancer.

Conclusion:
There are only a few studies in the literature regarding the incidence of solid tumor malignancies and PID. These two cases add additional evidence that patients with PID may not only be at risk for lymphoproliferative tumors but perhaps of solid tumors as well.
The diagnosis of PID should alert the clinician to this potential relationship and ensure patients with PID undergo age appropriate primary prevention strategies. Additional studies are required to validate these conclusions.  Background: An estimated 2.5 million Canadians (approximately 7 %) report living with at least one food allergy. Some experts suggest this number is increasing. Epinephrine use and emergency medical services are recommended at the first sign of allergic reactions or anaphylaxis, yet little is known about the utilization of these resources for allergies in Canada. This study examines emergency department (ED) visits for anaphylaxis and allergic reactions and epinephrine auto-injector prescriptions. Methods: Using data from CIHI's National Ambulatory Care Reporting System, this analysis examines unscheduled ED visits that occurred between 2006/07 and 2013/14 with a diagnosis of anaphylaxis or allergic reaction. In addition, claims for epinephrine auto-injectors were estimated between 2006/07 and 2013/14 using data from the National Drug Utilization Information System. The analysis describes the patients who use the ED for anaphylaxis or allergic reaction and looks at trends over time in ED use as well as in prescriptions for epinephrine auto-injectors. Results: About 1 % of total ED visits were for anaphylaxis or allergic reaction. Children and residents of rural areas were over-represented. Most visits occurred in the summer months. Since 2006-07, the rate of all allergy-related ED visits increased by 6 %, with increases particularly high for children under 18 (29 %) and for anaphylaxis-specific visits (80 %). At the same time, epinephrine auto-injector prescriptions increased by 64 %, again particularly among children.

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Conclusions: While overall anaphylaxis and allergy rates remained stable at 1 %, the proportion of visits specifically for anaphylaxis increased significantly over time. In addition, an increased number of children are receiving prescriptions for epinephrine auto-injectors. Given the small increase in overall allergy-related visits, this may reflect a growing awareness of allergies in Canada and changes in coding practices. ED visits remain uncommon and rates of epinephrine auto-injector prescriptions are well below the estimated 7 % of Canadians with allergies. Background: Non-celiac gluten/wheat sensitivity (NCGS) is an emerging entity in the medical literature and lay press. Characterized by nonspecific gastrointestinal symptoms that improve with gluten restriction, it often remains a self-reported illness [1]. This population represents a common and often challenging clinical encounter for practicing allergists. Method: Canadian allergists were identified using publically available physician registries maintained by each province's College of Physicians and Surgeons. A letter of information was faxed to eligible participants and interested parties were invited to complete a brief, semi-structured telephone interview discussing their clinical approach to NCGS. Preliminary Results: A letter of information was faxed to the office of 55 Canadian allergists. At the time of abstract submission, two interviews were completed and three were scheduled for a later date. One respondent declined participation. Of the completed interviews, 50 % of participants were female with an average participant age of 36 years and an average time in practice of 27 months. Both respondents endorsed routine use of wheat allergy skin testing but varied in their use of Celiac Disease serology. One endorsed routine referral to gastroenterology for consideration of endoscopy. Follow-up practices also varied with one participant endorsing routine follow up at six months and the other offering follow-up quite infrequently. Conclusions: Our desired sample size of 15-20 participants will allow us to document the Canadian allergist approach to NCGS. We intend to use this data to develop clinical care guidelines for NCGS in collaboration with our Canadian allergist colleagues.

START: Susceptibility to food allergies in a registry of twins
Background: Hypersensitivity to the staple foods, milk, egg and wheat, has been described through childhood. We aimed to describe staple food hypersensitivity (sFHS), including symptoms and sensitisation by   Background: With the burden of allergic disease increasing worldwide [1], prolonged wait times are a significant concern. Published reviews of referral patterns have focused on adult populations and do not report final diagnoses [2,3]. This is the first study that we are aware of to compare reasons for referral with final diagnoses from a pediatric allergy clinic. Methods: A review of first presentations to the BC Children's Hospital Allergy clinic is currently underway. Data on age, gender, referral source, reason for referral, and final diagnoses were recorded. Descriptive statistics were used to characterize reasons for referral and final diagnoses. Results: Among 68 referrals reviewed to date, 78 % were from general practitioners, while 22 % came from specialists. Median patient age was 4 years (IQR4), and 51 % were female. Most had a single reason for referral (84 %). Table 7 shows referral indications and final diagnoses. Food allergy was the most common reason for referral (71 %), followed by allergic rhinoconjunctivitis (22 %), asthma (10 %), drug allergy (7 %), parent request (1 %), and laboratory result (1 %). Multiple diagnoses were assigned in 10 %. Food allergy was the most common final diagnosis (35 %), followed by allergic rhinoconjunctivitis (24 %), asthma (4 %), drug allergy (1 %) and food protein induced enterocolitis (1 %). Among those referred for suspected food allergy, only 50 % had a final diagnosis of food allergy. Nearly half (44 %) of all referrals received a non-allergic diagnosis. Conclusions: We report a higher proportion of referrals for food allergy (71 %) than seen in prior reports from mixed adult/pediatric practices (19-24 %) [2,3]. Only half of the patients referred for food allergy received a confirmed diagnosis, suggesting many may not have required referral. Greater efforts to educate parents and referring physicians about when to truly suspect a food allergy and the pitfalls of food allergy testing are warranted. Background: Unverified, self-reported penicillin allergy is a common clinical problem among hospitalized patients. These patients often receive broader spectrum, more expensive, and often inferior antibiotics secondary to their unverified penicillin allergy. The large majority of patients with self-reported allergy to penicillin do not have a true type-I mediated penicillin allergy and could benefit from de-labelling.

Methods:
We conducted a retrospective cohort study of 575 consecutive patients admitted to the internal medicine ward at the Montreal General Hospital between April 1st, 2014 and September 9th, 2014. Each patient's electronic chart was reviewed for documentation of reported penicillin allergy. For patients with reported penicillin allergy, their full chart was reviewed to determine what their documented drug reaction was, if they had received antibiotics during their admission, the indication for antibiotic use, antibiotics received, and presence or absence of inpatient or outpatient allergy consultation for evaluation. Results: A total of 74 patients out of the 575 total admissions during the study period reported a penicillin allergy, with a prevalence of 12.9 %. Forty patients (54 %) with an unverified penicillin allergy received antibiotics during their hospitalization. The most common antibiotics prescribed to these patients were moxifloxacin, ciprofloxacin, ceftriaxone, and vancomycin. The most common allergic reaction listed in the electronic medical record was unknown (46 %). Only four patients (5.4 %) received inpatient consultation with an allergist and all of these patients were thought to have suffered an allergic reaction during their hospitalization. There were zero outpatient referrals made for hospitalized patients with a history of unverified penicillin allergy. Conclusion: Referral rates for penicillin allergy evaluation continue to be extremely low-5.4 % in our study. Given the potential impact de-labelling programs may have on antibiotic utilization and stewardship, educational programs and de-labelling projects are currently being explored.  Background: Graded drug challenge is used to determine amoxicillin allergy. However, the risk of future reaction upon subsequent treatment in those with a negative challenge is currently unknown. We aimed to assess the risk of amoxicillin hypersensitivity upon subsequent use in children referred due to suspected amoxicillin allergy who had a negative graded oral challenge. Methods: All children referred to the Montreal Children's Hospital for potential antibiotic allergy were recruited for the study between March 2013 and 2015. A standardized survey with questions on treatment, symptoms, and possible associated factors was filled out and an oral challenge (10 and 90 % of the oral dose) was conducted at the clinic visit. Six months after the challenge and every 6 months thereafter, the patients were contacted by phone to be asked questions on subsequent antibiotic use and associated reactions. Results: Among 366 patients with a negative oral challenge eligible for a follow-up, 250 (68.3 %) patients responded. Of the contacted patients, 60 (24.0 %) reported amoxicillin use and 7 [11.7 % (95 % CI 5.2, 23.2 %)] patients reacted to a subsequent treatment. Amoxicillin was primarily used to treat acute otitis media (AOM). Of those seven patients that did not tolerate the amoxicillin, 57.1 % were male with a median age of 0.9 years (IQR 0.5, 3.9) at the time of reaction and 2.1 years (IQR 1.8, 5.3) at the time of challenge. Sociodemographic characteristics and co-morbidities as well as personal and familial history of atopy were similar between respondents and nonrespondents to follow-up and also between those that reacted and those that tolerated amoxicillin treatment (Table 8). All subsequent reactions presented as hives and 85.7 % (95 % CI 42.0, 99.2 %) developed in the first 3 days of treatment. Conclusion: The risk of a subsequent reaction among those with a negative challenge is almost 10 %. All reactions were limited to the skin, but some of the reported skin reactions may have been triggered by viral infections and hence the risk may be an overestimate. Clinicians can rely on oral challenges to safely assess true allergy among children with suspected skin-related reactions to amoxicillin. Background: 10 % of people claim to have a penicillin allergy. Verifying a penicillin allergy is important because it reduces patient exposure to other antibiotics that can be associated with increased patient morbidity and healthcare costs. The aim of this study is to report the validity of self-reported penicillin allergies in patients presenting to an allergy clinic. Methods: Retrospective chart review of 284 patients who presented to an allergy clinic between April 2011 to December 2014 for penicillin allergy assessment. Patients had undergone skin, intradermal testing of penicillin and a 5-day oral dose challenge of amoxicillin. Patients whose reactions were negative to skin and intradermal testing went on to receive a 5-day oral dose challenge of amoxicillin. Patients with history of serum sickness or Steven-Johnson syndrome/TENS were excluded from this clinic. Results: 8.1 % (23 of 284) of self-reported penicillin allergies were found to be truly allergic as determined by either skin test, intradermal test or 5-day oral challenge. There were 6 reactions to skin and intradermal testing, and these patients did not go on to receive oral doses of amoxicillin. Of those who received the oral challenge, a small number of patients (5 of 284) reacted within 24 h of ingestion of the first dose of amoxicillin. A majority of patients (12 of 284) had a delayed reaction with a rash occurring 24 h after initial ingestion penicillin. Of the oral challenges, the reactions included 6 with hives and 11 with a rash. No oral challenge resulted in cardiopulmonary compromise. Conclusions: Of those reporting a penicillin allergy, only 8.1 % were proven to have a reaction. Of these, the majority had a delayed reaction to penicillin, which typically only involved a rash. There were no life-threatening reactions. Penicillin allergy testing can determine whether patients should actually be avoiding penicillin. Background: Currently there is no consensus on the optimal treatment of eosinophilic esophagitis (EoE). One of the options, an elimination diet guided by allergy test results, has been shown to be effective to varying degrees with greater efficacy in pediatric cohorts [1,2]. However, results in adults have been less promising as higher rates of negative allergy tests hinder efforts to guide the diet [3]. This study explores the results of allergy-test directed elimination diets in a group of patients (n = 16) treated at the Allergy and Immunology Clinic in London, Ontario. Methods: A retrospective chart review was performed using a database of patients diagnosed with EoE (histology ≥ 15 eo/hpf in esophageal biopsy) and treated at the Allergy and Immunology Clinic at St. Joseph's Hospital, London, ON. Patients were included in the review if they had been prescribed an elimination diet guided by allergy testing [skin-prick test (SPT) and/or atopy patch test (APT)], and had esophageal biopsies taken ≥ 8 weeks after initiation of the diet. Pre-treatment eosinophil counts were recorded from peak eosinophil counts of the most recent biopsy prior to initiation of the elimination diet.

Results:
The average age of subjects at diet initiation was 43.75 years (see Table 9 for subject demographics). On average, each subject eliminated 1.7 foods from their diet. Post-diet biopsies displayed a significantly lower level of peak eosinophils/hpf compared to pre-diet biopsies on average (37.9 vs. 89.8, p = 0.043; Fig. 4). Three patients had post-diet biopsies below the histological threshold of diagnosis for EoE (<15 eo/hpf ).
Conclusions: This chart review shows that patients undergoing elimination diets directed by allergy tests have significant histological improvement after their diets. It must be noted that this review did not control for the effects of confounding treatments such as PPIs and corticosteroids, with the latter being of greater concern to histological results. Half of the subjects examined (8 out of 16) had been, at some time before the post-diet biopsy, prescribed swallowed corticosteroids for EoE. However, only 1/4 of steroid-prescribed subjects reported using the steroids during the 30-day period immediately prior to their post-diet biopsy.
Background: Foods are a major trigger for eosinophilic esophagitis (EoE) in children; however, the optimal method for identifying the causative foods is unclear. We investigated the role of allergy testing in a pediatric tertiary centre and its use in identifying causative foods in children with biopsy-confirmed EoE.  Background: Cutaneous disease is known to impact psychosocial wellbeing. This sentiment is especially true in the chronic inflammatory dermatoses such as atopic dermatitis and idiopathic urticaria. Degree of itch plays a role, as do age and socioeconomic status. There is poor correlation, nonetheless, between severity and impact of skin disease, and physicians are themselves poor at gauging the psychosocial impact of skin problems [1]. We set out to visualize this impact by means of a word cloud.

Methods:
Participants answered the open-ended question "How has your skin affected you (e.g. your mood, self-image, relationships, discomfort)?" Responses were transcribed into the word cloud software Wordle [http://www.wordle.net]. Results: Eighty responses were recorded, with a mean age of 44 and a mean word count of 20. Twenty-five of 80 participants screened positive for depression by scoring three or above on the two-item PHQ-2 tool. Seven of eight participants whose complaints included the atopic or allergic screened positive-these included patients with atopic dermatitis, idiopathic urticaria, hand eczema, and allergic contact dermatitis. More frequent phrases were given a proportionally larger size in the graphic. Figure 5 visualizes the answers provided by the eight atopic and allergic patients.

Conclusions:
Clinicians cannot overlook psychosocial wellbeing in skin disease. Specialists pressed for time may consider aligning themselves with a skin-emotion expert, be it a social worker or psychiatrist [2].
Background: Sinonasal disease is often diagnosed in patients with cystic fibrosis (CF). Some studies suggest that CF patients with nasal polyps have less severe pulmonary disease and overall improved survival. Our study examines factors associated with nasal polyposis in pediatric CF patients. Conclusions: Patients with CF and nasal polyposis may constitute a clinical subgroup within the spectrum of the disease. These patients appear to have a higher exposure to Aspergillus. This, together with the higher prevalence of atopy to Aspergillus, may suggest an association with nasal polyposis. Also more likely are: ΔF508/ΔF508 genotype, better pulmonary function/nutritional status, and lower vitamin D levels in winter. Our results confirm and complement those of previous studies.
are diagnosed without further evaluation and are labelled as allergic to the implicated antibiotic. There is sparse data regarding the percentage of established macrolide allergy among children who present with suspected macrolide hypersensitivity. Furthermore, there are no standardized skin tests to confirm the presence of macrolide hypersensitivity [2]. Our objective was to assess the risk of a hypersensitivity reaction through the use of a graded oral challenge in patients with a suspected macrolide allergy. Methods: As part of the LAACTAM (β-LActam and other Antibiotics allergy in Children: Tests, assessment and Management) study, children presenting to the allergy clinic at the Montreal Children's Hospital for the assessment of a potential macrolide antibiotic allergy were recruited. Data on demographics and reaction characteristics was collected through a standardized questionnaire. Patients underwent a graded challenge (10 and 90 % of the dose) of either azithromycin or clarithromycin, and were observed for 1 h after the last dose. In addition, patients were contacted every 12 months to query on potential non-immediate reactions or reactions on subsequent use. Results: Fifty-one subjects with a macrolide allergy were recruited. 80.4 % (95 % CI 66.5, 89.7 %) had reported a reaction to clarithromycin and 19.6 % (95 % CI 10.3, 33.5 %) to azithromycin. The majority of reactions were isolated to the skin and occurred within the first 3 days of the antibiotic course (Table 10). Three subjects out of 51 (5.9 % [95 % CI 1.5, 17.2 %]) had a positive graded challenge. All three reactions were limited to the skin and occurred within the first hour of observation. No late reactions were documented and none of the patients reported repeated use of the culprit macrolide.

Conclusion:
The risk of a reaction in children with a history of a macrolide hypersensitivity is low and seems to occur within 1 h of the oral challenge. Currently an oral provocation is the best tool in diagnosing a macrolide allergy. Larger studies are needed to support these findings and identify risk factors associated with positive challenges.
Background: Many institutions recommend a stepwise approach to intradermal testing for venom allergy [1]. This is costly and uncomfortable for the patient. The rational for this approach is the risk of potential adverse reactions to testing with the maximal dose alone. Strohmeier et al. [2] recently described the safety of a simultaneous approach to testing different venom concentrations, and Yocum has previously described the safety of a two-step approach to testing [3]. Our objective of this study was to evaluate the safety of a single step approach to venom allergy testing.

Methods:
We retrospectively reviewed charts of 300 consecutive patients with suspected hymenoptera venom allergy based on history that underwent venom allergy testing in a single allergist's clinic where a single step protocol had been adopted. Charts were reviewed for patient characteristics including medications, testing protocol used, results of testing, and reported immediate and delayed adverse reactions to testing. Results: All patients underwent testing with an identical single-step protocol with an intradermal dose of 0.02 mL of a 1.0 μg/mL concentration of each of the five commercially available vespid and bee venoms. Patients ranged from 4 to 83 years of age. Only one patient reported an adverse reaction to testing, which was delayed until the morning following his visit. There were no immediate adverse reactions. This patient was successfully started on venom immunotherapy subsequent to his reaction. Conclusion: A single step venom allergy intradermal testing protocol with a 1.0 μg/mL concentration of commercially available extracts is a safe option, which, if adopted into practice, would potentially lead to more streamlined care for patients and cost savings for the medical system.

Background:
Characterizing reactions and assessing the safety of future cephalosporin administration in children is important, given the critical role these antibiotics play in the empirical treatment of serious infections. Because skin tests to cephalosporins remain to be validated [1], we aimed to evaluate the usefulness of oral challenges in assessing the risk of future reaction to these drugs. Methods: Children presenting to drug allergy clinics at the Montreal Children's Hospital during a consecutive 3-year period starting in March 2012, with a history of suspected hypersensitivity to cephalosporins, received graded oral challenges (10 %, followed by the remaining 90 % reactions (one to cefprozil and the other to cephalexin).

Conclusion:
The risk of reaction is low in children with a history of suspected hypersensitivity to cephalosporins. Oral challenges appear to be safe in this population, and may be the best tool available to diagnose cephalosporin hypersensitivity. Larger studies are needed to support these results.

Background:
The impact of breastfeeding on asthma and allergy development is controversial. We aimed to characterize the association of breastfeeding with childhood wheeze, atopy and atopic dermatitis in the first year of life. Methods: We studied 2587 infants with complete breastfeeding data from the Canadian Healthy Infant Longitudinal Development (CHILD) birth cohort. Infant diet and wheezing episodes were reported by mothers at 3, 6, and 12 months. Atopy was determined by skin testing and atopic dermatitis was diagnosed at 12 months. Breastfeeding was classified as exclusive (human milk only), partial (supplemented with formula, other beverages or solid foods) or none. Results: Breastfeeding rates were 82 % at 3 months (52 % exclusive, 30 % partial), 74 % at 6 months (13 % exclusive, 61 % partial), and 46 % at 12 months (partial). In their first year, 21 % of infants experienced ≥ 1 wheezing episode, 14 % were sensitized to ≥1 allergen, and 12 % were diagnosed with atopic dermatitis. Breastfeeding rates were lower among younger mothers, First Nations women, and those who smoked or did not have a postsecondary degree. Independent of these maternal characteristics, increasing duration and intensity of breastfeeding were associated with a reduced risk of wheezing: adjusted odds ratio ( Background: Inflammation is a key mechanism of asthma pathogenesis [1]. The bronchial epithelium acts as a barrier involved in innate and adaptive immunity through secretion of inflammatory mediators [2]. Interleukin (IL) 33 is an alarmin cytokine released by airway epithelial cells [3] that has been identified as a gene of susceptibility in asthma in several studies [4][5][6], as well as being a potential severity biomarker of asthma [7]. IL33 gene expression was increased in epithelial cells from asthmatic individuals [8]. However, less is known about the epigenetic regulation of IL33 particularly in severe asthma. In this context, we aimed to characterize DNA methylation (DNA-me) and expression signatures of IL33 in epithelial cells obtained from mild and severe asthmatic individuals. Methods: A total of 21 bronchial epithelial cell (BEC) lines from asthmatics individuals (mild n = 7; severe n = 4) and control individuals (n = 10) were used for DNA and mRNA extraction. DNA-me was measured by bis-pyrosequencing and mRNA level was assessed by qRT-PCR. Student t tests were performed to analyze the association between DNA-me and asthma severity (significant for Δβ > 5 % and p > 0.05).
Pearson correlations were used to analyze the correlation between DNA-me and mRNA level. We sought to examine the role of NRF2, a critical transcription factor involved in mediating the endogenous antioxidant response, in bronchial epithelial cells following OD exposure. We hypothesized that OD exposure would increase NRF2 activity and antioxidant production in human bronchial epithelial cells.

Methods:
A human bronchial epithelial cell line (BEAS-2B) was stimulated for 24 h with 100 µg OD. Supernatant was retained for evaluation of IL-8 by ELISA. qPCR was performed for NRF2-dependent and NRF2independent antioxidant genes. NRF2 nuclear translocation was quantified at various time points using an NRF2 luciferase reporter assay and by immunofluorescence. Results: OD exposure resulted in an increase of IL-8 release. mRNA expression levels of NRF2-dependent antioxidant genes HO-1, NQO1 and GCLM, but not of NRF2-independent antioxidant genes SOD 1, and catalase were increased following OD exposure compared to control cells. OD exposure induced a time and dose-dependent increase in luminescence indicating NRF2 nuclear translocation, a result confirmed by quantification of NRF2 nuclear localization by immunofluoresence.
Conclusions: OD exposure induces IL-8 release, NRF2 nuclear translocation, and upregulation of antioxidant gene expression in BEAS-2B cells. These results suggest a dual role for bronchial epithelial cells in mediating neutrophil recruitment as the endogenous antioxidant response. We demonstrated that the endogenous oxidative properties of OD are specific to NRF2 and that NRF2 is a critical mediator of ODinduced oxidative stress in bronchial epithelial cells.  [1]. Maternal psychosocial distress is associated with excess prenatal stress hormones [2] and reduction in the quality of maternal-infant interaction [3], which may affect biomarkers of infant immunity such as interleukin (IL) levels and predispose the growing child to rash [4,5]. This study will: (1) describe the association between perinatal distress and infant interleukins at 3 months of age, (2) describe the association of interleukins and atopic dermatitis (rash), and (3) build a best fit model from the identified associations in (1) and (2). Methods: 120 women reported distress levels during pregnancy and at 3 months postpartum. Venous blood was collected from their 3-month-old infants to assess plasma interleukin levels. Maternal-child interaction was measured 6 months postpartum with the nursing child assessment teaching scale. Presence and number of skin areas affected by rash were assessed via parent report at 18 months. Correlation and multiple regression analyses identified the best fit model for rash using forward stepwise regression. Results: Prenatal depression (r = −0.23, p = 0.01) and stressful life events pre-and post-natally (r = 0.27, p = 0.00) were associated with IL2p70. Pre-and post-natal anxiety were associated with IL8 (r = −0.28, p = 0.02) and IL4 (r = −0.24, p = 0.04). IL10 was associated with child skin rash (r = −0.25, p = 0.01) at 18 months. 20 % of the variance in childhood rash at 18 months was explained by the model (Table 11). Conclusions: Perinatal distress is associated with elevated infant ILs. Demographic variables (maternal age, education), IL10, perinatal stressful life events (e.g. separation/divorce, family death) and maternal-infant interaction best predicted skin rash in 18-month-old infants.

The effects of perinatal distress, immune biomarkers and mother-infant interaction quality on childhood atopic dermatitis (rash) at 18 months
We will now evaluate how maternal-child interaction moderates associations between both (1) perinatal distress and (2) immune biomarkers, and atopic dermatitis in children at 18 months. Background: Previous studies have demonstrated a link between early-life exposure to secondhand tobacco smoke (SHS) and allergenspecific immunoglobulin E (IgE) mediated sensitization to food allergens. However, it is unclear whether this association extends to clinical symptoms following food consumption [1]. We aimed to determine if Background: Allergic rhinitis (AR) is an IgE-mediated inflammatory condition of the nasal mucosa induced after allergen exposure [1]. Cat allergy affects 10-15 % of patients with allergic rhinitis and/or asthma [2]. A novel immunotherapy, Cat-Synthetic Peptide Immuno-Regulatory Epitopes (Cat-SPIRE), composed of seven synthetic peptide T-cell epitopes, acts on allergen-specific T-cells to induce subsequent clinical tolerance to cat allergen. Methods: In this study, 19 participants with a clinical history of cat allergies with significant cat exposure received Cat-SPIRE (4 × 6 nmol intradermal injection, 1 dose every 4 weeks). Clinical symptoms were Fig. 6 LC-MS/MS chromatogram of a 12 C-dimethylaminophenacyllabeled metabolites and corresponding 13 C-internal standards and b 12 C-dansyl-labeled metabolites and corresponding 13 C-internal standards, in control urine assessed by Nasal Allergen Challenge (NAC) [3]. Whole blood was collected into PAXgene tubes at baseline and post NAC (1, 2, and 6 h), before and 1 month post treatment. 770 immune genes in the PAXgene blood lysates at 6 h post NAC were profiled using the nanoString nCounter PanCancer Immune Profiling Panel. After normalization, a statistical comparison of pre-versus post-treatment changes was performed and an enrichment pathway analysis undertaken (Enrichr). Results: 70 immune genes were significantly down regulated compared to pre-treatment at the 6 h post NAC time point (FDR < 10 %). These genes were associated with T-cell effector pathways, particularly canonical Th2 cytokines such as IL-4, IL-5, IL-3, IL-6 and TSLP. These changes were accompanied by significant post-versus pre-treatment reductions in clinical symptoms, Total Nasal Symptom Score and Peak Nasal Inspiratory Flow. Conclusion: Following Cat-SPIRE treatment, systemic immune pathways of T-cell effectors were changed in peripheral blood of cat exposed, allergic individuals. The effect on these pathways provides insight towards the mechanism by which Cat-SPIRE induces immune tolerance. Whole blood immune transcriptome profiling in larger sample sizes and/or various time points after NAC may provide biomarkers or tools to discover the immune response or tolerance mechanism.
Background: Children of low-income families access more urgent care and less preventive care for asthma [1]. Children with a respiratory disease from low-income families also experience a lower quality of life [2,3]. Our previous online peer/professional support programs have improved children's asthma and allergy self-management skills, and decreased loneliness [4][5][6][7][8]. However, in our previous programs, participants' have come from high-income families [4][5][6][7][8]. Consequently, the objective of this research was to determine low-income participants' perceptions of the impact of the support intervention, the factors influencing these impacts, their satisfaction with the intervention, and recommended changes. Methods: Peer and professional mentors who lived with asthma and allergies and had experience with vulnerable families were recruited and trained to facilitate sessions. Participants in the cohort included 16 children aged 7-11, and adolescents 12-17 from across Canada. Children were provided with internet services for the program duration, chromebooks, and headsets/microphones that they could keep. Eight weekly meetings were offered on the Internet using GoToMeeting ® ; a secure online meeting platform. Quantitative data on health-related outcomes were elicited by standardized measures administered preand post-intervention. Qualitative data on the intervention processes was also collected. Results: Preliminary analysis post-intervention, has shown an increase in coping skills and perceived support, and reduced loneliness after participating in the online sessions. Even more significant, in comparison to online programs with higher income families, was the increased understanding and appreciation of asthma/allergy triggers in participants. They also learned new ways to manage their triggers. Many parents reported that their children were less resistant to taking their medication and had a higher adherence to medication post-intervention due to an increased understanding about their medications and use. Conclusion: It is evident that online-peer-support programs for lower income families require a different focus compared to programs developed for higher income families, as they face different challenges and have different needs.

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Epigenetic association of PSORS1C1 and asthma in the Saguenay-Lac-Saint-Jean asthma study Background: Asthma is a chronic respiratory disease involving genetic and environmental interactions [1,2]. More than 300 genes have been associated with asthma or related phenotypes, and the number continues to increase [3]. The associated common SNPs represent a small part of the genetic component and the exact nature of the causal genetic variants remains to be discovered [4]. One reason for this "missing heritability" is that many genetic factors act primarily through complex mechanisms involving interactions with other genes and environmental factors and/or epigenetic mechanisms [5].
We have shown that genetic variants related to asthma can be mechanistically studied using epigenetic and functional genomic assessment of individual variants [6,7]. Therefore, we plan to focus on IL33 pathway following the previous study demonstrating a correlation between methylation signature, expression and asthma in bronchial epithelial cells. Method: DNA methylation (Δβ) has been measured with an epigenome wide association study (EWAS) using Illumina Allergy Asthma Clin Immunol 2016, 12(Suppl 1):22 HumanMethylation450K arrays among 69 asthmatic individuals and 91 controls. Data were extracted for 21,720 genes including 26 in the pathway of IL33 and the association with asthma was assessed by logistic regression using methylation percentage, asthma phenotype, sex, age, IgE level, smoking status and eosinophils, lymphocytes, monocytes, neutrophils, and basophils counts as covariates. Batch effect was corrected for the analysis.
Conclusion: This study shows differences in methylation marks between asthmatic individuals and non-asthmatic non-allergic controls for four genes (CLSTN2, CDSN, PSORS1C1, CCDC57). Interestingly, PSORS1C1, a susceptibility gene for psoriasis, has already been associated with asthma in a genome wide association study in Latino children [8]. The pyrosequencing of this gene will allow us to confirm this association.

IL-33 induces cytokine and chemokine production in human mast cells
Stephanie Background: Sterile inflammation is a major mechanism by which tissue damage occurs throughout the body and is also a major determinant of disease progression. It is initiated after sterile physical damage has occurred in local tissues, but can also be initiated in a number of inflammatory disorders, such as asthma and arthritis. Many different cell types appear to be involved in sterile inflammation, but the role of mast cells has been of particular interest. Mast cells are innate immune sentinel cells that reside in many tissues throughout the body that synthesize and secrete many pro-and anti-inflammatory mediators. The alarmin IL-33 is an important component of the sterile inflammatory process and has been shown to directly activate populations of mast cells [1,2]. Furthermore, IL-33 has been implicated as a potential early-life predictor of childhood asthma and allergy [3]. Therefore, the purpose of this study was to determine the cytokine and chemokine profile of human mast cells activated with IL-33. Methods: Cord blood-derived mast cells (CBMCs) were activated for 24 h with IL-33 at a concentration of 30 ng/mL. To analyse protein production from CBMCs, supernatants were collected and a Luminex assay was conducted to analyse the concentration of 29 cytokines and chemokines. Additionally, gene expression data was analyzed through qPCR to determine gene expression changes upon activation of mast cells with IL-33. Results: It was found that after IL-33 activation, CBMCs had a statistically significant increase in production of IL-13, but not other T H 2-related cytokines such as IL-4. There was no increase in production of T H 1-related cytokines, such as IFNγ and IL-12. Production of the cytokines VEGF and GM-CSF were also statistically significantly increased after IL-33 activation of CBMCs.

Conclusions:
In conclusion, IL-33 activation of human mast cells results in the production of cytokines supportive of T H 2-driven responses and tissue regeneration.  Fig. 7 CMP-specific IgA to casein (a) and ALA (c) increased significantly from pre-therapy to 300 mL challenge with CM (unpaired t test, **P < 0.01 and *P < 0.05 respectively for casein and ALA). Casein (d), BLG (e), and ALA (f) specific IgG4 increased significantly baseline at the completion of OIT (unpaired t test, *p < 0.05, ***p < 0.001, ***p < 0.001 respectively for casein, BLG, and ALA)