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Allergy, Asthma and Clinical Immunology 2014, Volume 10 Suppl 2
http://www.aacijournal.com/supplements/10/S2
ALLERGY, ASTHMA & CLINICAL
IMMUNOLOGY
MEETING ABSTRACTS
Open Access
Canadian Society of Allergy and Clinical
Immunology and AllerGen Abstracts 2014
Ottawa, ON, Canada. 23-26 October 2014
Published: 18 December 2014
These abstracts are available online at http://www.aacijournal.com/supplements/10/S2
MEETING ABSTRACT
A1
An overview of the advanced data collection techniques in the
environmental exposure unit (EEU)
Daniel E Adams1*, Barnaby Hobsbawn1, Terry JB Walker1, Lisa M Steacy1,
Anne K Ellis1,2
1
Allergy Research Unit, Kingston General Hospital, Ontario, Canada;
2
Department of Medicine, Queen’s University, Kingston, Ontario, Canada
Allergy, Asthma and Clinical Immunology 2014, 10(Suppl 2):A1
Background: Capturing symptom data for large studies (≥60 participants)
in ≤30 minutes is hard to achieve using manual data entry without
substantial costs and resources. This challenge is highlighted if the data
are needed to make real-time clinical decisions. The 140 participant
capacity of the Environmental Exposure Unit (EEU) requires an advanced
method to process symptom data.
Methods: Advanced scanning technologies are used with a customized
two-step quality assurance data collection process. Optical Mark
Recognition (OMR) and Optical Character Recognition (OCR) capture data
from paper symptom diary cards into the EEU’s clinical data management
system (CDMS). A template is configured to read the static diary card
format and assign zones where the specific diary card data are located.
The user configures field requirements within the zones to validate data
captured. Cards that do not meet a predefined confidence level for any
particular zone will be flagged for a quality check. The quality checking
process involves one user visually confirming all data captured and a
second user inputting all values from the card to ensure accuracy. Invalid
data are rejected from the batch and returned to the participant for
correction. Corrected cards are scanned again and all valid data are
transferred into the CDMS.
Results: Capturing data using the advanced scanning system allows a
team of 3 to process 120 symptom diary cards containing 9 symptoms
and 3 peak nasal inspiratory flow (PNIF) scores, with 99.9% accuracy in
<15 minutes. In comparison, manual data entry would require a team of
8 to achieve similar results.
Conclusions: For large studies with short assessment periods, the
scanning system utilized in the EEU is significantly more efficient in all
aspects of data acquisition than manual entry. This ability to
accommodate large studies in an accurate, efficient manner leads to an
ideal setting for the conduct of time-sensitive clinical trials.
A2
Epinephrine auto injector administration by parents or patients for
anaphylaxis during supervised oral food challenges and
assessment of confidence
Ingrid Baerg*, Angela Alexander, Tiffany Wong, Timothy Teoh, Kyla Hildebrand,
Sara Leo, Joanne Yeung, John Dean, Edmond Chan
Division of Allergy and Immunology, Department of Pediatrics, BC Children’s
Hospital, University of British Columbia, Vancouver, BC, V6H 3V4, Canada
Background: Barriers to administering epinephrine auto injectors include
failure to recognize signs and symptoms of anaphylaxis, administering oral
antihistamines or asthma inhalers due to lack of education, failing to
administer epinephrine correctly, fear of giving a needle, auto injector
misplaced, and past experiences with spontaneous recovery. The aim of
this study is to assess the impact of supervised auto injector administration
by parents/patients on confidence, knowledge and skill for future
treatment of severe allergic reactions.
Methods: Patients with confirmed IgE-mediated food allergy at BC
Children’s Hospital (2013-14), aged 2-17 years undergoing a physician
supervised oral food challenge were approached and participation was
voluntary. A pre- challenge questionnaire on patient and caregiver
background information, confidence in recognizing a severe allergic
reaction, and knowledge/skill in using an epinephrine auto-injector was
completed by each participant. If an auto injector was deployed during the
challenge, a post encounter questionnaire was administered to
participants and practitioners collecting similar variables and qualitative
data.
Results: There have been 39 participants in this ongoing study. Mean age
was 7.3 years (SD 4.3). 87% of parents were university educated, 26%
health professionals, and 64% reported English as their first language.
Parents ranked their child’s food allergy as severe (2.74/3.00, 95%CI, 2.393.10), but had only experienced using an auto injector 0.28 (95%CI, 0.100.46) times in the past. Confidence levels with auto injector use were
3.31/5.00 (95%CI,2.91-3.71) and skill levels 2.51/5.00 (95%CI,2.13-2.90).
Parents who were health professionals had almost twice as much
confidence and skill as non-health professionals (p<0.05). There was no
statistically significant difference in confidence based on the number of
times participants had experienced a severe reaction or used an auto
injector in the community. Post challenge, 4 participants have required
epinephrine, all administered by a parent.
Conclusions: Our data suggest a moderate level of confidence but
suboptimal skills in epinephrine auto injector use, influenced by whether
parents are health professionals.
© 2014 various authors, licensee BioMed Central Ltd. All articles published in this supplement are distributed under the terms of the
Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and
reproduction in any medium, provided the original work is properly cited.
A3
C-CARE: comparing three years of anaphylaxis in children treated at the
Montreal Children’s Hospital
Sarah De Schryver1†, Elana Hochstadter2, Ann Clarke3, Sebastien LaVieille4,
Reza Alizadehfar1, Alizee Dery5, Christopher Mill6, Harley Eisman2,
Moshe Ben-Shoshan1*†
1
Division of Allergy and Clinical Immunology, Department of Pediatrics,
Montreal Children’s Hospital, McGill University Health Center, Montreal, QC,
Canada; 2Emergency Department, Department of Pediatrics, Montreal
Children’s Hospital, McGill University Health Center, Montreal, QC, Canada;
3
Division of Rheumatology, Department of Medicine, University of Calgary,
Calgary, AB, Canada; 4Food Directorate, Health Canada, Ottawa, ON, Canada;
5
Department of Experimental Medicine, McGill University, Montreal, QC,
Canada; 6Department of Public Health, University of British Columbia,
Vancouver, BC, Canada
Background: The Cross-Canada Anaphylaxis Registry (C-CARE) aims to
examine burden, triggers, management and temporal trends in
anaphylaxis.
Methods: Over a three-year period (April 2011 to April 2014), data were
collected on anaphylaxis cases at the Montreal Children’s Hospital
emergency department (ED). Cases were recruited either prospectively or
identified retrospectively based on chart review through ICD10 codes
related to anaphylaxis. Logistic regressions were conducted to determine
the association between sociodemographic and clinical characteristics
and development of severe reactions as well as epinephrine use.
Results: Among 624 cases the median age was 5.7 years (IQR 2.4-11.7) and
the majority (56.6%) were males. The percentage of anaphylaxis among all
ED visits increased from 0.22% (95% CI 0.18%, 0.24%) in 2011 to 0.3% (95%
CI 0.25%, 0.33%) in 2014, yielding a difference of 0.08% (95%CI, 0.03%,
0.13%). The major trigger was food (81.4%), mainly peanut and tree-nut.
Most cases were moderate (70.2%) (breathing difficulties, stridor, diarrhea,
crampy abdominal pain, recurrent vomiting).
Of all reactions 28.7% were not administered epinephrine. Almost 95%
were prescribed or had an epinephrine auto-injector (71.6% Epipen,
22.7% Allerject).
Factors associated with severe reactions included history of peanut
allergy, asthma and steroid treatment in ED. (Table 1).
Management of anaphylaxis with at least one dose of epinephrine was
associated with known food allergy and use of steroids in ED.
Administration of two or more epinephrine doses in ED was less likely in
those who received epinephrine outside ED and more likely with severe
reactions, reactions triggered by tree-nut and in those treated with
steroids in ED.
Conclusions: The percentage of anaphylaxis cases among all ED visits
increased by almost 40% over a three-year period. Prompt use of
Table 1(abstract A3) Logistic regressions assessing severe
reactions and use of epinephrine
Severe reactions
Variable
OR, 95%CI
Asthma
2.3 (1. 5)
Use of steroids in ED
2.5 (1.2, 5.2)
Peanut allergy
2.2 (1, 4.9)
No use of epinephrine
0.2 (0.1, 0.4)
Known food allergy
0.3 (0.2, 0.5)
Use of more than 2 epinephrine in ED
Use of epinephrine outside
0.06 (0.01, 0.6)
9.0 (2.6, 31)
Severe reaction
16.8 (4.7, 61)
Tree-nut allergy
5.4 (1.2, 24)
Page 2 of 22
epinephrine may prevent use of subsequent multiple doses of
epinephrine in ED. Reactions triggered by tree-nut are more prone to
require treatment with multiple doses of epinephrine.
Acknowledgment: This project was supported by AllerGEN, Health
Canada and Sanofi
A5
Xolair® (omalizumab) enrollment in a tertiary care allergy and asthma
clinic in Canada
Jodi Cameron1*, Jennifer Forgie1, Alicia Ring1, Stephanie Santucci1,
Caroline Rizk2, Hoang Pham3, John O’Quinn1, William H Yang1,3
1
Allergy and Asthma Research Centre, Ottawa, ON, Canada; 2Department of
Clinical Immunology and Allergy, McGill University, Montreal, Canada;
3
University of Ottawa Medical School, Ottawa, ON, Canada
Background: Xolair® (omalizumab) has been approved in Canada since
2004 for the treatment of moderate to severe persistent allergic asthma
in patients 12 years of age. The use of omalizumab in severe persistent
allergic asthma may lead to decrease health care utilization through
emergency room (ER) visits, hospitalizations, visits to health care
providers, as well as, decrease the use of corticosteroids and improve the
overall quality of life (QoL).
Methods: Data collected from patient enrollment and QoL questionnaires
completed at specific intervals during treatment with omalizumab at our
large tertiary care clinic from 2004 to 2014 was analyzed.
Results: A steady number of patients were enrolled each year since 2004,
showing its greatest increase in enrollment numbers since 2012. Our data
indicates that the majority of patients improved with significantly less
asthma exacerbation, less ER visits and hospitalizations, less use of
inhaled and oral corticosteroids and better QoL.
Conclusion: Omalizumab is effective in the treatment of moderate and
severe allergic asthma. It improves QoL and reduces asthma exacerbations,
ER visits and hospitalizations, and use of inhaled and oral corticosteroids.
A6
Raisin allergy in an 8 year old patient
S Chibuluzo1*, T Pitt2
1
St. George’s University, School of Medicine, Grenada, West Indies; 2Humber
River Hospital, Toronto, Ontario, Canada
Introduction: Raisin allergy is uncommon despite worldwide cultivation of
grapes, which belong to the Vitis vinifera species of the Vitaceae family.
There have only been rare reports of anaphylaxis in adults related to the
consumption of grapes, wine or other grape products, mostly in Europe
[1-4]. In children, even fewer case reports to grape exist [5]. We report an
8-year-old patient who developed itching of the mouth and nausea within
a few minutes of ingestion of fresh raisin on repeated occasions.
Interestingly, he tolerates grapes.
Methods: Skin prick testing (via prick-by-prick method) to fresh seedless
raisin, birch pollen, a mixture of trees, grass, and ragweed was performed
on the patient. Skin prick testing to fresh seedless raisin (via prick-byprick method) was also performed on a non-atopic healthy control.
Results: Skin testing was positive to fresh seedless raisins (~5 mm) in our
8-year-old patient and negative in the healthy control. The patient was
advised to avoid raisins and to carry an Epinephrine auto-injector. He was
encouraged to continue to consume fresh grapes.
Conclusions: We report one of the first cases of presumed allergy to fresh
raisin, in the absence of pollen food syndrome, in a North American patient
who currently tolerates fresh grapes. Further research is required to
determine the etiology and prevalence of this allergy. We propose that a
chemical component used in the processing of raisins may be responsible
for this allergy.
Consent: Written informed consent was obtained from the patient for
publication of this abstract and any accompanying images. A copy of the
written consent is available for review by the Editor of this journal.
References
1. Alcoceba Borràs E, Botey Faraudo E, Gaig Jané P, Bartolomé Zavala B:
Alcohol-induced anaphylaxis to grapes. Allergol Immunopathol (Madr)
2007, 35(4):159-61.
2. Kalogeromitros DC, Makris MP, Gregoriou SG, Mousatou VG, Lyris NG,
Tarassi KE, Papasteriades CA: Grape anaphylaxis: a study of 11 adult onset
cases. Allergy Asthma Proc 2005, 26(1):53-8.
3. Caiaffa MF, Tursi A, Macchia L: Grape anaphylaxis. J Investig Allergol Clin
Immunol 2003, 13(3):211-2.
4. Senna G, Mistrello G, Roncarolo D, Crivellaro M, Bonadonna P, Schiappoli M,
Passalacqua G: Exercise-induced anaphylaxis to grape. Allergy 2001,
56(12):1235-6.
5. Cardinale F, Berardi M, Chinellato I, Damiani E, Nettis E: A child with anaphylaxis
to grapes without reaction to grape seed oil. Allergy 2010, 65(6):800-1.
A8
Omalizumab is effective in the treatment of difficult-to-treat chronic
spontaneous urticaria
Jennifer Forgie1*, Stephanie Santucci1, Diana Pham1, Genevieve Gavigan2,
Melanie Pratt2, Simone Fahim2, John O’Quinn1, William H. Yang1,3
1
Allergy and Asthma Research Centre, Ottawa, ON, Canada; 2Division of
Dermatology, University of Ottawa, ON, Canada; 3University of Ottawa
Medical School, Ottawa, ON, Canada
Background: Chronic spontaneous urticaria (CSU) is a condition, lasting at
least 6 months, where patients experience frequent episodes of red, itchy
hives and/or angioedema with no apparent external trigger. For
approximately 30-50% of patients this condition can resolve spontaneously
but has been known to persist for years. CSU can have a major impact on a
patient’s quality of life as it can affect daily activities, sleep, emotional
wellbeing and social interactions. In March 2014, omalizumab was approved
in Europe and eight other countries for the treatment of CSU in patients
with inadequate response to H1-antihistamines at approved doses. However,
as yet there is no approved indication for its use in CSU in Canada and the
US. We report on the effectiveness of omalizumab as a treatment option for
difficult-to-treat CSU in our clinic.
Methods: After receiving a diagnosis of CSU with inadequate response to
H1-antihistamines, and oral prednisone, patients completed a quality of life
(QoL) questionnaire prior to beginning treatment with omalizumab. Patients
were requested to complete the QoL questionnaires every two weeks
throughout the treatment and, in addition, were monitored closely for
clinical response.
Results: A total of 10 patients, who started on omalizumab for CSU were
evaluated. All were taking H1-antihistamines prior to treatment with 8 out of
the 10 patients able to decrease or stop the use of H1- antihistamines after
the 3rd dose of omalizumab.
The results of the questionnaires indicated a 15% improvement in QoL with
an accompanying 18% decrease in the symptom score. Of the 10 patients,
9 indicated an overall improvement in their symptoms while only 6 had an
overall improvement in their QoL.
Conclusion: Omalizumab is an effective therapy in difficult-to-treat CSU
in our tertiary community based allergy and asthma clinic.
Page 3 of 22
by small erythematous papules, and diffuse general edema affecting the
face, and upper and lower extremities. The rash developed over a few
hours and was associated with shortness of breath, chills, and dysuria. The
rash persisted for 14 days at which point a 5 day course of prednisone was
prescribed which led to improvement. Imatinib (generic) had been started
3 months earlier; was temporarily interrupted for 2-3 weeks after 1 month;
then restarted 2 months prior to onset of the rash. On exam there was
pitting edema to lower 2/3 anterior tibia, erythematous papular
generalized excoriated rash with xerosis. No blistering, sloughing of skin,
target lesions, or pustules. CBC normal, creatinine unremarkable and urine
negative for eosinophils.
Imatinib (generic) was discontinued and brand name Gleevec® was started.
Two weeks later the rash recurred. Eosinophil count increased to 2.84 ×
109/L. A skin biopsy was arranged which showed parakeratosis containing
neutrophils with formation of intracorneal pustules, in keeping with AGEP.
Gleevec® was discontinued and Nilotinib 400mg PO BID was substituted
2 weeks later. The rash resolved and eosinophilia decreased over the next
month and has not recurred.
Conclusion: AGEP is a rare complication of imatinib therapy, and should
be considered in patients who present with atypical rash on imatinib.
A10
Type-III hereditary angioedema resolved by surgery
Lisa W Fu*, Fanny Silviu-Dan
Department of Medicine, McGill University, Montreal, QC, Canada
A9
Acute generalized exanthematous pustulosis from imatinib
Lisa W Fu1*, Amanda Jagdis2, Jason K Lee2
1
Department of Medicine, McGill University, Montreal, QC, Canada; 2Division
of Clinical Immunology and Allergy, Department of Medicine, University of
Toronto, Toronto, ON, Canada
Background: In classic hereditary angioedema, inadequate C1-inhibitor (C1INH) failing to restrict factor-XII activity leads to increased production of
bradykinin, a potent vasodilator and mediator of angioedema. Hereditary
angioedema with normal C1-INH (Type-III) manifests with sporadic recurrent
angioedema but normal C1-INH concentration and activity. Here, bradykinin
accumulation appears dependent on Factor XII and Factor XII gene
mutations are sometimes found. Type-III angioedema affects almost
exclusively females, worse in pregnancy, on oral contraceptives as estrogen
may increase total bradykinin. Diagnosis is difficult given the clinical
heterogeneity and lack of biochemical indicators. Treatment carries various
risks when given for prophylaxis and a challenge for timely administration in
an acute crisis. This is the first case report in the literature of a woman
whose repeated angioedema episodes resolved with surgical resection of an
ovarian cyst.
Case presentation: A 41-year-old woman presented with recurrent severe
episodes of face, tongue, and throat swelling occurring under variable
circumstances and without clear triggers. C4 and C1-INH level and function
were normal. Many years after symptom onset, a large ovarian cyst was
diagnosed. Measured estrogen level was high. Once the cyst was surgically
removed, no further angioedema occurred. Recently a son developed
vibratory angioedema, a rare form of physical urticaria. A first cousin and
niece in Italy have angioedema. Genome exome sequencing is underway
to determine if specific genetic variations are contributing to this family
cluster of angioedema.
Conclusion: Resolution of Type-III hereditary angioedema manifestations
by surgery upon diagnosing ovarian cysts as the source of estrogen excess
adds a new facet to the evaluation and therapy for this condition. This
family cluster of angioedema proposes an interesting question of genetic
variations predisposing to angioedema.
Background: Acute generalized exanthematous pustulosis (AGEP) is rare
cutaneous drug reaction involving drug-specific T lymphocytes and
neutrophilic inflammation. Imatinib is a tyrosine kinase inhibitor used widely
in treatment of chronic myeloid leukemia (CML). Rash is a common side
effect of imatinib, occurring in up to 30% of patients. However, there are
only two case reports to date describing AGEP secondary to imatinib.
Case presentation: A 71-year-old woman known for chronic myeloid
leukemia presented with acute onset of generalized pruritus, accompanied
A11
Growth factors regulate proteinase activated receptor – 2 (PAR-2) on
airway epithelium
Vivek Gandhi*, Drew Nahirney, Harissios Vliagoftis
Pulmonary Research Group, Department of Medicine, University of Alberta,
Edmonton, Alberta, T6G 2S2, Canada
Background: Many aeroallergens activate PAR-2 receptors on the airway
epithelium. We have shown that PAR-2 activation participates in allergic
sensitization and allergic airway inflammation in animal models of asthma.
Moreover, PAR-2 is upregulated on the airway epithelium of asthmatics, but
the mechanisms and factors responsible are unknown. As asthmatic airways
are under various types of physiological stress, we hypothesized that cellular
stress upregulates PAR-2 on airway epithelium and this upregulation is
functional.
Methods: Human bronchial epithelial cells were cultured with or without
growth factors for 24hrs/48hrs and PAR-2 mRNA levels were studied by qRTPCR. PAR-2 functions were assessed by measuring PAR-2-mediated calcium
release from intracellular stores into the cytoplasm and IL-8 release in
supernatants.
Results: We have previously shown that growth factor deprivation, but not
oxidative stress or hypoxia, significantly upregulates PAR-2 mRNA in normal
bronchial epithelial cells. We now show that growth factor deprivation also
induces PAR-2 upregulation in airway epithelial cells from asthmatic
individuals (2.1 +/- 0.1 fold, n=2); this upregulation was reversible upon
growth factor addition. We omitted individual growth factor from the culture
media. Omission of only insulin caused significant PAR-2 mRNA upregulation
(1.6 +/- 0.1 fold, n=4). In addition, supplementation of stressed cells with
insulin reversed the growth factor deprivation-induced PAR-2 upregulation
(n=3). PAR-2-mediated activation of stressed cells induced more calcium
release from internal stores and higher release of the inflammatory mediator
IL-8 (2.1 +/- 0.2 fold, n=6) compared to non-stressed cells.
Conclusions: Growth factor deficiency could be the driving force for PAR-2
upregulation in asthmatic airways. Insulin may be one of the growth factors
that regulate PAR-2 transcription. In conditions of growth factor deprivation,
PAR-2 upregulation may lead to increased activation of airway epithelial
cells resulting in the higher release of pro-inflammatory mediators.
Therefore, understanding PAR-2 regulation may allow the development of
new anti-inflammatory approaches for airways diseases.
A12
Lessons learned from the development of a school age food allergy
education program
Cathy A Gillespie1*, Nancy L Ross1, Allan B Becker1,2
1
Children’s Allergy and Asthma Education Centre, Health Sciences Centre,
Winnipeg, Manitoba, Canada; 2University of Manitoba, Winnipeg, Manitoba,
Canada
Background: Education is required to effectively manage food allergy. In
young children, parents are the primary managers. Once children enter
school, a shift should begin towards a shared care model with children
beginning to take on more responsibility. We previously developed a food
allergy education program for parents of pre-school children and now
have developed a new program for school age children and their parents
building on our experience with the pre-school program.
Method: Development steps included: synthesizing knowledge gained
from expert advice, a literature review and parents; creation of program
objectives, content, teaching tools and facilitator notes; sharing a program
draft with experts for feedback; piloting the revised program; making
further revisions during the pilot.
Results: The pilot phase included 6 groups and 22 families (37 parents, 23
children). Children liked the activity-based sessions and benefited from
meeting with peers. Parents appreciated the learning opportunity for
children. Some parents suggested a less structured format for the adult
sessions. Many parents highly valued the peer-to-peer discussions. Parents
were interested in the practical aspects of dealing with other people,
educating their child, avoiding risk and recognizing and treating reactions.
Conclusions: In our experience, finding the right approach to food allergy
education for school age parents is more complex than for parents of young
children or even asthma education for school age parents. Most school age
parents have lived with food allergy for a few years and have basic
knowledge. However, at this stage their child’s expanding world and
relationships present new issues for which many parents value practical
advice from others living with the experience.
Health care providers should consider the importance of both professional
and peer input into education for this population to ensure parents have
Page 4 of 22
correct current knowledge and practical skills to help them support and
educate their child.
Acknowledgements: Program development funding provided by
Anaphylaxis Canada
A13
SCIg vs. IVIg: let’s give patients the choice!
Kathryn K Samaan1, Marie-Claude RN Levasseur1, Hélène Decaluwe1,
Claire St-Cyr1, Hugo Chapdelaine2, Anne Des Roches1, Elie Haddad1,3*
1
Department of Pediatrics, University of Montreal, Centre Hospitalier
Universitaire Sainte-Justine, Montreal, Canada; 2Department of Allergy,
University of Montreal, Centre Hospitalier Universitaire de Montreal, Montreal,
Canada; 3Department of Microbiology and Immunology, University of
Montreal, Centre Hospitalier Universitaire Sainte-Justine, Montreal, Canada
Purpose: Criteria governing the choice between intravenous (IV) and
subcutaneous (SC) routes for immunoglobulin (Ig) substitution are not well
defined. We assessed the consequences of giving the choice to the patient.
Methods: We retrospectively analyzed 143 patients with primary
immunodeficiency, followed in a single center, which were offered the
choice of IVIg or SCIg. We analyzed the route more frequently chosen, and
the consequences on compliance. In a first cohort (n = 51, average follow
up 52 months), patients already on IVIg were offered the choice to stay on
IVIg or to switch to SCIg (switch cohort). In a second cohort (n = 92, average
follow up 11 months), newly diagnosed patients were offered the choice
between IVIg and SCIg before the first injection (new cohort).
Results: In the switch cohort, 50/51 patients chose to switch to SCIg. Of
these, 90% remained on SCIg. In the new cohort, 44/92 patients chose SCIg,
of which 95% remained on SCIg. Among the 48 patients who chose IVIg,
73% switched to SCIg. Compliance issues were observed in only 10 patients.
Conclusion: Giving patients the choice of treatment modality is a safe
strategy in terms of compliance. Home-based SCIg is much more frequently
chosen than hospital-based IVIg. Given the equal efficacy and safety
between hospital-based IVIg and home-based SCIg, we believe that all
patients should be given the choice regardless of physician’s belief of
“idealness” of the candidate.
A14
Use of tiotropium bromide in an adolescent with adrenal suppression
secondary to inhaled mometasone furoate
Mariam Hanna1*, Douglas P Mack2
1
Dept of Clinical Immunology and Allergy, McMaster University, Hamilton,
ON, Canada; 2Dept of Pediatrics, McMaster University, Hamilton, ON, Canada
Introduction: With emerging cases of adrenal suppression being reported
in pediatric patients, finding appropriate steroid sparing agents is of
clinical importance. Tiotropium bromide (TB), a long-acting anticholinergic,
has recently been investigated in adults as a steroid-sparing agent in
asthma step-up therapy. We report the first case of tiotropium bromide
(TB) used as a step-up steroid sparing agent in an adolescent with adrenal
suppression secondary to inhaled mometasone furoate (MF).
Case description: A sixteen-year-old female with asthma and allergic
rhinitis treated MF/formoterol fumarate 800/ 20 mcg per day in addition to
intranasal MF presented with increasing fatigue, weight loss, nausea and
striae. Extensive initial hospital investigations were normal. An AM cortisol
was reported < 50 nmol/L (170-540). She was started on hydrocortisone
therapy and changed to ciclesonide 400 mcg, as well as montelukast and
formoterol. Her energy and weight improved after initiation of replacement
hydrocortisone therapy. Despite using sublingual grass immunotherapy,
during grass pollen season the patient’s asthma control worsened. Rather
than increase the dose of inhaled corticosteroids, 18 mcg of daily TB was
added for a therapeutic trial. The patient experienced symptomatic
improvement with less nocturnal cough, normal exercise tolerance and 4%
improvement in FEV1.
Discussion: There is a limited repertoire of steroid sparing agents available
for use in the pediatric asthma population. While adrenal suppression due to
inhaled corticosteroids is considered relatively uncommon, and prior MFinduced adrenal suppression has only been reported by the authors, finding
suitable alternatives to inhaled corticosteroids is paramount in this
population. Physicians may consider a trial of TB in an attempt to decrease
the dose of inhaled corticosteroids in their pediatric patients to avoid
adrenal suppression.
A15
The prophylactic use of C1 esterase inhibitor in HAE patients
undergoing invasive procedures
Rachel Harrison1*, Stephanie Santucci1, Geneviève Gavigan2, Jacob Karsh2,
William H. Yang1,2
1
Allergy and Asthma Research Centre, Ottawa, ON, Canada; 2University of
Ottawa Medical School, Ottawa, ON, Canada
Background: For a patient with Hereditary Angioedema (HAE),
physiological and/or psychological stress can cause insufficient control of
local inflammatory pathways. This leads to complement and contact system
activation and excess bradykinin resulting in angioedema. Therefore, an
invasive procedure or surgery can trigger an HAE attack; this in turn can
cause further medical complications and pose an added danger to the postprocedure patient. C1 inhibitor, Berinert®, was approved in the US and
Canada in 2009 and 2010, respectively, for the treatment of acute attacks. In
April 2013, Berinert® was approved in Europe for short-term prophylaxis
prior to medical, dental, or surgical procedures to prevent HAE attacks.
Currently, Berinert® is not approved in Canada or the US for prophylaxis. We
aim to demonstrate the effectiveness of C1 esterase inhibitor, Berinert®, as a
prophylactic treatment for HAE patients undergoing invasive procedures.
Method: A retrospective chart review from our Canadian Tertiary Care
Allergy and Asthma Clinic of our entire database of HAE patients was
performed.
Results: Between 1997 and June 2014, C1 esterase inhibitor for prophylactic
use was administered prior to invasive procedures. There were a total of 28
procedures, performed on 15 patients.
The 28 procedures breakdown as follows: 9 dental surgeries, 3 open heart
surgeries, 8 other surgical procedures, 3 child birth, 5 invasive procedures.
In all 28 procedures, there was no incidence of post-procedure HAE
attacks after prophylactic administration of C1 esterase inhibitor.
Conclusion: We found that C1 esterase inhibitor decreased the incidence of
post-procedure HAE attacks and was an effective prophylactic treatment.
A16
Efficacy and safety of MK-7243: a grass allergy sublingual
immunotherapy tablet evaluated in Canadian adults and children
Jacques Hébert1*, Michael Blaiss2, Susan Waserman3, Harold Kim3, Peter Creticos4,
Jennifer Maloney5, Amarjot Kaur5, Harold S Nelson6, Hendrik Nolte5
1
Centre de Recherche Appliquée en Allergie de Québec, Québec City, QC,
Canada; 2Departments of Medicine and Pediatrics, University of Tennessee
Health Science Center, Memphis, TN, USA; 3Department of Medicine,
McMaster University, Hamilton, ON, Canada; 4Department of Medicine, Johns
Hopkins University School of Medicine, Baltimore, MD, USA; 5Merck & Co.,
Inc., Whitehouse Station, NJ, USA; 6Departments of Medicine and Pediatrics,
National Jewish Health, Denver, CO, USA
Background: The effect of MK-7243 (2800 BAU/75,000 SQ [~15 µg of
Phleum pratense p 5], Merck/ALK-Abelló), a sublingual Timothy grass
immunotherapy tablet, has been evaluated in several randomized, placebocontrolled, double-blind trials; three of these trials were conducted in adults
and children in North America (the United States and Canada) who have
allergic rhinitis with or without conjunctivitis (AR/C). We conducted a posthoc analysis to investigate the effect of MK-7243 in Canadian subpopulations.
Methods: Data from Canadian subjects from the three trials were used in
this investigation: P05238 (adults ≥18 y; pollen season: 2009); P05239
(children 5−<18 y; pollen season=2009); and P08067 (adults ≥65 y and
children 5−<18 y; pollen season: 2012). Trial data from the same grass
pollen seasons (GPS) were pooled. Subjects received once-daily MK-7243
or placebo starting ≥12 wk before and continuing throughout the GPS, for
Page 5 of 22
a mean total of ≥23 wk. The therapeutic effect of MK-7243 was evaluated
for rhinoconjunctivitis symptoms and symptomatic medication use,
measured as a total combined score (TCS=daily-symptom score [DSS;
max=18]+daily-medication score [DMS; max=36]) averaged over the entire
GPS. Safety was assessed by monitoring adverse events (AEs).
Results: Canadian subjects taking MK-7243 (n=42) in the pooled adultpediatric 2009 trials showed a 38% mean TCS reduction versus placebo
(n=54; −2.06 difference [95% CI: −3.72, −0.39]; 3.32 vs. 5.37). Canadian
subjects taking MK-7243 (n=122) in the adult-pediatric 2012 trial showed a
33% mean TCS reduction relative to placebo (n=122; −1.62 difference [95%
CI: −2.54, −0.71]; 3.34 vs. 4.96). Approximately 90% of treatment-related
AEs were mild or moderate in severity. No serious or life-threatening
treatment-related AEs occurred.
Conclusions: MK-7243 Timothy grass sublingual tablet significantly
improved AR/C induced by Timothy grass pollen in Canadian adults and
children 5 y and older. Similar efficacy and safety results were obtained for
the overall populations of the three trials.
Trial registration: ClinicalTrials.gov Identifiers: NCT00562159;
NCT00550550; NCT01385371.
Acknowledgements: Medical writing and editorial assistance was
provided by Erin P. Scott, PhD. This assistance was funded by Merck & Co.,
Inc., Whitehouse Station, NJ, USA. Editorial assistance was also provided by
Jorge Moreno-Cantu, PhD, Global Scientific and Medical Publications,
Office of the Chief Medical Officer, Merck & Co., Inc., Whitehouse Station,
NJ, USA
A17
The efficacy and safety of the short ragweed sublingual immunotherapy
tablet MK-3641 is similar in asthmatic and nonasthmatic subjects treated
for allergic rhinitis with/without conjunctivitis
Jennifer Maloney1, David I. Bernstein2, Jacques Hébert3*, Martha White4,
Robert Fisher5, Thomas B. Casale6, Amarjot Kaur1, Hendrik Nolte1
1
Merck & Co., Inc., Whitehouse Station, NJ, USA; 2Bernstein Allergy Group,
Cincinnati, OH, USA; 3Centre de Recherche Appliquée en Allergie de
Québec, Québec City, QC, Canada; 4Institute for Asthma & Allergy, Wheaton,
MD, USA; 5Allergy Research & Care, Milwaukee, WI, USA; 6Department of
Medical Microbiology/Immunology, Creighton University Medical Center,
Omaha, NE, USA
Background: We conducted a post-hoc analysis of two short-ragweed
sublingual immunotherapy tablet (SLIT-T) trials to investigate whether the
subjects with allergic rhinitis with/without conjunctivitis (AR/C) and
comorbid asthma reported different efficacy or safety events than those
with AR/C and no asthma.
Methods: Data from two trials evaluating the short-ragweed SLIT-T MK3641 (Ambrosia artemisiifolia; Merck/ALK-Abelló) were pooled. Subjects
with ragweed-pollen–induced AR/C were randomized to once-daily MK3641 (6 or 12 Amb a 1-U doses) or placebo for approximately 52 weeks.
Subjects with AR/C and stable asthma not requiring medium- or high-dose
inhaled corticosteroids and ≥70% predicted FEV1 were eligible. Efficacy
and safety outcomes were assessed in subjects with AR/C with/without
reported asthma. Efficacy measurements included AR/C total combined
score (TCS; combined symptom+medication scores); safety was assessed
by reported adverse events (AEs).
Results: Among subjects with AR/C and asthma receiving MK-3641 6 or 12
Amb a 1-U, TCS was reduced by 17% (−1.27; 95% CI: −3.48, 0.93; n=56) and
22% (−1.68; 95% CI: −3.69, 0.33; n=64), respectively, versus placebo (mean
TCS=7.65; n=64) over the 15-day peak season. Among subjects without
asthma receiving MK-3641 6 or 12 Amb a 1-U, TCS was reduced by 21%
(−1.83; 95% CI: −2.84, −0.82; n=261) and 27% (−2.34; 95% CI: −3.33, −1.35;
n=247), respectively, versus placebo (mean TCS=8.73; n=269). At least one
treatment-related AE was experienced by 33%, 63%, and 65% of placebo
and MK-3641 6 and 12 Amb a 1-U subjects with asthma, respectively, versus
24%, 54%, and 60% of subjects without asthma. No treatment-related
serious or life-threatening AEs or hypersensitivity or systemic reactions were
observed.
Conclusions: The overall number of subjects with asthma was low and the
data must be interpreted with caution. However, the SLIT-T treatment MK3641 appeared to demonstrate similar efficacy and safety results in subjects
with ragweed AR/C with or without asthma.
NCT00770315.
Acknowledgements: Medical writing and editorial assistance was
provided by Erin P. Scott, PhD. This assistance was funded by Merck & Co.,
Inc., Whitehouse Station, NJ, USA. Editorial assistance was also provided by
Jorge Moreno-Cantu, PhD, Global Scientific and Medical Publications,
Office of the Chief Medical Officer, Merck & Co., Inc., Whitehouse Station,
NJ, USA.
A18
Treatment of angiotensin-converting enzyme inhibitor related
angioedema with icatibant
Peter Ho*, Chrystyna Kalicinsky
Section of Allergy and Clinical Immunology, Department of Internal
Medicine, University of Manitoba, Winnipeg, Manitoba, MB R3A 1R9, Canada
Background: The absolute risk of angiotensin-converting enzyme (ACE)
inhibitor angioedema is 0.3% [1]. The mechanism is felt to be accumulation
of bradykinin. The current treatment is discontinuation of ACE-I inhibitor,
and intubation if necessary. Icatibant is a bradykinin receptor antagonist,
useful in treating hereditary angioedema [2]. We present a patient from a
Canadian center who had ACE-inhibitor induced angioedema requiring
intubation who did not respond to epinephrine or C1 esterase inhibitor
concentrate, then later responded favorably to Icatibant.
Case presentation: We present a case of a 76 year old male with
hypertension, type II diabetes, no allergies, who was seen in the ER with
acute new-onset tongue and facial swelling. He had a virus 2 weeks prior.
His medications included quinapril, simvastatin, repaglinide, metformin,
pioglitazone, and aspirin.
He had a swollen tongue, oral cavity, neck and was unable to swallow.
There was no urticaria. He was given diphenhydramine 50mg IV,
methylprednisolone 125mg IV, epinephrine 0.3mg IM, and ranitidine 50mg
IV. Swelling progressed and he was intubated.
Over the next 24 hours, he received methylprednisolone 80mg every
8 hours, ranitidine 50mg every 8 hours, diphenhydramine 50mg every
6 hours, two doses of C1 esterase inhibitor concentrate, 1500 units IV
followed by 1000 units. Quinipril was discontinued. Computed tomography
of the neck showed no abscess.
Over the next 2 days there was minimal improvement. Therefore, on
hospital day 3, he received 3 doses of Icatibant 30 mg over 24 hours.
Improvement was noted, and by the next day, he was extubated. Following
overnight monitoring, he was transferred to the medicine ward. There was
no recurrence and he was discharged. C1 esterase inhibitor level and
function was normal (drawn prior to infusion).
At his two month follow up he remained asymptomatic. ACE inhibitors and
Angiotensin Receptor Blockers are avoided. He was diagnosed with
myelodysplastic syndrome following work up for anemia noted on
admission.
There have been published reports outside of Canada describing the use
of Icatibant in ACE-inhibitor induced angioedema [3].
Icatibant is not indicated in Canada for ACE-inhibitor induced
angioedema. However, it may need to be considered in severe cases.
Conclusion: Icatibant may be helpful in ACE-inhibitor induced angioedema
when the patient has not responded to the discontinuation of the ACE
inhibitor and alternative therapies.
References
1. Makani H, M F-P: Meta-analysis of randomized trials of angioedema as an
adverse event of renin-angiotensin system inhibitors. American Journal of
Cardiology, 2010, 110(3):383-91.
2. C P: AAAAI: Third Time a Charm for Novel HAE Drug. 2011, Retrieved July
13, 2014, from Med Page Today: http://www.medpagetoday.com/
MeetingCoverage/AAAAI/25501.
3. Bas M, G J: Therapeutic Efficacy of Icatibant in Angioedema Induced by
Angiotensin-Converting Enzyme Inhibitors: A Case Series. Annual
Emergency Medicine 2010, 56(3):278-82.
Page 6 of 22
A19
Anti-Ige monoclonal antibody therapy for the treatment of chronic
rhinosinusitis: a systematic review
Chris J Hong1*, Adrian C Tsang1, Jason Quinn2, James Bonaparte3,
Adrienne Stevens4, Shaun J Kilty3
1
Faculty of Medicine, University of Ottawa, Ottawa, ON, Canada;
2
Department of Pathology, Dalhousie University, Halifax, NS, Canada;
3
Department of Otolaryngology-Head and Neck Surgery, The University of
Ottawa, The Ottawa Hospital, Ottawa, ON, Canada; 4Center for Practice
Changing Research, Ottawa Hospital Research Institute (OHRI), University of
Ottawa, Ottawa, Canada
Background: Several treatment options are available for chronic
rhinosinusitis (CRS), but disease control remains elusive for many patients.
Recently, literature has emerged describing anti-IgE monoclonal antibody as
a potential therapy for CRS. However, its effectiveness and safety are not
well known. The purpose of this systematic review was three-fold: to assess
the effectiveness and safety of anti-IgE monoclonal antibody therapy for
the treatment of adult patients with CRS and to identify evidence gaps to
guide future research on anti-IgE monoclonal antibody therapy for the
management of CRS.
Methods: Methodology for the systematic review was registered with
PROSPERO (No. CRD42014007600). A comprehensive literature search was
performed of standard research databases, ClinicalTrials.gov and relevant
grey literature sources. Only randomized controlled trials assessing anti-IgE
therapy in adult patients for the treatment of CRS were included. Quality of
evidence was evaluated using the GRADE approach. Two independent
reviewers extracted data and discrepancies were settled by consensus and
discussion amongst the reviewers.
Results: Two studies met our inclusion criteria. The GRADE assessment of
the quality of evidence was low. Comparison of anti-IgE therapy to placebo,
there was significant differences in CT score and quality of life. There was a
significant improvement in Lund-McKay score (n=1, 4.0 vs. -0.5, p=0.04) and
AQLQ (n=1, 0.81 vs. 0.27, p=0.003). Mixed results were found for total nasal
endoscopic polyp score in the two studies. No significant difference was
seen with regards to nasal airflow and olfaction as measured by PNIF and
UPSIT. No serious complications were reported with this therapy in either
trial.
Conclusions: Currently insufficient evidence exists to determine whether
anti-IgE is more effective than placebo for the treatment of CRS. High quality
studies are needed to supplement the evidence base in order to make a firm
conclusion and to further assess anti-IgE monoclonal antibody therapy
efficacy in this population.
A20
Penicillin allergies: referral and management practices of
anesthesiologists
V Jain1*, N Joshi2, M Sidhu3, C Kalicinsky1, T Pun1
1
Allergy & Clinical Immunology, University of Manitoba, Winnipeg, MB, R3T
2N2, Canada; 2Department of Internal Medicine, Memorial University of
Newfoundland, St. John’s, NL, A1B 3X9, Canada; 3Department of Family
Medicine, University of Western Ontario, London, ON, N6A 3K7, Canada
Rationale: Penicillin and other beta-lactams are the most commonly used
antibiotics due to their narrow spectrum of activity, low cost and safety
profile. However, an “allergy” to Penicillin is also the most commonly reported
allergy. Approximately, 5-10% of all patients self-report an allergy to Penicillin
and of these <10% are found to have true IgE mediated allergy on skin
testing.
Numerous studies have confirmed the usefulness and strong negative
predictive value (>99%) of skin testing to rule out true IgE mediated
Penicillin allergy. Less than 10% of patients with a history of penicillin allergy
are found to be actually allergic to penicillin on skin testing. Despite this,
most physicians forgo further investigations in favor of the usage of
alternative antibiotics.
Methods: A questionnaire was designed to evaluate the referral practices of
Anesthesiologists for a presumed Penicillin allergy.
The preliminary study was administered as a semi-structured interview to
Anesthesiology Staff Physicians and Senior Residents at Memorial University
of Newfoundland. The responses were analyzed using recursive abstraction.
Results: 89.5% of respondents have never referred patients for evaluation
of drug allergy, although, an equal number felt a referral would be
helpful. However, 47.3% said they have verbally communicated to their
patients that they should speak to their Family Doctor for work up of
their allergy. 21.1% of participants felt time constraint was a barrier to
creating a referral; another 15.8% felt that this was the responsibility of
another physician (Surgeon or Family Doctor). An additional 26.3% did
not comment on barriers but stated they would just give an alternative
medication rather than refer. Another 15.8% mentioned that surgery is
generally imminent and would not delay surgery to a referral. All
participants stated they would choose an alternative antibiotic in the case
of a history of penicillin allergy.
Conclusion: Carrying a presumed diagnosis of penicillin ‘‘allergy’’ has
significant consequences on the health care system and patient outcome.
Anesthesiologists in our study do inquire about specifics of allergy
history, however, the referrals are virtually non-existent. As a result,
anesthesiologists are prescribing more expensive antibiotics, which have
higher potential for emergence of antibiotic resistance. Our future plans
are to complete data collection at other centers and to develop an
intervention to improve referral practices and study its impact.
References
1. Lee AU, et al: The incidence of antimicrobial allergies in hospitalized
patients: implications regarding prescribing patterns and emerging
bacterial resistance. Arch Intern Med 2000, 160(18):2819.
2. Gadde J, Spence M, Wheeler B, et al: “Clinical experience with penicillin
skin testing in a large inner-city STD clinic”. JAMA 1993, 270:2456-63.
3. Macy Eric, Richard Contreras: “Health Care Use and Serious Infection
Prevalence Associated with Penicillin “allergy” in Hospitalized Patients: A
cohort Study.”. Journal of Allergy and Clinical Immunology 2013.
4. Phillips Elizabeth: “Cost-effectiveness Analysis of Six Strategies for
Cardiovascular Surgery Prophylaxis in Patients Labeled Penicillin
Allergic.”. Am. J. of Health-Systems Pharm 2000, 57:339.
5. Picard Matthieu, Philippe Bégin: “Treatment of Patients with a History of
Penicillin Allergy in a Large Tertiary-Care Academic Hospital.”. The
Journal of Allergy and Clinical Immunology 2013, 252-57, Practice 1.3.
6. Sade K, Holtzer I, Levo Y: “The Economic Burden of Antibiotic Treatment
of Penicillin-allergic Patients in Internal Medicine Wards of a General
Tertiary Care Hospital.”. Clinical Experimental Allergy 2003, 33(4):501-06.
7. Warrington , Silviu-Dan : Allergy, Asthma & Clinical Immunology 2011,
7(Suppl 1):S10.
A21
Clinical evaluation of an allergen Challenge TheatreTM
Jacob Karsh*, Suzanne Kelly, Jimmy Yang, Rob Perrins, William H Yang
Red Maple Trials Inc., Ottawa, Ontario, Canada
Background: Allergen challenge chambers expose allergen-sensitive
subjects to a predetermined concentration of allergen in a closed,
controlled environment and provide a mechanism to induce clinical
symptoms and measure the effect of medication.
Methods: A preliminary evaluation of the capabilities of the newly
constructed Red Maple Trials Allergen Challenge TheatreTM was performed.
Health Canada and a provincial Ethics Board approved the study. After
signing informed consent, patients with a history of grass allergy, not on
allergy medications and with a positive skin prick test to grass antigen (≥ 3
mm) were exposed for 3 hours to timothy grass pollen (Phleum pratense) in
the allergen challenge theatre. Total nasal (TNSS) and rhinoconjunctivitis
symptom scores (TRSS) were recorded at baseline and every 30 minutes
during the challenge.
Results: 32/50 patients evaluated demonstrated a positive skin prick test
and were challenged. Baseline TNSS and TRSS (Mean± SD) were 0.6±1.04
and 0.6±1.07 respectively. Symptom scores reached a plateau at 30 minutes
(TNSS 4.8±2.68; TRSS 5.8±3.69) and remained steady for the 180-minute
exposure period reaching final values of TNSS 3.7±2.16; and TRSS 5.8±3.79.
Because entry to a therapeutic trial usually requires achieving a TNSS ±5
Page 7 of 22
during a priming exposure, we calculated the results for the 17/32 patients
reaching this score at 30 minutes (TNSS 6.65±2.21; TRSS 8.35±3.18). Scores
held steady and at 180 minutes were: TNSS 4.71±1.69; TRSS 7.88±3.06. No
unexpected adverse events were reported during the challenge.
Conclusions: The Red Maple Trials allergen exposure theatre demonstrated
the capacity to induce symptoms of appropriate intensity upon allergen
challenge. The chamber with a seating capacity of 99 places has the ability
to evaluate large test groups at a time.
A22
Technical evaluation of an allergen Challenge TheatreTM
Suzanne Kelly*, Jimmy Yang, Rob Perrins, Jacob Karsh, William H Yang
Red Maple Trials Inc., Ottawa, Ontario, Canada
Background: Allergen challenge chambers expose allergen-sensitive
subjects to a predetermined concentration of allergen in a closed, controlled
environment and provide a mechanism to induce clinical symptoms and
measure the effect of medication.
Methods: A technical evaluation of the capabilities of the Red Maple Trials
Allergen Challenge TheatreTM was performed. The theatre is a 4-zone facility
holding up to 99 seats in a series of elevated rows. Grass (Phleum pratense)
and ragweed (Ambrosia artemisiifolia) pollens were injected into the air
supply and blown into the facility through ducts located across the top of
the front wall. Grass and ragweed pollen concentrations were measured on
impact samplers set at face level in 5 sections of a T-shaped quadrant.
Concentrations were measured every 30 minutes for 150 minutes.
Continuous pollen counts were also read by a laser particle counter (LPC) set
to read particles > 5µm and positioned 5 feet above floor level.
Results: The impact sampler pollen concentration for the theatre quadrant
during the entire 180-minute exposure was 3992 ± 975 grains m 3 .
Concentrations for the quadrant were consistent at each 30-minute
measurement with means ranging from 3648 to 4523 and SDs from 678 to
1105. Pollen concentrations were consistent in each of the 5 sections of the
quadrant over time with means ranging from 3112 to 5268 and SDs ranging
from 308 to 926. Pollen counts measured by LPC remained consistent at
4000 per m3 during the experiment. There was a linear relationship between
the LPC pollen readings and the impact sampler readings.
Conclusions: The Red Maple Trials allergen exposure theatre demonstrated
the capacity to achieve and maintain a concentration of pollen grains at a
magnitude consistent with the literature and associated with the ability to
induce symptoms of appropriate intensity upon allergen challenge. The use
of an LPC provided a significant advantage by monitoring pollen counts on
a continuous basis. The chamber with a seating capacity of 99 places has
the ability to evaluate large test groups at a time.
A23
Anaphylaxis associated with folic acid: domestic case review
Pauline E. Kerr*, David Cunningham
Marketed Health Products Directorate, Health Products and Food Branch,
Health Canada, Ottawa, Ontario, Canada, K1A 0K9
Background: Synthetic folic acid has been shown to cause serious,
potentially life-threatening IgE mediated anaphylaxis [1-3]. Synthetic folic
acid does not occur naturally and is distinct from naturally occurring folic
acid [1,4,5].
Methods: A search of the Canada Vigilance Database from April 1, 2008
to August 31, 2013 identified 15 cases of anaphylaxis and 16 reports of
serious non-anaphylactic allergic reactions.
Results: All 15 cases of anaphylaxis involved multi ingredient products
with NHP doses (up to and including 1 mg). Fourteen cases were female
(93%). One case of anaphylaxis and 3 cases of serious allergic reaction
involved women taking prenatal supplements, two of which reported
spontaneous abortion. There was insufficient case information available to
assess any causal association between the allergic reaction and the fetal
loss. Three medically important cases involved pharmaceutical doses of
folic acid (5 mg), one of which was a pediatric case involving a multi
ingredient intravenous total parental nutrition product (Multi-12/K1
pediatric) containing folic acid.
Confirmatory allergy tests for folic acid were not available for any of the
cases. None of the reports noted a known diagnosis of folic acid allergy.
Conclusions: Folic acid allergy appears to be rare and would not be
expected to be well known among health providers or consumers.
Increasing awareness amongst health providers regarding folic acid allergy
may improve the identification and counselling of patients with this allergy.
References
1. Dykewicz MS, Orfan NA, Sun W: In vitro demonstration of IgE antibody to
folate-albumin in anaphylaxis from folic acid. J Allergy Clin Immunol 2000,
106:386-89.
2. Smith J, Empson M, Wall C: Recurrent anaphylaxis to synthetic folic acid.
The Lancet 2007, 370:652.
3. Jandus P, et al: Anaphylaxis to supplemental folic acid. Allergy 2012, 67:260-1.
4. Stoevesandt J, Brocker E, Trautmann A: Folic acid allergy: no breakfast
cereal hazard. EJD 2011, 21:280-1.
5. HC: Health Canada: Monograph: Folate. Ottawa (ON): Health Canada 2009
[http://webprod.hc-sc.gc.ca/nhpid-bdipsn/monoReq.do?id=90].
A24
Anti-Ige monoclonal antibody therapy for the treatment of patients
with chronic rhinosinusitis: a multi-disciplinary practice review
Shaun J. Kilty1,2,3*, Andrea Lasso1, Stephanie Santucci4, William Yang3,4
1
The Department of Otolaryngology-Head and Neck Surgery, The Ottawa
Hospital, Ottawa, ON, Canada; 2Ottawa Hospital Research Insitute (OHRI),
Ottawa, ON, Canada; 3The University of Ottawa, Ottawa, ON, Canada; 4Allergy
and Asthma Research Centre, Ottawa, ON, Canada
Background: Several treatment options have been described for chronic
rhinosinusitis (CRS), yet many patients remain poorly responsive to medical
and surgical therapy. Recently, anti-IgE monoclonal antibody has emerged
as a potential therapy for CRS. However, to date evidence for its efficacy in
this patient population is sparse. The purpose of this study is to evaluate the
clinical effect of anti-IgE monoclonal antibody therapy for patients with
recalcitrant CRS and asthma treated in a multi-disciplinary clinic.
Methods: A review of the charts for the 194 patients on anti-IgE
monoclonal antibody therapy was performed. 20 patients diagnosed with
CRS with poorly controlled disease having failed surgical and/or medical
therapy were identified. Data extraction targeted demographic details,
asthma, environmental allergy and CRS specific disease related data. For
data analysis, for nonparametric data the Mann-Whitney test was used and
for binary data Fisher’s exact test was used.
Results: Mean age of the cohort was 49 years (range 33-67); eleven patients
were male. Mean IgE level was 331.14 IU/ml (57.54-1338.96 IU/ml). Mean
treatment duration was 17 (3-71) months. The most common skin prick test
positive environmental allergens were dust mite (100%) and cat (65%). 75%
of patients had CRS with polyps. Six patients (30%) had AERD. The mean
polyp score decreased from 1.8 to 1.0 (p=0.106). Patient olfaction improved
in 11 patients (55%) with therapy. Two patients on chronic prednisone
treatment were able to discontinue this treatment. None of the patients
progressed to require surgical treatment.
Conclusions: Anti-IgE monoclonal antibody therapy allowed for clinical
CRS disease control in this cohort of patients with severe and recalcitrant
CRS. A well-designed clinical trial is needed to further assess the efficacy
and safety of this treatment in the CRS population.
Page 8 of 22
A25
Food allergy and PPI-responsive esophageal eosinophilia
Jason K Ko1*, David JT Huang2, Jorge A Mazza2
1
Schulich School of Medicine & Dentistry, University of Western Ontario,
London, Ontario, Canada; 2Division of Allergy & Clinical Immunology,
Department of Medicine, University of Western Ontario, London, Ontario,
Canada
Background: Eosinophilic esophagitis (EoE) is considered a chronic
condition mediated by immune reaction to food and/or environmental
allergens. Though first recognized decades ago, the characterization of EoE
is ongoing and an important aspect of this process is the distinction
between EoE and other forms of esophageal eosinophilia [1,2]. One group of
patients exhibit marked esophageal eosinophilia (>15 eo/HPF), negative
esophageal pH-monitoring studies and yet have clinicopathologic response
to proton-pump inhibitor (PPI) treatment: this group is categorized as
having PPI-responsive esophageal eosinophilia (PPI-REE) [1,3]. It is not
certain whether those with PPI-REE are cases of GERD undiagnosed by pHmonitoring, EoE responding to PPI therapy as in-vitro studies suggest [4], or
some combination thereof. GERD is orders of magnitudes more prevalent
than EoE and thus misdiagnosed cases of GERD could have significant
impact on any study of EoE patients [5,6]. Other groups have attempted to
distinguish cases of PPI-REE and EoE, but failed to do so using
clinicopathologic criteria [7,8]. This retrospective review of patients
diagnosed with EoE aimed to differentiate PPI-REE and non-responsive
patients, with an emphasis on prevalence of food allergy between the two
groups.
Methods: A chart review was performed for 30 patients diagnosed with
EoE, prescribed PPI therapy and tested with atopic patch tests for a panel of
food allergens. Patients were categorized as having PPI-REE if past clinical
assessments noted significant symptomatic improvement with PPI therapy.
Results: Of the 30 patients reviewed, 12 were found to have PPI-REE. There
was no significant difference in other treatments offered to PPI-REE and
non-responsive patients, the eosinophil counts at diagnosis, nor in likelihood
of food allergy as detected by skin prick or food patch testing (Table 1).
Conclusions: It was hypothesized that PPI-REE cases would be less atopic, with
regards to foods, than non-responders due to the possible prevalence of
undiagnosed GERD in the former group. However, this review failed to show
any statistically significant differences between the two groups. This is
consistent with attempts of other groups to distinguish PPI-REE and EoE
patients.
References
1. Liacouras CA, Furuta GT, Hirano I, Atkins D, Attwood SE, Bonis PA, Burks AW,
Chehade M, Collins MH, Dellon ES, et al: Eosinophilic esophagitis: updated
consensus recommendations for children and adults. The Journal of allergy
and clinical immunology 2011, 128:3-20, e26; quiz 21-22.
2. Rodrigo S, Abboud G, Oh D, DeMeester SR, Hagen J, Lipham J, DeMeester TR,
Chandrasoma P: High intraepithelial eosinophil counts in esophageal
squamous epithelium are not specific for eosinophilic esophagitis in adults.
The American journal of gastroenterology 2008, 103:435-442.
3. Molina-Infante J, Ferrando-Lamana L, Ripoll C, Hernandez-Alonso M,
Mateos JM, Fernandez-Bermejo M, Duenas C, Fernandez-Gonzalez N,
Quintana EM, Gonzalez-Nunez MA: Esophageal eosinophilic infiltration
responds to proton pump inhibition in most adults. Clinical
gastroenterology and hepatology : the official clinical practice journal of the
American Gastroenterological Association 2011, 9:110-117.
Table 1(abstract A25) Characteristics of PPI-REE and non-responder groups
PPI-REE
Non-responders
N
12
18
p-value
N/A
Average eosinophil count at diagnosis (eo/HPF)
65.7 ± 29.2
42.6 ± 15.6
0.14
Use of other treatments (Swallowed steroid and/or dilatation)
10/12 (83%)
8/18 (44%)
0.21
Food allergy on atopic patch test
9/12 (75%)
9/18 (50%)
0.60
Food allergy on skin prick test
5/11 (45%)
6/16 (38%)
0.98
4.
5.
6.
7.
8.
Zhang X, Cheng E, Huo X, Yu C, Zhang Q, Pham TH, Wang DH, Spechler SJ,
Souza RF: Omeprazole blocks STAT6 binding to the eotaxin-3 promoter
in eosinophilic esophagitis cells. PloS one 2012, 7:e50037.
Dent J, El-Serag HB, Wallander MA, Johansson S: Epidemiology of gastrooesophageal reflux disease: a systematic review. Gut 2005, 54:710-717.
Hruz P: Epidemiology of eosinophilic esophagitis. Digestive diseases 2014,
32:40-47.
Dellon ES, Speck O, Woodward K, Gebhart JH, Madanick RD, Levinson S,
Fritchie KJ, Woosley JT, Shaheen NJ: Clinical and endoscopic
characteristics do not reliably differentiate PPI-responsive esophageal
eosinophilia and eosinophilic esophagitis in patients undergoing upper
endoscopy: a prospective cohort study. The American journal of
gastroenterology 2013, 108:1854-1860.
Moawad FJ, Schoepfer AM, Safroneeva E, Ally MR, Chen YJ, Maydonovitch CL,
Wong RK: Eosinophilic oesophagitis and proton pump inhibitor-responsive
oesophageal eosinophilia have similar clinical, endoscopic and histological
findings. Alimentary pharmacology & therapeutics 2014, 39:603-608.
A26
B cell Semaphorin 4c expression mitigates the airway
hyperresponsiveness and acute inflammation which characterize
allergic airway disease
Alex Lei1*, Di Xue1, Marylin Desjardins1, Marianne Beland1, Bruce Mazer1,2
1
Meakins-Christie Laboratories, Department of Experimental Medicine, McGill
University, Montreal, Quebec, H2X 2P2, Canada; 2Montreal Children’s
Hospital, Department of Pediatrics, McGill University Health Center, Montreal,
Quebec, H3H 1P3, Canada
Background: Semaphorin signaling proteins, initially examined in the
context of neuronal axon development, have recently been implicated as
regulators of immune cell migration. Our laboratory has determined that
expression of Semaphorin 4C (Sema4C) is strongly induced on B cells
exposed to Th2 stimulation, and we seek to elucidate its mechanism of
controlling allergic airway disease.
Methods: Wild-type and Sema4C-/- mice were sensitized intraperitoneally
using 100 μL OVA (0.5 mg/mL ovalbumin and 4 mg/mL aluminum
hydroxide in PBS) on days 0 and 14, and were challenged intranasally using
20 μL OVA (10 mg/mL ovalbumin in PBS) from days 28 to 30. Sacrifice and
analysis of Airway Hyperresponsiveness via flexiVent was performed on day
31. Serum IgE and IL-10 expression levels were measured by ELISA. B cells
were phenotyped by fluorescence-activated cell sorting (FACS). B cell
motility was measured by migration assays.
Results: Please see figure 1.
Conclusions: Semaphorin 4C regulates the allergic airway disease
through immune synapse-governed cytoskeletal rearrangements in B
cells, and minimizes the inflammatory cellular lung infiltration that
contributes to airway hyperresponsiveness.
A28
The observed incidence of anaphylaxis and serum sickness in patients
receiving omalizumab in a tertiary allergy and asthma clinic in Canada
Megan MacRae1*, Stephanie Santucci1, Jacob Karsh2, William H. Yang1,2
1
Background: In a post-marketing analysis last updated in July 2007, the
FDA reported that an estimated 0.2% of patients suffered treatment related
anaphylaxis and rare incidence of serum sickness. To substantiate this, the
occurrence of treatment related anaphylaxis and serum sickness in our large
Canadian allergy and asthma tertiary clinic was assessed.
Methods: A retrospective chart review of our database of omalizumab
administration between 1998 and June 2014 was performed.
Results: During clinical trials and with our post market experience, between
1998 and June 2014, over 21,000 injections of omalizumab to more than
250 patients were administered and no cases of anaphylaxis or serum
sickness like symptoms were observed.
Conclusion: Meticulous care was taken by our omalizumab administration
clinic to ensure optimal safety based on the emphasized warnings of
Page 9 of 22
anaphylaxis, as well as, the indicated warnings and precautions for serum
sickness. Data collected in this analysis observed no cases of anaphylaxis or
serum sickness like symptoms in the treatment of over 250 patients, during a
period of 15.5 years, who combined received 21,000 injections of omalizumab
thus confirming the low incidence of both anaphylaxis and serum sickness.
A29
Value of skin testing children with a family history of food allergy
before ingestion of suspect food allergens
Arunmozhi Dominic1*, Vaishaali Manga1, Immaculate Nevis2, Laura Kim3,
Harold Kim1,4
1
Division of Clinical Immunology and Allergy, Western University, London,
Ontario, Canada; 2Department of Clinical Epidemiology and Biostatistics,
McMaster University, Hamilton, Ontario, Canada; 3McGill University, Montreal,
Quebec, Canada; 4Division of Clinical Immunology and Allergy, McMaster
University, Hamilton, Ontario, Canada
Background: A family history of food allergy can cause anxiety in parents.
This may prevent food introduction in their children. Current guidelines
recommend skin testing only when there is a reaction to a food in that
specific patient. When there is a family history of food allergy, parents
frequently ask their physicians for food testing of their children prior to
introduction of specific foods. We conducted this study to determine
whether allergy skin testing reduces anxiety levels in parents thereby
leading to food introduction.
Methods: The parents of 50 children with a family history of food allergy
completed a Visual Analog Score (VAS) to estimate their anxiety to give their
children the specific food of concern. Previously, the children had not eaten
the food. The VAS scores were recorded pre- and post-skin testing on a scale
from 0 to 10. The likelihood of food introduction pre- and post-skin testing was
estimated.
Results: The mean age of the children was 3.6 years; the majority were
males (62%). Approximately 58% of patients’ parents, 38% siblings and 4%
other relatives had food allergy. Most children (78%) had family history of a
single food allergen and 60% had a family history of allergy to peanuts. All
children tested negative for the food allergen of concern. Mean VAS was
statistically different pre- and post-skin testing (pre VAS mean= 7.83 vs post
VAS mean = 2.15; p=<0.0001). The likelihood of food introduction pre- and
post testing was 4% and 92% respectively.
Conclusion: Skin testing reduces the anxiety of parents of children with a
family history of food allergy prior to introduction of the food allergen of
concern. The food is more likely to be introduced into the diet after
negative skin testing. Although it did not occur in this study, there is a still a
risk of false positive skin testing.
A30
Severe allergic reaction to diethyltoluamide (DEET) containing insect
repellent
Mary McHenry1*, Gina Lacuesta2
1
Department of Pediatrics, Dalhousie University, Halifax, Nova Scotia, Canada;
2
Division of Allergy and Clinical Immunology, Dalhousie University, Halifax,
Nova Scotia, Canada
Background: Contact and generalized urticaria to DEET-containing
repellents have been reported, but few cases of severe allergic reaction
with angioedema.
Case presentation: A 53 year-old female bridge inspector presented with
allergic reaction to diethyltoluamide (DEET) - containing insect repellent. She
had prior use without difficulty. In 2013, she used the insect repellent and
with only a small amount making contact with her forehead, she had
immediate pruritus and erythema on her forehead, persisting for an hour.
The following week, she used a different insect repellent and sprayed her
face and body. Within minutes, she became diffusely pruritic with
generalized urticaria and angioedema of her eyes. She called 911 and was
given intramuscular diphenhydramine. Her symptoms gradually eased and
she was subsequently well. Her regular medications include venlafaxine and
ketorolac. She has no history of atopy. Since the reaction, she has been
avoiding all forms of insect repellent, including riding in separate vehicles as
Page 10 of 22
Figure 1(abstract A26) A-H. Sema4C localized at B cellular synapses for wild-type mice (WT). Immunofluorescence staining of B cells stimulated with CD40L, IL-4,
and IL-21 for 24 hours (A-D), or 72 hours (E-H). I-L. Sema4C-/- (KO) B cells have aberrant actin cytoskeletal structural organization. M. KO mice have narrower
airway diameter than WT mice. H&E staining of WT (n=6) and KO (n=5) lungs with Allergic Airway Disease (AAD). N. KO mice with AAD had a greater percentage
of lung-infiltrating lymphocytes (CD4+ T cells, CD19+ B cells, and CD138+ plasma cells) than WT mice. Lymphocytes were recovered using Bronchoalveolar
Lavage. E. KO mice with AAD had higher serum OVA-specific IgE levels than WT mice. F. KO mice with AAD had lower serum IL-10 levels than WT mice
her co-workers who use insect repellent. She carries an epinephrine device
at all times. Skin testing was performed using two DEET-containing insect
repellents: Lloyd’s Bug Spray © (23.75% DEET) and OFF Family Care Bug
Spray© (5% DEET). She had positive skin prick test to both insect repellents,
more prominent with the higher containing DEET repellent. There was also a
significant reaction on the skin adjacent to the test site where the repellent
had not made contact. She developed significant pruritus and was treated
with oral anti-histamine. She had appropriate controls. A control subject
tested in the office was negative to both insect repellents.
Conclusion: The patient had a severe allergic reaction to insect repellent,
and exhibits sensitization based on skin testing. This represents a unique
case of severe cutaneous reaction to insect repellent and such patients may
be at risk of anaphylaxis with future exposure.
A31
Efficacy of short-ragweed sublingual immunotherapy tablet MK-3641 in
monosensitized and polysensitized subjects
David I Bernstein1, Kevin R Murphy2, Hendrik Nolte3*, Amarjot Kaur3,
Jennifer Maloney3
1
Bernstein Allergy Group, Cincinnati, OH, USA; 2Boys Town National Research
Hospital, Boys Town, NE, USA; 3Merck & Co., Whitehouse Station, NJ, USA
Background: Immunotherapy for allergic rhinitis with/without conjunctivitis
(AR/C) may exhibit different efficacy characteristics in patients with multiple
allergen sensitizations than monosensitized patients. It has been considered
that monosensitized patients may benefit more from immunotherapy than
polysensitized patients. Evidence from randomized, blinded, placebocontrolled trials of Timothy grass sublingual immunotherapy tablet (SLIT-T)
MK-7243 (Merck/ALK-Abelló) indicates that treatment in mono- and
polysensitized subjects is equally effective.
Methods: A prospective efficacy analysis was performed between
monosensitized and polysensitized subjects treated with the short-ragweed
SLIT-T MK-3641 (Ambrosia artemisiifolia; Merck/ALK-Abelló). Pooled data from
2 randomized placebo-controlled trials investigating MK-3641 (6 and
12 Amb a 1-U doses) were used. The primary efficacy outcome was the total
combined score (TCS=symptom+medication scores) during the 15-day peak
season.
Results: Differences versus placebo for the MK-3641 6 and 12 Amb a 1-U
pooled groups (mono- and polysensitized subjects combined) for the peak
season TCS were 20% (−1.70; 95% CI, −2.55 to −0.86) and 23% (−2.02; 95%
CI, −2.87 to −1.17), respectively (P<0.001 for both). Differences versus
placebo in the monosensitized MK-3641 pool (n = 175) were 15% (−1.34;
95% CI, −3.40 to 0.73) and 19% (−1.72; 95% CI, −3.63 to 0.20) for 6 and 12
Amb a 1-U, respectively. In the polysensitized MK-3641 pool (n = 784)
difference versus placebo were 21% (−1.78; 95% CI, −2.80 to −0.75) and 27%
(−2.27; 95% CI, −3.27 to −1.28) for 6 and 12 Amb a 1-U, respectively.
Conclusions: In the whole study population, treatment with MK-3641 6 and
12 Amb a 1-U for ragweed-induced AR/C was superior to placebo. Although
the sample size for the 2 subpopulations was not balanced and data must
be interpreted cautiously, it appears that the treatment effect is similar in
the mono- and polysensitized subpopulations, with a numerical trend of a
greater treatment effect in polysensitized subjects.
NCT00770315.
Acknowledgements: Medical writing and editorial assistance was provided
by Erin P. Scott, PhD. This assistance was funded by Merck & Co., Inc.,
Whitehouse Station, NJ, USA. Editorial assistance was also provided by Jorge
Moreno-Cantu, PhD, Global Scientific and Medical Publications, Office of the
Chief Medical Officer, Merck & Co., Inc., Whitehouse Station, NJ, USA
A32
The effect of the ragweed sublingual immunotherapy tablet MK-3641
on rescue medication use
Sandra Gawchik1, Peter Creticos2, Kevin R. Murphy3, Gary Berman4,
David I. Bernstein5, Jennifer Maloney6, Amarjot Kaur6, Hendrik Nolte6*
1
Asthma & Allergy Associates, Chester, PA, USA; 2Department of Medicine,
Johns Hopkins University School of Medicine, Baltimore, MD, USA; 3Boys
Town National Research Hospital, Boys Town, NE, USA; 4Minneapolis Allergy
& Asthma Specialists, Minneapolis, MN, USA; 5Bernstein Allergy Group,
Cincinnati, OH, USA; 6Merck & Co., Inc., Whitehouse Station, NJ, USA
Background: Allergic rhinitis with/without conjunctivitis (AR/C) sufferers
often rely on pharmacotherapy to relieve symptoms. Although the main
goal of immunotherapy is long-term disease modification, reducing or
eliminating the need for pharmacotherapy is also an important and
desirable treatment goal.
Methods: Data were pooled from two trials that evaluated the efficacy
and safety of short-ragweed sublingual immunotherapy tablet (SLIT-T), MK3641 (Ambrosia artemisiifolia; Merck/ALK-Abelló). Subjects with ragweedpollen–induced AR/C were randomized ~16 weeks before the 2010 pollen
season to once-daily MK-3641 (6 or 12 Amb a 1-U doses; one trial also
included a no-effect dose of 1.5 Amb a 1-U) or placebo. During the trial, all
subjects, whether taking MK-3641 or placebo, could use AR/C rescue
medication, including oral/ocular antihistamines and intranasal/oral
corticosteroids. We examined rescue medication use in all groups.
Results: In pooled results from the two studies, 159 of 318 (50.0%) subjects
receiving MK-3641 12 Amb a 1-U and 144 of 324 (44.4%) subjects receiving
6 Amb a 1-U used no rescue medication over the entire ragweed season,
compared with 109 of 340 (32.1%) subjects receiving placebo. These
differences represented 56% and 38% improvements over placebo. Similarly,
during the peak ragweed season 173 of 311 (55.6%) subjects and 161 of 317
(50.8%) subjects in the 12 Amb a 1-U and 6 Amb 1-U groups, respectively,
reported no rescue medication use, in contrast to 136 of 333 (40.8%)
subjects receiving placebo. Fewer subjects taking 12 and 6 Amb a 1-U (28%
and 19%, respectively) used oral antihistamine than those taking placebo;
35% and 28% fewer subjects used ocular antihistamine; and 43% and 27%
fewer subjects used intranasal corticosteroid (oral corticosteroid was used by
<5 subjects in any group, so rates were not calculated).
Conclusions: Compared with placebo, the SLIT-T treatment MK-3641
reduced rescue-medication use among subjects with ragweed-pollen–
induced AR/C.
Trial registration: ClinicalTrials.gov Identifiers: NCT00783198; NCT00770315.
Chief Medical Officer, Merck & Co., Inc., Whitehouse Station, NJ, USA.
A33
Magnitude of changes in patient symptom and medication scores in
grass allergy immunotherapy trials: dependency on levels of pollen
exposure
Hendrik Nolte1*, Stephen R. Durham2, Harold S Nelson3, David I Bernstein4,
Peter Creticos5, Ziliang Li1, Jens Andersen6, Bente Riis6
1
Merck & Co., Inc., Whitehouse Station, NJ, USA; 2Department of Allergy and
Respiratory Medicine, Imperial College London, London, UK; 3Departments of
Medicine and Pediatrics, National Jewish Health, Denver, CO, USA; 4Bernstein
Page 11 of 22
Allergy Group, Cincinnati, OH, USA; 5Department of Medicine, Johns Hopkins
University School of Medicine, Baltimore, MD, USA; 6ALK-Abelló, Hørsholm,
Denmark
Background: Seasonal allergic rhinitis/rhinoconjunctivitis symptoms are
dependent on pollen exposure and may impact the observed treatment
effect of drugs used to treat seasonal allergic rhinitis. We conducted a posthoc analysis to investigate the impact of pollen exposure on the overall
magnitude of the recorded immunotherapy treatment effect across multiple
seasons and trials of Timothy grass sublingual immunotherapy tablet MK7243 (2800 BAU/75,000 SQ-T Phleum pratense p 5, Merck/ALK-Abelló).
Methods: Data from seven North American and European randomized
placebo-controlled trials of MK-7243 were included in the analysis (GT-02,
GT-07, GT-08, GT-12, P05238, P05239, and P08067; data from GT-14 were
not included since the observed lack of pollen-count/symptom relationship
in this trial suggested etiology other than grass pollen exposure). Boundaries
of three consecutive days with a pollen count ≥10 grains/m3 defined the
grass pollen seasons (GPS). We assessed the correlation of betweentreatment difference in total combined score (TCS; combined symptom
+medication scores) per trial or trial year to the first-20-days-of-GPS
cumulative grass pollen count and entire-GPS average pollen count.
Results: Data from 1798 subjects on MK-7243 and 1765 subjects on
placebo were included in the analysis. TCS for both groups increased
with grass pollen counts. The treatment effect in TCS in each trial (or trial
year) was correlated to the cumulative grass pollen count during the first
20 days of GPS (R2=0.803). A correlation was also seen between TCS and
average pollen count over the entire GPS (R2=0.464).
Conclusions: Post-hoc analysis of seven MK-7243 trials demonstrates that
the magnitude of the treatment effect observed in the trials was highly
correlated to the early-season grass pollen exposure observed in each
trial. Therefore, differences in pollen exposure levels should be
considered when comparing results among pollen immunotherapy trials
and may contribute to observed differences in magnitude of efficacy
between trials using the same immunotherapy formulation.
Trial registration: ClinicalTrials.gov Identifiers: NCT00227279; NCT00408616;
NCT00562159; NCT00550550; NCT01385371, 2 trials not registered.
Chief Medical Officer, Merck & Co., Inc., Whitehouse Station, NJ, USA.
A34
Omalizumab treatment of moderate to severe asthma in the
adolescent and pediatric population
John O’Quinn1*, Stephanie Santucci1, Diana Pham1, Zave Chad2,
Ian MacLusky2, Joseph Reisman2, William Yang1,3
1
llergy and Asthma Research Centre, Ottawa, ON, Canada; 2Department of
Pediatrics, University of Ottawa, ON, Canada; 3University of Ottawa Medical
School, Ottawa, ON, Canada
Background: In Canada and the US, omalizumab is indicated for adults and
adolescents (>12 years of age) with moderate to severe persistent allergic
asthma. In the EU, omalizumab has been approved for children (age 6 – 11
years) since 2009. The pediatric population within Canada and the United
States has very few treatment options available for severe asthma. Current
treatments options can lead to other health concerns such as adrenal
insufficiency and osteoporosis. These cases demonstrate that early
treatment of moderate to severe asthma with omalizumab is an effective
treatment and can help to prevent or reverse damage done by long-term
use of other treatment options.
Methods: A retrospective chart review of our database was performed and
patients ≤ 17 years of age receiving omalizumab treatment were
evaluated. Data was collected on FEV1, inhaled corticosteroid (ICS) and oral
corticosteroid (OCS) use.
Results: 12 patients were identified as 17 years old or younger at the
start of treatment with omalizumab. After the first 6 months of treatment,
all 12 patients showed an increase in FEV1 results and a decrease in ICS
dose. Results also indicated a decrease in OCS use for those patients
taking daily dose as well as those who required periodic bursts to control
asthma exacerbations.
Conclusion: Early treatment of moderate to severe asthma with
omalizumab in adolescent/pediatric patients may improve quality of life
and help prevent health concerns associated with side effects and/or long
term use of ICS and OCS in growing children. Juvenile osteoporosis can be
a significant problem because it occurs during the prime bone-building
years and may lead to reduced peak bone mass and increased risk for
osteoporosis later in life. Regular re-evaluation of the treatment regime to
ensure the use of the lowest effective dose of corticosteroids and
consideration of other treatments would also be beneficial.
A36
Early presentation of clinical hereditary angioedema symptoms in
an infant
Hoang Pham1*, Stephanie Santucci2, William H. Yang1,2
1
University of Ottawa Medical School, Ottawa, ON, Canada; 2Allergy and
Asthma Research Centre, Ottawa, ON, Canada
Background: Timely diagnosis of hereditary angioedema (HAE) is
challenging in children. The barriers include lack of awareness of HAE,
communication difficulties, diagnostic testing limitations, and broad
differential diagnoses for symptoms of HAE. Consequently, there has been
no definitive study on the age of onset of symptoms of HAE in children. This
lack of awareness can result in reduced quality of life due to suboptimal
treatment of symptoms, significant delay in diagnosis, and/or misdiagnosis,
which can result in unnecessary tests, treatments, and procedures. Current
literature suggests that the mean age of onset is in the second decade of
life, which is worsened by puberty, estrogen containing contraception, or
estrogen hormone replacement therapy, but symptoms can also be present
under one year. Here we present a case report of an infant not previously
diagnosed with clinical symptoms of HAE but born from a mother with type
I HAE.
Method: Cord blood for C1-INH and C4 protein quantities were obtained at
time of delivery. Parents were requested to monitor the child for symptoms
and pictures were taken to document any clinically suspicious edema and/or
rashes. Repeat laboratory testing was done after 1 year of age.
Results: Cord blood results show C1-INH <0.12 (0.21-0.39) g/L and C4 0.08
(0.07 – 0.30) g/L. At 9 months, the child’s mother noted slight periorbital
edema, which was documented with pictures. At 14 and 18 months, the
child developed a rash on her torso and arms that resembled erythema
marginatum; both episodes were documented with pictures.
Conclusion: Clinical symptoms of HAE may begin as early as 9 months
without any triggers. Parents and clinicians need to be vigilant and
properly diagnose HAE to optimize the quality of life for these young
patients and their families. We emphasize a high index of clinical suspicion
of HAE should begin even in the early infant period.
A37
A pilot study of quality of life, mood, sleepiness and fatigue in patients
with primary humoral immunodeficiency transitioning to subcutaneous
immunoglobulin therapy
Persia Pourshahnazari1*, Gina Tsai2, Adriana Martin3, Amin Kanani3,
Donald Stark3, R Robert Schellenberg3
1
Department of Internal Medicine, University of British Columbia, Vancouver,
British Columbia, Canada; 2Department of Medicine, Division of Allergy &
Immunology, Schulich School of Medicine & Dentistry, Western University,
London, Ontario, Canada; 3Department of Medicine, Division of Allergy and
Clinical Immunology, University of British Columbia, Vancouver, British
Columbia, Canada
Background: Immunoglobulin replacement therapy is standard of care for
patients with primary humoral immunodeficiency [1]. Compared with
intravenous immunoglobulin (IVIG), subcutaneous immunoglobulin (SCIG)
offers comparable efficacy, lower costs and reduced systemic reactions [2,3].
However, little is known about effects on quality of life when patients
transition from IVIG to SCIG. It was our objective to assess changes in quality
Page 12 of 22
of life, mood, sleepiness and fatigue in patients transitioning from IVIG to
SCIG.
Methods: Adult patients with common variable immunodeficiency or
X-linked agammaglobulinemia transitioning from IVIG to SCIG were invited
to participate in this prospective, open-label, pilot study. At least one set of
Short-Form 36 Health Survey (SF-36), Profile of Mood States (POMS),
Epworth Sleepiness Scale (ESS) and nighttime sleep questionnaires was
administered prior to the final IVIG infusion. These were repeated monthly
for 3 months following the transition. Magnitude of change was estimated
between IVIG trough and final SCIG steady-state data. Statistical significance
was determined using linear mixed models for repeated measures with
Kenward-Rogers correction.
Results: Twenty-seven patients were included in the analysis. Two of
eight SF-36 quality of life domains showed significant improvement: role
limitations due to physical health (p = 0.01) and emotional problems (p =
0.04). Two of six POMS mood subscales significantly improved: depression
(p = 0.03) and anger (p = 0.04). One of six POMS mood subscales
(tension, p = 0.08) and POMS total mood disturbance scores (p = 0.09)
trended towards improvement. No significant changes were noted in ESS
or nighttime sleepiness scores.
Conclusions: Patients transitioning from IVIG to SCIG for treatment of
primary antibody immunodeficiency showed significant improvement in
several quality of life and mood subscales. A larger study verifying these
findings could encourage patients to switch to SCIG self-administration,
producing quality of life benefits while decreasing health care costs.
References
1. Chapel HM: Consensus panel for the diagnosis and management of
primary antibody deficiencies: consensus on diagnosis and management
of primary antibody deficiencies. Br Med J 1994, 308:581-585.
2. Abolhassani H, Sadaghiani MS, Aghamohammadi A, Ochs HD, Rezaei N: Homebased subcutaneous immunoglobulin versus hospital-based intravenous
immunoglobulin in treatment of primary antibody deficiencies: systematic
review and meta analysis. J Clin Immunol 2012, 32(6):1180-92.
3. Ho C, Membe S, Cimon K, Roifman C, Kanani A, Morrison A: Subcutaneous
versus intravenous immunoglobulin for primary immunodeficiencies:
systematic review and economic evaluation. Technology report number 98
Ottawa: Canadian Agency for Drugs and Technologies in Health 2008.
A38
Buckwheat anaphylaxis: a case report
Persia Pourshahnazari1*, Gordon Sussman2
1
Department of Internal Medicine, University of British Columbia, Vancouver,
British Columbia, Canada; 2Department of Clinical Immunology and Allergy,
University of Toronto, Toronto, Ontario, Canada
Case: A healthy 32-year-old Chinese female presented with three episodes
of allergic reactions after ingestion of buckwheat. She was assessed in the
allergy clinic after eating cake containing buckwheat flour. After a few bites
she experienced tongue tingling and throat tightness. Within 30 minutes
she developed urticaria, nausea and abdominal cramping, which subsided
with diphenhydramine. Eight months prior she had an episode of
abdominal cramping, urticaria and lip angioedema within 45 minutes of
eating multigrain toast. Two years earlier she had eaten buckwheat noodles
at a restaurant in China. She developed abdominal cramping, emesis and
throat tightness 30 minutes after ingestion, and was treated at a local
emergency department. There was no other history of food, drug, insect or
latex allergy.
Skin prick testing was performed for food allergies. All food skin tests were
negative with appropriate controls. Skin prick testing was performed to the
extracted cake and was strongly positive at 9mm (W9F29). Prick testing to
extracted buckwheat was remarkably positive at 48mm (W48F70). Specific
IgE to buckwheat was obtained and was high at 6.13KU/L.
Discussion: Common (Fagopyrum esculentum) and tartary (Fagopyrum
tartaricum) buckwheat are members of the Polygonaceae family that are
taxonomically unrelated to wheat [1,2]. They contain no gluten and have
emerged as a popular substitute for celiac or wheat intolerant patients.
Buckwheat has been described as a potent allergen in Asia where it is
commonly consumed, with fewer cases described in Europe and North
America [1]. Severe symptoms including anaphylaxis can occur after
ingestion or inhalation of buckwheat, with Fag e 1 and Fag e 2 proteins
identified as major allergens [3].
Conclusions: Buckwheat represents a major food allergen in Asia where
consumption is high. With growing popularity in North American diets,
increased awareness is necessary as exposures to this potent allergen
become more common.
References
1. Sammut D, Dennison P, Venter C, Kurukulaaratchy RJ: Buckwheat allergy: a
potential problem in 21st century Britain. BMJ Case Rep 2011, pii:
bcr0920114882.
2. Sujin L, Youngshin H, Jeong-Ryong D, Sangsuk O: Allergenic potential and
enzymatic resistance of buckwheat. Nutr Res Pract 2013, 7(1):3-8.
3. Kimiko T, Kunie K, Hitoshi T, Hiroaki M, Satoshi N, Eishin M: Usability of Fag
e 2 ImmunoCAP in the diagnosis of buckwheat allergy. Arch Dermatol
Res 2011, 303(9):635-42.
A39
Reconciliation of health records following penicillin allergy testing of
hospitalized patients
Rebecca Pratt1*, Anna Romanova2, Joseph Greenbaum1, Michael Cyr1
1
Department of Medicine, Division of Clinical Immunology and Allergy,
McMaster University, Hamilton, Ontario, Canada; 2Department of Medicine,
University of Ottawa, Ottawa, Ontario, Canada
Background: Medication errors are common and can lead to substantial
morbidity. Similarly, inaccurate medication allergy lists can result in
increased costs to the system, unnecessary allergy testing, prescription of
inappropriate antibiotics, and allergic reactions. We hypothesized that
most inpatients tested for penicillin allergy were not allergic and this
information was not documented in the EMR or communicated to general
practitioners.
Methods: We retrospectively reviewed charts of all inpatients seen at a
teaching hospital by a consultant allergist in 2012. Data collected included
basic demographics, penicillin allergy test results, current allergy status in
the EMR, readmission rates, prescribed antibiotics, and discharge summary
contents.
Results: 146 patients were tested for penicillin allergy and 144 (98.6%) were
not allergic. Although orders were written in 145 (99.3%) charts to update
the allergy status after testing, 32 (22.23%) patients with negative tests were
still listed as allergic to penicillin in the EMR. Only 19 (15.2%) discharge
summaries notified family physicians of the allergy testing results and
discharge summaries were missing for 25 (20%) patients. Further
assessment of half the charts revealed that in 41% of cases the negative
allergy test resulted in a change of antibiotic to penicillin or its derivative. Of
the 60 readmitted patients, 20 (33%) were still listed as allergic to penicillin
in the EMR (only one patient tested positive) and 14 (70%) of the 20
patients required antibiotics. 12 of these 14 patients (86%) were prescribed
antibiotics in the penicillin family despite their positive allergy status.
Conclusions: A significant proportion of health records were not amended
following antibiotic allergy testing and the new allergy status was not
communicated to most general practitioners in the discharge summary.
A more efficient and reliable system needs to be implemented to ensure
allergy status changes are communicated to all members of the healthcare
team.
A41
A case of acquired angioedema associated with Waldenstrom’s
macroglobulinemia treated with rituximab
Caroline Rizk1*, William H. Yang2,3, Jason Tay2, Jacob Karsh2
1
Department of Clinical Immunology and Allergy, McGill University, Montreal,
QC Canada; 2Department of Internal Medicine, University of Ottawa, Ottawa,
ON, Canada; 3Ottawa Allergy Research Corporation, Ottawa, ON, Canada
Background: Acquired angioedema (AAE) is a rare disorder caused by
acquired deficiency of C1 inhibitor (C1-INH), very often seen in association
Page 13 of 22
with lymphoproliferative diseases. The key elements of AAE are acquired
deficiency of C1 inhibitor, hyperactivation of the classical pathway of
complement, and recurrent angioedema symptoms.
Case presentation: We report a case of Waldenstrom´s macroglobulinemia
causing an acquired deficiency of C1 esterase inhibitor in a 40-year-old
woman. She initially presented with an episode of angioedema followed by
many episodes of abdominal distention associated with pain, vomiting, and
diarrhea for 1.5 years. Work-up revealed low C1 esterase inhibitor levels,
normal C3, and nonexistent C4. A diagnosis of acquired C1 esterase inhibitor
deficiency was proposed at the time. However, it was also noted that her
IgM was very elevated with an IgM monoclonal gammopathy with kappa
light chains, and an enlarged spleen. Bone marrow biopsy and aspirate
revealed clonal B-cells staining positively for CD20. She was diagnosed with
Waldenstrom´s macroglobulinemia in association with C1 esterase inhibitor
deficiency. Although the association is recognized, it is rare, and likely
secondary to antibodies against C1 esterase inhibitor. After treatment with
rituximab, cyclophosphamide, and prednisone, her paraprotein levels fell to
normal range, and her autoimmune parameters normalized with significant
clinical improvement. She has not had any further episodes of angioedema.
She will continue on rituximab as maintenance therapy for 2 more years.
Conclusion: Acquired deficiency of C1 esterase inhibitor is quite rare with
just over 100 cases in the literature. Given that most cases are related to
antibodies against C1 esterase inhibitor, rituximab may be the treatment of
choice. However, treatment of the underlying lymphoproliferative disorder
may need to be considered as well and could provide a more definitive
treatment.
A42
Diagnosis of autoimmune disease in the setting of immunodeficiency
Lana Rosenfield1*, Richard Warrington2
1
Department of Internal Medicine, University of Manitoba, Winnipeg, Manitoba,
Canada; 2Section of Allergy and Clinical Immunology , Department of Internal
Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
Background: Autoimmune disease and immunodeficiency in the same
patient can be a diagnostic dilemma but there is evidence of these
conditions occurring simultaneously.
Case: A 41-year-old male presented with abdominal pain, diarrhea,
weakness, and shock. He was diagnosed with cardiac tamponade,
underwent pericardial drainage and initiation of broad-spectrum antibiotics.
The patient had a recent admission with bilateral pleural effusions, with
negative infectious and malignancy workup. Macrocytic anemia, increased
white blood cells, incidental abdominal abscess and splenic infarcts were
found during this admission.
Investigations again demonstrated elevated white blood cells (53.8%
neutrophils, 12.1% lymphocytes, 29.7% monocytes) and anemia.
Autoimmune workup was unremarkable except for presence of atypical
ANCA and lupus inhibitor. Bone marrow biopsy was non-specific. He had
low IgM and IgG levels suggesting a diagnosis of Common Variable
Immunodeficiency (CVID). He received intravenous Solumedrol after his
respiratory status deteriorated. He improved and was transitioned to
prednisone, but a pathogen was never found.
His positive response to steroids with worsening symptoms with prednisone
taper initiation suggested that this was an autoimmune process. He was
started on Hydroxychloroquine and intravenous immunoglobulin by
Rheumatology. However he was subsequently diagnosed with Chronic
Myelomonocytic Leukemia (CMML) based on cytogenetic studies by
Hematology. Current treatment includes hydroxyurea and prednisone.
Discussion: This patient demonstrates the challenge of diagnosing
autoimmunity in a patient with low levels of immunoglobulins such as in
CVID. How to interpret autoimmune antibody titres in autoimmune conditions
is unknown. Most literature describes immunodeficiency being diagnosed
after the autoimmune condition [1] and often after immunosuppressant use.
Studies on systemic lupus erythematosus and CVID have shown low levels of
autoantibodies after immunodeficiency diagnosis.
Conclusion: This case indicates the dilemma of excluding autoimmune
disease in CVID. Although CMML was present, its presentation was atypical
and is not known to be associated with CVID.
Reference
1. Agarwal S, Cunningham-Rundles C: Autoimmunity in common variable
immunodeficiency. Curr Allergy Asthma Re 2009, 9:347-52.
A43
Diagnosing penicillin allergy in the absence of minor determinant
mixture
Lana Rosenfield1*, Chrystyna Kalicinsky2, Richard Warrington2
1
Department of Internal Medicine, University of Manitoba, Winnipeg,
Manitoba, Canada; 2Section of Allergy and Clinical Immunology, Department
of Internal Medicine, University of Manitoba, Winnipeg, Manitoba, Canada
Background: Penicillin allergy is a common presentation in allergy clinic.
The diagnosis of immediate hypersensitivity is made using clinical history,
skin testing, specific IgE levels and oral challenge. Skin testing is done
using benzyl penicilloyl-polylysine (PPL) and a minor determinant mixture
(MDM) consisting of penicillin byproducts. Although using PPL and MDM
is considered first line for diagnosis [1], our clinic is unable to consistently
obtain MDM. We have undertaken a retrospective chart review to assess
our current protocol in diagnosing penicillin allergy using Penicillin G (PG)
alone instead of MDM.
Methods: Charts of patients presenting to Allergy clinic with penicillin
allergy between December 2005-Dec 2013 were reviewed. Skin testing by
intradermal and skin prick testing was done using PPL and MDM or PG in
addition to other possible suspected antibiotics. Patients who were
negative for specific IgE testing to penicillin V and G (Immunocap) and
had negative skin tests had oral challenge to penicillin.
Results: Of 520 charts reviewed, 240 patients met criteria for analysis. 18
out of 240 patients had positive skin testing, eight to PPL, five to PG, four
to MDM, six to ampicillin and one to ceftriaxone. Three patients had
positive specific IgE levels with negative skin tests to PPL and PG. 222
patients underwent challenge. 88/222 had been skin tested to MDM and
8/88 had a positive challenge. 134/222 had been skin tested to PG and 4/
134 had a positive challenge.
Conclusion: 9% of patients with positive oral challenge had negative
testing with MDM compared to 3% with PG. Therefore we conclude that
our current protocol is appropriate in diagnosing patients with penicillin
allergy.
Reference
1. Romano A, Bousquet-Rouanet L, Viola M, Gaeta F, Demoly P, Bousquet PJ:
Benzylpenicillin skin testing is still important in diagnosing immediate
hypersensitivity reactions to penicillins. Allergy 2009, 64:249-253.
A44
Food allergic teens: education, anaphylaxis and concerns
NL Ross1*, CA Gillespie1, CR Unruh2, AB Becker1,2
1
Children’s Allergy & Asthma Education Centre, Health Sciences Centre,
Winnipeg, Manitoba, R3E 0Z2, Canada; 2University of Manitoba, Winnipeg,
Manitoba, R3E 0W2, Canada
Background: Adolescents with food allergy are at particular risk for life
threatening anaphylaxis. Management of food allergies includes preventing,
recognizing and responding to reactions. Focus groups were held as a
preliminary step in the planning and development of effective education for
this group.
Methods: Focus groups were held from January to April 2014. Semi
structured interviews were conducted to gather information about what
teens with food allergy needed to know and how they like to learn.
Interviews were digitally recorded, transcribed and reviewed.
Page 14 of 22
Results: 16 adolescents (M = 11, F = 5); age 12-19; 15/16 peanut allergic,
10/16 other food allergens.
All had epinephrine auto-injectors (EpiPen = 11; Allerject = 5).
Teens believe they are well informed; often from parents; however they did
identify important topics to incorporate into an education program for teens.
Teens need/want to learn more about: cross-contamination, advisory
statements on food labels, allergens in non-food products, recognizing a
reaction, staying calm during a reaction, teaching friends – signs of a reaction
and auto-injector use, communicating confidently with others – strategies for
what to say in situations and hands on practice with the auto-injectors.
Food allergy related topics teens would like to discuss: travelling, dating,
partying, grocery shopping, cooking, symptoms of a reaction versus
anxiety, new treatments and research.
Concerning themes around anaphylaxis noted were: reactions are dealt
with by “waiting it out” or “sleeping it off”; epinephrine is only used if you
can’t breathe, can’t talk or think you’re dying); antihistamines can be used
as first line treatment.
Conclusion: This study highlights knowledge gaps that exist around
anaphylaxis in this group and identifies important topics to incorporate into a
program. An education program delivered in an effective manner for
adolescents that addresses these gaps and provides strategies to help manage
food allergy may be helpful and increase confidence for this high-risk group.
Acknowledgement: Funding provided by Canadian Allergy, Asthma and
Immunology Foundation (CAAIF).
A45
Self-administration of a novel subcutaneous bradykinin b2 receptor
antagonist, icatibant, as an effective treatment option in patients with
hereditary angioedema
Stephanie Santucci1*, Hoang Pham2, Rachel Harrison1, William Yang1,2
1
Background: Hereditary Angioedema (HAE) is a rare disease characterized
by recurrent angioedema attacks involving larynx, abdomen, extremities and
various body parts. The reactions are by and large self-limited, but potentially,
could be fatal. Until recently, the only approved treatment in Canada is an
intravenous C1-esterase inhibitor infusion. However, intravenous therapy can
be challenging for those who have co-morbid disorders. Icatibant (Firazyr®) —
which received approval in Canada in June 2014 — offers administration
through subcutaneous delivery. Through a special access program, here we
present self-administered icatibant treatment on a female subject with
Charcot-Marie-Tooth disease, a rare genetic, neuromuscular disorder, which
limits her ability to self-administer intravenous therapy.
Methods: During each icatibant self-administration event, a diary method
was used to collect the following patient-reported outcomes: attack
intensity, anatomical location & trigger, number of doses, onset of relief,
time elapsed until complete resolution, and adverse reactions.
Results: From 2012- May 2014, the patient logged a total of 12 events, in
which she treated each attack with a single self-administered 30 mg dose of
icatibant via subcutaneous injection. She experienced moderate to severe
abdominal and peripheral HAE attacks. Onset of relief occurred within 15 – 30
minutes and complete resolution occurred within 4-hours to 5-days. Adverse
reactions were mild in severity, transient, and resolved without further
intervention. They included local injection site reaction (100%), headache
(58%), fatigue (25%), feeling “fuzzy-brained” (25%), and hot flush (8%).
Conclusion: This case report provides supporting evidence for icatibant
as an effective, safe and viable subcutaneous therapeutic alternative to
intravenous treatments for patients with HAE.
A47
Trafficking of TNF via recycling endosomes in neutrophils
Nutan Srivastava*, Paige Lacy
Pulmonary Research Group, Department of Medicine, University of Alberta,
Edmonton, Alberta, Canada
Background: Neutrophils are highly abundant innate immune cells that
contribute to asphyxic episodes of acute asthma exacerbations, and secrete
the proinflammatory cytokine tumour necrosis factor-a (TNF). Recycling
endosomes (REs) are specialized secretory compartments that perform
multiple functions including trafficking of cytokines to cell surfaces, although
these are not characterized in neutrophils. Our objective is to identify
trafficking components in neutrophils that may contribute to cytokine
secretion.
Methods: The effect of bacterial lipopolysaccharide (LPS) stimulation on
the trafficking of stored and newly synthesized TNF was determined by
treatment of human peripheral blood neutrophils with or without
cycloheximide. To visualize intracellular TNF, neutrophils were adhered to
glass slides and treated with LPS for 1 h (10 ng/ml). Colocalization of
TNFa in neutrophils was performed with transferrin-Alexa 488 and antiVAMP3 (markers for RE), anti-CD63 and anti-CD66b a membrane markers
for the primary and secondary granules in neutrophils, respectively. We
also determined Rab5 and Rab7 colocalization with TNF (markers for early
and late endosomes, respectively). Imaging was carried out by Deltavision
OMX super resolution microscopy.
Results: LPS induced 30-40% TNF secretion from stored sources, with the
remainder newly synthesized. We found that neutrophils possess REs as
determined by transferrin uptake and VAMP3 labeling. TNF also colocalized
with REs, primary and secondary granules as well as early and late
endosomes, suggesting multiple sites of TNF storage and trafficking in
neutrophils. However, TNF only colocalized with VAMP3 around periphery of
cells after 1 h stimulation with LPS, suggesting TLR4-induced TNF trafficking
via REs.
Conclusions: The present study provides evidence that movement of TNF+
VAMP-3 + vesicles towards the cell periphery in response to LPS. This
suggests that neutrophils utilize REs for trafficking of TNF to the cell surface
in response to TLR4 signalling. These findings contribute to our
understanding of how neutrophils package, transport, and release cytokines.
A48
A post-hoc qualitative analysis of real time heads-up pollen counting
versus traditional microscopy counting in the environmental exposure
unit (EEU)
Lisa M Steacy1*, Terry JB Walker1, Barnaby Hobsbawn1, Jenny Thiele2,
Anne K Ellis1,2
1
Allergy Research Unit, Kingston General Hospital, Ontario, Canada;
2
Department of Medicine, Queen’s University, Kingston, Ontario, Canada
Background: A custom digital imagery method for real time identification
and counting of pollen was qualitatively evaluated in the Environmental
Exposure Unit (EEU).
Methods: Airborne grass pollen was collected in the EEU via a Rotorod®
impact sampler. The pollen grains on each sampling rod were counted
using both traditional and heads-up microscopy. The heads-up technique
incorporated a microscope camera to create an on-screen image of the
sampling rod. Firstly, unique images were created by manually advancing
the stage, without duplicating previously captured pollen grains. Welldefined, sharp images were obtained by fine focus and zoom
combinations to enhance certainty and recognition speed. Secondly, using
a custom application, each pollen grain was identified and counted onscreen by “point and click” or “screen touch”, simultaneously counting and
permanently anchoring opaque dots to the pollen grain locations. Counts
were stored in real time on a central database.
Results: Increased clarity of the pollen grains resulted in higher counting
accuracy. Duplicate counting of pollen grains was eliminated by digitally
labelling counted grains. Additional need for manual counting devices,
commonly associated with mechanical and human errors, was eliminated.
Error free counts can be obtained with increased speed, therefore,
improving the overall efficiency of the process and the EEU system as a
whole.
Conclusions: This validated heads-up counting technique will allow for
an increased response time to changes in the EEU pollen levels. This
advancement could also enhance pollen counting processes followed by
others using direct microscopy pollen counting techniques.
Page 15 of 22
A49
Teenagers and food allergy education: a systematic review
Claire R Unruh1,2*, Cathy A Gillespie2, Nancy L Ross2, Allan B Becker1,2
1
Pediatric Allergy and Immunology, University of Manitoba, Canada; 2Children’s
Allergy and Asthma Education Centre, Winnipeg, Manitoba, Canada
Background: As adolescents transition away from the comforts of their
homes and parental guidance and into a more independent and changing
lifestyle, those who are food allergic also become part of a high at-risk
population for severe anaphylaxis.
Many fatal and near fatal anaphylaxis due to foods occur in young adults
and teens and this age group has a great need for food allergy education
as they encounter themselves developing hypothetical-deductive logic,
risk-taking and greater self-consciousness.
Methods: Systematic literature review and analysis of 142 articles. Terms
included in the search included; Teens, Teen Learning Styles, Teens and
Allergies/Asthma, Teens and Technology, Teens and Social Media.
Results: It is important to understand that the most common themes
found in the literature concerning teens and food allergies were very
closely tied to changes that teens face in their transition to independence.
Understand that teens are constantly changing and as such, their critical
thinking is developing, affecting their decision-making. The ego-centrism
that develops in many teens includes the feelings that they believe they
are immune to harm and less vulnerable to negative events that threaten
their safety as they take risks, especially those with food allergies.
Deviations from the norm pose a threat to adolescent development and can
harm teens’ psychological well-being and even their lives. To save face and
preserve this norm, adolescents with food allergies are more likely to take
risks (including with their allergies) and increase the potential to cause harm
to themselves, especially when with peers.
Teen learning styles are also changing and now include much more
technology and internet-oriented learning. Internet usage is high in teens,
and they are very comfortable with cell phones and smart phones. With the
help of text messages, apps, and social media networking, teens are able to
make many different connections around them.
Conclusion: This literature review showed that transition through
adolescence to early adult life is a crucial time to equip teens with an
understanding of how to handle food allergies in a safe manner.
Expanding teen’s knowledge and establishing safe behaviors regarding
food allergies is important when approaching to develop a teen food
allergy education program.
Planning a program that interests, engages and educates teens about
their allergies and aids them to become advocates for themselves and
others with food allergies may be a crucial part in keeping this age group
out of harm’s way.
A50
Proteinase-activated receptor-2 (PAR-2) expression on inflammatory
cells in severe asthma
Drew Nahirney, Nami Shrestha Palikhe, Cheryl Laratta, Vivek Gandhi,
Dilini Vethanayagam, Mohit Bhutani, Irvin Mayers, Lisa Cameron,
Harissios Vliagoftis*
Pulmonary Research Group, Department of Medicine, and Alberta Asthma
Center, University of Alberta, Edmonton, AB, Canada
Background: PAR-2, a G-coupled receptor activated by serine proteinases,
is widely expressed in the human body and is involved in inflammation.
We have shown that PAR-2 activation in the airways plays a pathogenetic
role in mouse models of asthma. PAR-2 expression is increased in the
epithelium of asthmatic subjects, but its expression on immune and
inflammatory cells of asthmatic individuals has not been. Severe asthma
has different phenotypic characteristics from mild-moderate disease. In
this study we compared PAR-2 expression on immune cells between
subjects with mild/moderate and severe asthma.
Methods: A total of 36 asthma subjects (24 mild/moderate; 12 severe by
ATS guidelines) were recruited at the University of Alberta Hospital and
peripheral blood obtained. PAR-2 expression was analyzed by flow
cytometry and qRT-PCR in whole blood.
Results: There were no differences in the % of eosinophils, neutrophils or
CD4+ T cells expressing PAR-2 between severe and mild/moderate
asthmatics. CD14high monocytes were classified as classical (CD14++CD16-)
or intermediate (CD14++CD16+). No difference in total numbers of either
monocyte sub-population was noted between the two asthma groups. More
intermediate monocytes from patients with severe asthma (33.6±5.1%)
expressed PAR-2 compared to patients with mild/moderate asthma
(22.4±4.0%, p=0.039), but there was no difference between asthma
phenotypes in the percent of classical monocytes expressing PAR-2
(11.7±2.8% vs. 12.5±2.9%). PAR-2 mRNA expression was not different
between severe and mild/moderate asthmatics, however, PAR-2 mRNA
correlated with total dose of inhaled steroids and inversely correlated with
% predicted FEV1.
Conclusions: PAR-2 expression is increased on intermediate monocytes in
subjects with severe asthma. Intermediate monocytes are pro-inflammatory
and their numbers are increased in inflammatory diseases. Our data suggest
that PAR-2-mediated activation of intermediate monocytes may play a role
in the pathogenesis of severe asthma, although the effects of PAR-2mediated activation of these cells are not known.
A51
Analysis of icatibant for the treatment of laryngeal hereditary
angioedema attacks in the FAST-3 study
William Yang1*, Jacques Hébert2, Bruce Ritchie3, Jovanna Baptista4, Marc Riedl5,
William R Lumry6
1
Allergy & Asthma Research Centre, Ottawa, ON, Canada; 2Centre de
Recherche Appliquée en Allergie de Québec, Québec City, QC, Canada;
3
University of Alberta, Edmonton, AB, Canada; 4Shire, Lexington, MA, USA;
5
University of California - San Diego, La Jolla, CA, USA; 6AARA Research
Center, Dallas, TX, USA
Background: The efficacy and safety of icatibant for the treatment of
edematous hereditary angioedema (HAE) attacks was established in three
Phase III trials, including the For Angioedema Subcutaneous Treatment-3
study (FAST-3; NCT00912093). Here, data from the double-blind, controlled
phase and open-label extension (OLE) of FAST-3 were analyzed post-hoc to
specifically evaluate icatibant for the treatment of laryngeal attacks, which
can cause potentially fatal airway obstruction.
Methods: Controlled phase: adults with HAE type I/II were randomized to
a single subcutaneous injection of icatibant 30 mg or placebo for their first
mild-to-moderate laryngeal attack or moderate-to-very severe cutaneous/
abdominal attack; severe laryngeal attacks were treated with open-label
icatibant. OLE: attacks were treated with up to three icatibant injections, at
≥6-hour intervals. Three outcomes were analyzed for first icatibant-treated
laryngeal attacks: 1) time to onset of symptom relief (earliest of three
consecutive measurements for which there was a 50% reduction of
patient–assessed 5-symptom composite 100 mm visual analog scale [VAS]);
2) time to almost complete symptom relief (earliest of three consecutive
measurements for which all VAS symptom scores <10 mm); 3) patient- and
investigator-assessed time to initial symptom improvement. Reinjection
rates were also recorded.
Results: For first icatibant-treated laryngeal attacks in the controlled phase
or OLE (n=27), median (95% CI) time to onset of symptom relief was 2.0
(1.5-3.5) hours, median (95% CI) time to almost complete symptom relief
was 6.0 (3.0–24.3) hours, and median (95% CI) patient- and investigatorassessed time to initial symptom improvement was 0.7 (0.4-0.9) and 0.8 (0.51.1) hours, respectively. In the OLE, 41/43 (95.3%) laryngeal attacks were
treated with one icatibant injection, 2/43 (4.7%) were treated with two
injections, and none required three injections.
Conclusions: Icatibant provided symptom relief for mild-to-severe
laryngeal HAE attacks in FAST-3. In the OLE, almost all laryngeal attacks
were treated with one injection only.
Page 16 of 22
A52
Tiotropium respimat® add-on therapy reduces airflow obstruction in
patients with symptomatic moderate asthma, independent of TH2
inflammatory status
WH Yang1*, T Casale2, ED Bateman3, R Dahl4, E Pizzichini5, M Vandewalker6,
JC Virchow7, M Engel8, PM Moroni-Zentgraf8, H Schmidt9, HAM Kerstjens10
1
Allergy & Asthma Research Centre, Ottawa, Canada, K1Y 4G2; 2Division of
Allergy and Immunology, Creighton University, Omaha, NE, USA; 3Department
of Medicine, University of Cape Town, Cape Town, South Africa; 4Aarhus
University Hospital, Aarhus, Denmark; 5NUPAIVA (Asthma Research Centre),
Universidade Federal de Santa Catarina, Florianópolis, Brazil; 6Clinical Research
of the Ozarks, Columbia, MO, USA; 7Department of Pulmonology, Intensive
Care Medicine, Zentrum für Innere Medizin, Klinik I, University Clinic Rostock,
Rostock, Germany; 8TA Respiratory Diseases, Boehringer Ingelheim Pharma
GmbH & Co. KG, Ingelheim am Rhein, Germany; 9Boehringer Ingelheim
Pharma GmbH & Co. KG, Biberach an der Riss, Germany; 10Department of
Pulmonary Medicine, University Medical Center Groningen, University of
Groningen, Groningen, The Netherlands
Rationale: In patients with symptomatic asthma receiving ICS or ICS+
LABA, Phase III studies have demonstrated improved lung function with
tiotropium Respimat®, a once-daily long-acting anticholinergic
bronchodilator. The efficacy of some treatments (eg ICS and omalizumab),
appears higher in T H2-high phenotypes, but no specific treatments are
available that work equally well in both TH2-high and TH2-low phenotypes.
We explored whether T H 2 biomarker status influenced responses to
tiotropium in patients with moderate symptomatic asthma.
Methods: In two replicate Phase III, randomized, double-blind, placebocontrolled, parallel-group trials (NCT01172808/NCT01172821), patients with
moderate symptomatic asthma, using medium-dose ICS (400-800 µg
budesonide equivalent), were administered once-daily tiotropium Respimat®
5 µg or 2.5 µg, placebo, or salmeterol (active comparator without inferential
analysis). Co-primary endpoints included peak and trough FEV1 response
(difference from baseline) at 24 weeks. Pre-planned analyses (pooled
population) were performed in TH2-high and TH2-low subgroups defined at
baseline as total serum IgE ≤ or >430 µg/L) or blood eosinophils ≤ or
>0.6×109/L.
Results: Of 1545 patients in the full analysis set who received tiotropium
or placebo, 915/1455 were reported with IgE >430 µg/L and 300/1461
with an eosinophil count of >0.6×10 9 /L. Peak FEV 1 improved with
tiotropium versus placebo, independent of IgE (p<0.0001 both doses) and
eosinophil count (p<0.0001 both doses). Trough FEV1 also improved with
tiotropium versus placebo, irrespective of IgE (p<0.0001 both doses) and
eosinophil count (p<0.005 both doses).
Conclusions: Once-daily tiotropium Respimat® as add-on to ICS reduces
airflow obstruction in patients with moderate symptomatic asthma,
independent of T H 2 phenotype, and thus may potentially provide an
important therapeutic option.
Funding source: Study supported by Boehringer Ingelheim. Previously
presented at AAAAI 2014 in San Diego, CA, USA.
Acknowledgements: We thank Dr W.H. Yang for presenting this study
on behalf of the authors
A53
Deep TCR repertoire sequencing reveals relative change in peanut
specific clonotype in subjects undergoing rush oral immunotherapy
Philippe Bégin1,2*, Kari C Nadeau1
1
Department of Pediatrics, Stanford University, Stanford, California, 943055208, USA; 2Department of Medicine, University of Montreal, Montreal,
Quebec, H3A 1A1, Canada
E-mail: [email protected]
Background: Oral immunotherapy is an emerging therapy currently under
investigation for the treatment of food allergy [1]. Underlying mechanisms
are thought to involve a switch in the food specific T cell response from
Th2 to either Th1, Tr1 and/or Treg. It is unknown whether this change in
response results from re-education of existing pathological food-specific
Page 17 of 22
T cells or from their replacement by new healthy T cells (change of guard
hypothesis).
Methods: The objective was to evaluate the clonal distribution of peanut
specific T cell in subjects with peanut allergy and follow changes in
clonotype with treatment using a high-throughput T cell receptor (TCR)
sequencing platform. Peripheral blood mononuclear cells (PBMCs) from
three subjects undergoing rush oral immunotherapy in a previous trial [2]
and three control subjects on avoidance diet were cultured with peanut
extract at baseline and at 9 and 18 months. Carboxyfluorescein succinimidyl
ester (CFSE)-low peanut proliferating T cells were then isolated by
fluorescence-activated cell sorting (FACS) and TCR analysis was performed.
Results: The CFSE-low proliferating fraction was found to be comprised of
between 2000 and 12,000 different T cell clones. However, only between 15
and 25% of proliferating T cells (from 100-400 different clones) were
consistently found at all three time points and probably represented true
peanut-specific T cells. While the relative frequency of these peanut-specific
clones was stable over time in subjects on avoidance diet (R=0.633 to 0.760),
it was found to change in subjects undergoing oral immunotherapy (R=
0.123 to 0.350), following two characteristic patterns.
Conclusions: Using a deep TCR sequencing platform, we found that only
a fraction of CFSE-low peanut proliferating T cells were consistent in time
and likely to represent true peanut specific T cells. Oral immunotherapy
was associated with changes in relative frequency of clones within this
fraction, which would support the change of guard hypothesis.
Acknowledgements: P. Bégin was supported by AllerGen NCE Inc. (the
Allergy, Gene and Environment Network), a member of the Networks of
Centre of Excellence Canada program
References
1. Bégin P, Chinthrajah RS, Nadeau KC: Oral immunotherapy for the
treatment of food allergy. Hum Vaccin Immunother 2014, 10:8.
2. Bégin P, Dominguez T, Wilson SP, Bacal L, Mehrotra A, Kausch B, Trela A,
Tavassoli M, Hoyte E, O’Riordan G, Blakemore A, Seki S, Hamilton RG,
Nadeau KC: Phase 1 results of safety and tolerability in a rush oral
immunotherapy protocol to multiple foods using Omalizumab. Allergy,
Asthma & Clinical Immunology 2014, 10:7.
A54
Impact of air pollution on physician office visits for common childhood
conditions in Ontario, Canada
Laura Feldman1,2*, Chenwei Gao1,3, Jingqin Zhu1,3, Jacqueline Simatovic1,
Teresa To1,2,3
1
Child Health Evaluative Sciences, The Hospital for Sick Children, Toronto,
Ontario, M5G 1X8, Canada; 2University of Toronto, Toronto, Ontario, M5S
1A1, Canada; 3Institute for Clinical Evaluative Sciences, North York, Ontario,
M5T 3M6, Canada
Background: Children are particularly sensitive to air pollutants, due to
factors such as ongoing lung development and choice of activities [1].
We evaluated the impact of fine particulate matter (PM2.5) on physician
office visits for common conditions in children in Ontario, Canada.
Methods: PM 2.5 and temperature measurements were obtained from
satellite data for all of Ontario [2]. Physician office visits were stratified
into two groups based on the literature: air pollution-sensitive (acute
respiratory infections, allergic rhinitis, asthma, bronchiolitis, diabetes, otitis
media) and air pollution-insensitive (gastroenteritis, injuries). Claims data
were obtained for every month in 2010 from health administrative
databases for children 0-14 years of age. Age- and sex-standardized
morbidity ratios (SMRs) were calculated by region in Ontario. Spatial
Poisson regression models were used to analyze the relationship between
PM2.5 and physician office visits, with temperature as a covariate.
Results: Crude rates of physician office visits are presented in Table 1. As
expected, fine particulate was significantly associated with monthly rates
of physician office visits for air pollution-sensitive conditions, and not for
insensitive conditions. Fitted SMRs for air pollution-sensitive conditions
are presented in Figure 1. SMRs for sensitive and insensitive conditions
were strongly positively correlated (r = 0.53), and data were spatially
autocorrelated. This suggests an underlying spatial process that
influences physician office visit rates for common childhood conditions,
both for air pollution-sensitive and -insensitive conditions.
Conclusions: In this analysis PM 2.5 , was significantly associated with
physician office visits for air pollution-sensitive conditions. Areas with
high PM2.5 levels and SMRs higher than 1 were identified; children with
air pollution-sensitive conditions in these areas may benefit from targeted
air pollution reduction interventions. Additionally, future analysis should
evaluate the role of household income and access to care in influencing
the spatial pattern of primary health care utilization for common
childhood conditions across Ontario.
References
1. WHO-Europe: Effects of Air Pollution on Children’s Health and
Development. A Review of the Evidence. Special Programme on Health
and Environment Bonn: World Health Organization, European Centre for
Environment and Health 2005.
2. Battelle Memorial Institute, Center for International Earth Science Information
Network CIESIN - Columbia University: Global Annual Average PM2.5 Grids
from MODIS and MISR Aerosol Optical Depth (AOD). Palisades, NY: NASA
Socioeconomic Data and Applications Center (SEDAC) 2013.
A55
Tobacco smoke induces changes in IL-1 family in bronchial epithelial
cells obtained from asthmatic individuals
Valérie Gagné-Ouellet1*, Éric Jacques2, Anne-Marie Boucher-Lafleur1,
Sophie Plante2, Luigi Bouchard3,4, Jamila Chakir2, Catherine Laprise1,3
1
Département des sciences fondamentales, Université du Québec à
Chicoutimi, Chicoutimi, Quebec, G7H 2B1, Canada; 2Centre de recherche,
Institut Universitaire de Cardiologie et de Pneumologie, Ste-Foy, Quebec,
G1V 4G5, Canada; 3Département de biochimie, Université de Sherbrooke,
Sherbrooke, Quebec, J1K 2R1, Canada; 4ECOGENE-21 et la Clinique Lipidique,
Hôpital de Chicoutimi, Chicoutimi, Quebec, G7H 5H6, Canada
Background: Exposure to tobacco smoke (ETS) induces epigenetic
modifications including DNA methylation [1]. In asthma, it has been
shown that those modifications affect immune cell differentiation by
downregulating expression of specific pro-inflammatory cytokines [2-4].
Interleukin 1 (IL-1) is recognized to be increased in asthma [5] and by
cigarette smoke [5,6]. Based on previous genetic association [7,8] and
DNA methylation signature of receptors in asthma and/or atopy the aim
of this study is to evaluate the changes in expression and methylation
pattern induced by ETS for IL-1 subunit alpha (IL-1A) and beta (IL-1B),
receptors type I (IL-1R1), type II (IL-1R2) and antagonist (IL-1RA) and for
interleukin 33 (IL-33) in lung tissue.
Methods: Primary epithelium cells isolated from bronchial biopsies of mild
asthmatics and non-asthmatics individuals were exposed to whole tobacco
smoke according to method described [9]. Level of mRNA was measured
Table 1(abstract A54) Crude rates of air pollution-sensitive and air pollution-insensitive conditions in Ontario for each
month in 2010
Crude rates of physician office visitsa
Jan
Feb
Mar
Apr
May
June
July
Aug
Sept
Oct
Nov
Dec
Air pollution-sensitive
8.05
8.84
8.94
7.80
7.21
6.55
5.15
4.73
6.57
7.52
9.27
10.89
Air pollution-insensitive
1.48
1.52
1.61
1.55
1.63
1.63
1.34
1.29
1.34
1.38
1.54
1.22
a
Number of claims per 100 population aged 0-14 years
Page 18 of 22
Figure 1(abstract A54) Distribution of (a) fine particulate matter (PM2.5, in μg/m3) and (b) fitted sex-standardized morbidity ratios (SMRs) from spatial
Poisson regression for physician office visits for air pollution-sensitive conditions; all by Forward Sortation Area (FSA) in Southern Ontario in July 2010
by qRT-PCR and methylation was assessed by bis-pyrosequencing for IL-1A,
IL-1B, IL-1R1, IL-1R2, IL-1RA and IL-33.
Results: ETS increased mRNA level of IL-1A and IL-1B in both asthmatic
and non-asthmatic individuals. IL-33 showed a significant decrease in
gene expression following ETS in asthmatic individuals but not in nonasthmatics. IL-1R1 was decreased in non-asthmatic individuals but no
change was observed in asthmatics. IL-1R2 and IL-1RA increased in both
asthmatic and non-asthmatic individuals. We observed DNA methylation
differences in IL-1R1 promoter between ETS and non-ETS cells.
Conclusions: Modifications of genes expression induced by tobacco
smoke could modify IL-1 family resulting in an increase of inflammation
in lung tissues of asthmatic and non-asthmatic individuals. These
changes may be induced by DNA methylation. Efforts to better interpret
and integrate data from genetics and epigenetics are needed to better
understand the biology of asthma as well as a better comprehension of
the impact of tobacco smoke in the inflammatory component of
asthma.
References
1. Wilhelm-Benartzi CS, et al: Association of secondhand smoke exposures
with DNA methylation in bladder carcinomas. Cancer causes & control :
CCC 2011, 22(8):1205-13.
2. Lange P, et al: A 15-year follow-up study of ventilatory function in adults
with asthma. The New England journal of medicine 1998, 339(17):1194-200.
3. White GP, et al: CpG methylation patterns in the IFNgamma promoter in
naive T cells: variations during Th1 and Th2 differentiation and between
atopics and non-atopics. Pediatric Allergy and Immunology: official publication
of the European Society of Pediatric Allergy and Immunology 2006, 17(8):557-64.
4. Jones B, Chen J: Inhibition of IFN-gamma transcription by site-specific
methylation during T helper cell development. The EMBO Journal 2006,
25(11):2443-52.
5. Dinarello CA: Biologic basis for interleukin-1 in disease. Blood 1996,
87(6):2095-2147.
6. Fu JJ, et al: Systemic inflammation is associated with differential gene
expression and airway neutrophilia in asthma. Omics: A Journal of
Jntegrative Biology 2013, 17(4):187-199.
7. Daley D, et al: Analyses of associations with asthma in four asthma
population samples from Canada and Australia. Human Genetics 2009,
125(4):445-459.
8. Daley D, et al: Associations and interactions of genetic polymorphisms in
innate immunity genes with early viral infections and susceptibility to
asthma and asthma-related phenotypes. The Journal of Allergy and Clinical
Immunology 2012, 130(6):1284-1293.
9.
Semlali A, et al: Whole cigarette smoke promotes human gingival
epithelial cell apoptosis and inhibits cell repair processes. Journal of
Periodontal Pesearch 2011, 46(5):533-541.
A56
Lineage specific role of Ship1 in development of allergic airway
inflammation
Matthew J Gold*, Michael R Hughes, Frann Antignano, Colby Zaph,
Kelly M McNagny
The Biomedical Research Centre, University of British Columbia, Vancouver,
British Columbia, V6T 1Z3, Canada
Background: The PI3K pathway is a potent mediator of several functions
associated with asthma pathogenesis, including supporting leukocyte survival,
activation, migration and cytokine release. Proper negative regulation of this
pathway is integral in order to restrict overactive immune responses.
Negative regulation of PI3K is predominantly controlled by the lipid
phosphatases PTEN and SHIP-1. Inpp5d (Ship1) deficient mice develop
spontaneous airway inflammation and have enhanced sensitivity to allergen
induced airway inflammation. We hypothesized that deleting Ship1
expression specifically in lineages known to be crucial for adaptive Th2
responses would uncover more subtle effects that could either positively or
negatively regulate disease severity in a mouse model of allergic airway
inflammation (AAI).
Methods: Ship1 expression was deleted in B cell, T cell and dendritic cell
(DC) lineages and the resulting Ship1ΔB cell, Ship1ΔT cell and Ship1ΔDC mice
were exposed to house dust mite (HDM) antigen over an 18-day period.
Infiltrating leukocytes in the bronchoalveolar lavage (BAL) and lung, serum
antibody levels and Th1 and Th2 cytokine responses were quantified to
assess disease severity.
Results: Deletion of Ship1 in either the B cell, T cell or DC lineages did not
result in spontaneous airway inflammation, and loss of Ship1 in the B cell
linage did not affect HDM-induced AAI. Surprisingly, loss of Ship1 in either of
the T cell or DC lineages protected from development of AAI by skewing the
HDM-induced immune response to a Th1 phenotype instead of the
characteristic Th2 phenotype associated with allergic asthma.
Conclusions: While loss of Ship1 expression throughout the hematopoietic
populations leads to spontaneous lung inflammation, selective deletion of
Ship1 in T cells and DCs impairs the formation of an adaptive Th2 response
and protects from the development of AAI.
Acknowledgments: This work was supported by AllerGen Inc. and the
Canadian Institutes of Health Research (CIHR).
A57
Co-exposure to allergen and diesel exhaust enhance inflammatory
responses in human airway submucosa
Ali Hosseini1,2*, Tillie L Hackett2, Jeremy Hirota1,2, Kelly McNagny3,
Chris Carlsten1,2
1
Department of Medicine, University of British Columbia, Vancouver, British
Columbia, V6T 1Z3, Canada; 2University of British Columbia, James Hogg
Research Centre of the Heart + Lung Institute, Vancouver, British Columbia,
V6Z 1Y6, Canada; 3University of British Columbia, Biomedical Research
Centre, Vancouver, British Columbia, V6T 1Z3, Canada
Background: Asthma is a chronic condition described by inflammation of
the airways and lungs. Diesel exhaust (DE) is a major contributor to ambient
particulate matter (PM) air pollution. There is rising evidence that PM acts as
adjuvant on the immune responses and may lead to augmentation of
allergic inflammation [1,2]. We aim to elucidate if DE increases allergeninduced inflammation and cellular immune response in the airways of
atopic human subjects.
Methods: 15 volunteer participants with allergy to house dust mite
allergen (Der p 1), birch or Timothy grass were recruited. In a randomized
fashion, subjects inhaled DE (300µg PM 2.5 /m 3 ) or filtered air for 120
minutes. One hour following the exposure, the extract of an aeroallergen
to which the individual is sensitive, or placebo (sterile saline), was instilled
into contralateral lung segments through bronchoscopy. Endobronchial
biopsies from these same segments were then acquired 48 hours after
each exposure. This was repeated 4 weeks later in each subject with the
alternative inhalant. Thus, biopsies under 4 different conditions were
created: filtered air + saline (FAS), DE + saline (DES), filtered air + allergen
(FAA) and DE + allergen (DEA). Biopsies were processed and embedded in
glycol methanlacrylate acrylic resin and serial sections were cut to 2µm
and used for immunostaining with monoclonal antibodies to tryptase and
eosinophil cationic protein (ECP). The percent positivity and distribution of
activated mast cells (tryptase+) and eosinophils (ECP+) were quantified in
the bronchial submucosa by Aperio ImageScope software.
Results: The percent positivity for tryptase expression: FAS=0.54±0.05,
DES=0.51±0.18, FAA=0.63±0.24, DEA= 0.94±0.23. The percent positivity
for ECP expression: FAS=0.35±0.17, DES=0.38±0.11, FAA=0.61±0.14,
DEA=0.73±0.33. Data are presented as mean ± SEM (n=6).
Conclusions: Our preliminary data suggest that DE may enhance the
inflammatory response to allergen in atopic individuals. This data is novel
in the context of human lung tissue.
Acknowledgements: This study is funded by the Canadian Institutes of
Health Research (CIHR). A.H. is supported by CIHR Transplantation
Scholarship Training Program
References
1. Riedl M, Diaz-Sanchez D: Biology of diesel exhaust effects on respiratory
function. Journal of Allergy and Clinical Immunology 2005, 115(2):221-228.
2. Nel AE, Diaz-Sanchez D, Ng D, Hiura T, Saxon A: Enhancement of allergic
inflammation by the interaction between diesel exhaust particles and
the immune system. Journal of Allergy and Clinical Immunology 1998,
102(4):539-554.
A58
Transcriptional networks in whole blood of asthmatics
Young Woong Kim1,2*, Amrit Singh1,2, Casey P Shannon3, Gail M Gauvreau4,
Scott J Tebbutt1,2,3
1
Experimental Medicine, University of British Columbia, Vancouver, British
Columbia, V5Z 1M9, Canada; 2James Hogg Research Centre, St. Paul’s
Hospital, Vancouver, British Columbia, V6Z 1Y6, Canada; 3Prevention of
Organ Failure (ROOF) Centre of Excellence, Vancouver, British Columbia, V6Z
2K5, Canada; 4Department of Medicine, McMaster University, Hamilton,
Ontario, L8S 4L8, Canada
Page 19 of 22
Background: Allergen inhalation challenge causes significant changes in
the blood transcriptomes of mild atopic asthmatic individuals [1]. Systems
biology approaches have been used to identify transcriptional networks that
reflect underlying disease processes. Such networks provide insights into the
correlation patterns among genes and may identify specific molecular
processes associated with asthmatic responses. Transcriptional networks can
be identified using blood expression data and are associated with allergeninduced asthmatic responses.
Methods: 14 participants (8 early responders and 6 dual responders) with
mild, atopic asthma underwent a cat allergen inhalation challenge as part of
the AllerGen Clinical Investigator Collaborative. The subjects’ whole blood
samples were collected immediately prior to allergen challenge (prechallenge) and 2 hours after the challenge (post-challenge). Whole blood
transcriptional profiling was performed using Affymetrix GeneChip ® Human
Gene 1.0 ST Arrays. The correlation networks (modules) were identified
using weighted gene correlation network analysis (WGCNA) [2]. Pathway
analysis was performed using GeneGo.
Results: 21,727 mRNA transcripts were profiled across 28 samples (14 pre
and 14 post). Highly expressed mRNA transcripts (10,044, mean expression
> log (base2) 6) were retained for WGCNA. WGCNA identified nine
modules many of which were associated with various immune cell-types. A
gene module consisting of 384 genes was significantly (p=0.0008)
associated with the late phase asthmatic response and also significantly
(p=1e-07) correlated with the compositional abundance of T cells.
Pathways analysis of these genes indicated T cell receptor signaling
pathway, TCR and CD28 co-stimulation in activation of NF-kb and ICOS
pathway in T-helper cells as the top significant pathways (FDR=10%).
Conclusion: Transcriptional networks can be identified using whole
blood expression data. Many transcriptional networks were associated
with various cell-types frequencies, which may indicate the role of cellspecific gene expression in the development of asthmatic responses.
Validation of these transcriptional networks will be performed using a
larger asthma blood expression dataset.
Acknowledgements: This research is supported by AllerGen Inc
References
1. Kam SH, Singh A, He JQ, Ruan J, Gauvreau GM, et al: Peripheral blood
gene expression changes during allergen inhalation challenge in atopic
asthmatic individuals. J Asthma 2012, 49:219-226.
2. Langfelder P, Horvath S: WGCNA: an R package for weighted correlation
network analysis. BMC Bioinformatics 2008, 9:559-571.
A59
Optimizing pediatric venipuncture: ensuring successful blood sample
collection with minimal stress and pain
Mary Ann Mauro*, Linda Warner, Robby Mamonluk, Stuart E. Turvey,
the CHILD study investigators
Department of Pediatrics, Child & Family Research Institute, University of
British Columbia, Vancouver, British Columbia, V5Z 4H4, Canada
Background: The Canadian Healthy Infant Longitudinal Development
(CHILD) study is a multicenter prospective birth cohort study designed to
examine genetic and environmental factors related to the development of
childhood asthma, allergies, and atopic dermatitis. The CHILD study events
include the collection of blood samples at ages 1 and 5 years for all
subjects. Blood collection is a critical aspect of the CHILD study, and all the
following factors require thoughtful consideration: (a) optimizing the success
rate of blood collection to ensure scientific integrity; (b) recognizing and
relieving stress and pain during the pediatric venipuncture process; and (c)
retaining subjects in this longitudinal study.
Methods: At the Vancouver site of the CHILD study, we reviewed and
compared current topical anesthetic creams used for pediatric venipuncture,
specifically Ametop Gel (tetracaine hyrdrochloride gel 4%) versus EMLA
(eutectic mixture of lidocaine 2.5% and prilocaine 2.5%). We conducted
regular in-service training to ensure all members of the study team were
informed and educated in understanding the importance of collecting the
blood sample and dealing with pediatric populations at different
developmental stages. Training also addressed parental anxiety related to
the procedure and strategies to establish rapport and trust were shared.
Finally, we developed a repertoire of comfort and distraction techniques to
support the child, the parent, and the phlebotomist. We used quantitative
and qualitative approaches to assess outcomes, including the number of
blood samples successfully collected at the 1 and 5 year clinic visits and
analysis of responses to our parent satisfaction survey evaluating
perceptions of the venipuncture procedure.
Results: Based on our analysis, we adopted the topical anaesthetic,
Ametop Gel (tetracaine hyrdrochloride gel 4%). Rationale for this choice
included: vasodilation vs. vasoconstriction, timing of onset, cost
effectiveness, and previous experience of team members. Staff training
demonstrated consistent ability to prepare and review process with
parents before the blood collection event, evident in the number of blood
samples successfully collected (35/40 successful collections at the 5 year
visits of the pilot vanguard cohort, 87.5%). Parental survey responses
indicated satisfaction with use of the topical anesthetic and their child’s
comfort with procedure.
Conclusion: Minimizing stress and pain during the collection of blood
samples in research studies is important to the child’s comfort, parental
satisfaction, and subject retention. These factors are critical to the success
of any longitudinal study. Our detailed and methodical approach to the
planning and execution of venipuncture at the Vancouver site of the
CHILD study resulted in greater than 85% success rate in obtaining blood
samples at the 1 year clinic visit while achieving high levels of parental
satisfaction.
A60
IL-4 and IL-13 regulate TLR expression and eosinophil-basophil
differentiation of cord blood CD34+ progenitor cells
Pia Reece1*, Gail M Gauvreau1, Roma Sehmi2, Judah A Denburg1
1
Division of Clinical Immunology and Allergy, McMaster University, Hamilton,
Ontario Canada, L8S 4K1; 2Asthma Research Group, Firestone Institute for
Respiratory Health, McMaster University Hamilton, Ontario, Canada L8N 4A6
Background: Intrauterine environmental exposures have been shown to
influence neonatal immunity and subsequent allergic disease development
[1]. We have previously shown that cord blood (CB) progenitor cells of
high atopic risk infants have reduced toll-like receptor (TLR) expression
and produce fewer lipopolysaccharide (LPS)-stimulated eosinophil-basophil
(Eo/B) colonies, compared to low-atopic risk infants. In the present study,
we investigated whether a surrogate ex vivo TH2 milieu (i.e., either IL-4 or
IL-13), could represent an underlying mechanism to explain our previous
findings.
Methods: CB CD34+ cells from healthy donors were cultured with IL-4 or
IL-13 (in combination with LPS) and assessed for TLR-2, TLR-4, and TLR-9
expression using flow cytometry, as well as Eo/B differentiation using
methylcellulose cultures. Pharmacological inhibitors were added to the
methylcellulose cultures to determine the effect of blocking IL-4 or IL-13
signalling in CB CD34+ cells in relation to Eo/B colony forming unit (CFU)
formation.
Results: Stimulation of CD34+ cells with IL-4 or IL-13 trended to decreased
expression of TLR-2 (p=0.063), whereas IL-4, but not IL-13, reduced Eo/B CFU
formation in the presence of LPS. The latter was found to be dependent on
IL-4Ra and not IL-13Ra1.
Conclusions: Thus, the responsiveness of CB CD34+ progenitor cells to LPS
is differentially regulated by the TH2 cytokines, IL-4 and IL-13, and may be
related to TLR expression on these cells. Therefore, in utero interactions
between placental-derived pro-allergic cytokines and neonatal progenitor
cells influences CD34+ phenotype and function, with implications for Eo/Bmediated inflammatory responses in early life.
Reference
1. Hinz D, Bauer M, Roder S, Olek S, Huehn J, Sack U, Borte M, Simon JC,
Lehmann I, Herberth G, for the LINA study group: Cord blood Tregs with
stable FOXP3 expression are influenced by prenatal environment and
associated with atopic dermatitis at the age of one year. Allergy 2012,
67:380-389.
Page 20 of 22
A61
Blood biomarkers of the late phase asthmatic response using RNA-Seq
Amrit Singh1,2*, Casey P Shannon2, Gail M Gauvreau3, Paul M O’Byrne3,
J Mark FitzGerald4, Louis-Philippe Boulet5, Scott J Tebbutt1,2
1
James Hogg Research Centre, St. Paul’s Hospital, University of British
Columbia, Vancouver, British Columbia, V6Z 1Y6, Canada; 2Prevention of
Organ Failure (PROOF) Centre of Excellence, Vancouver, British Columbia,
V6Z 2K5, Canada Department of Medicine, McMaster University, Hamilton,
Ontario, L8S 4L8, Canada; 3Department of Medicine, McMaster University,
Hamilton, Ontario, L8S 4L8, Canada; 4Vancouver Coastal Health Research
Institute, Vancouver General Hospital, Vancouver, British Columbia, V5Z 1M9,
Canada; 5Centre de Pneumologie de L’Hopital, Université Laval, Sainte-Foy,
Québec, G1V 0B4, Canada
Background: Asthmatic individuals respond differently, but reproducibly, to
allergen inhalation challenge. Some individuals develop an isolated early
response (ER), while others develop a dual response (DR). Peripheral blood
cell transcriptome signatures can discriminate isolated early responders from
dual asthmatic responders undergoing allergen inhalation challenge.
Methods: 35 individuals (17 ERs and 18 DRs) participated in the allergen
inhalation challenge. Blood samples were obtained prior to and 2 hours post
allergen inhalation challenge. HiSeq-Illumina paired-ends 100bp sequencing
was performed. A UCSC transcriptome using both the UCSC gene and geneisoform transcripts was created using the RSEM (RNA-Seq by Expectation
Maximization) package. RSEM uses Bowtie to align read files to the reference
transcripts and estimates the expected number of counts per transcript. The
biomarker pipeline consisted of 20x5-fold deep cross-validation using limma
voom (linear models for microarrays and RNA-Seq using variance modeling
at the observational level) for differential expression and elastic net for
classification. Gene set enrichment analysis was performed using GeneGo.
Results: Classification performance of the pre-challenge classifier across the
100 panels included an AUC of 0.76±0.02, a sensitivity of 0.70±0.03 and a
specificity of 0.72±0.02. There were 511 gene transcripts identified across
the 100 panels. Pathway analysis of the 511 gene transcripts identified lectin
induced complement pathway, integrin inside-out signaling, alternative
complement pathway and function of MEF2 in T lymphocytes as the top
ranked pathways. Classification performance of the post-challenge classifier
across the 100 panels included an AUC of 0.62±0.002, a sensitivity of 0.67
±0.002 and a specificity of 0.54±0.003. There were 301 gene transcripts
identified across the 100 panels. Pathway analysis of the 301 gene
transcripts identified clathrin coated vesicles formation, CDC42 in cellular
processes and regulation of actin cytoskeleton by Rho GTPases as the top
ranked pathways.
Conclusion: The pre-challenge classifier out-performed the post-challenge
classifier in the internal deep cross-validation as depicted by the classification
performance measures. The lower performance of the post-challenge
classifier in discriminating ERs from DRs may be due to a dilution of signal,
given that both responder groups are undergoing an immune response to
allergen inhalation. Incorporating changes in cellular composition and gene
isoform expression estimates may improve classification performance and
also reveal new insights into the mechanisms of the late phase asthmatic
response.
A62
The Allergic Rhinitis - Clinical Investigator Collaborative (AR-CIC) optimizing the Nasal Allergen Challenge (NAC) model
Mena Soliman1*, Jenny Thiele1, Lisa Steacy2, Marie-Eve Boulay3,
Angela Hillaby4, Susan Waserman5, Paul Keith5, Harissios Vliagoftis4,
Louis-Philippe Boulet3, Helen Neighbour6, Anne K. Ellis1,2
1
Departments of Medicine and Biomedical & Molecular Science, Queen’s
University, Kingston, Ontario, K7L 3N6, Canada; 2Allergy Research Unit,
Kingston General Hospital, Kingston, Ontario, K7L 2V7, Canada; 3Institut
Universitaire de Cardiologie et de Pneumologie de Quebec, Quebec City,
Quebec, G1V 4G5, Canada; 4Pulmonary Research Group, University of Alberta,
Edmonton, Alberta, T6G 2R7, Canada; 5Department of Medicine, McMaster
University, Hamilton, Ontario, L8S 4K1, Canada; 6Firestone Institute for
Respiratory Health, McMaster University, Hamilton, Ontario, L8N 4A6, Canada
Background: We sought to optimize the Nasal Allergen Challenge (NAC)
model to ensure reliability and repeatability of results by modifying the
qualifying criteria and allergen concentration during the challenge.
Methods: 20 Allergic Rhinitis (AR) participants underwent NAC to determine
the concentration at which a Total Nasal Symptom Score (TNSS) of 10/12 OR
a Peak Nasal Inspiratory Flow (PNIF) reduction of 50 % was achieved. 4-fold
increases in allergen concentration were administered every 15 minutes
until qualification criteria were met. The Qualifying Allergen Concentration
(QAC) reached was used as a single challenge dose at the subsequent NAC
visit. 10 additional ragweed allergic and 4 non-allergic participants were
qualified at a TNSS of 8/12 AND a PNIF reduction of 50%. Cumulative
Allergen Concentration (CAC) of all incremental doses was used during the
subsequent NAC visit. Participants recorded TNSS and PNIF at baseline, 15
minutes, 30 minutes, 1 hour and hourly afterwards up to 12 hours postchallenge during the NAC visit.
Results: QAC study participants qualifying only based on PNIF reduction
had significantly lower TNSS scores than those qualifying on TNSS only or
TNSS+PNIF (p<0.01). Participants in both studies’ NAC visit reached peak
TNSS at 15 minutes post-challenge followed by a gradual symptom decline,
while the “PNIF only” group had significantly lower TNSS compared to
others. All 3 groups experienced a decline in peak TNSS following NAC
compared to screening, although groups qualifying on TNSS and TNSS+PNIF
maintained their PNIF scores.
Conclusion: The NAC model is well-suited to study AR symptoms. TNSS
and PNIF are complementary and must be integrated in the qualifying
criteria. Further protocol modifications, such as with multiple allergen
challenges during the NAC visit, may produce even more repeatable
results. Through optimizing the NAC protocol, the model achieves
reproducible results and becomes more reliable; suitable for testing new
medications in clinical trials.
A63
The early life gut microbiota and atopic disease
Leah T. Stiemsma1,2*†, Marie-Claire Arrieta3†, Pedro A. Dimitriu1, Lisa Thorson3,
Sophie Yurist3, Rollin Brandt4, Diana L. Lefebvre5,6, Padmaja Subbarao7,8,
Piush Mandhane9,10, Allan Becker11, Malcolm Sears5,6, Tobias Kollmann2,12,
William W. Mohn1, B Brett Finlay1,3,13, Stuart E. Turvey2,12,
the CHILD Study Investigators1
1
Department of Microbiology & Immunology, University of British Columbia,
Vancouver, British Columbia, V6T 1Z4, Canada; 2The Child and Family
Research Institute, Vancouver, British Columbia, V4Z 4H4, Canada; 3Michael
Smith Laboratories, University of British Columbia, Vancouver, British
Columbia, V6T 1Z4, Canada; 4Department of Statistics, University of British
Columbia, Vancouver, British Columbia, V6T 1Z4, Canada; 5St. Joseph’s
Healthcare, Hamilton, Ontario, L8N 4A6, Canada; 6Department of Medicine,
McMaster University, Hamilton, Ontario, L8S 4L8, Canada; 7Department of
Pediatrics, University of Toronto, Toronto, Ontario, M5S 2J7, Canada;
8
Hospital for Sick Children, Toronto, Ontario, M5G 1X8, Canada; 9Department
of Pediatrics, University of Alberta, Edmonton, Alberta, T6G 2R3, Canada;
10
School of Public Health, University of Alberta, Edmonton, Alberta, T6G 2R3,
Canada; 11Department of Pediatrics and Child Health, University of Manitoba,
Winnipeg, Manitoba, R3T 2N2, Canada; 12Department of Pediatrics, University
of British Columbia, Vancouver, British Columbia, V6T 1Z4, Canada;
13
Department of Biochemistry and Molecular Biology, University of British
Columbia, Vancouver, British Columbia, V6T 1Z4, Canada
Background: Asthma is the most prevalent of all childhood diseases and
accounts for the majority of hospitalizations and school absences in
children [1]. Current mouse model research has identified the early life
gut microbiota as a potential therapeutic target for the prevention of
asthma and atopic diseases [2-4]. We hypothesize that the early life gut
microbiota could play a similar preventative role against atopic disease
development in humans.
Methods: 1262 children enrolled in the Canadian Healthy Infant
Longitudinal Development (CHILD) Study with complete skin prick test and
wheeze data at one year were grouped into four clinically relevant
phenotypes: atopy + wheeze, atopy only, wheeze only, and control. Bacterial
Page 21 of 22
16S rDNA from 3-month and 1-year stool samples of 319 children in these
four phenotypes was extracted, amplified, and subjected to high throughput
Illumina sequencing. Quantitative polymerase chain reaction (qPCR) and
short chain fatty acid (SCFA) analysis were also conducted on 44 children in
the two extreme phenotypes (atopy + wheeze vs. control).
Results: 16S sequence analysis of our sample cohort (319 subjects)
identified bacterial populations that differed in abundance in the atopy +
wheeze group at 3-months of age but not at 1-year of age. Additionally,
significant changes in the abundance of certain bacterial genera were found
in the atopy + wheeze group when compared to controls by qPCR at
3-months of age only. Changes in stool short chain fatty acid production
between the atopy + wheeze group and the control group were also
observed at 3-months of age only.
Conclusions: Shifts in the relative abundance of certain gut bacterial
populations and differences in the levels of stool SCFAs before 3-months
of age are associated with atopy and wheeze at one year of age.
References
1. Asthma. World Health Organization 2011.
2. Zeng B, Li G, Yuan J, Li W, Tang H, Wei H: Effects of age and strain on the
microbiota colonization in an infant human flora-associated mouse
model. Current Microbiology 2013, 67:313-21.
3. Russell SL, Gold MJ, Willing BP, Thorson L, McNagny KM, Finlay BB: Perinatal
antibiotic treatment affects murine microbiota, immune responses and
allergic asthma. Gut Microbes 2013, 4:158-64.
4. Arnold IC, Dehzad N, Reuter S, Martin H, Becher B, Taube C, Muller A:
Helicobacter pylori infection prevents allergic asthma in mouse models
through the induction of regulatory T cells. The Journal of Clinical
Investigation 2011, 121:3088-3093.
A64
Mediators of allergic rhinitis: optimization of RNA isolation, reverse
transcription, and qPCR protocols
Caroline Conway1, Jenny Thiele2*, Mena Soliman1, Anne Ellis1,2,3
1
Department of Biomedical and Molecular Sciences, Queen’s University,
Kingston, Ontario, K7L 3N6, Canada; 2Department of Medicine, Queen’s
University, Kingston, Ontario, K7L 3N6, Canada; 3Division of Allergy &
Immunology, Kingston General Hospital, Kingston, Ontario, K7L 2V7, Canada
Background: Optimizing methods for the study of allergic rhinitis (AR),
especially when using samples likely containing small amounts of material
for analysis, ensures the integrity of results that may potentially enhance the
understanding of AR disease mechanisms. In order to conduct future mRNA
expression analysis, examining the differential expression of AR mediators
such as IL33, TSLPR, HPGDS, and CRTH2 at baseline and 6 hours following
Nasal Allergen Challenge (NAC) in allergic individuals, this study aims to
optimize the RNA isolation, reverse transcription (RT), and qPCR protocols
used for the study of nasal mucosal samples.
Methods: Several RNA isolation and RT kits were evaluated using nasal
scrapings from healthy individuals, similar to those collected from allergic
participants. These kits were evaluated based on the yield and purity of
RNA and cDNA, assessed using spectrophotometry, qPCR amplification,
and gel electrophoresis. Reference gene analysis using cDNA isolated from
allergic participants was conducted using qPCR and the statistical software
GenEx (MultID). Primer design and evaluation of primers for the targets of
interest—IL33, TSLPR, HPGDS, and CRTH2—was also pursued.
Results: RNA isolation and RT kit optimization determined that the Life
Technologies-Qiagen (LT-Q) kit combination produced cDNA with maximal
purity and qPCR efficiency compared with the other kit combinations
evaluated. Reference gene analysis demonstrated that expression of
ubiquitin C (UBC) showed limited variability among the differing conditions
(time point and study) of nasal sample collection. Primer evaluation yielded
inconsistent results.
Conclusions: Future processing of nasal scraping samples should use the
optimal LT-Q kit combination. Following successful primer evaluation, the
expression levels of the targets of interest in the allergic nasal mucosal
cDNA samples at both baseline and 6h post-NAC will be conducted via the
optimized qPCR reaction, using UBC as a reference gene.
A65
Food allergy education: teen learning preferences
Claire R. Unruh1,2*, Cathy A. Gillespie2, Nancy L. Ross2, Allan B. Becker2
1
Department of Pediatrics and Child Health, University of Manitoba,
Winnipeg, Manitoba, R3A 1S1, Canada; 2Children’s Allergy and Asthma
Education Centre, Winnipeg, Manitoba, R3E 0Z2, Canada
Background: Food allergic teens are at increased risk for fatal anaphylaxis
[1]. Food allergy education is needed to address the transition of care from
their parents to the teens. Teen input into education approaches is
essential in order to effectively develop programs that will modify
behavior. Allergy educators will need to be familiar with effective
approaches to education for this important population.
Methods: Teens with food allergy were invited into focus groups in our
education centre as a preliminary step to determine their preferred learning
styles to begin development of effective educational resources for teens.
Semi-structured interviews were conducted, digitally recorded, transcribed
and reviewed for themes.
Results: 16 teens (mean 16 yr.) participated in three focus groups
facilitated by a food allergy educator. Common themes from these
interviews highlighted the need for different methods of communication
(both from and to the teens) and behavioral approaches to self-advocacy,
risk assessment and reduction, reaction recognition and treatment. Indepth information about allergic reactions and on-going research were
also of interest. Learning preferences included spatial, auditory, verbal and
kinesthetic style examples. All groups emphasized a need for some handson classroom experiences, including: practice with auto-injectors, playing
out different scenarios, and distance and mobile information.
The teens expressed interest in small group participation where they
could voice their opinions, have questions answered, and comfortably
communicate with others. Many teens said they liked hybrids of different
learning styles, such as auditory and visual instruction followed by handson experience in the classroom. Most teens preferred a group facilitator
expert in food allergies and/or who had food allergies, educator skills,
and could relate to younger people. Online and mobile learning was of
interest but most had not yet used these resources.
Conclusion: Teens are interested in small group interactive education with
hands-on experience, as well as mobile-based learning. Food allergy topics
must be adapted to teen specific situations, and a teen program needs to
include a variety of approaches to connect with teens. These focus groups
have led to the deployment of an online survey for teens to acquire a
greater breadth of feedback for topics and teens’ learning preferences.
Reference
1. Bock S, Muñoz-Furlong A, Sampson H: Fatalities due to anaphylactic
reactions to foods. J Allergy Clin Immunol 2001, 107(1):191-193.
A66
Uncovering T cell-specific differential expression patterns associated
with pollen exposure in individuals with allergic rhinitis
Chen Xi Yang1*, Casey P Shannon1,3, Amrit Singh1, Anne K Ellis2, Scott J Tebbutt1,3
1
UBC James Hogg Research Centre and Centre for Heart + Lung Innovation,
University of British Columbia, Vancouver, British Columbia, V6Z 1Y6, Canada;
Page 22 of 22
2
Kingston General Hospital and Queen’s University, Kingston, Ontario, K7L
2V7, Canada; 3Prevention of Organ Failure (PROOF) Centre of Excellence,
Vancouver, British Columbia, V6Z 2K5, Canada
Background: Investigating transcriptomics in whole blood is a promising
avenue of research for helping to understand the allergic response [1].
However, the heterogeneity of peripheral whole blood significantly
complicates the interpretation of whole blood expression data. Statistical
deconvolution approaches, which can model and infer the sample
composition and the cell type-specific expression, may provide a powerful
means of studying complex tissues, such as whole blood, in an integrated
fashion [2].
Methods: 14 individuals with allergic rhinitis were simultaneously
exposed to ragweed pollen in the Environmental Exposure Unit.
Peripheral blood samples were collected using PAXgene Blood RNA tubes
before and after the 3 hours of pollen exposure. Gene expression
profiling was performed using Affymetrix GeneChip® Human Gene 1.0 ST
Arrays. Publicly available expression data (E-GEOD-48558) was used to
estimate the cellular composition from whole blood expression profiles.
The estimated proportions were compared against those measured by an
automated hematology analyzer.
Results: The estimated proportions of lymphocytes, granulocytes and
monocytes were compared against the observed proportions. The
prediction was good in lymphocytes (R 2 =0.70, RMSE=0.036) and
granulocytes (R2=0.75, RMSE= 0.046), but relatively poor in monocytes
(R 2 =0.52, RMSE=0.030). No significant changes in cellular proportions
between pre-challenge and post-challenge samples were identified. 261
(110 up-regulated and 151 down-regulated) differentially expressed probe
sets were identified comparing pre and post-challenge samples at a false
discovery rate (FDR) of 10%.
Conclusions: Statistical deconvolution is accurate in predicting the
cellular proportions of lymphocytes and granulocytes but relatively poor
in predicting monocytes. Allergen exposure causes significant changes in
the blood transcriptomes of participants with allergic rhinitis undergoing
pollen exposure. The inferred proportions will be used for cell typespecific significance analysis of microarrays (csSAM), to assess differential
expression in T cells. The CD4+ T cell expression profiles from E-GEOD43497, a similar study of allergic rhinitis, will be used to validate our
findings.
References
1. Chaussabel D, Pascual V, Banchereau J: Assessing the human immune
system through blood transcriptomics. BMC biology 2010, 8:84.
2. Shen-Orr SS, Tibshirani R, Khatri P, Bodian DL, Staedtler F, et al: Cell type–
specific gene expression differences in complex tissues. Nat Meth 2010,
7:287-289.
Cite abstracts in this supplement using the relevant abstract number,
e.g.: Yang et al.: Uncovering T cell-specific differential expression
patterns associated with pollen exposure in individuals with allergic
rhinitis. Allergy, Asthma and Clinical Immunology 2014, 10(Suppl 2):A66

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