Publications by authors named "Anne K Ellis"

114 Publications

Immunoregulatory T cell epitope peptides for the treatment of allergic disease.

Immunotherapy 2021 Oct 24;13(15):1283-1291. Epub 2021 Sep 24.

Department of Medicine, Queen's University, Kingston, ON, K7L 3N6, Canada.

Allergic diseases are type 2 inflammatory reactions with an increasing worldwide prevalence, making the search for new therapeutic options pertinent. Allergen immunotherapy is the only disease-modifying approach for allergic rhinitis, though it can result in systemic reactions. Recently, peptide immunotherapy (PIT), involving T-cell epitope peptides that bind to major histocompatibility complexes, have been developed. It is speculated that they can induce T helper cell type 2 anergy, Treg cell upregulation or immune deviation. Promising results in cat dander, honeybee venom, Japanese cedar pollen, grass pollens, ragweed and house dust mite clinical trials have shown safety, efficacy and tolerability to PIT. Hence, PIT may hold the potential to change the treatment algorithm for allergic rhinitis.
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http://dx.doi.org/10.2217/imt-2021-0133DOI Listing
October 2021

Efficacy, Safety and Tolerability of a New 10% Intravenous Immunoglobulin for the Treatment of Primary Immunodeficiencies.

Front Immunol 2021 8;12:707463. Epub 2021 Jul 8.

Allergy Partners of North Texas Research, Dallas, TX, United States.

We report here the results of a phase 3 study to assess the efficacy, safety, and tolerability of GC5107, a new 10% liquid intravenous immunoglobulin (IVIG) in preventing serious bacterial infections in patients with primary immunodeficiency (ClinicalTrials.gov: NCT02783482). Over a 12-month study period, 49 patients aged 3 to 70 years with a confirmed diagnosis of primary immunodeficiency received GC5107 at doses ranging from 319 to 881 mg/kg body weight every 21 or 28 days, according to their previous IVIG maintenance therapy. A total of 667 infusions of GC5107 were administered comprising a total of 45.86 patient-years of treatment. A single acute serious bacterial infection occurred during the study, resulting in an incidence of 0.02 events per patient-year (upper 99% one-sided confidence interval limit: 0.21), meeting the prespecified primary efficacy endpoint. The mean incidence of infections other than acute serious bacterial infections was 2.9 infections per patient-year. Efficacy was also demonstrated by the low mean annualized rate of hospitalizations due to infection (0.1 day) and the mean annualized duration of hospitalizations (0.1 day). The mean rate of intravenous and oral antibiotic use was 0.1 day and 13.2 days, respectively. There was a mean of 7.1 days of missed work, school, or daycare days. The proportion of infusions with temporally associated adverse events (TAAEs) occurring during or within 72 hours after GC5107 infusion was 0.24 (upper 95% one-sided confidence interval limit: 0.31), meeting the pre-specified primary safety endpoint. Overall, 149 of 667 infusions (22%) were associated with TAAEs. The most common TAAE was headache, reported by 49% of patients. More than 98% (731/743) of all adverse events that occurred throughout the 12-month study period were mild or moderate. More than 98% of infusions were completed without discontinuation, interruption or rate reduction. There were no treatment-emergent serious adverse events related to GC5107 or study discontinuations due to an adverse event. Overall, pharmacokinetic parameters for GC5107 were within the range of those reported in studies of other marketed IVIG products. Results of the present study demonstrate that GC5107 is an effective, safe and well-tolerated treatment for patients with primary immunodeficiency.
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http://dx.doi.org/10.3389/fimmu.2021.707463DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8297997PMC
July 2021

Sublingual immunotherapy tablet: a cost-minimizing alternative in the treatment of tree pollen-induced seasonal allergic rhinitis in Canada.

Allergy Asthma Clin Immunol 2021 Jul 8;17(1):66. Epub 2021 Jul 8.

PDCI Market Access Inc., Ottawa, ON, Canada.

Background: A cost-minimization analysis (CMA) was performed to evaluate the economic implications of introducing the SQ Tree sublingual immunotherapy (SLIT)-tablets marketed as ITULATEK® (Health Canada regulatory approval in April 2020) for the treatment of pollen-induced (birch, alder and/or hazel) seasonal allergic rhinitis in Canada (Ontario and Quebec), where Tree Pollen subcutaneous immunotherapy (SCIT) is already an available treatment option.

Methods: A CMA was deemed appropriate and was based on the assumption that the SQ Tree SLIT-tablets have comparable efficacy to Tree Pollen SCIT. A societal perspective was adopted in the model, including relevant costs of medications, costs of health care services, and productivity losses. The time horizon in the model was three years, which corresponds to a minimal treatment course of allergy immunotherapy. Resource use and costs were based on published sources, where available, and validated by Canadian specialist clinicians (allergists) in active practice in Ontario and in Quebec, where applicable. A discount rate of 1.5% was applied in accordance with the Canadian Agency for Drugs and Technologies in Health (CADTH) guidelines. To assess the robustness of the results, scenario analyses were performed by testing alternative assumptions for selected parameters (e.g., Tree Pollen SCIT resource use, discount rates, number of injections, annual SCIT dosing with maintenance injections, and nurse time support), to evaluate their impact on the results of the analysis.

Results: The direct costs, including the drug costs, and physician services costs, for three years of treatment, were similar for both SQ Tree SLIT-tablets vs. Tree Pollen SCIT in both Ontario and Quebec ($2799.01 and $2838.70 vs. $2233.76 and $2266.05 respectively). However, when the indirect costs (including patient's travel expenses and lost working hours) are included in the model, total savings for the treatment with SQ Tree SLIT-tablets of $1111.79 for Ontario and $1199.87 for Quebec were observed. Scenario analyses were conducted and showed that changes in assumptions continue to result in the savings of SQ Tree SLIT- tablets over Tree Pollen SCIT.

Conclusions: The CMA indicates that SQ Tree SLIT-tablets are a cost-minimizing alternative to Tree Pollen SCIT when considered from a societal perspective in Ontario and Quebec.
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http://dx.doi.org/10.1186/s13223-021-00565-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8264484PMC
July 2021

Environmental exposure unit simulates natural seasonal birch pollen exposures while maximizing change in allergic symptoms.

Ann Allergy Asthma Immunol 2021 10 26;127(4):488-495.e5. Epub 2021 Jun 26.

Regeneron Pharmaceuticals, Inc., Tarrytown, New York.

Background: Birch pollen is a prevalent aeroallergen during the springtime allergy season. In field studies, variable allergen exposure and environmental factors can affect data quality while environmental exposure units (EEUs) deliver controlled, standardized, and reproducible allergen exposures.

Objective: To inform study design for EEU trials evaluating antiallergic therapies.

Methods: In this prospective study, 76 participants with birch allergy experienced 3 exposures to birch pollen: (1) an out-of-season EEU challenge (two 3-hour sessions on consecutive days); (2) a natural seasonal exposure; and (3) an in-season EEU challenge (3-hour exposure for 2 weeks after birch pollen season initiation).

Results: The total nasal symptom score, total ocular symptom score, and total symptom score (TSS = total nasal symptom score plus total ocular symptom score) were assessed every 30 minutes and daily during EEU and natural exposures. A high association between TSSs and day 2 of the out-of-season and in-season EEU challenges was noted, with a good association between the maximum TSS during the natural and in-season EEU challenges, and natural season and day 2 of the out-of-season EEU challenge (P < .001 for all). Participants had higher maximum change from the baseline TSS during day 2 of the out-of-season EEU challenge (12.4) vs the following: (1) first day (9.8); (2) in-season EEU challenge (8.4); and (3) natural seasonal exposure (7.6) (P < .001 for all).

Conclusion: A strong association was seen between the presence of allergy symptoms and exposure to birch pollen in the EEU (maximum change in symptom scores during day 2) and in the field. A hybrid trial design may be useful to demonstrate the clinical efficacy of novel antiallergic therapies requiring fewer participants and shorter timelines and expediting treatment availability.
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http://dx.doi.org/10.1016/j.anai.2021.06.015DOI Listing
October 2021

The Risk of Allergic Reaction to SARS-CoV-2 Vaccines and Recommended Evaluation and Management: A Systematic Review, Meta-Analysis, GRADE Assessment, and International Consensus Approach.

J Allergy Clin Immunol Pract 2021 10 18;9(10):3546-3567. Epub 2021 Jun 18.

Department of Paediatrics, Royal College of Surgeons, Dublin, Ireland.

Concerns for anaphylaxis may hamper severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) immunization efforts. We convened a multidisciplinary group of international experts in anaphylaxis composed of allergy, infectious disease, emergency medicine, and front-line clinicians to systematically develop recommendations regarding SARS-CoV-2 vaccine immediate allergic reactions. Medline, EMBASE, Web of Science, the World Health Organizstion (WHO) global coronavirus database, and the gray literature (inception, March 19, 2021) were systematically searched. Paired reviewers independently selected studies addressing anaphylaxis after SARS-CoV-2 vaccination, polyethylene glycol (PEG) and polysorbate allergy, and accuracy of allergy testing for SARS-CoV-2 vaccine allergy. Random effects models synthesized the data to inform recommendations based on the Grading of Recommendation, Assessment, Development, and Evaluation (GRADE) approach, agreed upon using a modified Delphi panel. The incidence of SARS-CoV-2 vaccine anaphylaxis is 7.91 cases per million (n = 41,000,000 vaccinations; 95% confidence interval [95% CI] 4.02-15.59; 26 studies, moderate certainty), the incidence of 0.15 cases per million patient-years (95% CI 0.11-0.2), and the sensitivity for PEG skin testing is poor, although specificity is high (15 studies, very low certainty). We recommend vaccination over either no vaccination or performing SARS-CoV-2 vaccine/excipient screening allergy testing for individuals without history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient, and a shared decision-making paradigm in consultation with an allergy specialist for individuals with a history of a severe allergic reaction to the SARS-CoV-2 vaccine/excipient. We recommend further research to clarify SARS-CoV-2 vaccine/vaccine excipient testing utility in individuals potentially allergic to SARS-CoV2 vaccines or their excipients.
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http://dx.doi.org/10.1016/j.jaip.2021.06.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8248554PMC
October 2021

Comparative nasal airflow with loratadine-pseudoephedrine and fluticasone nasal spray for allergic rhinitis.

Ann Allergy Asthma Immunol 2021 09 14;127(3):342-348.e2. Epub 2021 May 14.

Allergy Research Unit, Kingston Health Sciences Centre, Kingston General Hospital Site, Kingston, Ontario, Canada; Division of Allergy and Immunology, Department of Medicine, Queen's University, Kingston, Ontario, Canada; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada. Electronic address:

Background: Although it is known that oral antihistamine-pseudoephedrine combination tablets have a faster onset than intranasal corticosteroid sprays in the treatment of allergic rhinitis after the first dose, the magnitude of change has not been measured in a comparative manner. Furthermore, the sensation of sprayed liquid in the nose may lead patients to mistakenly believe that intranasal steroid sprays work instantly.

Objective: To evaluate, numerically, nasal airflow changes provided by a single dose of loratadine-pseudoephedrine tablet (LP) and fluticasone propionate nasal spray (FP) in participants experiencing allergic rhinitis symptoms, including nasal congestion.

Methods: This single-center, double-blinded, placebo-controlled, crossover study evaluated objective nasal airflow changes in patients with a documented sensitivity to ragweed pollen. Participants were randomized to receive 1 of 4 treatment sequences, and their peak nasal inspiratory flow (PNIF) was measured in a span of 4 hours after pollen exposure in an environmental exposure unit.

Results: Average change in PNIF was 31% with LP in the course of the study, significantly greater than with placebo and FP (12% and 15%, respectively; P < .001). Nevertheless, FP did not produce a significant change compared with its placebo. At hour one post-dose, LP had a clinically significant 31% increase in PNIF, whereas FP only yielded an 8.6% increase (P < .001). Measurable nasal airflow improvements are associated with the opening of nasal passages, allowing congested patients to breathe more freely.

Conclusion: A single dose of LP quickly and significantly (P < .001) improved nasal airflow after ragweed pollen challenge in an environmental exposure unit. Comparatively, FP did not display this same benefit.

Trial Registration: ClinicalTrials.gov Identifier: NCT03443843.
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http://dx.doi.org/10.1016/j.anai.2021.05.001DOI Listing
September 2021

Insights into allergic risk factors from birth cohort studies.

Ann Allergy Asthma Immunol 2021 09 7;127(3):312-317. Epub 2021 May 7.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada; Allergy Research Unit, Kingston Health Sciences Center - KGH Site, Kingston, Ontario, Canada; Department of Medicine, Queen's University, Kingston, Ontario, Canada. Electronic address:

Objective: To present an update of birth cohort study designs and their contributions to allergic risk.

Data Sources: The PubMed database was used to search for relevant articles.

Study Selections: Peer-reviewed prospective and retrospective studies involving the assessment of allergy using human birth cohorts between 2014 and 2021 were evaluated.

Results: Parental history of allergic diseases, especially in cases involving both parents, is associated with increased risk of allergy. Exposure to prenatal and postnatal smoking and limited diet diversity were associated with increased allergic burden. The impact of early-life infections and antibiotics on disease development may be associated with the onset of asthma, though this remains debated. Cohort studies also revealed that the mode of delivery and breastfeeding duration affect the odds ratio of asthma and eczema development. Household exposures, including pets, house dust mites, and scented aeroallergens may confer protective effects, whereas high air pollution exposure and low socioeconomic status may be risk enhancing. Exposure to antibiotics during early life may be associated with increased asthma risk, whereas viral infections may lead to disease protection, though the impact of the coronavirus disease 2019 pandemic on allergic risk is yet to be understood.

Conclusion: Although evaluating the risk of allergic disease development is complex, clinicians can apply these insights on the multifactorial nature of atopy to better understand and potentially mitigate disease development.
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http://dx.doi.org/10.1016/j.anai.2021.04.025DOI Listing
September 2021

Future of allergic rhinitis management.

Ann Allergy Asthma Immunol 2021 08 7;127(2):183-190. Epub 2021 May 7.

Allergy Research Unit, Kingston Health Sciences Center-Kingston General Hospital Site, Kingston, Ontario, Canada; Department of Medicine, Queen's University, Kingston, Ontario, Canada; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada. Electronic address:

Objective: To present a comprehensive, clinically focused scoping review of therapeutic agents and practices comprising the future of allergic rhinitis (AR) management.

Data Sources: A review of the published literature was performed using the PubMed database, published abstracts, and virtual presentations from scientific meetings and posted results on ClinicalTrials.gov.

Study Selections: Primary manuscripts with trial results, case reports, case series, and clinical trial data from ClinicalTrials.gov, PubMed, and articles highlighting expert perspectives on management of AR were selected.

Results: Telemedicine, social media, and mHealth facilitate integrated care for AR management. Pharmacotherapy remains the standard of care for AR management; however, treatment combinations are recommended. Intralymphatic immunotherapy and peptide immunotherapy are the most promising new allergen immunotherapy options. Studies of targeted biologics for AR are ongoing. Probiotics may be beneficial for AR management, particularly Bifidobacterium spp, and as an add-on to allergen immunotherapy.

Conclusion: AR is a chronic and often comorbid condition that requires integrated care for optimal management. New formulations and combinations of existing AR therapies are the most promising and merit future research.
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http://dx.doi.org/10.1016/j.anai.2021.04.029DOI Listing
August 2021

Indoor exposure to phthalates and polycyclic aromatic hydrocarbons (PAHs) to Canadian children: the Kingston allergy birth cohort.

J Expo Sci Environ Epidemiol 2021 Apr 14. Epub 2021 Apr 14.

Department of Physical and Environmental Sciences, University of Toronto Scarborough, Toronto, ON, Canada.

Background: Canadian children are widely exposed to phthalates and polycyclic aromatic hydrocarbons (PAHs) from indoor sources. Both sets of compounds have been implicated in allergic symptoms in children.

Objective: We characterize concentrations of eight phthalates and 12 PAHs in floor dust from the bedrooms of 79 children enrolled in the Kingston Allergy Birth Cohort (KABC).

Method: Floor dust was collected from the bedrooms of 79 children who underwent skin prick testing for common allergens after their first birthday. Data were collected on activities, household, and building characteristics via questionnaire.

Results: Diisononyl phthalate (DiNP) and phenanthrene were the dominant phthalate and PAH with median concentrations of 561 µg/g and 341 ng/g, respectively. Benzyl butyl phthalate (BzBP) and chrysene had the highest variations among all tested homes, ranging from 1-95% to 1-99%, respectively.

Significance: Some phthalates were significantly associated with product and material use such as diethyl phthalate (DEP) with fragranced products and DiNP and DiDP with vinyl materials. Some PAHs were significantly associated with household characteristics, such as benzo[a]pyrene with smoking, and phenanthrene and fluoranthene with the presence of an attached garage. Socioeconomic status (SES) had positive and negative relationships with some concentrations and some explanatory factors. No significant increases in risk of atopy (positive skin prick test) was found as a function of phthalate or PAH dust concentrations.
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http://dx.doi.org/10.1038/s41370-021-00310-yDOI Listing
April 2021

Comparing the nasal allergen challenge and environmental exposure unit models of allergic rhinitis.

Ann Allergy Asthma Immunol 2021 08 20;127(2):163-164. Epub 2021 Apr 20.

Department of Medicine, Queen's University, Kingston, Ontario, Canada; Allergy Research Unit, Kingston Health Sciences Center-Kingston General Hospital Site, Kingston, Ontario, Canada; Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.anai.2021.04.012DOI Listing
August 2021

Effect of fexofenadine hydrochloride on allergic rhinitis aggravated by air pollutants.

ERJ Open Res 2021 Apr 6;7(2). Epub 2021 Apr 6.

Air Pollution Exposure Laboratory, University of British Columbia, Vancouver, BC, Canada.

In recent decades, seasonal allergic rhinitis (SAR) prevalence has increased and recent studies have shown that air pollutants, such as diesel exhaust particles (DEP), can increase inflammatory and allergic biomarkers. The aim of this study was to investigate the effects of DEP on SAR symptoms induced by ragweed and to evaluate the efficacy and safety of fexofenadine HCl 180 mg placebo. This phase 3, single-centre, sequential, parallel-group, double-blind, randomised study (NCT03664882) was conducted in an environmental exposure unit (EEU) during sequential exposures: Period 1 (ragweed pollen alone), Period 2 (ragweed pollen+DEP), and Period 3 (ragweed pollen+DEP+single-dose fexofenadine HCl 180 mg or placebo). Efficacy and safety were evaluated in Period 3. Primary endpoints were the area under the curve (AUC) of total nasal symptom score (TNSS) from baseline to hour 12 (AUC) during Period 1 and Period 2; and the AUC of the TNSS from hour 2 to 12 (AUC) during Period 3. 251 out of 257 evaluable subjects were included in the modified intent-to-treat population. Least squares mean difference (95% CI) for TNSS Log AUC in Period 2 Period 1 was 0.13 (0.081-0.182; p<0.0001). Least squares mean difference in TNSS Log AUC for fexofenadine HCl placebo during Period 3 was -0.24 (-0.425--0.047; p=0.0148). One fexofenadine HCl-related adverse event was observed. SAR symptoms evoked by ragweed were aggravated by DEP. Fexofenadine HCl 180 mg was effective in relieving pollen-induced, air pollution-aggravated allergic rhinitis symptoms.
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http://dx.doi.org/10.1183/23120541.00806-2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8021806PMC
April 2021

Clinical validation of controlled exposure to house dust mite in the environmental exposure unit (EEU).

Allergy Asthma Clin Immunol 2021 Mar 26;17(1):34. Epub 2021 Mar 26.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.

Rationale: The Environmental Exposure Unit (EEU), a controlled allergen exposure model of allergic rhinitis (AR), has traditionally utilized seasonal allergens. We sought to clinically validate the use of house dust mite (HDM), a perennial allergen, in the HDM-EEU, a specially designed facility within the larger EEU.

Methods: Forty-four HDM-allergic and eleven non-allergic participants were screened and deemed eligible for one of two 3-h exposure sessions in the HDM-EEU. Participants were exposed to a modest or higher HDM target, with blood and nasal brushing samples collected before and after allergen exposure. Symptomatic data, including Total Nasal Symptom Score (TNSS), Total Ocular Symptom Score (TOSS), Total Rhinoconjunctivitis Symptom Score (TRSS), and Peak Nasal Inspiratory Flow (PNIF) were collected at baseline, every 30 min until 3 h, on an hourly basis for up to 12 h, and at 24 h following the onset of HDM exposure.

Results: The modest and higher HDM target sessions respectively featured cumulative total particle counts of 156,784 and 266,694 particles (2.5-25 µm), Der f 1 concentrations of 2.67 ng/m and 3.80 ng/m, and Der p 1 concentrations of 2.07 ng/m and 6.66 ng/m. Allergic participants experienced an increase in symptoms, with modest target participants plateauing at 1.5 to 2 h and achieving a mean peak TNSS of 5.74 ± 0.65, mean peak TOSS of 2.47 ± 0.56, and mean peak TRSS of 9.16 ± 1.32. High HDM-target allergics reached a mean peak TNSS of 8.17 ± 0.71, mean peak TOSS of 4.46 ± 0.62, and mean peak TRSS of 14.08 ± 1.30 at 3 h. All allergic participants' symptoms decreased but remained higher than baseline after exiting the HDM-EEU. Sixteen participants (37.2%) were classified as Early Phase Responders (EPR), eleven (25.6%) as protracted EPR (pEPR), seven (16.3%) as Dual Phase Responders (DPR), and nine (20.9%) as Poor Responders (PR). Allergic participants experienced significant percent PNIF reductions at hours 2 and 3 compared to healthy controls. Non-allergics were asymptomatic during the study period.

Conclusions: The HDM-EEU is an appropriate model to study HDM-induced AR as it can generate clinically relevant AR symptoms amongst HDM-allergic individuals.
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http://dx.doi.org/10.1186/s13223-021-00536-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7995585PMC
March 2021

The use of nasal allergen vs allergen exposure chambers to evaluate allergen immunotherapy.

Expert Rev Clin Immunol 2021 May 8;17(5):461-470. Epub 2021 Apr 8.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada.

Introduction: Allergen-specific immunotherapy (AIT) is the only disease-modifying treatment option for allergic rhinitis (AR) patients with persistent moderate-severe AR for whom traditional pharmacotherapies are ineffective. The nasal allergen challenge (NAC) and allergen exposure chamber (AEC) are two translational models of AR that can be used to investigate the properties, safety, and efficacy of AIT.

Areas Covered: Peer-reviewed, human-centered articles utilizing AEC or NAC models to investigate AIT between 2010 and 2020 were curated from PubMed, EMBASE, and OVID Medline databases. AECs have been used to evaluate traditional subcutaneous and sublingual administrations of AIT, including cross-protective effects and different dosing regimens. More recently, the effectiveness of novel AIT formulations has been evaluated. NACs are another model used to study AIT, including using novel intralymphatic routes of administration. It is an especially powerful and versatile tool to determine if basic science and animal model findings are clinically translatable.

Expert Opinion: The AEC and NAC models both produce clinically relevant and reproducible results. AECs are more effective for studying many participants but are limited because they require a specialized facility. As more AIT therapies and new formulations are developed over time, the versatility of the NAC will be especially useful.
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http://dx.doi.org/10.1080/1744666X.2021.1905523DOI Listing
May 2021

COVID-19 vaccine testing & administration guidance for allergists/immunologists from the Canadian Society of Allergy and Clinical Immunology (CSACI).

Allergy Asthma Clin Immunol 2021 Mar 15;17(1):29. Epub 2021 Mar 15.

Department of Pediatrics, Section of Allergy and Clinical Immunology, University of Manitoba, Winnipeg, MN, Canada.

Background: Safe and effective vaccines provide the first hope for mitigating the devastating health and economic impacts resulting from coronavirus disease 2019 (COVID-19) and related public health orders. Recent case reports of reactions to COVID-19 vaccines have raised questions about their safety for use in individuals with allergies and those who are immunocompromised. In this document, we aim to address these concerns and provide guidance for allergists/immunologists.

Methods: Scoping review of the literature regarding COVID-19 vaccination, adverse or allergic reactions, and immunocompromise from PubMed over the term of December 2020 to present date. We filtered our search with the terms "human" and "English" and limited the search to the relevant subject age range with the term "adult." Reports resulting from these searches and relevant references cited in those reports were reviewed and cited on the basis of their relevance.

Results: Assessment by an allergist is warranted in any individual with a suspected allergy to a COVID-19 vaccine or any of its components. Assessment by an allergist is NOT required for individuals with a history of unrelated allergies, including to allergies to foods, drugs, insect venom or environmental allergens. COVID-19 vaccines should be offered to immunocompromised patients if the benefit is deemed to outweigh any potential risks of vaccination.

Interpretation: This review provides the first Canadian guidance regarding assessment of an adolescent and adult with a suspected allergy to one of the COVID-19 vaccines currently available, or any of their known allergenic components, and for patients who are immunocompromised who require vaccination for COVID-19. As information is updated this guidance will be updated accordingly.
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http://dx.doi.org/10.1186/s13223-021-00529-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7957441PMC
March 2021

Treatment Effect of the Tree Pollen SLIT-Tablet on Allergic Rhinoconjunctivitis During Oak Pollen Season.

J Allergy Clin Immunol Pract 2021 05 3;9(5):1871-1878. Epub 2021 Feb 3.

ALK, Hørsholm, Denmark.

Background: Birch, alder, hazel, and oak are members of the birch homologous group based on cross-reactivity toward the birch pollen allergen Betula verrucosa 1. Theoretically, allergy to these tree pollens may be treated by immunotherapy with one representative allergen extract.

Objective: To evaluate post hoc whether treatment of birch pollen-induced allergic rhinoconjunctivitis with a standardized tree sublingual immunotherapy (SLIT)-tablet containing birch pollen extract reduces symptoms and symptom-relieving medication use during the oak pollen season (OPS).

Methods: In a randomized, multinational, double-blind trial (EudraCT-2015-004821-15), 634 participants (ages 12-65 years) received daily tree SLIT-tablet (12 SQ-Bet) or placebo before and during tree pollen season (alder/hazel plus birch pollen season [BPS]). Symptom-relieving medication was allowed. The primary end point was the average total combined score (sum of rhinoconjunctivitis daily symptom score and daily medication score) during BPS. Outcomes during the OPS (excluding overlapping BPS days) were analyzed post hoc.

Results: Relative improvements in average total combined score, daily symptom score, and daily medication score with the tree SLIT-tablet versus placebo during the OPS were 25%, 22%, and 32%, respectively (all P < .001). Significant correlations were observed between birch and oak serum immunoglobulin E (sIgE) at baseline (r = 0.86) and between birch and oak IgG after treatment (r = 0.72). Oak sIgE and IgG kinetics in response to tree SLIT-tablet treatment were similar to birch.

Conclusions: The tree SLIT-tablet leads to significant improvement of rhinoconjunctivitis outcomes during the OPS, supporting the clinical relevance of immunological cross-reactivity toward birch and oak allergens.
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http://dx.doi.org/10.1016/j.jaip.2021.01.035DOI Listing
May 2021

Allergy to oak pollen in North America.

Allergy Asthma Proc 2021 01;42(1):43-54

ALK, Bedminster, New Jersey.

Oak pollen is an important allergen in North America. The genus Quercus (oak) belongs to the family Fagaceae under the order Fagales. The objective of this article was to narratively review the oak pollen season, clinical and epidemiologic aspects of allergy to oak pollen, oak taxonomy, and oak allergen cross-reactivity, with a focus on the North American perspective. A PubMed literature review (no limits) was conducted. Publications related to oak pollen, oak-related allergic rhinitis with or without conjunctivitis, and oak-related allergic asthma were selected for review. Oak species are common throughout the United States and contribute up to 50% to overall atmospheric pollen loads. Mean peak oak pollen counts can reach >2000 grains/m³. The start of the oak pollen season generally corresponds to the seasonal shift from winter to spring based on latitude and elevation, and may begin as early as mid February. The duration of the season can last > 100 days and, in general, is longer at lower latitudes. In the United States, ∼30% of individuals with allergy are sensitized to oak. The oak pollen season correlates with increased allergic rhinitis symptom-relieving medication use and asthma-related emergency department visits or hospitalizations. Oak falls within the birch homologous group. Extensive immunologic cross-reactivity has been demonstrated between oak pollen and birch pollen allergens, and, more specifically, their major allergens Que a 1 and Bet v 1. The cross-reactivity between oak and birch has implications for allergy immunotherapy (AIT) because guidelines suggest selecting one representative allergen within a homologous group for AIT, a principle that would apply to oak. Allergy to oak pollen is common in North America and has a substantial clinical impact. Oak pollen allergens are cross-reactive with birch pollen allergens, which may have implications for AIT.
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http://dx.doi.org/10.2500/aap.2021.42.200089DOI Listing
January 2021

Practical guide for evaluation and management of beta-lactam allergy: position statement from the Canadian Society of Allergy and Clinical Immunology.

Allergy Asthma Clin Immunol 2020 Nov 10;16(1):95. Epub 2020 Nov 10.

Division of Allergy and Immunology, Department of Pediatrics, University of British Columbia, Vancouver, BC, Canada.

The vast majority of individuals labelled as allergic are not deemed truly allergic upon appropriate assessment by an allergist. A label of beta-lactam allergy carries important risks for individual and public health. This article provides an overview of beta-lactam allergy, implications of erroneous beta-lactam allergy labels and the impact that can be provided by structured allergy assessment. We provide recommendations on how to stratify risk of beta-lactam allergy, beta lactam challenge protocols as well as management of patients at high risk of beta-lactam allergy.
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http://dx.doi.org/10.1186/s13223-020-00494-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7653726PMC
November 2020

Patient Engagement Partnerships in Clinical Trials: Development of Patient Partner and Investigator Decision Aids.

Patient 2020 12 7;13(6):745-756. Epub 2020 Oct 7.

Patient Partner, Diabetes Action Canada, Toronto, ON, Canada.

Background: A 2017 systematic review suggested patient engagement in clinical trials has been limited, with little active engagement in trial design or data analysis, interpretation or dissemination. Additionally, there remains limited sex/gender reporting in clinical trial research.

Objectives: The overall goal of this project was to disseminate sex/gender knowledge and build capacity for patient engagement in clinical trials. Specific objectives were to (1) create capacity and identify opportunities for patient engagement in clinical trials and sponsor- or investigator-led activities (e.g. clinical trial design and conduct); and (2) enhance new/early investigator sex/gender knowledge and skills related to patient-oriented research (POR).

Methods: We used the Canadian Institutes of Health Research Strategy for Patient-Oriented Research (SPOR) Capacity Development Framework and the SPOR Patient Engagement Framework to guide three phases of this project: (1) conduct a scoping review using methods described by the Evidence for Policy and Practice Information (EPPI) and the Coordinating Centre at the Institute of Education (Phase 1); (2) host a 1-day POR consultation workshop (Phase 2); and (3) deliver a new/early investigator POR training day (Phase 3). Six electronic databases (CINAHL, MEDLINE, EMBASE, PsychInfo, the Cochrane Library, and AMED) were searched from 1996 using keywords and Medical Subject Heading (MeSH) terms in accordance with the International Association for Public Participation (IAP2) and the search criteria in the bibliographic databases. Standard approaches were used to search the grey literature.

Results: A total of 79 studies and over 150 websites were subject to data abstraction by team members, capturing information on sex/gender and SPOR's patient engagement guiding principles of inclusiveness, support, mutual respect, and co-building. Results were presented to 32 key stakeholders at the consultation workshop and input was sought on next steps using nominal group techniques. Based on the plethora of existing POR resources, relevant POR information from the scoping review was collated into two decision aids (patient and investigator) to determine readiness to engage with/as a patient partner in a clinical trial. The decision aids were presented at a POR training day with 88 new/early investigators, clinicians, patient partners and decision makers. The decision aids showed 'good' usability, assessed using the System Usability Scale (SUS). Attendees thought the decision aids were engaging, they increased their understanding of sex/gender, patient engagement and POR, and they would recommend them to others. POR principles and practices were integrated across all phases of the project. Patient partners (1) identified research priorities/search terms; (2) collected/analyzed data; (3) designed the patient partner decision aid; and (4) disseminated the results through presentation.

Conclusion: Our digital patient partner and investigator decision aids are the first to provide information technology to deliver sex/gender, POR knowledge, and decision support beyond the traditional decision aids used for health screening and/or treatment decisions. The decision aids have the potential to make a significant contribution to Canada's Strategy for POR and support the collaborative efforts of patients and investigators to build a sustainable, accessible and equitable health care system.
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http://dx.doi.org/10.1007/s40271-020-00460-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7655585PMC
December 2020

Exposomal research in the context of birth cohorts: What have they taught us?

Ann Allergy Asthma Immunol 2020 12 12;125(6):639-645. Epub 2020 Sep 12.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada; Allergy Research Unit, Kingston Health Sciences Centre, Kingston General Hospital Site, Kingston, Ontario, Canada; Division of Allergy & Immunology, Department of Medicine, Queen's University, Kingston, Ontario, Canada. Electronic address:

Objective: To review birth cohorts with an exposomal approach and their key outcomes and challenges. Exposome encompasses all human environmental exposures from conception onward. The impact of environmental exposures is greatest in critical stages of life, including fetal and early childhood. Birth cohorts provide a good study setting to assess exposome in the sensitive periods of life. Here, we review birth cohorts with an exposomal approach and their key outcomes and challenges.

Data Sources: MEDLINE was searched for birth cohorts that have used an exposomal approach.

Study Selections: Relevant studies in English language were selected and reviewed.

Results: The outcomes of birth cohorts with an exposomal approach improve our understanding of the association between environmental exposures and childhood diseases. For example, results from The Canadian Healthy Infant Longitudinal Development Study suggest an association between first trimester exposure to traffic-related air pollution and increased risk of allergic sensitization at 12 months of age (P = .6). In a smaller Canadian birth cohort study, it was found that regular use of air fresheners (adjusted P = .04) and presence of mold in the residence (adjusted P < .001) were associated with early childhood wheezing and cough. The application of emerging molecular omics technologies and new analytical tools has facilitated the comprehensive assessment of exposome in birth cohorts.

Conclusion: Birth cohort studies with an exposomal approach improve our understanding of the origin of childhood diseases by examining a complex network of environmental exposures during pregnancy and years beyond birth. International collaboration is required to develop large birth cohorts for better and more extensive assessment of exposome with standardized protocols and new statistical frameworks.
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http://dx.doi.org/10.1016/j.anai.2020.09.006DOI Listing
December 2020

Air Pollution and Allergic Rhinitis: Role in Symptom Exacerbation and Strategies for Management.

J Asthma Allergy 2020 26;13:285-292. Epub 2020 Aug 26.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.

This article reviews the current understanding of the role of air pollution in both the symptom exacerbation and rising prevalence of allergic rhinitis (AR) for the development of future AR therapeutics and management strategies. We discuss the epidemiological evidence for this relationship through birth cohort studies, the economic impact of AR, and the influence of air pollution through the lens of the exposome framework of allergic disease development. This is followed by a discussion on the influence of diesel exhaust and diesel exhaust particles (DEP) from motor vehicle emissions and their implication in the rising prevalence of allergic disease and allergic sensitization through triggering inflammatory signalling pathways that exacerbate AR symptoms. Finally, a summary is provided of clinical trials assessing the influence of air pollution on AR with a depiction of currently available therapies and management strategies. Future directions in the development of AR modalities given the air pollution-mediated symptom exacerbation are challenged with unfolding the complex gene-environment interaction product of heterogenous AR presentation.
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http://dx.doi.org/10.2147/JAA.S237758DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7457822PMC
August 2020

Rhinitis 2020: A practice parameter update.

J Allergy Clin Immunol 2020 10 22;146(4):721-767. Epub 2020 Jul 22.

Division of Allergy and Immunology, Department of Pediatrics, The Elliot and Roslyn Jaffe Food Allergy Institute, Icahn School of Medicine at Mount Sinai, New York, NY.

This comprehensive practice parameter for allergic rhinitis (AR) and nonallergic rhinitis (NAR) provides updated guidance on diagnosis, assessment, selection of monotherapy and combination pharmacologic options, and allergen immunotherapy for AR. Newer information about local AR is reviewed. Cough is emphasized as a common symptom in both AR and NAR. Food allergy testing is not recommended in the routine evaluation of rhinitis. Intranasal corticosteroids (INCS) remain the preferred monotherapy for persistent AR, but additional studies support the additive benefit of combination treatment with INCS and intranasal antihistamines in both AR and NAR. Either intranasal antihistamines or INCS may be offered as first-line monotherapy for NAR. Montelukast should only be used for AR if there has been an inadequate response or intolerance to alternative therapies. Depot parenteral corticosteroids are not recommended for treatment of AR due to potential risks. While intranasal decongestants generally should be limited to short-term use to prevent rebound congestion, in limited circumstances, patients receiving regimens that include an INCS may be offered, in addition, an intranasal decongestant for up to 4 weeks. Neither acupuncture nor herbal products have adequate studies to support their use for AR. Oral decongestants should be avoided during the first trimester of pregnancy. Recommendations for use of subcutaneous and sublingual tablet allergen immunotherapy in AR are provided. Algorithms based on a combination of evidence and expert opinion are provided to guide in the selection of pharmacologic options for intermittent and persistent AR and NAR.
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http://dx.doi.org/10.1016/j.jaci.2020.07.007DOI Listing
October 2020

The home environment's influence on cytokine profiles and atopic disease in 6- to 7-year-old children.

Ann Allergy Asthma Immunol 2020 12 8;125(6):699-701. Epub 2020 Jun 8.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Ontario, Canada; Allergy Research Unit, Kingston Health Sciences Centre, Kingston General Hospital, Kingston, Ontario, Canada; Department of Medicine, Queen's University, Kingston, Ontario, Canada. Electronic address:

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http://dx.doi.org/10.1016/j.anai.2020.06.002DOI Listing
December 2020

Towards definitive management of allergic rhinitis: best use of new and established therapies.

Allergy Asthma Clin Immunol 2020 27;16:39. Epub 2020 May 27.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, Canada.

Background: Allergic rhinitis (AR) is an inflammatory disease of the nasal mucosa impacting up to 25% of Canadians. The standard of care for AR includes a treatment plan that takes into account patient preferences, the severity of the disease, and most essentially involves a shared decision-making process between patient and provider.

Body: Since their introduction in the 1940s, antihistamines (AHs) have been the most utilized class of medications for the treatment of AR. First-generation AHs are associated with adverse central nervous system (CNS) and anticholinergic side effects. On the market in the 1980s, newer generation AHs have improved safety and efficacy. Compared to antihistamines, intranasal corticosteroids (INCS) have significantly greater efficacy but longer onset of action. Intranasal AH and INCS combinations offer a single medication option that offers broader disease coverage and faster symptom control. However, cost and twice-per-day dosing remain a major limitation. Allergen immunotherapy (AIT) is the only disease-modifying option and can be provided through subcutaneous (SCIT) or sublingual (SLIT) routes. While SCIT has been the definitive management option for many years, SLIT tablets (SLIT-T) have also been proven to be safe and efficacious.

Conclusion: There is a range of available treatment options for AR that reflect the varying disease length and severity. For mild to moderate AR, newer generation AHs should be the first-line treatment, while INCS are mainstay treatments for moderate to severe AR. In patients who do not respond to INCS, a combination of intranasal AH/INCS (AZE/FP) should be considered, assuming that cost is not a limiting factor. While SCIT remains the option with the most available allergens that can be targeted, it has the potential for severe systemic adverse effects and requires weekly visits for administration during the first 4 to 6 months. SLIT-T is a newer approach that provides the ease of being self-administered and presents a reduced risk for systemic reactions. In any case, standard care for AR includes a treatment plan that takes into account disease severity and patient preferences.
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http://dx.doi.org/10.1186/s13223-020-00436-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7251701PMC
May 2020

Utility of Environmental Exposure Unit Challenge Protocols for the Study of Allergic Rhinitis Therapies.

Curr Allergy Asthma Rep 2020 06 6;20(8):34. Epub 2020 Jun 6.

Department of Biomedical and Molecular Sciences, Queen's University, Kingston, ON, Canada.

Purpose Of Review: This paper explores how the Environmental Exposure Unit (EEU) experimental model can be used to further our understanding of pharmacotherapies and immunotherapies for the treatment of allergic rhinitis (AR).

Recent Findings: EEUs are used increasingly for the study of combination therapies, immunotherapies, and novel AR treatments. A combined antihistamine/corticosteroid nasal spray formulation was seen to have a faster onset of action relative to the therapies individually in the Environmental Exposure Chamber. House dust mite sublingual immunotherapy tablets are both safe and efficacious as evaluated by the Vienna Challenge Chamber. The Kingston EEU found that a novel peptide-based immunotherapy approach to be effective in reducing grass pollen-induced AR. Lastly, nasal filters were determined to reduce seasonal AR symptoms, given out-of-season in the Denmark Environmental Exposure Unit. EEUs are controlled, replicable models that provide valuable insight into the efficacy, onset and duration of action, and dose-related impacts of AR therapeutics, with direct clinical relevance.
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http://dx.doi.org/10.1007/s11882-020-00922-8DOI Listing
June 2020

A Phased Approach to Resuming Suspended Allergy/Immunology Clinical Services.

J Allergy Clin Immunol Pract 2020 Jul - Aug;8(7):2125-2134. Epub 2020 May 22.

Children's Hospital Colorado, University of Colorado School of Medicine, Aurora, Colo. Electronic address:

In early 2020, the first US and Canadian cases of the novel severe acute respiratory syndrome coronavirus 2 infection were detected. In the ensuing months, there has been rapid spread of the infection. In March 2020, in response to the virus, state/provincial and local governments instituted shelter-in-place orders, and nonessential ambulatory care was significantly curtailed, including allergy/immunology services. With rates of new infections and fatalities potentially reaching a plateau and/or declining, restrictions on provision of routine ambulatory care are lifting, and there is a need to help guide the allergy/immunology clinician on how to reinitiate services. Given the fact that coronavirus disease 2019 will circulate within our communities for months or longer, we present a flexible, algorithmic best-practices planning approach on how to prioritize services, in 4 stratified phases of reopening according to community risk level, as well as highlight key considerations for how to safely do so. The decisions on what services to offer and how fast to proceed are left to the discretion of the individual clinician and practice, operating in accordance with state and local ordinances with respect to the level of nonessential ambulatory care that can be provided. Clear communication with staff and patients before and after all changes should be incorporated into this new paradigm on continual change, given the movement may be forward and even backward through the phases because this is an evolving situation.
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http://dx.doi.org/10.1016/j.jaip.2020.05.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7242939PMC
July 2020

Efficacy and Safety of Ragweed SLIT-Tablet in Children with Allergic Rhinoconjunctivitis in a Randomized, Placebo-Controlled Trial.

J Allergy Clin Immunol Pract 2020 Jul - Aug;8(7):2322-2331.e5. Epub 2020 Apr 15.

Merck & Co., Inc., Kenilworth, NJ.

Background: Ragweed sublingual immunotherapy (SLIT) tablet reduces symptoms and symptom-relieving medication use in adults with allergic rhinitis with or without conjunctivitis (AR/C) but has not been evaluated in children.

Objective: This international, multicenter, double-blind, placebo-controlled trial evaluated the efficacy and safety of ragweed SLIT-tablet in children with AR/C.

Methods: Children (N = 1025; 77.7% polysensitized) aged 5 to 17 years with ragweed pollen-induced AR/C with or without asthma (FEV ≥80% predicted) were randomized 1:1 to daily ragweed SLIT-tablet (12 Amb a 1-Unit) or placebo for up to 28 weeks (NCT02478398). The primary end point was the average total combined score (TCS; sum of rhinoconjunctivitis daily symptom score [DSS] and daily medication score [DMS]) during peak ragweed pollen season (RPS). Key secondary end points were TCS during the entire RPS, and DSS and DMS during the peak RPS.

Results: Relative TCS (95% CI) improvements with ragweed SLIT-tablet versus placebo were -38.3% (-46.0% to -29.7%; least square [LS] mean difference, -2.73; P < .001) during peak RPS and -32.4% (-40.7% to -23.3%; LS mean difference, -1.86; P < .001) during the entire RPS. DSS and DMS during peak RPS improved with SLIT-tablet versus placebo by -35.4% (-43.2% to -26.1%; LS mean difference, -1.40; P < .001) and -47.7% (-59.8% to -32.5%; LS mean difference, -1.84; P < .001), respectively. Asthma DSS, short-acting β-agonist use, and nocturnal awakenings during peak RPS improved with SLIT-tablet versus placebo by -30.7%, -68.1%, and -75.1%, respectively (all nominal P ≤ .02). No events of anaphylaxis, airway compromise, or severe treatment-related systemic allergic reactions were reported.

Conclusions: Ragweed SLIT-tablet significantly improved symptoms and decreased symptom-relieving medication use in children with ragweed pollen-induced AR/C and was well tolerated.
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http://dx.doi.org/10.1016/j.jaip.2020.03.041DOI Listing
May 2021

Effective Asthma Management: Is It Time to Let the AIR out of SABA?

J Clin Med 2020 Mar 27;9(4). Epub 2020 Mar 27.

Division of Allergy & Immunology, Department of Medicine, Queen's University, Kingston K7L 3N6, Ontario, Canada.

For years, standard asthma treatment has included short acting beta agonists (SABA), including as monotherapy in patients with mild asthma symptoms. In the Global Initiative for Asthma 2019 strategy for the management of asthma, the authors recommended a significant departure from the traditional treatments. Short acting beta agonists (SABAs) are no longer recommended as the preferred reliever for patients when they are symptomatic and should not be used at all as monotherapy because of significant safety concerns and poor outcomes. Instead, the more appropriate course is the use of a combined inhaled corticosteroid-fast acting beta agonist as a reliever. This paper discusses the issues associated with the use of SABA, the reasons that patients over-use SABA, difficulties that can be expected in overcoming SABA over-reliance in patients, and our evolving understanding of the use of "anti-inflammatory relievers" in our patients with asthma.
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http://dx.doi.org/10.3390/jcm9040921DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7230470PMC
March 2020
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