Evidence-based use of antihistamines for treatment of allergic conditions.

Available since the 1940s, H1 antihistamines are mainstay treatments for allergic conditions such as allergic rhinitis and urticaria. They function as inverse agonists that bind to the H1 receptor to inhibit histamine-induced inflammation. The older, first-generation drugs are no longer recommended for patient use because of their well-documented negative adverse effect profile. Evidence has been accumulating to support a newer generation of H1 antihistamines in oral and intranasal formulations, including in combination with intranasal corticosteroids. The literature is replete with large meta-analyses and systematic reviews establishing the safety and efficacy of second-generation H1 antihistamines in adult and pediatric allergic rhinitis populations, including combination nasal spray agents (eg, MP29-02 or MP-AzeFlu). Although intraclass differences do exist, patient preference, access, and costs should be the priority. Robust data on the regular, not as needed use of H1 antihistamines for urticaria have been published, including in the management of children and pregnant or lactating women. In addition, H1 antihistamines can be used in other related allergic conditions, such as the secondary symptoms of anaphylaxis, to provide patients with greater comfort, including in allergic asthma, depending on the individual.

Evaluating the effectiveness of let's talk period's high school educational outreach program: A pilot study.

INTRODUCTION: Menorrhagia impacts ~40% of adolescent females, with about half having an underlying bleeding disorder, most commonly von Willebrand Disease (VWD). VWD affects ~1 in 1000 individuals, though many are unaware of their condition. Let's Talk Period (LTP) is an online knowledge translation platform aimed at increasing awareness of bleeding disorders symptoms, with a validated self-administered bleeding assessment tool (Self-BAT). AIM: To evaluate the effectiveness of the LTP high school outreach program in Grade 9 girls' health classes quantitatively, using baseline, post-presentation, and follow-up quiz scores, and qualitatively, with student and teacher feedback forms. METHODS: The 75-minute in-class presentations, developed in alignment with the 2015 Ontario Curriculum for Grade 9 Health and Physical Activity, were led by a haemophilia nurse, clinical research assistant, and undergraduate student from the LTP team. Students completed baseline, post-presentation, and 4-6-week follow-up Kahoot quizzes featuring the same nine questions to evaluate change in knowledge levels and retention. Both student and teacher feedback were collected. RESULTS: There was a significant increase (p < 0.001) from baseline to post-presentation scores, with a significant gain in knowledge, for all questions (p < 0.01). Students found content related to the basics and management of menstruation to be most interesting. Many had constructive feedback on how the presentation method could be improved. On average, the presentations were rated an 8.6 of 10 by students and 8.75 of 10 by teachers. CONCLUSION: The LTP high school outreach program effectively increases student knowledge of menorrhagia and bleeding disorders. It was well-received by students and staff alike.

Future of allergic rhinitis management.

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.

Insights into allergic risk factors from birth cohort studies.

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.

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

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.

Anxiety in adults with asthma during the coronavirus disease 2019 pandemic: a Canadian perspective.

BACKGROUND: Asthma is a chronic airway inflammatory disease that affects millions of Canadians and often contributes to higher levels of anxiety among patients. Since the coronavirus disease 2019 (COVID-19) pandemic was a time of increased anxiety and fear among the Canadian population, it was thought that those with asthma may experience heightened anxiety levels due to uncertain access to care, the potential to misinterpret asthma symptoms for symptoms of COVID-19 (or vice versa), and the concern about being treated differently by those around them when experiencing asthma symptoms. Therefore, this study sought to perform a cross-sectional analysis of the asthma-anxiety relationship in adults with and without asthma in the unique context of the COVID-19 pandemic from a Canadian perspective. METHODS: This study employed the COVID-19 Associated Anxiety in Allergic Rhinitis and Asthma patients Experiencing Symptoms (CAAARES) survey, consisting of COVID-19-specific questions, the Generalized Anxiety Disorder Assessment-7 (GAD-7) and the Asthma Control Questionnaire-6 (ACQ-6). Data collection occurred through the Qualtrics XM platform and data analyses were conducted with the IBM SPSS Statistics 28 software. RESULTS: A total of 741 valid responses were collected (asthma group, n = 244; control group, n = 497). 31.6% and 26.2% of respondents in the asthma and control groups, respectively, met the diagnostic criteria for GAD. There was no significant difference (p = .067) in mean GAD-7 scores between the two groups. A Hierarchal Multiple Regression (HMR) model was developed, and neither asthma status nor ACQ-6 score had a significant predictive effect on the GAD-7 score. There was a statistically significant (p < .001) weak positive correlation (r = .22) between GAD-7 and ACQ-6 scores. In a simple mediation (SMM) model, perceived COVID-19 stress of others was not identified as a significant mediator of the relationship between ACQ-6 and GAD-7 (indirect effect ß = 0.014). CONCLUSION: Our study of a Canadian cohort demonstrates elevated levels of anxiety overall, amongst both asthma and control groups. While AR status was significantly greater in the asthma group, it was not a significant predictive variable of GAD-7 score. Our data suggests that COVID-19-specific factors appear to have a greater contribution to anxiety than asthma status or control.

Study of Cat Allergy Using Controlled Methodology-A Review of the Literature and a Call to Action.

The prevalence of cat allergen-induced AR is increasing worldwide, prompting its study using controlled methodology. Three general categories of allergen exposure models currently exist for the study of cat allergen-induced AR: natural exposure cat rooms, allergen exposure chambers (AEC), and nasal allergen challenges (NAC). We evaluated existing literature surrounding the use of these models to study cat allergen induced AR using online research databases, including OVID Medline, Embase, and Web of Science. We report that natural exposure cat rooms have been important in establishing the foundation for our understanding of cat allergen-induced AR. Major limitations, including variable allergen ranges and differing study designs highlight the need for a more standardized protocol. In comparison, AECs are an exceptional model to mimic real-world allergen exposure and study long-term implications of AR with large sample sizes. Existing AECs are limited by heterogeneous facility designs, differing methods of cat allergen distribution, and issues surrounding cost and accessibility. Conversely, NACs allow for smaller participant cohorts for easier biological sampling and are ideal for phase I, phase 2 or proof-of-concept studies. NACs generally have a standardized protocol and are less expensive compared to AECs. Nevertheless, NACs solely capture acute allergen exposure and have the further limitation of using allergen extracts rather than natural allergen. As the use of combined controlled methodologies is sparse, we recommend concurrent use of AECs and NACs to study short- and long-term effects of AR, thereby providing a more holistic representation of cat allergen-induced AR.

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

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.

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

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.

Lay abstract Allergen immunotherapy is the only disease-modifying treatment option for patients with chronic allergic rhinitis, typically featuring formulations to promote the development of immune tolerance. Although effective, the use of whole allergen has been found to promote unintended IgE crosslinking, resulting in local and systemic adverse effects. To overcome such limitations, the use of T-cell epitope peptides in allergen immunotherapy has been explored with hopeful outcomes. Compared with allergen immunotherapy, peptide immunotherapy is quicker, safer and more efficacious, making it quite promising. Although peptides for pet dander, honeybee venom, pollen and house dust mite allergies have been developed, more extensive research is necessary to prior to widespread usage.

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

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/m3 and 3.80 ng/m3, and Der p 1 concentrations of 2.07 ng/m3 and 6.66 ng/m3. 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.

Biologic Responses to House Dust Mite Exposure in the Environmental Exposure Unit.

Introduction: Allergic rhinitis (AR) is an inflammatory disease of the nasal mucosa that can be modeled using Controlled Allergen Exposure Facilities (CACF). Recently, we clinically validated the house dust mite (HDM) Environmental Exposure Unit (EEU) facility. In the current study, we aimed to assess biological responses in the blood following HDM exposure in the HDM-EEU. Methods: Fifty-five participants passed a screening visit, where they provided consent and completed a skin prick test (SPT), then attended a modest or higher HDM exposure session. Baseline and post-exposure blood samples were collected. Complete blood counts with differentials were measured, and isolated serum was used to determine Dermatophagoides farinae- and Dermatophagoides pteronyssinus-specific IgE (sIgE) and cytokine concentrations (IL-4, IL-5, IL-6, IL-10, IL-13, TNF-α). Results: HDM-allergic participants had significantly greater SPT wheal sizes than healthy controls. sIgE concentrations were significantly greater in allergic participants, with a strong correlation between Dermatophagoides farinae and Dermatophagoides pteronyssinus. Serum eosinophil counts were significantly decreased post-exposure for allergic participants. White blood cell, neutrophil, and lymphocyte counts were significantly increased for both allergic and non-allergic participants post-exposure. Serum IL-13 concentrations were significantly reduced post-exposure in allergics while TNF-α was significantly reduced in non-allergics. Conclusion: The HDM-EEU is a useful model for investigating biologic mechanisms of HDM-induced AR. Allergic participants produced measurable biological changes compared to healthy controls following allergen exposure, specifically with serum expression of eosinophils and related markers, namely IL-5, which promotes the proliferation and differentiation of eosinophils, and IL-13, a cytokine released by eosinophils. The exact mechanisms at play require further investigation.

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

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.