The Allergic Rhinitis Clinical Investigator Collaborative (AR-CIC): verification of nasal allergen challenge procedures in a study utilizing an investigational immunotherapy for cat allergy

Abstract Background The Allergic Rhinitis Clinical Investigator Collaborative (AR-CIC) is a network of experienced Allergic Rhinitis (AR) researchers developing better research tools based on the nasal allergen challenge (NAC). A key objective of such is the ability to detect efficacy in a small population. AR-CIC sought to test its NAC protocol as a secondary objective in two small mechanistic research trials of a novel form of immunotherapy [Cat Peptide Antigen Desensitisation (Cat-PAD)] for which efficacy had previously been demonstrated. The primary objective (not presented here) was to identify potential biomarkers of efficacy for peptide immunotherapy, and this provided an ideal opportunity to corroborate the NAC protocol. We aim to clinically validate the AR-CIC NAC methodology in a pooled analysis of secondary endpoints measured in two open label mechanistic studies of cat allergic participants treated with Cat-PAD. Methods Cat allergic AR sufferers with ongoing cat exposure were included. Participants had to demonstrate a total nasal symptom score (TNSS) of at least 8 (max 12) and/or achieve a reduction in peak nasal inspiratory flow (PNIF) of ≥ 50% during a screening titrated NAC. Eligible participants then underwent a baseline NAC visit with the allergen dose that produced a positive challenge at screening, followed by four monthly injections of 6 nmol Cat-PAD. A follow up NAC visit documented changes in nasal response 1 month following the completion of treatment. Results Nineteen subjects completed the study protocol in the two studies combined. Four injections of Cat-PAD resulted in a significant reduction in TNSS responses generated via NAC following allergen challenge (15 min p < 0.05, 30 min p < 0.05, 1 h p < 0.01, 2 h p < 0.05). There was modest correlation between symptom scores and PNIF measurements. Conclusions This study supports the validity of the AR-CIC’s optimised NAC protocol for conducting research of the potential efficacy of novel therapeutics in multi-centre studies. Trial registration Both studies reported herein were registered clinicaltrials.gov (NCT01383590 and NCT01383603

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

Abstract 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 β = 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

Kingston Allergy Birth Cohort (KABC); Exposome Characteristics and Parentally- Reported Respiratory Outcomes to Age 2

Background: The Kingston Allergy Birth Cohort (KABC) is a prenatally-recruited cohort initiated to study the developmental origins of allergic disease. Kingston General Hospital was chosen for recruitment, as it serves a population with notable diversity in exposures relevant to the emerging concept of the exposome. Objective: Establish a profile of the KABC cohort using the exposome framework, and examine parentally-reported respiratory symptoms to age 2. Methods: Data on phase 1 of the cohort (n=560 deliveries) were compiled and multivariate Cox proportional hazard models were used to determine associations with respiratory symptoms. Results: The KABC exhibits diversity within the three exposome domains; “general external” (SES, rural/urban residency), “specific external” (cigarette smoke, breastfeeding, mold/dampness), and “internal” (respiratory health, gestational age). We demonstrate relationships between exposome domains, as residential locale and SES significantly affected characteristics of the home environment. Significant associations emerged between parental reports of wheeze/cough without a cold and exposures within all three domains, including SES, 70 breastfeeding, gestational age, prenatal cigarette smoke exposure, and mold/dampness. Conclusions: The KABC is a unique cohort with diversity that can be leveraged for exposomics- based studies, and a notably high prevalence of prenatal smoke exposure. This study demonstrated the impacts of all three domains of the exposome on the respiratory health of KABC children. Ongoing studies using phase 1 of the KABC are further exploring the internal exposome through allergy skin testing and epigenetic analyses, and the specific external domain through in-home environmental analyses, air pollution modeling and ultimately the potential convergence of the two.MLN; J.A. Stewart Award, Department of Medicine, Queen’s University, Ontario Ministry of Research & Innovation Award, and AllerGen N.C.E. Canadian Allergy and Immune Diseases Advanced Training Initiative (CAIDATI). The study was supported by an Ontario Thoracic Society & Canadian Lung Association Grant-in aid of Research, an Allergy/Asthma Information Association (AAIA) and Canadian Allergy, Asthma & Immunology Foundation (CAAIF) Award for Ontario Research in Food Allergy, and an American College of Allergy, Asthma & Immunology (ACAAI) Young Faculty Support Award