Differential modulation of allergic rhinitis nasal transcriptome by dupilumab and allergy immunotherapy: correspondenceChun-Ting Lin1, Chi-Wei Lin2, Su-Boon Yong3,4,5 Chin-Yuan Yii61. Department of pharmacy, Chung Shan Medical University Hospital, Taiwan.2. College of Nursing, Asia University, Taichung, Taiwan.3. Department of Allergy and Immunology, China Medical University Children’s Hospital, Taichung, Taiwan.4. Department of Medicine, College of Medicine, China Medical University, Taichung, Taiwan5. Center for Allergy, Immunology, and Microbiome (A.I.M.), China Medical University Hospital, Taichung, Taiwan.6. Division of Gastroenterology and Hepatology, Department of Internal Medicine, Landseed International Hospital, Taoyuan, Taiwan.Corresponding author:1.Chin-Yuan Yii, MDDivision of Gastroenterology and Hepatology, Department of Internal Medicine, LandseedInternational Hospital, Taoyuan, TaiwanEmail: [email protected] Yong, MD, PhDDepartment of Allergy and Immunology, China Medical University Children’s Hospital, Taichung, Taiwan, Republic of ChinaE-mail: [email protected] word count of the manuscript: 541Dear Editor,We have carefully examined the study conducted by Dr. Matthew F. Wipperman and colleagues, titled ”Differential Modulation of Allergic Rhinitis Nasal Transcriptome by Dupilumab and Allergy Immunotherapy1.” The research offers significant insights into how treatment with dupilumab alone, or in combination with subcutaneous immunotherapy, affects gene expression in allergic rhinitis. The team’s diligent efforts in this domain are highly commendable. However, it is also crucial to acknowledge certain limitations within the scope of this investigation.Firstly, the reliance on Timothy grass (Phleum pratense) as the principal allergen in this research prompts consideration of its geographic and demographic relevance. While Timothy grass serves as a prevalent allergen in Europe and North America, its distribution and incidence differ across other regions2. This study lacks specific information about the geographic or demographic profiles of the participants, which is crucial given the predominance of Timothy grass in temperate zones. Consequently, the generalizability of the results may be constrained, particularly in tropical or subtropical regions where Timothy grass is uncommon, potentially limiting the applicability of the findings.Second, this study incorporated data from two independent trials, with sample sizes of 15 and 103 participants, respectively. Considering the global prevalence of allergic rhinitis, estimated at 19.1%3, the small sample sizes may undermine the statistical power and the wider applicability of the study’s outcomes. To bolster the statistical robustness and reliability of subsequent investigations, an increase in sample size is recommended. Expanding the cohort would enhance the accuracy in reflecting population variability and ensure more dependable results. Moreover, the initial participant pool was limited to specific geographic areas. Future studies should strive for a more heterogeneous sample by including individuals from diverse geographic and ethnic backgrounds. Such inclusivity would broaden the applicability of the results, ensuring they reflect a more comprehensive demographic spectrum. This methodological refinement is crucial for a deeper understanding of the therapeutic efficacy across varied patient groups.Third, exclusion criteria of this investigation barred participants who had used antihistamines shortly before the screening and nasal allergen challenge visits. Yet, it remains uncertain if the researchers monitored ongoing antihistamine use post-screening through the follow-up period. Notably, research by Erwin W. Gelfand and colleagues4has shown that fexofenadine-a widely used H1 antihistamine in Europe and the United States-can modulate IL-4 and IL-5 levels, which could significantly affect study outcomes. Consequently, this oversight raises concerns regarding the potential influence of antihistamines on the results, emphasizing the necessity for vigilant monitoring of antihistamine use during follow-up assessments. To mitigate these risks and ensure the integrity of the findings, future research should rigorously track all concurrent medication use, including antihistamines, both during and subsequent to the screening phase. Such meticulous oversight will safeguard the study’s conclusions from confounding variables, thus providing a more accurate evaluation of treatment effects.In summary, the research conducted by Dr. Matthew F. Wipperman et al. significantly advances our knowledge of how dupilumab can normalize nasal tissue gene expression. Prior studies highlight that the United States spends roughly $3.4 billion annually on treating allergic rhinitis, a large part of which goes towards medications5. Further research yielding deeper insights and robust data could lessen the impact of allergic rhinitis on patients globally and might also diminish the considerable economic strain it places on healthcare systems.