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Background: The diagnosis of the culprit allergen depends on exposure, symptoms at exposure, and the presence of specific IgE (sIgE). Pet allergens are sticky and can sensitize individuals without adoption history. Exclusive dog owners frequently exhibit both dog (e5) and cat dander sIgE (e1). We assessed whether the measurement of Fel d 1 sIgE (e94) can discriminate true cat sensitization from false positivity by cross-reactivity in the exclusive dog owners. Methods: Thirty-one patients with respiratory allergies who exclusively owned dogs were enrolled for this study. e5, e1, and e94 were measured with ImmunoCAP. ELISA inhibition was performed to assess cross-reactivity. Results: About 81% of patients (25/31) were both e5 and e1 positive, and 8 were also positive for e94. In the e94 positive, cat dander exhibited higher maximum inhibition of cat sIgE (94% vs 88%) and demonstrated lower IC50 (6.5 vs 737.9 BAU/mL) compared to dog dander. Conversely, in the e94 negative, dog dander demonstrated higher maximum inhibition of cat dander sIgE (71.9% vs 56.2%) and lower IC50 (172 vs 1947 BAU/mL) compared to cat dander. In the e94 positive, dog dander exhibited higher maximal inhibition for dog sIgE (91.5 vs 76.1%) and lower IC50 (10.6 vs 1679 BAU/mL) compared to cat dander, whereas in the e94 negative, the IC50 for cat dander could not be determined. Conclusions: Genuine co-sensitization to cats is notable even in individuals who exclusively own dogs. Positive e94 results could discriminate authentic cat sensitization from false positivity by cross-reactivity in these patients, underscoring the importance of comprehensive allergy assessment.

Background: Several biologics have been developed and used to treat severe asthma. However, commercialized biologics have limitations in treating T2-low asthma because their main target is the T2 inflammation marker. Therefore, there is an unmet need for treating T2-low severe asthma. Aminoacyl-tRNA synthetase-interacting multifunctional protein 1 (AIMP1) is an auxiliary protein in the mammalian multi-aminoacyl-tRNA synthetase complex. AIMP1 also acts as a cytokine and induces the secretion of proinflammatory cytokines. Since anti-AIMP1 has been shown to reduce interleukin (IL)-6, tumor necrosis factor-α, and IL-17A levels in a mouse model, it could be effective in the treatment of T2-low severe asthma. Methods: Wild-type BALB/c mice were sensitized and challenged with intranasal inoculation of a crude HDM extract. Atliximab, a chimeric AIMP1 antibody, was administered once (20 μg, 40 μg, 100 μg) on Day 14. We evaluated airway hyperresponsiveness (AHR), performed cellular analyses of the bronchoalveolar lavage fluid (BALF), measured inflammatory cytokine levels, and examined peribronchial histological features. Results: Atliximab reduced AIMP1 levels in asthmatic mice in a dose-dependent manner. AHR and Inflammatory cells such as neutrophils and eosinophils in the BALF decreased in asthmatic mice treated with atliximab. The levels of IL-6, IL-13, and transforming growth factor-β (TGF-β) in the lung tissue decreased in asthmatic mice treated with a high dose of atliximab (100 μg). Atliximab also reduced goblet cell hyperplasia and peribronchial fibrosis. Conclusions: Atliximab improved asthmatic airway inflammation including neutrophilic inflammation in HDM-induced asthma mice. These data suggest that anti-AIMP1 plays an important role in the treatment of severe T2-low asthma.

Background: Few studies have evaluated the comparative efficacy of biologics for asthma. This network meta-analysis aimed to compare the efficacy of biologics. Methods: This study included randomized controlled trials (RCTs) evaluating the efficacy of a biologic compared to a placebo or another biologic in patients with inadequately controlled asthma despite high-intensity treatment, published by January 6, 2022. Two researchers independently searched the PubMed, Embase, Web of Science, and Scopus and assessed the risk of bias using the Cochrane tool. The outcomes of interest were the annual asthma exacerbation rate (AER), forced expiratory volume per second before bronchodilator use (preBD FEV1), the asthma control questionnaire (ACQ), and asthma quality of life questionnaire (AQLQ) results. A frequentist network meta-analysis was conducted, and a random effects model was used to draw pooled incidence rate ratio or standardized mean differences. Results: Twenty-three RCTs with 8376 participants were retrieved. All biologics included in this study were associated with significantly better effects than placebo in AER, preBD FEV1, and ACQ outcomes. Although there were no significant differences between the biologics in the overall study population, patients with eosinophil levels ≥300 cells/μL or eosinophilic asthma showed that dupilumab and tezepelumab were significantly better than anti-IL-5 biologics in improving preBD FEV1. Additionally, in patients with eosinophil levels ≥300 cells/μL, benralizumab, unlike reslizumab, performed significantly better than placebo in improving ACQ and AQLQ outcomes. Conclusion: The comparative effects of biologics can be considered with phenotypes and biomarkers to help clinicians select an appropriate treatment for inadequately controlled asthma.

Background: Tiotropium, a long-acting muscarinic antagonist, is recommended for add-on therapy to inhaled corticosteroids (ICS)-long-acting beta 2 agonists (LABA) for severe asthma. However, real-world studies on the predictors of response to tiotropium are limited. We investigated the real-world use of tiotropium in asthmatic adult patients in Korea and we identified predictors of positive response to tiotropium add-on. Methods: We performed a multicenter, retrospective, cohort study using data from the Cohort for Reality and Evolution of Adult Asthma in Korea (COREA). We enrolled asthmatic participants who took ICS-LABA with at least 2 consecutive lung function tests at 3-month intervals. We compared tiotropium users and non-users, as well as tiotropium responders and non-responders to predict positive responses to tiotropium, defined as 1) increase in forced expiratory volume in 1 s (FEV1) ≥ 10% or 100 mL; and 2) increase in asthma control test (ACT) score ≥3 after 3 months of treatment. Results: The study included 413 tiotropium users and 1756 tiotropium non-users. Tiotropium users had low baseline lung function and high exacerbation rate, suggesting more severe asthma. Clinical predictors for positive response to tiotropium add-on were 1) positive bronchodilator response (BDR) [odds ratio (OR) = 6.8, 95% confidence interval (CI): 1.6–47.4, P = 0.021] for FEV1 responders; 2) doctor-diagnosed asthma-chronic obstructive pulmonary disease overlap (ACO) [OR = 12.6, 95% CI: 1.8–161.5, P = 0.024], and 3) initial ACT score