Journal of Asthma and Allergy最新文献

Background: Multiple biologics are now available for severe asthma, creating opportunities to switch between therapies.

Purpose: To identify characteristics of patients with asthma who switch biologics.

Methods: We examined biologic switching in 1611 patients with moderate-to-severe asthma on maintenance therapy who initiated a biologic between 2014 and 2023 within a large health system and had no alternate indication. Chart reviews were performed to determine reasons for switching. We compared the characteristics of patients who: 1) did not switch therapy versus switched due to suboptimal response, and 2) switched once versus switched multiple times using descriptive statistics. Exacerbation incidence rates were assessed using Poisson regression. Inverse-probability-weighted-logistic regression accounting for demographic and clinical variables was conducted to evaluate factors associated with switching.

Results: Fourteen percent (230/1611) switched: 81% once, 19% ≥2 times. Suboptimal response accounted for >70% of switches. Higher pre-initiation exacerbation rates were associated with a stepwise increase in likelihood of switching (1.4 in non-switchers vs 2.3 in patients who switched twice; 2.8 switched twice; and 3.4 in patients switching ≥3 times). Patients using ≥3 biologics had more baseline exacerbations (2.9 vs 2.3 in one-time switchers, p=0.01) and higher maximum blood eosinophil counts (BEC) in the year prior to treatment (662 vs 334 cells/µL, p=0.02), though median baseline BEC did not differ (229 vs 244 cells/µL, p=0.60). In weighted analyses, exacerbations (odds ratio, OR: 1.03; 95% Confidence Intervals, CI: 1.01-1.04, p<0.001) and baseline BEC (OR, 2.0 for each 50 cells/mcl increase; 95% CI: 1.2-3.4, p=0.002) were significantly different between switchers and non-switchers. However, only higher baseline exacerbations differentiated those who switched once to those who switched two or more times (1.02, 1.00-1.05, p=0.04). Exacerbations declined significantly in non-switchers during the first treatment year (1.42 to 0.99, p<0.001) but not among switchers.

Conclusion: Patients with more severe asthma and higher maximum eosinophil counts at biologic initiation were more likely to switch therapies, predominantly due to suboptimal response. These findings emphasize the importance of selecting the first biologic carefully and optimizing timing of initiation.

Purpose: Dupilumab's recent approval in China as an add-on therapy for asthma provides a novel therapeutic alternative for severe asthma management, but its economic benefits remain unsubstantiated in China. This study aimed to adopt a cost-utility analysis to evaluate the economics of dupilumab in the treatment of uncontrolled severe asthma and provide an evidence-based reference for clinical decision-making and therapeutic regimen selection.

Methods: From the healthcare perspective, a Markov model was developed to simulate costs and quality-adjusted life years (QALYs) over a five-year time horizon for uncontrolled severe asthma patients aged ≥12 years receiving either dupilumab add-on therapy or standard-of-care (SoC) therapy alone. The incremental cost-utility ratio (ICUR) served as the primary outcome and was compared with the willingness-to-pay (WTP) threshold based on per capita gross domestic product (GDP) of China ($13,444.68/QALY) to determine the economics of therapeutic alternatives. The robustness of the results was verified using sensitivity analysis, and the impact of the dupilumab price on outcomes was evaluated using scenario analysis.

Results: Compared with SoC therapy, dupilumab add-on therapy incurred higher costs but provided greater utility gains, with an ICUR of $83,941.87 per QALY gained, which exceeded the WTP threshold. One-way sensitivity analysis identified the utility of controlled asthma as the predominant influential factor, followed by the price of dupilumab. Probabilistic sensitivity analysis showed that 98.8% of simulations were consistent with the base-case results, and SoC therapy had a higher probability of cost-utility acceptability than dupilumab add-on therapy. Scenario analysis revealed that reducing dupilumab's price to $70.38 would render its ICUR below the WTP threshold.

Conclusion: Based on the current Chinese healthcare system, it was not cost-utility to apply dupilumab as an add-on therapy for patients aged ≥12 years with uncontrolled severe asthma. A substantial price reduction of dupilumab could improve affordability in this patient population.

Objective: The impairment of smell has become a crucial evaluation in determining disease severity, control status, and therapeutic response in patients with chronic rhinosinusitis and nasal polyps (CRSwNP). This study aimed to evaluate the minimal clinically important difference (MCID) of the Taiwan Smell Identification Test (TWSIT) in patients with CRSwNP undergoing endoscopic sinus surgery (ESS).

Methods: Patients with bilateral CRSwNP who underwent ESS were prospectively enrolled. The 22-item Sino-Nasal Outcome Test questionnaire and TWSIT were utilized to evaluate both subjective and objective olfactory function before surgery and 3 months postoperatively.

Results: Eighty-six patients with bilateral CRSwNP (53 males, 33 females) were enrolled. Moderate-to-high correlations were observed between the subjective smell loss scores and baseline TWSIT scores (r_s = 0.709 before treatment and r_s = 0.413 after treatment, both P < 0.001). The change in patient-reported smell loss was also significantly correlated with the change in TWSIT score (r_s = 0.675, P < 0.001). A TWSIT change of 6.5 points yielded a sensitivity of 71.6%, specificity of 91.7%, and an AUC of 0.789 (P < 0.001). Using the distribution-based method, the MCID was estimated as 7.4 (half the baseline standard deviation, SD) and 6.9 (half the delta SD). Based on both distribution- and anchor-based analyses, a TWSIT change of ≥ 7 points was determined to be the MCID.

Conclusion: This study established that a TWSIT score change ≥ 7 is clinically meaningful for patients with CRSwNP following sinus surgery. Bridging objective test results with subjective perceptions can help clinicians identify patients with suboptimal therapeutic outcomes and guide decisions regarding additional treatments.

Background: Moderate-to-severe allergic asthma caused by dust mite sensitization is challenging to treat. Allergen-specific immunotherapy (AIT) is the only disease-modifying option but is limited by delayed effects, allergic side reactions, and poor adherence. Omalizumab, an anti-IgE antibody, may improve AIT's safety and effectiveness.

Objective: To assess whether combining omalizumab with AIT is more effective and safer than AIT alone in patients with dust mite-induced moderate-to-severe asthma.

Methods: This prospective study involved 37 patients divided into two groups: AIT alone (n=18) and omalizumab + AIT (n=19). Over 48 weeks, asthma control (ACT, ACQ), lung function (FEV₁%, PEF%, FEV₁/FVC), and airway inflammation (FeNO) were measured. Secondary outcomes included IgE levels, eosinophil counts, quality of life (AQLQ), and safety.

Results: Both groups improved, but the combination group showed significantly better asthma control, lung function, and quality of life at week 48. Only the combination group had significant reductions in FeNO and eosinophils, suggesting stronger anti-inflammatory effects. IgE levels followed expected trends with no major group differences. Fewer adverse reactions occurred in the combination group; severe systemic events were reported only in the AIT-alone group.

Conclusion: Adding omalizumab to AIT significantly enhances asthma control, lung function, and inflammation reduction while improving treatment safety. This supports its role as an effective adjunct in managing moderate-to-severe dust mite-allergic asthma in Chinese patients.

Background: An increase of ≥ 12% in forced expiratory volume in the first second (FEV₁) after inhalation of bronchodilator indicates airway reversibility. However, it is difficult to measure FEV₁ in children. The aim of the study is to determine whether respiratory muscle electromyograms recorded from chest wall surface electrodes can be used to distinguish children with uncontrolled asthma from healthy subjects.

Methods: Fourteen children with uncontrolled asthma [aged 6.1 (3 ~ 13) years] and 28 healthy children [aged 7.6 (3 ~ 13) years] were recruited. Uncontrolled asthma was defined as having poorly controlled symptoms, along with an increase in FEV₁ of at least 12%, or presenting with a wheezing symptom that improved after inhaling a bronchodilator. Diaphragm electromyogram (EMG_di), parasternal intercostal EMG (EMG_para), airflow, FEV₁, and wheezing were recorded before and after inhalation of bronchodilator.

Results: Good-quality EMG_di and EMG_para could be recorded in all subjects. However, 18 of 42 children could not perform the spirometer properly. Changes in EMG_di [-24.6% (-43.5 ~ -12.4%) vs -0.1% (-13.2 ~ 16.9%), p<0.001] and EMG_para [-11.2% (-31.5 ~ 32.4%) vs -0.5% (-24.9 ~ 13.0%), p<0.05] in children with asthma were, respectively, significantly larger than those in healthy subjects during bronchodilator response. The area under the receiver operating characteristic curves for the changes of EMG_di and EMG_para were 0.995 (95% CI 0.906 to 1.000) and 0.755 (95% CI 0.598 to 0.874).

Conclusion: Surface respiratory muscle EMG could be feasible and useful to assess bronchodilator response to differentiate children with uncontrolled asthma from healthy subjects.

Objective: Allergen immunotherapy (AIT) is an established treatment for mild to moderate allergic asthma. However, limited data are available regarding its safety and efficacy in patients with severe asthma. This study aimed to gather real-world evidence (RWE) on the safety and effectiveness of AIT in individuals with severe asthma caused by sensitization to at least 1 allergen, who were either currently undergoing AIT or had received it within the past five years.

Methods: A retrospective study was conducted in Spain, including patients aged ≥6 years with severe asthma (Spanish Guideline for Asthma Management [GEMA] steps 5-6 and Global Initiative for Asthma [GINA] step 5) sensitized to at least 1 allergen who had received AIT within the previous 5 years, to evaluate safety and effectiveness.

Results: The study included 93 patients (54.8% female) with a median age of 40.3 years, including 5 under 14. A total of 16 systemic reactions (SRs) were reported in 8 patients (8.6%), mostly immediate (13/16) and occurring during the initiation phase (12/16), all in patients receiving subcutaneous immunotherapy. Most SRs were mild to moderate, except for 2 severe reactions in 1 patient. Only 3 patients discontinued treatment. Significant improvements in both FeNO and FEV₁ (%) were observed after 6 and 12 months of AIT, respectively. Quality of Life (through mini-AQLQ) scores improved at 1, 2 and 3 years after initiation of AIT compared to baseline. The number of patients who did not require rescue medication for asthma was significantly higher after starting AIT than before treatment. AIT was also associated with a 75.8% reduction in the number of emergency visits.

Conclusion: This study confirms the safety and effectiveness of AIT in patients with well-controlled severe asthma in routine clinical practice. Additional prospective real-world studies are needed to better understand the efficacy of AIT in severe asthma.

Purpose: Pediatric allergic conjunctivitis (PAC) is a prevalent inflammatory eye condition caused by hypersensitivity to allergens. This study performs a scientometric assessment to uncover global research patterns, collaboration networks, and thematic evolution in PAC literature.

Methods: Publications related to PAC from 1963 to 2025 were retrieved from the Web of Science Core Collection database. Data were analyzed and visualized using VOSviewer (version 1.6.20), CiteSpace (version 6.3.R1), and the "bibliometrix" package in R (version 4.3.3).

Results: A total of 378 documents were analyzed, revealing a significant increase in publications over the years, especially after 2010. China led with 99 publications, followed by the USA and Japan. Notable international collaboration was observed, particularly between China and Germany. China Medical University Taiwan, Sun Yat Sen University, and China Medical University Hospital Taiwan were identified as the leading institutions. The journal Pediatric Allergy and Immunology was the most prolific, followed by Allergy. The most cited authors included Wei CC and Lin CL, with key research themes encompassing asthma, rhinitis, and pediatric allergic diseases. Keyword analysis indicated a growing interest in environmental factors such as air pollution and the comorbidity of PAC with other allergic conditions.

Conclusion: This bibliometric analysis offer valuable insights for future research directions and clinical strategies aimed at enhancing PAC diagnosis and treatment. Future research should evaluate the long-term efficacy of immunotherapy and investigate environmental determinants in PAC pathogenesis. Special emphasis is needed on multicenter studies incorporating regional diversity and standardized methodologies. Diverse regional data was incorporated to enhance global applicability and reduce public health burdens.

Background: Tissue remodeling is a key feature of allergic rhinitis (AR), but its underlying molecular mechanisms remain unclear. Lysyl oxidase-like 2 (LOXL2), a regulator of tissue remodeling, has not been studied in AR.

Methods: Proteomic analysis was performed on nasal mucosal tissues from 8 AR patients and 8 healthy controls (HCs) to identify differentially expressed proteins (DEPs). The top three upregulated DEPs and their association with tissue remodeling markers were validated by immunofluorescence, Western blot, and RT-qPCR in an independent cohort of 30 AR patients and 30 HCs. In vitro, human nasal epithelial cells (HNECs) were treated with IL-4, and the effects of candidate protein inhibitors on remodeling were assessed. An AR mouse model was used to evaluate the impact of these inhibitors on nasal inflammation and remodeling.

Results: Proteomic analysis revealed a disease-specific protein expression profile in the nasal mucosa of AR patients, with the top three upregulated proteins being LOXL2, TGF-β1, and TIRAP. Tissue validation showed that LOXL2 was significantly upregulated in the nasal mucosa of AR patients compared to HCs and was significantly correlated with EMT markers (TGF-β1, α-SMA, and E-cadherin). In vitro, IL-4 stimulation significantly upregulated LOXL2, TGF-β1, and α-SMA, while downregulating E-cadherin in a dose-dependent manner in human nasal epithelial cells. These effects were reversed by inhibition of LOXL2. Further investigations demonstrated that LOXL2 promotes tissue remodeling through activation of the TGF-β1/Smad signaling pathway. In the AR mouse model, LOXL2 inhibitors significantly reduced nasal mucosal inflammation and tissue remodeling.

Conclusion: Our proteomic analysis suggests that LOXL2 may be involved in the pathological remodeling processes of AR, potentially through modulation of the TGF-β1/Smad signaling pathway. These findings provide preliminary evidence that LOXL2 could serve as a candidate biomarker and a possible therapeutic target in AR, warranting further investigation.

Purpose: To investigate the morphological characteristics of the meibomian glands (MGs) in children with allergic conjunctivitis (AC)-related dry eye (DE).

Methods: Children with a clinical diagnosis of seasonal allergic conjunctivitis (SAC) and perennial allergic conjunctivitis (PAC) were recruited. Age- and sex-matched children without a history of allergy or dry eye were recruited as controls. All participants completed the 5-item Dry Eye Questionnaire (DEQ-5) and ocular surface examination, including assessment of the tear meniscus height (TMH), noninvasive tear breakup time (NIBUT), and morphology of the upper lower MGs by noncontact infrared meibography (Oculus Keratograph 5M). Receiver operating characteristic (ROC) curve analysis was performed to determine the predictive value of the morphological characteristics of the MGs for AC-related DE.

Results: Sixty-two children with AC (31 with DE and 31 without DE) and 33 healthy children were enrolled in the study. The mean age was 7.67 (ranging from 5-13.5) years. More morphological changes were observed in the upper eyelids of AC children with DE than in healthy children. No morphological feature difference was found between AC children without DE and healthy children. ROC curve analysis showed that the morphological characteristics with good predictive value for DE were shortened upper eyelid MGs (AUC=0.72, P<0.001) and hooked upper eyelid MGs (AUC=0.71, P<0.001).

Conclusion: The grading of MG morphology according to the DREAM Study may be a valuable predictor for AC-related DE in children.

Objective: Magnetic particle chemiluminescence is a novel allergen detection technology recently introduced in clinical practice in China. This study analyzed the application of the ALLEOS assay using real-world clinical data from Guangzhou to identify regional allergen sensitization patterns.

Methods: A retrospective review of 20,406 suspected allergy patients, tested for 28 specific allergens using the ALLEOS 2000 system at the First Affiliated Hospital of Guangzhou Medical University from June 2021 to January 2024.

Results: The highest positive rate was observed for Dermatophagoides farinae (53.4%), followed by D. pteronyssinus (43.2%) and tropical mites (20.4%). Children showed significantly higher positivity rates for most allergens compared to adults, except for dog dander and German cockroach (P < 0.05). Among allergic diseases, children predominated in rhinitis (84.9%), while adults predominated in asthma (56.5%). In terms of severity, asthma and rhinitis patients exhibited higher sensitization levels (Class 3-6) to D. pteronyssinus (81.6% and 86.3%) and D. farinae (86.7% and 87.3%), while dermatitis patients were more sensitized to egg (19.7%) and milk (17.9%) allergens. Allergen positivity rates varied by season, with children showing significantly higher sensitization to both daisy and dandelion in autumn (11.1% and 8.8%) and winter (11.8% and 16.7%). In childhood (ages 0-4), egg (31.4%) and milk (27.1%) sensitization rates peaked and declined with age, whereas animal dander showed lower rates (<10.0%). Multiple sensitizations were observed in 22.2% of patients. Analysis of sensitization patterns revealed three main categories for inhalation allergens: mite-dominant, animal dander-dominant, and pollen-dominant sensitizations, with a Cronbach's α of 0.889. Similarly, food allergies were categorized into egg and milk-dominant, nut-dominant, and seafood-dominant patterns, with a Cronbach's α of 0.932.

Conclusion: This real-world study revealed age-, disease-, and season-specific allergen sensitization patterns in southern China. Inhalant and food allergens formed three major sensitization clusters each. These findings support region- and population-specific testing strategies and may inform clinical decision-making.