Journal of Asthma and Allergy最新文献

Background: The prevalence of hypersensitivity reactions to different allergens varies according to the population studied and is subject to environmental and lifestyle factors. Early and delayed hypersensitivity are diagnosed with skin prick test and patch test.

Objective: This study aimed to identify the common environmental and chemical allergens sensitizing Yemeni allergic patients.

Subjects and methods: A retrospective study was conducted using registries of patients who attended Elaj Medical Center in Sana'a city, Yemen, from January 1^st to December 31^st 2023. The collected data included sex, age, and the clinical laboratory test results of the skin prick test and the patch test.

Results: The skin prick test was performed on sixty-five patients compared to twenty-two who were tested with a patch test. Most of the positive participants were male, aged between 18 and 40 years. The most frequent environmental allergens causing immediate hypersensitivity were Dermatophagoides farinae and Dermatophagoides pteronyssinus mites (64.6% and 69.2%, respectively), Aspergillus (47.7%), cat dander and dog dander (43.1% and 35.4%, respectively). Dermatophagoides farinae mites mostly sensitized females with an odds ratio of 3.43 (95% CI, 1.13-10.42, p=0.05). The most common chemical allergens that caused delayed hypersensitization were paraphenylenediamine (45.5%), potassium bichromate (45.5%), cobalt sulfate (36.4%), thiuram mix (27.3%), Vaseline (27.3%), and nickel sulfate (27.3%). Polysensitization was more frequent. The age of patients was directly proportional to the number of allergens responsible for immediate hypersensitivity (r-0.298, p=0.016).

Conclusion: Yemeni patients exhibited high sensitization to aeroallergens and chemical allergens. Females showed a higher propensity for polysensitization. The pattern of sensitization to environmental and chemical allergens in Yemen differs somewhat from neighboring Arab and Asian countries. Further multi-center studies are needed to support and establish a standard country-specific allergens panel for testing.

Purpose: Asthma is a heterogeneous disease with phenotypic variations potentially influenced by dietary factors. This cross-sectional study aimed to estimate the prevalence of current allergic asthma (AA), characterize its phenotypic variants, and examine dietary associations with asthma manifestations among young Chinese adults in Singapore.

Patients and methods: We assessed 10,544 young Chinese participants (mean age 22.3 ± 5.5 years; male: female = 0.74) using a standardized, investigator-administered questionnaire adapted from the International Study of Asthma and Allergies in Childhood. Current AA was defined as a history of doctor diagnosis with symptoms in the past 12 months and having allergic sensitization to common house dust mites. Dietary intake across 16 food groups was assessed using a semi-quantitative food frequency questionnaire. Multivariable logistic regression, adjusted for sociodemographic and lifestyle factors, examined dietary associations with AA outcomes.

Results: The prevalence of current AA was 5.24%. Among those with current AA, 67.0% (370/552) had mild, 21.7% (120/552) moderate, and 11.2% (62/552) severe asthma. Asthma was well-controlled in 60.7% (319/552), partly controlled in 39.3% (217/552), and poorly controlled in 2.9% (16/552). Common phenotypes included cough-variant (57.6%), wheezy variant (55.1%), and exercise-induced asthma (31.5%), with overlapping symptoms. Frequent intake (most or all days) of pulses (Adjusted odds ratio [AOR]: 0.65; 95% confidence intervals [CI]: 0.47-0.89; p < 0.001), probiotic drinks (AOR: 0.69; 95% CI: 0.50-0.94; p < 0.001), fruits (AOR: 0.47; 95% CI: 0.31-0.71; p = 0.001), and vegetables (AOR: 0.58; 95% CI: 0.35-0.99; p = 0.003) was associated with protective odds of current AA. Pulses were also associated with reduced odds of exacerbated and wheezy AA, while occasional (once or twice per week) intake of probiotic drinks was associated with reduced odds of cough-variant and wheezy AA.

Conclusion: While certain plant-based foods and probiotic drinks were associated with reduced odds of AA and its phenotypes, these findings should be interpreted with caution given the cross-sectional design. Longitudinal or interventional studies are needed to clarify causality and underlying mechanisms.

Background: Pediatric atopic dermatitis (AD), a common chronic relapsing inflammatory skin disorder, often co-occurs with iron deficiency. However, the causal relationship and mechanisms linking iron homeostasis to AD pathogenesis remain unclear. This study investigates etiopathogenetic role of iron deficiency in childhood AD by analyzing molecular pathways and clinical impacts on disease progression.

Methods: We have enrolled 298 pediatric AD patients based on the Hanifin and Rajka criteria to evaluate the relationship between peripheral iron and the severity of AD, as well as the levels of serum iron, ferritin, and transferrin in children with AD. The percentages of Th2 cells and IL-10-producing CD24⁺CD38⁺CD19⁺ regulatory B (Breg) cells were quantified by flow cytometry. RNA-sequencing and bioinformatic analysis were performed to explore the iron deficiency-sensitive genes in CD19⁺ B cells treated with Ciclopiroxolamine (CPX). The differentially expressed genes, including T cell immunoreceptor with immunoglobulin and tyrosine-based inhibitory motif (ITIM) domain (TIGIT) and IL10, were further confirmed by RT-qPCR. 5-mC level was determined to evaluate the effect of iron deficiency on DNA methylation. TIGIT was inhibited in CD19⁺ B cells using a blocking antibody to assess its regulatory role in Breg cells.

Results: Children with severe AD have lower levels of iron ions in peripheral blood compared with the mild patients (P<0.0001). Children with AD exhibited decreased serum levels of iron (P<0.01), ferritin (P< 0.01), and transferrin (P<0.05), along with an elevated percentage of Th2 cells (P<0.01) and reduced CD24⁺CD38⁺CD19⁺ Breg cells (P<0.01). CPX-mediated iron chelation suppressed IL-10-producing Breg cells (P<0.01) by inducing DNA methylation (P<0.05) and downregulating TIGIT (P<0.001), while promoting the expansion of IL-4-producing Th2 cells (P<0.05).

Conclusion: Iron deficiency contributes to Th2 cell expansion in pediatric AD via DNA methylation and TIGIT suppression in IL-10-producing Breg cells.

Background: Hereditary angioedema (HAE) is typically autosomal dominant, though recessive cases exist. It is characterized by recurrent episodes of swelling affecting the subcutaneous tissues, oropharyngeal mucosa, and gastrointestinal tract. This report describes a misdiagnosed case with a novel "SERPING1" variant.

Case presentation: A 22-year-old Chinese male presented with recurrent acute abdominal pain since March 2018, initially misdiagnosed as gastroenteritis or intestinal obstruction at multiple hospitals. During current hospitalization, detailed history revealed non-pitting eyelid edema in July 2019 that progressed to facial edema within 24 hours after a cold. Over the subsequent three years, he experienced recurrent subcutaneous edema involving face and extremities, typically resolving spontaneously within one week. Family history showed his father had similar self-limiting episodes of abdominal pain and edema between ages 20-30, with no recurrence after age 40. Physical examination demonstrated upper abdominal tenderness without rebound pain. Low C4 levels prompted C1INH testing and genetic analysis, confirming HAE due to C1INH deficiency type 1 (HAE-C1INH-Type1) with a novel SERPING1 variant. Since initiating lanadelumab (300mg biweekly) on April 26, 2023, the patient has completed 11 injections and remains in good condition.

Conclusion: HAE is a rare disease that is often misdiagnosed. Complement C4 remains a critical screening biomarker for patients with HAE. In addition, we reported a novel frameshift variant in the coding region of the SERPING1 gene, and the specificity of the position offers a unique point of interest in the discussion of the disease's causative locus.

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.