Journal of Asthma最新文献

Objective: The present study aims to evaluate the prevalence and risk factors of asthma in children through a meta-analysis.

Data sources: The PubMed, Embase, Cochrane, and Web of Science databases were comprehensively retrieved for studies on the prevalence and risk factors of childhood asthma (CA) published between January 1, 2015, and July 8, 2024. Studies were screened and selected based on predefined eligibility criteria, and pertinent data were extracted. The quality of eligible studies was evaluated through the Newcastle-Ottawa Scale (NOS). Statistical analyses were undertaken via Stata 16 and R 4.4.1.

Study selection: 45 studies comprising 647,414 participants were included.

Results: The pooled prevalence of CA was 11.9% (95% CI: 8.8-15.8%). The meta-analysis identified several risk factors for CA, including prenatal exposure to per- and polyfluoroalkyl substances (PFAS) (OR = 0.89, 95% CI: 0.80-0.98, P = 0.021), prenatal exposure to acid-suppressive medications (OR = 1.11, 95% CI: 1.04-1.19, P = 0.002), maternal folic acid supplementation during pregnancy (OR = 1.18, 95% CI: 1.10-1.27, p < 0.001), as well as Helicobacter pylori infection in childhood (OR = 2.07, 95% CI: 1.35-3.15, p = 0.001).

Conclusions: The prevalence rate of asthma among children was approximately 11.9%. Prenatal exposure to PFAS and acid-suppressive medications, Helicobacter pylori infection in childhood were proved to be risk factors for asthma. Folic acid supplementation during pregnancy is positively associated with a reduced risk of asthma in children. Further large-scale prospective research is warranted to unveil the roles and significance of these factors.

Background: The Global Initiative for Asthma (GINA) recommended using spacers or valved holding chambers to counter the common problems of poor pressurized metered dose inhaler (pMDI) technique. However, many subjects avoid using conventional spacers because they are bulky and inconvenient to carry around in public.

Objective: We aimed to compare the novel, MDI PLUS^® spacer, with AeroChamber2go™ on their in vitro and in vivo aerosol performance, as well as their user training requirements.

Methods: In vitro, aerosol characteristics were assessed using an Andersen cascade impactor at 28.3 L/min with Ventolin^® pMDI (5 puffs, 100 µg/puff); HPLC quantified drug deposition on each stage. In vivo, 20 asthmatic subjects received 500 µg salbutamol via pMDI alone, and pMDI + AeroChamber2go™ or MDI PLUS^®. Urine samples were collected at 30 min and cumulatively over 24 h after inhaler use, and salbutamol samples were extracted and assessed using HPLC. Ex vivo delivery and user inhaler mastery were also assessed.

Results: The fine-particle dose increased from 94.98 µg (pMDI alone) to 128.45 µg with AeroChamber2go™ and 130.04 µg with MDI PLUS^®, while the fine-particle fraction rose from 26.58% to 65.72% and 67.19%, respectively (p < .05). Thirty-minute urinary salbutamol excretion nearly doubled with both the MDI PLUS^® and the AeroChamber2go, whereas systemic bioavailability over 24 h was significantly reduced from 143.35 µg with pMDI alone to approximately 60 µg with either device (p < .01). Notably, MDI PLUS required the fewest training sessions to master (1.03, p < .05).

Conclusions: Both the MDI PLUS^® and the AeroChamber2go™ significantly enhanced pulmonary delivery and reduced systemic exposure compared to pMDI alone, while MDI PLUS^® might potentially show a superior ease of use. These findings support the adoption of either device to optimize inhaler therapy.

Objective: To synthesize current understanding of type 1 (T1) and type 2 (T2) asthma endotypes and evaluate how their integration can advance precision biological therapy selection for improved patient outcomes.

Data sources: Comprehensive literature review of peer-reviewed articles from PubMed, Embase, and Cochrane databases focusing on asthma immunopathology, endotype characterization, biomarker development, and biological therapies. Additional sources included clinical trial registries, regulatory agency documents, and recent conference proceedings.

Study selection: Studies were selected based on relevance to T1/T2 inflammatory pathways, biomarker validation, biological therapy efficacy, and endotype-guided treatment strategies. Priority was given to randomized controlled trials, systematic reviews, and large observational studies with clear endotype characterization.

Results: T2 inflammation, characterized by interleukin-4 (IL-4), IL-5, and IL-13 pathways with eosinophilic involvement, has well-established biomarkers (blood eosinophils, fractional exhaled nitric oxide (FeNO), periostin) and successful targeted biologics (anti-IL-5, anti-IL-4 receptor alpha (anti-IL-4Rα), anti-immunoglobulin E (anti-IgE)). T1 inflammation, involving interferon-gamma (IFN-γ), tumor necrosis factor-alpha (TNF-α), and IL-17 with neutrophilic predominance, lacks validated biomarkers and effective therapeutics. Emerging evidence demonstrates significant T1/T2 overlap in severe asthma, challenging traditional dichotomous classification. Multi-pathway targeting strategies and upstream cytokine inhibition show promise for mixed endotypes.

Conclusion: Integration of T1 and T2 endotype characterization through validated biomarkers and multi-omics approaches is essential for advancing precision medicine in asthma. Future therapeutic strategies must address endotype plasticity and mixed inflammatory patterns to optimize biological therapy selection and improve treatment outcomes in heterogeneous asthma populations.

Background: Pediatric asthma (PA) is the prevailing chronic respiratory ailment in childhood. A better understanding of plasma metabolites is the goal for elucidating the molecular pathological mechanisms of PA and investigating novel therapeutic approaches.

Methods: Data for PA from Genome-Wide Association Studies (GWAS) was derived from the IEU-OpenGWAS project, featuring a collection of 1400 plasma metabolites. The inverse-variance weighting (IVW) method assessed causal relationships between plasma metabolites and PA, with measures taken to mitigate horizontal pleiotropy and heterogeneity. To select instrumental variables, a genome-wide significance threshold (p < 5 × 10-8) was applied to ensure robust genetic instruments. A Bonferroni correction controlled for multiple testing, with statistical significance defined as p < 3.57 × 10-5) (0.05/1400). To further substantiate outcomes, a reverse Mendelian randomization analysis was conducted.

Results: Research found 91 plasma metabolites linked to PA, ten of which showed significant associations. Of note, 20:4n6 levels (IVW: OR (95% CI) = 1.062 (1.030 to 1.094) and G/C16 (IVW: OR (95% CI) = 0.886 (0.832 to 0.943) were identified as pivotal exposure factors for PA.

Conclusions: This study highlights 10 plasma metabolites that may have significant associations with PA incidence, with 20:4n6 levels and G/C16 potentially serving as valuable biomarkers for the early detection and management of PA.

Objective: To assess the real-world impact of mepolizumab on healthcare resource utilization (HCRU) and work productivity and activity impairment (WPAI) in patients with severe asthma.

Methods: Asthma-related HCRU and WPAI were assessed over 2 years in the REALITI-A study-an international, prospective, observational cohort study in adults with severe asthma newly initiating mepolizumab (100 mg subcutaneous). Secondary endpoints of the study compared the proportion of patients with HCRU use, HCRU events, and WPAI component scores 12 months before mepolizumab initiation with 24 months follow-up. The relative rates of HCRU outcomes were calculated, with a treatment policy estimand for discontinuation.

Results: Patients (N = 822) had a mean age of 54 years and 63% were female. Hospitalization rates were reduced by 53% in the 0-12-month follow-up period (p < 0.001) and sustained for 24 months. The rates of asthma-related hospitalizations, emergency department visits, and outpatient visits reduced by 59-64% (p < 0.001) across the 24-month follow-up. The mean number of overnight hospital stays reduced from 2.4 in the pre-treatment period to 1.0 and 0.5 in the 0-12-month and 12-24-month follow-up periods, respectively. The WPAI Asthma activity impairment score was reduced from baseline by 47% and 55% at 12 and 24 months of follow-up. Overall work impairment was reduced by 62% and 74%.

Conclusions: Mepolizumab treatment reduced HCRU while improving activity and productivity in patients with severe asthma over 2 years. These data provide further evidence of real-world benefits of mepolizumab and may help inform healthcare system resource allocation.

Objective: To describe the clinical outcomes of patients with severe uncontrolled asthma who received dual biologic therapy after showing only partial improvement with a single biologic agent.

Methods: We conducted a descriptive case series of four patients with severe asthma who remained inadequately controlled on biologic monotherapy. A second biologic targeting a different inflammatory pathway was added based on persistent symptoms and biomarker profiles. Clinical outcomes including Asthma Control Test (ACT) scores, asthma exacerbation frequency, oral corticosteroid (OCS) use, and lung function (FEV₁) were evaluated over 12 months of follow-up.

Results: Following dual biologic therapy, all the patients showed significant improvement in Asthma Control Test (ACT) scores, reduction in exacerbations (from a median of 9 to 0.5/year), and reduced oral corticosteroid (OCS) usage (median 9 to 0.5/year). FEV1 remained stable or improved. No significant adverse effects were noted during 12 months of follow-up.

Conclusion: This series highlights that dual biologic therapy is effective and safe in a carefully selected difficult subgroup of severe uncontrolled asthma.

Objective: This study aimed to confirm the efficacy and safety of the inhaled fixed-dose combination of beclomethasone dipropionate (BDP) plus formoterol fumarate (FF) vs. BDP in patients with asthma.

Methods: After a two-week run-in period with asthma maintenance therapy switched to BDP via pressurized metered-dose inhaler (pMDI), eligible patients were randomized to BDP/FF or BDP, both via pMDI, for 12 wk. The primary objective was to demonstrate superiority of BDP/FF over BDP for change from baseline at Week 12 in area under the curve between 0 and 12 h post-dose (AUC_0-12h) of forced expiratory volume in 1 sec (FEV₁). The key secondary objective was to demonstrate superiority of BDP/FF over BDP for change from baseline at Week 12 in peak FEV₁ within the first 3 h post-dose. Safety and tolerability were assessed as secondary endpoints.

Results: Of 576 patients randomized to treatment, 543 completed the study (BDP/FF: 276/287 [96.2%]; BDP: 267/289 [92.4%]). The primary and the key secondary objectives were met, with BDP/FF vs. BDP adjusted mean differences of 104 (95% confidence interval 61, 148) mL and 124 (76, 173) mL for FEV₁ AUC_0-12h and peak FEV₁ at Week 12, respectively (p < 0.001 for both). A similar proportion of patients experienced adverse events in the two treatment groups (26.9% vs. 26.4%), with most events mild or moderate in severity and not considered related to study drug.

Conclusions: The study met its aims, demonstrating the contribution of FF to BDP in lung function improvement, with both treatments being well tolerated.

ClinicalTrials.gov NCT05292586.

Background: Asthma is a multifactorial disease affecting approximately 300 million people worldwide. Multiple genes, environmental risk factors, and their interactions have been associated with asthma. Smoking triggers an IL-17-mediated inflammatory response. The IL-17-related inflammatory response may differ between individuals, and this difference is associated with IL-17 polymorphisms.

Objective: Our aim was to investigate the effect of IL-17 polymorphism and its interaction with secondhand smoke on pediatric asthma.

Methods: The study comprised 100 pediatric asthma patients and 100 healthy children. Cotinine levels were analyzed to show SHS exposure (SHSe). A genetic study was conducted to reveal IL-17F(rs763780) and IL-17A (rs8193036, rs2275913) polymorphisms. The study participants were categorized into four groups based on the cotinine results: asthma with SHSe, asthma without SHSe, control with SHSe, and control without SHSe.

Results: The median cotinine concentration was 11.06 ng/ml. Children with asthma had lower cotinine levels than healthy children (p < 0.001). Genotype distributions and allele frequencies of rs763780, rs8193036, and rs2275913 were compared among the four groups, and no significant differences were found.

Conclusion: This study is the first to demonstrate the relationship between IL-17 polymorphisms and SHS interaction in childhood asthma. Neither the presence of IL-17 polymorphisms nor the interaction of these polymorphisms with SHS was found to be associated. The lower cotinine levels in asthmatic children suggest that parents are more susceptible to SHSe. Cotinine levels in our cohort were significantly greater than those found in developed countries. This demonstrates that exposure to SHS is still a serious environmental issue in our country.