This study was performed to evaluate the effects of dupilumab on sleep disturbance in adults with uncontrolled moderateto-severe asthma in the phase 4 MORPHEO study (NCT04502862). The study population comprised adults (18-65 years) with uncontrolled (Asthma Control Questionnaire [ACQ] 5 score ≥2.5), type 2 (baseline eosinophils ≥150/μL and fractional exhaled nitric oxide [FeNO] ≥25 ppb), moderate-to-severe-asthma, and frequent nocturnal awakenings (≥1/night average). Patients were randomized 1:1 to receive dupilumab 200 mg or placebo every 2 weeks for 12 weeks. The primary endpoint was change from baseline to week 12 in the Asthma Sleep Disturbance Questionnaire (ASDQ) score. Other endpoints included changes from baseline in nocturnal awakenings, sleep quality, restorative sleep, wakefulness after sleep onset (WASO), prebronchodilator forced expiratory volume in 1 second (FEV1), ACQ-7 score, and FeNO. Of the 202 patients included, 185 (91.6%) completed the intervention. The primary endpoint was not met. Groups differed nonsignificantly at week 12 in terms of the improvement in the ASDQ score (least squares mean difference [standard error], -0.07 [0.107]; P=.512) and did not differ in terms of the decrease in the number of nocturnal awakenings (0.00 [0.110]; 95%CI, -0.21 to 0.22). Both arms improved in the secondary sleep-diary endpoints sleep quality (0.17 [0.211]; 95%CI, -0.24 to 0.59), restorative sleep (0.13 [0.212]; 95%CI, -0.29 to 0.54), and WASO (-4.10 [5.510]; 95%CI, -14.99 to 6.79) at week 12. Compared with placebo, dupilumab improved prebronchodilator FEV1, ACQ-7, and FeNO. The results were nominally statistically significant. Although most sleep outcomes improved comparably in the groups, dupilumab (vs placebo) improved asthma symptoms, lung function, and airway inflammation in adults with uncontrolled, type 2, moderate-to-severe asthma and frequent nocturnal awakenings.

Air pollution in high-poverty neighborhoods contributes to disparities in asthma morbidity. Housing mobility programs help families move to better-resourced neighborhoods and improve asthma outcomes. Whether housing mobility-related improvements in asthma morbidity are explained by reductions in air pollution is unknown. Evaluate change in concentrations of fine particulate matter and its components and associated changes in asthma morbidity among a cohort of children with asthma who moved out of high-poverty neighborhoods. Caregiver-reported asthma exacerbations, symptoms, and asthma control test scores were examined among 123 children (age 5-17) with persistent asthma participating in the Baltimore Regional Housing Partnership housing mobility program. Exposures considered are annual average concentrations of PM2.5 and major PM2.5 components (black carbon, organic carbon, ammonium, nitrate, and sulfate). Children moved to neighborhoods with 0.64 μg/m3 [95% CI: 0.50-0.82] lower PM2.5 concentrations, with greatest reductions in black carbon and organic carbon. One standard deviation higher exposure to PM2.5 was associated with a 60% [95% CI: 21%-112%] higher odds of exacerbations and 20% [14%-27%] higher odds of symptom days/2 weeks. Reductions in PM2.5 exposure explained 77% [39% - 100%] and 22% [16%-36%] of moving-related reductions in exacerbations and symptom days, respectively. Some PM components were also associated with asthma exacerbations and symptoms and showed mediating effects. Moving from high-poverty neighborhoods to better-resourced neighborhoods through a housing mobility program is associated with lower air pollution exposure, contributing to moving-related asthma improvements. Housing mobility may be a useful complement to pollution-focused environmental justice interventions.

Licochalcone A from Ma-Xing-Shi-Gan decoction to prevent Asthma through the inhibition of ferroptosis CD4+ T Cell by GART/HSP90α signaling pathway.

Asthma is more common among athletes than in the general population. The diagnosis can be difficult to detect as objective examinations such as resting spirometry often remain normal and are masked by the athletes' good cardio-pulmonary capacity, as well as overlapping with what is expected in a normal training response. Evaluation should include exercise testing and provocation in a real training environment. Training environments involving cold and dry air, as well as inhalation of chlorine compounds from pool water, can trigger asthmatic symptoms. Both over- and under-treatment occurs, which makes careful diagnosis and monitoring of prescribed treatment important. With proper treatment, athletes can train and compete on equal terms, and it is important to encourage physical activity among people with asthma.

Bronchoalveolar lavage holds potential therapeutic value for moderate-to-severe asthma that is poorly controlled with standard nebulizer therapy. To evaluate the efficacy and safety of bronchoalveolar lavage (BAL) as an adjunctive therapy in patients with moderate-to-severe allergic asthma inadequately controlled by standard inhaled corticosteroids and long-acting beta₂-agonists therapy. In this retrospective study conducted between July 2021 and December 2024, eligible patients were allocated to a control group receiving standard high-pressure nebulizer therapy or a study group receiving additional BAL. Outcomes included changes in asthma symptom scores, pulmonary function, fractional exhaled nitric oxide (FeNO) levels, adverse events, and bronchoalveolar lavage fluid pathogen distribution. The study group demonstrated significantly greater improvement in subjective symptom scores and small airway function parameters compared to controls (P < 0.05). This superiority was particularly pronounced in a predefined subgroup with more severe impairment (FEV1% pred < 50%, FVC% pred < 80%, FEV1/FVC < 65%). No significant differences were observed in FeNO levels or overall adverse event incidence (P > 0.05). BALF analysis in 72 study patients identified 43 distinct pathogens (detection rate: 39.8%), predominantly bacterial species (72.1%). Adjunctive BAL significantly improved lung function, especially in small airways, without increasing adverse reactions, demonstrating a favorable safety profile in patients with uncontrolled allergic asthma, supports BAL's potential as a therapeutic procedure.

Lower-income countries have lower asthma prevalence. However, how differences in human development and inequality can explain changes in the prevalence of asthma and allergic diseases is not known. The Global Asthma Network Phase I study reported prevalence of asthma and allergic diseases in children (6-7 years), adolescents (13-14 years), and their parents/guardians in 16, 25 and 17 countries. Gini inequality index (GinI) and human development index (HDI), together with mean annual relative humidity and temperature, and latitude, were used as potential explanatory factors of prevalence differences using meta-regression models, fitted values and heatmaps of prevalence. GinI and HDI explained some proportion of asthma prevalence variability, which was highest in children (up to ~70% for disease indicators such as current wheeze or symptoms of severe asthma) and lowest in adolescents (~22% for symptoms of severe asthma or asthma ever). Rhinoconjunctivitis prevalence variability was poorly explained by covariates (from ~53% for current rhinoconjunctivitis among children-an exception-to none). Eczema indicators were explained in a range from ~60% in children (current eczema symptoms and symptoms of severe eczema) to ~12% in adolescents (current eczema symptoms). Overall, heatmaps showed areas of higher prevalence in the intersection of high GinI and high HDI values. HDI and Gini explain part of the worldwide variability in the prevalence of asthma, rhinoconjunctivitis, and eczema. This explanatory power is highest for asthma and lowest for rhinoconjunctivitis. Lower-resourced communities in highly developed countries show the greatest hazard, particularly for asthma.

One of the optimal asthma management goals is to improve patients' quality of life. Limited Saudi studies assessed quality of life (QoL) among vulnerable groups like schoolchildren. This study conducted quantitative and qualitative approaches to examine asthma-related QoL in Saudi adolescent students. A mixed-approach study was conducted among guardians of Saudi schoolchildren with confirmed asthma disease during May and November 2025. Based on in-depth asthma QoL interviews, a qualitative approach was completed, and quantitative methods were applied for comprehensiveness. Both approaches were influenced by the reliable and verified Arabic PedsQL Asthma Module. MAXQDA was used to assess guardians' comprehensive responses, and the PedsQL Asthma Module scale was used to categorize and analyze the conclusion responses.Qualitative and quantitative analyses include 46 interviews. As some feelings of anxiety and worry among children were shown to be linked with asthmatic symptoms and complications, it appears that this nervousness impacts guardians and might affect their QoL. Some found asthma to be challenging to manage, leading to anxiety and fear of complications. The quantitative approach revealed a substantial effect size of high asthma QoL compared to moderate to poor QoL (Hedges' g = - 0.690, p 0.001). Conclusion: This study shows that Saudi asthmatic adolescents have moderate QoL, but clinical and school-based care gaps exist. QoL is driven by asthma symptoms and management, which may create worry in children and parents. Furthermore, environmental differences in Saudi Arabia may affect asthmatic students'respiratory health. These issues should be addressed to improve asthmatic adolescents'QoL.

Early childhood asthma and adenotonsillectomy: From upper airway microbiota to type 2 biomarkers and clinical outcomes.

Clinician and Family Perspectives on the Use of Single Maintenance and Reliever Therapy for Children.

IntroductionAsthma is one of the most prevalent long-term health conditions affecting pregnant women. Poorly controlled asthma during pregnancy is associated with adverse maternal and fetal outcomes and may predispose offspring to long-term respiratory morbidity. The current ‘one size fits all’ approach to asthma management during pregnancy is not optimally effective for approximately half of the pregnant women with asthma. A personalised medicine approach to managing airways disease is required. The treatable traits approach focuses on the identification and treatment of traits in the pulmonary, extra-pulmonary and behavioural domains, which are identifiable, measurable, clinically relevant (linked to exacerbation risk or poor asthma control) and treatable. This manuscript outlines the protocol for the Treatable Traits for Asthma Management in Pregnancy (TTAP) study. The purpose of the TTAP study is to prospectively determine the prevalence of a range of treatable traits from these three domains in pregnant women with asthma and determine which traits are associated with exacerbation risk, poor asthma control and poor asthma-related quality of life. Additionally, this study will assess differences in trait prevalence and clinical relevance in pregnant women from regional versus metropolitan hospitals in Australia and in different antenatal models of care.Methods and analysisThe TTAP study is a multicentre, prospective observational cohort study. Study participants are pregnant women with asthma attending antenatal clinics at 10 metropolitan and regional hospitals (public and private) in NSW and Victoria, Australia. Assessment of traits from the pulmonary, extrapulmonary and behavioural domains as well as asthma outcomes is conducted at three gestational timepoints: 12–16 weeks, 22–26 weeks and 32–36 weeks of pregnancy. A follow-up assessment of asthma outcomes is conducted at 2–4 weeks postpartum. The outcomes assessed are asthma exacerbations requiring medical intervention (primary outcome), asthma symptom control and asthma-related quality of life. Traits and outcomes will be assessed using questionnaires, direct questioning, measurement of biomarkers, physical measurements and assessment of routinely collected data from medical records.Ethics and disseminationThe Hunter New England Human Ethics Committee (2024/ETH01289) has approved the TTAP study protocol. Outcomes will be published in peer-reviewed journals, presented at scientific conferences and disseminated online to participants, clinicians and other pregnant women with asthma and their families via the Asthma in Pregnancy Toolkit website https://asthmapregnancytoolkit.org.au/.

Asthma is a classical inflammation-related disease, and its pathogenesis is closely associated with mitochondrial dysfunction and mitophagy. Although Anemoside B4 (AmB4) exhibits anti‑inflammatory properties in various diseases, its role in regulating mitochondrial dysfunction-related mitophagy in asthma remains unknown. In vivo and in vitro asthma models were constructed using house dust mite (HDM)-stimulated BALB/c mice and HDM-treated BEAS-2B cells. Hematoxylin and eosin and periodic acid-Schiff staining were used for the pathological examination of lung tissues. Mitophagy-related proteins were assessed by Western blotting and immunofluorescence. Mitochondrial membrane potential (MMP) and reactive oxygen species (ROS) levels were measured using JC-1 and DCFH‑DA assays, respectively. Mitochondria was observed by transmission electron microscopy. Cytokine concentrations were determined by ELISA. The mito‑Keima reporter was employed to directly quantify mitophagy and analyzed by flow cytometry. The effect of KAT2B on IRF3 protein stability was determined by cycloheximide chase assay. The ubiquitination of IRF3 was assessed by immunoprecipitation. Intermolecular interactions were analyzed using co-immunoprecipitation, chromatin immunoprecipitation, and dual-luciferase reporter assays. The results illuminated AmB4 alleviated asthma by downregulating KAT2B expression, thereby ameliorating mitochondrial dysfunction and suppressing mitophagy in vivo. Furthermore, AmB4 increased the MMP of BEAS-2B cells and reduced levels of ROS, LC3B, and Tomm20 via KAT2B inhibition. Mechanistically, KAT2B promoted the lysine acetylation of interferon regulatory factor 3 (IRF3) at K315, and IRF3 enhanced PTEN-induced putative kinase 1 (PINK1) expression by binding to its promoter. Additionally, AmB4 inhibited mitochondrial dysfunction-related mitophagy by targeting the KAT2B/IRF3/PINK1 axis, thereby alleviating asthma. Specifically, AmB4 suppressed IRF3-mediated PINK1 transcription by inhibiting KAT2B-dependent acetylation of IRF3 at K315, thereby ameliorating mitochondrial dysfunction and suppressing mitophagy, which ultimately improved asthma symptoms.

The evolution of mite sensitization profiles from childhood to adulthood is associated with distinct clinical outcomes. Longitudinal sensitization trajectories have never been addressed across two generations over an extended time frame. Using molecular diagnosis, we aimed to investigate how the evolution of mite sensitization relates to the expression of rhinitis and asthma in adult versus pediatric patients over a 20-year period. Specific IgE (sIgE) to mite molecular allergens was determined using the MeDALL allergen chip (Der p 1, 2, 4, 5, 7, 10, 11, 14, 15, 37, 18, 21 and 23; Der f 1, Der f 2, Lep d 2, Blot t 5). Assessment was made in adult (n = 21), adolescent (n = 11), and pediatric patients (n = 19) with rhinitis and/or asthma, in T1 (20-years ago) and in T2 (current time). After the 20-year period, the adult cohort significantly decreased the number of sIgE responses to mite components-T1: 7 [3-9] versus T2: 4 [2-6], median [IQR], p = .0040. A strong negative correlation was observed between age and the 20-year variation of sensitization count (r = -0.5305; p < .0001). In adults, the reduction in mite molecular IgE responses was associated with improvement in rhinitis (p = .0010) and asthma (p = .0020), reflecting disease progression patterns not observed in the pediatric cohort. This is the first analysis to show that molecular mite sensitization declines with aging, and this reduction may relate to decreased asthma and rhinitis symptoms and severity. This age-associated decline highlights the importance of careful clinical interpretation in older adults to avoid overtreatment and missed diagnoses.

Mechanistic study of inspiratory training in childhood Asthma: Rationale and methods of a pediatric clinical trial.

Asthma is a chronic inflammatory disorder of the airways. Standard treatments, such as inhaled corticosteroids like fluticasone, beclomethasone, and budesonide, are effective in managing asthma symptoms by reducing inflammation through immune suppression. However, prolonged corticosteroid therapy can impair vitamin D metabolism, exacerbating vitamin D deficiency, which is essential for immune regulation and anti-inflammatory responses via the vitamin D receptor (VDR). Activation of the pregnane X receptor (PXR) by corticosteroids induces cytochrome P450 enzyme CYP24A1, accelerating vitamin D catabolism and reducing its anti-inflammatory efficacy. This effect is mediated through the interaction between PXR and its nuclear partner, the retinoid X receptor (RXR), which together regulate gene transcription. Disrupting this PXR-RXR dimerization could offer a selective means to prevent vitamin D degradation without interfering with other physiological functions of PXR or RXR.In this study, we aimed to inhibit the PXR and retinoid X receptor (RXR) interaction by designing peptidomimetic molecules based on the key RXR residues interacting with PXR. To achieve this, we used a multifaceted approach, incorporating pharmacophore and similarity-based peptidomimetics screening, molecular docking, ADMET analysis, and molecular dynamics (MD) simulations. The molecular docking results indicated that 38 compounds had a docking score higher than -7. Among them, six showed favorable ADMET properties. These molecules were then subjected to MD simulations, where two molecules, notably MMs02510246 and MMs03733211, showed strong interaction with PXR during the 300ns of MD simulation. Two others partially changed the starting binding site, while two others completely retained their initial binding site and bound to another site. Our study identified two potential molecules that could inhibit the PXR-RXR interaction. These two molecules could potentially inhibit the PXR-RXR interaction, which may help reduce corticosteroid-induced vitamin D inactivation, thereby improving asthma management outcomes without compromising vitamin D's anti-inflammatory benefits. Further experimental analyses are needed to validate our results.

The 5-item Asthma Control Questionnaire (ACQ-5) is widely used in clinical trials to assess the adequacy of asthma symptom control and any changes in asthma control as a result of treatment. Evidence supporting the psychometric properties of the ACQ-5, including a 0.5-threshold for meaningful improvement, was derived using methods that are no longer recommended in the literature or by regulatory authorities. The primary objective of this research was to derive meaningful change estimates using contemporary methods to evaluate clinically important change for the ACQ-5. A secondary objective was to evaluate the applicability of the existing ACQ-5 asthma control threshold for defining "well-controlled" asthma (ACQ-5 ≤ 0.75). Measurement properties (item performance, reliability, validity, and responsiveness) were assessed prior to evaluating meaningful change, using data from a sample of 196 adults with inadequately controlled moderate-to-severe asthma from a placebo-controlled, Phase 2 study of rilzabrutinib (NCT05104892). Anchor- and distribution-based analyses were used to derive meaningful within-patient change (MWPC) and meaningful between-group difference (MBGD). Applicability of the existing ACQ-5 asthma control threshold was evaluated by plotting the positive predictive value (PPV) and negative predictive value (NPV) of the ACQ-5 total score in the current study against the PPV and NPV calculated in the original Juniper et al. (2006) study. High internal consistency (Cronbach's alpha = 0.90), moderate-to-strong convergent validity (r range: 0.52-0.83), and ability to detect improvements in asthma control based on psychometric and physiological measures were demonstrated for the ACQ-5. Test-retest reliability results were poor-to-moderate (intraclass correlation coefficient range: 0.30-0.66). Of the anchor-based estimates derived (0.2 to 1.6), empirical cumulative distribution function plots supported 0.6 or 0.8 as appropriate MWPC thresholds. Estimated MBGD ranged from 0.2 to 0.6. PPV/NPV plots supported continued use of a 0.75- threshold to determine "well-controlled" asthma. Contemporary score interpretation methods support a MWPC threshold of ≥ 0.6, which is functionally identical to the extant threshold of ≥ 0.5, given the 0.2 increments of the ACQ-5 scale. MBGD ranged from 0.2 to 0.6, further supporting use of the established ≥ 0.5 threshold to define clinically important change between groups of patients. A "well-controlled" threshold of ≤ 0.75 was also supported.

Urban African adolescents suffer from undiagnosed and uncontrolled asthma symptoms. The purpose of this pilot study was to identify factors related to poorly controlled asthma symptoms and evaluate whether the objective measures suggested by the European Respiratory Society task force (ERS-TF) diagnostic algorithm for children assisted with asthma diagnosis. Between July 2019 and November 2021, we conducted a cross-sectional cohort study of urban school-going adolescents between 12 and 14 years as part of the Achieving Control of Asthma in Children in Africa (ACACIA) project. The study comprised two stages; (a) screening for asthma symptoms and diagnosis and (b) asthma control test (ACT), pre and post-bronchodilator spirometry, and FeNO measurements in those who were screen-positive. Of 2093 adolescents screened, 180 were included, and 56% were female. Most participants had severe asthma symptoms (n = 128; 71%) and uncontrolled asthma (n = 157; 87%). Half (n = 90) had a previous asthma diagnosis, and were more likely to have uncontrolled asthma, p = 0.04. A significantly higher number of adolescents with uncontrolled asthma were exposed to traffic near their home (58% vs. 35%, p value < 0.01). Those who were exposed to kerosene lamps and insect sprays were more likely to have airway inflammation; p = 0.02 and p = 0.01; respectively. The prevalence of abnormal spirometry and bronchodilator response (BDR) was 12%. By performing the BDR test in those with normal spirometry, we increased the diagnostic yield of the ERS-TF algorithm by 50%. In this at-risk population, asthma symptoms are common, uncontrolled and related to environmental factors. In over half of those who undergo screening procedures such as spirometry, BDR and FeNO, the likelihood of a diagnosis remains low. Additional research involving non symptomatic control groups and longitudinal assessment is required to validate these results.

The purpose of this study is to assess the feasibility of measuring differences in asthma symptoms, lung function, asthma biomarkers, and allergic sensitization in children with asthma living in areas undergoing environmental greening compared to control areas. This was a single-site prospective observational pilot study enrolling children living in either areas undergoing systematic environmental greening or in a designated control area. Eligible children were ages 6-18 with an asthma diagnosis. Children were followed for one year. The pre-specified primary endpoint was the change in Standardized Pediatric Asthma Quality of Life Questionnaire (PAQLQ(S)) scores between the initial and final visit. Secondary outcomes included changes in spirometry values, impulse oscillometry results, and asthma biomarkers (exhaled nitric oxide, IgE, blood eosinophils). Observational endpoints included healthcare utilization and self-reported rescue inhaler use. Urine samples were collected to measure plant metabolites. The trial was designed to provide key data to inform future larger studies in this domain. Ten children in the control area (mean age 12.1 years) and nine children in the intervention area (mean age 11.9 years) with similar baseline PAQLQ(S) scores and lung function were enrolled. From initial to final measurement, mean PAQLQ(S) asthma symptom domain scores improved in children living in the intervention areas (baseline 5.4, final 6.1, p = 0.048) while scores in the control areas showed no change (baseline 5.6, final 5.2, p = 0.66). There were statistically significant declines in FEV1 and FEF25-75% from initial to final measurement in the control group. There were no significant changes in any lung function parameter in the intervention group. There were no statistically significant differences in exhaled nitric oxide, blood eosinophils, and IgE in either group. Urine plant metabolite data suggested higher plant exposure in the intervention group. Subjects attended 96.8% of expected visits and were able to complete nearly all study-related tasks. In this small pilot study, children with asthma living in areas undergoing systematic environmental greening had improvements in asthma quality of life scores. Study interventions were feasible for subjects to complete. Larger studies with appropriate power are needed to study the direct impact of greening interventions on pediatric asthma.

Different pathogens cause pneumonia with overlapping symptoms, labs, and imaging, complicating early diagnosis. The modified lung ultrasound score (MLUS) shows value in lung disease evaluation, but its ability to differentiate pathogens is unclear. This study assessed MLUS for early identification of mycoplasma, viral, and bacterial pneumonia in children. We enrolled 186 children with suspected pneumonia (Jan-Dec 2023). Clinical data, labs, lung ultrasound findings (A-lines, B-lines, solid lesions, pleural effusion), and pathogens were recorded. MLUS was assigned. Based on pathogens, cases were grouped into mycoplasma (n=74), viral (n=63), and bacterial (n=49) pneumonia for comparison. 1. The median age of the mycoplasma pneumonia group was 6 (4.58,8) years, greater than that of the bacterial pneumonia group (3 [1.1,4.83] years) and the viral pneumonia group (3.41 [1.16,4.75] years) (P＜ 0.05). The mycoplasma pneumonia group had more febrile symptoms, extensive solid lung lesions, and fewer asthmatic symptoms than the other two pathogen groups (P < 0.05). 2. The median MLUS for mycoplasma pneumonia group was 15 (10,22), significantly higher than the median score of 9 (5,16) in the bacterial pneumonia group and 8 (5,15) in the viral pneumonia group (P < 0.05). 3. Coughing up sputum and small lung solid changes were significantly more common in the mycoplasma pneumonia group than in the bacterial pneumonia group (P < 0.05). A high modified lung ultrasound score, extensive solid lung lesions, older age, fever, and fewer shortness-of-breath symptoms strongly suggest mycoplasma pneumoniae infection. These findings provide critical evidence for early, targeted clinical management.

BackgroundThe Asthma Daytime and Nighttime Symptom Diaries (ADSD and ANSD) were developed to provide an accurate and standardized instrument for assessing patient-reported severity of asthma symptoms. While previous evidence supports the content validity and cross-sectional measurement properties of the ADSD and ANSD, the US Food and Drug Administration (FDA) qualification statement for these tools recommended further evaluation of their longitudinal measurement properties and the interpretation of within-patient meaningful change (WPMC). Therefore, two complementary studies were designed to assess cross-sectional and longitudinal measurement properties and estimate thresholds for WPMC for the ADSD/ANSD in patients with moderate-to-severe asthma, responding to measurement gaps identified in the FDA statement.MethodologyQuantitative evaluation of ADSD/ANSD (score range 0 to 10) measurement properties was performed in a real-world observational study (RWS; ≥16 years old; moderate-to-severe asthma) and a randomized controlled trial (RCT; ≥12 years old; severe asthma with type 2 inflammation). Cross-sectional and longitudinal measurement properties were assessed and WPMC thresholds estimated.ResultsA total of 576 patients with moderate-to-severe asthma were recruited across both studies. The RWS (n = 241) and RCT (n = 335) both found the ADSD/ANSD to have high internal consistency and test-retest reliability with Cronbach’s α-coefficients ≥0.94 and intraclass correlation coefficients ≥0.90. Evidence in support of the unidimensional scoring solution for both the ADSD and ANSD was established via confirmatory factor analysis across timepoints and studies, and evidence of construct validity was demonstrated via convergent and known-groups validity testing. In the blinded RCT analysis, the threshold for WPMC was estimated at 1.2 for the ADSD and 1.5 for the ANSD. In the RWS, the WPMC threshold for within-patient improvement was estimated to be from 0.6 to 1.3 for ADSD and from 0.8 to 1.4 for ANSD across 6- and 10-week intervals. ConclusionsThis study directly addresses the evidence gaps identified by the FDA, demonstrating that the ADSD and ANSD are reliable and valid tools for the measurement of daily symptoms in patients with moderate-to-severe asthma, and are capable of detecting WPMC. Values derived from the RCT analysis support a recommendation for thresholds for meaningful within-patient change of 1.2 and 1.5 for the ADSD and ANSD, respectively.Clinical trial registrationGSK ID: 217640; NCT04719832.Supplementary InformationThe online version contains supplementary material available at 10.1186/s41687-026-01066-5.

Outer membrane vesicles (OMVs) derived from Akkermansia muciniphila (A. muciniphila) are known to have immunomodulatory properties; however, their role in allergic asthma remains largely unexplored. In this study, we isolated OMVs from A. muciniphila and conjugated them with polymyxin B (PMB) to neutralize membrane-associated lipopolysaccharide (LPS). In a murine asthma model, both PMB-conjugated A. muciniphila OMVs (PMB-A. muciniphila OMVs) and native OMVs alleviated asthma symptoms, with PMB-A. muciniphila OMVs exhibiting superior efficacy. The enhanced therapeutic effect of PMB-A. muciniphila OMVs was attributable to a more potent suppression of alternative macrophage polarization (M2). Mechanistically, PMB-A. muciniphila OMVs disrupt oxidative phosphorylation and inhibit the AP-1 transcription complex and downstream PI3K/AKT signaling, which are essential for M2 polarization. In conclusion, our findings demonstrate that PMB conjugation augments the therapeutic potential of A. muciniphila OMVs against allergic asthma by specifically targeting M2 macrophage polarization via metabolic reprogramming and suppression of AP-1/PI3K/AKT signaling. These findings suggest that PMB-A. muciniphila OMVs present a novel and promising microbiota-derived therapeutic strategy for asthma.