Inhalers and climate change: A sustainable approach to severe asthma management.

Severe uncontrolled asthma (SUA) represents a complex and heterogeneous form of asthma that persists despite treatment. Allergic immunoglobulin E (IgE)-mediated SUA can be treated with tezepelumab or omalizumab. The aim was to estimate the cost-effectiveness of tezepelumab compared to omalizumab in the treatment of patients with allergic SUA, from the perspective of the Spanish National Health System (NHS). A Markov model was developed with a time horizon of 60 years, 28-day cycles, and five health states: controlled asthma; uncontrolled asthma; controlled asthma with exacerbation; uncontrolled asthma with exacerbation; and death. The efficacy parameters of the model were based on the NAVIGATOR and SOURCE clinical trials for tezepelumab and standard therapy, and on a network meta-analysis for omalizumab. Utilities and disutilities were extracted from NAVIGATOR and SOURCE and from the literature. The model considered direct costs (€, 2025): pharmacological, administration, exacerbations, disease management, and adverse events arising from oral corticosteroid use, obtained from Spanish data sources. Incremental costs per quality-adjusted life-year (QALY) gained were estimated for tezepelumab compared to the 106 omalizumab dosing profiles defined by weight and IgE. The results were contextualized to the Spanish setting using weight and IgE data obtained from the Primary Care Clinical Database and the literature. Deterministic sensitivity analysis (DSA) and probabilistic sensitivity analysis (PSA) were performed. Tezepelumab was cost-effective compared with omalizumab (450 mg/4 weeks;incremental cost-effectiveness ratio €17,213.44/QALY), considering a willingness-to-pay threshold of €30,000/QALY, and was dominant (more effective and less costly) at higher doses. This represents 69.81% of the dosing profiles and 53.47% of the population with allergic SUA in Spain. The DSA confirmed that tezepelumab was cost-effective compared to omalizumab (450 mg) despite the variations in the parameters used. Tezepelumab was cost-effective or dominant in 80.00% of the PSA simulations. In this analysis, tezepelumab was a cost-effective option compared with omalizumab (≥450mg/4weeks) for the treatment of patients with allergic SUA aged 12years and older from the perspective of the Spanish NHS.

Asthma remission with benralizumab therapy in severe eosinophilic Indian asthmatics.

To analyse metered-dose inhaler disposal behaviour in asthma patients, determine the patient characteristics that contribute to appropriate disposal and quantify the effect of a pharmacy-led educational intervention. We conducted a multicentre cross-sectional study in 40 Spanish hospitals followed by a pre-post quasi-experimental evaluation. We surveyed adults with uncontrolled severe asthma receiving biological therapy to determine sociodemographic, health, environmental attitude and disposal behaviour characteristics. At the time of biological therapy dispensation, we provided patients with an infographic on inhaler environmental impact and appropriate disposal. We resurveyed participants 3months later to assess changes in knowledge, attitude and disposal behaviour. We identified factors associated with correct inhaler disposal and quantified the impact of the intervention using a multivariate logistic regression and McNemar test, respectively. Despite 86.7% (435/502) of our study participants valuing environmental conservation and 91.6% (460/502) being aware of medication disposal programmes, only 46.6% (234/502) correctly disposed of inhalers. Factors associated with appropriate disposal included practising household recycling, high perception of inhaler environmental impact, awareness of medication disposal programme, low income and self-reported limitations to daily activities. On resurveying patients 3months after our pharmacy-led intervention, we observed an increase in correct inhaler disposal to 84.1% (418/497) with parallel gains in awareness and recycling behaviours. We revealed a discrepancy between the environmental concerns of asthma patients and inhaler disposal behaviour, due to limited knowledge of inhaler environmental impact. We demonstrated that this knowledge gap can be reduced, doubling the correct disposal of inhalers, through a targeted pharmacy-led intervention.

Asthma is a prevalent chronic respiratory disease characterised by airway inflammation, reversible airflow obstruction and airway hyper-responsiveness. Most patients with severe asthma (SA) remain uncontrolled despite the availability of multiple therapies, representing a significant global health burden.Thymic stromal lymphopoietin (TSLP) is an epithelial cell-derived cytokine that plays a central role in asthma initiation via both allergic and non-allergic mechanisms as well as in the persistence of airway inflammation in patients with asthma, acting upstream in the inflammatory cascade.Tezepelumab, a monoclonal antibody that targets TSLP, has shown clinical efficacy and safety in pivotal trials in patients with T2 and non-T2 asthma. Tezepelumab was approved for use in Europe in October 2022, and the marketing authorisation was issued in Spain in October 2023. The T-ROSS II study is a retrospective, observational, single-arm, multicentre study planned to include 400 patients aged ≥12 years treated in SA units. T-ROSS II will represent the largest published series of patients with SA who initiated tezepelumab after its market authorisation.Eligible patients must have at least 12 months of medical history prior to treatment initiation and a minimum of 3 months of follow-up data recorded in the electronic health records.The co-primary outcomes are to describe baseline patient demographics and clinical characteristics and evaluate changes in the annualised asthma exacerbation rate before and after the initiation of tezepelumab. These findings will complement clinical trial data and inform physicians and healthcare decision-makers about the real-world effectiveness and utilization of tezepelumab in patients with SA. This study is expected to provide valuable insights into the clinical outcomes and treatment patterns of this population. The final protocol of the study has been approved by the ethics committee/Institutional Review Board (EC/IRB) of the University Hospital 12 de Octubre (Madrid, Spain) (EC/IRB number: 25/226). The results will be disseminated through scientific publications, including manuscripts submitted to peer-reviewed journals and presentations at national and international congresses. NCT07013760.

To assess the association between adherence to MD and asthma control in severe asthmatics. During the period between March 2022-2023, patients with severe asthma from 16 pulmonary centers all over Greece were recruited. Adherence to MD was assessed through a short interviewer-administered questionnaire, the MD Adherence Screener, previously validated in Mediterranean populations. The level of asthma control was assessed by the Asthma Control Test. A multiple logistic regression model was applied, adjusting for gender, age, body mass index, corticosteroid intake, comorbidities, treatment. The study sample included 315 severe asthmatics (30% males) with mean age 56.6 years (SD = 14.3 years). There is an indication, albeit not statistically significant, that higher adherence to MD was associated with better asthma control in patients with severe asthma (OR: 1.19, 95% CIs: 0.61, 2.34). Furthermore, controlling for the patients' personal characteristics and dietary habits, other diet related conditions and metabolic diseases, such as obesity or diabetes, were significantly associated with poorer asthma control. In a cross-sectional study undertaken in a Mediterranean population, we observed a positive, but not statistically significant, association between higher adherence to MD and better asthma control in severe asthmatic patients. However, our findings are limited by the study design which does not allow us to infer causality and by the use of a screener to assess adherence to Mediterranean diet.

Traditionally, mucus plugs have been evaluated using two-dimensional computed tomography (CT) images through expert visual assessment, a process that requires substantial experience and specialized knowledge of airway anatomy. In the present study, we propose a novel approach employing three-dimensional CT (3D-CT) with semi-automated quantification, which can be performed in routine clinical practice without requiring expert readers. We aimed to demonstrate its feasibility and clinical relevance for assessing mucus plug burden and exacerbation severity in asthma. This exploratory, single-center, retrospective study included 23 patients with asthma and a history of exacerbations. Using a clinically available 3D-CT application, we semi-automatically quantified bronchial endpoint count and bronchial volume in both stable and exacerbation phases, and calculated their percentage change. We further assessed correlations of these parameters with mucus plug scores and arterial blood gas measurements. The bronchial endpoint count and bronchial volume were significantly lower during exacerbations than during the stable phase; both showed a significant negative correlation with mucus plug scores during exacerbations. The percentage change of bronchial endpoint count and bronchial volume from the stable to exacerbation phase also correlated with mucus plug scores. The bronchial endpoint count and bronchial volume at exacerbation-related admission did not correlate with the PaO2/FiO2 (P/F) ratio; however, their percentage change from the stable phase to exacerbation-related admission significantly correlated with the P/F ratio. Clinically available semi-automated 3D-CT analysis enables objective and reproducible quantification of bronchial endpoint count and bronchial volume during asthma exacerbations, eliminating the need for expert readers. Their percentage change from the stable to exacerbation phase not only reflect mucus plug burden but also correlate with oxygenation status. These imaging biomarkers enable objective and quantitative assessment of structural airway abnormalities, including airway narrowing, distal airway obstruction, and mucus impaction. They are not intended to replace conventional clinical or physiological assessment, but rather to provide complementary structural information regarding the underlying causes of physiological abnormalities, such as impaired oxygenation, when detected by physiological evaluation. Furthermore, such quantitative structural assessment may contribute to a better understanding of airway structural changes and airway dynamics during asthma exacerbations.

Current biological treatments are not suitable for many patients with severe asthma. The aim of this meta-analysis was to determine the efficacy of tezepelumab in patients with asthma. The authors conducted systematic searches of PubMed, Embase, the Cochrane Library, and clinicaltrials.gov without language restrictions. Randomized Controlled Trials (RCTs) on treatment of asthma with tezepelumab were reviewed. The authors summarized findings as Risk Ratios (RR) for dichotomous outcomes and Weighted Mean Differences (WMD) for continuous outcomes, each with 95% Confidence Intervals (95% CI). Seven RCTs (enrolling 2050 participants) met the inclusion criteria. Tezepelumab showed significant effects on asthma exacerbation (RR = 0.72, 95% CI 0.65% to 0.80), percentage change in Forced Expiratory Volume in 1 s (FEV1) (WMD = 7.97%, 95% CI 3.10% to 13.83%), percentage change in Forced Vital Capacity (FVC) (WMD = 3.80%, 95% CI 2.48% to 5.12%), Asthma Control Questionnaire (ACQ)-6 score (WMD = -0.35, 95% CI -0.45 to -0.25), Asthma Quality of Life Questionnaire (standardized) for patients 12-years of age or older (AQLQ[S]+12) score (WMD = 0.33, 95% CI 0.22 to 0.43), and serious adverse events (RR = 0.74, 95% CI 0.57 to 0.95). Tezepelumab appears safe and effective; further long-term and real-world studies are warranted.

Objective: Heated high flow nasal cannula (HHFNC) use in pediatric critical asthma is rising despite concerns regarding its ability to effectively deliver nebulized medications to the lower airway. We aim to measure the association of low versus high HHFNC flow rates for delivery of continuously inhaled short acting beta agonist (cSABA) on clinical outcomes in the Pediatric Intensive Care Unit (PICU).Methods: This is a retrospective cohort study investigating PICU patients admitted with critical asthma who were prescribed HHFNC for cSABA delivery. Patients were divided into two groups based on the average flow rate used to deliver cSABA: low flow (≤5 L/min) versus high flow (>5 L/min). Outcomes including total duration of cSABA, total duration of noninvasive respiratory support (HHFNC, continuous (CPAP) and bilevel (BPAP) positive airway pressure), PICU LOS, and hospital LOS were explored. Data were analyzed by Wilcoxon-Rank Sum, Chi-squared and Fisher's Exact tests.Results: 112 patients were included. Patients in the low flow group (n = 56) had a median HHFNC flow rate of 4.0 L/min (IQR 3.9-4.0) versus patients in the high flow group (n = 56) at 9.6 L/min (IQR 7.0-15.0; p < 0.001). Pediatric Asthma Severity Scores (PASS) were similar (p = 0.095). The low flow group had significantly shorter total duration of cSABA (p = 0.048), shorter duration of noninvasive respiratory support (p = 0.0234), and shorter PICU (p < 0.001) and hospital (p = 0.0063) LOS.Conclusions: Low HHFNC flow rates for cSABA delivery are associated with shorter durations of cSABA, noninvasive respiratory support, PICU and hospital LOS.

Inhaled corticosteroid (ICS) use in pregnancy has shown associations with decreased offspring asthma in childhood, whereas exacerbations in pregnancy may increase the risk. However, these findings have not been tested in population-based cohorts with rigorous assessment of confounding structures. The aim was to describe asthma exacerbations and ICS utilisation during pregnancy and to assess causal pathways between pregnancy exacerbations, ICS use and offspring asthma. Register-based cohort study of pregnancies in New South Wales (NSW), Australia and Sweden. Maternal monthly asthma exacerbations (hospital visits and/or oral corticosteroid (OCS) dispensings) and ICS dispensing rates were calculated 12 months prepregnancy to 12 months post partum. Among mothers with asthma (35 194 NSW, 102 248 Sweden), Hazard Ratios (HR)s were calculated for pregnancy exacerbations or ICS use and offspring asthma adjusting for confounders including asthma severity. Associations between paternal exposures and offspring asthma and sibling analyses assessed the likelihood of unmeasured confounding. Maternal asthma prevalence was 8.6% in NSW and 7.1% in Sweden. While ICS use was maintained over the course of pregnancy, a postpartum decline was observed, accompanied by a rise in OCS use. Adjusted HRs for offspring asthma were 1.47 (95% CI 1.32 to 1.64, NSW) and 1.30 (95% CI 1.24 to 1.36, Sweden) following maternal exacerbations, and 1.37 (95% CI 1.26 to 1.49, NSW) and 1.23 (95% CI 1.19 to 1.27, Sweden) following maternal ICS use. Paternal exposures were also associated with offspring asthma, while associations in sibling analyses were not significant. Observed associations between maternal exacerbations, ICS use and offspring asthma appear to be due to unmeasured confounding. Management of maternal asthma remains a priority in pregnancy and post partum.

Histidine metabolic reprogramming drives oxidative stress induced mtDNA release to promote necroptosis and airway inflammation in severe asthma.

A 73-year-old man with severe asthma developed secondary adrenal insufficiency after long-term high-dose inhaled fluticasone therapy. Switching to inhaled ciclesonide worsened the symptoms (fatigue, muscle pain, diarrhea, and eosinophilia), and oral hydrocortisone had little effect. Reintroducing fluticasone rapidly improved the symptoms and normalized eosinophilia, suggesting that fluticasone may exert a uniquely strong individualized effect on the hypothalamic-pituitary-adrenal axis. Tapering requires prolonged management, but treatment with Saireito, a Kampo medicine, may have facilitated adrenal recovery. This case highlights that inhaled corticosteroids can significantly affect the systemic corticosteroid physiology, suggesting the need for careful monitoring when changing the preparations.

Severe asthma and remission prospects in Europe (SHARP): insights from a multicentre observational study based on the European Severe Asthma Registry.

Switching Biologics in Severe Asthma: Cautionary Lessons from NIMBLE.

Kv1.3 Modulates Macrophage M2 Polarization via the STAT3 Pathway: A Novel Mechanism and Therapeutic Target for Steroid-Resistant Asthma.

Heterogeneity of severe asthma in Europe: a SHARP-er view.

A cross-sectional study of oxidative stress pathway genotypes and their interactions with environmental pollutant levels identifies associations with gene expression and lung function.

Robust unsupervised modeling is critical in medical applications where high-dimensional noise and outliers can destabilize clustering and mislead clinical interpretation. However, existing internal validation indices- such as the Silhouette score, Davies-Bouldin index, and Calinski-Harabasz index- mainly quantify cohesion and separation, providing limited insight into noise resistance. In addition, adversarial robustness techniques developed for supervised learning cannot be directly applied to unsupervised biomedical phenotyping, leaving a critical methodological gap. We introduce Noise-Induced Analysis for Robustness Evaluation (NIARE), a framework that quantifies robustness by augmenting datasets with synthetic noise-only features drawn from controlled distributions. NIARE operates in two modes: (i) feature-reduction scoring, which identifies the onset of noise-dominated components to guide dimensionality selection, and (ii) clustering scoring, which measures the importance assigned to injected noise features relative to real features to assess cluster stability. Applied to a high-dimensional asthma cohort of 1,112 patients across 3,471 clinical visits, NIARE selected a five-component PCA representation and a five-cluster operating point, yielding clinically distinct asthma phenotypes characterized by differences in lung function, inflammatory markers, oral corticosteroid burden, and visit frequency. External validation on the Severe Asthma Research Program (SARP) cohort further supported generalizability by recovering the established five-phenotype asthma structure without requiring ground-truth labels. Compared with conventional validation indices, NIARE provides a scalable and interpretable measure of robustness for highdimensional biomedical clustering, offering a practical alternative to supervised adversarial methods in unsupervised clinical phenotyping.

100years ago, the main treatments for asthma were the sympathomimetic ephedrine, theophylline tablets, inhaled anticholinergics in the form of "asthma cigarettes". Together with adrenaline injections for acute exacerbations, these treatments were all bronchodilators derived from natural products. Adrenaline injections evolved into inhaled β2-agonists as the most effective bronchodilators in asthma, whereas theophylline and inhaled anticholinergics are less useful treatments. The efficacy of desiccated adrenal glands extract, used since 1900, is likely due to steroids derived from the adrenal cortex. Corticosteroids are the most effective treatment for asthma and target the underlying eosinophilic airway inflammation. Combination inhalers of corticosteroid and long-acting β2-agonist are now the mainstay of asthma therapy. Recently, short-acting β2-agonists as relievers have been replaced by relievers containing an inhaled corticosteroid, together with a rapid onset long-acting β2-agonist formoterol (anti-inflammatory reliever). This addresses the major issue of poor adherence with inhaled corticosteroids. Poor inhaler technique is being addressed with the development of smart inhalers. In patients with severe asthma not controlled by inhaled therapy, antibodies that block cytokines involved in eosinophilic inflammation have been very effective. In the future, longer acting antibodies will simplify the treatment of these patients. New drugs are also in development for severe non-eosinophilic asthma. There have been remarkable advances in asthma therapy over the last century, although our current treatments have their origins in the therapies used in 1925.

Timing of High-Risk Asthma Specialist Enrollment and Severe Asthma Exacerbations in Children.