Results
- Showing results for:
- Reset all filters
Search results
-
Journal articleWang M, He Y, Hu H, et al., 2026, , Redox Rep, Vol: 31
BACKGROUND: Fatty acid oxidation (FAO) is implicated in lung diseases, but its role in bronchial asthma is not fully understood. We investigated its effect on airway epithelial barrier integrity. METHODS: Using a house dust mite (HDM)-induced murine asthma model and HDM, IL-4, IL-13, or TNF-α stimulated human primary bronchial epithelial cells (BECs) and bronchial epithelial (Beas-2b) cells, we modulated FAO with L-carnitine (agonist) and Etomoxir (inhibitor). BECs and Beas-2b cells were infected with lentivirus-mediated CPT1A shRNA prior to stimulation. Barrier function, mitochondrial oxidative stress, inflammation, and metabolism were assessed. RESULTS: FAO level in lungs negatively correlated with increased inflammation and tissue injury in HDM-induced asthmatic mice (all p < 0.05), while positively regulating tight junction protein expression. In BECs and Beas-2b cells, Etomoxir treatment and CPT1A knockdown exacerbated the impairment of FAO caused by various stimulants (all p < 0.05). Furthermore, FAO negatively regulated HDM/cytokine-induced epithelial barrier damage, hyperactive inflammatory response, and mitochondrial dysfunction in Beas-2b cells (all p < 0.05). In contrast, treatment with L-carnitine significantly alleviated these pathophysiological features in both in vivo and in vitro models. CONCLUSION: FAO plays a protective role in the occurrence and development of asthma by maintaining airway epithelial cell homeostasis and barrier function.
-
Journal articleMoffatt MF, Nishimura T, Cox MJ, et al., 2026, , American Journal of Respiratory and Critical Care Medicine, Vol: 212, Pages: 1962-1974, ISSN: 1073-449X
RationaleAsthma is characterized by disruption of the thoracic airway mucosae and loss of microbial diversity. Spatial profiling of the mucosal transcriptome may systematically discover mechanisms for microbial influences on immunity.ObjectivesWe investigated relationships between clinical measures, microbial communities, and the host mucosal transcriptome within different strata of bronchial biopsies in subjects with and without asthma.MethodsWe bronchoscoped 65 adult asthmatics and 44 healthy controls, quantifying bacterial operational taxonomic units (OTUs) in bronchial brushings by 16S rRNA gene amplicon sequences. Biopsy histologic features were scored blind to diagnosis. Following 16S rRNA in situ hybridization of 44 biopsies, bacterial foci were scored in epithelium, basement membrane and stroma. Global human gene expression was quantified in epithelial and stromal compartments using Digital Spatial Profiling.Measurements and main resultsClinical asthma was independently predicted by basement membrane abnormalities (BaseMA), endobronchial bacterial diversity and circulating eosinophil counts, but not by specific OTU abundances. 16S rRNA staining revealed bacteria within epithelium and mucosa of all biopsies. Intra-mucosal bacteria (IMCBs) counts correlated negatively with spatially organized co-expression networks encoding antigen-specific immunity, neutrophil functions, and matrix activation, whereas BaseMA correlated positively with the adaptive immunity module. Eosinophil counts correlated with epithelial bacterial counts and senescence pathways. Clinical asthma was accompanied by upregulation of a Treg cell network.ConclusionsAsthma and its related phenotypes are accompanied by complex mucosal events that extend beyond eosinophilic pathways. Components of diverse airway microbiota may modify immunity by beneficial interactions within the mucosa.
-
Journal articleBaraldi F, Mah JSY, Almuhanna A, et al., 2026, , Am J Respir Crit Care Med, Vol: 212, Pages: 2071-2074
-
Journal articleSong W-J, Kermani NZ, Versi A, et al., 2026, , Allergy, Vol: 81, Pages: 3273-3285
BACKGROUND: Asthma severity increases with age, suggesting a role for accelerated biological ageing. We hypothesised that cellular senescence pathways such as the senescence-associated secretory pathway (SASP) and the p53-cellular senescence pathway are enriched in the airways of patients with severe asthma. METHODS: We utilised transcriptomic data from the U-BIOPRED cohort to analyse enrichment scores (ES) of p53 and SASP pathways in different airway compartments using gene set variation analysis. Findings in bronchial biopsies were validated in the independent NOVA cohort. We examined associations between senescence ES, clinical parameters and other asthma-related gene signatures. Functional clusters of the SASP gene set were also explored. RESULTS: In the U-BIOPRED cohort, p53 and SASP ES were significantly elevated in bronchial biopsies of severe asthmatics compared to mild-to-moderate asthmatics and healthy volunteers, with SASP enrichment validated in the NOVA cohort. In bronchial biopsies, higher senescence ES correlated with frequent exacerbations, oral corticosteroid use, comorbid nasal polyps and lower FEV1%. No significant enrichment was found in other airway samples according to asthma severity. In nasal brushings, SASP ES was significantly higher in participants with comorbid nasal polyps. A distinct SASP functional cluster related to lung injury and repair (Cluster 2) was strongly associated with clinical severity and nasal polyps. Senescence signatures correlated positively with oxidative phosphorylation and macrophage activation signatures, but not with eosinophil signatures. CONCLUSIONS: Cellular senescence pathways are enriched in severe asthmatic bronchial tissues and correlate with disease severity, remodelling and nasal polyps. These findings warrant further investigation into their therapeutic implications. TRIAL REGISTRATION: NCT01982162.
-
Journal articleKumar A, Chan R, Zounemat-Kermani N, et al., 2026, , Allergy, Vol: 81, Pages: 3185-3196
BACKGROUND: Asthma remission is a feasible treatment goal. However, remission definitions vary, and predictive biomarkers remain underexplored. METHODS: We conducted a post hoc analysis of ATLANTIS (NCT02123667), a multinational prospective study including 684 adult asthmatics. Remission was defined by 3-component (3C) and 4-component (4C) criteria. 3C remission included: (1) ACQ-6 < 1.5, (2) no maintenance oral corticosteroids, (3) no exacerbations. An absolute decline < 10% in pre-bronchodilator FEV1% predicted, was added for the 4C definition. Multivariate logistic regression identified remission predictors. A novel Low Disease Activity (LDA) score was developed using factor analysis of five clinical variables (ACQ-6, FeNO, BEC, and FEV1) including an innovative small airways dysfunction questionnaire tool (SADT). Nasal transcriptomics were analysed for differential gene expression and pathway enrichment and were replicated in U-BIOPRED (NCT01976767) using sputum transcriptomics. U-BIOPRED was included only to study omics replication of remission pathways identified in ATLANTIS. FINDINGS: Remission occurred in 48% (3C) and 45% (4C) of patients. Predictors included male sex, better lung function, fewer previous exacerbations, and higher SADT (fewer small airways symptoms). LDA identified milder disease and was associated with remission [OR 3C 4.43 (2.80, 7.10) and 4C 3.46 (2.23, 5.43)], improved QoL [OR 2.07 (1.65, 2.60)], and fewer future exacerbations [OR 0.43 (0.22, 0.85)]. Transcriptomic analyses revealed remission-associated upregulation of interleukin 4/13 signalling and downregulation of coagulation pathways, in both ATLANTIS and U-BIOPRED. INTERPRETATION: SAD was associated with reduced asthma remission. A novel LDA tool demonstrated clinical utility in stratifying prospective asthma risk. Key immunologic and haemostatic pathways may underpin remission, offering potential targets for future intervention.
-
Journal articleShih Y-S, Han C-L, Lee YL, et al., 2026, , Expert Rev Respir Med, Vol: 20, Pages: 1055-1066
INTRODUCTION: Climate change has significantly increased the frequency and intensity of extreme temperature events, posing growing threats to respiratory health. Among the underlying mechanisms, airway dehydration is a critical yet underrecognized pathway that disrupts the airway surface liquid (ASL), which is essential for mucociliary clearance, epithelial integrity, and immune defense. AREAS COVERED: This article examines evidence linking airway dehydration to respiratory disease during temperature extremes. We discuss how hot, dry air and cold, low-humidity conditions disrupt airway hydration balance, leading to impaired mucociliary clearance and increased susceptibility to infection and inflammation. The review summarizes the impacts of airway dehydration on vulnerable populations, including individuals with pre-existing respiratory conditions (asthma, allergic rhinitis, chronic obstructive pulmonary disease (COPD), and cystic fibrosis), children, older adults, outdoor workers, and socioeconomically disadvantaged groups. EXPERT OPINION: Airway dehydration represents a unifying mechanism linking climate extremes to respiratory vulnerability but remains underrepresented in clinical practice and public health strategies. We advocate for greater recognition of airway hydration in disease prevention, development of practical measurement tools, and targeted interventions for at-risk populations. Emphasizing airway dehydration as a key mediator offers opportunities to improve clinical management and develop effective climate adaptation strategies for respiratory health protection.
-
Journal articlePiga NN, Portelli MA, Shrine N, et al., 2026, , ERJ Open Res, Vol: 12, ISSN: 2312-0541
BACKGROUND: In ∼10% of asthma patients, symptoms remain uncontrolled despite maximal treatment, representing an unmet clinical need. The causal variants, genes and pathways underlying genetic risk factors have not been fully elucidated, and it is unclear whether there are unique genetic risk factors for this asthma subtype. METHODS: We used electronic healthcare records linked to UK Biobank to identify asthma patients with high treatment burden and/or worse outcomes. We performed a genome-wide association study (GWAS) with this case population and healthy controls. We sought replication for associated (p≤5×10-6) signals in four independent studies (12 152 cases and 32 316 controls). Replicated signals were fine-mapped and linked to genes and pathways. RESULTS: In total, 7681 participants met our case definition and showed enrichment for adult-onset asthma, female gender and higher body mass index compared to asthma individuals not meeting case criteria. GWAS with 7681 cases and 38 405 controls revealed 21 reproducible association signals that had previously been associated with asthma, but had a larger effect size in our study. Variant-to-gene mapping highlighted 85 candidate genes, five of which were considered high confidence (BACH2, D2HGDH, IL1RL1, RPS26, SMAD3). CONCLUSION: We present the first use of electronic healthcare records in UK Biobank to identify a subtype of asthma enriched for patients with high treatment burden and/or worse outcomes. Our findings support the role of known asthma genes, highlighting genetic risk variants with stronger effect in these groups of patients. The prioritised genes provide potential therapeutic opportunities for this difficult-to-treat patient population.
-
Journal articleAndersson LI, Kupczyk M, Dahlén B, et al., 2026, , Allergy, Vol: 81, Pages: 3206-3220
BACKGROUND: Obesity-related asthma (OBA) is a distinct asthma phenotype, with increased severity. Adipokine release from excessive adipose tissue is suggested to be a key feature of OBA pathophysiology. However, it is unclear how the clinical characteristics of severe asthma associate with adipokine mediators. We examined systemic adipokine levels and evaluated relationships with disease severity, weight, sex, and steroid treatment in asthma. METHODS: A multiplex immunoassay for nine adipokines with proposed involvement in obesity-related inflammation (adiponectin, adipsin, BAFF, chemerin, FGF-21, leptin, lipocalin-2/NGAL, osteonectin and resistin) was designed. Plasma adipokines were measured in 127 patients with mild-to-moderate asthma (MMA) or severe asthma (SA) from the European BIOAIR cohort at baseline and after a controlled 2-week oral corticosteroid (OCS) intervention. RESULTS: Leptin and chemerin were significantly increased in patients with SA vs. MMA. Leptin, adiponectin, adipsin, and NGAL were affected by sex, whereas leptin and adipsin were strongly affected by weight. OCS increased leptin and adiponectin, decreased adipsin and BAFF, and did not affect osteonectin, resistin, or chemerin. No adipokines showed positive associations with exhaled NO, blood or sputum eosinophils, although certain correlations with serum CRP, blood, and sputum neutrophils were observed. CONCLUSIONS: Overall, we observe variable relationships between the nine adipokines, obesity and asthma severity. There were no relationships between adipokine levels and type-2 airway inflammation, yet associations with systemic neutrophilic inflammation were seen. Although one adipokine, chemerin, was independently associated with asthma severity, deciphering the role of adipokines in OBA is complex due to the influence of sex, BMI, and OCS.
-
Journal articleShamji MM, Rider NL, Adcock I, et al., 2026, , J Allergy Clin Immunol, Vol: 158, Pages: 694-714
Artificial intelligence (AI), first defined in 1955 by John McCarthy, has transformed daily life across industries through applications such as chatbots, autonomous vehicles, and navigation systems. The 2022 release of ChatGPT marked a pivotal moment, highlighting AI's rapidly expanding potential. The health care industry is increasingly embracing AI-enabled tools across oncology, pathology, and radiology to augment disease screening and clinical workflows. Ambient listening technologies support clinical documentation, reduce administrative burden, and improve patient-physician interactions. Large language models combined with natural language processing are being evaluated for generating clinical summaries managing patient portal messaging and converting freehand notes to electronic health records, while also uncovering patterns in patient data to support more personalized treatments. Forward-thinking health systems are establishing informatics departments to optimize these models. Notably, with 1 in 6 adults sourcing health information from AI, rising to nearly one-quarter among individuals younger than 30 years, there is a growing need to ensure that these technologies provide accurate and reliable information to safeguard patient safety and support appropriate clinical use. PRACTALL, a collaboration between the American Academy of Allergy, Asthma & Immunology and the European Academy of Allergy & Clinical Immunology, aims to equip allergist-immunologists with essential AI insights highlighting tools for clinical practice, education, and research. By addressing potential pitfalls and biases, PRACTALL illustrates how AI can enhance efficiency, improve patient care, and alleviate administrative burdens in health care.
-
Journal articleShen J, Chaudhuri R, Bicknell S, et al., 2026, , Allergy, Vol: 81, Pages: 3300-3317
Severe asthma is a heterogeneous disease. The mechanisms driving airway pathology when type 2 (T2) cytokine activity is suppressed remain poorly understood. This study aimed to provide insight by identifying the airway molecular pathways of T2 biomarker-high and -low severe asthma. We analysed clinical and transcriptomic data from bronchial biopsies and brushes in the UK Refractory Asthma Stratification Programme multi-centre severe asthma cohort (18 corticosteroid-resistant T2 biomarker-high [T2-high], 23 T2 biomarker-intermediate [T2-intermediate], 11 T2 biomarker-low [T2-low]) plus 20 healthy controls pre- and post-treatment with high-dose inhaled corticosteroids (ICS). Many genes dysregulated in asthma vs. health were concordantly dysregulated in healthy subjects receiving ICS. Severe asthma as a whole, independent of confounding by ICS, was characterised by upregulation of mucins, CEACAM5, typical T2-genes (POSTN, CLCA1, CCL26), epithelial mast cell genes, and CPA4. T2-high severe asthma demonstrated upregulated T2-dependent genes, epithelial barrier and keratin genes, adaptive immune responses, and impaired ciliary function. T2-low asthma showed upregulated Th1- and IL-17-associated genes (IDO1, CXCL10, GBP1, LAG3), interferon-γ signalling, neuroimmune pathways, airway smooth muscle-related genes, and neutrophil enrichment. T2-intermediate asthma exhibited a mixed molecular profile sharing features of T2-high and T2-low endotypes, with selective expression of the pathogen defence and antiviral response genes. The results were validated using bronchoscopy data from the U-BIOPRED Consortium. This study defines airway molecular endotypes of severe asthma associated with T2 biomarker high and low phenotypes, independent of corticosteroid effects. These findings offer insights for severe asthma management and the development of targeted biologic therapies.
-
Journal articleMatīsa D, Bansal AT, Rink S, et al., 2026, , ERJ Open Res, Vol: 12, ISSN: 2312-0541
BACKGROUND: Multimorbidity refers to the presence of multiple coexisting conditions, but is often underappreciated in the context of severe asthma (SA) management. We sought to identify differences in approaches to multimorbidity management in SA, variability in access to multidisciplinary team (MDT) resources, and whether physician perspectives on multimorbidity differ between SA specialists and general respiratory physicians. METHODS: The Severe Heterogeneous Asthma Registry, Patient-centred (SHARP) Clinical Research Collaboration circulated an online physician survey via European national respiratory societies to assess 1) available resources to address multimorbidity and 2) physician perspectives on multimorbidity in SA. RESULTS: 495 responses from 25 European countries included 48% SA specialists and 52% general respiratory physicians. SA specialists had more experience with SA patients (20% were seeing >60 patients per month) compared to general respiratory physicians. SA specialists had greater access to multidisciplinary care - including better access to MDTs, allied health professionals and referrals to external specialists, and therefore more routinely assessed comorbidities and considered them greater influences on their practice. They also considered multimorbidity to a greater degree and rated its impact on their patients' asthma outcomes (and general health outcomes) as more substantial. CONCLUSIONS: Alongside more experience of treating SA, SA specialists have increased awareness of multimorbidity and better resources to manage it. However, access to MDTs remains a significant gap for both SA specialists and general respiratory physicians. Furthermore, both groups identified a high need for further education and training about multimorbidity. These findings highlight key areas for improvement in clinical practice, resources and training.
-
Journal articleWang H, Fung NH, Aloe C, et al., 2026, , Clin Transl Allergy, Vol: 16, ISSN: 2045-7022
BACKGROUND: Severe asthma is a chronic inflammatory disease characterised by airway dysfunction, persistent immune activation and corticosteroid resistance. While macrophages are key regulators of lung immunity, how individual subsets, particularly interstitial macrophages (IMs), contribute to disease remains poorly understood. METHODS: Lung macrophages were profiled using single-cell RNA-sequencing (scRNA-seq) and flow cytometry in a C57BL/6 mouse model of severe asthma induced by Complete Freund's Adjuvant (CFA) and house dust mite (HDM). Human transcriptomic data from the U-BIOPRED asthma cohort were analyzed for translational validation. The dual CCR2/CCR5 antagonist Cenicriviroc (CVC) was used to evaluate the therapeutic potential of targeting pathogenic macrophages. RESULTS: CFA-HDM treatment led to marked depletion of resident alveolar macrophages (rAMs) and their replacement by recruited AMs (recAMs) associated with tissue remodeling. A distinct Lyve1loMHCIIhi IM subset emerged as the dominant inflammatory cell population, displaying high Ccr2 and Ccr5 expression, potent pro-inflammatory and antigen-presenting signatures, and extensive ligand-receptor communication with T cells, neutrophils and rAMs. Trajectory analysis demonstrated that both recAMs and Lyve1loMHCIIhi IMs arise from classical monocytes. Consistently, sputum transcriptomic data from the U-BIOPRED asthma cohort showed reduced AM-associated gene signatures and enrichment of IM/monocyte and CCR-chemokine programs in patients with severe disease. Pharmacological blockade of CCR2/CCR5 with CVC markedly reduced IM infiltration, limited T-cell and neutrophil recruitment, restored macrophage balance, and improved lung function. CONCLUSIONS: Lyve1loMHCIIhi IMs orchestrate airway inflammation in severe asthma. Dual CCR2/CCR5 antagonism inhibits their recruitment, restores macrophage balance, and halts disease progression, highlighting this pathway as a promising therapeutic target.
-
Journal articleYang F, Seo S, Hasegawa T, et al., 2026, , Allergy, Vol: 81, Pages: 3286-3299
BACKGROUND: Longer asthma duration predicts non-remission in Type-2 (T2) biologic-treated severe asthma, but underlying mechanisms remain unclear. We investigated associations between asthma duration and inflammatory biomarkers that may explain differential biologic response. METHODS: We analysed cross-sectional data from adults with severe asthma in U-BIOPRED. Asthma duration was defined as years from diagnosis to study entry. T2 and non-T2 biomarkers were measured in blood and sputum. Identical assays were performed in PRISM, a validation cohort of biologic-initiators. Multivariable regression models adjusted for age, sex, ethnicity, BMI, smoking and oral corticosteroid dose. Associations between duration-related biomarkers and 12-month biologic remission were explored in PRISM. RESULTS: In U-BIOPRED (n = 411), median asthma duration was 23 years (IQR 12-38). Longer duration was associated with higher non-T2 biomarkers including sputum CXCL9 (β = 0.024, 95% CI 0.011-0.038), sputum IL-6 (β = 0.024, 95% CI 0.011-0.037) and sputum neutrophils (β = 0.009, 95% CI 0.001-0.017), but lower T2 biomarkers including plasma periostin (β = -0.006, 95% CI -0.009 to -0.003), eosinophils (blood: β = -0.002, 95% CI -0.003 to -0.001; sputum: β = -0.023, 95% CI -0.035 to -0.011), sputum EDN (β = -0.032, 95% CI -0.049 to -0.014) and FeNO (β = -0.006, 95% CI -0.010 to -0.001). PRISM (n = 474) confirmed these associations. Higher sputum CXCL9 was associated with reduced remission in anti-IL-4Rα-treated patients with asthma duration ≥ 20 years (β = -1.73, 95% CI -3.180 to -0.276). CONCLUSION: Longer asthma duration was associated with elevated airway non-T2 inflammation and reduced systemic and airway T2 inflammation. This highlights the importance of airway bio
-
Journal articleTran XN, Lee Y-L, Chang L-T, et al., 2026, , Pediatr Res
The prevalence of pediatric asthma exacerbations (AEs) has risen alongside climate change, yet how climate change modifies these exposures to raise pediatric AEs remains unclear. This review synthesizes epidemiological and mechanistic evidence on the contribution of air pollution, temperature, and relative humidity (RH) to pediatric AEs under climate change, drawing on a narrative search of PubMed and Web of Science (2000-2025) prioritizing systematic reviews, epidemiological studies, and climate-attribution/modeling studies. Climate change intensifies environmental drivers of AEs, to which children's higher ventilation and reactive airways heighten susceptibility. Air pollutants trigger oxidative stress, epithelial injury, and type 2 inflammation, while rising temperatures and extreme weather increase oxidative stress, C-fiber activation, and systemic inflammation. Climate-driven shifts in RH cause airway dehydration at low humidity and impaired mucus clearance at high humidity. Lengthening pollen seasons, transitional-weather viral circulation, and more frequent wildfires, hurricanes, floods, and dust storms further increase exacerbation risk. Climate-driven environmental changes contribute to pediatric AEs, though attribution is quantified for only selected exposures. Prevention strategies, including heat- and air-quality warning systems, environmental adaptation, and equity-focused targeting of high-risk populations, are needed. IMPACT: Climate change amplifies environmental triggers of pediatric asthma exacerbations, a burden concentrated among disadvantaged children by socioeconomic and structural disparities. Children's physiological vulnerability heightens their sensitivity to these triggers. Closing pediatric-specific attribution gaps and integrating climate-adaptation strategies into asthma care could reduce this burden.
-
Journal articleKc S, Hopkinson NS, Neves AL, et al., 2026, , Online J Public Health Inform, Vol: 18, ISSN: 1947-2579
BACKGROUND: Patient portals are increasingly used to support self-management and facilitate care coordination in people with chronic diseases. Although some asthma quality-of-care gains and modest chronic obstructive pulmonary disease (COPD) improvements have been reported in wider digital health studies, a comprehensive review of patient portal-specific evidence is lacking. OBJECTIVE: This study aimed to systematically synthesize evidence on the impacts of patient portals on adult asthma and COPD outcomes across 6 quality-of-care domains (effectiveness, patient-centeredness, equity, efficiency, safety, and timeliness). METHODS: We searched 5 databases (MEDLINE/PubMed, Embase, PsycINFO, CINAHL, and Google Scholar) for quantitative evaluations published up to March 2026 (CRD42022316044). The Newcastle-Ottawa Scale and Cochrane Risk of Bias-2 tool were used for quality assessments, and certainty of evidence was evaluated using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. Findings were narratively synthesized using the SWiM (Synthesis Without Meta-analysis) framework. RESULTS: We identified 4038 records, and 16 papers published between 2007 and 2024 met the inclusion criteria (asthma=13, COPD=2, both=1). Three were randomized controlled trials, all rated high risk of bias. Of the other studies, 5 had low risk, 6 had moderate risk, and 2 had high risk of bias. Effectiveness and patient-centeredness were most frequently reported, with 12 papers each. Eight papers were on equity, 5 each on efficiency and safety, and 4 on timeliness. In asthma, modest disease control improvements were reported in 27.8% (42/151) of participants using patient portals with home visit support versus portal use alone (35/150, 23.3%). In COPD, one large, interrupted time series study (N=909,724) reported post-implementation reductions in hospitalizations (slope change from 1.33 to -4.38 per 10,000 patients per month; P<.001) but no mortality benefit
-
Journal articleWang R, Chen Y, Liu X, et al., 2026, , Chin Med J (Engl), Vol: 139, Pages: 2392-2408
Chronic lung diseases, such as chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis, obstructive sleep apnea, asthma, bronchiectasis, and lung cancer, are intricately linked to the aging process. These diseases are characterized by a high prevalence rate and a paucity of effective treatment options. Emerging evidence highlights the critical role of extracellular vesicles (EVs) in the pathogenesis and progression of these diseases. EVs, released by senescent cells, mediate intercellular communication and modulate immune responses through their cargo of microRNAs, proteins, and other molecules. These vesicles contribute to disease progression by promoting inflammation, fibrosis, tissue remodeling, and cellular senescence. Specifically, certain microRNAs, such as miR-21, miR-34a, and miR-570-3p, along with several proteins in EVs, have been identified as key factors influencing these processes. Additionally, EVs play significant roles in immune regulation and have potential anti-inflammatory effects, making them promising candidates for therapeutic applications. Recent advances in the use of EVs as therapeutic agents, including their application in nanotechnology for targeted drug delivery, have demonstrated potential in reducing inflammation, modulating immune responses, and enhancing tissue repair. Understanding the role of EVs in these diseases offers insights into potential therapeutic targets to mitigate disease progression and improve patient outcomes. Future research should focus on standardizing EV isolation and characterization methods, verifying the safety and efficacy of EV-based therapies in clinical trials, and elucidating the complex biological mechanisms of EVs in aging and disease.
-
Journal articleSaralaya D, Mustapa MN, Ferreira J, et al., 2026, , Eur Respir J
BACKGROUND: Neutrophilic inflammation is a common feature of chronic obstructive pulmonary disease (COPD). Mitiperstat, an inhibitor of myeloperoxidase expressed in neutrophils, may have potential as a COPD treatment. METHODS: This phase 2a, randomised, placebo-controlled, double-blind, parallel-arm, event-driven trial evaluated the efficacy and safety of mitiperstat 5 mg daily up to 24 weeks (NCT05492877). Adults (40-80 years) with moderate-to-severe COPD, at high risk of exacerbation, and receiving dual or triple inhaled therapy were included. The primary endpoint was time to first composite endpoint for exacerbations in COPD (COPDCompEx) event. Secondary endpoints included time to first moderate-to-severe COPD exacerbation, post-bronchodilator forced expiratory volume in 1 s (post-BD FEV1) change at Week 12, respiratory symptoms, disease impact and safety. RESULTS: Overall, 381 participants (mean age, 66.0 years; 39.6% female) were randomised to mitiperstat (n=189) or placebo (n=192). In total, 125 (66.1%) mitiperstat-treated versus 125 (65.1%) placebo-treated participants experienced COPDCompEx events over 24 weeks. There was no improvement in time to first COPDCompEx event (hazard ratio [HR] 1.07 [90% confidence interval (CI) 0.87, 1.32]; p=0.599) or time to first moderate-to-severe COPD exacerbation (HR 1.23 [90% CI 0.88, 1.73]) with mitiperstat versus placebo. Improvements in post-BD FEV1, respiratory symptoms or disease impact were not seen with mitiperstat. A similar proportion of participants in both groups reported adverse events; seven mitiperstat-treated participants and two placebo-treated participants had pneumonia during the study. CONCLUSION: These results indicate that the risks outweigh the benefits of mitiperstat as a treatment for COPD.
-
Journal articleMakrufardi F, Chuang H-C, Lin Y-C, et al., 2026, , World Allergy Organ J, Vol: 19, ISSN: 1939-4551
OBJECTIVE: We aimed to investigate the associations of the daily mean and short-term variation in ambient relative humidity (RH), temperature, and fine particulate matter (PM2.5) with asthma treatment steps. METHODS: We consecutively recruited 288 newly diagnosed adult patients with asthma and followed them for at least 6 months according to the Global Initiative for Asthma (GINA) strategy. Odds ratios (ORs) for higher GINA treatment steps required to achieve asthma control were estimated using logistic regression. We also conducted exposure-response analyses to explore potentially nonlinear relationships between environmental exposure and asthma treatment step across seasons. RESULTS: A 1% increase in the 1-day RH difference and a 1-μg/m3 increase in the 7-day PM2.5 difference were associated with 1.054-fold and 1.052-fold higher odds of step 4 treatment, respectively. A 1% increase in the 1-day RH difference and a 1-μg/m3 increase in the 7-day PM2.5 difference were associated with 1.047-fold and 1.056-fold higher odds of medium-dose inhaled corticosteroids plus long-acting beta-agonists (ICS + LABA), respectively. A 1% increase in the 7-day RH mean and a 1-μg/m3 increase in the 30-day PM2.5 difference were associated with 1.075-fold and 1.205-fold higher odds of triple inhaler therapy and biologics use, respectively. Exposure-response analyses suggested noticeable seasonal patterns for temperature and RH in relation to asthma treatment strategy. CONCLUSIONS: Our exploratory and hypothesis-generating findings showed that greater short-term variation in RH and PM2.5 was associated with higher treatment intensity in adult asthma, particularly the use of medium-dose ICS + LABA and biologics. Higher RH mean was also associated with triple inhaler therapy. These associations were more evident during the cold season. Multicenter validation studies in larger population studies are warranted.
-
Journal articleBaylis S, Hopkinson NS, Feliu A, et al., 2026, , Eur Respir J, Vol: 68
-
Journal articleChae W, An J, Lee W, et al., 2026, , Clin Exp Allergy, Vol: 56, Pages: 935-938
Plasma 1‐methylnicotinamide is elevated in dupilumab responders, outperforming conventional type‐2 biomarkers. Combining 1‐methylnicotinamide with FeNO achieves the highest predictive accuracy for dupilumab treatment response.
This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.