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 articleShen J, Chaudhuri R, Bicknell S, et al., 2026, , Allergy
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 articleBloom CI, Foer D, Aroda VR, et al., 2026, , European Respiratory Journal, ISSN: 0903-1936
-
Journal articleEvison M, Naylor R, Malcolm R, et al., 2026, , Thorax, Vol: 81, Pages: 758-765
INTRODUCTION: Integrating smoking cessation supports into lung cancer screening can improve abstinence rates. However, healthcare decision-makers need evidence of cost-effectiveness to understand the cost/benefit of adopting this approach. METHODS: To evaluate the cost-effectiveness of smoking cessation interventions, and service delivery, we used a cohort-based Markov model, adapted from previous National Institute for Health and Care Excellence (NICE) guidelines on smoking cessation. This uses long-term epidemiological data to capture the prevalence of the smoking-related illnesses, updated through targeted literature searches as required from the core NICE model, with costs extracted from publicly recognised UK sources. RESULTS: All smoking cessation interventions appeared cost-effective at a threshold of £20 000 per quality-adjusted life year, compared with no intervention or behavioural support alone. Offering immediate smoking cessation as part of lung cancer screening appointments, compared with usual care (onward referral to stop smoking services), was also estimated to be cost-effective with a net monetary benefit of £2198 per person, and a saving of between £34 and £79 per person in reduced workplace absenteeism among working age attendees. Estimated healthcare cost savings were more than four times greater in the most deprived quintile compared with the least deprived, alongside a fivefold increase in quality adjusted life years accrued. CONCLUSIONS: Smoking cessation interventions within lung cancer screening are cost-effective and should be integrated, so that treatment is initiated during screening visits. This is likely to reduce overall costs to the health service, and wider integrated care systems, improve quality and length of life, and may lessen health inequalities.
-
Journal articleChung KF, 2026, , ERJ Open Research, Pages: 00951-2026
-
Journal articleYang F, Seo S, Hasegawa T, et al., 2026, , Allergy
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 articleWang M, Hu H, Wang K, et al., 2026, , Allergy
BACKGROUND: Mitochondrial fatty acid oxidation through carnitine palmitoyltransferase-1A (CPT1A) leads to ATP generation. We examined its role in regulating permeability and mitochondrial metabolic homeostasis of airway epithelial cells in asthma. METHODS: Primary nasal epithelial cells (NECs) from healthy controls and severe asthma (SA) patients in air-liquid interface (ALI) were exposed to CPT1A siRNA/CPT1A overexpression lentiviral/L-carnitine (LCA). Epithelial TEER and FITC-dextran transport were measured. Bronchial biopsies from healthy and SA subjects and house dust mite (HDM) asthma mouse model were also studied. RESULTS: In NECs-ALI and in bronchial epithelial cells (BECs) from bronchial biopsies of SA, CPT1A expression was reduced compared to healthy controls. Knock-down of CPT1A in healthy NECs reduced expression of Occludin and E-cadherin and impaired epithelial barrier integrity (EBI), while upregulation of CPT1A with CPT1A overexpression lentiviral/LCA in SA-NECs increased the barrier proteins with improved EBI. CPT1A knockdown in healthy BECs increased release of mtROS, with mitochondrial disruption and activation of ERK1/2-NF-κB signaling pathway. These were aggravated with HDM exposure but N-acetyl-cysteine and MitoTempo reduced p-ERK1/2 and p-P65 activation, as well as EBI with CPT1A knockdown and HDM. In the mouse model, there was decreased airway epithelial CPT1A protein expression, associated with reduced airway hyperreactivity and inflammation, and in Occludin and ZO-1 expression, effects partly reversed by LCA, with restoration of mitochondrial integrity and EBI. CONCLUSION: CPT1A maintains epithelial barrier function through restoration of mitochondrial function in asthmatic airway epithelial cells. Restoration of deficient epithelial CPT1A of SA may represent a new treatment approach.
-
Journal articleKlimek L, Mullol J, Reitsma S, et al., 2026, , Allergy, Vol: 81, Pages: 2568-2570
-
Journal articleCecchi L, Annesi-Maesano I, Biagioni B, et al., 2026, , Allergy
Developed using the GRADE methodology, these EAACI guidelines provide evidence-based recommendations on the effectiveness of pollen reduction/avoidance strategies for allergic rhinitis (AR) and asthma, the utility of biomarkers for monitoring pollen-induced asthma and the efficiency of mitigation measures and of public health strategies. Systematic and narrative reviews and health economic analysis support the recommendations. According to GRADE, the certainty of evidence was moderate to very low, therefore conditional recommendations are provided to guide healthcare professionals, patients, and policymakers in developing personalized, preventive, and scalable interventions. Reducing/avoiding exposure to pollen should be recommended to reduce the risk of severe asthma exacerbations. Lung function decrease and exhaled nitric oxide increase may be predictive for pollen-induced asthma exacerbations. Real-time pollen monitoring and pollen concentration-based forecast may be recommended for managing pollen-induced AR and/or asthma. Pollutant information should be included in pollen information systems. Combined forecast (weather, pollen, pollutants) and warning systems might reduce the impact of thunderstorm asthma (TA). Emergency department/asthma-related services should be strengthened during pollen season and in TA. Personalized frameworks covering the types and allergenic potential of pollen, the coaggressors and the vulnerability of each patient are needed in daily practice. The fundamental role of prevention should be further prioritized.
-
Journal articleAlzahrani A, Alghamdi S, Majrshi M, et al., 2026, , Chronic Respiratory Disease, Vol: 23, ISSN: 1479-9723
IntroductionEffective airway clearance is crucial in COPD management, and oscillatory positive expiratory pressure (OPEP) devices are a potential adjunct therapy for this. However, their clinical efficacy remains uncertain due to limited trial data.AimTo update our previous (2020) systematic review investigating the use of OPEP devices to augment sputum clearance in COPD.MethodsRandomised Clinical Trails s evaluating OPEP devices in COPD were identified from PubMed, CINAHL, Medline, Cochrane, and Embase (2020–2024). Outcomes included lung function, exercise capacity, exacerbations, and health-related quality of life (HRQoL), with pooled estimates calculated using random-effects models.ResultsTwelve trials (741 participants) were included. OPEP devices significantly reduced exacerbations (Odds Ratio: 0.39) and improved exercise capacity (+49 m at 6MWD). Small improvements were observed in FVC%, while HRQoL changes were not statistically significant. Accumulating evidence suggests benefits for sputum clearance and reduced antibiotic use. Devices were generally well accepted and safe.ConclusionOPEP devices appear to be safe and may reduce exacerbations, improve functional exercise capacity, and support sputum clearance in COPD.
-
Journal articleBaraldi F, Mah JSY, Almuhanna A, et al., 2026, , Am J Respir Crit Care Med
-
Journal articleSong W-J, Kermani NZ, Versi A, et al., 2026, , Allergy
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 articleHopkinson N, 2026,
Effect of Dietary Nitrate Supplementation on Exercise Performance in Hypoxic IPF (EDEN-OX3): a double-blind, placebo-controlled, randomised crossover study
, Thorax, ISSN: 0040-6376Dietary nitrate (NO鈧冣伝) supplementation has been shown to improve vascular function and exercise capacity in COPD and in pulmonary hypertension. In a double-blind, placebo-controlled cross-over study in 20 patients with idiopathic pulmonary fibrosis who desaturated on exercise, endurance shuttle walk test improved by a median[IQR] difference of 31s [–9.5 to 100.0;(p=0.043], following a single dose of 140mls nitrate rich beetroot juice, as did brachial artery flow mediated dilatation; +4.25% (95% CI: –0.71 to 8.45; p=0.036), compared to following placebo nitrate depleted placebo juice. Longer-term studies are needed to see if these acute effects translate into sustained benefit.
-
Journal articleKinoshita R, Sathyapala A, Polkey MI, 2026, , Thorax, Vol: 81, Pages: 638-641
-
Journal articleWilliams PJ, Hopkinson NS, 2026, , Thorax, Vol: 81, Pages: 635-637
-
Journal articleHopkinson NS, 2026, , BMJ, Vol: 393
-
Journal articlePhilip K, Buttery S, Hopkinson N, et al., 2026,
The relationship of breathlessness with social isolation and loneliness: a nationally representative cohort study of older adults in England
, BMJ Public Health, ISSN: 2753-4294Introduction Breathlessness is a common and distressing symptom impacting quality of life and limiting activities of daily living. Social isolation and loneliness are associated with increased morbidity and mortality, being problems in themselves and risk factors for poor health. Qualitive studies indicate breathlessness impacts social health, however quantitative evaluation is limited. We aimed to assess the relationship of breathlessness with social isolation and loneliness in adults. Methods Using a nationally representative sample of older adults aged ≥50years from the English Longitudinal Study of Ageing (N=6,623). The sample had 44% males, mean age of 70years (SD=10). We examined associations of baseline breathlessness (mMRC breathlessness scale) with loneliness (3-item UCLA loneliness scale) and social isolation (low social contact, low community participation, living alone), at baseline, and follow-up at 4- and 8-years later, using regression models adjusted for confounders. Results At baseline, breathlessness was associated with higher levels of loneliness (coef.=0.161, 95%CI 0.1130.209), and social isolation, including low social contact (coef.=0.094, 95%CI 0.028-0.159), low community participation (coef.=0.169, 95%CI 0.117-0.221), and living alone (OR 1.089, 95%CI 1.0261.157). Longitudinally, breathlessness was associated increasing loneliness and reducing social contact and community participation at 4 and 8-year follow-up. Breathlessness was not associated with change in living alone. Findings were independent of identified confounders. Conclusions Breathlessness is related to increasing social isolation and loneliness, potentially due to limiting the amount and quality of social interactions. These findings suggest important psychosocial impacts of breathlessness requiring holistic management strategies.
-
Journal articleButtery SC, Barraclough R, Batchelor TJP, et al., 2026, , Thorax, ISSN: 0040-6376
Lung volume reduction procedures are an established evidence-based aspect of chronic obstructive pulmonary disease (COPD) care. We conducted a research prioritisation exercise involving people with COPD and healthcare professionals across a range of disciplines, to identify a clear set of 10 questions to guide the development of research proposals in this area. Priorities were identified using an iterative approach based on the James Lind Alliance methodology. The final set of 10 priorities address the identification, assessment and optimisation of patients with COPD prior to any procedure, how lung volume reduction procedures are conducted and how care after the procedure has taken place should be organised.
-
Journal articleBloom CI, 2026, , Thorax
-
Journal articleMacLeod MA, Knott KD, Nicol ED, et al., 2026, , Am J Respir Crit Care Med, Vol: 212, Pages: 1368-1369
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.