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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.
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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) 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.
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Journal articleKinoshita R, Sathyapala A, Polkey MI, 2026, , Thorax, Vol: 81, Pages: 638-641
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Journal articleKocks JWH, Harrison T, Bell JP, et al., 2026, , Pulm Ther
INTRODUCTION: Many essential inhaled medicines recommended in guidelines are delivered to the lung via pressurized metered-dose inhalers (pMDIs). Global environmental legislation will lead to phasing out of hydrofluoroalkane propellants currently used in pMDIs, owing to their global warming potential (GWP). Furthermore, the European Chemicals Agency is reviewing proposed legislation to ban per- and polyfluoroalkyl substances (PFAS) on the basis of chemical structure, which could also impact pMDI availability. Here, we estimated pMDI use as a proportion of all inhaler use in 60 countries, spanning six geographical regions, to understand the relevance of any pMDI restrictions to patients and prescribers. METHODS: pMDI use as a percentage of total inhaler use during 2022 was calculated by country and geographical region using inhaler sales data (a surrogate of use) from the IQVIA Quarterly MIDAS database; inhaler use for the 10-year period from 2013 to 2022 was also evaluated for these regions. Data were compared by individual inhalations. The total patient population living with asthma and/or chronic lower respiratory disease was calculated on the basis of Eurostat (the statistical office of the European Union [EU]) 2019 data and available disease prevalence statistics. Maintenance pMDI utilization was estimated by adjusting for ratio of maintenance pMDI use to total inhaler use. RESULTS: Across all countries analyzed, pMDIs accounted for the largest proportion of inhaler use in 2022 (77.3%). In 51 out of 55 countries with available country-level data, pMDIs represented > 50% of total inhaler use. After adjusting for pMDI usage, an estimated 8.1 million EU patients received a maintenance pMDI in 2022, with the greatest proportion in Germany and France. CONCLUSIONS: pMDIs are vital inhalers for most patients in Europe and around the world. While transitioning to near-zero or low-GWP inhalers, it is essential to avoid unintended consequences from the pr
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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.
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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.
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Journal articleWilliams PJ, Hopkinson NS, 2026, , Thorax
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Journal articleBloom CI, 2026, , Thorax
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Journal articleMacLeod MA, Knott KD, Nicol ED, et al., 2026, , Am J Respir Crit Care Med, Vol: 212, Pages: 1368-1369
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Journal articlePortacci A, Ventura L, Menzella F, et al., 2026, , Eur Respir J
BACKGROUND: Obesity is associated with poorer asthma outcomes and an increased risk of exacerbations, but the underlying mechanisms remain incompletely understood. Small airway dysfunction (SAD) may represent a key mechanistic link between excess body weight and adverse asthma outcomes. METHODS: In this multicenter observational study, adult patients with asthma underwent clinical characterization, spirometry and impulse oscillometry (IOS). SAD was defined using a composite criterion based on peripheral airway resistance (R5-20), reactance area (AX) and the ratio of peripheral to total airway resistance (R5-20)/R5. Associations between body mass index (BMI), SAD and severe asthma exacerbations were assessed using multivariable regression models. Non-linear relationships were explored using generalized additive models and mediation analyses quantified the contribution of SAD to the obesity-exacerbation association. FINDINGS: Among 1169 patients, IOS-defined SAD was significantly more prevalent in individuals with BMI≥30kg·m-2. Increasing BMI was associated with worse oscillometric parameters (p<0.0001), following a non-linear pattern with steeper deterioration beyond BMI values of approximately 28-30kg·m-2. SAD was independently associated with obesity (adjusted OR 2.11, 95% CI 1.56-2.86) and with severe asthma exacerbations in the previous year (adjusted OR 2.01, 95% CI 1.53-2.65, both p<0.0001). Mediation analyses showed that SAD accounted for 26%-41% of the association between obesity and exacerbation risk (p=0.004 and 0.03). Spirometric indices provided limited additional information. INTERPRETATION: Oscillometry-defined small airways dysfunction (SAD) represents a non-linear functional trait underlying the association between obesity and severe asthma exacerbations, supporting its clinical relevance in obese patients with asthma and identifying SAD as a potential treatable trait.
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Journal articleSathyapala A, Parthasarathy S, 2026, , American Journal of Respiratory and Critical Care Medicine, ISSN: 1073-449X
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Journal articleShih Y-S, Han C-L, Lee YL, et al., 2026, , Expert Rev Respir Med, Pages: 1-12
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.
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Journal articleSadatsafavi M, Miravitlles M, Quint JK, et al., 2026, , Thorax, Vol: 81, Pages: 541-547
OBJECTIVES: In patients with chronic obstructive pulmonary disease (COPD), severe exacerbations (ECOPDs) impose significant morbidity and mortality. Current guidelines emphasise using ECOPD history to inform preventive treatments but offer limited guidance for risk stratification for the first severe ECOPD. METHODS: We developed and validated PRECISE-X using a cohort of newly diagnosed COPD patients from the UK's Clinical Practice Research Datalink (2004-2022), to predict first severe ECOPD over 5 years (primary outcome) and 12 months (secondary outcome). Predictors were selected via clinical expertise and data-driven methods. Internal-external cross-validation was performed across practice regions to evaluate the model's out-of-sample performance in terms of discrimination (c-statistic), calibration and net benefit. RESULTS: The study included 2 19 015 patients (mean age 66.0; 42.4% female). Observed risk of first severe ECOPD was 29.5% at 5 years (4.2% at 1 year). The final model included four mandatory predictors (sex, age, Medical Research Council dyspnoea score and forced expiratory volume in 1 second) and 28 optional predictors. In internal-external cross-validation, the average out-of-sample c-statistic was 0.836 (95% CI 0.827 to 0.846) for 5-year prediction and 0.756 (95% CI 0.746 to 0.766) for 1-year prediction. Calibration across regions was robust, and the model showed positive NB across a wide range of risk thresholds. In a secondary validation assessment among those with available spirometry data with confirmed airflow obstruction, the model was well calibrated and had only a modest decline in discriminatory performance. CONCLUSIONS: PRECISE-X accurately predicts the first severe COPD exacerbation using routine clinical data, supporting earlier risk stratification and proactive disease management.
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Journal articleMakrufardi F, Chuang H-C, Lin Y-C, et al., 2026, , Eur J Pediatr, Vol: 185
To estimate the risk projection of temperature on pediatric asthma severity and hospitalization under four Shared Socioeconomic Pathways (SSPs) possible future climate scenarios using the Intergovernmental Panel on Climate Change (IPCC) model. A retrospective study was conducted involving 102,160 pediatric asthma patients from the Taipei Medical University Clinical Research Database (TMUCRD). We utilized global climate model (GCM) outputs to project future temperature for each subject from optimistic (SSP126) to pessimistic (SSP585) projections. A multinomial logistic regression was used to examine the odds ratio of pediatric asthma severity and hospitalization. A 1 °C increase in 1-year, 5-year, and 10-year average temperatures was associated with 1.004-fold (95% CI: 1.003-1.005) and 1.332-fold (95% CI: 1.327-1.338), 1.004-fold (95% CI: 1.002-1.005) and 1.303-fold (95% CI: 1.298-1.308), and 1.005-fold (95% CI: 1.004-1.006) and 1.282-fold (95% CI: 1.278-1.287) increase in the OR for mild persistent and hospitalization of pediatric asthma. We observed a non-linear association between temperature under SSP126, SSP245, SSP370 and SSP585 with moderate persistent pediatric asthma and pediatric asthma hospitalization, with the highest OR increases observed in 2033 at 33.4% and 32.3%, 27.6% and 32.3%, 29.1% and 32.4%, and 27.2% and 32.3%, respectively. Conclusion: Projected future temperature changes as a result of climate change may be associated with a possible increase in pediatric asthma severity and hospitalization in the coming years, with an expected increase of 8.0% and 2.5% per 1 °C increase, respectively. Pediatric asthma patients may be more susceptible to poorer outcomes under climate change in the future. What is Known: • Rising temperatures have been linked to increased asthma severity and hospitalization. • Climate change worsening pediatric asthma outcomes and increasing the healthcare burden. What is New: &bu
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Journal articlePhilip KEJ, Owles H, McVey S, et al., 2026, , The Lancet Digital Health, Pages: 10098-10098, ISSN: 2589-7500
BackgroundPost-COVID-19 condition (also known as long COVID) breathlessness is a common, complex, and frequently debilitating problem for which few evidence-based interventions exist. A previous randomised trial found that participation in an online 6-week breathing and wellbeing programme (ENO Breathe), using singing techniques, was associated with improvements in health-related quality of life (HRQOL) and breathlessness. We aimed to assess the impact of this intervention outside a trial setting.MethodsIn this cohort study, participants were referred from 51 UK-based National Health Service (NHS) long COVID clinics, where they had been diagnosed with breathlessness due to long COVID. The eligibility criteria of ENO Breathe were age 18 years or older, having long COVID with associated breathlessness, diagnosis and referral from a specialist collaborating NHS long COVID clinic, and access and ability to engage with the online programme. We compared baseline and post-intervention data to assess the effect of the ENO Breathe programme on HRQOL assessed using the RAND-36 Mental and Physical Health Composite (MHC and PHC) primary outcome, with an estimated minimally clinically important difference of 3; breathlessness (assessed using Dyspnoea-12 scores and visual analogue scales [VAS] for breathlessness at rest, walking, using stairs, and running); anxiety (assessed using the Generalised Anxiety Disorder-7 questionnaire [GAD-7]); and respiratory symptoms (assessed using the COPD Assessment Test [CAT]).Findings1413 programme participants were included in this analysis (mean age 49 years [SD 11·9], BMI 28 kg/m2 [7·2]). 1130 (80%) participants were female, 273 (19%) were male, and ten (1%) did not disclose their gender. 1165 (82%) participants were White, 87 (6%) were Asian, 47 (3%) were Black, 48 (3%) were of mixed or multiple ethnic backgrounds, 31 (2%) reported their ethnicity or race as other (ie, not one of the categories specified), and 35 (2%) did not d
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Journal articleChae W, An J, Lee W, et al., 2026, , Clin Exp Allergy
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Journal articleLai K, Xu T, Chen P, et al., 2026, , ERJ Open Res, Vol: 12, ISSN: 2312-0541
BACKGROUND: There is limited information available on patients with asthma in hospitals in China. We investigated their clinical and phenotypic characteristics and management. METHODS: The China Asthma Data Registry Project (CHART) study is a multicentre, hospital-based, prospective, observational study in which patients were recruited from outpatient clinics. This analysis used baseline cross-sectional data from patients with asthma (≥12years) enrolled at 58 tertiary hospitals in China between 25 March 2018 and 11 July 2019. RESULTS: A total of 20 683 patients with asthma (56.2% female, 15.0% patients with active tobacco use) were enrolled. Overall, 22.8% had uncontrolled asthma, 39.5% had partially controlled asthma. Furthermore, 45.3% experienced ≥1 exacerbation annually, including 31.7% who required hospitalisation, with only 21.4% having previously used inhaled corticosteroids (ICSs) in the past year. Cough (80.0%) was the most common symptom, followed by wheezing (70.7%), with 14.6% having cough-predominant asthma and 11.4% having cough-variant asthma. Multivariate logistic regression revealed that cough severity independently predicted poor control, irrespective of airflow limitation or inflammatory status. The association was stronger in ICS users than in nonusers across all cough severity metrics: a visual analogue scale (VAS) score ≥40 (aOR 3.88-5.47 versus 2.49-2.94), a cough evaluation test (CET) score ≥12 (aOR 11.15-20.91 versus 3.97-5.55), and a Leicester Cough Questionnaire (LCQ) score <15 (aOR 6.15-13.66 versus 2.45-3.18). CONCLUSIONS: We found significant suboptimal control, a high prevalence of cough-related phenotypes, frequent exacerbations and hospital admissions in patients with asthma attending hospitals. This underscores the need to prioritise the assessment and treatment of cough in asthma.
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Journal articleDinh C-T, Lee Y-L, Chang L-T, et al., 2026, , Expert Rev Hematol, Vol: 19, Pages: 529-538
INTRODUCTION: Air pollution and household fuel use may impair hematologic health through inflammation and oxidative stress. We synthesized evidence on associations of ambient/household air pollution with anemia risk and erythrocyte indices. METHODS: We searched PubMed, Embase, and Web of Science (inception-27 September 2025). Two reviewers independently screened and extracted data, and assessed risk of bias using Joanna Briggs Institute checklists. Random-effects meta-analyses pooled risk ratios (RRs) per 10 µg/m3 for particulate matter with aerodynamic diameter ≤10 µm (PM10), ≤2.5 µm (PM2.5), and nitrogen dioxide (NO2), and by household fuel type. RESULTS: Thirty-six studies were included. Each 10 µg/m3 increase in PM2.5 and NO2 was associated with higher anemia risk (RR 1.200, 95% CI 1.041-1.384, I2 98.2%; RR 1.127, 95% CI 1.025-1.241, I2 98.0%). Solid and biomass fuel increased anemia risk (RR 1.143, 95% CI 1.027-1.274, I2 82.9%; RR 1.271, 95% CI 1.050-1.539, I2 91.7%). PM10 was associated with lower hemoglobin (0.074 g/dL, 95% CI -0.124 to -0.023, I2 90.7%). Effects were generally stronger in males and in low- and middle-income countries. CONCLUSIONS: Ambient and household air pollution are associated with increased anemia risk and reductions in hemoglobin; high heterogeneity and observational designs limit causal inference.
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Journal articleToumpanakis D, Usmani OS, Wells AU, et al., 2026, , Chest, Vol: 169
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Journal articleFu H, Sun P, Yuan X, et al., 2026, , Allergy, Vol: 81, Pages: 1522-1535
BACKGROUND: IL-25 is a key epithelial-derived alarmin associated with T2-high asthma, yet its downstream mechanisms remain poorly defined. CD207 (Langerin)+ dendritic cells (DCs) are localized at the airway epithelial interface. However, whether these cells respond to epithelial-derived cytokines and contribute to the Th2 immune response in asthma remains unclear. METHODS: Single-cell RNA-seq from healthy human lungs was analyzed to define the transcriptomic features of CD207+ DCs. Their function was validated in a house dust mite (HDM)-induced asthma model using Cd207-/- mice. Flow cytometry was performed on lung and mediastinal lymph nodes. DC-T cell co-cultures were used to assess Th2 polarization. Epithelial-DC interactions were evaluated using transwell co-culture with ALI-differentiated tracheal epithelial cells. Clinical relevance was examined in airway samples from asthma patients in the U-BIOPRED cohort. RESULTS: CD207+ DCs were enriched in intraepithelial compartments and exhibited increased MHC-II and Claudin-1 expression. In asthma, their abundance correlated with T2 signatures and Th2 markers (CRTH2, ST2). CD207 deletion reduced HDM uptake, Th2 cytokines, airway inflammation, and Th2 differentiation. IL-25 induced CD207+ DCs and enhanced their Th2-polarizing capacity in vitro. An IL-25-CD207 co-expression score correlated with IL-4/IL-5/IL-13 levels and was higher in steroid-naïve patients with severe asthma. CONCLUSION: Our study identifies CD207+ DCs as epithelial-associated antigen-presenting cells that bridge IL-25 signaling and Th2 polarization in allergic asthma. Targeting the IL-25-CD207 axis may offer therapeutic opportunities for T2-high asthma.
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