Josa-Culleré A, Koch S, Rivas I
… +11 more, Gimeno-Santos E, Buekers J, Delgado-Ortiz L, Alcaraz V, Blanco I, Garcia-Olivé I, Rodríguez-Chiaradía D, Cirach M, Valentin A, Morawska L, Garcia-Aymerich J
OBJECTIVES: Walking activity can improve the prognosis of people with chronic obstructive pulmonary disease (COPD), but might worsen the harmful effects of pollution if practised in polluted environments. We aimed to det...OBJECTIVES: Walking activity can improve the prognosis of people with chronic obstructive pulmonary disease (COPD), but might worsen the harmful effects of pollution if practised in polluted environments. We aimed to determine the combined effect of walking activity and air pollution on daily respiratory symptoms in people with COPD. METHODS: This multicentre panel study assessed 105 people with COPD from Catalonia (Spain) over two 7 days periods. Daily walking activity (walking duration, step count) was measured via activity monitors. Daily air pollutant concentration (particulate matter with an aerodynamic diameter <2.5 µm (PM), black carbon (BC), nitrogen dioxide (NO)) was estimated by combining geolocation data with land use regression models. Dyspnoea, cough, expectoration and wheezing were recorded in diaries every evening (0-10 scale). We estimated the individual association of daily walking activity and air pollution and their interaction on symptoms using multivariable mixed-effects negative binomial models. RESULTS: Participants (20% female) were mean±SD 68±7 years old and had a forced expiratory volume in 1 s of 53±23% predicted. Walking duration was associated with higher levels of cough and expectoration. All pollutants were associated with higher cough and BC also with higher expectoration, dyspnoea and wheezing. After including an interaction term, more walking duration was associated with higher cough and expectoration only on days with high BC concentrations (p for interaction <0.05). No interaction was observed between walking duration and PM or NO. Results were similar for step count. CONCLUSIONS: Daily walking activity may worsen cough and expectoration in people with COPD when BC concentrations are high. Actions to ensure accessible low-traffic spaces to walk are paramount.
INTRODUCTION: Bronchopulmonary dysplasia (BPD) remains a major complication of preterm birth, with increasing incidence despite advances in neonatal care. Mesenchymal stromal cells (MSCs) and their extracellular vesicles...INTRODUCTION: Bronchopulmonary dysplasia (BPD) remains a major complication of preterm birth, with increasing incidence despite advances in neonatal care. Mesenchymal stromal cells (MSCs) and their extracellular vesicles (EVs) have emerged as potential therapeutic strategies targeting key pathogenic mechanisms of the disease. METHODS: This narrative review critically summarises preclinical and clinical evidence on MSC- and EV-based therapies for BPD, focusing on therapeutic effects, mechanisms of action and translational challenges. RESULTS: Preclinical studies consistently show that MSC-EVs improve lung structure and function, promoting alveolarisation and angiogenesis while reducing inflammation, fibrosis, oxidative stress and apoptosis. These effects translate into improved pulmonary outcomes in animal models. Early-phase clinical studies of MSCs demonstrate safety and feasibility but provide limited and inconsistent evidence of efficacy. Clinical data on EV-based therapies remain scarce, with ongoing trials. Significant heterogeneity in study design, EV characterisation, dosing and administration routes limits comparability and clinical translation. DISCUSSION: MSCs and their EVs represent promising therapeutic approaches for BPD; however, their clinical implementation is hindered by limited efficacy data and a lack of standardisation. Addressing these challenges through rigorous trial design, standardised manufacturing and characterisation and mechanistic understanding will be essential to advance EV-based therapies towards clinical application.
INTRODUCTION: Optimal management for patients with acute pulmonary embolism (PE) at elevated risk of decompensation remains unclear given the lack of predictors and the limitations of existing risk stratification tools....INTRODUCTION: Optimal management for patients with acute pulmonary embolism (PE) at elevated risk of decompensation remains unclear given the lack of predictors and the limitations of existing risk stratification tools. Thus, we aimed to evaluate the prognostic association between clinical variables and short-term mortality in patients with acute PE. METHODS: Medline and EMBASE were searched from inception through 19 May 2025. We included English-language studies that described adult inpatients with a confirmed acute PE and evaluated prognostic factors associated with short-term mortality. Two authors performed citation screening and data extraction. Only adjusted OR were included in the data synthesis. We performed pooling using a random-effects model and inverse variance weighting. Risk of bias was evaluated using the Quality in Prognosis Studies tool. We assessed certainty of evidence using the Grading of Recommendations, Assessment, Development, and Evaluations approach. RESULTS: We included 70 studies involving 1 446 190 participants in our review. Variables with a moderate or high certainty association with short-term mortality in acute PE include increasing age, an elevated Pulmonary Embolism Severity Index (PESI) Score, an abnormal simplified PESI Score, an elevated heart rate, a reduced systolic blood pressure, a lower oxygen saturation, a higher respiratory rate, active malignancy, heart failure, chronic lung disease, an elevated troponin, a larger right ventricle (RV) to left ventricle ratio and evidence of RV dysfunction. DISCUSSION: We identified multiple variables associated with early mortality in acute PE. Notably, we demonstrate that RV function, a marker omitted from commonly used risk stratification tools, represents an important prognostic variable that is supported by multiple society guidelines. REGISTRATION: We registered the protocol with the Open Science Framework (https://osf.io/9w2jg).
INTRODUCTION: Respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infection in infants globally. Newborns, especially those born prematurely, are at increased risk of severe RSV-relat...INTRODUCTION: Respiratory syncytial virus (RSV) is the leading cause of severe lower respiratory tract infection in infants globally. Newborns, especially those born prematurely, are at increased risk of severe RSV-related illness, yet the influence of age on early-life airway epithelium innate immune responses remains relatively understudied. METHODS: We established ex-vivo/in-vitro well-differentiated paediatric nasal epithelial cell (WD-PNEC) cultures derived from preterm and term infants at birth and again at 1-year old. Infection characteristics and innate immune responses were determined following in vitro RSV infection. RESULTS: RSV growth kinetics and cytopathology were similar irrespective of gestation or age. Secretion of interferon lambda-1 (IFN-λ1), CXCL10, CCL5 and CXCL8 was comparable between RSV-infected preterm-newborn and term-newborn WD-PNECs. Importantly, following RSV infection, secretion of RSV-induced IFN-λ1 (p<0.05) and CCL5 (p<0.01) and expression of the IFN-stimulated gene, ( (p<0.05) were significantly higher in 1 year- compared with newborn-derived WD-PNECs. Interestingly, secretion of the cell signalling cytokine pleiotrophin increased significantly with longer gestation (p<0.01) and older age (p<0.001). Differential gene expression analysis demonstrated 156 differentially expressed genes (DEGs) with age and revealed transcriptomic changes linked to gestation in newborns that persisted at 1 year. CONCLUSION: These findings indicate two major conclusions. First, we report transcriptomic differences in airway epithelial cell (AEC) development between term and preterm infants across the first year of life. Second, we demonstrate that RSV infection responses of AECs become more robust with age in early life. Further investigation of identified DEGs and differentially expressed chemokines/cytokines is warranted to clarify their role in increased susceptibility of very young infants to severe RSV disease as well as the significance of these factors in the emergence of wheezing phenotypes and long-term respiratory outcomes.
BACKGROUND: CFTR modulators have transformed cystic fibrosis (CF) treatment, but individual responses vary even among patients with identical genotypes. This underscores the need for predictive biomarkers to optimise th...BACKGROUND: CFTR modulators have transformed cystic fibrosis (CF) treatment, but individual responses vary even among patients with identical genotypes. This underscores the need for predictive biomarkers to optimise therapeutic selection. METHODS: We evaluated 24 paediatric patients homozygous for F508del-, assessing lung function (FEV1pp) and sweat chloride (SC) before and after CFTR modulator therapy. Whole-gene sequencing was utilised to identify and pharmacogene variants. Patient-derived human nasal epithelial cells (HNECs) were expanded and differentiated at the air-liquid interface to assess CFTR function via ion transport (ΔIsc). RESULTS: Clinical responses varied widely. Twelve participants changed modulators during the study. Sequencing identified 231 additional variants and pharmacogene polymorphisms, but none correlated with response variability. However, a significant linear relationship emerged between ΔIsc and FEV1pp improvement in patients with baseline FEV1pp<90 (R² = 0.652, p =0.001) and SC reduction (R² = 0.535, p=0.004). Receiver operating characteristic analysis demonstrated high predictive accuracy for SC reduction (area under the curve (AUC)=0.88) and combined FEV1pp/SC response in patients with baseline FEV1pp<90 (AUC=1.00). Exploratory analysis confirmed that ΔIsc predicts FEV1pp changes, modulated by baseline lung function and CFTR modulator type. CONCLUSION: Patient-derived differentiated HNEC cultures serve as a robust predictive tool for CFTR modulator response in paediatric CF patients. Their integration into clinical practice can enhance personalised treatment strategies, minimising ineffective therapy use and improving CF patient outcomes with precision medicine.
Anxiety and/or depression are common in fibrotic interstitial lung disease (ILD) but with unclear treatment implications. A prospective multicentre registry of 4009 patients was used to evaluate the association of depres...Anxiety and/or depression are common in fibrotic interstitial lung disease (ILD) but with unclear treatment implications. A prospective multicentre registry of 4009 patients was used to evaluate the association of depression and/or anxiety with clinical features and outcomes in fibrotic ILD.Anxiety and/or depression was associated with female sex and worse dyspnoea and cough but not lung function or ILD medication intolerance. Having anxiety and/or depression was associated with greater odds of patients declining referral for lung transplant assessment.Patients with anxiety and/or depression experience worse ILD symptoms and are more likely to decline referral for lung transplant assessment.
Tate M, Roche JJ, Tsim S
… +39 more, McGlinchey N, Ferguson K, Reid P, Short P, Chetty M, Ali C, O'Rourke N, MacGregor C, MacRae C, McNaughton L, Bloomfield R, Petrie T, Smyth S, Latham J, Hunter L, Bilancia R, Kirk A, Dick C, Roberts F, MacDuff E, Slavin J, Pitchamuthu H, Cowell GW, Sheridan S, Gronski M, Peng L, Thomson L, Noble C, Maguire J, Kelly L, Sage E, Thomson F, Alluri R, MacKenzie J, Liddicoat H, Darlison L, Smith E, Morton A, Blyth KG
INTRODUCTION: Equitable delivery of high-quality care is challenging in mesothelioma. Previous UK audits report variable practice and outcomes. The Scottish Mesothelioma Network was launched in April 2019, funding lead c...INTRODUCTION: Equitable delivery of high-quality care is challenging in mesothelioma. Previous UK audits report variable practice and outcomes. The Scottish Mesothelioma Network was launched in April 2019, funding lead clinicians and clinical nurse specialists, a weekly national multidisciplinary team meeting and service improvement driven by quality performance indicators. We report outcomes from an embedded impact assessment. RESEARCH DESIGN AND METHODS: A multicentre ambispective cohort study was performed, including all cases diagnosed from April 2017 to April 2022. Baseline data, treatment and survival outcomes were collected prospectively in all network cases (April 2019 to April 2022) and West of Scotland (WoS) pre-network cases (April 2017 to March 2019). Data were retrieved retrospectively for pre-network non-WoS cases via cancer networks, supplemented by Public Health Scotland registry data. Overall survival (OS) was compared between pre-network and network cohorts using restricted mean survival time (RMST). RMST differences were integrated with baseline features and treatment utilisation, including ipilimumab-nivolumab and surgery. Treatment effects were modelled by propensity score matching. RESULTS: 659 consecutive patients were included (pre-network n=273; network n=386). Cohort demographics were well-balanced. In the network era, data quality improved and diagnostic pathways were not delayed. Adjusted RMST was 4.13 months longer in non-epithelioid network cases (p<0.001), but did not differ in epithelioid cases. Ipilimumab-nivolumab was used more commonly in network cases (47/279 (16.8%) vs 4/154 (2.6%) performance status (PS) 0-1 pre-network), but similar RMST extension was observed in untreated patients (+4.45 months, p=0.01). RMST differences were associated with improved PS at diagnosis, but not with stage, ipilimumab-nivolumab or surgery (in 17/659 (2.6%)). CONCLUSION: Establishment of a national mesothelioma network was associated with improved OS in non-epithelioid patients. Causal inferences cannot be drawn using the methods used, but these data support wider development of specialist mesothelioma networks.
INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a disease of high morbidity and mortality. We previously identified a novel subset of pathological fibroblasts, characterised by CTHRC1 expression, uniquely present in...INTRODUCTION: Idiopathic pulmonary fibrosis (IPF) is a disease of high morbidity and mortality. We previously identified a novel subset of pathological fibroblasts, characterised by CTHRC1 expression, uniquely present in fibrotic lung diseases. The aim of this study was to determine the association of serum CTHRC1 with clinical outcomes in IPF to assess its potential as a biologically relevant biomarker. METHODS: A retrospective longitudinal cohort study was performed using two cohorts including a discovery cohort of 352 patients with IPF from the University of California San Francisco (UCSF) and a validation cohort of 1156 patients with IPF from the Pulmonary Fibrosis Foundation (PFF) as well as 41 healthy controls. Serum CTHRC1 was measured by ELISA and patients were stratified by quartiles of CTHRC1 for analysis. For a subset of patients, serial serum and lung CTHRC1 expression was measured. Associations between CTHRC1 and clinical outcomes, including baseline lung function, lung function trajectory and transplant-free survival were assessed. RESULTS: Serum CTHRC1 was elevated in patients with IPF compared with healthy controls (UCSF 31 661±11 651 and PFF 33 916±14 547 vs 24 409±8630 pg/mL, p<0.001). Elevated circulating CTRHC1 was associated with lower forced vital capacity (FVC) per cent predicted and diffusing capacity of carbon monoxide per cent predicted at baseline and a greater decline in FVC over 1 year. In both cohorts, higher CTHRC1 level was associated with worse transplant-free survival (p<0.03). DISCUSSION: Circulating CTHRC1 levels are elevated in patients with IPF and associated with disease severity and overall survival. These findings further support the biological significance of CTHRC1 in IPF as a pathological marker and potential biomarker reflecting the burden of pathological fibroblasts in IPF.
INTRODUCTION: Interstitial lung abnormalities (ILAs) are early imaging markers of interstitial lung disease and pulmonary fibrosis. Occupational exposures to fumes and dusts are widespread and may especially impact indiv...INTRODUCTION: Interstitial lung abnormalities (ILAs) are early imaging markers of interstitial lung disease and pulmonary fibrosis. Occupational exposures to fumes and dusts are widespread and may especially impact individuals with familial susceptibility. We aimed to investigate the associations between occupational inhaled exposures and the risk of ILAs in individuals with potential familial susceptibility to pulmonary fibrosis. METHODS: We analysed data from 266 relatives of patients with familial or sporadic pulmonary fibrosis, enrolled in two cohorts: the Clinical Genetics and Screening for Pulmonary Fibrosis (n=184) and the Genetics of Pulmonary Fibrosis Study (n=82). Occupational exposures were determined through standardised questionnaires and categorised as vehicle fumes, non-vehicle fumes, mineral dusts, organic dusts, any fumes, any dusts or any dusts or fumes. Risk of ILAs was evaluated using modified Poisson models adjusted for age, sex and smoking status. RESULTS: The mean age of participants was 59.7 years and 23.7% had ILAs. Any occupational inhalational exposure was more common among participants with ILAs (27.0% for any fume) than among those without ILAs (16.7% for any fume). Exposure to any fumes, encompassing both vehicle and non-vehicle fumes, was associated with increased risk of ILAs (risk ratio (RR): 1.59, 95% CI 1.02 to 2.49). Similar positive but non-significant associations were observed for other exposures, including organic dusts, vehicle fumes, non-vehicle fumes and composite exposure. DISCUSSION: Occupational inhaled fume exposure is associated with higher risk of ILAs in individuals with potential familial susceptibility to pulmonary fibrosis. This highlights the potential value of considering occupational exposures in screening at-risk populations.
A 64-year-old male presented with progressive breathlessness and wheezing, initially suspected to be worsening asthma. Inhaled therapies were commenced and further investigations were conducted, including CT thorax, bron...A 64-year-old male presented with progressive breathlessness and wheezing, initially suspected to be worsening asthma. Inhaled therapies were commenced and further investigations were conducted, including CT thorax, bronchoscopy, pulmonary function tests and autoimmune screening. Imaging revealed tracheobronchomalacia and bronchoscopy confirmed a grossly abnormal endobronchial tree with appearances suggestive of relapsing polychondritis. A multidisciplinary discussion led to a diagnosis of tracheobronchomalacia secondary to relapsing polychondritis. Worsening symptoms of breathlessness led to commencement of corticosteroids, nocturnal non-invasive ventilation and immunosuppression with infliximab. Subsequent escalation of management included endobronchial stenting, argon laser therapy and adjustment of therapy to rituximab with the addition of intravenous immunoglobulins.Relapsing polychondritis is a rare inflammatory disease with airway involvement in up to 50% of cases. Respiratory symptoms may be the first sign, often misdiagnosed as asthma, delaying appropriate care. This case highlights the need for early recognition and treatment to prevent irreversible airway damage in relapsing polychondritis.