Introduction Chronic obstructive pulmonary disease (COPD) is increasingly recognized as a disease of accelerated biological aging characterized by progressive lung function decline, emphysema progression and multiple age-related comorbidities. Current therapies improve symptoms and reduce exacerbations but have limited effects on disease progression. Metformin has demonstrated anti-aging properties through modulation of pathways involved in oxidative stress, inflammation, mitochondrial dysfunction and cellular senescence, making it a potential disease-modifying treatment in COPD.Methods AMICO (A Trial of Metformin In COPD) is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled phase III trial conducted in anonymous. A total of 212 patients with clinically stable COPD, centrilobular emphysema on computed tomography, post-bronchodilator FEV1 40%–70% predicted and accelerated FEV1 decline (>40 mL·year−1) will be randomized (1:1) to receive metformin (850 mg twice daily) or matching placebo for 36 months in addition to standard COPD treatment. Assessments include pulmonary function, chest computed tomography, exercise capacity, health status, muscle strength, body composition, age associated comorbidities development and aging-related biomarkers.The primary endpoint is the annual rate of FEV1 decline over 36 months. Secondary endpoints include emphysema progression, changes in diffusing capacity, COPD Assessment Test score, 6-minute walk distance, BODE index, handgrip strength, exacerbations, major cardiovascular events, cancer incidence and renal dysfunction.Conclusions AMICO is the first randomized trial specifically designed to evaluate metformin as a gerotherapeutic and disease-modifying intervention in COPD. The study may provide novel evidence supporting geroscience-based approaches to slow disease progression and improve long-term outcomes in patients with COPD.
Objective Limited data describe outcomes in people with comorbid schizophrenia when admitted with acute hypercapnic respiratory failure (AHRF). This study compared outcomes in people with COPD requiring non-invasive ventilation (NIV), with and without schizophrenia, to identify priorities for intervention and research.Methods This is a retrospective cohort study from a single Australian quaternary referral hospital of people with COPD requiring NIV for AHRF over 5 years from 1 January 2017 to 31 December 2024, excluding admissions between 1 January 2020 and 31 December 2022, when the COVID-19 pandemic disrupted usual practices. Primary outcomes were length of stay (LOS) and NIV duration (days). Secondary outcomes included NIV discontinuation reason, challenges to NIV and readmission. Descriptive and comparative statistics summarised variables by schizophrenia status and assessed between-group differences. Cox proportional hazards models assessed survival, while association between schizophrenia and readmission was analysed using competing-risks regression.Results Prevalence of schizophrenia is higher in this cohort than general population, comprising 36 (19%) of 186 individuals, and 97 (30%) of 328 admissions. Those with schizophrenia were younger (66.6 vs. 72.5 years, p = 0.001), with more current smokers (75% vs. 42.7%, p = 0.005) and had admissions with shorter LOS (6 vs. 9 days, p = 0.043) and NIV duration (3 vs. 5 days, p = 0.021). There was no significant difference in reason for NIV discontinuation between the groups. Readmission rates were higher in the schizophrenia group (44.4% vs. 24.0%, p = 0.025). Age at death was lower for those with schizophrenia (67.3 vs. 77.4 years, p < 0.001).Conclusion People with schizophrenia had shorter LOS and NIV use, higher readmission rates, higher prevalence of current smokers and younger age at presentation and death. These findings suggest that schizophrenia is an at-risk subgroup in AHRF, highlighting the need for collaborative action.
Exacerbations of Chronic Obstructive Pulmonary Disease (ECOPD) are often triggered by bacterial and viral infections, yet current diagnostic methods are time-consuming and biomarkers (e.g. C-reactive protein (CRP)) show limited accuracy in differentiating between these triggers. Hemocytometric parameters derived from routine blood analysis may provide a rapid, accessible alternative. This study evaluated whether machine learning applied to routine hemocytometric parameters can accurately distinguish between bacterial and viral etiology in ECOPD. We performed a post hoc, exploratory analysis on 64 patients hospitalized for an ECOPD. Bacterial and viral pathogens were detected using sputum culture and/or polymerase chain reaction on nasopharyngeal swab samples. After preprocessing 53 hemocytometric parameters, Random Forest models were developed using selected hemocytometry features for bacterial (n = 12) and viral (n = 6) presence. Model performance was assessed using repeated stratified train-test splits with out-of-sample predictions. Hemocytometry-based models showed good performance for classification of bacterial presence (AUC 0.783; 95% CI 0.713-0.853), with accuracy, sensitivity, and specificity of 72%, 73%, and 70%, respectively, outperforming CRP (AUC 0.585, p < 0.001). For classification of viral presence, the model achieved an AUC of 0.717 (95% CI 0.636-0.798), with accuracy, sensitivity, and specificity of 72%, 59%, and 80%, respectively. In this exploratory analysis, hemocytometry-based machine learning models show promising performance for classifying the presence of bacterial and viral infections in ECOPD, outperforming CRP. The worldwide, routine availability of hemocytometry underscores the relevance of our findings as a practical tool for identifying bacterial and viral causes and supports potential for rapid clinical implementation. However, they require validation in larger cohorts.Clinical trial registration NCT04961060.
Bronchoscopic lung volume reduction (BLVR) is a minimally invasive option for advanced COPD, but carries bleeding risk. A significant proportion of COPD patients requiring BLVR are on chronic anticoagulation, yet data on procedural safety in this population remains scarce. We conducted a retrospective study using the National Inpatient Sample (NIS) database (2016-2023). Adult BLVR patients were stratified by chronic anticoagulation status. The primary outcomes were hemothorax and pulmonary bleeding. Secondary outcomes included any bleeding (gastrointestinal, pulmonary, intracranial, retroperitoneal, hematuria, hemothorax, or acute blood loss anemia), pneumothorax, in-hospital mortality, major adverse cardiac events (MACE), and prolonged hospitalization (>= 7 days). Multivariable logistic regression yielded adjusted odds ratios (aORs) controlling demographics, comorbidities, and hospital characteristics. Of 16,340 weighted BLVR hospitalizations, 1,275 (7.8%) involved anticoagulated patients. Anticoagulated patients were older (68.6 vs. 65.7 years) and more frequently male (70.6% vs. 58.5%), with a higher burden of cardiovascular comorbidities. Hemothorax and pulmonary bleeding occurred in 2.7% and 7.1% of anticoagulated patients versus 1.1% and 4.7% of non-anticoagulated patients, respectively. Any bleeding occurred in 14.1% of anticoagulated versus 10.8% of non-anticoagulated patients. These differences were not statistically significant, and chronic anticoagulation was not independently associated with any increased bleeding on multivariable analysis. No significant differences were observed in mortality (aOR 0.88), pneumothorax (aOR 0.72), MACE (aOR 1.13), or prolonged hospitalization (aOR 1.09). Chronic anticoagulation was not independently associated with adverse outcomes following BLVR, suggesting comparable short-term outcomes in this population. Prospective studies examining the timing and types of anticoagulation in BLVR are warranted.
Long-term oxygen therapy (LTOT) for patients with severe chronic hypoxemia is a well-established treatment, but data on long-term outcomes are limited. This study aims to describe the characteristics and survival of patients using LTOT in Belgium. Data from patients receiving LTOT were extracted from the Belgian Social Security databank with 4 years of follow-up and compared with a more detailed tertiary care cohort from the University Hospital of Leuven. Kaplan-Meier curves for overall and transplant-free survival were constructed. We performed log-rank univariate analyses for diagnosis and starting treatment modality and applied a Cox proportional hazards model adjusting for age and underlying diagnosis. In Belgium, 4973 patients started LTOT in 2017. Overall 4-year survival was 22% and determined by age, baseline oxygen modality and diagnosis. LTOT was primarily prescribed for patients with COPD (75%) who had higher 4-year survival (24%) compared to patients with restrictive pulmonary disease (17%) (HR 1.23, p < 0.005). In the University hospital cohort (n = 533), 4-year transplant-free survival was 26% with significantly lower survival rates of patients with ILD (13%) (HR 1.98, p < 0.005) and other obstructive lung diseases (24%) (HR 1.56, p < 0.01) as compared to COPD (33%). Survival for patients receiving LTOT remains poor. Best prognosis is seen in patients with COPD, while patients with restrictive pulmonary disease and ILD in particular have the poorest outcome. Palliative care and end-of-life discussions should be an integral part of prescribing LTOT.
