搜索结果：Pulmonary and Respiratory Medicine

Mechanical chest compressions during cardiopulmonary resuscitation (CPR) can produce pulmonary edema, described as cardiopulmonary resuscitation-associated lung edema (CRALE), which has been largely interpreted as a hydrostatic phenomenon. However, whether early molecular changes associated with epithelial injury, coagulation, and inflammation are also present during resuscitation remains uncertain. We hypothesized that bronchoalveolar lavage fluid proteomics would identify early protein signatures of lung injury after CPR. Bronchoalveolar lavage fluid (BALF) was collected separately from the right and left caudal lung lobes of nine pigs before cardiac arrest and again after ventricular fibrillation, 8&#xa0;min of untreated arrest, and up to 45&#xa0;min of CPR. In animals achieving return of spontaneous circulation, post-CPR BALF was obtained immediately after resuscitation; in the remaining animals, sampling was performed at the end of CPR. Proteins were digested, tandem mass tag 18-plex labeled, and analyzed by high-resolution liquid chromatography-mass spectrometry. Differentially abundant proteins were defined by fold change >1.5 or <0.67 with P&#xa0;<&#xa0;0.05. Functional enrichment, histologic assessment, and western blot validation were performed. A total of 1088 proteins were identified in left lung BALF and 1200 in right lung BALF. Comparison of pre- and post-CPR samples identified 74 and 78 differentially abundant proteins in the left and right lungs, respectively, with 28 shared proteins across both lungs. Among the most increased proteins were plasminogen activator inhibitor-1 (SERPINE1/PAI-1), apolipoprotein A1, inter-alpha inhibitor family proteins, vitronectin, histones, and advanced glycation end-product receptor (AGER). Functional enrichment showed over-representation of proteins related to complement and coagulation, platelet degranulation, lipid metabolism, and extracellular matrix signaling. Histology showed mild septal thickening, vascular neutrophilic infiltration, interstitial edema, and patchy fibrin deposition, consistent with early pneumocyte injury and mild inflammation. Western blot confirmed increased post-CPR abundance of PAI-1 and apolipoprotein A1. Early after resuscitation, BALF proteomics identified molecular changes characterized by increased antifibrinolytic and complement-related proteins, together with proteins associated with epithelial and endothelial stress. These findings suggest that pulmonary abnormalities after CPR may involve not only hydrostatic edema but also an early biologic response consistent with lung injury, which may contribute to post-cardiac arrest respiratory dysfunction and progression to acute respiratory distress syndrome.

Pulmonary lymphangitic carcinomatosis (PLC) and pulmonary tumor embolism (PTE) are rare manifestations of metastatic malignancy that may mimic more common causes of dyspnea and pulmonary hypertension, often leading to delayed diagnosis. Both conditions are associated with poor prognosis and may present with rapidly progressive right ventricular failure. A 45-year-old female lifelong non-smoker with no significant past medical history presented with a two-week history of cough, pleuritic chest pain, and worsening fatigue. CT pulmonary angiography was negative for central macrovascular pulmonary embolism but demonstrated interlobular septal thickening, ground-glass opacities, pulmonary nodules, and vertebral lesions. Initial echocardiography showed mild to moderate pulmonary hypertension with preserved right ventricular function. Despite supportive management, the patient experienced rapid clinical deterioration, progressing to severe pulmonary hypertension, right ventricular failure, cardiogenic shock, and pulseless electrical activity arrest. Post-mortem examination revealed invasive pulmonary adenocarcinoma with extensive lymphovascular invasion and metastatic disease, consistent with PLC and PTE. This case emphasizes the need to take into account PLC and PTE in patients with rapidly progressive pulmonary hypertension despite negative pulmonary embolism imaging. Recognition of subtle radiographic clues may facilitate earlier diagnosis, although prognosis remains poor once right ventricular failure develops.

Digital health technologies offer a promising approach to strengthening self-management capacity among patients with chronic obstructive pulmonary disease (COPD), yet clinical application is hampered by poor adherence, low sustained engagement, and limited self-management ability. Although previous studies have identified general self-management challenges in COPD, few have systematically investigated patients' preferences for digital tools or translated these insights into actionable design principles. This hinders the user-centred development and effective deployment of digital interventions for this population. This study aimed to explore the self&#x2011;management challenges and preferences for mobile health (mHealth) among COPD patients, with the ultimate goal of translating these findings into design principles for a persuasive self&#x2011;management application. We conducted in-depth personal interviews with 15 patients with COPD and five healthcare professionals to explore the challenges of self-management and preferences for mHealth. Data were analyzed using thematic analysis. Subsequently, a structured expert consultation was held to translate the findings into key principles for a persuasive self-management application. Five themes regarding barriers to effective self-management were identified: (1) negative emotional experience, (2) poor health literacy, (3) insufficient family support, (4) inadequate professional health care, and (5) economic burden. Patients expressed four key preferences for digital health technologies: (1) simplicity, (2) personalized decision support, (3) self-report, (4) early warning of deterioration. Furthermore, the panel discussion distilled these findings into eight essential key principles: motivation, simplicity, credibility, guidance, personalization, self-report, warning, and continuity. This study provides new insights into user-centered mHealth tools for COPD self-management. We derived core design principles from patients' demands to inform targeted digital interventions. These principles require validation in female, higher-literacy and multi-center samples before wide application. Future work will complete the remaining CeHRes Roadmap stages of design, operationalization and evaluation to refine this framework. What is Already Known about this Topic? Many patients with chronic obstructive pulmonary disease hope to use mobile applications to manage their respiratory conditions and daily health. Properly designed mobile applications can assist patients in better self-care. Nevertheless, there are still very few development standards formulated according to the actual daily needs of patients with COPD, which makes it difficult for developers to create self-management applications that are both user-friendly and clinically effective. What this Paper Adds? We collected feedback from patients with chronic obstructive pulmonary disease and medical staff through one-on-one interviews, and also gathered professional advice from an interdisciplinary expert panel. Based on these inputs, we identified practical approaches to support routine health management and developed eight actionable design guidelines for creating user-friendly mobile health tools. The Implications of this Paper Our results help medical teams better grasp what people with COPD actually want from mobile health self-management tools. Clinicians and app developers can build mobile health apps that match COPD users&#x2019; real needs and preferences. This work offers clear practical guidance to create health tools that center on the person living with COPD.

Single-inhaler triple therapy (SITT) combining an inhaled corticosteroid, long-acting &#x3b2;2-agonist, and long-acting muscarinic antagonist (ICS/LABA/LAMA) represents the current ceiling of inhaled pharmacotherapy for moderate-to-very-severe chronic obstructive pulmonary disease and severe uncontrolled asthma. Five device platforms are currently approved: two extrafine formulations delivering beclomethasone dipropionate/formoterol/glycopyrronium (the Modulite solution pressurised metered-dose inhaler [pMDI] and the NEXThaler breath-actuated dry powder inhaler [DPI]); the co-suspension pMDI Aerosphere platform (budesonide/glycopyrrolate/formoterol); the standard-particle Ellipta DPI (fluticasone furoate/umeclidinium/vilanterol); and the low-resistance, single-dose capsule-based DPI Breezhaler (mometasone furoate/indacaterol/glycopyrronium). Despite a shared pharmacological class, these systems differ in aerosol physics, particle engineering, intrapulmonary deposition patterns, and device-patient interaction. Furthermore, some of them are authorized only for COPD or asthma. This narrative review examines the technology and in vivo deposition evidence for each SITT platform, discusses real-world performance determinants (particle size, flow dependency, technique robustness), and proposes an expert-informed framework for patient-level device selection. Methodological limitations include reliance on in silico Functional Respiratory Imaging data when in vivo scintigraphy is unavailable, and inconsistent dose denominators across studies (emitted vs. metered dose). Cross-platform comparisons are limited by heterogeneous methodologies, and no SITT platform has demonstrated universal superiority. In platform-specific studies, NEXThaler shows relatively high lung deposition (&#x223c;55% of emitted dose) though flow-dependent; Aerosphere is robust to inhalation technique variations; Modulite provides extrafine, peripheral delivery; Ellipta and Breezhaler offer once-daily convenience with moderate deposition. Rational device selection requires structured assessment of patient inspiratory capacity, disease phenotype, coordination, and adherence. Head-to-head scintigraphy and prospective imaging-outcome studies represent major evidence gaps.

To compare routine blood biomarkers, lung function, and medication-associated biomarker patterns between hospitalized asthma patients classified as having asthma-COPD overlap (ACO) and those with asthma-only. This retrospective cross-sectional analysis included 505&#xa0;hospitalized asthma patients admitted between January 2020 and December 2024, comprising 190 with ACO and 315 with asthma-only. Disease history, pulmonary function parameters, complete blood cell counts, differential percentages, immunoglobulin E, and medication exposure were extracted from electronic medical records and analyzed using complete cases. Multivariable logistic regression, multivariable linear regression, Spearman correlation, and receiver operating characteristic (ROC) analyses were used to evaluate associations and discriminatory performance. Medication analyses were exploratory because treatment was not randomized. Compared with asthma-only patients, patients with ACO were older, had a lower prevalence of allergy history, used inhaled corticosteroids, long-acting beta2-agonists, and long-acting muscarinic antagonists more frequently, and had worse airflow limitation and lower diffusing capacity. Higher neutrophil percentage (adjusted odds ratio: 2.15, 95% confidence interval: 1.62-2.85, p<0.001) and lower lymphocyte percentage (adjusted odds ratio: 0.51, 95% confidence interval: 0.39-0.67, p<0.001) were independently associated with ACO after Bonferroni correction. In ACO patients, inhaled corticosteroid and long-acting beta2-agonist exposure was nominally associated with higher neutrophil-related and lower lymphocyte-related measures, but these observational findings should not be interpreted as treatment effects. FEV1/FVC showed the best discrimination for ACO (area under the curve [AUC]: 0.696), whereas neutrophil percentage showed modest complementary discrimination (AUC: 0.596). Within this hospitalized asthma cohort, ACO was associated with older age, more severe airflow limitation, impaired diffusing capacity, and a more neutrophil-dominant systemic inflammatory profile than asthma-only. Routine blood biomarkers, particularly neutrophil and lymphocyte percentages, may complement pulmonary function parameters in identifying ACO, but their standalone diagnostic performance was modest. Medication-associated biomarker differences were exploratory and require prospective validation.

Background and AimsPulmonary embolism (PE) is a frequent and potentially fatal diagnosis in the emergency department (ED). The Pulmonary Embolism Rule-out Criteria (PERC), an eight-item clinical decision rule used to identify patients at very low risk of pulmonary embolism, is widely applied to exclude PE in low-risk patients; however, its real-world diagnostic performance and impact on imaging utilization remain incompletely defined. This systematic review aimed to evaluate the diagnostic accuracy of PERC and its effect on reducing computed tomography pulmonary angiography (CTPA) use.Materials and MethodsThis review followed the Joanna Briggs Institute (JBI) methodology for diagnostic test accuracy studies. Eligible studies enrolled ED patients with suspected PE who were classified as low risk according to the original study-specific approaches, including clinician gestalt, Wells score, revised Geneva score, or YEARS-based assessment. PubMed, Web of Science Core Collection, the Cochrane Library, and ClinicalTrials.gov were searched for eligible studies published between 2004 and 2025.ResultsTen studies involving 13,672 patients were included. The pooled PE prevalence was 7%. The pooled sensitivity, specificity, and negative predictive value of PERC were 95% (95% CI: 89%-98%), 26% (95% CI: 16%-40%), and 98.2% (95% CI: 97.8%-99.0%), respectively. PERC application was associated with a significant reduction in imaging utilization (RR = 0.85, 95% CI: 0.80-0.91).ConclusionsPERC provides a highly sensitive and safe strategy for ruling out PE in low-risk ED patients and significantly reduces unnecessary use of advanced imaging without compromising diagnostic safety.

The evaluation of diastolic function in patients with diabesity (i.e., combined obesity and type-2 diabetes mellitus) undergoing incretin-based therapy could facilitate its early detection and help prevent its progression to heart failure. In this small descriptive study, performed for exploratory and proof-of-concept purposes, a group of 15 diabesity cases with chest x-ray examinations (<&#x2009;1 month) before and after &#x2265;&#x2009;12 months of incretin-based therapy (absent ventricular/valvular dysfunction) were identified. Standard diabesity characteristics (Body Weight (kg), Body Mass Index (kg/m2), and Hemoglobin A1c) and AI-model diagnostic predictions of pulmonary venous hypertension (aka "pulmonary congestion") [None; Stage 1: vascular distention/redistribution but minimal interstitial edema; or Stage&#x2009;&#x2265;&#x2009;2: vascular congestion with &#x2265;&#x2009;mild interstitial or alveolar edema] by validated AI-enabled chest x-ray staging, representing mean left atrial pressure in diastolic dysfunction, were evaluated pre- and post-therapy. According to weight-loss response to incretin therapy, cases clustered into equal-sized therapeutic categories as follows: (1) Significant Responders (9-30% decreases); (2) Insignificant Responders (0-2% decreases); and (3) Non-Responders (2-12% increases). Regarding hemoglobin A1c changes: (1) Significant Responders collectively decreased; (2) Insignificant Responders varied; and (3) Non-Responders were largely stable. Pre-therapy, all 15 cases demonstrated AI-enabled chest x-ray pulmonary venous hypertension staging evidence of diastolic dysfunction; post-therapy, 4 improved (especially the cases of greatest weight loss or hemoglobin A1c reduction), 5 were stable, and 6 worsened. Per therapeutic category, AI-enabled chest x-ray signs of functional response were: (1) Significant Responders (all demonstrating unequivocally decreased obesity and improved diabetes) collectively showed stable-decreased dysfunction; (2) Insignificant Responders (all demonstrating at most minimally decreased obesity, but stable-worsening diabetes in most) reflected stable-increased dysfunction in 60%; and (3) Non-Responders (all demonstrating increased obesity, but stable-improved diabetes) showed increased dysfunction in 80%. AI-enabled chest x-ray pulmonary venous hypertension staging potentially detects background subclinical diastolic dysfunction in diabesity and monitors its functional response to incretin-based therapy. The confirmation (or disproof), and assessments of durability and generalizability, of these preliminary results await a larger more definitive and controlled prospective study on the subject.

Mechanical ventilation remains a cornerstone of organ support in critically ill patients, yet modern intensive care ventilators incorporate increasingly complex modes and proprietary terminology that can obscure the physiological principles underpinning their use. A clear understanding of these principles is essential to enable safe, individualised, and lung protective ventilation. This article provides the physiological foundation for a four-part educational series on mechanical ventilation in adult critical care. Key concepts including positive end-expiratory pressure, airway pressures, resistance, compliance, elastance, and respiratory time constants are reviewed. Evidence supporting contemporary ventilation strategies is summarised, emphasising the importance of low tidal volume ventilation and individualisation of ventilator settings according to patient physiology. The ventilator breath cycle is described in terms of triggering, delivery, cycling, and expiration, providing a framework that is independent of manufacturer-specific nomenclature. A structured approach to ventilator modes based on control variables, breath sequence, and targeting schemes is presented using the Taxonomic Attribute Grouping system. Conventional pressure- and volume-controlled modes are discussed alongside assisted and mandatory ventilation strategies. Advanced modes, including airway pressure release ventilation and closed-loop systems, are reviewed with reference to their physiological rationale and current evidence base. Mechanical ventilation should be understood as a set of physiological principles rather than a collection of proprietary mode names. By focusing on pressure, flow, volume, timing, and patient-ventilator interaction, clinicians can better adapt ventilatory support to the changing pathophysiology of individual patients. This article aims to provide a practical framework for trainees and clinicians seeking to understand contemporary mechanical ventilation and to support subsequent articles addressing lung-protective ventilation, difficult weaning, and extracorporeal respiratory support.

Intravascular large B-cell lymphoma (IVLBCL) is a rare extranodal neoplasm in which malignant B cells proliferate predominantly within small blood vessels. Because lymphadenopathy, mass lesions, circulating malignant cells, and specific radiological findings may be absent, IVLBCL can closely mimic other medical conditions, resulting in delayed diagnosis. This case is notable for a prolonged culture-negative sepsis-like presentation with persistent unexplained hypoxemia due to predominant pulmonary microvascular involvement, further obscured by lupus-like autoimmune features and subsequent COVID-19 infection. An older woman in her early 70s presented with fever, lethargy, weight loss, back pain, hypotension, raised inflammatory markers, cytopenia, markedly elevated lactate dehydrogenase (LDH), and progressive hypoxemia. She was initially treated for presumed sepsis, but repeated microbiological investigations and serial imaging did not identify an infectious source, and clinical improvement was not sustained. A transient malar rash and a positive antinuclear antibody raised concern for a lupus-like autoimmune disease; however, testing for anti-double-stranded DNA and extractable nuclear antigen was negative, and the broader autoimmune workup did not support systemic lupus erythematosus as the unifying diagnosis. Subsequent severe acute respiratory syndrome coronavirus 2 infection further complicated the interpretation of hypoxemia and deterioration. Despite antimicrobial therapy, corticosteroids, antiviral treatment, and supportive care, she developed progressive multiorgan failure and died approximately six weeks after admission. Postmortem examination revealed widespread multiorgan IVLBCL involving the lungs, heart, kidneys, liver, spleen, and multiple additional extranodal sites. Pulmonary capillary involvement provided a clinicopathological explanation for persistent unexplained hypoxemia. This case demonstrates how IVLBCL may remain concealed when several plausible diagnoses coexist. Persistent culture-negative fever, constitutional decline, cytopenia, high LDH, nondiagnostic imaging, treatment nonresponse, and unexplained hypoxemia should prompt consideration of IVLBCL and early tissue-based investigation.

Cryptococcus gattii is an etiological agent of invasive pulmonary cryptococcosis in both immunocompetent and immunocompromised individuals. Current antifungal therapy is limited by toxicity, high cost, and emerging tolerance, supporting the need for new therapeutic alternatives. Although the organoselenium compound LQA_78 previously demonstrated antifungal activity against Cryptococcus neoformans, its effect on C. gattii remains unclear. Then, the aim of this work is to evaluate the antifungal activity of LQA_78 against C. gattii strains, its effects on virulence factors, and the underlying mechanisms of fungal cell death. Clinical isolates and morphotypes of C. gattii were subjected to susceptibility testing to determine inhibitory and fungicidal concentrations. Capsule thickness and permeability, melanin production, and laccase activity were assessed. Oxidative stress parameters, including reactive oxygen species (ROS) production, lipid peroxidation, glutathione (GSH) levels, and superoxide dismutase activity, were evaluated. Mitochondrial membrane potential, DNA fragmentation, and chromatin condensation were analyzed to investigate cell death pathways. In vivo efficacy was assessed using the Galleria mellonella infection model. LQA_78 inhibited fungal growth at concentrations comparable to fluconazole (2-32 &#x3bc;g/mL), increased capsule permeability without reduction in capsule thickness, and melanin production and laccase activity were significantly reduced. LQA_78, at higher concentrations (16-32 &#x3bc;g/mL), induced and increased plasma membrane permeability, lipid peroxidation, ROS accumulation, GSH depletion, reduced superoxide dismutase activity, mitochondrial dysfunction, DNA fragmentation, chromatin condensation, and phosphatidylserine externalization, indicating apoptosis- and necrosis-like cell death. In G. mellonella, nontoxic doses reduced the larvae mortality and fungal burden and increased hemocyte density. Therefore, the organoselenium LQA_78 demonstrates significant in vitro and in vivo antifungal activity against C. gattii, supporting its potential as a lead compound for cryptococcosis therapy.

The heterogeneity and complex tumor microenvironment of lung adenocarcinoma lead to poor prognosis. Autophagy, as a key cellular process, interacts with tumor immune infiltration and jointly affects the progression of lung adenocarcinoma, but its core regulatory genes and mechanisms are still unclear.This study integrated three lung adenocarcinoma transcriptome datasets from the GEO database and performed cross-analysis with the human autophagy gene set to screen for differentially expressed autophagy-related genes. Identify core prognostic genes by constructing protein interaction networks and combining them with machine learning algorithms (Cox regression, SHAP analysis). Use the independent dataset GSE68465 to validate the model through a combination of 100 algorithms. Further elucidate the function, cellular localization, and association with smoking risk of core genes through enrichment analysis, immune infiltration assessment, single-cell transcriptome analysis, and network toxicology.A total of 276 shared autophagy&#x2011;related differentially expressed genes were identified. Using machine learning, five core genes-ENG, CDH1, KLF4, IL6, and MMP9-were selected. In the independent validation cohort, the prognostic model based on these genes demonstrated strong diagnostic performance (AUC&#x2009;>&#x2009;0.9). Enrichment analysis revealed that the core genes were significantly enriched in pathways such as cellular senescence, autophagy, and FoxO signaling. Immune infiltration analysis showed that M1 macrophages and na&#xef;ve B cells were significantly upregulated in tumor tissues, whereas resting dendritic cells were downregulated. Single&#x2011;cell analysis identified specific expression of genes including CDH1 and TGFB1 in type II alveolar cells and immune cells. Network toxicology and molecular docking confirmed that nicotine, a major component of cigarette smoke, exhibits high&#x2011;affinity binding to the core genes CDH1, HIF1A, KLF4, TGFB1, and BCL2.This study successfully identified and validated a robust prognostic feature consisting of five autophagy-related genes. These genes play a key role in the development of lung adenocarcinoma by regulating the tumor immune microenvironment, cell communication, and responding to external risk factors, providing new potential targets for prognosis prediction and targeted therapy.

Chronic obstructive pulmonary disease (COPD) is a major public health problem. Research over the past few years has shown that COPD is the result of dynamic and cumulative gene-environment interactions starting early in life. This opens new opportunities for the Prediction, Prevention, Personalized and Precise management (P4) of COPD in young adults. The P4COPD study sought to: (1) investigate the genomic and environmental/lifestyle determinants of COPD in young adults (18-50 years); (2) contrast them with those determined in children, adolescent and older individuals; and (3) explore the feasibility and cost of implementing a P4 strategy for COPD in young adults in clinical practice. The P4COPD study leverages from already existing cohorts (EarlyCOPD, INMA, LEVANTE, Aduheart) of young subjects (18-50 years) and de novo recruitment from primary care centers, in whom we: (1) analyzed demographic, epidemiological, clinical and physiologic information; (2) measured genetic, epigenetic and proteomic markers; (3) used analytical methods to identify endotypes, biomarkers and potential therapeutic targets associated with the presence of COPD, pre-COPD and/or low peak lung function. Results in young individuals: (4) were contrasted with healthy controls from the general population (IMPACT cohort) and COPD cohorts in older patients (BIOMEPOC, CHAIN and ECLIPSE). Besides, we (5) explored how to implement results in clinical practice; and (6) estimated its potential health cost implications. First results are expected in the third and fourth quarters of 2026. Identifying young individuals at risk of COPD, in whom to establish a P4 strategy is highly relevant to promote healthy aging. La enfermedad pulmonar obstructiva cr&#xf3;nica (EPOC) es un problema mayor de salud p&#xfa;blica. La investigaci&#xf3;n de los &#xfa;ltimos a&#xf1;os ha demostrado que la EPOC es el resultado de interacciones din&#xe1;micas y acumulativas entre los genes y el medio ambiente que comienzan en la vida temprana. Esto abre nuevas oportunidades para la predicci&#xf3;n, prevenci&#xf3;n y el manejo personalizado y preciso (P4) de la EPOC en adultos j&#xf3;venes. El estudio P4COPD tuvo como objetivos: (1) investigar los determinantes gen&#xf3;micos y ambientales/de estilo de vida de la EPOC en adultos j&#xf3;venes (20&#x2013;50 a&#xf1;os); (2) compararlos con los determinados en ni&#xf1;os, adolescentes y personas de mayor edad; y (3) explorar la viabilidad y el coste de implementar una estrategia P4 para la EPOC en adultos j&#xf3;venes en la pr&#xe1;ctica cl&#xed;nica. El estudio P4COPD aprovecha cohortes ya existentes (EarlyCOPD, INMA, LEVANTE, Aduheart) de sujetos j&#xf3;venes (18&#x2013;50 a&#xf1;os), as&#xed; como un reclutamiento de novo desde centros de atenci&#xf3;n primaria, en los que: (1) analizaremos informaci&#xf3;n demogr&#xe1;fica, epidemiol&#xf3;gica, cl&#xed;nica y fisiol&#xf3;gica; (2) mediremos marcadores gen&#xe9;ticos, epigen&#xe9;ticos y prote&#xf3;micos; (3) utilizaremos m&#xe9;todos anal&#xed;ticos para identificar endotipos, biomarcadores y posibles dianas terap&#xe9;uticas asociadas con la presencia de EPOC, pre-EPOC y/o bajo pico de funci&#xf3;n pulmonar. Los resultados en individuos j&#xf3;venes (4) se contrastar&#xe1;n con controles sanos de la poblaci&#xf3;n general (cohorte IMPACT) y con cohortes de EPOC en pacientes de mayor edad (BIOMEPOC, CHAIN y ECLIPSE). Adem&#xe1;s, (5) exploraremos c&#xf3;mo implementar los resultados en la pr&#xe1;ctica cl&#xed;nica; y (6) estimaremos sus posibles implicaciones en costes sanitarios. Se espera que los primeros resultados est&#xe9;n disponibles en el tercer y cuarto trimestre de 2026. Identificar a individuos j&#xf3;venes en riesgo de EPOC, en quienes establecer una estrategia P4, es altamente relevante para promover un envejecimiento saludable.

Interstitial lung disease (ILD) is a serious pulmonary complication and a major cause of morbidity and mortality in several connective tissue diseases, notably rheumatoid arthritis (RA). We developed a study to compare the healthcare resource utilisation in patients with RAILD and RA-non-ILD and establish the impact of ILD diagnosis in the treatment of patients with RA using natural language processing (NLP) of electronic health records (EHRs). This observational, retrospective, multicentre study analysed unstructured clinical data from EHRs of patients with RA with and without ILD (RAILD and RA-non-ILD) from 9 hospitals in Spain, spanning January 2014 to December 2019. NLP was used to extract and standardise data into Systematized Nomenclature of Medicine - Clinical Terms (SNOMED-CT) terminology. The study aimed to compare healthcare resource utilisation and treatment patterns between the 2 groups, focusing on changes in treatment following ILD diagnosis in patients with RAILD. Among 13,958 patients with RA, 712 (5.1%) were identified as having RA-ILD, with 433 diagnosed during the study period. Patients with RAILD had significantly higher healthcare resource utilisation than patients with RA-non-ILD, particularly in pneumology (60.5% vs 9.0%), internal medicine (37.4% vs 19.9%), and emergency departments (57.3% vs 39.1%). Hospitalisation rates were also higher in patients with RAILD (64.5% vs 31.9%). Prior to ILD diagnosis, tumour necrosis factor inhibitors were the most commonly prescribed treatments, whereas after diagnosis, drugs with different mechanisms, such as rituximab and abatacept, were more frequently initiated. The development of ILD in patients with RA is associated with increased healthcare resource utilisation and different treatment patterns. NLP on EHRs is a valuable tool for offering insights into disease management and healthcare burden in patients with RAILD.

Pulmonary artery tumours are rare and may mimic thromboembolism or nodal recurrence on imaging. We report a woman in her 70s with a history of resected stage IB lung adenocarcinoma who underwent endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for a mediastinal lesion suspected to be nodal recurrence. During the second needle pass, synchronous lesion movement and increased bleeding were observed. Histopathology revealed high-grade sarcomatous cells with weak focal thyroid transcription factor-1 (TTF-1) positivity and h-caldesmon/myogenin expression, unlike the primary adenocarcinoma. Subsequent imaging confirmed that the lesion was intravascular within the pulmonary artery. EBUS-TBNA may inadvertently sample a pulmonary artery tumour when it mimics nodal recurrence during post-resection surveillance. Synchronous lesion movement and unexpected bleeding may indicate pulmonary artery puncture. Sarcomatoid transformation of adenocarcinoma and primary intimal sarcoma remained competing diagnoses because tissue was insufficient for molecular confirmation.

Anti-melanoma differentiation-associated gene 5 (anti-MDA5) antibody-positive dermatomyositis (DM) can manifest with a severe vasculopathic phenotype. We report a case of anti-MDA5 DM in a woman in her early 30s complicated by refractory cutaneous ulcers and pulmonary arterial hypertension (PAH). Despite the escalation of immunosuppressive therapy with glucocorticoids, tacrolimus, intravenous immunoglobulin, and cyclophosphamide, the cutaneous ulcers remained refractory. A progressive decline in diffusing capacity of the lung for carbon monoxide raised suspicion of PAH, which was subsequently confirmed by right heart catheterization. Consequently, combination therapy with mycophenolate mofetil (MMF) and rituximab (RTX) was initiated alongside bosentan. This regimen resulted in the prompt resolution of ulcers and improvement of PAH. Bosentan was discontinued, and azathioprine was initiated to maintain remission, allowing for a successful pregnancy and delivery of a healthy infant. This case suggests a potential role for an MMF- and RTX-containing combination regimen in refractory cutaneous ulcers and PAH associated with anti-MDA5 DM.

Pneumothorax is the presence of air in the pleural cavity, often resulting in respiratory distress and impaired lung function. Although clinical observations have shown that high intensity physical activity and frail state affect respiratory health, their causal role in pneumothorax development is unclear. This study is the first to use a two-sample Mendelian randomization method (TSMR) to investigate the causal relationship between physical activity and frailty and the risk of pneumothorax, with a view to providing new insights into the pathogenesis of pneumothorax and preventive strategies. Using Mendelian randomization (MR) analyses, we examined the potential causal relationship between physical activity, frailty, and the risk of pneumothorax. Genetic instrumental variables (IVs) for relevant exposure factors were selected from genome wide association studies (GWAS). The study was analyzed using five different methods, mainly using inverse variance weighted (IVW) to draw causal inferences. Sensitivity analyses were performed to ensure the validity of the MR results. Sensitivity analyses included the detection of horizontal pleiotropy, i.e., genetic variants affecting the outcome through pathways other than the target exposure, which may lead to biased causal inference. Heterogeneity between genetic instrumental variables was also assessed and used to detect variability in effect estimates, which may reflect violations of MR assumptions or differences between populations. Our analyses found that light DIY reduced the risk of pneumothorax, but did not identify a causal association between other levels of physical activity and pneumothorax. In addition, frailty index (FI) showed a positive association with the risk of developing spontaneous pneumothorax, and this causal relationship persisted after adjustment for body mass index (BMI) and light DIY. Sensitivity analyses further validate the robustness of our findings. Our findings support the ability of light DIY to reduce the risk of pneumothorax development. It also emphasizes the need for frail individuals to be more aware of the need to protect against pneumothorax in their daily lives. We encourage appropriate exercise to improve fitness and reduce the risk of pneumothorax.

The current state of respiratory physical therapy for adult pneumonia in Japan is insufficiently characterized. This study aimed to elucidate the current practices of respiratory physical therapy in Japan, including its implementation specifics, clinical frameworks, and medical reimbursement, with the aim of optimization respiratory physical therapy for adult pneumonia. A cross-sectional questionnaire survey comprising 21 questions was administered to members of the Japanese Society of Respiratory Physical Therapy. The survey items encompassed basic institutional information, existence of protocols, timing of rehabilitation prescriptions, clinical and educational systems for respiratory physical therapy (such as training systems), and content of respiratory physical therapy. The timing of rehabilitation prescriptions for adult pneumonia "varies depending on clinical decision-making by attending physicians" in 35.4% of institutions, and only 8.3% of facilities had established rehabilitation protocols. Furthermore, the most pressing issue concerning respiratory physical therapy for adult pneumonia was identified as "the lack of guidelines for respiratory physical therapy (pulmonary rehabilitation) for pneumonia," with 92 institutions citing this as the most significant problem. The practice of respiratory physical therapy for adult pneumonia in Japan varies across institutions, with a lack of reference materials, including clinical practice guidelines, potentially contributing to this variability. These findings highlight the need for further research and the development of optimized clinical guidance.

COVID-19 is linked to diverse cardiovascular complications, including myocarditis, new-onset heart failure, and ventricular arrhythmias. Although premature ventricular contractions and bigeminy are recognized, the specific pattern of quadrigeminy remains rarely documented in this setting. A 57-year-old male with untreated hypertension presented with acute exertional chest pressure, dyspnea, and nocturnal wheezing over two weeks. On arrival, BP was 176/100 mmHg, HR was 101 bpm, and O2 saturation was 93% on room air. ECG showed sinus tachycardia with bigeminy and trigeminy, without QT or QTc prolongation. Lab results showed troponin 0.04 ng/mL, B-type natriuretic peptide (BNP) 241 pg/mL, and the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) polymerase chain reaction (PCR) was positive. Chest CT revealed pulmonary edema, and echocardiogram showed a left ventricular ejection fraction&#xa0;(LVEF) of 40-45% with myocardial speckling. Telemetry showed runs of bigeminy, trigeminy, and quadrigeminy. He was diagnosed with acute hypoxic respiratory failure and COVID-19 myocarditis complicated by&#xa0;heart failure with mildly reduced ejection fraction (HFmrEF) and ventricular arrhythmias.&#xa0;Long-term follow-up is ongoing. This single-case report is based on comprehensive clinical, laboratory, electrocardiographic, telemetry, and imaging data from a community hospital admission. However, the limitations of this report are that this was a single case without cardiac MRI or biopsy confirmation. Hence, causality cannot be definitively established. To conclude,&#xa0;COVID-19 infection can cause myocarditis complicated by HFmrEF with rare arrhythmias, including quadrigeminy. Careful evaluation and individualized treatment are critical for optimal outcomes.

Pulmonary fibrosis is often framed as a problem of excess collagen causing stiffening of the lung, but that framing misses the more dynamic reality: fibrosis is built through ongoing conversations between fibroblasts, neighboring cells, and extracellular matrix (ECM) that interpret and reinforce injury signals. Over the last three years, single-cell, spatial, and multi-omics tools, paired with lineage tracing and functional models, have revealed distinct fibroblast states, trajectories, and spatial niches with increasing resolution. Here, we summarize emerging principles from this sharpened point of view. First, lung fibroblasts are not a single "myofibroblast" entity, rather they include a spectrum of states, ranging from resident niche-supporting lipofibroblasts, to transitional and inflammatory intermediate states, to CTHRC1&#x207a; pathological states. These transitions are not strictly linear, potentially reversible, and are context-dependent. Second, fibroblast state transitions are shaped by signals from injury-associated epithelial and immune cell populations within multicellular niches. Third, the ECM is not a passive scar, rather an active signaling hub whose composition, crosslinking, and stiffness engage mechanotransduction pathways that reinforce and, in chronic fibrosis, may lock in pathological fibroblast states. These insights motivate more precise therapeutic strategies - targeting fibroblast state-specific vulnerabilities, disrupting the fibrotic niche, and correcting dysregulated mechanosensing - and raise open questions about fibroblast state reversibility and niche plasticity that will shape next-generation approaches.