Pulmonary Circulation最新文献

The natural history of late-onset pulmonary arterial hypertension (PAH) with features of venous/capillary involvement and the associations with rare variants in PAH genes are not well known. We report a case of a female patient who developed severe PAH at the age of 70. Two years before, lung histology was obtained showing features of pulmonary veno-occlusive disease. Genetic testing revealed that the patient was harbouring two rare genetic variants in the KDR and EIF2AK4 genes. She received a triple combination therapy alongside diuretics and survived remarkable 8 years after the PAH diagnosis.

Treatment options for acute pulmonary embolism (PE) have evolved rapidly, with an increasing number of interventional options, necessitating interhospital transfer for consideration of advanced therapies and optimal care. Utilizing the National PERT Consortium database, this study analyzed 12,346 patients from 35 institutions between October 16, 2015 and June 1, 2024. Patients were categorized as directly presenting to a PERT hospital or transferred from a referring hospital. Demographics, clinical presentations, treatments, and outcomes were compared. Multivariable logistic regression was used to evaluate the association between transfer status and outcomes. Transferred patients (n = 3277) were younger, more frequently White, more often obese, and had lower malignancy rates. They were more likely to be classified as high-risk PE (16.7% vs. 13.8%, p < 0.01) and intermediate-high risk PE (55.9% vs. 54.3%, p < 0.01). Transferred patients more frequently received advanced therapies, including ECMO (2.8% vs. 1.1%, p < 0.01), surgical embolectomy (2.0% vs. 0.8%, p < 0.01), systemic thrombolysis (5.3% vs. 3.8%, p < 0.001), and catheter-based interventions (32.3% vs. 17.1%, p < 0.01). After adjustment, transfer was associated with lower odds of 30-day mortality (OR 0.82, 95% CI 0.69-0.98), 1-year mortality (OR 0.77, 95% CI 0.67-0.89), and in-hospital mortality (OR 0.78, 95% CI 0.65-0.97), with no significant difference in major bleeding risk. Subgroup analysis showed mortality benefits were most evident among intermediate-low and high-risk patients. In conclusion, acute PE patients transferred to PERT hospitals were more likely to receive advanced therapies and had improved short- and long-term survival, with no increase in bleeding risk, despite presenting with higher clinical severity.

Mechanical ventilation (MV), though life-saving in acute respiratory distress syndrome (ARDS), can cause ventilator-induced lung injury (VILI). MicroRNA-24 (miR-24) has been implicated in regulating inflammation and apoptosis, but its role in VILI remains unexplored. Therefore, our study aimed to explore the role of mechanism of miR-24 in VILI. MiR-24 expression was analyzed in MV-induced ARDS rat models (GSE57223), plasma from ARDS patients, and cyclic stretch (CS)-treated alveolar epithelial cells. Functional studies included intratracheal delivery of miR-24-agomir in rats with VILI and transfection of miR-24 mimic in CS-exposed cells. Inflammatory cytokines, oxidative stress markers, apoptosis, and mitochondrial dysfunction were assessed using ELISA, RT-qPCR, TUNEL, JC-1 staining, and ATP assays. BOK was identified as a target of miR-24 via bioinformatics, luciferase reporter, and RNA pull-down assays. Rescue experiments using BOK overexpression vectors (pcDNA3.1/BOK) were conducted in both models to confirm functional interaction. MiR-24 was significantly downregulated in ARDS patients and VILI models and positively correlated with oxygenation index. Overexpression of miR-24 attenuated MV- and CS-induced inflammation, oxidative damage, and mitochondrial apoptosis dysfunction. BOK was confirmed as a direct target of miR-24; its expression was upregulated in ARDS and VILI and inversely correlated with miR-24 levels. Silencing of BOK attenuated MV-induced inflammation, oxidative damage, and apoptosis in rats. Importantly, BOK overexpression reversed the protective effects of miR-24 both in vivo and in vitro, confirming its role as a key downstream effector. Receiver operating characteristic (ROC) analysis showed that miR-24 had good diagnostic potential (AUC = 0.834). Overall, MiR-24 protects against MV-induced lung injury by targeting BOK and modulating key injury pathways. The miR-24/BOK axis offers a promising therapeutic avenue for ARDS-associated VILI.

Pulmonary perfusion assessment is essential for the management of chronic thromboembolic pulmonary hypertension (CTEPH). Lung perfusion scintigraphy and contrast-enhanced CT are occasionally limited by the need for radionuclides or allergy to the contrast agents. Dynamic chest radiography (DCR) can evaluate the pulmonary perfusion non-invasively using conventional X-ray technology. We validated pulmonary perfusion measurements using DCR by comparing them with those obtained using perfusion scintigraphy in CTEPH. Thirty-three patients with CTEPH who underwent both DCR and lung perfusion scintigraphy within 1-month interval from December 2019 to December 2022 were included. DCR was performed with patients in both standing and supine positions. To assess lung perfusion, each lung was divided into six fields (right and left; upper, middle, and lower). The blood flow rates per field were quantified by using analysis software as 100% of the sum of the six sites. The correlation between blood flow rates of each area in DCR and perfusion scintigraphy was evaluated using intraclass correlation coefficients (ICC). DCR showed a strong correlation with pulmonary perfusion scintigraphy in both standing (ICC(2,1) = 0.86; confidence interval [CI], 0.81-0.89) and supine (ICC(2,1) = 0.82; CI, 0.77-0.86) positions. When analyzed by region, all regions except the left lower lung showed significant correlations with perfusion scintigraphy findings. Intra- and intra-inspector reliabilities at both positions were excellent. The quantitative assessment of lung perfusion using DCR is reliable in patients with CTEPH. However, perfusion in the left lower lung was underestimated using DCR.

Dyspnea, a debilitating symptom of COPD, worsens health-related quality of life (HRQL), reduces daily physical activity, increases health care utilization, and is more closely associated with survival than airflow limitation. Thus, having treatments that reduce dyspnea in COPD is important. Pulmonary hypertension (PH) is a common complication of COPD that is associated with severe dyspnea, more frequent COPD exacerbations, and increased mortality. Multiple causes of PH, including a reduction in bioavailable vasodilator nitric oxide (NO), are associated with COPD (COPD-PH). Phosphodiesterase type-5 inhibitor (PDE5i) therapy restores NO signaling and improves hemodynamics and dyspnea in patients with Group 1 Pulmonary Arterial Hypertension, but has not been proven effective in COPD-PH. In a prior study (ClinicalTrials. gov identifier: NCT01862536), we investigated effects of 12 months of oral PDE5i therapy with tadalafil on 6-min walk distance (6MWD) in a multi-center, randomized, placebo-controlled trial funded by the Department of Veterans Affairs. While tadalafil did not change 6MWD at 12 months, the treatment group experienced clinically meaningful improvements in patient-reported dyspnea and HRQL at 6 months. Because of the importance of mitigating dyspnea in COPD-PH, we developed a new study protocol examining the effect of PDE-5i therapy in COPD-PH, with a reduction in dyspnea the primary outcome. In the current study (NCT05937854), we will conduct a prospective, randomized, double-blind, multi-center clinical trial to evaluate the effects of 6 months of maximally tolerated therapy with tadalafil (target dose 40 mg/day) versus placebo on dyspnea, as measured by University of California San Diego Shortness of Breath Questionnaire.

Identifying noninvasive measures to assess intravascular volume status and risk stratify patients with pulmonary hypertension (PH) and chronic kidney disease (CKD) is needed. We assessed the predictive value of estimated plasma volume status (ePVS) using the Strauss-derived Duarte formula in PH-CKD patients. This single-center retrospective cohort analysis included patients with PH and CKD Stage 3b (CKD3b), Stage 4 (CKD4), or Stage 5 (CKD5) who underwent right heart catheterization from 2018 to 2023. Patients were categorized into low ePVS (< 6.2) and high ePVS (≥ 6.2) using Youden's J statistics. We used the Cox-proportional hazards model, adjusting for age, sex, and body mass index, to investigate the association between high ePVS and major adverse cardiovascular events (MACE) and all-cause mortality within 1 year after ePVS measurement date. Of 305 patients with PH-CKD, 30% (n = 91) had low ePVS, and 70% (n = 215) had high ePVS. Compared to the low ePVS group, patients with high ePVS had higher left ventricular ejection fraction, right atrial pressure, pulmonary artery wedge pressure, and cardiac index, lower pulmonary vascular resistance, worse kidney function, and more chronic anemia. Among patients with precapillary or Cpc-PH, high ePVS was associated with a greater incidence of 1-year all-cause mortality (adjusted HR = 2.11, 95% CI 1.06-4.22 p = 0.034). Among PH-CKD patients, high ePVS was associated with hyperdynamic circulation, worse kidney function, and anemia. High ePVS was associated with greater 1-year all-cause mortality among patients with a precapillary PH component.

Pulmonary hypertension (PH) in children requires complex medical management. Health-related quality of life (HRQoL) remains understudied in this population. During an 8-month period children and parents attending PH outpatient appointments completed the generic PedsQL (measuring physical, emotional, social, and school functioning). Parents completed the Hospital Anxiety and Depression scale, a validated measure of anxiety and depression, about their own mental health. Clinical data were extracted from the medical notes. Analyses explored relationships between clinical factors, parental mental health and HRQoL and compared scores with published norms. Parents of 94 of 98 (96%) eligible children with PH and 48 of 54 (89%) eligible children aged ≥ 5 years completed the PedsQL. All HRQoL scores were significantly below healthy norms, with 49% scoring > 2 S.D. below normative means. Physical HRQoL was associated with disease severity and survival outcomes. Multiple regression analyses showed age, learning disability, functional class, and parental depression explained 38% of parent-reported HRQoL variance (F(6, 86) = 7.67; p < 0.001) while learning disability explained 33% of child-reported variance (F(3, 45) = 6.78; p < 0.001). These findings support routine HRQoL evaluation and development of disease-specific measures for paediatric PH.

Porto-pulmonary hypertension (PoPH) represents a rare but significant form of pulmonary arterial hypertension (PAH) in children. Despite its clinical importance, systematic analyses of paediatric presentations and outcomes remain limited. We analysed the United Kingdom National Registry for Paediatric Pulmonary Hypertension (2001-2022) identifying children with PoPH through standardised diagnostic criteria including cardiac catheterisation and cross-sectional imaging. In our cohort of 12 patients (58% female, median age 4 years, range: 3 months-12 years), congenital porto-systemic shunts (CPSS) were the predominant pathology (58%). We found a high prevalence of genetic abnormalities (50%) and congenital heart disease (50%). Haemodynamic assessment revealed evidence of pulmonary vascular disease (mean pulmonary artery pressure 38 mmHg, range 20-52 mmHg; mean pulmonary vascular resistance index 6.1 WU·m², range 4.2-9.0 WU·m²) without vaso-reactivity. Over a median follow-up of 8.2 years, three patients achieved resolution of pulmonary hypertension after definitive treatment of underlying liver pathology. Four deaths occurred during follow-up: three from progressive PAH and one unrelated death that occurred 2 years following PAH resolution. Our analysis reveals distinctive features of paediatric PoPH, including predominant CPSS aetiology, and earlier age of onset than previously reported. Multi-modality imaging proved essential for diagnosis, as initial ultrasound missed CPSS in 5/7 cases. The variable treatment outcomes emphasise the importance of individualised therapeutic approaches and sustained clinical surveillance.

Fibrotic lung diseases are often characterized by chronic inflammation and the progressive destruction of the vasculature, parenchyma, and airways, leading to cellular metabolic changes. As a result, these changes activate several pathological pathways, contributing to the disease's progression and worsening. However, the precise impact of metabolic changes and their contributions to the progression of fibrotic lung diseases need deeper exploration. The current review highlights the interplay between immunometabolites and hypoxia in bringing out cellular and epigenetic changes that progress and further exacerbate pulmonary fibrosis. Notably, the mitochondrial-linked immunometabolites such as lactate, succinate, 2-hydroxyglutarate (2-HG), fumarate, and itaconate have the potential to determine cellular fate in health and disease. For instance, lactate accumulation is one of the vital factors associated with pulmonary fibrosis (PF). The metabolite succinate promotes hypoxia response, inflammatory markers accumulation, fibroblast activation, and PF, whereas L-2-HG impairs the TCA cycle, reduces glycolysis, and disrupts the nicotinamide adenine dinucleotide (NADH/NAD+) ratio, ultimately leading to dysfunctional mitochondrial respiration and contributing to lung fibrosis. Due to the progressive and degenerative nature of fibrotic lung diseases, individuals affected by them need ongoing clinical support and monitoring. The currently available pharmacological treatments are limited and come with multiple side effects. Therefore, the search for newer therapeutics in the form of small molecules targeting these metabolites is increasingly being formulated to treat chronic fibrotic pulmonary conditions through their exhaustive mechanistic investigations backed by robust preclinical and clinical trials.