CHANGES IN PULMONARY VASCULATURE IN LUNG DISEASES WHICH LEAD TO PULMONARY HYPERTENSION.
Ontology highlight
ABSTRACT:
SUBMITTER: Batra RB
PROVIDER: S-EPMC5531120 | biostudies-other | 1997 Oct
REPOSITORIES: biostudies-other
Similar Datasets
Project description:Database studies have reported several associations between the diagnosis of idiopathic pulmonary arterial hypertension (IPAH) and mortality attributable to IPAH, including older age, black race, and diabetes.We investigated reported deaths and hospital discharges coded as IPAH and compared these with other forms of pulmonary hypertension. Three databases were used: the US National Center for Health Statistics database (1979-2006), queried for mortality data; the Nationwide Inpatient Sample database (1993-2007), queried for hospital discharge data; and the University of Texas Southwestern Hospital-Zale Lipshy discharge database (1999, 2002).Marked increases in mortality attributable to IPAH and to pulmonary hypertension (all codes combined) generally were reported from 1979 until 2002 in the National Center for Health Statistics database. In 2003, reported IPAH mortality fell sharply while total pulmonary hypertension deaths increased. The Nationwide Inpatient Sample database showed a similar pattern of changes beginning approximately 2 years earlier. In both cases, the timing of these observations corresponded with changes made to the International Classification of Diseases (ICD) coding system in use for pulmonary hypertension in that particular database. Review of pulmonary hypertension discharge data from the University of Texas Southwestern Hospital-Zale Lipshy showed similar changes in diagnosis code use.Sudden shifts in reported IPAH mortality and hospital discharges were seen in all databases, likely related to coding changes. These findings raise questions about the accuracy of pulmonary hypertension diagnosis codes. Studies based on International Classification of Diseases, Ninth Revision and International Classification of Diseases, 10th Revision codes may have inadvertently included patients with other forms of pulmonary hypertension and should be reevaluated in this context. Validation studies of the IPAH diagnosis code are needed, and changes to the ICD coding system should be considered.
| S-EPMC3047288 | biostudies-other
Project description:The current treatment of pulmonary arterial hypertension (PAH) uses vasodilator drugs. Although they improve symptoms associated with PAH, their chronic effects on the pulmonary vasculature and the right ventricle (RV) in humans remain unknown. We report the autopsy findings from a patient with idiopathic PAH treated with epoprostenol successfully for 18 years. The patient died of colon cancer. The pulmonary vasculature surprisingly showed extensive changes of a proliferative vasculopathy. Immunohistochemical studies confirmed ongoing cellular proliferation. Studies of the RV demonstrated concentric hypertrophy with seemingly preserved contractility. The myocardium shifted to glycolytic metabolism. Although the long-term use of epoprostenol contributed to the patient's increased survival, it did not prevent progression of the underlying vascular disease. Remarkably, the RV was able to sustain a normal cardiac output in the face of advanced vascular pathology. The mechanisms by which the RV adapts to chronic PAH need further study.
| S-EPMC2972625 | biostudies-other
Project description:BackgroundPulmonary hypertension occurs in approximately 1% of the global population, and the prognosis for such patients may be poor. However, the mechanisms underlying the development of this disease remain unclear. Thus, understanding the development of pulmonary hypertension and finding new therapeutic targets and approaches are important for improved clinical outcomes.MethodsLung tissue specimens were collected from six patients with atrial septal defect and pulmonary hypertension (all women, with a mean age of 46.5 ± 4.7 years, and their condition could not be corrected with an internal medical occlusion device) and from nine control patients with lung cancer who underwent lobectomy (six men and three women, with a mean age of 56.7 ± 1.7 years). Isobaric tags for relative and absolute quantitation and liquid chromatography tandem mass spectrometry analyses were used to detect protein expression levels.ResultsWe found 74 significantly upregulated and 88 significantly downregulated differentially expressed proteins between control and pulmonary hypertensive lung tissue specimens. Gene ontology analyses identified the top 20 terms in all three categories, that is, biological process, cellular component, and molecular function. Kyoto Encyclopedia of Genes and Genomes and protein-protein interaction analyses determined the top 10 signaling pathways and found that the six hub proteins associated with the differentially expressed upregulated proteins (PRKAA1, DHPR, ACTB, desmin, ACTG1, and ITGA1) were all involved in hypertrophic cardiomyopathy, arrhythmogenic right ventricular cardiomyopathy, and dilated cardiomyopathy.ConclusionOur results identified protein expression profile changes in lung tissue derived from patients with pulmonary hypertension, providing potential new biomarkers for clinical diagnosis and prognosis for patients with pulmonary hypertension and offering candidate protein targets for future therapeutic drug development.
| S-EPMC6996500 | biostudies-literature
Project description:AbstractTo investigate the importance of pulmonary vascular measurements on computed tomography (CT) in predicting pulmonary hypertension (PH) and worse outcomes in diffuse cystic lung diseases (DCLDs).We conducted a cross-sectional study of patients with DCLDs. Patients underwent pulmonary function tests, a six-minute walk test (6MWT), chest CT, transthoracic echocardiography, and right heart catheterization. Pulmonary artery (PA) diameter and PA-ascending aorta ratio (PA-Ao ratio) were obtained from CT. Mean pulmonary artery pressure (mPAP) from right heart catheterization was correlated with tomographic, functional, and echocardiographic variables. The association between the PA-Ao ratio with outcomes was determined by Kaplan-Meier curves.Thirty-four patients were included (18 with pulmonary Langerhans cell histiocytosis and 16 with lymphangioleiomyomatosis, mean age 46 ± 9 years). Forced expiratory volume in the first second and lung diffusing capacity for carbon monoxide were 47 ± 20% and 38 ± 21% predicted, respectively. PA diameter and PA-Ao ratio were 29 ± 6 mm and 0.95 ± 0.24, respectively. PA-Ao ratio > 1 occurred in 38.2% of patients. PA-Ao ratio was a good predictor of PH. mPAP correlated best with PA-Ao ratio, PA diameter, oxygen desaturation during six-minute walk test, and echocardiographic variables. Patients with PA-Ao ratio > 1 had greater mPAP, and a higher risk of death or lung transplantation (log-rank, P < .001) than those with PA-Ao ratio ≤ 1.The PA-Ao ratio measured on CT scan has a potential role as a non-invasive tool to predict the presence of PH and as a prognostic parameter in patients with DCLDs.
| S-EPMC8238321 | biostudies-literature
Project description:ObjectivesPulmonary arterial hypertension (PAH) is a major cause of morbidity and mortality in adults with systemic autoimmune rheumatic diseases (ARDs). The aim of this study was to determine whether adults with ARDs and PAH on right-sided heart catheterization (ARD-PAH) have increased mortality following lung transplantation compared with those with PAH not due to an ARD.MethodsWe conducted a retrospective cohort study of 93 adults with ARD-PAH and 222 adults with PAH who underwent lung transplantation in the USA between 4 May 2005 and 9 March 2015 using data from the United Network for Organ Sharing. We examined associations between diagnosis and survival after lung transplantation using stratified Cox models adjusted for potential confounding recipient factors.ResultsAmong adults undergoing lung transplantation in the USA, we did not detect a difference in the multivariable-adjusted mortality rate between those with ARD-PAH and those with PAH [hazard ratio 0.75 (95% CI 0.47, 1.19)].ConclusionThe presence of an ARD was not associated with increased mortality after lung transplantation in adults with PAH.
| S-EPMC6124248 | biostudies-literature
Project description:There is increasing interest in the potential for metabolic profiling to evaluate the progression of pulmonary hypertension (PH). However, a detailed analysis of the metabolic changes in lungs at the early stage of PH, characterized by increased pulmonary artery pressure but prior to the development of right ventricle hypertrophy and failure, is lacking in a preclinical animal model of PH. Thus, we undertook a study using rats 14 days after exposure to monocrotaline (MCT), to determine whether we could identify early stage metabolic changes prior to the manifestation of developed PH. We observed changes in multiple pathways associated with the development of PH, including activated glycolysis, increased markers of proliferation, disruptions in carnitine homeostasis, increased inflammatory and fibrosis biomarkers, and a reduction in glutathione biosynthesis. Further, our global metabolic profile data compare favorably with prior work carried out in humans with PH. We conclude that despite the MCT-model not recapitulating all the structural changes associated with humans with advanced PH, including endothelial cell proliferation and the formation of plexiform lesions, it is very similar at a metabolic level. Thus, we suggest that despite its limitations it can still serve as a useful preclinical model for the study of PH.
| S-EPMC4777490 | biostudies-literature
Project description:Pulmonary arterial hypertension (PAH) is a life-threatening disease that is characterized by an increase in pulmonary vascular pressure, leading to ventricular failure and high morbidity and mortality. Resveratrol, a phenolic compound and a sirtuin 1 pathway activator, has known dietary benefits and is used as a treatment for anti-inflammatory and cardiovascular diseases. Its therapeutic effects have been published in the scientific literature; however, its benefits in PAH are yet to be precisely elucidated. Using a murine model of PAH induced by monocrotaline, the macroscopic and microscopic effects of a daily oral dose of resveratrol in rats with PAH were evaluated by determining its impact on the lungs and the right and left ventricular function. While most literature has focused on smooth muscle cell mechanisms and lung pathology, our results highlight the relevance of therapy-mediated improvement of right ventricle and isolated cardiomyocyte physiology in both ventricles. Although significant differences in the pulmonary architecture were not identified either micro- or macroscopically, the effects of resveratrol on right ventricular function and remodeling were observed to be beneficial. The values for the volume, diameter, and contractility of the right ventricular cardiomyocytes returned to those of the control group, suggesting that resveratrol has a protective effect against ventricular dysfunction and pathological remodeling changes in PAH. The effect of resveratrol in the right ventricle delayed the progression of findings associated with right heart failure and had a limited positive effect on the architecture of the lungs. The use of resveratrol could be considered a future potential adjunct therapy, especially when the challenges to making a diagnosis and the current therapy limitations for PAH are taken into consideration.
| S-EPMC7023844 | biostudies-literature
Project description:Pulmonary hypertension (PH) is classically considered a disease of pulmonary vasculature which has been the predominant target for drug development and PH therapy. Despite significant advancement in recent years in identification of new drug targets and innovative treatment strategies, the prognosis of PH remains poor, with median survival of 5 years. Recent studies have demonstrated involvement of neuroinflammation, altered autonomic and gastrointestinal functions and increased trafficking of bone marrow-derived cells in cardiopulmonary pathophysiology. This has led to the proposal that PH could be considered a systemic disease involving complex interactions among many organs. Our objectives in this review is to summarize evidence for the involvement of the brain, bone marrow and gut in PH pathophysiology. Then, to synthesize all evidence supporting a brain-gut-lung interaction hypothesis for consideration in PH pathophysiology and finally to summarize unanswered questions and future directions to move this novel concept forward. This forward-thinking view, if proven by further experiments, would provide new opportunities and novel targets for the control and treatment of PH.
| S-EPMC6981289 | biostudies-literature
Project description:IntroductionEndoscopic Lung Volume Reduction has been used to reduce lung hyperinflation in selected patients with severe emphysema. Little is known about the effect of this procedure on the intraparenchymal pulmonary vasculature. In this study we used CT based vascular reconstruction to quantify the effect of the procedure on the pulmonary vasculature.MethodsIntraparenchymal vasculature was reconstructed and quantified in 12 patients with CT scans at baseline and 12 weeks following bilateral introduction of sealants in the upper lobes. The volume of each lung and each lobe was measured, and the vascular volume profile was calculated for both lower lobes. The detected vasculature was further labeled manually as arterial or venous in the right lower lobe.ResultsThere was an increase in the volume of the lower lobes (3.14L to 3.25L, p=0.0005). There was an increase in BV5, defined as the volume of blood vessels with cross sectional area of less than 5mm2, (53.2ml to 57.9ml, p=0.03). This was found to be correlated with the increase in lower lobe volumes (R=0.65, p=0.02). The changes appear to be symmetric for veins and arteries with a correlation coefficient of 0.87 and a slope of near identity.ConclusionIn the subjects studied, there was an increase, from baseline, in BV5 in the lower lobes that correlated with the change in the volume of the lower lobes. The change appeared to be symmetric for both arteries and veins. The study illustrates the use of intraparenchymal pulmonary vascular reconstruction to study morphologic changes in response to interventions.
| S-EPMC4648543 | biostudies-literature
Project description:Background: Pulmonary hypertension is a complication of chronic lung diseases (PH-CLD) associated with significant morbidity and mortality. Management guidelines for PH-CLD emphasize the treatment of the underlying lung disease, but the role of PH-targeted therapy remains controversial. We hypothesized that treatment approaches for PH-CLD would be variable across physicians depending on the type of CLD and the severity of PH. Methods and Results: Between May and July 2020, we conducted an online survey of PH experts asking for their preferred treatment approach in seven hypothetical cases of PH-CLD of varying severity. We assessed agreement amongst clinicians for initial therapy choice using Fleiss' kappa calculations. Over 90% of respondents agreed that they would treat cases of severe PH in the context of mild lung disease with some form of PH-targeted therapy. For cases of severe PH in the context of severe lung disease, over 70% of respondents agreed to use PH-targeted therapy. For mild PH and mild lung disease cases, <50% of respondents chose to start PH-specific therapy. There was overall poor agreement between respondents in the choice to use mono-, double or triple combination therapy with PH-specific agents in all cases. Conclusion: Although management guidelines discourage the routine use of PH-targeted therapies to treat PH-CLD patients, most physicians choose to treat patients with some form of PH-targeted therapy. The choice of therapy and treatment approach are variable and appear to be influenced by the severity of the PH and the underlying lung disease.
| S-EPMC8677825 | biostudies-literature