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European Respiratory Review : An... Mar 2009High-altitude pulmonary hypertension (HAPH) is a specific disease affecting populations that live at high elevations. The prevalence of HAPH among those residing at high... (Review)
Review
High-altitude pulmonary hypertension (HAPH) is a specific disease affecting populations that live at high elevations. The prevalence of HAPH among those residing at high altitudes needs to be further defined. Whereas reduction in nitric oxide production may be one mechanism for the development of HAPH, the roles of endothelin-1 and prostaglandin I₂ pathways in the pathogenesis of HAPH deserve further study. Although some studies have suggested that genetic factors contribute to the pathogenesis of HAPH, data published to date are insufficient for the identification of a significant number of gene polymorphims in HAPH. The clinical presentation of HAPH is nonspecific. Exertional dyspnoea is the most common symptom and signs related to right heart failure are common in late stages of HAPH. Echocardiography is the most useful screening tool and right heart catheterisation is the gold standard for the diagnosis of HAPH. The ideal management for HAPH is migration to lower altitudes. Phosphodiesterase 5 is an attractive drug target for the treatment of HAPH. In addition, acetazolamide is a promising therapeutic agent for high-altitude pulmonary hypertension. To date, no evidence has confirmed whether endothelin-receptor antagonists have efficacy in the treatment of high-altitude pulmonary hypertension.
Topics: Altitude; Humans; Hypertension, Pulmonary
PubMed: 20956117
DOI: 10.1183/09059180.00011104 -
Jornal Brasileiro de Pneumologia :... 2010Over the last five years, knowledge in the field of pulmonary hypertension has grown consistently and significantly. On the basis of various clinical studies showing the... (Review)
Review
Over the last five years, knowledge in the field of pulmonary hypertension has grown consistently and significantly. On the basis of various clinical studies showing the usefulness of new diagnostic tools, as well as the efficacy of new medications and drug combinations, new diagnostic and treatment algorithms have been developed. Likewise, in order to simplify the clinical management of patients, the classification of pulmonary hypertension has been changed in an attempt to group the various forms of pulmonary hypertension in which the diagnostic and therapeutic approaches are similar. The objective of this review was to discuss these modifications, based on the 2005 Brazilian guidelines for the management of pulmonary hypertension, emphasizing what has been added to the international guidelines.
Topics: Humans; Hypertension, Pulmonary; Practice Guidelines as Topic
PubMed: 21225184
DOI: 10.1590/s1806-37132010000600018 -
Journal of Internal Medicine Aug 2017Pulmonary arterial hypertension (PAH), at one time a largely overlooked disease, is now the subject of intense study in many academic and biotech groups. The... (Review)
Review
Pulmonary arterial hypertension (PAH), at one time a largely overlooked disease, is now the subject of intense study in many academic and biotech groups. The availability of new treatments has increased awareness of the condition. This in turn has driven a change in the demographics of PAH, with an increase in the mean age at diagnosis. The diagnosis of PAH in more elderly patients has highlighted the need for careful phenotyping of patients and for further studies to understand how best to manage pulmonary hypertension associated with, for example, left heart disease. The breadth and depth of expertise focused on unravelling the molecular pathology of PAH has yielded novel insights, including the role of growth factors, inflammation and metabolic remodelling. The description of the genetic architecture of PAH is accelerating in parallel, with novel variants, such as those reported in potassium two-pore domain channel subfamily K member 3 (KCNK3), adding to the list of more established mutations in genes associated with bone morphogenetic protein receptor type 2 (BMPR2) signalling. These insights have supported a paradigm shift in treatment strategies away from simply addressing the imbalance of vasoactive mediators observed in PAH towards tackling more directly the structural remodelling of the pulmonary vasculature. Here, we summarize the changing clinical and molecular landscape of PAH. We highlight novel drug therapies that are in various stages of clinical development, targeting for example cell proliferation, metabolic, inflammatory/immune and BMPR2 dysfunction, and the challenges around developing these treatments. We argue that advances in the treatment of PAH will come through deep molecular phenotyping with the integration of clinical, genomic, transcriptomic, proteomic and metabolomic information in large populations of patients through international collaboration. This approach provides the best opportunity for identifying key signalling pathways, both as potential drug targets and as biomarkers for patient selection. The expectation is that together these will enable the prioritization of potential therapies in development and the evolution of personalized medicine for PAH.
Topics: Biomarkers; Genetic Predisposition to Disease; Hemodynamics; Humans; Hypertension, Pulmonary; Ventricular Function, Right
PubMed: 28524624
DOI: 10.1111/joim.12623 -
Pneumologie (Stuttgart, Germany) Nov 2023The new guidelines for the diagnosis and treatment of pulmonary hypertension include a new diagnostic algorithm and provide specific recommendations for the required...
The new guidelines for the diagnosis and treatment of pulmonary hypertension include a new diagnostic algorithm and provide specific recommendations for the required diagnostic procedures, including screening methods. These recommendations are commented on by national experts under the auspices of the DACH. These comments provide additional decision support and background information, serving as a further guide for the complex diagnosis of pulmonary hypertension.
Topics: Humans; Hypertension, Pulmonary; Algorithms
PubMed: 37963477
DOI: 10.1055/a-2145-4678 -
Cellular and Molecular Life Sciences :... Sep 2012The pathobiology of pulmonary arterial hypertension (PAH) involves a remodeling process in distal pulmonary arteries, as well as vasoconstriction and in situ thrombosis,... (Review)
Review
The pathobiology of pulmonary arterial hypertension (PAH) involves a remodeling process in distal pulmonary arteries, as well as vasoconstriction and in situ thrombosis, leading to an increase in pulmonary vascular resistance, right heart failure and death. Its etiology may be idiopathic, but PAH is also frequently associated with underlying conditions such as connective tissue diseases. During the past decade, more than welcome novel therapies have been developed and are in development, including those increasingly targeting the remodeling process. These therapeutic options modestly increase the patients' long-term survival, now approaching 60% at 5 years. However, non-invasive tools for confirming PAH diagnosis, and assessing disease severity and response to therapy, are tragically lacking and would help to select the best treatment. After exclusion of other causes of pulmonary hypertension, a final diagnosis still relies on right heart catheterization, an invasive technique which cannot be repeated as often as an optimal follow-up might require. Similarly, other techniques and biomarkers used for assessing disease severity and response to treatment generally lack specificity and have significant limitations. In this review, imaging as well as current and future circulating biomarkers for diagnosis, prognosis, and follow-up are discussed.
Topics: Biomarkers; Diagnostic Imaging; Familial Primary Pulmonary Hypertension; Humans; Hypertension, Pulmonary
PubMed: 22446747
DOI: 10.1007/s00018-012-0950-4 -
Respiratory Medicine Oct 2015Breathlessness is a common symptom in pulmonary hypertension (PH) and an important cause of morbidity. Though this has been attributed to the well described pulmonary... (Review)
Review
Breathlessness is a common symptom in pulmonary hypertension (PH) and an important cause of morbidity. Though this has been attributed to the well described pulmonary vascular abnormalities and subsequent cardiac remodelling, changes in the airways of these patients have also been reported and may contribute to symptoms. Our understanding of these airway abnormalities is poor with conflicting findings in many studies. The present review evaluates these studies for the major PH groups. In addition we describe the role of cardiopulmonary exercise testing in the assessment of pulmonary arterial hypertension (PAH) by evaluating cardiopulmonary interaction during exercise. As yet, the reasons for the abnormalities in lung function are unclear, but potential causes and the possible role of inflammation are discussed. Future research is required to provide a better understanding of this to help improve the management of these patients.
Topics: Exercise Test; Humans; Hypertension, Pulmonary; Predictive Value of Tests; Pulmonary Diffusing Capacity; Respiratory Function Tests
PubMed: 26033642
DOI: 10.1016/j.rmed.2015.05.022 -
American Journal of Respiratory and... Sep 2022Pediatric pulmonary hypertension is an important cause of childhood morbidity and mortality, but there are limited data on the range of associated diseases,...
Pediatric pulmonary hypertension is an important cause of childhood morbidity and mortality, but there are limited data on the range of associated diseases, contributions of different pulmonary hypertension subtypes, therapeutic strategies, and clinical outcomes in children. To report the 20-year experience of a large UK National Pediatric Pulmonary Hypertension Service focusing on epidemiology and clinical outcomes. Consecutive patients presenting between 2001 and 2021 were included, and survival analysis was performed for incident patients. Of 1,353 patients assessed, a pulmonary hypertension diagnosis was made in 1,101 (81.4%) patients (51% female, median age, 2.6 [interquartile range, 0.8-8.2] years). The most common form was pulmonary arterial hypertension in 48%, followed by 32.3% with pulmonary hypertension due to lung disease. Multiple contributory causes of pulmonary hypertension were common, with 16.9% displaying features of more than one diagnostic group. The annual incidence of childhood pulmonary hypertension was 3.5 (95% confidence interval [CI], 3.3-3.8) per 1 million children, and the prevalence was 18.1 (95% CI, 15.8-20.4) per 1 million. The incidence was highest for pulmonary hypertension due to lung disease in infancy (15.0 [95% CI, 12.7-17.2] per 1 million per year). Overall, 82.4% patients received pulmonary arterial hypertension therapy, and escalation to triple therapy during follow-up was required in 13.1%. In 970 (88.1%) incident patients, transplant-free survival was 86.7% (95% CI, 84.5-89%) at 1 and 68.6% (95% CI, 64.7-72.6%) at 10 years. Pulmonary hypertension due to left heart disease had the lowest survival (hazard ratio, 2.0; 95% CI, 1.36-2.94; < 0.001). Clinical phenotypes of pediatric pulmonary hypertension are heterogeneous and overlapping, with clinical phenotypes that evolve throughout childhood. Despite widespread use of pulmonary arterial hypertension therapy, the prognosis remains poor.
Topics: Familial Primary Pulmonary Hypertension; Female; Humans; Hypertension, Pulmonary; Incidence; Male; Pulmonary Arterial Hypertension; Risk Factors
PubMed: 35579610
DOI: 10.1164/rccm.202110-2428OC -
Respiratory Care Jul 2009Postoperative pulmonary hypertension is a challenging and feared complication of many types of surgery, including lung and heart transplantation, pulmonary... (Review)
Review
Postoperative pulmonary hypertension is a challenging and feared complication of many types of surgery, including lung and heart transplantation, pulmonary thromboendarterectomy, congenital-heart-disease repair, and others. The most severe manifestation is acute right heart syndrome, characterized by right heart failure and cardiovascular collapse-a daunting therapeutic challenge associated with a high mortality. Patients with postoperative pulmonary hypertension must be carefully evaluated to identify reversible contributing factors such as fluid and metabolic imbalance, hypoxemia, and right heart ischemia. A pulmonary arterial catheter and echocardiogram are recommended for evaluation, although their value has not been established in carefully designed trials. Basic principles of management include maintenance of systemic perfusion pressure, optimization of cardiac inotropy, use of lung-protective ventilator strategies, and attempting to reduce right-ventricular afterload using pulmonary vasodilators. Unfortunately, controlled trials upon which to base therapy are lacking, and most approaches are supported only by uncontrolled or anecdotal evidence. Better understanding of the pathophysiology of right heart failure and controlled trials testing therapeutic approaches are needed if we are to make progress in treating this heretofore highly mortal condition.
Topics: Cardiac Output; Humans; Hypertension, Pulmonary; Postoperative Complications; Risk Factors; Vasodilator Agents
PubMed: 19558745
DOI: 10.4187/002013209793800439 -
Medical Science Monitor : International... Apr 2012Pulmonary arterial hypertension (PAH) is a chronic progressive disease of the pulmonary vasculature characterized by elevated pulmonary arterial pressure and secondary... (Review)
Review
Pulmonary arterial hypertension (PAH) is a chronic progressive disease of the pulmonary vasculature characterized by elevated pulmonary arterial pressure and secondary right ventricular failure. PAH is considered a life-threatening condition unless treated. This article provides a comprehensive review of controlled and uncontrolled trials to define the risk-benefit for different therapeutic options of this clinical disorder. Relevant published articles were identified through searches of the National Center for Biotechnology PubMed database. All therapeutic measures for PAH were discussed. Six drugs have been approved in the United States for the treatment of PAH. Extensive medical advancement has been achieved in treatment of PAH. However, none of the approved therapies have shown ability to cure the disease. New research should be performed to develop promising new therapies.
Topics: Antihypertensive Agents; Drug Therapy, Combination; Humans; Hypertension, Pulmonary
PubMed: 22460104
DOI: 10.12659/msm.882607 -
European Respiratory Review : An... Mar 2009Recent advances in the field of pulmonary hypertension (PH) have provided clinicians with a range of treatment options, but effective disease management in children... (Review)
Review
Recent advances in the field of pulmonary hypertension (PH) have provided clinicians with a range of treatment options, but effective disease management in children presents a unique challenge. The present article will discuss the steps being taken to address unmet needs in paediatric PH. Understanding the epidemiology of paediatric PH is essential to guide management decisions, but such epidemiological data are scarce. The first international paediatric PH registry, Tracking Outcomes in Paediatric Pulmonary Hypertension (TOPP), promises to become a vital resource. Studies of PH therapies are rare in children, and treatment of paediatric PH is generally guided by the adult treatment algorithm, with some adaptations. However, invasive management options, such as continuous prostacyclin infusion, even if effective, are challenging in children, and further research is required to develop appropriate treatment strategies, formulations and doses for paediatric PH. Measures of treatment success must also be defined, and the applicability of end-points from adult clinical studies remains an open question. In summary, further epidemiological and treatment data are needed for paediatric pulmonary hypertension. The international TOPP registry will provide a valuable insight, but this must be complemented by research and development of adapted paediatric therapies. Dedicated childhood pulmonary hypertension services would optimise the diagnosis and management of this life-threatening disease.
Topics: Adolescent; Adult; Child; Child, Preschool; Humans; Hypertension, Pulmonary
PubMed: 20956118
DOI: 10.1183/09059180.00011109