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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pulmonary hypertension (PH) is associated with impaired production of the vasodilator nitric oxide (NO). Riociguat (BAY 63-2521; Bayer Healthcare AG, Wuppertal, Germany) acts directly on soluble guanylate cyclase, stimulating the enzyme and increasing sensitivity to low NO levels. The present study evaluates riociguat safety, tolerability and efficacy in patients with moderate-to-severe PH (pulmonary arterial hypertension, distal chronic thromboembolic PH or PH with mild to moderate interstitial lung disease). The optimal tolerated dose was identified by incremental dosing in four patients with PH; pharmacodynamic and pharmacokinetic parameters were assessed following single-dose administration (2.5 mg or 1 mg) in 10 and five patients with PH, respectively. All subjects (n = 19) were analysed for safety and tolerability. Riociguat had a favourable safety profile at single doses < or =2.5 mg. It significantly improved pulmonary haemodynamic parameters and cardiac index in patients with PH in a dose-dependent manner, to a greater extent than inhaled NO. Although riociguat also had significant systemic effects and showed no pulmonary selectivity, mean systolic blood pressure remained >110 mmHg. The present report is the first to describe the use of riociguat in patients with pulmonary hypertension. The drug was well-tolerated and superior to nitric oxide in efficacy and duration. Riociguat, therefore, has potential as a novel therapy for pulmonary hypertension and warrants further investigation.
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PMID:First acute haemodynamic study of soluble guanylate cyclase stimulator riociguat in pulmonary hypertension. 1933 88

Pulmonary manifestations of SSc are leading causes of disease-related morbidity and mortality. Key clinical issues relate to the early detection of fibrotic lung disease, the interpretation of its significance, and decisions on when to start therapy. Respiratory symptoms are common in patients with SSc, but physical examination often fails to establish if the underlying cause is interstitial lung disease (ILD), pulmonary arterial hypertension (PAH), impaired locomotion due to systemic disease or loss of fitness. Impaired lung function is usually evident on pulmonary function testing, with the pattern of functional impairment often discriminating usefully between ILD and PAH. The presence of PAH can be indicated by echocardiography and must be confirmed by right heart catheterization. Whereas chest radiographs detect established ILD, high-resolution CT can identify earlier or very mild inflammatory changes. Treatment options for ILD are limited to immunosuppressive agents, notably cyclophosphamide, often given in combination with low-dose prednisolone. Recent studies have shown that cyclophosphamide is effective in stabilizing pulmonary function--especially in patients with severe fibrotic disease--and in improving health-related quality of life. Progression of pulmonary manifestations and responses to treatment are best monitored using pulmonary function testing. For patients with severe end-stage pulmonary fibrosis, lung transplantation may offer a viable alternative therapeutic option.
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PMID:Pulmonary complications: one of the most challenging complications of systemic sclerosis. 1948 23

The 4th World Symposium on Pulmonary Hypertension was the first international meeting to focus not only on pulmonary arterial hypertension (PAH) but also on the so-called non-PAH forms of pulmonary hypertension (PH). The term "non-PAH PH" summarizes those forms of PH that are found in groups 2 to 5 of the current classification of PH, that is, those forms associated with left heart disease, chronic lung disease, recurrent venous thromboembolism, and other diseases. Many of these forms of PH are much more common than PAH, but all of them have been less well studied, especially in terms of medical therapy. The working group on non-PAH PH focused mainly on 4 conditions: chronic obstructive lung disease, interstitial lung disease, chronic thromboembolic PH, and left heart disease. The medical literature regarding the role of PH in these diseases was reviewed, and recommendations regarding diagnosis and treatment of PH in these conditions are provided. Given the lack of robust clinical trials addressing PH in any of these conditions, it is important to conduct further studies to establish the role of medical therapy in non-PAH PH.
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PMID:Diagnosis, assessment, and treatment of non-pulmonary arterial hypertension pulmonary hypertension. 1955 62

The respiratory system is commonly involved in systemic lupus erythematosus. Lung disorders are classified as primary (due to lupus) and secondary to other conditions. Pleuritis and pulmonary infections are the most prevalent respiratory manifestations of each type. Other infrequent manifestations include interstitial lung disease, acute lupus pneumonitis, diffuse alveolar haemorrhage, pulmonary arterial hypertension, acute reversible hypoxaemia and shrinking lung syndrome. Even when current diagnostic tests contribute to an earlier diagnosis, the treatment of these manifestations is based on clinical experience and small series. Larger controlled trials of the different therapies in the treatment of those lung manifestations of lupus are needed. Overall malignancy is little increased in lupus, but lung cancer and non-Hodgkin's lymphoma are among the most frequent types of cancer found in these patients. As survival in lupus patients has improved over recent decades, avoiding pulmonary damage emerges as an important objective.
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PMID:Respiratory manifestations of systemic lupus erythematosus: old and new concepts. 1959 78

Scleroderma is a generic term for autoimmunological diseases having thickened sclerotic skin lesions in common. Scleroderma belongs to a group of connective tissue diseases. The systemic form of scleroderma is called progressive systemic sclerosis (PSS) or systemic sclerosis (SSc). Lung impairments, namely interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH), are one of the most common manifestations in SSc. This article summarises the forms of lung impairment in SSc with special emphasis on interstitial lung diseases and draws attention to the so far identified pathogenetic mechanisms and the presently accepted therapeutic options.
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PMID:[Lung impairment in systemic sclerosis]. 1970 6

Measurement of exercise capacity is an integral element in assessment of patients with cardiopulmonary disease. The 6-min walk test (6MWT) provides information regarding functional capacity, response to therapy and prognosis across a range of chronic cardiopulmonary conditions. A distance less than 350 m is associated with increased mortality in chronic obstructive pulmonary disease, chronic heart failure and pulmonary arterial hypertension. Desaturation during a 6MWT is an important prognostic indicator for patients with interstitial lung disease. The 6MWT is sensitive to commonly used therapies in chronic obstructive pulmonary disease such as pulmonary rehabilitation, oxygen, long-term use of inhaled corticosteroids and lung volume reduction surgery. However, it appears less reliable to detect changes in clinical status associated with medical therapies for heart failure. A change in walking distance of more than 50 m is clinically significant in most disease states. When interpreting the results of a 6MWT, consideration should be given to choice of predictive values and the methods by which the test was carried out.
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PMID:The six-minute walk test: a useful metric for the cardiopulmonary patient. 1973 97

Evidence is accumulating for the early sustained usage of disease-modifying anti-rheumatic drugs (DMARDs) in rheumatoid arthritis. Leflunomide was licensed for the treatment of rheumatoid arthritis in 1998. Postmarketing surveillance, case reports and observational studies have highlighted less common or unexpected adverse events. Therefore, it is appropriate that we review the benefit-risk profile of leflunomide after 10 years of widespread usage. A wide-based search of relevant literature was performed to formulate this assessment. The improvements in rheumatoid arthritis shown by double-blind, randomized controlled trials (RCTs) of leflunomide have now been shown to be maintained beyond 4 years in open-label extension studies. Leflunomide is comparable to methotrexate, but better than sulfasalazine at 24 months in only one study. However, tolerance in clinical practice research shows higher than expected withdrawal rates due to both toxicity and lack of efficacy when compared with methotrexate and placebo. Adverse events reported include gastrointestinal upset, hypertension, headache, hepatotoxicity and hair loss, as well as predisposition to infection and peripheral neuropathy. The incidence of gastrointestinal adverse effects for leflunomide is similar to sulfasalazine but higher than those seen with methotrexate. Serious drug-induced hepatotoxicity leading to hospitalization is rare (0.02%), but isolated fatalities from liver failure have been documented. It is considered likely, but not yet proven, that there may be an increased incidence of weight loss and interstitial lung disease with leflunomide. Leflunomide in combination with methotrexate or sulfasalazine is an effective regimen in RCTs utilizing placebo controls, but more research is needed to confirm its effectiveness in combination with other DMARDs, particularly biologicals. The active metabolite of leflunomide is teratogenic in animal studies and is also found in breast milk. Therefore, contraception is advised in both males and females of child-bearing potential. There are genetic, pharmacokinetic and biochemical reasons to explain variation in both patient response and adverse event profile. Hence, blood and blood pressure monitoring are recommended and therapeutic drug monitoring should be considered in clinical nonresponders. Leflunomide is an effective DMARD that sustains a clinical and radiological response comparable to sulfasalazine and methotrexate. However, adverse effects necessitate frequent monitoring. It should be used with caution in those of child-bearing potential and with pre-existing lung and liver disease.
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PMID:Benefit-risk assessment of leflunomide: an appraisal of leflunomide in rheumatoid arthritis 10 years after licensing. 2048 33

Pulmonary involvement is second in frequency only to esophageal involvement as a visceral complication of systemic sclerosis (SSc) and has surpassed renal involvement as the most common cause of death. Interstitial lung disease and pulmonary vascular disease, particularly pulmonary arterial hypertension, are the most commonly encountered types of lung involvement. Chronic aspiration, airway disease, neuromuscular weakness, extrinsic pulmonary restrictive pathology, pleural effusions, pneumothorax, and lung cancer cause clinically significant disease and occur commonly enough to be routinely considered in the assessment of the SSc patient with respiratory symptoms. Affected patients have a significantly worse prognosis than patients with SSc who are free of pulmonary involvement.
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PMID:Scleroderma lung disease. 2006 8

PAH (pulmonary arterial hypertension) is the leading cause of fatal right ventricular failure. However, rarely detectable, cTnT [cardiac TnT (troponin T)] is a significant prognostic marker. Therefore the aim of the present study was to evaluate the usefulness of a novel high-sensitive cTnT (hsTnT) assay as a parameter for functional and prognostic evaluation of PAH patients. In 55 PAH patients (idiopathic, n=20; chronic thromboembolic, n=30; and interstitial lung disease, n=5) with a mean pulmonary artery pressure of 45+/-18 mmHg, cTnT was measured by a fourth-generation conventional assay and a novel hsTnT assay with a lower detection limit at 2 pg/ml [total imprecision <10% at the 99th percentile value (13.4 pg/ml)]. In 90.9% of patients, cTnT was detectable using the hsTnT assay and in 30.9% using the fourth-generation assay. Concentrations >99th percentile were observed in 27.3% using hsTnT compared with 10.9% using the fourth-generation assay. A total of five out of six patients with cTnT values >30 pg/ml (fourth-generation assay) or >29.5 pg/ml (hsTnT assay) died during the 12-month follow-up. There was a correlation between hsTnT and 6-min walk distance (r=-0.92, P=0.0014), right ventricular systolic strain (r=0.95, P=0.0018) and strain rate (r=0.82, P=0.0021). In AUC (area under the curve) analysis, hsTnT predicted death at least as effectively as hFABP (heart-type fatty-acid-binding protein) or NT-proBNP (N-terminal pro-brain natriuretic protein). Moreover, hsTnT predicted a WHO (World Health Organization) functional class >II better than NT-proBNP or hFABP. In conclusion, in PAH patients, the novel biomarker hsTnT is associated with death and advanced WHO functional class, and is related to systolic right ventricular dysfunction and an impaired 6-min walk distance.
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PMID:High-sensitive troponin T: a novel biomarker for prognosis and disease severity in patients with pulmonary arterial hypertension. 2044 64

In systemic sclerosis (SSc), major determinant of morbidity and mortality is pulmonary complication including pulmonary interstitial lung disease (ILD) and pulmonary arterial hypertension (PAH). In this study, the natural course of pulmonary involvement in SSc patients was investigated. This was a historical cohort study of SSc patients at a referral center for SSc in Iran between February 1998 and December 2007. Patients had a standardized initial evaluation, and interstitial pulmonary involvement was established by high-resolution CT scan (HRCT). Pulmonary hypertension was assessed by tricuspid gradient on echocardiography. Development of abnormal FVC or DLCO was considered as secondary outcome. Analysis of pulmonary survival was performed for primary and secondary outcomes. Ninety-one SSc patients were included in the study with the mean age of 44.1 (14.8). Among these, 65 (71.4%) patients were classified as limited subtype (lcSSc) and 84 (93.3%) were women. PAH was investigated in 8 (8.2%) patients, 1 (6.7%) in dcSSc and 7 (15.9%) in lcSSc subtype of disease. ILD had developed after a median of 107 (SE = 24.4) months after the first symptom of SSc, and 29 patients (31.9%) developed pulmonary fibrosis. Alveolitis and fibrosis had developed after a median of 129.0 (22.9) and 259.0 (74.2) months, respectively. There was a significant difference in Alveolitis-free pulmonary survival between two subgroups of the disease, which showed pulmonary alveolitis developed later in limited SSc (P = 0.03). The difference was not significant in two subtypes when Cox regression model was used to identify the effect of other prognostic factors on pulmonary survival in patients. In the present study, clinical manifestations of two subtypes of disease were divergent at first; however they became convergent in late stages, and this was the same as results in previous studies. Echocardiography for evaluation of pulmonary hypertension and pulmonary function tests for early detection of ILD and PAH is recommended for SSc patients to detect early stages of pulmonary involvement before significant vascular and fibrotic changes occur.
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PMID:Pulmonary survival study in 91 patients with systemic sclerosis. 2049 69


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