Diagnosis and management of idiopathic pulmonary fibrosis: Implications for respiratory care

Although poorly understood, idiopathic pulmonary fibrosis is the most common of the idiopathic interstitial lung diseases. Its etiology is unknown, but how this fibrotic process develops in the lung has been studied over the last 60 years. It is a relatively rare disease, afflicting those 50-70 years of age, slightly more common among men than women, without racial predilection. The most common complaint is progressive shortness of breath. Pulmonary function testing reveals a restrictive ventilatory defect with a diminished diffusion capacity. The lungs demonstrate fibrotic and cystic areas interspersed with normal lung on radiographic and pathologic examination. No definitive medical treatment is available, although most patients are given trials of corticosteroids, alone or in combination with cytotoxic agents. On average, patients survive 2-4 years after diagnosis. Lung transplantation has been the only therapy shown to improve survival of those with idiopathic pulmonary fibrosis.     

When cure is care: diagnosis and management of pulmonary arterial hypertension

PURPOSE: The purpose of this article is to provide nurse practitioners with an understanding of the pathophysiology of pulmonary arterial hypertension (PAH) disease, clinical manifestations, diagnostic evaluation, drug therapy, strategies for health promotion, and relevant care issues for patients and families. DATA SOURCES: Selected clinical and research articles, as well as current government guidelines. CONCLUSIONS: Symptoms expressed are more apparent as PAH disease progresses, leaving fewer treatment options in advanced disease stages. New drugs are currently being tested for the treatment of PAH; however, the costs of many of the currently approved treatments may be prohibitive. IMPLICATIONS FOR PRACTICE: Earlier recognition of disease symptoms leads to prompt initiation of diagnostic evaluation and referral to specializing medical centers. Upon referral, specialty centers may begin appropriate treatment regimens earlier in the disease process, which could improve clinical outcomes and quality of life.     

Ambrisentan for the management of pulmonary arterial hypertension

BACKGROUND: Approved by the US Food and Drug Administration in 2007, ambrisentan is the second oral endothelin A-receptor antagonist available for the management of pulmonary arterial hypertension (PAH) in patients with World Health Organization class II or III symptoms. OBJECTIVE: This article examines the clinical pharmacology of ambrisentan, its efficacy and adverse effects, and future directions for research. METHODS: Pertinent articles and abstracts were identified through searches of MEDLINE and Current Contents from 1966 to January 15, 2008, using the term ambrisentan. The reference lists of identified articles were searched for additional publications. Abstracts presented at professional meetings from 2005 through 2007 were also reviewed. RESULTS: The literature review identified 3 studies of ambrisentan in PAH: 1 dose-ranging study; 2 randomized, double-blind, placebo-controlled studies; and 1 drug-conversion study. In the dose-ranging study, ambrisentan at doses of 1 to 10 mg was associated with significant improvements from baseline in the 6-minute walk distance at 12 weeks that ranged from 33.9 m with ambrisentan 1 mg (P = 0.003) to 38.1 m with ambrisentan 5 mg (P = 0.001). In the placebo-controlled studies, ambrisentan at doses of 2.5 to 10 mg/d was associated with significant improvements versus placebo in the 6-minute walk distance at 12 weeks that ranged from 22 m with ambrisentan 2.5 mg (P = 0.022) to 59 m with ambrisentan 5 mg (P 相似文献   

Diagnosis and treatment of pediatric pulmonary arterial hypertension

Introduction: Pediatric pulmonary arterial hypertension (PAH) remains a rare and severe disease with a poor prognosis. PAH may be idiopathic, heritable or associated with systemic conditions in particular associated with congenital heart disease.

Areas covered: A thorough and extensive diagnostic approach is required for a correct diagnosis. The outcome has improved over the last decade with a better diagnostic approach and with the initiation of new targeted therapies. However, there is still significant progress to achieve as there is still no cure for this devastating disease.

Expert opinion: Adapted clinical studies to define the best therapeutic approach are needed. Even if the treatment approach is still mainly derived from adult data and expert consensus, several studies and registries are currently underway and should deliver important information in the next future.

This review aims to give an overview of the current diagnosis and treatment strategies of PAH.     

Evidence-based pharmacologic management of pulmonary arterial hypertension

BACKGROUND: Pulmonary arterial hypertension (PAH) is a debilitating chronic disorder of the pulmonary vasculature characterized by elevated mean pulmonary arterial pressure, right-sided heart failure, and early mortality. OBJECTIVES: This paper reviews the available information on PAH, including its pathophysiology, classification of its severity, current treatment options, drug interactions, pharmacokinetics, and cost considerations. The results of clinical trials of the available treatments are summarized, and a suggested treatment algorithm is provided as a guide to the medical management of PAH. METHODS: Pertinent articles were identified by a search of MEDLINE through May 2007 using the terms primary pulmonary hypertension, pulmonary arterial hypertension, prostacyclin, pulmonary vasodilators, endothelin-receptor antagonists, and phosphodiesterase inhibitors. Trials with prospective, randomized designs were given precedence, and prospective studies having nonrandomized, open-label designs or using historical controls were included if they contributed useful knowledge. Retrospective studies were not included. Results: In two 12-week, randomized, open-label trials in patients with moderate to severe PAH (N = 81 and N = 111), exercise capacity, measured on the 6-minute walk test (6-MWT), was significantly improved with intravenous epoprostenol compared with conventional therapy (+31 vs -29 m, respectively, in one study [P = 0.002]; +46 vs -48 m in the other [P < 0.001]). In one of these trials, intravenous epoprostenol also was associated with a significant survival benefit (P < 0.003). In a 12-week, randomized, doubleblind, placebo-controlled trial in 470 patients with moderate to severe PAH, subcutaneous treprostinil plus conventional therapy was associated with a significant improvement on the 6-MWT compared with conventional therapy alone (+10 vs 0 m, respectively; P = 0.006). In a 16-week, randomized, double-blind, placebo-controlled trial in 213 patients with mild to moderate symptoms, the oral endothelin-receptor antagonist bosentan was associated with a significant improvement on the 6-MWT compared with placebo (+36 vs -8 m, respectively; P 20% decrease in pulmonary arterial pressure and pulmonary vascular resistance immediately after challenge) had a survival rate of 94% at 1, 3, and 5 years. CONCLUSIONS: Patients who respond to an acute trial of a vasodilator may be treated with an oral calcium channel blocker, whereas oral therapies such as sildenafil and bosentan have been effective in patients with mild to moderate symptoms. Infusions of the prostacyclin analogues epoprostenol and treprostinil appear to be the treatment of choice for moderate to severe PAH, and agents with alternate routes of delivery such as inhaled iloprost may be advantageous in adjunctive roles. Future trials that focus on the long-term effects of currently available agents, as well as on combination therapy, are needed.     

Epoprostenol use for pulmonary arterial hypertension in the palliative care setting

Prostacyclin analogues such as epoprostenol (Flolan?) are commonly used in the treatment of pulmonary arterial hypertension (PAH). However, their complex administration and significant cost may limit the access that patients with PAH have to palliative and hospice care. We herein report our experience using epoprostenol in a dedicated palliative care unit and present our inpatient protocol for the drug's administration.     

Iloprost for idiopathic pulmonary arterial hypertension

Idiopathic pulmonary arterial hypertension is a rare but serious and life-threatening disease that leads to right heart failure and death within 2.8 years without specific treatment. This review focuses on the stable prostacyclin analog iloprost, its biologic action and pharmacology and, finally, on its clinical development, efficacy and safety in patients with idiopathic pulmonary arterial hypertension, which led to its approval for this indication. Furthermore, this review assesses the role of iloprost compared with other newly developed drugs, such as the endothelin receptor antagonist bosentan and the phosphodiesterase-5 inhibitor sildenafil, as well as other modes of application of prostacyclin and its analogs for the treatment of idiopathic pulmonary arterial hypertension. Based on the different modes of action of these substances, a combination of these treatments could be most promising for the future.     

微小RNA与肺动脉高压

肺动脉高压(PAH)是一类以肺循环阻力增高为主要特征、最终导致右心功能不全、乃至死亡的慢性肺疾病,其病因复杂,预后差.微小RNA(miRNA)是一种内源性的非编码RNA,与PAiH的发生、发展密切相关,可能是潜在的药物治疗靶点.本文主要对miRNA在PAH慢性缺氧、骨形成蛋白Ⅱ型受体(BMPRR2)、apelin-APJ、以及右心功能不全等方面的研究进展进行综述,为探索PAH的发病机制、诊疗研究提供新的方向和思路.     

Understanding pulmonary arterial hypertension

New therapies improve the management of pulmonary arterial hypertension.     

Drug-associated pulmonary arterial hypertension

Introduction: While pulmonary arterial hypertension remains an uncommon diagnosis, various therapeutic agents are recognized as important associations. These agents are typically categorized into “definite”, “likely”, “possible”, or “unlikely” to cause pulmonary arterial hypertension, based on the strength of evidence.

Objective: This review will focus on those therapeutic agents where there is sufficient literature to adequately comment on the role of the agent in the pathogenesis of pulmonary arterial hypertension.

Methods: A systematic search was conducted using PubMed covering the period September 1970– 2017. The search term utilized was “drug induced pulmonary hypertension”. This resulted in the identification of 853 peer-reviewed articles including case reports. Each paper was then reviewed by the authors for its relevance. The majority of these papers (599) were excluded as they related to systemic hypertension, chronic obstructive pulmonary disease, human immunodeficiency virus, pulmonary fibrosis, alternate differential diagnosis, treatment, basic science, adverse effects of treatment, and pulmonary hypertension secondary to pulmonary embolism.

Agents affecting serotonin metabolism (and related anorexigens): Anorexigens, such as aminorex, fenfluramine, benfluorex, phenylpropanolamine, and dexfenfluramine were the first class of medications recognized to cause pulmonary arterial hypertension. Although most of these medications have now been withdrawn worldwide, they remain important not only from a historical perspective, but because their impact on serotonin metabolism remains relevant. Selective serotonin reuptake inhibitors, tryptophan, and lithium, which affect serotonin metabolism, have also been implicated in the development of pulmonary arterial hypertension.

Interferon and related medications: Interferon alfa and sofosbuvir have been linked to the development of pulmonary arterial hypertension in patients with other risk factors, such as human immunodeficiency virus co-infection.

Antiviral therapies: Sofosbuvir has been associated with two cases of pulmonary artery hypertension in patients with multiple risk factors for its development. Its role in pathogenesis remains unclear.

Small molecule tyrosine kinase inhibitors: Small molecule tyrosine kinase inhibitors represent a relatively new class of medications. Of these dasatinib has the strongest evidence in drug-induced pulmonary arterial hypertension, considered a recognized cause. Nilotinib, ponatinib, carfilzomib, and ruxolitinib are newer agents, which paradoxically have been linked to both cause and treatment for pulmonary arterial hypertension.

Monoclonal antibodies and immune regulating medications: Several case reports have linked some monoclonal antibodies and immune modulating therapies to pulmonary arterial hypertension. There are no large series documenting an increased prevalence of pulmonary arterial hypertension complicating these agents; nonetheless, trastuzumab emtansine, rituximab, bevacizumab, cyclosporine, and leflunomide have all been implicated in case reports.

Opioids and substances of abuse: Buprenorphine and cocaine have been identified as potential causes of pulmonary arterial hypertension. The mechanism by which this occurs is unclear. Tramadol has been demonstrated to cause severe, transient, and reversible pulmonary hypertension.

Chemotherapeutic agents: Alkylating and alkylating-like agents, such as bleomycin, cyclophosphamide, and mitomycin have increased the risk of pulmonary veno-occlusive disease, which may be clinically indistinct from pulmonary arterial hypertension. Thalidomide and paclitaxel have also been implicated as potential causes.

Miscellaneous medications: Protamine appears to be able to cause acute, reversible pulmonary hypertension when bound to heparin. Amiodarone is also capable of causing pulmonary hypertension by way of recognized side effects.

Conclusions: Pulmonary arterial hypertension remains a rare diagnosis, with drug-induced causes even more uncommon, accounting for only 10.5% of cases in large registry series. Despite several agents being implicated in the development of PAH, the supportive evidence is typically limited, based on case series and observational data. Furthermore, even in the drugs with relatively strong associations, factors that predispose an individual to PAH have yet to be elucidated.     

Pulmonary arterial hypertension: evaluation and management

Pulmonary arterial hypertension (PAH), a rare disease involving the pulmonary vascular circuit, is defined as an elevation in pulmonary arterial pressures and is characterized by symptoms of dyspnea, chest pain, and syncope. If left untreated, the disease carries a high mortality rate, with the most common cause of death being decompensated right heart failure. Over the past 5 years, there have been significant advances in this field in regards to understanding the pathogenesis, diagnosis, and classification of PAH. The availability of newer drugs has resulted in a radical change in the management of this disease with significant improvement in both quality of life and mortality. Ongoing research promises to lead to a more comprehensive understanding of the genetics, etiology, and pathogenesis of pulmonary arterial hypertension, which may ultimately translate into more effective therapeutic options.     

雾化吸入伊洛前列素治疗肺动脉高压的护理管理及随访

目的 探讨雾化吸入伊洛前列素治疗肺动脉高压患者的护理安全管理及随访要点.方法 通过对25例肺高压患者在常见治疗基础上进行6个月伊洛前列素吸入及随访,对比吸入前后患者的6 min步行距离指标.结果 患者用药后疗效显著,且无严重不良反应.结论 雾化吸入伊洛前列素在治疗肺高压上效果较好,可明显改善患者身体状况与生活质量.在整个治疗过程中对患者实施全方位的护理安全管理,定期规律地进行随访,提高了患者治疗的信心和依从性,从而进一步增强治疗效果.     

风湿性瓣膜病变合并肺动脉高压87例观察

目的:总结87例风湿性瓣膜病变合并肺动脉高压患者行手术治疗的围术期处理经验。方法:87例风湿性瓣膜病变合并肺动脉高压患者行二尖瓣置换75例,二尖瓣置换 主动脉瓣置换12例。结果:此组患者手术过程顺利,术后并发低心输出量综合征5例,严重心律失常9例,早期死亡2例,病死率2.3%,其中低心排1例,1例因多脏器功能衰竭死亡。结论:风湿性瓣膜病变合并肺动脉高压患者病情较重,注意围术期各环节处理,即重视术前心功能改善,术中加强心肌保护,合理纠正病变,术后严密监护,可提高手术成功率。     

超声心动图对肺动脉高压和肺静脉高压的非侵入性鉴别诊断研究

目的 确定超声心动图是否能非侵入性鉴别诊断肺动脉高压(PAH)和肺静脉高压(PVH).方法 随机选择56例经超声心动图确定的肺动脉收缩压(PASP)≥40 mmHg的患者,并在7 d内进行心导管检查.依据左室舒张末压或肺毛细血管契压(PCWP)将患者分为PAH组30例,PVH组26例.两组患者应用常规和组织多普勒超声技术分别测定跨二尖瓣舒张早期峰值血流速度E峰,晚期A峰,E/A比值,二尖瓣血流减速时间(DT),舒张早期二尖瓣环运动速度(E')和E/E'值.结果 与PVH组比较,PAH组A峰、DT、PASP及E,增大,而E峰、E/A值和E/E'值却降低.E/E'值和E/A值是PAH和PVH鉴别诊断的最佳指标,其E/E'值和E/A值的ROC曲线下面积分别为97%和91%,而诊断PVH的最佳界值点是E/E'>9.2(敏感性为95%,特异性为97%),E/A>1.7(敏感性为75%,特异性为92%).结论 采用常规和组织多普勒超声技术可正确鉴别PAH和PVH.     

CT诊断肺动脉高压Meta分析

目的 采用Meta分析评价CT在肺动脉高压中的诊断价值。方法 通过检索Pubmed、Elsevier和中国期刊网数据库(CNKI),获得相关中、英文文献,采用QUADAS-2工具对纳入的研究进行质量评价。采用Meta-disc 1.40软件对纳入的文献进行异质性检验,根据随机效应模型,汇总敏感度、特异度,并绘制综合受试者工作特征(SROC)曲线,计算曲线下面积。结果 共12篇文献符合要求,纳入其中8篇文献、均以肺动脉直径/升主动脉直径>1或≥1作为肺动脉高压的诊断标准,纳入对象共计1111例。Deeks漏斗图分析提示各文献间无明显发表偏倚(P=0.501)。汇总后的敏感度、特异度分别为74%(95%可信区间:70%~77%)、81%(95%可信区间:76%~85%),SROC曲线下面积为0.8535。结论 CT检查肺动脉直径/主动脉直径诊断肺动脉高压具有一定的临床应用价值。     

Bosentan for the treatment of pulmonary arterial hypertension

OBJECTIVE: To describe the pharmacology, pharmacokinetics, efficacy, and safety of bosentan in the treatment of pulmonary arterial hypertension (PAH). DATA SOURCES: A MEDLINE and Current Contents search (1966-June 2002) of the English-language literature was conducted to identify published dose-ranging, pharmacokinetic, pivotal efficacy trials and review articles of bosentan and endothelin antagonists. Additional references were identified from the bibliographies of the retrieved articles. DATA SYNTHESIS: Bosentan is the first orally active, nonpeptide endothelin receptor antagonist approved by the Food and Drug Administration for use in patients with World Health Organization (WHO) functional class III and IV PAH. Titrated to a dose of 125 mg twice daily, bosentan produces pulmonary vasodilation, improving cardiopulmonary hemodynamics leading to better outcomes for patients. It is metabolized primarily by the hepatic system via the cytochrome P450 enzyme pathway and eliminated by biliary excretion. Bosentan is an inducer of the isoenzymes CYP3A4 and 2C9. It possesses a unique pharmacokinetic profile with a terminal elimination half-life of approximately 5 hours, yet steady-state plasma concentrations are not achieved for 3-5 days as a result of enhanced drug clearance and autoinduction following multiple daily dosing. The major adverse effects of bosentan are the potential for birth defects and hepatotoxicity. CONCLUSIONS: The use of bosentan in patients with WHO functional class III and IV PAH is associated with improved exercise tolerance, cardiopulmonary hemodynamics, and increased time to clinical worsening when compared with placebo. It offers significant advantage in ease of administration and quality of life compared with epoprostenol therapy, with similar efficacy.     

Anticoagulation in pulmonary arterial hypertension

In pulmonary arterial hypertension (PAH), thrombosis and thromboembolism occurs as a consequence of pulmonary microvasculopathy with a change of pulmonary vascular microenviroment toward a procoagulant, prothrombotic and antifibrinolytic pattern. Circulating antiphospholipid antibodies, increased plasma levels of platelet aggregating agents (serotonin, thromboxane), adhesion molecules (P selectin, von Willebrand factor), antifibrinolytic enzymes (plasminogen activator inhibitor 1) and prothrombotic cytokines have been identified in PAH patients so far. Thrombogenic pulmonary vasculopathy has been documented in many patients with PAH. Furthermore, most patients will not be diagnosed until right heart enlargement and impaired right ventricular function has developed. Thus, there is clear rationale for a treatment with anticoagulation. In four uncontrolled studies Warfarin improved the prognosis of patients with idiopathic and other forms of PAH. However, so far there are no prospective randomised studies evaluating the role of anticoagulants in the treatment of PAH. This review summarizes the current data and guidelines concerning anticoagulation in PAH.