Abstract:
:Our aim is to assess the safety and potential efficacy of a novel treatment paradigm in pulmonary arterial hypertension (PAH), immunomodulation by blocking interleukin-6 (IL6) signaling with the IL6 receptor antagonist, tocilizumab. Inflammation and autoimmunity are established as important in PAH pathophysiology. One of the most robust observations across multiple cohorts in PAH has been an increase in IL6, both in the lung and systemically. Tocilizumab is an IL-6 receptor antagonist established as safe and effective, primarily in rheumatoid arthritis, and has shown promise in scleroderma. In case reports where the underlying cause of PAH is an inflammatory process such as systemic lupus erythematosus, mixed connective tissue disease (MCTD), and Castleman's disease, there have been case reports of regression of PAH with tocilizumab. TRANSFORM-UK is an open-label study of intravenous (IV) tocilizumab in patients with group 1 PAH. The co-primary outcome measures will be safety and the change in resting pulmonary vascular resistance (PVR). Clinically relevant secondary outcome measurements include 6-minute walk distance, WHO functional class, quality of life score, and N-terminal pro-brain natriuretic peptide (NT-proBNP). If the data support a potentially useful therapeutic effect with an acceptable risk profile, the study will be used to power a Phase III study to properly address efficacy.
journal_name
Pulm Circjournal_title
Pulmonary circulationauthors
Hernández-Sánchez J,Harlow L,Church C,Gaine S,Knightbridge E,Bunclark K,Gor D,Bedding A,Morrell N,Corris P,Toshner Mdoi
10.1177/2045893217735820subject
Has Abstractpub_date
2018-01-01 00:00:00pages
2045893217735820issue
1eissn
2045-8932issn
2045-8940journal_volume
8pub_type
杂志文章abstract::Rapid access to lung-derived cells from stable subjects is a major challenge in the pulmonary hypertension field, given the relative contraindication of lung biopsy. In these studies, we sought to demonstrate the importance of evaluating a cell type that actively participates in disease processes, as well as the poten...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/688314
更新日期:2016-12-01 00:00:00
abstract::Late-onset pulmonary arterial hypertension (PAH) is a rare but fatal complication in patients with childhood surgical repair of dextro-transposition of great arteries (D-TGA), especially with the Mustard and Senning procedures. The pathogenic mechanisms of PAH in patients with repaired D-TGA are not well understood an...
journal_title:Pulmonary circulation
pub_type:
doi:10.1177/2045893217699228
更新日期:2017-04-01 00:00:00
abstract::Right ventricular (RV) dysfunction in acute respiratory distress syndrome (ARDS) contributes to increased mortality. Our aim is to identify reproducible transthoracic echocardiography (TTE) parameters of RV dysfunction that can be used to predict outcomes in ARDS. We performed a retrospective single-center cohort pilo...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/685549
更新日期:2016-06-01 00:00:00
abstract::There are limited data on the management of pulmonary arterial hypertension (PAH) in the elderly; therefore, this analysis compared the safety and efficacy of tadalafil between patients ≥65 and <65 years old. This was a post hoc analysis of the randomized, double-blind, placebo-controlled phase 3 Pulmonary Arterial Hy...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/674901
更新日期:2014-03-01 00:00:00
abstract::Low-grade albuminuria, determined by the urinary albumin to creatinine ratio, has been linked to systemic vascular dysfunction and is associated with cardiovascular mortality. Pulmonary arterial hypertension is related to mutations in the bone morphogenetic protein receptor type 2, pulmonary vascular dysfunction and i...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018824564
更新日期:2019-04-01 00:00:00
abstract::Abstract Changes in voltage-gated K(+) (Kv) channel function contribute to the pathogenesis of pulmonary hypertension. Yet the mechanisms underlying Kv channel impairments in the pulmonary circulation remain unclear. We tested the hypothesis that reactive oxygen species (ROSs) contribute to the Kv channel dysfunction ...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/674307
更新日期:2013-09-01 00:00:00
abstract::Pulmonary capillary hemangiomatosis (PCH) is a rare form of pulmonary arterial hypertension (PAH) characterized by pulmonary capillary proliferation and pseudoinvasion of collagenous septal structures. PCH is often accompanied by veno-occlusive changes and pulmonary hypertensive arterial remodeling. The clinical and p...
journal_title:Pulmonary circulation
pub_type:
doi:10.1086/682227
更新日期:2015-09-01 00:00:00
abstract::Right-ventricular function is a good indicator of pulmonary arterial hypertension (PAH) prognosis; however, how the right ventricle (RV) adapts to the pressure overload is not well understood. Here, we aimed at characterizing the time course of RV early remodeling and discriminate the contribution of ventricular geome...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018800439
更新日期:2018-10-01 00:00:00
abstract::African Americans (AA) have a higher incidence of pulmonary hypertension (PH) risk factors. Few studies have examined the racial differences in the prevalence and etiology of PH and direct comparison of invasive hemodynamics between AAs and Caucasians has rarely been reported. In this study, we examined whether racial...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018764273
更新日期:2018-04-01 00:00:00
abstract::Pulmonary hypertension (PH) comprises a group of pathophysiological syndromes characterized by elevated pulmonary artery pressure and pulmonary vascular resistance, which lead to right ventricular overload, and even right heart failure. PH has a poor prognosis and severely leads to a decline in quality of life. Histor...
journal_title:Pulmonary circulation
pub_type: 杂志文章,评审
doi:10.1177/2045894020937129
更新日期:2020-07-07 00:00:00
abstract::Pulmonary arterial hypertension (PAH) patients have distinct disease courses and responses to treatment, but current diagnostic and treatment schemes provide limited insight. We aimed to see if cluster analysis could distinguish clinical phenotypes in PAH. An unbiased cluster analysis was performed on 17 baseline clin...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045893217705891
更新日期:2017-04-01 00:00:00
abstract::This study aimed to identify receptors mediating sphingosine-1-phosphate (S1P)-induced vasoconstriction in the normotensive and chronic hypoxia-induced hypertensive rat pulmonary circulation. In isolated perfused lungs from normoxic rats, infusion of S1P caused a sustained vasoconstriction, which was not reduced by co...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.4103/2045-8932.87309
更新日期:2011-07-01 00:00:00
abstract::Limited data about the long-term prognosis and response to therapy in pulmonary arterial hypertension patients with World Health Organization functional class I/II symptoms are available. PubMed and Embase were searched for publications of observational registries and randomized, controlled trials in pulmonary arteria...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020935291
更新日期:2020-11-25 00:00:00
abstract::Pharmacokinetic studies with oral treprostinil demonstrate that three times daily (TID) dosing reduces peak-to-trough plasma trepostinil fluctuations compared with twice daily (BID) dosing. TID dosing may allow for faster titration, higher total daily doses, and potentially improve the tolerability of oral trepostinil...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894018770654
更新日期:2018-04-01 00:00:00
abstract::[This corrects the article DOI: 10.1086/688060.]. ...
journal_title:Pulmonary circulation
pub_type: 已发布勘误
doi:10.1086/689215
更新日期:2016-12-01 00:00:00
abstract::Abstract Chronic thromboembolic pulmonary hypertension (CTEPH) is a life-threatening condition characterized by single or recurrent pulmonary thromboemboli, which promote pulmonary vascular remodeling. MicroRNA (miRNA), is a small, noncoding RNA that is involved in multiple cell processes and functions and may partici...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/674310
更新日期:2013-09-01 00:00:00
abstract::Most subtypes of pulmonary arterial hypertension (PAH) are characterized by a greater susceptibility to disease among females, although females with PAH appear to live longer after diagnosis. While this "estrogen paradoxȍ of enhanced female survival despite increased female susceptibility remains a mystery, recent pro...
journal_title:Pulmonary circulation
pub_type: 杂志文章,评审
doi:10.4103/2045-8932.114756
更新日期:2013-04-01 00:00:00
abstract::Insulin resistance is highly prevalent in pulmonary arterial hypertension (PAH) patients. However, the long-term impact of diabetes mellitus (DM) on survival in PAH is unclear. Insulin resistance and DM are associated with left ventricular steatosis and dysfunction, but whether the right ventricle (RV) might be affect...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/675994
更新日期:2014-06-01 00:00:00
abstract::Andeans and Tibetans have less altitude reduction in birth weight than do shorter-resident groups, but only Tibetans are protected from pulmonary hypertension and chronic mountain sickness (CMS). We hypothesized that differences in neonatal oxygenation were involved, with arterial O2 saturation (SaO2) being highest in...
journal_title:Pulmonary circulation
pub_type: 杂志文章,评审
doi:10.1086/679719
更新日期:2015-03-01 00:00:00
abstract::Riociguat is approved for the treatment of pulmonary arterial hypertension and chronic thromboembolic pulmonary hypertension. Some patients have difficulty swallowing tablets; therefore, 2 randomized, nonblinded, crossover studies compared the relative bioavailability of riociguat oral suspensions and immediate-releas...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/685020
更新日期:2016-03-01 00:00:00
abstract::Transforming growth factor-β (TGF-β) inhibition is an investigational therapy for pulmonary arterial hypertension with promising results in experimental studies. The present work compared this approach with endothelin-receptor blockade and evaluated the effects of combined administration. Pulmonary arterial hypertensi...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.4103/2045-8932.105034
更新日期:2012-10-01 00:00:00
abstract::Pulmonary arterial dilatation associated with pulmonary hypertension may result in significant compression of local structures. Left main coronary artery and left recurrent laryngeal nerve compression have been described. Tracheobronchial compression from pulmonary arterial dilatation is rare in adults, and there are ...
journal_title:Pulmonary circulation
pub_type:
doi:10.1086/683687
更新日期:2015-12-01 00:00:00
abstract::Inhaled treprostinil (Tyvaso) has been shown to be a safe and effective addition to pulmonary arterial hypertension (PAH) oral therapies; however, the respiratory-related safety profile of inhaled treprostinil required further elucidation in the setting of routine clinical care. The objectives of this study were to ch...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1086/688059
更新日期:2016-09-01 00:00:00
abstract::Pulmonary arterial hypertension (PAH) is a rapidly progressive and fatal disease for which there is an ever-expanding body of genetic and related pathophysiological information on disease pathogenesis. The most common single culprit gene known is BMPR2, and animal models of the disease in several forms exist. There is...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.4103/2045-8932.87293
更新日期:2011-07-01 00:00:00
abstract::Endothelial dysfunction plays an important role in the pathogenesis of pulmonary arterial hypertension (PAH) in sickle cell disease (SCD). A variety of evidence suggests that circulating endothelial progenitor cells (EPCs) play an integral role in vascular repair. We hypothesized that SCD patients with PAH are deficie...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.4103/2045-8932.94834
更新日期:2012-01-01 00:00:00
abstract::Patients with chronic thromboembolic pulmonary hypertension (CTEPH) require lifelong anticoagulation therapy. However, the bleeding risk and recurrence of venous thromboembolism (VTE) in CTEPH patients who are administered warfarin have not been adequately evaluated. The purpose of this study was to evaluate the risk ...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045893217717258
更新日期:2017-07-01 00:00:00
abstract::While it is well established that the haemodynamic cause of hypoxic pulmonary hypertension is increased pulmonary vascular resistance, the molecular pathogenesis of the increased resistance remains incompletely understood. Macrophage migration inhibitory factor is a pleiotropic cytokine with endogenous tautomerase enz...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020941352
更新日期:2020-10-26 00:00:00
abstract::Infection, thrombosis, and catheter dislodgment are well-recognized potential complications of chronic intravenous prostanoid therapy for pulmonary arterial hypertension. As long-term outcomes of pulmonary hypertension patients improve, novel adverse events are likely to arise. We describe the sudden development of un...
journal_title:Pulmonary circulation
pub_type:
doi:10.1177/2045893217748054
更新日期:2018-01-01 00:00:00
abstract::Two oral medications targeting the prostacyclin pathway are available to treat pulmonary arterial hypertension in the United States: oral treprostinil and selexipag. We compared real-world hospitalization in patients receiving these medications. A retrospective administrative claims study was conducted using the Optum...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894020911831
更新日期:2020-11-10 00:00:00
abstract::Despite recent advances, the prognosis of pulmonary hypertension (PH) remains poor. While the initial insult in PH implicates the pulmonary vasculature, the functional state, exercise capacity, and survival of such patients are closely linked to right ventricular (RV) function. In the current study, we sought to inves...
journal_title:Pulmonary circulation
pub_type: 杂志文章
doi:10.1177/2045894019862435
更新日期:2019-07-01 00:00:00