Interactions between rheumatologists and cardio-/pulmonologists in the assessment and use of outcome measures in pulmonary arterial hypertension related to systemic sclerosis.

Objectives: Pulmonary arterial hypertension in patients with systemic sclerosis is a disease involving multiple organ systems. We investigated the differences in perceptions of how to measure PAH-SSc among cardiologists, pulmonologists and rheumatologists. We also examined how a Delphi exercise can improve agreement among these subspecialties.

Omalizumab-induced decrease of FcξRI expression in patients with severe allergic asthma.

Background: It is documented that omalizumab treatment reduces the cell surface expression of immunoglobulin E high-affinity receptor (FcɛRI) on several cell types. This has not been investigated in patients with uncontrolled severe persistent allergic asthma.

Methods: In a double-blind, randomized, placebo-controlled study, patients with severe allergic asthma uncontrolled by high dose inhaled corticosteroids and long-acting β(2)-agonist received either omalizumab (n = 20) or placebo (n = 11) over 16 weeks at appropriate doses and frequencies.

Survival in schistosomiasis-associated pulmonary arterial hypertension.

Objectives: The objective of this study was to evaluate the natural history of untreated schistosomiasis-associated pulmonary arterial hypertension (Sch-PAH) patients as compared to idiopathic pulmonary arterial hypertension (IPAH) with respect to hemodynamics recorded at presentation and 36 months survival.

Background: Schistosomiasis (Sch) is one of the most prevalent chronic infectious diseases in the world. Nevertheless data regarding one of its most severe clinical complications, pulmonary arterial hypertension (PAH), is scarce.

Endothelin A receptor blockade improves regression of flow-induced pulmonary vasculopathy in piglets.

Objectives: In patients with chronic thromboembolic pulmonary hypertension, high flow in unobstructed lung regions may induce small-vessel damage responsible for persistent pulmonary hypertension after pulmonary thromboendarterectomy. In piglets, closure of an experimental aortopulmonary shunt reverses the flow-induced vascular lesions and diminishes the elevated levels of messenger RNA (mRNA) expression for endothelin-1 and endothelin receptor A (ETA). We wanted to study the effect of the ETA antagonist TBC 3711 on reversal of flow-induced pulmonary vascular lesions.

Survival in patients with idiopathic, familial, and anorexigen-associated pulmonary arterial hypertension in the modern management era.

Background: Novel therapies have recently become available for pulmonary arterial hypertension. We conducted a study to characterize mortality in a multicenter prospective cohort of patients diagnosed with idiopathic, familial, or anorexigen-associated pulmonary arterial hypertension in the modern management era.

Methods And Results: Between October 2002 and October 2003, 354 consecutive adult patients with idiopathic, familial, or anorexigen-associated pulmonary arterial hypertension (56 incident and 298 prevalent cases) were prospectively enrolled.

Long-term response to calcium-channel blockers in non-idiopathic pulmonary arterial hypertension.

Aims: To assess the acute vasodilator response and long-term response to calcium-channel blockers (CCB) in pulmonary arterial hypertension (PAH) with associated conditions.

Methods And Results: The response to acute vasodilator testing [>20% decrease in mean pulmonary artery pressure (mPAP) and total pulmonary resistance] was assessed in 663 consecutive PAH patients with connective tissue disease (CTD; n = 168), portal hypertension (PoPH; n = 153), anorexigen use (n = 127), human immunodeficiency virus infection (HIV; n = 124), congenital heart disease (CHD; n = 50), and pulmonary veno-occlusive disease or capillary haemangiomatosis (PVOD/PCH; n = 41). An acute vasodilator response was observed in 13.

Absence of influence of gender and BMPR2 mutation type on clinical phenotypes of pulmonary arterial hypertension.

Background: Previous studies indicate that patients with pulmonary arterial hypertension (PAH) carrying a mutation in the bone morphogenetic protein receptor type 2 (BMPR2) gene, develop the disease 10 years earlier than non-carriers, and have a more severe hemodynamic compromise at diagnosis. A recent report has suggested that this may only be the case for females and that patients with missense mutations in BMPR2 gene have more severe disease than patients with truncating mutations.

Methods: We reviewed data from all patients with PAH considered as idiopathic and patients with a family history of PAH, who underwent genetic counselling in the French PAH network between January, 1st 2004 and April, 1st 2010.

Validation of the 6 min walk test according to the OMERACT filter: a systematic literature review by the EPOSS-OMERACT group.

Objective: To assess the validity of the 6 min walk test (6MWT) in pulmonary arterial hypertension secondary to systemic sclerosis (PAH-SSc) according to the OMERACT filter.

Methods: A systematic literature search was conducted from 1966 through June 2009. The assessment of validation of the 6MWT was based on the OMERACT filter criteria with the domains 'truth', 'discrimination' and 'feasibility'.

Pulmonary veno-occlusive disease: recent progress and current challenges.

Pulmonary veno-occlusive disease (PVOD) is an uncommon form of pulmonary arterial hypertension characterised by a progressive obstruction of small pulmonary veins that leads to elevation in pulmonary vascular resistance and right ventricular failure. Despite improved understanding and more efficacious treatment options for PAH overall, the prognosis of PVOD remains dismal. Without therapeutic intervention few patients would be expected to survive more than two years.

Evidence for the use of combination targeted therapeutic approaches for the management of pulmonary arterial hypertension.

The last decade has witnessed a remarkable increase in the number of effective treatment options available for the management of patients with pulmonary arterial hypertension. In this regard, agents belonging to the therapeutic classes that specifically target the prostacyclin, endothelin and nitric oxide pathways have shown the greatest efficacy in clinical studies to date. These various drug treatments have individually been shown to confer improvements in symptoms, exercise capacity, pulmonary haemodynamics and possibly survival in different patient subgroups.

Benfluorex and unexplained valvular heart disease: a case-control study.

Background: Recent case reports suggest that benfluorex, a fenfluramine derivative used in the management of overweight diabetic patients and dyslipidemia, is associated with cardiac valve regurgitation.

Methods: We conducted a case-control study. Eligible patients were those admitted in the cardiology or the cardiac surgery units of our hospital between January, 1(st) 2003 and June 30(th) 2009, with mitral insufficiency diagnostic codes (ICD-10 I340 and I051).

Endpoints in pulmonary arterial hypertension: the role of clinical worsening.

Purpose Of Review: Design and selection of endpoints used in clinical trials is a complex and compelling topic; the diverse needs of clinicians, patients and regulatory authorities represent a challenge in devising the most relevant, meaningful yet practical measures. In trials of therapies for pulmonary arterial hypertension (PAH), a variety of endpoints have been used, including assessments of exercise capacity (6-min walk distance [6MWD]), functional class, hemodynamics, and time to clinical worsening. Most have relied upon 6MWD as the primary endpoint.

Systemic sclerosis-associated pulmonary arterial hypertension.

Pulmonary arterial hypertension (PAH) is a devastating vascular complication of a number of connective tissue diseases, including systemic sclerosis (SSc), where it has a dramatic impact on the clinical course and overall survival and is the single most common cause of death in patients afflicted with this syndrome. Although remarkable advances have been achieved in elucidating the pathogenesis of PAH over the past 2 decades, leading to the development of disease-targeted therapies for the idiopathic form of this condition (IPAH), the response to therapy is suboptimal in SSc-related PAH (SSc-PAH), and survival remains very poor. Factors accounting for striking clinical and prognostic differences between these two syndromes are unclear but may include a more pronounced autoimmune, cellular, and inflammatory response, and a higher prevalence of comorbidities in SSc-PAH, including cardiac and pulmonary venous and parenchymal involvement.

Overall asthma control: the relationship between current control and future risk.

Background: Asthma guidelines emphasize both maintaining current control and reducing future risk, but the relationship between these 2 targets is not well understood.

Objective: This retrospective analysis of 5 budesonide/formoterol maintenance and reliever therapy (Symbicort SMART Turbuhaler(*)) studies assessed the relationship between asthma control questionnaire (ACQ-5) and Global Initiative for Asthma-defined clinical asthma control and future risk of instability and exacerbations.

Methods: The percentage of patients with Global Initiative for Asthma-defined controlled asthma over time was assessed for budesonide/formoterol maintenance and reliever therapy versus the 3 maintenance therapies; higher dose inhaled corticosteroid (ICS), same dose ICS/long-acting beta(2)-agonist (LABA), and higher dose ICS/LABA plus short-acting beta(2)-agonist.

Pulmonary arterial hypertension associated with systemic sclerosis in patients with functional class II dyspnoea: mild symptoms but severe outcome.

Objective: To describe the history of SSc-associated pulmonary arterial hypertension (SSc-PAH) in patients with New York Heart Association (NYHA) functional class (FC) II dyspnoea at diagnosis.

Methods: Data at the time of diagnosis were collected and analysed retrospectively for 77 consecutive patients with SSc-PAH.

Results: Twelve patients (15.

Characterization of pulmonary arterial hypertension patients walking more than 450 m in 6 min at diagnosis.

Background: At diagnosis of pulmonary arterial hypertension (PAH), some patients are considered to have a "near-normal" 6-min walk distance (6MWD) (ie, > 450 m). Because they are generally excluded from randomized controlled trials, little is known about these patients.

Methods: We analyzed the baseline characteristics and treatment responses of 49 consecutive patients with a 6MWD > 450 m at the time of newly diagnosed PAH.

Scleroderma lung disease.

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.

Clinical outcomes of pulmonary arterial hypertension in patients carrying an ACVRL1 (ALK1) mutation.

Rationale: Activin A receptor type II-like kinase-1 (ACVRL1, also known as ALK1) mutation is a cause of hereditary hemorrhagic telangiectasia (HHT) and/or heritable pulmonary arterial hypertension (PAH).

Objectives: To describe the characteristics of patients with PAH carrying an ACVRL1 mutation.

Methods: We reviewed clinical, functional, and hemodynamic characteristics of 32 patients with PAH carrying an ACVRL1 mutation, corresponding to 9 patients from the French PAH Network and 23 from literature analysis.

Long-term outcome of systemic sclerosis-associated pulmonary arterial hypertension treated with bosentan as first-line monotherapy followed or not by the addition of prostanoids or sildenafil.

Objective: Data on long-term efficacy of bosentan, an oral dual ET receptor antagonist, in SSc-associated pulmonary arterial hypertension (SSc-PAH) are lacking. We aimed to describe the long-term outcome of SSc-PAH treated with first-line monotherapy bosentan followed or not by the addition of prostanoids or sildenafil.

Methods: A prospective analysis of 49 consecutive SSc-PAH patients treated with first-line bosentan was performed.

Echocardiography as an outcome measure in scleroderma-related pulmonary arterial hypertension: a systematic literature analysis by the EPOSS group.

Objective: To assess the validation status of echocardiography with continuous Doppler (echo-Doppler) as an outcome measure in pulmonary arterial hypertension associated with systemic sclerosis (PAH-SSc).

Methods: Structured literature review on full-text English articles was performed using the PubMed and Cochrane databases. Assessment of validation of echo-Doppler was based on the OMERACT filter criteria with the domains truth (face, content, construct, and criterion validity), discrimination, and feasibility.

[Pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis].

The new classification of pulmonary hypertension proposed in the joint European Society of Cardiology (ESC) and European Respiratory Society (ERS) guidelines, combines pulmonary veno-occlusive disease (PVOD) and pulmonary capillary hemangiomatosis (PCH) from separate categories into a single subcategory within pulmonary arterial hypertension (PAH) because of specific similarities in their diagnosis, prognosis, and management. These diseases are characterized histologically by their predominant involvement of small pulmonary veins (PVOD) and capillaries (PCH). Their precise prevalence is not known, but they are thought to account for 5 to 10% of the forms of PAH initially considered idiopathic.

HIV-associated pulmonary arterial hypertension: survival and prognostic factors in the modern therapeutic era.

Objectives: To examine baseline characteristics and outcome, and to determine variables affecting survival in patients with pulmonary arterial hypertension (PAH) associated with HIV infection (PAH-HIV) in the modern era of highly-active antiretroviral therapy (HAART) and specific PAH therapy.

Design: Retrospective review of data from PAH-HIV patients without other associated risk factors for PAH, and comparison with previous series.

Methods: Data were reviewed for 77 consecutive patients treated at the French Reference Centre for Pulmonary Hypertension between October 2000 and January 2008.