Sasiharan Sithamparanathan

Survival in portopulmonary hypertension: Outcomes of the United Kingdom National Pulmonary Arterial Hypertension Registry

BACKGROUND Portopulmonary hypertension (PoPH) is a rare condition associated with poor survival, and the effect of modern therapies that target pulmonary arterial hypertension (PAH) on long-term outcome is unknown. This study investigated the baseline characteristics and survival in the cohort of patients diagnosed with PoPH in the United Kingdom National Pulmonary Hypertension Service. METHODS A retrospective review was conducted of all incident treatment-naïve patients with PoPH within the United Kingdom national registry diagnosed between January 2001 and December 2010. RESULTS Patients with PoPH (n = 110) had survival rates of 85%, 60%, and 35% at 1, 3, and 5 years. The prevalence of PoPH was 0.85 cases/1 million. Mean age at diagnosis was 53 ± 12 years, with a balanced distribution in gender. Alcohol (n = 57) and hepatitis C (n = 10) were the most common causes of portal hypertension. Phosphodiesterase V inhibitors were the most frequently used targeted therapy, in 63.6% (n = 70) of patients, endothelin receptor antagonists were used in 10% (n = 11) and prostacyclin analogs in 12.7% (n = 14). Univariate and multivariate analysis of baseline characteristics did not demonstrate a significant influence of severity of portal hypertension or liver cirrhosis, World Health Organization Functional Class, cardiopulmonary hemodynamics, or year of diagnosis on survival. CONCLUSIONS Survival of patients with PoPH remains poor despite targeted therapy and worse than patients with idiopathic PAH. The benefit of PAH therapies in PoPH on long-term morbidity and mortality outcomes needs further consideration and study.

The good the bad and the ugly

We were, of course, very interested to read the manuscript by Saggar et al ,1 and the accompanying editorial by Nathan2 relating to the use of parenteral treprostinil therapy in patients referred for lung transplantation with pulmonary hypertension (PH) in association with pulmonary fibrosis (PF). It is good that there is continued interest in finding a clinical phenotype of patient with PF who may benefit on both symptomatic and prognostic grounds from targeted PH therapy. It is also good because there is a great clinical need to help this group of desperate …

Skeletal muscle mitochondrial oxidative phosphorylation function in idiopathic pulmonary arterial hypertension: in vivo and in vitro study

Mitochondrial dysfunction within the pulmonary vessels has been shown to contribute to the pathology of idiopathic pulmonary arterial hypertension (IPAH). We investigated the hypothesis of whether impaired exercise capacity observed in IPAH patients is in part due to primary mitochondrial oxidative phosphorylation (OXPHOS) dysfunction in skeletal muscle. This could lead to potentially new avenues of treatment beyond targeting the pulmonary vessels. Nine clinically stable participants with IPAH underwent cardiopulmonary exercise testing, in vivo and in vitro assessment of mitochondrial function by 31P-magnetic resonance spectroscopy (31P-MRS) and laboratory muscle biopsy analysis. 31P-MRS showed abnormal skeletal muscle bioenergetics with prolonged recovery times of phosphocreatine and abnormal muscle pH handling. Histochemistry and quadruple immunofluorescence performed on muscle biopsies showed normal function and subunit protein abundance of the complexes within the OXPHOS system. Our findings suggest that there is no primary mitochondrial OXPHOS dysfunction but raises the possibility of impaired oxygen delivery to the mitochondria affecting skeletal muscle bioenergetics during exercise.

Lebrikizumab may benefit a subset of patients with asthma

Interleukin 13 (IL-13), a cytokine of type 2 helper T cells, may contribute to the heterogeneity of asthma in terms of clinical course and response to treatment. IL-13 leads to the production of periostin, a protein that may cause airway remodelling. In this randomised, double-blind, placebo-controlled study, lebrikizumab, a monoclonal antibody that binds to IL-13 thereby inhibiting …