Volume 13: Issue 3

Section editor's note: The diagnostic evaluation of pulmonary hypertension (PH) is an extensive, yet specific, process. Each individual study is significant, but it is truly the insightful analysis of the combination of studies that assists us most in making the correct diagnosis. In this issue's PH Grand Rounds, we congratulate Dr Al-Naamani and her colleagues for reminding us to consider a more in-depth examination of the data prior to making what seems to be an obvious diagnosis. This case not only imparts valuable information on this particular diagnosis, it also demonstrates how this type of thought process is vital to both the diagnosis and therapy for our patients.

There are currently 12 medications approved for use in the treatment of pulmonary arterial hypertension (PAH) in adults. These include endothelin receptor antagonists, phosphodiesterase type 5 inhibitors, soluble guanylate cyclase stimulators, and prostacyclins. However, in children there are no approved targeted PAH medications, with the exception of inhaled nitric oxide for treatment of hypoxemic respiratory failure in neonates. This review will address some of the challenges in the development of treatments for children, including lessons from recent trials, endpoints for clinical trials, and challenges with drug approval in children.

To improve long-term survival in pulmonary arterial hypertension (PAH), new treatment approaches that target occlusive vasculopathy instead of vasoconstriction of pulmonary arteries are necessary. Identifying genes or pathways that unify different pathologies and etiologies in PAH is a crucial first step for drug development. The bone morphogenetic protein receptor 2 (BMPR2) pathway, originally described as the cause of familial PAH, has gained significant interest over the past few years as a potential master switch in PAH, and therefore presents a promising treatment target in PAH. FK506 (tacrolimus) was found in a high-throughput screen of US Food and Drug Administration (FDA)-approved drugs to significantly increase BMPR2 signaling. Low-dose FK506 was able to restore normal BMPR2 signaling and function in patient pulmonary artery (PA) endothelial cells, inhibit proliferation and induce apoptosis in PA smooth muscle cells, and prevent and reverse pulmonary hypertension (PH) in 3 experimental rodent models of PH. As an FDA-approved drug, it was possible to relatively quickly (in approximately 2 years) translate the basic science discoveries from the bench to the clinic. A Phase 2 proof-of-concept safety and tolerability trial is underway (ClinicalTrials.gov Identifier: NCT01647945) to evaluate the use of low-dose FK506 in PAH and to identify patients who might respond best to FK506 depending on their impairment in BMPR2 signaling.

A record number of abstracts were submitted during PHA's 2014 International Conference and Scientific Sessions in June. The winning abstracts were presented as oral abstracts during the scientific sessions and are included in this issue of Advances.

MK Nies,

Johns Hopkins University, Baltimore, Maryland, USA

J Yang,

Johns Hopkins University, Baltimore, Maryland, USA

Z Fu,

Johns Hopkins University, Baltimore, Maryland, USA

AD Everett,

Johns Hopkins University, Baltimore, Maryland, USA

Non-Biased Proteomics Discovery of Pulmonary Artery Hypertension Biomarkers Periostin and Matrix Metalloproteinase 9

Background: Identification of a pulmonary hypertension (PH) biomarker would aid in risk stratification, noninvasive monitoring

Memos

Editor's Memo

PH Grand Rounds: Pulmonary Artery Filling Defects: Are They All the Same?

Challenges in Endpoint Development for Pulmonary Hypertension Trials in Children

Repurposing FK506 to Increase BMPR2 Signaling and Improve Pulmonary Arterial Hypertension: A Fast Track From Cells to People

Nitric Oxide Therapeutics in Pulmonary Vascular Disease

Conference Abstracts

Non-Biased Proteomics Discovery of Pulmonary Artery Hypertension Biomarkers Periostin and Matrix Metalloproteinase 9

Roundtable: Reflections on the Scientific Sessions

Ask the Expert: Should Providers Routinely “Prescribe” Support Group Participation for Their Patients with PAH?

PHPN: An Allied Health Professional's Experience at PHA's International Conference

News To Use

New! Diagnostic Notepad

PHA's 2015 PHPN Symposium: SUBMIT AN ABSTRACT!

Erratum for “Ask the Expert” Vol 13, No 2, page 92

Conference Abstracts

Guest Editor’s Memo

A Roundtable Discussion Addressing Patient-Centered Care and Quality of Life in Patients With Pulmonary Arterial Hypertension

Editor’s Memo

Pulmonary Hypertension Associated With Parenchymal Lung Disease