UPMC Tower - Pittsburgh Skyline for the UPMC Breathing Breakthroughs blog series with Team PHenomenal Hope. Photo credit: UPMC

UPMC Breathing Breakthroughs

February 23,2015

In this regular blog series “Breathing Breakthroughs” from UPMC, there will be news on the latest diagnostics and treatments for pulmonary hypertension, as well as discussion of what may be coming soon.

UPMC will bring you from the clinic to the lab and back to the bedside, sharing perspectives from UPMC clinicians and University of Pittsburgh researchers, many of whom are members of Team PHenomenal Hope. In this first article, we discuss the basics and give some background about pulmonary arterial hypertension.

Welcome to the first issue of the UPMC Breathing Breakthroughs series!

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What is Pulmonary Arterial Hypertension?

Overview
Pulmonary Arterial Hypertension (PAH) is a type of pulmonary hypertension in which high blood pressure in the lungs is due to intrinsic disease of the pulmonary arteries. The arteries become stiff and dysfunctional – less able to relax, and also can develop thickening or narrowing as the disease progresses. It is estimated to be prevalent in approximately 15 per million people.

There are other types of pulmonary hypertension, which we will discuss in future posts, but the remainder of this article will cover PAH, also known as “World Health Organization (WHO) Group 1 Pulmonary Arterial Hypertension.”

PAH can be associated with many causes including:

  • Idiopathic (IPAH) – PAH due to unknown cause
  • Heritable (HPAH) – PAH due to a genetic mutation
  • Drug and Toxin-induced
  • Associated PAH (APAH):
    • Connective Tissue Diseases/Scleroderma
    • HIV
    • Schistosomiasis
    • Chronic High Altitude Exposure

Idiopathic Pulmonary Arterial Hypertension

IPAH is a rare disease (defined as less than 200,000 cases in the United States), with a prevalence of five per 1 million people. Although it can affect anyone, it is 2.5 times more common in women than men. This is the most common disorder among the group of diseases within this category in the United States (Schistosomiasis-associated PAH, a disease found in developing countries, is the most common cause of PAH world-wide).

Early diagnosis is believed to be important, although because IPAH presents with symptoms similar to more common diseases such as asthma, COPD, obesity, the diagnosis is often delayed. Hence it is important for doctors to have a suspicion of PAH when they consider possible causes for shortness of breath.

Screening and diagnosis of IPAH is made using echocardiogram and right heart catheterization.

Treatment possibilities for IPAH include oral, inhaled, subcutaneous and intravenous medications. The medication chosen is based in large part on severity of disease. Often patients will be started on an oral agent, and if the disease worsens despite this, additional medicines will be prescribed. In addition patients are usually prescribed a low-salt diet to minimize fluid retention, and monitored pulmonary rehabilitation is often advised once the PAH is being treated.

Close follow up with a PH specialist is essential to monitor patients for need for adjustment in treatment or – in the event their disease is severe or they progress despite medicines – referral for lung transplantation evaluation.

Heritable Pulmonary Arterial Hypertension

In few cases, PAH can run in families, and this is due to a genetic mutation passed from generation to generation. Discoveries in genetic mutations have helped our understanding of how PAH can occur. The first gene to be associated with HPAH was a mutation in Bone Morphogenetic Protein Receptor 2 (BMPR2). Of note, patients with IPAH have been found to have mutations in this gene as well. HPAH has also been associated with ALK1 mutation in a disease caused hereditary hemorrhagic telangiectasia.

Inheriting a genetic mutation from one’s parent does not mean that a person will automatically get PAH, however it does mean that the risk is higher than in the general population. Approximately 20% of people with this gene mutation develop PAH.

Drug and Toxin-Induced PAH

PAH came to the forefront as an epidemic when the diet drug Fenfluramine/pheneturamine “Fen/phen” came on the market. The drug was removed from the market, but other drugs have been associated with PAH since then. There are other drugs that have been associated with PAH, including other appetite suppressants, stimulants and other drugs. For a broader list, check the UPMC website here.

Connective Tissue Disease-Associated PAH

The connective tissue diseases (CTDs) include systemic sclerosis (SSc), systemic lupus erythematosus, Sjogren’s syndrome, rheumatoid arthritis and polymyositis/dermatomyositis. Patients with CTD may have blood vessel injury and immune system activation and inflammation. By far the most common rheumatologic disease associated with WHO Group 1 PAH is systemic sclerosis followed by “mixed connective tissue disease” or MCTD. MCTD refers to when patients have features of more than one CTD, frequently with scleroderma features.

In general, patients with PAH related to CTD have a worse prognosis compared to patients with PAH not associated with a CTD. For this reason it is important to diagnose and treat early. The challenge in identifying CTD patients with PAH is that the findings may be subtle and the diagnosis difficult to make.

In future articles we will discuss other types of pulmonary hypertension, diagnosis and treatment of PAH, and the latest research in the field of pulmonary hypertension.

For more information about PAH and the conditions we treat, see the UPMC Comprehensive Pulmonary Hypertension Program website.

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