Remarkable progress has been made in understanding and treating pulmonary hypertension over the past decade. It’s worth noting that until the late 1970s, doctors had almost nothing they could offer patients with primary pulmonary hypertension. The prognosis for most patients was poor. Then calcium channel-blocking drugs were shown to improve pulmonary blood flow and ease the symptoms of PH, offering patients the first treatment option.

In 1995 the Food and Drug Administration approved an entirely new class of drugs, called prostacyclin analogues. These medications, based on substances produced by the body, lessen symptoms, slow the deterioration caused by pulmonary hypertension, and improve prognosis. In 2002 yet another new class of drugs, called endothelin-1 inhibitors, became available. Now new versions of old drugs, which are easier to take and have fewer side effects, are improving the quality of life for patients with PH. Meanwhile, other drugs, including sildenafil -- more popularly known as Viagra -- show promise in treating the condition.

These new treatments are the result of important advances in basic scientific research. For instance, endothelin-1 inhibitors were developed after scientists discovered a substance, released by cells that line the walls of arteries, that causes arteries to constrict. By creating drugs that block receptors for this substance, pharmaceutical scientists then found a way to keep vessels open and blood flowing.

New research initiatives under way promise even more advances, improving the quality of life and slowing the progress of PH. Some of the leading areas of research today include the following:

Now that doctors have several options for treating pulmonary hypertension, clinicians are beginning to investigate the benefits of combining different therapeutic approaches. In a report published in 2002 in the Annals of Internal Medicine, for instance, researchers showed that a combination of sildenafil and iloprost, an inhaled form of prostacyclin, lessened the symptoms of pulmonary hypertension more effectively than either drug alone. (In the United States, iloprost is only available for people with more severe symptoms of the disease.) In other research, clinicians are experimenting with combinations of prostacyclin analogues and endothelin-1 inhibitors. Over the next few years, controlled trials should provide doctors with important new information about how to best use existing drugs, either alone or together. One urgent need is for more information about how available drugs affect infants and children with pulmonary hypertension.

Many of the effective drugs for pulmonary hypertension are difficult to take and have serious side effects. Epoprostenol, for instance, has to be delivered continuously via an I.V. Another prostacyclin analog, trepostinil, recently approved by the Food and Drug Administration, has to be administered under the skin using a small pump.

But now new forms of PH treatment are becoming available which can be taken in pill form or with inhalers. Ongoing research will continue to make it easier for patients to get the benefits of drugs more easily. In a study currently being organized by the National Heart Lung and Blood Institute, for example, scientists plan to study whether nitric oxide gas mixed into room air can help relieve symptoms of pulmonary hypertension in patients with sickle cell disease. In another study, investigators are determining whether inhaled nitric oxide will help protect infants born with pulmonary hypertension.

Intensive efforts are under way to identify brand-new drugs to stop the progress of pulmonary hypertension and help patients live longer, more active lives. Basic scientific research is likely to lead the way. Not long ago, researchers spotted an enzyme called Rho-kinase, which plays a role in the constriction of blood vessels. A drug that inhibits this enzyme has been developed and is being tested. In October 2003, Japanese scientists at the 13th annual Symposium on Atherosclerosis reported that the drug, called fasudil, was effective in reducing resistance to blood flow in the pulmonary arteries in a small group of patients. Larger studies are expected to follow.

Meanwhile, in what could prove to be a major breakthrough in basic research, scientists reported in 2003 the discovery of certain key chemical characteristics in many patients with pulmonary hypertension. The researchers found unusually high levels of a protein produced by smooth muscle cells in pulmonary vessels, called angiopoietin-1. At the same time, they noted very low levels of markers for another protein, called BMPR1A. The scientists found that the higher the level of angiopoietin-1, the more severe the pulmonary hypertension.

These results suggest for the first time a common molecular basis to PH. The findings also point out directions for future drug development. If scientists can find substances that block angiopoietin-1, for example, they may be able to reverse the process that leads to pulmonary hypertension. In the same report, researchers linked abnormal levels of key proteins to abnormal gene expression. Eventually, gene therapies may be able to correct genetic abnormalities that sometimes underlie the condition.

For patients whose pulmonary hypertension is caused by small blood clots in the pulmonary artery, an operation called a thromboendarterectomy can offer dramatic benefits. The surgery involves removing these stubborn clots and opening up constricted blood vessels. As surgeons gain more experience performing this complicated and risky procedure, they are improving its success rate dramatically. For example, German researchers recently reported that a technique that involves cooling a patient’s body during surgery may improve outcome. Other recent findings suggest that the use of inhaled iloprost, a form of prostacyclin, after surgery may help reduce arterial blood pressure and improve the success of thrombendarerectomies.

An investigational procedure known as balloon atrial septostomy is also promising. In treating primary pulmonary hypertension, this procedure is used to reduce the work load on the right heart by creating a hold between the upper chambers of the left and right heart. This creates a path of lesser resistance for blood flow and allows the right heart to function better.

For selected patients with advanced pulmonary hypertension who don’t benefit from medications, lung or heart-lung transplants represent a last resort. The success rate for these complicated operations has improved dramatically over the past decade as surgeons have gained experience. One of the biggest challenges remains the threat of rejection.

Today, researchers are investigating ways to monitor organ rejection that won’t require invasive biopsies. Improved anti-rejection drugs with fewer long-term side effects are also being tested. Another challenge is developing a more effective and efficient system for getting donated organs to patients in need. At the moment, many patients may wait as long as two years for donor lungs to become available. Hospitals nationwide are working to develop a better system for identifying donors and matching donated organs to patients who need them. The use of the Internet has made it easier to manage the vast amount of information required. Transplant surgeons and patients awaiting organ transplants now have access to expanded data via the national Organ Procurement and Transplantation Network’s Web site at http://www.optn.org.

On the cutting edge of new treatments in development are stem cell gene therapies. In one small study reported in the Journal of Clinical Investigation, researchers discovered that a protein found primarily in cancer cells could also be found in the arteries of patients and rats with pulmonary hypertension. This protein, called survivin, prevents the body from restricting cell growth. In the study, researchers mutated the protein to negate this effect then used a virus to deliver the mutated gene to rats. The rats showed a reversal of pulmonary hypertension and a prolonged survival rate of 25 percent.

Another small study from the University of Toronto is examining the regenerative qualities of bone-marrow cells. These cells -- endothelial-like progenitor cells or ELPCs -- graft into vascular areas that are scarred or injured and have been shown to improve the survival and reduce pulmonary hypertension in rats. Currently, the Toronto research team is conducting a small human study on ELPCs, which is in phase I of a clinical trial.

On many fronts, research progress is offering new hope to patients diagnosed with pulmonary hypertension. The rapid pace of research makes it more important than ever to stay informed. Fortunately, a variety of Internet information sources is also making it easier than ever to follow the latest research results.

-- Peter Jaret is a contributing editor for Health magazine and a winner of the American Medical Association's award for medical reporting. His work has appeared in National Geographic, Newsweek, Hippocrates, and many other national magazines. He is also the author of In Self-Defense (Harcourt Brace Jovanovich), Active Living Every Day, and Heart Healthy for Life.

References

First published October 30, 2003
Last updated October 29, 2007
Copyright © 2003 Consumer Health Interactive

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