A rare, progressive condition, known as lymphangioleiomyomatosis or LAM, is usually found in young women. An increase of smooth muscle cells in the blood vessels and airways of the lungs eventually obstructs air flow and destroys lung tissue. The average age of diagnosis is 34 and, until recently, accurate diagnosis and effective treatment were hard to find.
But patients and physicians in the Midwest can now turn to the Washington University LAM clinic at Barnes-Jewish Hospital for specialized information and treatment. The clinic, one of only about 20 in the country, is under the direction of Washington University pulmonologists Adrian Shifren, MD, and Mario Castro, MD.
Adrian Shifren, MD
A Relentless Disease
Although LAM is currently not curable, a range of available treatments not only improve quality of life but, in some cases, may extend it, says Shifren. And research at centers such as Washington University offers hope that a cure will eventually be found, he says. Patients with LAM have been found to have abnormalities of the tuberous sclerosis complex gene, increasing their chances of developing the disease. But researchers haven’t found exactly what causes the gene to be abnormal or a way to fix it.
LAM’s progression is “relentless,” says Shifren. “Most women are diagnosed in their early 30s to 40s. But I think we’re missing a lot of the early cases.”
Two of the more serious complications of LAM often lead to its diagnosis. As LAM progresses, about two-thirds of patients suffer pneumothorax, a collection of air in the space between the lung and the chest wall. Or they may have pleural effusion, a build-up of fluid in the layers of tissue that line the lungs and chest wall. Both are painful and dangerous.
Looking at the Options
Once diagnosed, patients can begin a range of treatments that ease symptoms and, in some cases, extend life.
“As far as treatment goes, it’s a top-down, symptomatic approach,” says Shifren. For patients with low levels of oxygen, wearing supplemental oxygen can be very helpful in making them feel better. Other patients respond well to bronchial dilators used for asthma.
Pregnancy seems to exacerbate symptoms, leading to the belief that estrogen makes LAM worse. Therefore, doctors have treated LAM by reducing estrogen production. In the past, says Shifren, this resulted in women having oophorectomies—removal of the ovaries—in an effort to control the disease.
Now, large doses of progesterone, usually taken orally, are used to block the body’s production of estrogen.
Doctors may also prescribe drugs, such as the breast cancer medication tamoxifen, that block the effects of estrogen in the body. Lung transplant is also an option for patients.
“Transplant in and of itself is not a cure-all,” says Shifren. “It is generally a last-resort sort of option, done in patients whose prognosis is very poor.”
The Washington University and Barnes-Jewish Transplant Center has long been considered one of the leading lung transplant centers in the world and is among the top in number of LAM patients transplanted.
Drugs and treatments haven’t been very helpful in stopping the progressio nof LAM, says Shifren. However, the newest therapy, sirolimus, a drug used in transplant and cancer patients, shows considerable promise, says Shifren. It works by regulating the pathways that control smooth muscle cellular growth. These pathways are disregulated in LAM.
Results of a safety and efficacy trial by the Multi-Center International LAM Efficacy and Safety for Sirolimus, or MILES study, were recently published in the New England Journal of Medicine.
"This was a very exciting trial,” Shifren says. “It showed significant benefits in several measures of lung function and showed improvements in patient symptoms.” Unfortunately, further testing is still needed, Shifren adds.
Although LAM is serious and not yet curable, earlier diagnosis, combined with treatments found at centers like the Washington University LAM clinic at Barnes-Jewish Hospital, is giving patients reason to breathe a bit easier.