Asbestos Diseases: Asbestos Pleural Disease

Asbestos Diseases: Asbestos Pleural Disease

Asbestos pleural disease is a nonmalignant disease caused by inhalation of asbestos fibers that scar the pleura. The pleura is the thin membrane lining the lung and chest cavity. If the scarring is diffuse and extends along the chest wall, it is called pleural thickening. If the scarring is more focused and well–defined, it is called pleural plaques.

Asbestos pleural disease results in a similar scarring process as the one that occurs inside the lung with asbestosis; however, it occurs in the lining of the lungs rather than in the lungs. Pleural thickening and pleural plaques can cause shortness of breath and impair lung function. Although its symptoms may be treated, asbestos pleural disease is permanent and progressive with no cure. Even after exposure to asbestos has ceased, scarring continues due to the body’s interaction with retained asbestos fibers.

Pleural scarring, which is often seen in conjunction with asbestosis, can be detected on chest x–rays and CT scans and usually reflects a significant history of exposure to asbestos. It normally takes at least 10 years after the first exposure to asbestos for asbestos pleural disease to develop.

Asbestosis Can Be Severely Disabling

Asbestosis Can Be Severely Disabling

Asbestosis and asbestos pleural disease are nonmalignant asbestos diseases that are slowly progressive. They can be severely disabling and potentially fatal. These asbestos diseases cause impairment of pulmonary function, including small airway obstruction, a reduction in lung capacity, breathing restriction, and a reduction in the ability to transfer oxygen from air into the blood. Approximately one in seven people who suffer from asbestosis eventually develop asbestos lung cancer (Asbestos Fact Sheet, Lung Cancer, American Cancer Society).

Asbestosis and asbestos pleural disease are the result of cumulative exposure to asbestos. In individuals who develop these asbestos diseases, every nontrivial occupational exposure to asbestos is significant.

Human lung showing asbestosis

Asbestos Diseases: Asbestosis

Asbestosis is a scarring of lung tissue caused by the inhalation of asbestos fibers. A portion of the fibers reach the alveoli (air sacs) where oxygen is transferred into the blood. Asbestos activates the lung’s immune system and starts a reaction best described as an inflammatory process. Scavenger white blood cells (macrophages) try to break down the asbestos (phagocytosis) but are not successful, causing other cells (fibroblasts) to grow and form connective–tissue–based scars.

The formation of scar tissue or collagen in the lungs is known as fibrosis. The scar tissue slowly builds up, often reducing the lung’s ability to deliver oxygen to the blood and remove carbon dioxide (reduced diffusion capacity). The total lung capacity or TLC may also be reduced. In severe cases, the impairment of lung function can strain the heart, or even result in heart disease, such as right–sided heart failure or “cor pulmonale.”

Asbestosis and the Inflammatory Process

The inflammatory process starts within hours or days after inhalation of asbestos and injury at the cellular level begins shortly thereafter. In people who develop asbestosis, the inflammatory process continues to progress, fueled by indestructible asbestos fibers, even after exposure to asbestos ceases.

This asbestosis inflammatory process may continue undetected for decades causing no pain or respiratory symptoms. In many people, the process eventually produces symptoms—breathing abnormalities and radiographic changes. Usually, the first symptoms are shortness of breath and a dry cough. These symptoms often precede abnormalities on chest x–ray or pulmonary function tests. The period between exposure and diagnosis is called “latency” and may range from 10 to 50 years. See Asbestosis Diagnosis for more details.

Mass. General leading international trial of novel breast cancer drug

A clinical trial of a new targeted breast cancer drug, led by physicians at Massachusetts General Hospital (MGH) Cancer Center, has begun enrolling patients. The TEACH (Tykerb Evaluation After CHemotherapy) trial will investigate the experimental drug Tykerb (lapatinib) in patients with early-stage, HER2-positive breast cancer who have not been treated with Herceptin, another targeted drug used for the same type of tumor. The MGH is the lead institution for the international trial, which is being sponsored by GlaxoSmithKline, the manufacturer of Tykerb.

“This trial represents another step toward understanding the role of targeted therapies in extending disease-free survival,” said Paul Goss, MD, PhD, director of Breast Cancer Research at the MGH Cancer Center, who proposed the TEACH study and chairs the International Steering Committee.

About one quarter of breast cancer patients have tumors that overexpress or produce too many copies of a receptor molecule called HER2. Because cellular growth is stimulated by the overactivity of this molecule, which also is called ErbB2, these tumors are more likely to recur and are less responsive to hormone-based treatments. Herceptin, a monoclonal antibody that blocks the HER2 receptor, is approved by the FDA as an adjuvant treatment – given along with chemotherapy after surgical removal and/or radiation therapy – for early-stage, node-positive and HER2-positive tumors as well as for metastatic tumors.

Tykerb blocks both the HER2/ErbB2 receptor and a related molecule called ErbB1. Earlier clinical trials have indicated that it may have advantages over Herceptin in a number of settings related to treatment of HER2-positive breast cancer without significant side effects. Tykerb has not yet received approval from the U.S. Food and Drug Administration, and the TEACH study is a Phase III trial of its use in patients with early-stage HER2-positive tumors. To enroll in the study – which is being conducted at 450 sites around the world – patients must have completed adjuvant chemotherapy but not have received Herceptin. Study participants will be randomized to receive a daily oral dose of either Tykerb or a placebo for up to one year.

“The TEACH study will be the first to investigate the use of a dual ErbB1 and ErbB2 inhibitor as an adjuvant treatment for women with HER2-positive breast cancer, who are at a high risk of their disease recurring,” says Goss.

The concept of the TEACH study arose from our clinics, says Beverly Moy, MD, a medical oncologist at the MGH Breast Center and a member of the TEACH International Steering Committee.We have patients with HER2-positive breast cancer who had never received Herceptin because they were diagnosed before we knew about the benefits of Herceptin in early-stage breast cancer. The results of this study could reveal whether the targeted therapy Tykerb could benefit women several years after the initial diagnosis of breast cancer.