November 2002

Research Capsules
Edited by Harrison Wein, Ph.D.

Do Cats Cause Asthma?
Understanding Rheumatoid Arthritis
Molecular Treadmills for Hearing

Do Cats Cause Asthma?

For years, scientists thought that cat exposure increased a child's asthma risk. Recent studies, however, have suggested that exposure to cats during infancy can actually protect children from developing asthma. A new study supported by NIH's National Institute of Allergy and Infectious Diseases (NIAID), National Institute of Environmental Health Sciences (NIEHS) and National Heart, Lung, and Blood Institute (NHLBI) confirms the protective effect of cat exposure, but with an important caveat. When the child's mother has asthma, then a cat in the home actually triples the risk that a child will develop persistent wheezing — an initial indication of asthma — by age five.

"For years, physicians have been advising families with allergies to stay away from pets," says lead author Dr. Juan C. Celedón, who, along with primary investigator Dr. Diane R. Gold and colleagues conducted the research at Brigham and Women's Hospital in Boston, Massachusetts. "However, it appears that for a vast majority of children, being exposed to a cat early in life may be beneficial. That said, there is a subgroup of children — those whose mothers have asthma and, perhaps, those whose mothers are allergic to cats — who should probably avoid cat exposure." Children with documented cat allergy or with asthmatic symptoms triggered by a cat should also avoid cats, he adds.

The study followed 448 children with a family history of allergic diseases from birth to age five. Through periodic telephone interviews with caretakers, the researchers gathered information on the children's exposure to pets and how often the children experienced episodes of wheezing. In addition, the researchers tested dust samples from each child's home for levels of cat allergen (the compounds that cause allergies to cats). The researchers then analyzed the data they collected, adjusting for factors such as gender, household income, and daycare attendance.

In the group of children with non-asthmatic mothers, those exposed to a cat were 40 percent less likely to experience persistent wheezing as compared to those with no cat exposure. In the group of children with asthmatic mothers, however, those exposed to a cat were significantly more likely to wheeze compared to those with no cat exposure. In fact, the risk of wheezing increased in each of the five years of the child's life. By the third year, the risk of wheezing doubled, and by the fifth year it more than tripled.

The father's asthma status had no effect on the relation between childhood wheezing and cat exposure. And interestingly, there was no association between wheezing and exposure to dog or dog allergen. With each new research result, the development of asthma seems to be a more complex process.

"Asthma is a complex disease in which there appear to be many factors, both genetic and environmental," says Dr. Marshall Plaut, chief of the allergic mechanisms section at NIAID. "To better understand asthma, we need studies like this one that sort out these factors and define the relationships among them."

— a report from The NIH Word on Health, November 2002
Lancet 360,9335:781-782

For more information about asthma, visit http://www.niaid.nih.gov/publications/asthma.htm.

Information about children and asthma can be found at http://www.nlm.nih.gov/medlineplus/asthmainchildren.html.

Understanding Rheumatoid Arthritis

The cause of rheumatoid arthritis has remained something of a mystery. Now, a new study by NIH grantees shows that one type of immune cell known to play a key role in allergy and asthma plays a key role in rheumatoid arthritis as well.

The immune systems of people with rheumatoid arthritis, for unknown reasons, attack their own joints. The disease most often affects the joints of the hands and feet, but can affect other joints in the body as well. It causes pain, swelling, stiffness and potentially serious joint damage in over one percent of the US population.

The type of immune cells involved in the new finding, mast cells, are well known for their role in causing the symptoms of allergy. They are "activated" by molecules called antibodies that are manufactured by the immune system to bind very specifically to foreign invaders and direct the immune system to attack. In the nose, when antibodies bind pollens and molds, mast cells are activated and release little packets of chemicals that cause local inflammation, leading to sneezing, runny nose, and the other symptoms of allergies. Mast cells are also relatively abundant in arthritic joints, but no one knew their significance until now — in part because of how difficult it is to study these cells in humans.

A team of scientists at Harvard Medical School, in work funded by NIH's National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS) and National Institute of Allergy and Infectious Diseases (NIAID), turned to genetically engineered mice to see if mast cells might play a role in rheumatoid arthritis. They started with a strain of mice called K/BxN that spontaneously develops arthritis. When blood serum from K/BxN mice is injected into other mice, it quickly causes their paws to swell. The reason for this is that the K/BxN serum contains antibodies that mistakenly bind to components in the joint and direct the host's immune system to attack it.

The researchers used two additional strains of mice that couldn't produce mast cells. When scientists injected either of these strains with the K/BxN serum, their joints didn't become inflamed, showing that mast cells played a key role in causing the inflammation. When mast cells from normal mice were transplanted into these mice, the K/BxN serum once again induced arthritis. The researchers looked at samples of joint tissue and found that mast cells released their packets of chemicals within hours of K/BxN serum transfer, before the joint became inflamed. In contrast, mast cells in other parts of the body were not activated.

Researchers still don't know why the immune systems of people with rheumatoid arthritis make antibodies to direct attacks against their own joints. But this new research explains how, once those antibodies are made, mast cells get involved to cause inflammation and bring further destruction to the joint. Now that scientists are convinced that mast cells play a key role in rheumatoid arthritis, they can use that knowledge to pursue new treatments for the disease.

— a report from The NIH Word on Health, November 2002
Science 297:1689-1692

For more information about rheumatoid arthritis, see http://www.niams.nih.gov/hi/topics/arthritis/artrheu.htm and http://www.niams.nih.gov/hi/topics/arthritis/rahandout.htm or contact:

The NIAMS Information Clearinghouse
Phone: 301-495-4484
Fax: 301-718-6366
TTY: 301-565-2966

Molecular Treadmills for Hearing

Hearing loss caused by exposure to loud noises — if it's not permanent — typically lasts about 48 hours. New NIH research reveals a molecular explanation for this time period as well as a general explanation of how hearing is maintained throughout a lifetime. The finding may lead researchers toward new strategies for treating hearing disorders.

Researchers at NIH's National Institute on Deafness and Other Communication Disorders (NIDCD) were studying stereocilia, the microscopic hair bundles at the top of hair cells in the inner ear. Their role is to sense the vibrations caused by sound, beginning the process of changing sound into nerve impulses for the brain to interpret. Stereocilia contain a rigid core of filaments made of a protein called actin, and it was this protein that the scientists focused on.

The scientists wanted to understand how stereocilia are formed and maintained, so they turned to hair cells from rats, which can be studied outside of the body. They inserted a modified gene for actin that made the protein turn green in certain light, to track its incorporation into stereocilia under a microscope. They found that the modified action was incorporated into the tips of stereocilia within a few hours and then progressed toward their bases until their entire lengths were green.

The researchers concluded that actin protein is continually added into the actin filaments at the tips of the stereocilia, and that the actin filaments "treadmill" toward the base. These are known characteristics of actin filaments elsewhere in the body, but no one had previously shown this renewal process in the ear's hair cells. The turnover rate of actin in the hair bundles, the researchers found, was 48 hours — about the amount of time it takes to recover from noise-induced hearing loss. The core actin structure of stereocilia, then, likely plays a part in this recovery.

The continuous renewal of the core actin structure in stereocilia also likely plays a role in maintaining hearing throughout a lifetime. Some hearing disorders may now prove to involve problems in stereocilia maintenance and renewal.

— a report from The NIH Word on Health, November 2002
Nature 418:837

For more information about noise-induced hearing loss, see http://www.nidcd.nih.gov/health/pubs_hb/noise.htm or contact:

NIDCD Information Clearinghouse
Phone: 1-800-241-1044
TTY: 1-800-241-1055
e-mail: nidcdinfo@nidcd.nih.gov