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Life, Death, and Second Chances

Before Diane Cushman-Neal was referred to Dr. Richard Martin her asthma had gotten so severe that she was beginning to fear for her life. Was there any hope at all?

Dr. Richard Martin, with Diane Cushman-Neal

Dr. Richard Martin, with Diane Cushman-Neal
Photo: Courtesy, National Jewish Medical and Research Center

By the time Richard Martin, M.D., saw Diane Cushman-Neal, her doctors had given her the prognosis that she likely had only six months to live because of the severity of her asthma. She had been hospitalized several times and could hardly walk to the bathroom without taking a rest. Her doctors in California had been providing textbook asthma care, but she was only getting worse. They sent her to Dr. Martin, Chairman of the Department of Medicine at the National Jewish Medical and Research Center in Denver, one of the world's leading centers of research on asthma and other lung diseases.

Dr. Martin took a biopsy of Cushman-Neal's lung, looking for damage to the tiny hairs that line the airways. In an electron micrograph of the biopsy the hairs looked fine, but technician Jan Henson spotted suspicious squiggles, which she pointed out to Dr. Martin. The squiggles turned out to be Mycoplasma pneumoniae, a bacteria that can cause pneumonia. Although Cushman-Neal did not have pneumonia, Dr. Martin decided to treat her infection with antibiotics.

Slowly but surely, Cushman-Neal's condition improved. She was able to reduce her medication s and her lung function improved dramatically. She skied for the first time in years and ran a 10-kilometer race. Recently, she married and adopted two children.

"Dr. Martin was the one who made all the difference," says Cushman-Neal, who moved from San Diego to Denver to be close to Dr. Martin and National Jewish. "He gave me the ability to breathe."

But the giving went both ways. Inspired by what had happened to Cushman-Neal, Dr. Martin began studying the role that bacterial infections can play in asthma. Initial research indicated that more than half of adults with chronic, stable asthma have bacterial infections, and that treatment with antibiotics can improve their lung function.

The NIH's National Institute of Allergy and Infectious Diseases (NIAID) considered the initial research so promising that it awarded Dr. Martin $7.5 million to lead a multi-center study to see if those results can be replicated in a larger audience. Another trial, led at National Jewish by Stanley Szefler, M.D., and funded by the National Heart, Lung and Blood Institute (NHLBI), is looking for the same benefit in children with moderate to severe asthma. If the findings hold up, they could significantly change the way asthma is treated.

"Diane Cushman-Neal was the sentinel patient," said Dr. Martin. "Her case inspired a very fruitful avenue of research."

When Good Treatment Fails

In another area of research, Dr. Martin and colleagues recently investigated why certain patients with asthma do not experience improved lung function with anti-inflammatory therapy. Although revised guidelines recommend anti-inflammatory therapy for persistent asthma, many patients with asthma may not improve on this therapy. This is a different medical question than what prevented Cushman-Neil from leading a normal life, but this phenomenon does affect 25–35 percent of asthma patients. What Dr Martin discovered is that a six-week trial of inhaled corticosteroids may determine how patients will respond to continued treatment. The short-term response to inhaled corticosteroids, a type of anti-inflammatory drug used to treat asthma, was determined by measuring the amount of air that can be forced out of the lungs in one second after taking a deep breath; an important measure of lung function. Improvement in this measure predicts how well asthma can be managed for long-term control. The decision to use long-term inhaled steroids could be based on a short-term trial to determine if the patient will respond to the treatment. Different therapeutic strategies would need to be established for patients that do not experience improved lung function.

These findings have implications for what therapy will benefit patients that do not receive benefit. "Asthma is a syndrome not a disease,"says Dr Martin, "and there are a variety of causative factors that are important to identify."

Fall 2007 Issue: Volume 2 Number 4 Pages 16 - 17