Inactive Ingredient in Inhaler Drugs May Counteract Benefits
An inactive agent used in beta-agonist inhalers to treat asthma can reverse the beneficial anti-inflammatory effects of inhaled steroids, according to a recent study.

The findings may explain the paradoxical airway constriction and worsening of asthma in patients with continued use of beta-agonists such as albuterol.

Researchers at the University of Pittsburgh School of Medicine tested human airway smooth muscle cells to determine the effect of different isomers of albuterol—the active (R)-albuterol and the inactive (S)-albuterol—in combination with a simultaneously applied inhaled steroid. Recent advances allowed the separation, testing, and clinical administration of these compounds.

The researchers, led by Bill Ameredes, PhD, research assistant professor of medicine and assistant professor of cell biology and physiology, in the division of pulmonary, allergy, and critical care medicine, found that the active isomer amplified the anti-inflammatory effects of the steroid dexamethasone by reducing human airway smooth muscle cell production of a pro-inflammatory chemical signal.

The team found less favorable results for the inactive isomer. (S)-albuterol resulted in increased production of the same pro-inflammatory cell signal, Ameredes says.

“Thus, the reductions normally produced by the steroid were nullified by the inactive isomer of the beta-agonist. These results indicate that (S)-albuterol may diminish the beneficial anti-inflammatory effects of steroids by a mechanism that is not currently understood, and suggest that some of the paradoxical responses observed in asthmatics may derive from the pro-inflammatory effects of the (S)-isomer,” Ameredes says. He adds that the (S)-isomer of albuterol stays in the body three to four times longer than the beneficial (R)-isomer.

While Ameredes cautions that further research is needed, he says that some consideration should be given “to the possibility that current combination therapies involving racemic beta-agonists may not be realizing their full potential.

“It is possible that future focus on the therapeutic and nontherapeutic effects of isomers may reveal new combinatorial applications that can be beneficial to many sufferers of obstructive inflammatory lung diseases like asthma,” he says.

The study was presented March 23 at the annual meeting of the American Academy of Allergy, Asthma, and Immunology in San Francisco.

Group To Educate Congress on COPD
Concerned with the more than 13 million Americans diagnosed with some form of chronic obstructive pulmonary disease (COPD), Idaho Republican Senator Mike Crapo in April announced the founding of a congressional caucus dedicated to furthering awareness of the disease’s risks and promoting policies to improve the lives of COPD patients. Crapo will cochair the Congressional COPD Caucus with Senator Blanche Lincoln (D-Ark) and Representatives John Lewis (D-Ga) and Cliff Stearns (R-Fla). The caucus will partner with a broad coalition of physician, patient, and home care organizations, including the American College of Chest Physicians, the American Association for Homecare, Alpha-1 Association, American Thoracic Society, American Lung Association, and the American Association for Respiratory Care.

• Research Links Sleep Disorder to Persistent Allergies People with obstructive sleep apnea syndrome (OSAS) may have an increased risk of being allergic to perennial allergens and suffering from rhinitis all year long, a recent study shows. Comparing OSAS patients to chronic obstructive pulmonary disease (COPD) patients, Swiss researchers found that those with OSAS were more likely to be sensitized to perennial allergens such as house dust mites and dogs than COPD patients. In addition, more OSAS patients experienced perennial allergic rhinitis than COPD patients. The study appeared in the March/April issue of Respiration. • Lung Cancer Cause Different for Women A new theory that lung cancer in women might be a different disease than lung cancer in men is supported by recent research showing that lung cancer is now the number-one cause of cancer death among women. Among men, the lung cancer rate has declined, says Northwestern University researcher Jyoti D. Patel, MD. In an article in the April 14 issue of the Journal of the American Medical Association, Patel and colleagues from Memorial Sloan-Kettering Cancer Center, New York, discuss differences in the biology of lung cancer between the sexes, including genetic mutations, increased production of certain enzymes that help trigger cancer growth, and hormonal changes. During the 20th century, women’s tobacco use rose and the number of women who died of lung cancer increased by 600%, the researchers say. In the same period, the number of lung cancer deaths in men declined. “Mounting evidence suggests that these differences could be due, in part, to estrogen,” Patel says. Research has found that lung cancer cells have more estrogen receptors on their surface than normal lung cells. Other studies have shown an association between estrogen replacement therapy and development of adenocarcinoma of the lung and a positive interaction between estrogen replacement, smoking, and development of adenocarcinoma of the lung, Patel says.