Reducing eosinophilic airway inflammation in severe asthma

In a study of patients with severe asthma who had eosinophils in their sputum despite extensive antiasthma medication, investigators showed that a high dose of extra intramuscular corticosteroids resulted in almost complete disappearance of eosinophilic cells, led to decreased use of “rescue” medications, and helped improve patients’ lung function tests.

Eosinophils are a type of white blood cell that constitute from 1 to 3 percent of the total white cell count. When foreign substances or infectious cells enter the body, lymphocytes and neutrophils attract eosinophils which release toxic substances that can destroy abnormal cells. Eosinophils function in allergic responses and in helping resist some infections.

Writing in the second issue for September 2004 of the American Thoracic Society’s peer-reviewed American Journal of Respiratory and Critical Care Medicine, Elisabeth H. Bel, M.D., Ph.D., of the Department of Pulmonary Diseases, Leiden University Medical Center, Leiden, The Netherlands, along with four associates, studied 22 non-smoking outpatients with severe asthma in order to prove that patients with extensive eosinophilia, despite significant anti-inflammatory treatment, were sensitive to high dose injected corticosteroids. Of the 22 patients in the study, 11 received the steroids and 11 were given placebo over a 3-week period. All patients had sputum eosinophilia above the upper limit of normal. However, after treatment with the injected corticosteroids, sputum eosinophils returned to normal levels (from zero to 2 percent) in the 11 treated patients.

“This study shows that the intensity of airway inflammation and the level of symptoms and lung function can, and should be improved by intensifying treatment and/or administering via the systemic route,” said Dr. Bel. “Regular monitoring of sputum eosinophils to adjust anti-inflammatory treatment might be necessary in these patients to prevent severe exacerbations and airway fibrosis.”

The authors believe that corticosteroids by injection (parenteral administration) might be able to reach regions of the airways that are not accessible to inhaled corticosteroids. Such areas include peripheral airways in the lung, the upper airways, and the paranasal sinus.

They also note that injected corticosteroids also reach the bone marrow and could help reduce eosinophils being produced by processes involving inflamed tissue.

The 22 nonsmoking outpatients in the study included 15 women. Patient ages were from 21 to 73. They all had severe bronchial asthma, but had been clinically stable for at least 4 weeks. All patients used from 1,600 to 6,400 micrograms per day of inhaled corticosteroids and had long-acting bronchodilators that they accessed when needed.