The Effect of glucocorticoid on the change of nitric oxide and cytokine levels in induced sputum from patients with bronchial asthma

Kim, Tae Yon; Yoon, Hyeong Kyu; Choi, Young Mee; Lee, Sook Young; Kwon, Soon Seog; Kim, Young Kyoon; Kim, Kwan Hyoung; Moon, Hwa Sik; Park, Sung Hak; Song, Jeong Sup

Abstract

BACKGROUND
It has been well known that bronchial asthma is a chronic airway inflammatory disorder. Recently, sputum specimen induced with hypertonic saline was introduced as a simple and useful noninvasive medium to investigate airway inflammation and symptom severity in patients with asthma. We examined the eosinophil, cationic protein (ECP), interleukin(IL)-3, IL-5, granulocyte-macrophage colony-stimulating factor (GM-CSF), and nitric oxide (NO) derivatives in induced sputum from patients with bronchial asthma in order to determine the role of NO and various inflammatory cytokines as a useful markers of airway inflammation of changes in pulmonary function tests and symptoms.
METHODS
A total 30 patients with bronchial asthma received oral prednisolone 30 mg daily for 2 weeks. Forced expiratory volume in one second (FEV), total blood eosinophil count, and induced sputum eosinophil count, ECP, IL-3, IL-5, GM-CSF, and NO derivatives were determined before and after the administration of prednisolone.
RESULTS
Of the 30 patients, 13 (43.3%) were male and 17 (56.7%) were female. The mean age of patients was 41.8 years (range 19-64 years). Two patients could not produce sputum at the second study and 3 could not be followed up after their first visit. Two weeks after the prednisolone administration, there was a significant increase in FEV1 (% of predicted value) from 78.1±20.6% to 90.3±18.3% (P<0.001). The eosinophil percentages in induced sputum were significantly decreased after treatment with prednisolone, with values of 56.1±27.2% versus 29.6±21.3% (P<0.001), and ECP were 134.5±68.1 µm/L versus 41.5±42.4 µm/L (P<0.001) respectively. After the prednisolone treatments, the eotaxin concentration also showed a decreasing tendency from 26.7±12.8 pg/ml to 21.7±8.7 pg/ml. There was a decreasing tendency but no significant differences in total blood eosinophil count(425.7±265.9 vs 287.7±294.7) and in the concentration of NO derivatives (70.4±44.6 µmol%/L vs 91.548.3 µmol/L) after the predinisolone treatments. IL-3, IL-5, GM-CSF were undetectable in the sputum of most subjects either before the prednisolone treatments of after the treatments. Before the prednisolone treatments, a significant inverse correlation was observed between FEV1 and sputum ECP (r=-0.364, P<0.05) and there was a significant correlation between sputum eosinophils and eotaxin (r=0.369, P<0.05).
CONCLUSION
The eotaxin and ECP concentration in induced sputum may be used as markers of airway inflammation after treatments in bronchial asthma. In addition, the measurement of sputum eosinophil percentages is believed to be a simple method displaying the degree of airway inflammation and airway obstruction before and after the predinisolone treatment in bronchial asthma. However, unlike exhaled NO, the examination of NO derivatives with Griess reaction in induced sputum is considered an ineffective marker of changing airway inflammation and obstructing symptoms.