BACKGROUND: Airway hyperresponsiveness is expressed as the provocative dose or concentration of the stimulus required to achieve bronchoconstriction, a 20% fall in FEV1 (PD20 and PC20, respectively). A decrease in PC20 may be due to a steeper dose-response curve (hyperreactivity) or to a shift in the curve to the left (hypersensitivity), or both. It has been suggested that many factors, such as genetic factor, airway inflammation, epithelial damage or airway remodeling, are involved in the airway hyperresponsiveness in asthma. OBJECTIVE: In this study, we analyzed the relationship of airway sensitivity and reactivity with bronchial inflammation and structural change in asthmatics. METHOD: The PC20 for methacholine, as the airway sensitivity parameter, and the slope between PC20 and PC40, as the airway reactivity parameter, were measured. Total cell counts and differential cell counts in BAL fluid, percentage of epithelial shedding (ES), basement membrane thickness (BMT) and depth of submucosal collagen deposition (SMC) on bronchial tissue were measured. The patients (n=27) were divided into two groups by median values of ES, BMT, or SMC (32%, 7.3 micrometer, 68 micrometer, respectively). RESULTS: The PC20 showed a significant correlation with baseline FEV1% (r=0.498, p<0.05), and was significantly lower in patients with over 32% of ES than in those with under 32% of ES (2.89+/-1.05 mg/ml vs 5.70+/-3.70 mg/ml, p<0.05). The slope was significantly steeper in patients with thicker BMT or SMC. CONCLUSION: These results suggest that airway hypersensitivity is affected by airway caliber, and airway hyperreactivity is affected by bronchial remodeling in asthma.
Airway Remodeling ; Asthma ; Basement Membrane ; Bronchoconstriction ; Cell Count ; Collagen ; Humans ; Hypersensitivity ; Inflammation ; Methacholine Chloride ; Pathology*

BACKGROUND AND OBJECTIVES: This study was designed to evaluate the appropriate dose and dose-dependent effect of benidipine hydrochloride, a Ca+ +/- channel blocker, in patients with mild-moderate essential hypertension. Material and MethodsBenidipine was administered in 2 mg, 4 mg and 8 mg once daily with 1 month interval in 41 hypertensive patients with diastolic blood pressure over 90 mmHg and systolic blood pressure from 140 to 210 mmHg. Blood pressure, heart rate, subjective symptoms and adverse effects were checked every 4 weeks after benidipine administration. Laboratory examinations were performed before and after benidipine administration. RESULTS: The dose-dependent, antihypertensive effect of benidipine was evaluated in 41 patients. The blood pressure significantly reduced from 166+/-15 mmHg/103+/-7 mmHg to 13815 mmHg/88+/-11 mmHg at 12 weeks administration of benidipine and overall effective rate was 95%. The systolic and diastolic blood pressure was reduced significantly in proportion to dose of benidipine (p<0.0001). Antihypertensive effect was prominent at 4mg of benidipine. The heart rate was not affected by benidipine. No significant laboratory changes were observed. CONCLUSION: Benidipine has a dose-dependent effect in the treatment of mild-moderate hypertension, and the dosage to be needed may be 4mg or more for sufficient antihypertensive effect.
Blood Pressure ; Heart Rate ; Humans ; Hypertension*