Potential Mechanisms of Improvement of Airway Hyperresponsiveness by Inhaled Corticosteroid Therapy in Asthmatic Patients

Abstract

Objective. Recent clinical trials with administration of IL-5 antibodies to asthmatic patients have revealed reduction of eosinophilia but unaltered airway hyperresponsiveness (AHR). In contrast, inhaled corticosteroid (ICS) therapy eliminates both eosinophilia and AHR. This study was designed to examine the mechanisms by which ICS improves airway hyperresponsiveness in asthmatic patients.

Methods. Clinical variables of asthma involving vascular permeability and IL-5 levels were examined in 23 asthmatic patients and 11 normal control subjects. After the first sputum induction, inhaled beclomethasone dipropionate (BDP 800 μg/day) was administered to asthmatic patients for 8 weeks, and sputum induction was repeated.

Results. IL-5 levels in induced sputum and airway vascular permeability index were significantly higher in asthmatic patients. IL-5 was positively correlated with percentage of eosinophils in induced sputum, and negatively correlated with FEV1, but not correlated with PC₂₀ methacholine. After BDP therapy, eosinophils, ECP, and IL-5 levels were significantly decreased to the same levels as in normal subjects. Conversely, PC₂₀ methacholine and airway vascular permeability did not improve to the same levels as in normal subjects. Increase in PC₂₀ methacholine from before to after BDP therapy was significantly correlated with decrease in airway permeability index, but not with decrease in IL-5 level.

Conclusion. Our results suggest a clear dissociation between IL-5 and AHR. ICS therapy improves AHR at least in part through decrease in airway vascular permeability.

Keywords:

• airway vascular permeability
• bronchial asthma
• beclomethasone dipropionate
• airway hyperresponsiveness
• interleukin-5