s Anti-Inflammatory Drug Targeting in Asthma. Should Inhaled Corticosteroids Reach the Small Airways?

Bronchial asthma is characterized by an eosinophilic inflammatory process in the airways, and manifests itself functionally by bronchial hyperresponsiveness and variable airflow obstruction. In the past this inflammatory process was presumed to be predominantly present in the large and intermediate airways. This is not surprising since functional abnormalities in the small airways (or so-called silent zone) are much more difficult to establish in comparison to changes in the larger airways. As a consequence, changes in airway calibre and bronchial hyperresponsiveness are mainly measured in the central part of the lung, i.e. by means of the FEV1 at rest or after challenge with bronchoconstrictive stimuli like histamine and methacholine. Recently, advanced physiological, radiological and morphological studies have shown that the inflammatory process extends to the peripheral airways and even the alveolar compartment. This so-called peripheral inflammation may be related to the clinical manifestation of the severity of asthma. Targeting the small airways with inhaled corticosteroids (ICS) with a small particle size and a high peripheral deposition may result in better control of the disease in a subset of patients. Indeed, several clinical-mechanistic studies have shown that, in contrast to the ‘conventional’ ICS with ‘large’particles, these extrafine ICS may induce functional and immunologic alterations in the peripheral lung compartment The presence and clinical consequences of peripheral inflammation and its therapeutic consequences are discussed in this review.