Title:Anti-Inflammatory Drug Targeting in Asthma. Should Inhaled Corticosteroids Reach the Small Airways?
Volume: 7
Issue: 4
Author(s): P. N. Richard Dekhuijzen
Affiliation:
Keywords:
Asthma, inflammation, inhaled corticosteroids, MMAD, particle size, small airways
Abstract: 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.
