Alterations in Airway Inflammation and Lung Function During Corticosteroid Therapy for Atopic Asthma:

The search for associations between changes in measures of airway inflammation and physiology is made complex by the variability of measures over time, because variability is the hallmark of asthma. The current data suggest that changes in airway inflammation and lung function are closely related, but associations between changes in these two processes may be dependent on the duration of sampling interval.
The demonstration of a close association between longer-term (but not short-term) changes in EG1 and changes in lung function has several implications for our understanding of the kinetics of asthma. This result supports several previous animal and human studies that demonstrate that tissue damage due to eosinophils and the development of airway pathophysiology do not occur simultaneously itat on canada health and care mall. In humans, increases in sputum eosinophils have been observed prior to deteriorations in asthma control. Fluctuations in the severity of airway hyperreactivity are thought to result, in part, from prior injury to the bronchial mucosa by inflammatory cells, most notably the eosinophil. Moreover, in sensitized mice, increases in airway eosinophils precede the development of airway hyperreactivity after allergen chal-lenge. The cellular components of airway inflammation are dependent on one another for recruitment and survival. This article is, to our knowledge, the first investigation of associations between short-term and longer-term changes in bronchial immunopathology in the same set of asthmatic subjects during inhaled corticosteroid therapy. In this human, in vivo model of asthma, the associations between the rates of change of airway macrophages and T cells are consistent with in vitro models of macrophage and T-cell biology.
In the asthmatic airway, the cellular components of bronchial inflammation may be dependent on one another for survival and recruitment (both via cell-cell interactions and through the secretion of soluble factors, such as cytokines and chemokmes). We find that short-term and longer-term changes in eosinophils are not closely correlated with changes in T cells or macrophages. Although an association might have been observed if repeat measures were obtained at another time point, airway eosinophil recruitment and activation are probably not wholly orchestrated by local airway T cells and macrophages. Our results are consistent with the thinking that other factors (circulating eosinophils, serum IgE, and serum cytokines, for example) may influence bronchial eosinophilic inflam-mation.
In summary, significant associations exist between longer-term (but not short-term) changes in airway eosinophils and longer-term changes in bronchodi-lator responsiveness. Although changes in airway eosinophils are associated with changes in lung function, these two processes do not occur simultaneously.