Gene expression for MUC5AC is increased in airway epithelial cells in asthma, and MUC5B expression is decreased (1, 2), but it is uncertain how this abnormal gene expression for gel-forming mucins contributes to mechanisms of formation of pathologic airway mucus gels in asthma exacerbation and stable asthma. Recent studies in transgenic mice show different functions for MUC5AC and MUC5B in the lung. Whereas MUC5B has physiologic functions in the mucus gel that ensure normal mucus clearance (3), MUC5AC has pathologic roles in mechanisms of allergen-induced airway hyperresponsiveness, mucous metaplasia, and airway mucus plugging (4). Changes in the relative proportions of MUC5AC and MUC5B could also affect eosinophil survival in the airway mucus gel because glycoepitopes in the MUC5B glycan coat interact with Siglec-8 on eosinophils to induce apoptosis (5). Thus, a relative deficiency of MUC5B in airway mucus could create an environment that promotes eosinophil survival.

It is unknown whether abnormalities in airway gene expression for MUC5AC and MUC5B in asthma are mirrored in the mucin protein composition of the airway mucus gel. We therefore set out to examine the relative proportions of MUC5AC and MUC5B protein in induced sputum collected from healthy controls (n= 16), patients with stable asthma (n= 34), and patients with exacerbations of asthma (n= 13)(Table 1). Healthy and stable subjects with asthma participated in a research protocol involving at least two visits: one for disease characterization (including measurement of lung function and induced sputum collection for analysis of total and differential cell counts) and another for collection of induced sputum for purification of mucins. The patients with asthma exacerbation were recruited from the emergency room at University of California, San Francisco, Medical Center, using methods previously described (6), and their spontaneously expectorated sputum was divided to allow one aliquot to be processed for total and differential cell counts and one to be processed for mucin purification. Methods of characterization, sputum induction, and sputum processing for cell analysis have been described in detail in our prior publications (7, 8). A previous attempt to quantify sputum mucins by direct-binding ELISAs reported technical difficulties related to high levels of nonmucin proteins that interfered with the immobilization of the mucins on the plate (9). Another potential problem with mucin immunoassays is poor antibody recognition of mucin epitopes in protease-rich