An investigation of mucus plugging in severe asthma

The classic pathologic finding in patients with fatal asthma is of markedly hyperinflated lungs. This hyperinflation is the consequence of widespread plugging of the segmental and sub-segmental airways. In contrast to fatal asthma, the link between mucus plugs and airflow obstruction is not established in chronic asthma, and the role of eosinophils and their products in mucus plug formation is unknown. I hypothesize that patients with chronic asthma who have a significant number of airway mucus plugs are characterized by a low forced expiratory volume in 1s (FEV1), airway type 2 inflammation and abnormal mucin gene expression. Furthermore, I hypothesize that eosinophils play a role in mucus plugs formation. To test these hypotheses, I developed a novel bronchopulmonary segment-based scoring system to quantify mucus plugs on multidetector computed tomography (MDCT) lung scans. I applied the score to the MDCT lung scans of 146 subjects with asthma and 22 healthy controls in the Severe Asthma Research Program, and analysed relationships between mucus plug scores, FEV1, symptoms of chronic mucus hypersecretion (CMH), treatment responses, and measures of airway inflammation. In bench studies, I used model systems of airway mucus gels to explore whether oxidants generated by eosinophil peroxidase (EPO) oxidize cysteine thiol groups promote mucus plug formation. Mucus plugs were seen in 58% of subjects with asthma and in 4.5% of controls, and plugs in subjects with asthma were seen in the same segment for years. A high mucus score (plugs in ≥ 4 segments) occurred in 67% of subjects with asthma FEV1 80% (p