Description
Chronic infectious airway diseases such as cystic fibrosis are characterized by a scenario that typically reflects poor/absent clearance of mucus, infection of mucus by inhaled bacteria, chronic stimulation of host defenses by persistent bacterial mucus infection, and typically a failure to eradicate the infection due to the failure to clear mucus. In the absence of rectifying the primary defect in mucus clearance, the progression of the disease in the host reflects in part a balance between the effectiveness of the host defense mechanisms to suppress bacterial growth/spread and the destructive effects of "frustrated" host defense mechanisms on the airway wall. In addition, there is usual incidence of intercurrent lower respiratory viral infections in these patients, but the consequences to the host are more severe than in normal individuals. Whereas substantial knowledge is being achieved regarding the sequence of viral followed by bacterial infections in mucosal surfaces, there are relatively few studies of the reverse sequence, i.e., the effect of chronic bacterial infection on an intercurrent viral process.
The overarching goal of the workshop was to provide novel insights into critical new steps in the pathogenesis of diseases of persistent mucus adhesion/infection to yield new and better therapeutic strategies. This workshop reviewed the state of knowledge on: 1) Initiation and mechanism of mucus adhesion to airway surfaces; 2) how bacteria typically infect airways and interact with abnormal mucus to generate persistent infection; 3) how the persistent stimulation of host elements, e.g. epithelium macrophages, lymphocytes, and dendritic cells, leads to a balance between a persistent inflammatory response and tolerance to this antigenic load; and 4) how an airway plagued by chronic bacterial infection responds to intercurrent viral infections, e.g., with paramyxoviruses and rhinoviruses, to create a more adverse outcome to the host. Following evaluation of the current state of knowledge, the workshop participants identified gaps in our knowledge, established the important research questions, and made recommendations for future research directions.