A muco-inflammatory milieu characterizes early cf lung disease

Total airway mucins were elevated in CF compared to non-CF. Immunohistochemistry revealed higher staining intensities of secreted MUC5B (p<0.01) and MUC5AC (p<0.01) in mucus flakes from CF vs. non-CF. Microrheology measurement demonstrated presence of mucus flakes in CF BAL, which could be solubilized by reducing agents. Total CF mucins and mucus flakes correlated with inflammation, hypoxia, oxidative stress and oral flora, and these changes often preceded development of structural lung disease. Early CF lung disease is characterized by an increased burden mucus, including insoluble mucus flakes,that is associated with inflammatory and hypoxia markers and occurs prior to conventional bacterial pathogen infection or structural lung disease. These data suggest that early prevention therapies should focus on clearance of mucus and reduction of inflammation.