These results suggest: 1) an early and spontaneous (without any detectable precipitating infection) inflammatory phenotype in the lungs of CF mice, 2) progression to overt lung disease in CF mice corresponds to elevated levels of both S100A8 and S100A9 (or only S100A8), but not S100A9 alone, and 3) a prominent influence of secondary genetic factors on differential regulation of S100A8 expression. Here, S100A9 is linked to lung disorder.