The inflammation that characterizes the lower respiratory tract in CF is not primarily started by the genetic defect rather than viral infections that, already present in almost 40% of infants with CF at 3 months of age, impair the specific anti-bacterial defense, increase the adherence of bacteria to the mucous membrane, impact negatively nitric oxide synthase 2 (NOS2) activity, and, enhancing the pro-inflammatory cytokine production [interleukin (IL)-6 and IL-8], affect the immune defense in the human airway, resulting in severe respiratory illness in CF patients (4). Here, NOS2 is linked to cystic fibrosis.