Thus, our study is the first to show genome-wide gene expression profiles of neutrophils of CF patients colonized by bacteria in their airways and in a clinical condition of acute exacerbation. Recent work has focused on CF blood mononuclear cells in order to identify circulating transcripts as EX 527 biomarkers of the treatment for an acute exacerbation. Saavedra et al. found that 10 genes significantly changed with therapy and that three genes enhanced the predictive discriminating value of FEV1 alone. However, seven of the 10 genes are not specific to CF and they need further evaluation as their role and biomarker status in the CF disease. Interestingly, the same group has recently validated the 10 genes in a study on the whole blood in a cohort of CF patients treated for acute exacerbations. Their findings show that six out of 10 genes strongly predicted a reduction in airway bacterial load beyond FEV1 and CRP, adding specificity in predicting reduced pulmonary infection. The six genes were not coincident with our three-genes panel sensitive to treatment for an acute exacerbation. This may reflect that these six genes are related more to mononuclear cells than to neutrophils. One of the aims of this work is to find a set of genes which is differentially transcribed in CF as compared to “healthy” condition. This “CF signature” could be useful to identify CF patients unequivocally and start with therapy as soon as possible. A net separation between CF patients and healthy controls was obtained. A caveat to these findings is that, although we define a set of regulated genes in CF patients at the onset of an acute exacerbation, this clinical condition is not representative of the initial steps of disease, thereby further studies with different cohorts of patients in various clinical conditions are needed. It is not surprising that a distinct separation could be not possible when comparing patients before and after treatment, suggesting that patients can respond differently to antibiotic treatment for an acute exacerbation. Noxa is a member of Bcl-2 family of proteins, a critical mediator of the p53-dependent apoptosis and has been implicated in hypoxia-induced apoptosis. Noxa is also likely involved in apoptosis of virus-infected cells to limit viral dissemination. Recently, a strong pro-apoptotic role of Noxa in the final steps of neutrophil differentiation from progenitors has been described. A delayed apoptotic response has been described in blood neutrophils isolated from CF patients.