A reduced apoptotic response in acute Rapamycin exacerbation might be correlated with longer neutrophil survival and more damage to the airways. During phagocytosis, HVCN1 is involved in maintaining NADPH oxidase activity by preventing acidification to an intracytosolic pH low enough to inhibit NADPH oxidase. A low level of HVCN1 transcripts in CF patients before therapy as compared to non-CF subjects is suggestive of an impaired oxidative burst and pathogen survival in this condition. However, the respiratory burst in CF neutrophils has been demonstrated to be extremely variable as compared to “healthy” neutrophils. To the best of our knowledge, HVCN1 protein expression and function have not been studied in CF neutrophils and our data therefore open a novel avenue in the study of neutrophil antibacterial function in CF lung disease. ARRB1 is a scaffolding protein involved in platelet-activating factor-induced endocytosis and cytoskeleton rearrangement. b-arrestins may also be required for activating signaling pathways leading to exocytosis of primary and secondary granules in neutrophils. Like HVCN1,the ARRB1 protein has not been investigated in its expression and function in CF neutrophils. Functional studies are needed to elucidate which effect ARRB1, HVCN1 and PMAIP1 mRNA fluctuations exert on the granule exocytosis, respiratory burst, as well on the apoptotic response. The sensitivity of ARRB1, PMAIP1 and HVCN1 to the antibiotic treatment makes these three genes promising candidates for the evaluation of the response to therapy, although this should be substantiated by studies correlating these transcript to respiratory functional tests or follow up. Sputum neutrophils were found to have a limited set of expressed genes in common with blood neutrophils, and most of these genes were down-regulated in sputum neutrophils, while the contrary was found for blood neutrophils in the exacerbation status. These data point to a different transcriptome profile for airway neutrophils as compared to that of circulating neutrophils, giving strength to the observation that the airway environment is causative of reprogramming of extravasated neutrophils in CF, but are not consistent with results obtained with only 1050 genes by Adib-Conquy et al.. Moreover, this difference was seen in both pre-therapy and post-therapy neutrophils, suggesting that antibiotic treatment does not cause a profound modification in gene expression of extravasated neutrophils. Nevertheless, the three genes object of this study had the same trend as in blood neutrophils.