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Background: Asthma is a common chronic inflammatory airway affecting over 260 million people worldwide, and characterized, in the large majority of cases, by the so-called "type 2 inflammation". Fractional exhaled nitric oxide (FENO) testing is noninvasive point-of-care tool to assess type 2 inflammation and therefore improve asthma management. It has been suggested to determine eligibility for a specific biologic therapy and predict likelihood to respond. The aim of this study was to estimate the overall economic impact of an extensive use of FENO testing on the Italian population with asthma, including extra costs of testing and savings generated by more appropriate prescriptions, increased adherence and lower frequency of exacerbations. Methods: A cost of illness analysis was firstly performed to estimate the yearly economic burden from the National Healthcare Service (NHS) perspective in Italy of the management of asthmatic patients with standard of care (SOC) according to the application of GINA (Global Initiative for Asthma) guidelines; then, we evaluated the changes in the economic burden in patient management by introducing FENO testing into clinical practice. The cost items considered were: visits/exams, exacerbations, drugs, management of adverse events caused by short-term oral corticosteroids use. Efficacy of FeNO test and SOC is based on literature evidence. Costs refer to published data or Diagnosis Related Group/outpatient tariffs. Results: Considering one asthma visit every 6 months, the total yearly cost for the management of patients with asthma in Italy is 1,599,217,876€ (409.07€ per patient), while for FENO testing strategy this figure is 1,395,029,747€ (356.84€ per patient). An increased utilization rate of FENO testing from 50 to 100% of patients may lead to savings for the NHS from about 102 to 204 million € compared to SOC. Conclusions: Our study showed that FeNO testing strategy may improve the management of asthmatic patients leading to significant savings for the NHS. [ABSTRACT FROM AUTHOR]

Background: The discrepancy between functional and inflammatory airway response to ozone has been reported in normal subjects, but few data are available for stable asthmatics regularly treated with inhaled corticosteroids. Methods: Twenty-three well controlled, regularly treated, mild-to-moderate asthmatic patients underwent two sequential randomised exposures to either filtered air or ozone (0.3 ppm for 2 hours) in a challenge chamber. Pulmonary function (PF) was monitored, and patients with FEV1 decrease greater than 10% from pre-challenge value were considered as responders. Immediately after each exposure, exhaled breath condensate (EBC) was collected to measure malondialdehyde (MDA). Six hours after each exposure, PF and EBC collection were repeated, and sputum was induced to measure inflammatory cell counts and soluble mediators (IL-8 and neutrophil elastase). The response to ozone was also evaluated according to the presence of polymorphism in oxidative stress related NQO1 and GSTM1 genes. Results: After ozone exposure, sputum neutrophils significantly increased in responders (n = 8), but not in nonresponders (n = 15). Other markers of neutrophil activation in sputum supernatant and MDA in EBC significantly increased in all patients, but only in nonresponders the increase was significant. In nonresponders, sputum eosinophils also significantly increased after ozone. There was a positive correlation between ozoneinduced FEV1 fall and increase in sputum neutrophils. No difference in functional or inflammatory response to ozone was observed between subjects with or without the combination of NQO1wt- GSTM1null genotypes. Conclusions: Markers of neutrophilic inflammation and oxidative stress increase also in asthmatic subjects not responding to ozone. A greater functional response to ozone is associated with greater neutrophil airway recruitment in asthmatic subjects. [ABSTRACT FROM AUTHOR]

Background: Sperm protein 17 (Sp17) is a highly conserved mammalian protein characterized in rabbit, mouse, monkey, baboon, macaque, human testis and spermatozoa. mRNA encoding Sp17 has been detected in a range of murine and human somatic tissues. It was also recognized in two myeloma cell lines and in neoplastic cells from patients with multiple myeloma and ovarian carcinoma. These data all indicate that Sp17 is widely distributed in humans, expressed not only in germinal cells and in a variety of somatic tissues, but also in neoplastic cells of unrelated origin., Methods: Sp17 expression was analyzed by immunocytochemistry and transmission electron microscopy on spermatozoa., Results: Here, we demonstrate the ultrastructural localization of human Sp17 throughout the spermatozoa flagellar fibrous sheath, and its presence in spermatozoa during in vitro states from their ejaculation to the oocyte fertilization., Conclusion: These findings suggest a possible role of Sp17 in regulating sperm maturation, capacitation, acrosomal reaction and interactions with the oocyte zona pellucida during the fertilization process. Further, the high degree of sequence conservation throughout its N-terminal half, and the presence of an A-kinase anchoring protein (AKAP)-binding motif within this region, suggest that Sp17 might play a regulatory role in a protein kinase A-independent AKAP complex in both germinal and somatic cells.