Evaluation of multiple-flows exhaled nitric oxide and its clinical significance in severe asthmatic patients treated with biologics: a prospective real-life study.

BACKGROUND: Specific biomarkers, such as eosinophilia in peripheral blood or fractional exhaled nitric oxide (FeNO), can guide us in the choice of biologic therapy, allowing a more personalized approach. Although there are multiple evidences in the literature about the role of FeNO as a predictor of response to different biologic treatments, there are no data on the relationship between FeNO changes and clinical response to the four biologic drugs currently in use. OBJECTIVE: To evaluate and to compare the expression of multiple-flows FeNO parameters in a cohort of patients with severe asthma (SA) before and during the treatment with biologics to evaluate the performance of these biomarkers in predicting the achievement of clinical remission. METHODS: We prospectively enrolled 50 patients with severe asthma eligible for biologic therapy. Patients underwent clinical and functional monitoring at baseline (T0) and after 1, 6, and 12 months of treatment (T1, T6, T12), including multiple flows FeNO assessment. RESULTS: A statistically significant reduction of FeNO50 values and J'awNO was observed only in benralizumab and dupilumab subgroups. Among biomarkers, the reduction of FeNO 50 values at T1 was associated with a higher probability of achieving clinical remission at T12 (p = 0.003), which was also confirmed by ROC curve analysis (AUC 0.758, p = 0.002; sensitivity 60% and specificity 74% for a reduction of 16 ppb). CONCLUSION: These data confirm the potential of this biomarker in predicting clinical response to biologic treatment in patients with severe asthma in order to guide clinical decisions and evaluate a shift to other biologic therapy.

The response of Phaeodactylum tricornutum to quantum dot exposure: Acclimation and changes in protein expression.

Nanotechnology has a great potential to improve life and environmental quality, however the fate of nanomaterials in the ecosystems, their bioavailability and potential toxicity on living organisms are still largely unknown, mainly in the marine environment. Genomics and proteomics are powerful tools for understanding molecular mechanisms triggered by nanoparticle exposure. In this work we investigated the effect of exposure to CdSe/ZnS quantum dots (QDs) in the marine diatom Phaeodactylum tricornutum, using different physiological, biochemical and molecular approaches. The results show that acclimation to QDs reduced the growth inhibition induced by nanoparticles in P. tricornutum cultures. The increase of glutathione observed at the end of the lag phase pointed to cellular stress. Transcriptional expression of selected stress responsive genes showed up-regulation in the QD-exposed algae. A comparison of the proteomes of exposed and unexposed cells highlighted a large number of differentially expressed proteins. To our knowledge, this is the first report on proteome analysis of a marine microalga exposed to nanoparticles.

Interaction of CdSe/ZnS quantum dots with the marine diatom Phaeodactylum tricornutum and the green alga Dunaliella tertiolecta: a biophysical approach.

In this study, we investigated the interaction of nanoparticles, such as CdSe/ZnS quantum dots (QDs), with the marine diatom Phaeodactylum tricornutum and the green alga Dunaliella tertiolecta, as biological models in the marine environment. Fluorescence kinetics measurements indicated that 30min after dispersion in seawater QDs lost the 60% of the initial emission intensity, possibly due to the occurrence of aggregation processes. However, the presence of algae seemed to mitigate this effect. By using confocal microscopy, we highlighted the presence of QDs adsorbed on the surface of both algae, but not inside the cells. The toxicity of QDs was evaluated in terms of inhibition of growth rate, oxidative stress, and lipid peroxidation. QDs in the range of 1-2.5nM gradually inhibited the growth rate of P. tricornutum and increased the oxidative stress, as evinced by the increase in lipid peroxidation, reactive oxygen species (ROS) production and activity of two main antioxidant enzymes (superoxide dismutase and catalase). On the contrary, QDs did not inhibit the growth rate of D. tertiolecta, at most a modest stimulation was observed in the range of 0.5-2nM, suggesting a hormetic response. No effect in the parameters indicating oxidative stress was observed in the green alga. In conclusion our results showed that the biological effects were species-specific.