OBJECTIVE:Chest computed tomography (CT) is usually performed in patients with severe asthma (SA) to exclude concomitant conditions related to poor clinical control. Despite the growing evidence regarding the utility of CT in the characterization of morphological abnormalities and airway remodeling, its role in SA assessment is still largely unexplored. The aim of our systematic review was to evaluate published data investigating the role of chest CT in patients with SA. DATA SOURCES:The systematic search was conducted on the Medline database through the Pubmed search engine. STUDY SELECTIONS:A total of 53 studies has been included. RESULTS:Quantitative CT (qCT) parameters generally differ between SA patients compared to mild to moderate asthmatic patients or healthy controls and are related to functional decline. CT parameters allow to identify image-based clusters reflecting remodeling patterns and/or air trapping features. The detection of mucus plugs is more frequent in severe eosinophilic asthma, and it is related to marked airway obstruction and ventilation defects. Benralizumab treatment appears to reduce or vanish mucus plugging. Most studies regarding CT and bronchial thermoplasty (BT) detect the usefulness of this investigation in predicting treatment response. Lastly, conflicting results surround the relation between chest CT and SA assessment in children due to also the scarcity of studies focusing on pediatric population. CONCLUSIONS:The role of CT scans in SA is still debated. Most studies focus on the identification of CT-derived disease clusters while studies primarily evaluating the predicting role of CT scan to different biologics are lacking and could represent an interesting research area.

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.

Introduction: Sarcoidosis, a systemic granulomatous disorder with unknow origin, is characterized by a chronic inflammation due to exaggerated immune response consisting of activated CD4-lymphocytes, in which activation is also regulated by immune checkpoint (IC) molecules. The aim was analyse the role and expression of PD1 and TIGIT on peripheral CD4 from patients affected by sarcoidosis at stage 2, idiopathic pulmonary fibrosis (IPF) and compared with healthy controls. Methods: Patients followed at referral center for rare lung diseases of Siena university were enrolled. Peripheral blood samples were stained with monoclonal antibodies PD-1 and TIGIT though flow cytometry. Results: Twelve sarcoidosis, twenty IPF patients and fifteen healthy controls were enrolled. PD-1 and TIGIT expression on CD4-positive cells were lower in HC than patient groups. TIGIT+CD4+ cell percentages were higher in sarcoidosis than IPF, while PD1+CD4+ cells were lower in sarcoidosis than IPF. Conclusion: Sarcoidosis disease is characterized by an ongoing inflammation, due to an exaggerate activation and expression of T-cells providing a switching immune phenotype of T-cells. This explain the lymphocytes recruitment in the lung injury increasing the cytokines production. Spontaneous resolution occurs in 40-70% of sarcoidosis with stage II. Exploiting the synergy between PD-1/TIGIT axis, the anti-TIGIT target therapy could be helpful to avoid the progression of sarcoidosis.

Background: Fractional exhaled nitric oxide (FeNO) is a biomarker of airway inflammation associated with airway hyper-responsiveness and type-2 inflammation. Its role in the management of severe asthmatic patients undergoing biologic treatment, as well as FeNO dynamics during biologic treatment, is largely unexplored. Purpose: The aim was to evaluate published data contributing to the following areas: (1) FeNO as a predictive biomarker of response to biologic treatment; (2) the influence of biologic treatment in FeNO values; (3) FeNO as a biomarker for the prediction of exacerbations in patients treated with biologics. Methods: The systematic search was conducted on the Medline database through the Pubmed search engine, including all studies from 2009 to the present. Results: Higher baseline values of FeNO are associated with better clinical control in patients treated with omalizumab, dupilumab, and tezepelumab. FeNO dynamics during biologic treatment highlights a clear reduction in FeNO values in patients treated with anti-IL4/13 and anti-IL13, as well as in patients treated with tezepelumab. During the treatment, FeNO may help to predict clinical worsening and to differentiate eosinophilic from non-eosinophilic exacerbations. Conclusions: Higher baseline FeNO levels appear to be associated with a greater benefit in terms of clinical control and reduction of exacerbation rate, while FeNO dynamics during biologic treatment remains a largely unexplored issue since few studies have investigated it as a primary outcome. FeNO remains detectable during biologic treatment, but its potential utility as a biomarker of clinical control is still unclear and represents an interesting research area to be developed.

Background: FeNO is a well-known biomarker of type 2 inflammation and is widely used for patient phenotyping in severe asthma (SA). Few evidence is available on the value of multiple flows FeNO parameters on this topic. Aims: the study aims to investigate the role of alveolar nitric oxide concentration (CaNO) and maximum conducting airway wall flux (J9awNO) in a cohort of patients with SA treated with biologic drugs. Methods: We retrospectively collected clinical, demographic and respiratory functional data of SA patients whose multiple-flows FeNO analysis has been performed at baseline and after one year of biologic treatment (t0 and t1, respectively). Patients were classified into three groups (allergic, eosinophilic, mixed) according to SA endotype. Results: we enrolled 47 patients with SA, of which 14 with allergic SA, 14 with eosinophilic SA and 19 with mixed allergic-eosinophilic SA. At t0, allergic patients showed lower serum eosinophils (p=0.0005), lower FeNO and J'awNO values (both p<0.0001) than the other subgroups; no differences were found in serum IgE, CaNO, exacerbation rate and FEV1. At t1, we observed a significant reduction of FeNO, J'awNO and CaNO levels only in eosinophilic and mixed subgroups. Good responders showed a more pronounced decrease of FeNO and J'awNO than partial/bad responders (p=0.032 and p=0.002, respectively). Delta (t1-t0) J'awNO showed the best accuracy in predicting a good response to treatment (area under the curve: 0.857, p=0.005). Conclusions: J'awNO was differently expressed among the SA endotypes and showed a better accuracy than FeNO in predicting a good response to biologic treatment, supporting its potential use in clinical practice.

Coronavirus disease 2019 (COVID-19) is an infectious respiratory disorder caused by a new coronavirus called SARS-CoV-2. The pathophysiology of severe COVID-19 is associated with a "cytokine storm". IL-32 is a key modulator in the pathogenesis of various clinical conditions and is mostly induced by IL-8. IL-32 modulates important inflammatory pathways (including TNF-α, IL-6 and IL-1b), contributing to the pathogenesis of inflammatory diseases. Il-32 was never evaluated before in COVID-19 patients stratifying as mild-moderate and severe patients. A total of 64 COVID-19 patients, 27 healthy controls were consecutively enrolled in the study. Serum concentrations of biomarkers including IL-1β, IL-10, IFN-γ, TNF-α and IL-6 were quantified by bead-based multiplex analysis and Serum concentration of IL-8 and IL-32 were determined by enzyme-linked immunosorbent assay (ELISA) kits. Interestingly, among the blood parameters, neutrophil and lymphocyte counts were significantly lower in severe COVID-19 patients than in the other, on the contrary, CRP was significantly higher in severe patients than in other groups. The cytokines that best distinguished controls from COVID-19 patients were IL-8 and IL-32, while IL-6 resulted the better variables for discriminate severe group. The best model performance for severe group was obtained by the combination of IL-32, IL-6, IFN-γ, and CRP serum concentration showing an AUC = 0.83. A cut off of 15 pg/ml of IL-6 greatly discriminate survivor from death patients. New insights related to the cytokine storm in COVID-19 patients, highlighting different severity of disease infection.