Innate immunity but not NLRP3 inflammasome activation correlates with severity of stable COPD

Background In models of COPD, environmental stressors induce innate immune responses, inflammasome activation and inflammation. However, the interaction between these responses and their role in driving pulmonary inflammation in stable COPD is unknown. Objectives To investigate the activation of innate immunity and inflammasome pathways in the bronchial mucosa and bronchoalveolar lavage (BAL) of patients with stable COPD of different severity and control healthy smokers and non-smokers. Methods Innate immune mediators (interleukin (IL)-6, IL-7, IL-10, IL-27, IL-37, thymic stromal lymphopoietin (TSLP), interferon γ and their receptors, STAT1 and pSTAT1) and inflammasome components (NLRP3, NALP7, caspase 1, IL-1β and its receptors, IL-18, IL-33, ST2) were measured in the bronchial mucosa using immunohistochemistry. IL-6, soluble IL-6R, sgp130, IL-7, IL-27, HMGB1, IL-33, IL-37 and soluble ST2 were measured in BAL using ELISA. Results In bronchial biopsies IL-27+ and pSTAT1+ cells are increased in patients with severe COPD compared with control healthy smokers. IL-7+ cells are increased in patients with COPD and control smokers compared with control non-smokers. In severe stable COPD IL-7R+, IL-27R+ and TSLPR+ cells are increased in comparison with both control groups. The NALP3 inflammasome is not activated in patients with stable COPD compared with control subjects. The inflammasome inhibitory molecules NALP7 and IL-37 are increased in patients with COPD compared with control smokers. IL-6 levels are increased in BAL from patients with stable COPD compared with control smokers with normal lung function whereas IL-1β and IL-18 were similar across all groups. Conclusions Increased expression of IL-27, IL-37 and NALP7 in the bronchial mucosa may be involved in progression of stable COPD

Bronchiectasis insanity:Doing the same thing over and over again and expecting different results?

Bronchiectasis is an increasingly common disease with a significant impact on quality of life and morbidity of affected patients. It is also a very heterogeneous disease with numerous different underlying etiologies and presentations. Most treatments for bronchiectasis are based on low-quality evidence; consequently, no treatments have been approved by the US Food and Drug Administration or the European Medicines Agency for the treatment of bronchiectasis. The last several years have seen numerous clinical trials in which the investigational agent, thought to hold great promise, did not demonstrate a clinically or statistically significant benefit. This commentary will review the likely reasons for these disappointing results and a potential approach that may have a greater likelihood of defining evidence-based treatment for bronchiectasis

An experimental study on latency-aware and self-adaptive service chaining orchestration in distributed NFV and SDN infrastructures

Network Function Virtualization (NFV) and Software Defined Networking (SDN) changed radically the way 5G networks will be deployed and services will be delivered to vertical applications (i.e., through dynamic chaining of virtualized functions deployed in distributed clouds to best address latency requirements). In this work, we present a service chaining orchestration system, namely LASH-5G, running on top of an experimental set-up that reproduces a typical 5G network deployment with virtualized functions in geographically distributed edge clouds. LASH-5G is built upon a joint integration effort among different orchestration solutions and cloud deployments and aims at providing latency-aware, adaptive and reliable service chaining orchestration across clouds and network resource domains interconnected through SDN. In this paper, we provide details on how this orchestration system has been deployed and it is operated on top of the experimentation infrastructure provided within the Fed4FIRE+ facility and we present performance results assessing the effectiveness of the proposed orchestration approach

Impaired innate interferon induction in severe therapy resistant atopic asthmatic children

Deficient type I interferon-β and type III interferon-λ induction by rhinoviruses has previously been reported in mild/moderate atopic asthmatic adults. No studies have yet investigated if this occurs in severe therapy resistant asthma (STRA). Here, we show that compared with non-allergic healthy control children, bronchial epithelial cells cultured ex vivo from severe therapy resistant atopic asthmatic children have profoundly impaired interferon-β and interferon-λ mRNA and protein in response to rhinovirus (RV) and polyIC stimulation. Severe treatment resistant asthmatics also exhibited increased virus load, which negatively correlated with interferon mRNA levels. Furthermore, uninfected cells from severe therapy resistant asthmatic children showed lower levels of Toll-like receptor-3 mRNA and reduced retinoic acid inducible gene and melanoma differentiation-associated gene 5 mRNA after RV stimulation. These data expand on the original work, suggesting that the innate anti-viral response to RVs is impaired in asthmatic tissues and demonstrate that this is a feature of STRA

Effects of anti-IL5 biological treatments on blood IgE levels in severe asthmatic patients: A real-life multicentre study (BIONIGE)

Background: Mepolizumab and benralizumab are clinically effective biological treatments for severe eosinophilic asthmatic patients by hampering eosinophilic inflammation. The effects of these compound on the immunoglobulin (Ig)E T2 component are virtually unknown. Objectives: To evaluate the change in total IgE levels at 4 ± 2 months after initiation of the mepolizumab (primary outcome) or benralizumab. When available, the changes of blood inflammatory cell counts, lung function and asthma control test (ACT) were also assessed and correlated with changes in total IgE levels. Methods: Observational, retrospective, multicentre, cohort study. Severe eosinophilic atopic asthmatic patients treated with mepolizumab or benralizumab were included in the analysis. Results: Three-month treatment (on average) with mepolizumab (n = 104) or benralizumab (n = 82) resulted in significantly higher reduction of blood eosinophil and basophil levels in patients treated with benralizumab compared to mepolizumab. Mepolizumab did not significantly modified the levels of blood total IgE during the study period, whereas benralizumab significantly reduced (−35%, p < 0.001) total blood IgE levels. In patients treated with benralizumab the reduction of blood total Ig-E levels correlated with the reduction of blood basophils (but not eosinophils) and weakly with the improvement of asthma control. Conclusion: Benralizumab but not mepolizumab, treatment led to a significant reduction of circulating IgE level. The study provides different and specific mechanisms of action for anti-IL5-pathway treatments

Satisfaction with chronic obstructive pulmonary disease treatment: results from a multicenter, observational study

Background: Understanding the level of patients' satisfaction with treatment and its determinants have the potential to impact therapeutic management and clinical outcome in chronic conditions such as chronic obstructive pulmonary disease (COPD). Methods: A national, multicenter, longitudinal, observational study of COPD from 20 Italian pulmonary centers to explore patients' satisfaction to treatment [assessed by the Treatment Satisfaction Questionnaire, 9 items (TSQM-9)] and association with clinical parameters [including dyspnea score, COPD Assessment Test (CAT) score, exacerbation rate], adherence to treatment [Morisky Medication-Taking Adherence Scale (MMAS-4)], illness perception [evaluated by Brief Illness Perception Questionnaire (B-IPQ)] in a 1-year follow up. Results: A total of 401 COPD patients were enrolled [69.4% group B Global Initiative for COPD (GOLD), considering 366 patients with available GOLD 2017 classification at enrollment]. At enrollment, satisfaction with treatment was moderate, being TSQM-9 mean scores for effectiveness 64.2 [95% confidence interval (CI) 62.5-65.9], for convenience 75.8 (95% CI 74.2-77.3), and for global satisfaction 65.7 (95% CI 64.0-67.4). Global satisfaction was negatively associated with disease perception (beta = -0.4709, p < 0.0001), and grade of dyspnea (beta = -4.2564, p = 0.009). Satisfaction with treatment was lower in patients with poor compared with optimal adherence to treatment (beta = -4.5608, p = 0.002). Changes in inhalation regimens during follow up did not modify the satisfaction with treatment. Conclusions: The results of this real-life study showed that the patients' satisfaction with treatments is only moderate in COPD. A high grade of patients' satisfaction is associated mainly with a low perception of the disease, high adherence to treatment and lower level of dyspnea

Is the association between precarious employment and mental health mediated by economic difficulties in males? Results from two Italian studies

Flexible employment is increasing across Europe and recent studies show an association with poor mental health. The goal of the current study is to examine this association in the Italian population to assess the possible mediating role of financial strain. Methods: Data were obtained by two Italian cross-sectional studies (PASSI and HIS) aimed at monitoring the general population health status, health behaviours and determinants. Mental health status was assessed using alternatively two validated questionnaires (the PHQ-2 and the MCS-12 score) and Poisson regression models were performed to assess if precarious work was associated with poor mental health. A formal mediation analysis was conducted to evaluate if the association between precarious work and mental health was mediated by financial strain. Results: The analyses were performed on 31,948 subjects in PASSI and on 21,894 subjects in HIS. A nearly two-fold risk of depression and poor mental health was found among precarious workers, compared to workers with a permanent contract, which was strongly mediated by financial strain. Conclusions: Even with the limitations of a cross-sectional design, this research supports that precarious employment contributes through financial strain to reduce the mental health related quality of life and to increase mental disorders such as symptoms of depression or dysthymia. This suggests that when stability in work cannot be guaranteed, it would be appropriate to intervene on the wages of precarious jobs and to provide social safety nets for ensuring adequate income

Local control in metastatic neuroblastoma in children over 1 year of age

Background: Local control is always considered in metastatic neuroblastoma (NBL). The aim of this study is to evaluate the impact of radical surgery on survival in children over 1 year of age. Methods: Fifty-eight patients older than 1 year of age with metastatic NBL were treated with conventional plus high-dose chemotherapy with or without addition of local radiotherapy (RT, 21Gy). Surgery was classified as radical surgery (complete resection and gross total resection) or non-radical surgery. The Kaplan-Meier method and the Cox proportional hazard model were used to calculate the probability of progression free and overall survival (PFS and OS) and for multivariate analysis. Results: The 5-year PFS and OS for patients with radical surgery were 26% (95% CI 14-40%) and 38% (95% CI 23-53%) respectively, while the PFS and OS for patients without radical surgery were 33% (95% CI 10-59%) and 31% (95% CI 10-55%) (respectively, P 0.85 and P 0.42). The 5-year PFS and OS for patients who received RT were 36% (95% CI 19-53%) and 46% (95% CI 26-64%) respectively, while the 5-year PFS and OS for patients who did not receive RT were 22% (95% CI 9-38%) and 27% (95% CI 13-42%) respectively (P 0.02 for PFS). Multivariate analysis confirmed the role of well-known prognostic factors, such as the presence of MYCN amplification, age and response before high-dose chemotherapy. Conclusions: Our data suggest that the degree of resection does not influence survival in metastatic NBL patients treated with high-dose chemotherapy; local RT contributes to local disease control

From intensive care to rehabilitation: survey on the satisfaction with care received during prolonged hospitalization for COVID-19 at a northern Italian university hospital

Objective: Investigating the experiences perceived by COVID-19 inpatients is a fundamental research area that is starting to be explored. For this reason, our objective was to provide the first Italian survey on COVID-19 inpatients' satisfaction, obtained through a self-completed questionnaire previously used in a reference study in a UK cohort of COVID-19 patients. Subjects and methods: Hospitalized COVID-19 patients (>20 days) admitted to Ferrara University Hospital who underwent rehabilitation during their hospital stay were invited to complete an anonymous questionnaire. The survey's questions explored the patients' satisfaction with the health services received, and their completion took place approximately one year after hospitalization. Information on sex, number of wards, ICU stays, and hospital discharge dates was collected. Results: Sixty-two completed questionnaires were analyzed. The average overall satisfaction score obtained from the answers indicated by the participants in the tenth question was 4.7 out of 5.0. Very positive responses were observed for information about discharge plans, privacy, management of pain, sleep quality, and feeling of safety. The possibility of being consulted about medications and side effects received a very low satisfaction score. Considering overall satisfaction, no significant differences were noted for sex or ICU stay. The obtained results were almost superimposable to those reported in the cohort of COVID-19 patients of the reference study. Conclusions: This survey suggested that COVID-19 patients' healthcare satisfaction was high. Nevertheless, some areas must be improved, such as the communication and involvement of the patients in the decision-making of care and the discussion about medications or possible side effects

Minimal clinically important difference for asthma endpoints: an expert consensus report

Minimal clinically important difference (MCID) can be defined as the smallest change or difference in an outcome measure that is perceived as beneficial and would lead to a change in the patient's medical management.The aim of the current expert consensus report is to provide a "state-of-the-art" review of the currently available literature evidence about MCID for end-points to monitor asthma control, in order to facilitate optimal disease management and identify unmet needs in the field to guide future research.A series of MCID cut-offs are currently available in literature and validated among populations of asthmatic patients, with most of the evidence focusing on outcomes as patient reported outcomes, lung function and exercise tolerance. On the contrary, only scant and partial data are available for inflammatory biomarkers. These clearly represent the most interesting target for future development in diagnosis and clinical management of asthma, particularly in view of the several biologic drugs in the pipeline, for which regulatory agencies will soon require personalised proof of efficacy and treatment response predictors