Respiratory muscle training with normocapnic hyperpnea improves ventilatory pattern and thoracoabdominal coordination, and reduces oxygen desaturation during endurance exercise testing in COPD patients

Background: Few data are available about the effects of respiratory muscle training with normocapnic hyperpnea (NH) in COPD. The aim is to evaluate the effects of 4 weeks of NH (Spirotiger®) on ventilatory pattern, exercise capacity, and quality of life (QoL) in COPD patients. Methods: Twenty-six COPD patients (three females), ages 49-82 years, were included in this study. Spirometry and maximal inspiratory pressure, St George Respiratory Questionnaire, 6-minute walk test, and symptom-limited endurance exercise test (endurance test to the limit of tolerance [tLim]) at 75%-80% of peak work rate up to a Borg Score of 8-9/10 were performed before and after NH. Patients were equipped with ambulatory inductive plethysmography (LifeShirt®) to evaluate ventilatory pattern and thoracoabdominal coordination (phase angle [PhA]) during tLim. After four supervised sessions, subjects trained at home for 4 weeks 10 minutes twice a day at 50% of maximal voluntary ventilation. The workload was adjusted during the training period to maintain a Borg Score of 5-6/10. Results: Twenty subjects completed the study. After NH, maximal inspiratory pressure significantly increased (81.5±31.6 vs 91.8±30.6 cmH2O, P<0.01); exercise endurance time (+150 seconds, P=0.04), 6-minute walk test (+30 meters, P=0.03), and QoL (-8, P<0.01) all increased. During tLim, the ventilatory pattern changed significantly (lower ventilation, lower respiratory rate, higher tidal volume); oxygen desaturation, PhA, and dyspnea Borg Score were lower for the same work intensity (P<0.01, P=0.02, and P<0.01, respectively; one-way ANOVA). The improvement in tidal volume and oxygen saturation after NH were significantly related (R2=0.65, P<0.01). Conclusion: As expected, NH improves inspiratory muscle performance, exercise capacity, and QoL. New results are significant change in ventilatory pattern, which improves oxygen saturation, and an improvement in thoracoabdominal coordination (lower PhA). These two facts could explain the reduced dyspnea during the endurance test. All these results together may play a role in improving exercise capacity after NH training

Virtual Networking Performance in OpenStack Platform for Network Function Virtualization

The emerging Network Function Virtualization (NFV) paradigm, coupled with the highly flexible and programmatic control of network devices offered by Software Defined Networking solutions, enables unprecedented levels of network virtualization that will definitely change the shape of future network architectures, where legacy telco central offices will be replaced by cloud data centers located at the edge. On the one hand, this software-centric evolution of telecommunications will allow network operators to take advantage of the increased flexibility and reduced deployment costs typical of cloud computing. On the other hand, it will pose a number of challenges in terms of virtual network performance and customer isolation. This paper intends to provide some insights on how an open-source cloud computing platform such as OpenStack implements multitenant network virtualization and how it can be used to deploy NFV, focusing in particular on packet forwarding performance issues. To this purpose, a set of experiments is presented that refer to a number of scenarios inspired by the cloud computing and NFV paradigms, considering both single tenant and multitenant scenarios. From the results of the evaluation it is possible to highlight potentials and limitations of running NFV on OpenStack

Inflammatory and immunological mechanisms of virus induced asthma and chronic obstructive pulmonary disease (COPD) exacerbations

Asthma and chronic obstructive pulmonary disease (COPD) are the two most prevalent chronic airway diseases. Much of the morbidity, mortality and health care costs of the diseases are associated with exacerbations. Exacerbations are acute episodes that punctuated the natural history of the disease characterized by increased symptoms and airflow obstruction determining quality of life impairment and with possible effect on long term history of the disease. Thus, the prevention and the treatment of exacerbations are major tasks in the management of both asthma and COPD. However currently available treatment are only partially effective in reducing the incidence of such events. Over the last decade evidence has emerged implicating virus respiratory tract infections as a major cause of exacerbations both in asthma and in COPD. In particular, rhinovirus (i.e. the etiologic cause of the common cold) is the most frequently identify virus during exacerbations of both asthma and COPD. The comprehension of the inflammatory and immunological mechanisms that pave the way for exacerbation following respiratory tract infection in asthmatic and COPD patients will give the opportunity to highlight novel potential targets for pharmacological intervention. The recent development of in vivo experimental models of rhinovirus induced asthma and COPD exacerbations represents the unique tool to evaluate pathogenetic mechanisms and novel pharmacological pathways for treating and preventing COPD and asthma exacerbations. The aim of the present thesis is to review the data available on inflammatory and immunological mechanisms of virus induced exacerbations of asthma and COPD and to present the results of the studies conducted by the Candidate to enlighten the emerging field of virus induced asthma and COPD exacerbations

Inhaled corticosteroids and the lung microbiome in copd

The Global Initiative for Chronic Obstructive Lung Disease 2021 Report recommends inhaled corticosteroid (ICS)-containing regimens as part of pharmacological treatment in patients with chronic obstructive lung disease (COPD) and frequent exacerbations, particularly with eosinophilic inflammation. However, real-world studies reveal overprescription of ICS in COPD, irrespective of disease presentation and inflammatory endotype, leading to increased risk of side effects, mainly respiratory infections. The optimal use of ICS in COPD therefore remains an area of intensive research, and additional biomarkers of benefit and risk are needed. Although the interplay between inflammation and infection in COPD is widely acknowledged, the role of the microbiome in shaping lower airway inflammation has only recently been explored. Next-generation sequencing has revealed that COPD disease progression and exacerbation frequency are associated with changes in the composition of the lung microbiome, and that the immunosuppressive effects of ICS can contribute to potentially deleterious airway microbiota changes by increasing bacterial load and the abundance of potentially pathogenic taxa such as Streptococcus and Haemophilus. Here, we explore the relationship between microbiome, inflammation, ICS use and disease phenotype. This relationship may inform the benefit:risk assessment of ICS use in patients with COPD and lead to more personalised pharmacological management

Virtualized Network Infrastructures: Performance Analysis, Design and Implementation

In recent decades, there has been a tremendous evolution in the traffic on the Internet and enterprises networks. Networks assisted since the beginning to two phenomena: on the one hand, the birth of a multitude of applications, each posing different requirements; on the other hand, the explosion of personal mobile networking, with an ever increasing demand of devices that require connectivity. These trends resulted in increased network complexity, leading to difficult management and high costs. At the same time, evolution in the Information Technology (IT) field led to the birth of cloud computing and growth of virtualization technologies, opening new opportunities not only for companies but for individuals (be it PC or mobile users), as well as Service and Infrastructure Providers. Emerging technologies such as Software Defined Networking (SDN) and Network Functions Virtualization (NFV) seems to be promising solutions to today’s network problems. Neither standardized solutions, nor how to properly combine their usage to achieve flexible and proactive control management have been discovered yet. This Ph.D. thesis focuses on the exploration of three plane of functionality in which software-defined (computer) networks can be divided: the data, the control and the management plane. In this thesis, we present insights on several aspects of network virtualization, starting from virtual network performance of cloud computing infrastructures, and introducing the Service Function Chaining (SFC) mechanism, discussing its analysis, design and implementation. In particular, the original contribution of this dissertation concerns (i) performance evaluation of the OpenStack cloud platform (the data plane); (ii) the design and implementation of a stateful SDN controller for dynamic SFC (the control plane); (iii) design, implementation and performance analysis of a proposed Intent-based approach for dynamic SFC (the management plane)

Constraint Programming for Flexible Service Function Chaining Deployment

Network Function Virtualization (NFV) and Software Defined Networking (SDN) are technologies that recently acquired a great momentum thanks to their promise of being a flexible and cost-effective solution for replacing hardware-based, vendor-dependent network middleboxes with software appliances running on general purpose hardware in the cloud. Delivering end-to-end networking services across multiple NFV/SDN network domains by implementing the so-called Service Function Chain (SFC) i.e., a sequence of Virtual Network Functions (VNF) that composes the service, is a challenging task. In this paper we address two crucial sub-problems of this task: i) the language to formalize the request of a given SFC to the network and ii) the solution of the SFC design problem, once the request is received. As for i) in our solution the request is built upon the intent-based approach, with a syntax that focuses on asking the user what she needs and not how it should be implemented, in a simple and high level language. Concerning ii) we define a formal model describing network architectures and VNF properties that is then used to solve the SFC design problem by means of Constraint Programming (CP), a programming paradigm which is often used in Artificial Intelligence applications. We argue that CP can be effectively used to address this kind of problems because it provides very expressive and flexible modeling languages which come with powerful solvers, thus providing efficient and scalable performance. We substantiate this claim by validating our tool on some typical and non trivial SFC design problems

Sars-CoV-2 Infection Prompts IL-1β-Mediated Inflammation and Reduces IFN-λ Expression in Human Lung Tissue

Two years after its spreading, the severe acute respiratory syndrome coronavirus 2 (SARSCoV-2) is still responsible for more than 2000 deaths per day worldwide, despite vaccines and monoclonal antibody countermeasures. Therefore, there is a need to understand the immune–inflammatory pathways that prompt the manifestation of the disease to identify a novel potential target for pharmacological intervention. In this context, the characterization of the main players in the SARS-CoV-2-induced cytokine storm is mandatory. To date, the most characterized have been IL-6 and the class I and II interferons, while less is known about the proinflammatory cytokine IL-1β and class III interferons. Here, we report a preliminary study aimed at the characterization of the lung inflammatory context in COVID-19 patients, with a special focus on IFN-λ and IL-1β. By investigating IFN and inflammatory cytokine patterns by IHC in 10 deceased patients due to COVID-19 infection, compared to 10 control subjects, we reveal that while IFN-β production was increased in COVID-19 patients, IFN-λ was almost abolished. At the same time, the levels of IL-1β were dramatically improved, while IL-6 lung levels seem to be unaffected by the infection. Our findings highlight a central role of IL-1β in prompting lung inflammation after SARS-CoV-2 infection. Together, we show that IFN-λ is negatively affected by viral infection, supporting the idea that IFN-λ administration together with the pharmaceutical blockage of IL-1β represents a promising approach to revert the COVID-19-induced cytokine storm

Real-world, long-term effectiveness of allergy immunotherapy in allergic rhinitis: Subgroup analyses of the REACT study

Background: Randomized controlled trials have demonstrated the efficacy of allergy immunotherapy (AIT) in allergic rhinitis (AR) and the disease-modifying effects of the SQ grass sublingual immunotherapy (SLIT) tablet. // Objective: We sought to assess real-world, long-term effectiveness and safety across AIT subgroups: route of administration, therapeutic allergen, persistence to AIT, and SQ grass SLIT tablet. // Methods: The primary outcome of AR prescriptions from a retrospective cohort study (REAl-world effeCtiveness in allergy immunoTherapy; 2007-2017) was assessed across prespecified AIT subgroups in subjects with AR with and without AIT prescriptions (controls). Safety was assessed as anaphylaxis for 2 days or less of the first AIT prescription. Subgroup follow-up continued until samples were fewer than 200 subjects. // Results: Subcutaneous immunotherapy (SCIT) and SLIT tablets showed similarly greater reductions in AR prescriptions than controls (SCIT vs SLIT tablets: year 3, P = .15; year 5, P = .43). Comparably greater reductions in AR prescriptions were observed for grass- and house dust mite–specific AIT than for controls, but significantly smaller reductions were observed for tree-specific AIT (tree vs house dust mite, and vs grass: years 3 and 5, P < .0001). Persistence to AIT was associated with greater reductions in AR prescriptions versus nonpersistence (persistence vs nonpersistence: year 3, P = .09; year 5, P = .006). SQ grass SLIT tablet showed sustained reductions versus controls for up to 7 years (year 3, P = .002; year 5, P = .03). Rates of anaphylactic shock were low (0.000%-0.092%), with no events for SQ SLIT tablets. // Conclusions: These results demonstrate real-world, long-term effectiveness of AIT, complement disease-modifying effects observed in SQ grass SLIT-tablet randomized controlled trials, and highlight the importance of using newer evidence-based AIT products for tree pollen AR

Intent-based management and orchestration of heterogeneous openflow/IoT SDN domains

One of the main challenges in delivering end-toend service chains across multiple Software Defined Networking (SDN) and Network Function Virtualization (NFV) domains is to achieve unified management and orchestration functions. A very critical aspect is the definition of an open, vendoragnostic, and interoperable northbound interface (NBI) that should be as abstracted as possible from domain-specific data and control plane technologies. In this paper we propose a reference architecture and an intent-based NBI for end-to-end service orchestration across multiple technological domains. In particular, we consider the use case of an Internet of Things (IoT) infrastructure deployment and the corresponding cloudbased data collection, processing, and publishing services with quality differentiation.We also report the experimental validation of the proposed architecture over a heterogeneous OpenFlow/IoT SDN test bed

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