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Background: Severe eosinophilic asthma (SEA) is often linked to a dysregulation in the Interleukin-(IL)-5 axis. Mepolizumab, a humanized monoclonal antibody, reduces eosinophils by directly binging to IL-5, potentially restoring homeostatic eosinophil biology, with a significant impact on quality of life, acute exacerbations and oral corticosteroids (OCS) elimination in SEA patients. While its short- and middle-term effects are well described, no study has so far investigated its long-lasting effects in SEA patients. The aim of our study was therefore to explore the effects of a long-term, six-year continuous treatment with mepolizumab on clinical control and clinical remission in a cohort of SEA patients. Methods: We conducted a retrospective review of clinical records of patients who were prescribed mepolizumab between June 2017 and April 2018. We collected demographical, functional, and clinical data from visits performed at baseline and then at the specified timepoints and checked if patients had reached clinical remission after 6 years. We assessed asthma control test (ACT), exacerbation rate, and OCS elimination dose at 6 years. Clinical Remission (CR) was defined on the basis of the elimination of OCS and the contemporary presence of all the following: 1) stable lung function; 2) no exacerbation in the previous 12 months; 3) acceptable symptom control (ACT ≥ 20). Results: Of 86 patients screened, 62 were included in the final analysis. Our study suggests that mepolizumab is effective and well tolerated after a six-year course of continuous treatment in patients with SEA. We reported a prevalence of 28 (46.8%) patients who reached complete CR at 72 months from the treatment start. 75% of patients eliminated the maintenance OCS already after 1 year of treatment; this proportion reached the 87% within the sixth year of treatment. Conclusion: Mepolizumab proved to be effective in real-life after 6 years of treatment, inducing a complete clinical remission in the 46.8% of patients, with sustained improvements in quality of life, exacerbation rate, OCS intake and lung function.
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Biomarkers are indicators of a pathological or physiological state, and they are essential for facilitating the diagnosis of a subclinical condition, understanding the origin or progression of a disease, stratifying the risk, and assessing the response to a specific therapeutic approach [...].
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Allergic rhinitis, a common allergic disease affecting a significant number of individuals worldwide, is observed in 25% of children and 40% of adults, with its highest occurrence between the ages of 20 and 40. Its pathogenesis, like other allergic diseases, involves innate and adaptive immune responses, characterized by immunologic hypersensitivity to environmental substances. This response is mediated by type 2 immunity. Within type 2 allergic diseases, certain molecules have been identified as clinical biomarkers that contribute to diagnosis, prognosis, and therapy monitoring. Among these biomarkers, nitric oxide has shown to play a key role in various physiological and pathological processes, including neurotransmission, immunity, inflammation, regulation of mucus and cilia, inhibition of microorganisms, and tumor cell growth. Therefore, measurement of nasal nitric oxide has been proposed as an objective method for monitoring airway obstruction and inflammation in different settings (community, hospital, rehabilitation) and in various clinical conditions, including upper airways diseases of the nose and paranasal sinuses. The purpose of this review is to analyze the potential mechanisms contributing to the production of nasal nitric oxide in allergic rhinitis and other related health issues. Additionally, this review aims to identify potential implications for future research, treatment strategies, and long-term management of symptoms.
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High-flow nasal cannula (HFNC) has recently emerged as a crucial therapeutic strategy for hypoxemic patients both in acute and chronic settings. Indeed, HFNC therapy is able to deliver higher fractions of inspired oxygen (FiO2) with a heated and humidified gas flow ranging from 20 up to 60 L per minute, in a more comfortable way for the patient in comparison with Conventional Oxygen Therapy (COT). In fact, the flow keeps the epithelium of the airways adequately moisturized, thus positively affecting the mucus clearance. Finally, the flow is able to wash out the carbon dioxide in the dead space of the airways; this is also enhanced by a modest positive end-expiratory pressure (PEEP) effect. Recent evidence has shown applications of HFNC in exercise training and chronic settings with promising results. In this narrative review, we explored how HFNC might contribute to enhancing outcomes of exercise training and pulmonary rehabilitation among patients dealing with chronic obstructive pulmonary disease, interstitial lung diseases, and lung cancer.
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The molecular-scale structure and dynamics of confined liquids has increasingly gained relevance for applications in nanotechnology. Thus, a detailed knowledge of the structure of confined liquids on molecular length scales is of great interest for fundamental and applied sciences. To study confined structures under dynamic conditions, we constructed an in situ X-ray surface forces apparatus (X-SFA). This novel device can create a precisely controlled slit-pore confinement down to dimensions on the 10 nm scale by using a cylinder-on-flat geometry for the first time. Complementary structural information can be obtained by simultaneous force measurements and X-ray scattering experiments. The in-plane structure of liquids parallel to the slit pore and density profiles perpendicular to the confining interfaces are studied by X-ray scattering and reflectivity. The normal load between the opposing interfaces can be modulated to study the structural dynamics of confined liquids. The confinement gap distance is tracked simultaneously with nanometer precision by analyzing optical interference fringes of equal chromatic order. Relaxation processes can be studied by driving the system out of equilibrium by shear stress or compression/decompression cycles of the slit pore. The capability of the new device is demonstrated on the liquid crystal 4'-octyl-4-cyano-biphenyl (8CB) in its smectic A (SmA) mesophase. Its molecular-scale structure and orientation confined in 100 nm to 1.7 µm slit pores was studied under static and dynamic nonequilibrium conditions.
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The interfacial decomposition products forming the so-called solid-electrolyte interphase (SEI) significantly determine the destiny of a Li-ion battery. Ultimate knowledge of its detailed behavior and better control are required for higher rates, longer life-time, and increased safety. Employing an electrochemical surface force apparatus, it is possible to control the growth and to investigate the mechanical properties of an SEI in a lithium-ion battery environment. This new approach is here introduced on a gold model system and reveals a compressible film at all stages of SEI growth. The demonstrated methodology provides a unique tool for analyzing electrochemical battery interfaces, in particular in view of alternative electrolyte formulations and artificial interfaces.
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Multiple beam interferometry (MBI) evolved as a powerful tool for the simultaneous evaluation of thin film thicknesses and refractive indices in Surface Forces Apparatus (SFA) measurements. However, analysis has relied on simplifications for providing fast or simplified analysis of recorded interference spectra. Here, we describe the implementation of new optics and a generalized fitting approach to 4 × 4 transfer matrix method simulations for the SFA. Layers are described by dispersive complex refractive indices, thicknesses, and Euler angles that can be fitted, providing modeling for birefringent or colored layers. Normalization of data by incident light intensities is essential for the implementation of a fitting approach. Therefore, a modular optical system is described that can be retrofit to any existing SFA setup. Real-time normalization of spectra by white light is realized, alignment procedures are considerably simplified, and direct switching between transmission and reflection modes is possible. A numerical approach is introduced for constructing transfer matrices for birefringent materials. Full fitting of data to the simulation is implemented for arbitrary multilayered stacks used in SFA. This enables self-consistent fitting of mirror thicknesses, birefringence, and relative rotation of anisotropic layers (e.g., mica), evaluation of reflection and transmission mode spectra, and simultaneous fitting of thicknesses and refractive indices of media confined between two surfaces. In addition, a fast full spectral fitting method is implemented for providing a possible real-time analysis with up to 30 fps. We measure and analyze refractive indices of confined cyclohexane, the thickness of lipid bilayers, the thickness of metal layers, the relative rotation of birefringent materials, contact widths, as well as simultaneous fitting of both reflection and transmission mode spectra of typical interferometers. Our analyses suggest a number of best practices for conducting SFA and open MBI in an SFA for increasingly complex systems, including metamaterials, multilayered anisotropic layers, and chiral layers.
