72 research outputs found
Long-term treatment in pediatric asthma: an update on chemical pharmacotherapy
No full textIntroduction: Asthma is the most common chronic disease in childhood, affecting approximately 10% of all children, and is the leading cause of hospitalization in developed countries. In this paper we aimed to review the evidence on chemical pharmacotherapy for long-term treatment of pediatric asthma, according to the latest updates. Area covered: Long-term treatment, essential for controlling symptoms and reducing future risks including exacerbations and decline in lung function, includes control agents such as inhaled corticosteroids, long-acting beta2-adrenergic agonists, and leukotriene modifiers. More recent strategies based on the use of a biological drug such as omalizumab, which is a monoclonal antibody directed against immunoglobulin E (IgE), can be considered in selected patients with severe asthma. Expert opinion: In the near future, the challenge of childhood asthma treatment will be to improve the chemical drugs that already exist as well as to carefully characterize the several different asthma subtypes, with special regard to children with severe disease. A better definition of patient features, made possible by the current advanced knowledge of the pathobiology of severe asthma, can ultimately allow the identification of specific phenotypes and endotypes of severe asthma, aimed to personalize pharmacological treatment
Eosinophilic inflammation: An Appealing Target for Pharmacologic Treatments in Severe Asthma
No full textSevere asthma is characterized by different endotypes driven by complex pathologic mechanisms. In most patients with both allergic and non-allergic asthma, predominant eosinophilic airway inflammation is present. Given the central role of eosinophilic inflammation in the pathophysiology of most cases of severe asthma and considering that severe eosinophilic asthmatic patients respond partially or poorly to corticosteroids, in recent years, research has focused on the development of targeted anti-eosinophil biological therapies; this review will focus on the unique and particular biology of the eosinophil, as well as on the current knowledge about the pathobiology of eosinophilic inflammation in asthmatic airways. Finally, current and prospective anti-eosinophil therapeutic strategies will be discussed, examining the reason why eosinophilic inflammation represents an appealing target for the pharmacological treatment of patients with severe asthma
Interleukins 4 and 13 in Asthma: Key Pathophysiologic Cytokines and Druggable Molecular Targets
No full textPost-COVID-19 Patients Who Develop Lung Fibrotic-like Changes Have Lower Circulating Levels of IFN-β but Higher Levels of IL-1α and TGF-β
No full textPurpose: SARS-CoV-2 infection induces in some patients a condition called long-COVID-19, herein post-COVID-19 (PC), which persists for longer than the negative oral-pharyngeal swab. One of the complications of PC is pulmonary fibrosis. The purpose of this study was to identify blood biomarkers to predict PC patients undergoing pulmonary fibrosis. Patients and Methods: We analyzed blood samples of healthy, anti-SARS-CoV-2 vaccinated (VAX) subjects and PC patients who were stratified according to the severity of the disease and chest computed tomography (CT) scan data. Results: The inflammatory C reactive protein (CRP), complement complex C5b-9, LDH, but not IL-6, were higher in PC patients, independent of the severity of the disease and lung fibrotic areas. Interestingly, PC patients with ground-glass opacities (as revealed by chest CT scan) were characterized by higher plasma levels of IL-1α, CXCL-10, TGF-β, but not of IFN-β, compared to healthy and VAX subjects. In particular, 19 out of 23 (82.6%) severe PC and 8 out of 29 (27.6%) moderate PC patients presented signs of lung fibrosis, associated to lower levels of IFN-β, but higher IL-1α and TGF-β. Conclusions: We found that higher IL-1α and TGF-β and lower plasma levels of IFN-β could predict an increased relative risk (RR = 2.8) of lung fibrosis-like changes in PC patients
Effectiveness of Benralizumab in OCS-Dependent Severe Asthma: The Impact of 2 Years of Therapy in a Real-Life Setting
No full textPatients with severe OCS-dependent asthma can be considered a subgroup of asthma patients with severe disease and great risk of complications, related to chronic OCS use. The introduction of biological drugs has represented a turning point in the therapeutic strategy for severe asthma, offering a valid alternative to OCS. Benralizumab, like other anti-IL-5 agents, has been shown to reduce exacerbations and OCS intake/dosage and improve symptom control and lung function. While these findings have also been confirmed in real-life studies, data on long-term efficacy are still limited. Methods: In this retrospective study, we evaluated the effects of 2 years of treatment with benralizumab on 44 patients with OCS-dependent severe asthma by analyzing clinical, biological and functional data. Results: After 2 years of benralizumab, 59.4% discontinued OCS and patients who continued to use OCS had their mean dose reduced by approximately 85% from baseline. Meanwhile, 85% of patients had their asthma well-controlled (ACT score > 20) and had no exacerbations, and 41.6% had normal lung function. Conclusions: Our findings support the long-term effectiveness of benralizumab in severe OCS-dependent asthma in a real-life setting, suggesting potential reductive effects on costs and complications such as adverse pharmacological events
SIRT 1 and oxidative stress in COPD pathogenesis
No full textBackground: Increasing evidence indicates that oxidative stress and inflammation are strictly correlated to cellular senescence and aging. SIRT1, an anti-aging, anti-oxidative and anti-inflammatory protein, represents a connecting link among these processes characterizing COPD.
Objectives: 1) to compare the expression and activity of SIRT 1 in the peripheral blood mononuclear cells (PBMC) of smokers, non smokers and COPD patients; 2) to investigate the association between SIRT1 and markers of oxidative stress and inflammation and 3) to assess the correlation between the markers of oxidative stress, SIRT1 and lung function.
Methods: total oxidative status (TOS), total antioxidant capacity (TAC) and Oxidative Stress Index (OSI) in plasma, SIRT1 expression and activity levels, and IL-6 levels in PBMCs were measured in nonsmokers (NS), smokers (S) and COPD.
Results: OSI was higher in COPD than in controls both for S (p = 0.04) and NS (p <0.0001). TOS was similar between COPD and S, but was higher in COPD when compared to NS (p <0.0001). TAC was lower in COPD compared to S (p = 0.03) and NS (p = 0.007), while there were no differences between S and NS. IL-6 levels were higher in COPD than in controls, but the differences were not statistically significant. The expression of SIRT1 was similar in the two control groups and was lower in COPD compared to NS (p 0.04), of note SIRT1 activity was decreased in COPD compared to S (p 0.001) and NS (p 0.001). SIRT1 activity was inversely correlated to respiratory function in COPD patients but not in control subjects.
Conclusion: SIRT1 and oxidative stress seem to be actively involved in COPD pathogenesis.SIRT1 could be a promising therapeutic target for COPD in the future
Novel Biological Therapies for Severe Asthma Endotypes
No full textSevere asthma comprises several heterogeneous phenotypes, underpinned by complex pathomechanisms known as endotypes. The latter are driven by intercellular networks mediated by molecular components which can be targeted by specific monoclonal antibodies. With regard to the biological treatments of either allergic or non-allergic eosinophilic type 2 asthma, currently available antibodies are directed against immunoglobulins E (IgE), interleukin-5 (IL-5) and its receptor, the receptors of interleukins-4 (IL-4) and 13 (IL-13), as well as thymic stromal lymphopoietin (TSLP) and other alarmins. Among these therapeutic strategies, the best choice should be made according to the phenotypic/endotypic features of each patient with severe asthma, who can thus respond with significant clinical and functional improvements. Conversely, very poor options so far characterize the experimental pipelines referring to the perspective biological management of non-type 2 severe asthma, which thereby needs to be the focus of future thorough research
Biological Therapy of Severe Asthma with Dupilumab, a Dual Receptor Antagonist of Interleukins 4 and 13
No full textInterleukin-4 (IL-4) and interleukin-13 (IL-13) are key cytokines involved in the pathophysiology of both immune-inflammatory and structural changes underlying type 2 asthma. IL-4 plays a pivotal role in Th2 cell polarization, immunoglobulin E (IgE) synthesis and eosinophil recruitment into the airways. IL-13 synergizes with IL-4 in inducing IgE production and also promotes nitric oxide (NO) synthesis, eosinophil chemotaxis, bronchial hyperresponsiveness and mucus secretion, as well as the proliferation of airway resident cells such as fibroblasts and smooth muscle cells. The biological effects of IL-4 and IL-13 are mediated by complex signaling mechanisms activated by receptor dimerization triggered by cytokine binding to the α-subunit of the IL-4 receptor (IL-4Rα). The fully human IgG4 monoclonal antibody dupilumab binds to IL-4Rα, thereby preventing its interactions with both IL-4 and IL-13. This mechanism of action makes it possible for dupilumab to effectively inhibit type 2 inflammation, thus significantly reducing the exacerbation of severe asthma, the consumption of oral corticosteroids (OCS) and the levels of fractional exhaled NO (FeNO). Dupilumab has been approved not only for the add-on therapy of severe asthma, but also for the biological treatment of atopic dermatitis and nasal polyposis
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