Real-Life effects of benralizumab on exacerbation number and lung hyperinflation in atopic patients with severe eosinophilic asthma.

Background: The humanized monoclonal antibody benralizumab targets the α subunit of the interleukin-5 (IL-5) receptor and the FcγRIIIa receptor expressed by natural killer cells. Through this dual mechanism of action, benralizumab neutralizes the pro-eosinophil functions of IL-5 and promotes eosinophil apoptosis. Objectives and methods: The present real-life study aimed to evaluate, in 22 allergic patients with severe eosinophilic asthma, the effects of benralizumab on asthma exacerbations and lung hyperinflation. Results: In this regard here we show that, after 24 weeks of add-on treatment, benralizumab completely depleted peripheral blood eosinophils (from 810 to 0 cells/μL; p < 0.0001), and significantly decreased both asthma exacerbation number (from 4 to 0; p < 0.0001) and residual volume (from 2720 to 2300 mL; p < 0.01). Moreover, at the same time point (24 weeks) benralizumab also increased pre-bronchodilator FEV1 (from 1295 to 1985 mL; p < 0.0001), FVC (from 2390 to 2974 mL; p < 0.0001), FEF25−75 (from 0.6 to 1.42 L/sec; p < 0.0001), IC (from 1940 to 2460 mL; not significant), and ACT score (from 14.73 to 22.95; p < 0.0001), as well as reduced prednisone intake (from 25 to 0 mg; p < 0.0001). Conclusion: In conclusion, our results suggest that via its anti-eosinophil actions benralizumab improved airflow limitation, lung hyperinflation, and respiratory symptoms, as well as lowered asthma exacerbation rate and abrogated OCS consumption in most patients

Speech outcome in tongue cancer surgery: objective evaluation by acoustic analysis software

BACKGROUND. Cancer of the oral cavity is one of the most common malignancies of which 60% affect the tongue. Carcinoma of the tongue causes significant alterations of the articulatory and swallowing functions. The gold standard of care remains primary surgical resection with or without postoperative adjuvant therapy. Whereas T1 and T2 tongue tumors can be treated with more conservative surgeries, as partial glossectomies, the larger tumors require total and aggressive glossectomies which increase survival, but, on the other hand, they might often make speech, chewing and swallowing impossible. MATERIAL AND METHODS. Our study was performed on a total of 21 patients with Squamous Cell Carcinoma of the tongue who underwent either partial resection or hemiglossectomy. Each subject (either surgical patients or controls) was asked to pronounce the vowels /a/, /e/, /i/, /u/, and all signals were evaluated separately by two operators. Acoustic (F0, jitter, shimmer, NHR) and vowel metric (the ratio F2i/F2u, tVSA, qVSA, FCR) features have been extracted. In order to define the speech intelligibility, all patients were evaluated by two doctors and one speech therapist and all patients received the Speech Handicap Index (SHI) translated into Italian language before recording. RESULTS. No statistically significant variations were observed, regardless of the gender, between controls and surgically resected patients when tumor staging was T1-T2. On the contrary, when patients had to undergo more extensive surgical resection due to the presence of a T3-T4 tumor, a dramatic increase of F2u could be observed. This change, together with a decrease of F2i, led to a highly significant reduction in the F2i/F2u parameter in surgically resected patients as compared to controls. The other parameters which were reduced in a statistically significant manner in T3-T4 surgically resected patients were tVSA and qVSA. Instead, two parameters increased in a statistically significant manner in T3-T4 surgically resected patients: FCR and SHI. Again, none of the above-mentioned parameters was altered in a statistically significant manner in early tumor stage resected patients, regar dless of the gender. CONCLUSION. For the first time, we used a series of newly developed formant parameters, introduced by various authors for the study of the articulatory undershoot of the tongue in various neurodegenerative diseases. The statistical analysis of our results highlighted in an incontrovertible way a strong correlation and significance of each of our parameters F2 / i / / F2 / u /, FCR, tVSA, qVSA, with the entity of the TNM, and therefore of the surgical extension of the resection, and in parallel with the loss of the intelligibility of the speech that proportionally reaches higher values in the advanced stages of the disease as can be deduced from the SHI trend

Effects of continuous positive airway pressure on comprehensive geriatric assessment and cognitive function in elderly patients with obstructive sleep apnea syndrome

Obstructive sleep apnea syndrome (OSAS) can lead to cognitive impairment and depression affecting memory, attention, and executive functions. Continuous positive airway pressure (CPAP) treatment seems to be able to revert changes in brain networks and neuropsychological tests correlated to OSAS. The aim of the present study was to evaluate the effects of a 6-month treatment with CPAP on functional, humoral and cognitive parameters in a cohort of elderly OSAS patients with several comorbidities. We enrolled 360 elderly patients suffering from moderate to severe OSAS and indication for nocturnal CPAP. At baseline the Comprehensive Geriatric Assessment (CGA) revealed a borderline Mini-Mental State Examination (MMSE) score that improved after 6-month treatment with CPAP (25.3 +/- 1.6 vs 26 +/- 1.5; p &lt; 0.0001), as well as the Montreal Cognitive Assessment (MoCA) showed a mild improvement (24.4 +/- 2.3 vs 26.2 +/- 1.7; p &lt; 0.0001). Moreover, functionality activities increased after treatment, as documented by a short physical performance battery (SPPB) (6.3 +/- 1.5 vs 6.9 +/- 1.4; p &lt; 0.0001). Reduction of the Geriatric Depression Scale (GDS) from 6.0 +/- 2.5 to 4.6 +/- 2.2 (p &lt; 0.0001) was also detected. Changes of homeostasis model assessment (HOMA) index, oxygen desaturation index (ODI), sleep-time spent with saturation below 90% (TC90), peripheral arterial oxyhaemoglobin saturation (SpO(2)), apnea-hypopnea index (AHI) and estimation of glomerular filtration rate (eGFR), contributed, respectively, to 27.9%, 9.0%, 2.8%, 2.3%, 1.7% and 0.9% of MMSE variability for a total of 44.6% of MMSE variations. GDS score changes were due to the improvement of AHI, ODI and TC90, respectively, for 19.2%, 4.9%, 4.2% of the GDS variability, cumulative responsible for 28.3% of GDS modifications. The present real-world study shows that CPAP treatment is able to improve cognition and depressive symptoms in OSAS elderly patients

New potential biomarkers for early chronic kidney disease diagnosis in patients with different glucose tolerance status

Background: The purpose of the present study was to investigate the role of oxidative stress, platelet activation, and endocan levels in renal dysfunction in normal glucose tolerance (NGT) patients with 1-h plasma glucose values ≥155 mg/dl (NGT ≥ 155), compared to NGT &lt; 155, impaired glucose tolerance (IGT), and type 2 diabetes mellitus (T2DM) newly diagnosed subjects. We enlisted 233 patients subjected to an oral glucose tolerance test (OGTT). Materials and methods: The serum levels of platelet activation (glycoprotein VI and sP-selectin), oxidative stress biomarkers (8-isoprostane and Nox-2), and endocan were evaluated using an ELISA test. Results: Among NGT &lt; 155 patients and the T2DM group, there was a statistically significant increase in 8-isoprostane (p &lt; 0.0001), Nox-2 (p &lt; 0.0001), glycoprotein VI (p &lt; 0.0001), and sP-selectin (p &lt; 0.0001) serum levels. Higher serum endocan levels were found with the worsening of metabolic profile (p &lt; 0.0001); specifically, NGT ≥ 155 patients presented higher serum endocan values when compared to NGT &lt; 155 patients (p &lt; 0.0001). From the multivariate linear regression analysis, 1-h glucose resulted in the major predictor of estimated glomerular filtration rate (e-GFR) justifying 23.6% of its variation (p &lt; 0.0001); 8-isoprostane and Nox-2 added respectively another 6.0% (p &lt; 0.0001) and 3.2% (p = 0.001). Conclusion: Our study confirmed the link between 1-h post-load glucose ≥155 mg/dl during OGTT and the possible increased risk for chronic kidney disease (CKD) in newly diagnosed patients. The novelty is that we demonstrated a progressive increase in oxidative stress, platelet activation, and serum endocan levels with the worsening of metabolic profile, which becomes evident early during the progression of CKD

Single Inhaler LABA/LAMA for COPD

Chronic obstructive pulmonary disease (COPD) is a common disabling disease characterized by progressive airflow obstruction. Great efforts were spent in the development of drugs able to improve symptoms, quality of life, reduce exacerbations, hospitalizations and the frequency of death of patients with COPD. The cornerstones of treatment are bronchodilator drugs of two different classes: beta agonists and muscarinic antagonists. Currently the Global initiative for COPD suggests the use of long acting beta agonists (LABAs) and long acting muscarinic antagonists (LAMAs) in combination for the majority of COPD patients, thus great interest is associated with the developing of LAMA/LABA fixed combination in the maintenance treatment of stable COPD. Many LAMA/LABA fixed dose combinations have been licensed in different countries and the clinical use of these drugs stimulated the performance of many clinical trials. The purpose of this review is a complete criticism of pharmacological and clinical aspects related to the use of LAMA/LABA single inhalers for the maintenance treatment of stable COPD, with particular mention to the most debated topics and future prospects in the field

Real-life effects of dupilumab in patients with severe type 2 asthma, according to atopic trait and presence of chronic rhinosinusitis with nasal polyps

BackgroundThe efficacy of dupilumab as biological treatment of severe asthma and chronic rhinosinusitis with nasal polyps (CRSwNP) depends on its ability to inhibit the pathophysiologic mechanisms involved in type 2 inflammation.ObjectiveTo assess in a large sample of subjects with severe asthma, the therapeutic impact of dupilumab in real-life, with regard to positive or negative skin prick test (SPT) and CRSwNP presence or absence.MethodsClinical, functional, and laboratory parameters were measured at baseline and 24 weeks after the first dupilumab administration. Moreover, a comparative evaluation was carried out in relation to the presence or absence of SPT positivity and CRSwNP.ResultsAmong the 127 recruited patients with severe asthma, 90 had positive SPT, while 78 reported CRSwNP. Compared with the 6 months preceding the first dupilumab injection, asthma exacerbations decreased from 4.0 (2.0-5.0) to 0.0 (0.0-0.0) (p &lt; 0.0001), as well as the daily prednisone intake fell from 12.50 mg (0.00-25.00) to 0.00 mg (0.00-0.00) (p &lt; 0.0001). In the same period, asthma control test (ACT) score increased from 14 (10-18) to 22 (20-24) (p &lt; 0.0001), and sino-nasal outcome test (SNOT-22) score dropped from 55.84 ± 20.32 to 19.76 ± 12.76 (p &lt; 0.0001). Moreover, we observed relevant increases in forced expiratory volume in one second (FEV1) from the baseline value of 2.13 L (1.62-2.81) to 2.39 L (1.89-3.06) (p &lt; 0.0001). Fractional exhaled nitric oxide (FeNO) values decreased from 27.0 ppb (18.0-37.5) to 13.0 ppb (5.0-20.0) (p &lt; 0.0001). These improvements were quite similar in subgroups of patients characterized by SPT negativity or positivity, and CRSwNP absence or presence. No statistically significant correlations were detected between serum IgE levels, baseline blood eosinophils or FeNO levels and dupilumab-induced changes, with the exception of FEV1 increase, which was shown to be positively correlated with FeNO values (r = 0.3147; p &lt; 0.01).ConclusionOur results consolidate the strategic position of dupilumab in its role as an excellent therapeutic option currently available within the context of modern biological treatments of severe asthma and CRSwNP, frequently driven by type 2 airway inflammation

Asthma Control during COVID-19 Lockdown in Patients with Severe Asthma under Biological Drug Treatment

Introduction: Coronavirus disease 2019 (COVID-19) has deeply affected the management of patients with severe asthma, treated with add-on biological therapies. Objective: In this study, severe asthmatic patients on treatment with one of three different biologics (omalizumab, mepolizumab, benralizumab) underwent a survey to evaluate the effects of COVID-19 on the management of their clinical condition, with regard to the changes caused by the limited access to health facilities during the pandemic period. Methods: In this prospective observational study, 28 severe asthmatic outpatients referring to the Respiratory Unit of Magna Graecia University Hospital, Catanzaro (Italy), were asked to answer a telephone survey from May to July 2021. This survey included the evaluation of demographic and clinical data, as well as the number of lung function tests performed, exacerbations, biologic doses administered at hospital, or at general practitioner office, or through self-administration. Adherence to biological therapies before and during the pandemic period was also assessed. Moreover, the most recent asthma control test (ACT) score and the last forced expiratory volume in the first second (FEV1) measurement, recorded during the pandemic phase, were compared to the pre-pandemic (baseline) period. Results: When comparing the pre-pandemic data with the pandemic observations, the mean ACT score and the exacerbation rate did not significantly change [ACT, 21.5 &plusmn; 2.8 to 23.0 &plusmn; 3.9 (p = 0.1); exacerbation rate, 0.3 &plusmn; 0.6 and 0.5 &plusmn; 1.5 (p = 0.3)]. When considering some variables related to disease management in the same periods, a statistically significant difference was detected with regard to the mean number of outpatient visits (5.2 &plusmn; 3.8 vs. 0.9 &plusmn; 2.5, p &lt; 0.0001), as well as to the mean number of accesses to health facilities for the administration of biological drugs (from 7.0 &plusmn; 3.4 to 2.5 &plusmn; 3.9, p &lt; 0.0001). None of the patients reported to have been infected with the SARS-CoV-2 virus and no adverse drug reactions (ADR) occurred during the study. Conclusions: The above results suggest that COVID-19 pandemic did not induce any significant change related to severe asthma control. Indeed, add-on treatment with biological drugs was regularly continued, despite the obvious limited access to health facilities

Benralizumab in the treatment of severe asthma: Design, development and potential place in therapy

Asthma is a widespread and heterogeneous inflammatory disease of the airways, which is characterized by several different phenotypes and endotypes. In particular, eosinophilic airway inflammation is a common pathologic trait of both allergic and nonallergic asthma. The key cytokine responsible for maturation, activation, recruitment, and survival of eosinophils is interleukin (IL)-5, which is mainly produced by T helper 2 (Th2) lymphocytes and group 2 innate lymphoid cells. Therefore, for uncontrolled patients with severe eosinophilic asthma, who are not fully responsive to corticosteroids, IL-5 represents a very important molecular target for add-on biological therapies. Among these new treatments, anti-IL-5 monoclonal antibodies such as mepolizumab and reslizumab have been developed and clinically evaluated. Furthermore, benralizumab is currently the only available biologic drug that specifically binds to the IL-5 receptor, thus preventing the interaction with its ligand and the consequent pro-inflammatory effects. The effectiveness of benralizumab in improving severe eosinophilic asthma has been well-documented by many randomized controlled trials

Therapeutic Role of Tocilizumab in SARS-CoV-2-Induced Cytokine Storm: Rationale and Current Evidence

Among patients suffering from coronavirus disease 2019 (COVID-19) syndrome, one of the worst possible scenarios is represented by the critical lung damage caused by the severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2)-induced cytokine storm, responsible for a potentially very dangerous hyperinflammatory condition. Within such a context, interleukin-6 (IL-6) plays a key pathogenic role, thus being a suitable therapeutic target. Indeed, the IL-6-receptor antagonist tocilizumab, already approved for treatment of refractory rheumatoid arthritis, is often used to treat patients with severe COVID-19 symptoms and lung involvement. Therefore, the aim of this review article is to focus on the rationale of tocilizumab utilization in the SARS-CoV-2-triggered cytokine storm, as well as to discuss current evidence and future perspectives, especially with regard to ongoing trials referring to the evaluation of tocilizumab’s therapeutic effects in patients with life-threatening SARS-CoV-2 infection

Eosinophilic inflammation: An Appealing Target for Pharmacologic Treatments in Severe Asthma

Severe 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