Search Results (44)

Asthma has traditionally been viewed as a single disease, but recent research reveals its clinical and molecular complexity. This perspective highlights the need to shift from a traditional, uniform treatment paradigm to one that embraces the heterogeneity of asthma across individuals. Each patient presents a unique clinical story shaped by a complex interplay of genetic predispositions, developmental programming during critical early-life windows, the influence of sex and hormones, and lifelong environmental exposures. Asthma comprises multiple subtypes with distinct clinical and biological features. Furthermore, lifestyle factors such as obesity and smoking, along with highly prevalent comorbidities like allergic rhinitis and gastroesophageal reflux disease, significantly modify the disease’s course and response to treatment. This article explores how classifying the disease into clinical phenotypes (observable characteristics) and molecular endotypes (underlying mechanisms)—particularly the distinction between T2-high and T2-low inflammation—provides a crucial framework for managing this complexity. The application of this framework, guided by biomarkers, has enabled the development of targeted biologic therapies that can transform care for specific patient subgroups. Despite these advances, significant challenges remain. The pathophysiology of certain subgroups, particularly non-T2 asthma, remains poorly defined, and there is an urgent need for reliable predictive biomarkers to guide therapy and monitor outcomes. It is our opinion that future studies must adopt a systems-biology strategy, with a multi-omics approach that constructs a comprehensive molecular profile of each patient. This integrative methodology will require the use of advanced computational methods, including machine learning and artificial intelligence, to decipher the complex pathways linking genetic and environmental inputs to clinical disease. In conclusion, this article argues for a more personalized understanding of asthma, urging clinicians and researchers to consider each patient’s unique clinical presentation. Full article

Background: Small airway dysfunction (SAD) plays a critical role in the management of severe asthma, particularly in patients at risk of requiring biological therapies (BTs). Short-term studies have shown that switching to single-inhaler triple therapy (SITT) with extrafine beclomethasone–formoterol–glycopyrronium improves outcomes and helps achieve quiet asthma, a state marked by symptom control, no exacerbations or oral steroids, reduced inflammation, and better small airway function. This study investigated whether, over one year, patients could maintain this state as Steady Quiet Asthma (SQA) and whether baseline measures could predict this sustained response. Methods: Twenty-six patients with severe asthma and SAD were transitioned from open triple-inhaler therapy to a closed, single-inhaler triple therapy containing extrafine beclomethasone–formoterol–glycopyrronium. Assessments at baseline (T0) and at one-year follow-up (T12) included clinical evaluations, spirometry, and impulse oscillometry, with a focus on Fres as a predictor for the need for BT. When prescribed, biologic therapies included mepolizumab, benralizumab, and dupilumab. Results: Of the 26 patients, 9 (34.6%) achieved SQA and did not require biologic therapy at the one-year follow-up, while 17 patients (65.4%) initiated biologic treatment. At T0, patients who required biologics had significantly higher median Fres (21 (19.47; 24.58) vs. 17.61 (15.82; 20.63); p = 0.049) compared to those who remained biologic-free. They also exhibited higher residual volume to total lung capacity ratio (%RV/TLC) values and lower forced expiratory volume in one second/forced vital capacity ratios (FEV₁/FVC). At T12, patients spared from BT showed significant reductions in Fres (p = 0.014) and improvements in small airway function (difference in airway resistance between 5 Hz and 20 Hz (R5–20), forced expiratory flow between 25% and 75% of FVC (%FEF25–75), and better asthma control (ACT). In contrast, patients on BT demonstrated less favorable changes in these parameters. Conclusions: Baseline Fres, FEV1/FVC ratio, and %FEV25–75 are valuable predictors of achieving Steady Quiet Asthma (SQA) and sparing biologic therapy. These findings support the use of SITT in severe asthma and highlight the importance of early functional assessments to guide personalized management. Full article

Obstructive sleep apnea (OSA) is a highly prevalent sleep-related breathing disorder, primarily characterized by recurrent episodes of upper airway obstruction during sleep. Individuals affected by OSA are at increased risk for a variety of adverse health outcomes, particularly neurocognitive impairments and cardiovascular complications, highlighting the clinical significance of this condition. A defining feature of OSA is intermittent hypoxemia, which contributes to the excessive production of reactive oxygen species (ROS) and the subsequent development of oxidative stress. The primary objective of this narrative review was to comprehensively investigate the intricate mechanisms of oxidative stress and elucidate their complex interplay in the development and progression of OSAS. Subsequently, we examined the current literature to identify the most promising biomarkers and pharmacological treatments related to OSA and oxidative stress. We found that biomarkers of oxidative stress have shown potential in assessing disease severity and tracking individual responses to therapy. However, none have yet to be incorporated into standard clinical practice. Continuous positive airway pressure (CPAP) is the gold standard treatment for OSA. Nevertheless, antioxidant therapy has emerged as a potential adjunctive approach that may help address residual dysfunctions not fully resolved by CPAP alone. Both the use of oxidative stress biomarkers and antioxidant-based therapies require further validation through robust clinical studies before they can be routinely implemented in clinical settings. Full article

This study investigates, for the first time, using finite element analysis (FEA), the differential impact of middle ear prosthesis diameter on hearing gain in two distinct surgical techniques: stapedotomy and partial stapedectomy. The model represented the cochlea as two fluid-filled straight channels separated by the basilar membrane and considered pistons of 0.4 mm and 0.6 mm diameters. The results demonstrated that in stapedotomy, a 0.6 mm diameter piston yielded a significantly better reduction in ABG (8.31 dB) compared to the 0.4 mm piston (10.67 dB), indicating improved hearing gain. Conversely, in partial stapedectomy, the smaller 0.4 mm piston was more effective, reducing ABG to 11.2 dB versus 12.12 dB with the larger piston. These findings highlight that the optimal prosthesis diameter varies according to surgical technique, emphasizing the need for tailored prosthesis selection. Full article

Exhaled breath analysis using electronic noses (e-noses) is a promising non-invasive diagnostic tool. However, a lack of standardized protocols limits clinical implementation. This study evaluates the consistency of breathprints in healthy subjects using the Cyranose 320 e-nose to support standardization efforts. Breath samples from 139 healthy non-smoking subjects (age range 18–65 years) were collected using a standardized protocol. Participants exhaled into a Tedlar bag for immediate analysis with the Cyranose 320. Principal Component Analysis (PCA) was used to reduce data dimensionality, and K-means clustering grouped subjects based on breathprints. PCA identified four principal components explaining 97.15% of variance. K-means clustering revealed two clusters: 1 outlier and 138 subjects with highly similar breathprints. The median distance from the cluster center was 0.21 (IQR: 0.18–0.24), indicating low variability. Box plots confirmed breathprint consistency across subjects. The high consistency of breathprints in healthy subjects supports the feasibility of standardizing e-nose protocols. These findings highlight the potential of e-noses for clinical diagnostics, warranting further research in diverse populations and disease cohorts. Full article

Asthma is a prevalent chronic condition, affecting an estimated 260 million people worldwide, according to the 2021 Global Burden of Disease Study. This condition significantly impacts individuals of all ages. One notable finding is that asthma prevalence among adults was higher in females than males. Recent evidence suggests that these disparities in asthma prevalence and outcomes are likely due to complex interactions among hormonal, anatomical, and environmental factors, coupled with societal and behavioral influences. The interchangeable use of the terms “sex” and “gender” in the scientific literature is frequently inconsistent. Biological sex is defined by anatomical and physiological characteristics determined by genetics; “gender”, on the other hand, is a more complex construct and a universally accepted definition is still lacking. This lack of clarity, coupled with potential knowledge gaps, misunderstandings, or the inherent difficulty in differentiating sex- and gender-related effects, often leads to the terms being poorly defined or used interchangeably. Such imprecise usage hinders accurate data interpretation and research progress. This paper provides a perspective review synthesizing current knowledge regarding the influence of sex and gender on asthma, specifically focusing on their impact on disease pathogenesis, clinical presentation, severity, and management strategies. Full article

Hydrogenated amorphous silicon (a-Si:H) devices on flexible substrates are currently being studied for application in dosimetry and beam flux measurements. The necessity of in vivo dosimetry requires thin devices with maximal transparency and flexibility. For this reason, a thin (<10 µm) a-Si:H device deposited on a thin polyimide sheet is a very valid option for this application. Furthermore, a-Si:H is a material that has an intrinsically high radiation hardness. In order to develop these devices, the HASPIDE (Hydrogenated Amorphous Silicon Pixel Detectors) collaboration has implemented two different device configurations: n-i-p type diodes and charge-selective contact devices.Charge-selective contact-based devices have been studied for solar cell applications and, recently, the above-mentioned collaboration has tested these devices for X-ray dose measurements. In this paper, the HASPIDE collaboration has studied the X-ray and proton response of charge-selective contact devices deposited on Polyimide. The linearity of the photocurrent response to X-ray versus dose-rate has been assessed at various bias voltages. The sensitivity to protons has also been studied at various bias voltages and the wide range linearity has been tested for fluxes in the range from 8.3 × 10⁷ to 2.49 × 10¹⁰ p/(cm² s). Full article

Aim: The aim of this study was to assess the subjective experiences of adults with different cochlear implant (CI) configurations—unilateral cochlear implant (UCI), bilateral cochlear implant (BCI), and bimodal stimulation (BM)—focusing on their perception of speech in quiet and noisy environments, music, environmental sounds, people’s voices and tinnitus. Methods: A cross-sectional survey of 130 adults who had undergone UCI, BCI, or BM was conducted. Participants completed a six-item online questionnaire, assessing difficulty levels and psychological impact across auditory domains, with responses measured on a 10-point scale. Statistical analyses were performed to compare the subjective experiences of the three groups. Results: Patients reported that understanding speech in noise and tinnitus perception were their main concerns. BCI users experienced fewer difficulties with understanding speech in both quiet (p < 0.001) and noisy (p = 0.008) environments and with perceiving non-vocal sounds (p = 0.038) compared to UCI and BM users; no significant differences were found for music perception (p = 0.099), tinnitus perception (p = 0.397), or voice naturalness (p = 0.157). BCI users also reported less annoyance in quiet (p = 0.004) and noisy (p = 0.047) environments, and in the perception of voices (p = 0.009) and non-vocal sounds (p = 0.019). Tinnitus-related psychological impact showed no significant differences between groups (p = 0.090). Conclusions: Although speech perception in noise and tinnitus remain major problems for CI users, the results of our study suggest that bilateral cochlear implantation offers significant subjective advantages over unilateral implantation and bimodal stimulation in adults, particularly in difficult listening environments. Full article

Background/Objectives: This study evaluated the impact of continuous positive airway pressure (C-PAP) therapy combined with a rigorous diet regimen on obese patients with obstructive sleep apnea syndrome (OSAS). Methods: Sixty obese patients (BMI ≥ 30) diagnosed with severe OSAS were recruited in order to establish the evaluation of CPAP therapy with different extents of adherence to a rigorous diet regimen. After one year, significant improvements were observed. Results: BMI reduced by 12.32%, apnea–hypopnea index (AHI) by 22.04%, oxygen desaturation index (ODI) by 15.87%, total sleep time with oxygen saturation below 90% (TST90%) by 25.2%, and Epworth Sleepiness Scale (ESS) scores by 21.74%. Patients were, then, divided into three groups, based on adherence to the restricted diet, as well as to the correct use of the nocturnal C-PAP, showing different reductions in BMI, AHI, ODI, TST90%, and ESS, according to their adherence, based on the sum of % reduction in BMI + AHI into three groups. Conclusions: These findings underscore the effectiveness of combining C-PAP therapy with a strict diet in improving OSAS symptoms and overall health in obese patients. Future studies with larger cohorts and longer follow-up periods are needed to confirm these results and explore the long-term benefits of this integrated approach. Full article

Background/Objective: Patients with severe asthma (SA) and non-cystic fibrosis bronchiectasis (BE) without microbiological colonization represent a unique and understudied population. Type 2-targeted biologic therapies have emerged as a promising treatment for these patients. However, predictive factors for achieving clinical remission remain unclear. This study aims to identify the predictive factors for achieving clinical remission in patients with severe asthma and non-colonized bronchiectasis undergoing type 2-targeted biologic therapies. Methods: A retrospective longitudinal analysis was conducted on 14 patients with severe asthma and non-cystic fibrosis bronchiectasis without microbiological colonization. Clinical remission was assessed at baseline (T0) and after 12 months (T1) of biologic therapy. Clinical remission was defined according to the Severe Asthma Network Italy (SANI) criteria, including the absence of oral corticosteroid use, no asthma-related symptoms, stable lung function, and no exacerbations. Logistic regression was performed to identify predictors of remission. ROC curves were constructed to evaluate the predictive accuracy of lung function parameters, specifically FEV1 and FVC. Results: After 12 months of biologic therapy, 28.6% of patients (n = 4) achieved clinical remission. The mean FEV1 percentage at baseline was significantly higher in the remission group (92.25 ± 15.64%) compared to the non-remission group (65.10 ± 23.36%, p = 0.034). Logistic regression analysis identified baseline FEV1 as a significant predictor of remission (OR = 1.008, p = 0.050). ROC curve analysis revealed that an FEV1 cutoff of 72.5% had a sensitivity of 100% and a specificity of 70% (AUC = 0.900, p = 0.024) for predicting clinical remission. Conclusions: FEV1 is a crucial predictor of clinical remission in patients with severe asthma and non-colonized bronchiectasis treated with type 2-targeted biologic therapies. An FEV1 threshold of 72.5% can guide clinicians in identifying patients most likely to achieve remission. These findings underline the importance of preserving lung function to optimize therapeutic outcomes in this complex population. Full article

Background: Obstructive Sleep Apnea (OSA) is a prevalent disorder characterized by repetitive upper airway obstructions during sleep, leading to intermittent hypoxia and sleep fragmentation. Current treatments, particularly Continuous Positive Airway Pressure (CPAP), face adherence challenges, necessitating novel therapeutic approaches. Methods: This review explores the potential of Glucagon-like Peptide-1 receptor agonists (GLP-1RA), commonly used for type 2 diabetes and obesity, in managing OSA. GLP-1RA promotes weight loss, enhances insulin sensitivity, and exhibits anti-inflammatory and neuroprotective properties, potentially addressing key pathophysiological aspects of OSA. Results: Emerging evidence suggests that these agents may reduce OSA severity by decreasing upper airway fat deposition and improving respiratory control. Clinical trials have demonstrated significant reductions in the Apnea-Hypopnea Index (AHI) and improvements in sleep quality with GLP-1 therapy. Conclusions: Future research should focus on elucidating the mechanisms underlying GLP-1 effects on OSAS, optimizing combination therapies, and identifying patient subgroups that may benefit the most. Integrating GLP-1RA into OSAS management could revolutionize treatment by addressing both the metabolic and respiratory components of the disorder, ultimately enhancing patient outcomes. Full article

This study investigates volatile organic compound (VOC) profiles in the exhaled breath of normal subjects under different oxygenation conditions—normoxia (FiO2 21%), hypoxia (FiO2 11%), and hyperoxia (FiO2 35%)—using an electronic nose (e-nose). We aim to identify significant differences in VOC profiles among the three conditions utilizing principal component analysis (PCA) and canonical discriminant analysis (CDA). Our results indicate distinct VOC patterns corresponding to each oxygenation state, demonstrating the potential of e-nose technology in detecting physiological changes in breath composition (cross-validated accuracy values: FiO2 21% vs. FiO2 11% = 63%, FiO2 11% vs. FiO2 35% = 65%, FiO2 21% vs. FiO2 35% = 71%, and p < 0.05 for all). This research underscores the viability of breathomics in the non-invasive monitoring and diagnostics of various respiratory and systemic conditions. Full article

Epithelial barrier damage plays a central role in the development and maintenance of allergic inflammation. Rises in the epithelial barrier permeability of airways alter tissue homeostasis and allow the penetration of allergens and other external agents. Different factors contribute to barrier impairment, such as eosinophilic infiltration and allergen protease action—eosinophilic cationic proteins’ effects and allergens’ proteolytic activity both contribute significantly to epithelial damage. In the airways, allergen proteases degrade the epithelial junctional proteins, allowing allergen penetration and its uptake by dendritic cells. This increase in allergen–immune system interaction induces the release of alarmins and the activation of type 2 inflammatory pathways, causing or worsening the main symptoms at the skin, bowel, and respiratory levels. We aim to highlight the molecular mechanisms underlying allergenic protease-induced epithelial barrier damage and the role of immune response in allergic asthma onset, maintenance, and progression. Moreover, we will explore potential clinical and radiological biomarkers of airway remodeling in allergic asthma patients. Full article

Galectins are a group of β-galactoside-binding proteins with several roles in immune response, cellular adhesion, and inflammation development. Current evidence suggest that these proteins could play a crucial role in many respiratory diseases such as pulmonary fibrosis, lung cancer, and respiratory infections. From this standpoint, an increasing body of evidence have recognized galectins as potential biomarkers involved in several aspects of asthma pathophysiology. Among them, galectin-3 (Gal-3), galectin-9 (Gal-9), and galectin-10 (Gal-10) are the most extensively studied in human and animal asthma models. These galectins can affect T helper 2 (Th2) and non-Th2 inflammation, mucus production, airway responsiveness, and bronchial remodeling. Nevertheless, while higher Gal-3 and Gal-9 concentrations are associated with a stronger degree of Th-2 phlogosis, Gal-10, which forms Charcot–Leyden Crystals (CLCs), correlates with sputum eosinophilic count, interleukin-5 (IL-5) production, and immunoglobulin E (IgE) secretion. Finally, several galectins have shown potential in clinical response monitoring after inhaled corticosteroids (ICS) and biologic therapies, confirming their potential role as reliable biomarkers in patients with asthma. Full article

Background/Objectives: Several studies have demonstrated the positive clinical and functional impact of adding Long-Acting Muscarinic Antagonist (LAMA) to Inhaled Corticosteroids (ICS) and Long-Acting Beta-Agonists (LABA) therapy in the treatment of severe asthma. Aim and objectives: To demonstrate that treating Small Airways Disease (SAD) in severe asthma patients who are candidates for biologics can improve respiratory symptoms, lung function, and airways inflammation, potentially avoiding or delaying the use of biological therapy. Methods: Thirty-two severe asthma patients with SAD were transitioned from separate inhalers for ICS/LABA and LAMA to extrafine single-inhaler beclomethasone, formoterol, and glycopyrronium. None of these patients underwent biological therapy before the study. Follow-up evaluations were conducted at baseline (T0) and three months after initiation (T3). Assessments included clinical evaluations, spirometry, oscillometry, and inflammation markers. Results: Transitioning to single-inhaler triple therapy from T0 to T3 resulted in significant improvements in Asthma Control Test (ACT) and SAD parameters, including increased Forced Expiratory Volume in the mid-range of lung capacity and improved airway resistance and reactance measurements using impulse oscillometry. A significant reduction in airway inflammation was evidenced by lower levels of Fractional Exhaled Nitric Oxide 350 (FeNO 350) (p < 0.001 for all). Conclusions: Adopting a single-inhaler triple therapy notably enhanced clinical control and small airway function in patients with severe asthma and SAD, supporting the positive impact of target-therapy for the achievement of a stable state termed “Quiet Asthma”. Full article