The Global Initiative for Asthma (GINA) Strategy Report provides a comprehensive, annually updated evidence-based approach to asthma diagnosis, assessment, treatment, and prevention across the lifespan. Its central approach is personalized, iterative care based on the Assess-Adjust-Review cycle for both symptom control and reduction of future risk (including severe exacerbations, persistent airflow limitation, and treatment-related harm). GINA emphasizes objective confirmation of diagnosis wherever possible, and regular assessment of lung function, inhaler technique, adherence, multimorbidity, risk factors (including Type-2 biomarkers), and patient goals and preferences. GINA strongly recommends that all adults, adolescents, children and most preschoolers with asthma should receive inhaled corticosteroid (ICS)-containing treatment. GINA recommends against short-acting beta2-agonist (SABA)-only treatment. For adults/adolescents, GINA Track 1 using low-dose ICS-formoterol, an anti-inflammatory reliever (AIR), either as-needed-only (AIR-only) or as maintenance-and-reliever therapy (MART), is preferred because of its substantial reduction in severe exacerbations compared with SABA-based regimens, and its simplicity. Age-specific treatment pathways in children also emphasize ICS-containing therapy and exacerbation prevention. For difficult-to-treat and severe asthma, GINA provides structured guidance, emphasizing diagnostic verification, optimization of modifiable factors, inflammatory phenotyping, biologic therapy selection, and (as for all patients) systemic corticosteroid stewardship. Acute exacerbation care incorporates long-term preventive treatment, including post-discharge reassessment of management and action plan. Key 2026 updates include expanded AIR options for adults and children, revised guidance on severe asthma and selection of biologic treatment, and substantial updates to acute asthma management. GINA integrates evidence-based management with shared decision-making, self-management education, implementation, and global advocacy to reduce preventable asthma morbidity and mortality.

The blood-brain barrier (BBB) experiences dysfunction during physiological aging, potentially leading to cognitive decline and the onset of neurodegenerative diseases. Recent research highlights brain endothelial cell (BEC) senescence as a key factor contributing to BBB impairment. In this study, polymeric nanoparticles (NPs) loaded with a senolytic agent - Navitoclax - were designed to selectively eliminate senescent cells more effectively. These NPs are taken up by both proliferative and senescent BECs, but are only degraded in the latter due to the presence of senescence-associated beta-galactosidase (SA-β-gal), releasing the drug to induce cell death. NPs effectively and selectively eliminate senescent BECs at lower doses, without affecting proliferative cells, outperforming the soluble senolytic. NPs were then evaluated in a chronologically aged rat model exhibiting BEC senescence, increased BBB permeability, and diminished exploratory behavior. In comparison to high-dose soluble senolytic, the NPs successfully restored BBB integrity by reducing permeability, diminishing the burden of senescent BECs, and partially improving rat exploratory performance. Notably, only the NPs were able to reduce the presence of p21[+] and p16[+] BECs in vivo and enhance exploratory behavior. These findings suggest that NPs containing senolytics represent a promising intervention for decreasing BECs senescence, reducing BBB permeability, and enhancing exploratory behavior in naturally aged rats.

Senescent cells accumulate in various tissues as we age and are characterized by growth arrest and a senescence-associated secretory phenotype (SASP). This phenotype involves the release of various factors, such as pro-inflammatory molecules, reactive oxygen species (ROS) and extracellular vesicles (EVs), which can trigger senescence in neighboring cells. However, it remains unclear whether non-soluble factors produced by senescent cells, such as the extracellular matrix (ECM) or its associated molecules (collectively termed the matrisome), can induce paracrine senescence. In this study, vascular cells were used as an in vitro model system to investigate this hypothesis. These findings reveal that decellularized ECM from senescent vascular smooth muscle cells (S-ECM) or fibroblasts, but not from proliferating cells (P-ECM), robustly induces a senescence phenotype in human proliferative endothelial cells (ECs) over a two-week culture period, whereas ECM from proliferating cells (P-ECM) does not elicit this effect. This induction appears to be at least partially mediated by the transforming growth factor beta (TGF-β) signaling pathway. Notably, inhibiting TGF-β receptor 1 (TGFβR1) in proliferative ECs grown in S-ECM significantly attenuated the senescence phenotype. These results further show that one of the matrisome proteins able to mediate the pro-senescence effect of S-ECM is transforming growth factor beta 1 induced transcript 1 (TGFβ1|1). Importantly, when discs coated with S-ECM were implanted in young mice, an increase in senescence markers was observed compared to mice implanted with discs coated with P-ECM. Overall, this research demonstrates that senescent-derived ECM acts as a potent trigger of cellular senescence, both in vitro and in vivo, with the involvement of the TGF-β signaling pathway playing a crucial role.

BACKGROUND: The peak flow meter is considered a complementary tool to spirometry for monitoring obstructive lung diseases. In many countries, spirometry is not easily accessible for diagnosing asthma in primary care. In this context, there has been growing interest in evaluating the role of the peak expiratory flow meter (PEFM) for asthma management, particularly in primary care settings. This study aims to assess the usefulness of PEFM in detecting airflow limitation (AFL), as identified by conventional spirometry, in a primary health care (PHC) setting in Brazil. METHODS: This cross-sectional study was nested within a clinical trial. Participants aged 6 to 65, both sexes, with a history of respiratory symptoms suggestive of asthma and uncontrolled disease, from 28 PHC centers across all macroregions of Brazil were included. AFL was defined by spirometry according to international criteria and by PEFM when PEF was < 80% of the predicted value. The Global Lung Function Initiative (GLI) equations were used for parameterization. The accuracy of PEFM in detecting AFL, as identified by spirometry, was analyzed, and sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and area under the ROC curve (AUC) were reported. RESULTS: Among 298 participants, 107 (36%) had a confirmed asthma diagnosis. Spirometry identified AFL in 36% (n = 107) of participants, while PEFM detected AFL in 64.8% (n = 193). PEFM demonstrated an overall sensitivity of 82.4% (95% CI: 78.0%–86.7%) for detecting AFL compared with spirometry. Specificity was 44.4% (95% CI: 38.8%–50.0%), and AUC for the PEFM was 0.73. The Intraclass Correlation Coefficient (ICC) for absolute PEFM values was 0.01 (95% CI: -0.18 to 0.20, p = 0.473). CONCLUSIONS: The PEFM demonstrates high sensitivity for AFL, but it should be used with caution as a stand-alone tool for asthma diagnosis. Given its low cost and easy access in PHC settings, PEFM seems to be a useful initial screening tool for AFL, especially in resource-limited settings.

The International Severe Asthma Registry (ISAR) was established in 2017 to advance the understanding of severe asthma and its management, thereby improving patient care worldwide. As the first global registry for adults with severe asthma, ISAR enabled individual registries to standardize and pool their data, creating a comprehensive, harmonized dataset with sufficient statistical power to address key research questions and knowledge gaps. Today, ISAR is the largest repository of real-world data on severe asthma, curating data on nearly 35,000 patients from 28 countries worldwide, and has become a leading contributor to severe asthma research. Research using ISAR data has provided valuable insights on the characteristics of severe asthma, its burdens and risk factors, real-world treatment effectiveness, and barriers to specialist care, which are collectively informing improved asthma management. Besides changing clinical thinking via research, ISAR aims to advance real-world practice through initiatives that improve registry data quality and severe asthma care. In 2024, ISAR refined essential research variables to enhance data quality and launched a web-based data acquisition and reporting system (QISAR), which integrates data collection with clinical consultations and enables longitudinal data tracking at patient, center, and population levels. Quality improvement priorities include collecting standardized data during consultations and tracking and optimizing patient journeys via QISAR and integrating primary/secondary care pathways to expedite specialist severe asthma management and facilitate clinical trial recruitment. ISAR envisions a future in which timely specialist referral and initiation of biologic therapy can obviate long-term systemic corticosteroid use and enable more patients to achieve remission.