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Disruption of the airway epithelium triggers a defensive immune response that begins with the production and release of alarmin cytokines. These epithelial-derived alarmin cytokines, including thymic stromal lymphopoietin (TSLP), are produced in response to aeroallergens, viruses, and toxic inhalants. An alarmin response disproportionate to the inhaled trigger can exacerbate airway diseases such as asthma. Allergens inhaled into previously sensitized airways are known to drive a T2 inflammatory response through the polarization of T cells by dendritic cells mediated by TSLP. Harmful compounds found within air pollution, microbes, and viruses are also triggers causing airway epithelial cell release of TSLP in asthmatic airways. The release of TSLP leads to the development of inflammation which, when unchecked, can result in asthma exacerbations. Genetic and inheritable factors can contribute to the variable expression of TSLP and the risk and severity of asthma. This paper will review the various triggers and consequences of TSLP release in asthmatic airways. [ABSTRACT FROM AUTHOR]

This work introduces Spiromni, a single device incorporating three different pressurised metered-dose inhaler (pMDI) accessories: a pMDI spacer, an electronic monitoring device (EMD), and a spirometer. While there are devices made to individually address the issues of technique, adherence and monitoring, respectively, for asthma patients as laid out in the Global Initiative for Asthma's (GINA) global strategy for asthma management and prevention, Spiromni was designed to address all three issues using a single, combination device. Spiromni addresses the key challenge of measuring both inhalation and exhalation profiles, which are different by an order of magnitude. Moreover, the innovative design prevents exhalation from entering the spacer chamber and prevents medication loss during inhalation using umbrella valves without a loss in flow velocity. Apart from recording the peak exhalation flow rate, data from the sensors allow us to extract other key lung volume and capacities measures similar to a medical pulmonary function test. We believe this low-cost portable multi-functional device will benefit both asthma patients and clinicians in the management of the disease. [ABSTRACT FROM AUTHOR]

Bronchial asthma is characterized by airway inflammation, airway hyperresponsiveness, and reversible airway obstruction. Eosinophils contribute to the pathogenesis of airway disease mainly by releasing eosinophil-specific granules, lipid mediators, superoxide anions, and their DNA. Type-2 cytokines such as interleukin (IL)-4 and IL-13 also play roles in the development of bronchial asthma. Among these cytokines, IL-4 is involved in T-cell differentiation, B-cell activation, B-cell differentiation into plasma cells, and the production of immunoglobulin E. Although IL-13 has similar effects to IL-4, IL-13 mainly affects structural cells, such as epithelial cells, smooth muscle cells, and fibroblasts. IL-13 induces the differentiation of goblet cells that produce mucus and induces the airway remodeling, including smooth muscle hypertrophy. IL-4 and IL-13 do not directly activate the effector functions of eosinophils; however, they can induce eosinophilic airway inflammation by upregulating the expression of vascular cell adhesion molecule-1 (for adhesion) and CC chemokine receptor 3 ligands (for migration). Dupilumab, a human anti-IL-4 receptor α monoclonal antibody that inhibits IL-4 and IL-13 signaling, decreases asthma exacerbations and mucus plugs and increases lung function in moderate to severe asthma. In addition, dupilumab is effective for chronic rhinosinusitis with nasal polyps and for atopic dermatitis, and IL-4/IL-13 blocking is expected to suppress allergen sensitization, including transcutaneous sensitization and atopic march. [ABSTRACT FROM AUTHOR]

Asthma is a complex respiratory condition characterized by chronic airway inflammation and variable expiratory airflow limitation, affecting millions globally. Among athletes, particularly those competing at elite levels, the prevalence of respiratory conditions is notably heightened, varying between 20% and 70% across specific sports. Exercise-induced bronchoconstriction (EIB) is a common issue among athletes, impacting their performance and well-being. The prevalence rates vary based on the sport, training environment, and genetics. Exercise is a known trigger for asthma, but paradoxically, it can also improve pulmonary function and alleviate EIB severity. However, athletes' asthma phenotypes differ, leading to varied responses to medications and challenges in management. The unique aspects in athletes include heightened airway sensitivity, allergen, pollutant exposure, and temperature variations. This review addresses EIB in athletes, focusing on pathogenesis, diagnosis, and treatment. The pathogenesis of EIB involves complex interactions between physiological and environmental factors. Airway dehydration and cooling are key mechanisms, leading to osmotic and thermal theories. Airway inflammation and hyper-responsiveness are common factors. Elite athletes often exhibit distinct inflammatory responses and heightened airway sensitivity, influenced by sport type, training, and environment. Swimming and certain sports pose higher EIB risks, with chlorine exposure in pools being a notable factor. Immune responses, lung function changes, and individual variations contribute to EIB in athletes. Diagnosing EIB in athletes requires objective testing, as baseline lung function tests can yield normal results. Both EIB with asthma (EIBA) and without asthma (EIBwA) must be considered. Exercise and indirect bronchoprovocation tests provide reliable diagnoses. In athletes, exercise tests offer effectiveness in diagnosing EIB. Spirometry and bronchodilation tests are standard approaches, but the diagnostic emphasis is shifting toward provocation tests. Despite its challenges, achieving an optimal diagnosis of EIA constitutes the cornerstone for effective management, leading to improved performance, reduced risk of complications, and enhanced quality of life. The management of EIB in athletes aligns with the general principles for symptom control, prevention, and reducing complications. Non-pharmacological approaches, including trigger avoidance and warming up, are essential. Inhaled corticosteroids (ICS) are the cornerstone of asthma therapy in athletes. Short-acting beta agonists (SABA) are discouraged as sole treatments. Leukotriene receptor antagonists (LTRA) and mast cell stabilizing agents (MCSA) are potential options. Optimal management improves the athletes' quality of life and allows them to pursue competitive sports effectively. [ABSTRACT FROM AUTHOR]

Severe asthma is a complex and heterogeneous clinical condition presented as chronic inflammation of the airways. Conventional treatments are mainly focused on symptom control; however, there has been a shift towards personalized medicine. Identification of different phenotypes driven by complex pathobiological mechanisms (endotypes), especially those driven by type-2 (T2) inflammation, has led to improved treatment outcomes. Combining biomarkers with T2-targeting monoclonal antibodies is crucial for developing personalized treatment strategies. Several biological agents, including anti-immunoglobulin E, anti-interleukin-5, and anti-thymic stromal lymphopoietin/interleukin-4, have been approved for the treatment of severe asthma. These biological therapies have demonstrated efficacy in reducing asthma exacerbations, lowering eosinophil count, improving lung function, diminishing oral corticosteroid use, and improving the quality of life in selected patients. Severe asthma management is undergoing a profound transformation with the introduction of ongoing and future biological therapies. The availability of novel treatment options has facilitated the adoption of phenotype/endotype-specific approaches and disappearance of generic interventions. The transition towards precision medicine plays a crucial role in meticulously addressing the individual traits of asthma pathobiology. An era of tailored strategies has emerged, allowing for the successful targeting of immune-inflammatory responses that underlie uncontrolled T2-high asthma. These personalized approaches hold great promise for improving the overall efficacy and outcomes in the management of severe asthma. This article comprehensively reviews currently available biological agents and biomarkers for treating severe asthma. With the expanding repertoire of therapeutic options, it is becoming increasingly crucial to comprehend the influencing factors, understand the pathogenesis, and track treatment progress in severe asthma. [ABSTRACT FROM AUTHOR]