Role of exosomes in exacerbations of asthma and COPD: a systematic review.

Asthma and chronic obstructive pulmonary disease are chronic respiratory disorders characterized by airways obstruction and chronic inflammation. Exacerbations lead to worsening of symptoms and increased airflow obstruction in both airways diseases, and they are associated with increase in local and systemic inflammation. Exosomes are cell-derived membrane vesicles containing proteins, lipids, and nucleic acids that reflect their cellular origin. Through the transfer of these molecules, exosomes act as mediators of intercellular communication. Via selective delivery of their contents to target cells, exosomes have been proved to be involved in regulation of immunity and inflammation. Although, exosomes have been extensively investigated in different diseases, little is currently known about their role in asthma and COPD pathogenesis, and particularly in exacerbations. This review aims to systemically assess the potential role of exosomes in asthma and COPD exacerbations.

Pulmonary Function Tests: Easy Interpretation in Three Steps.

Pulmonary function tests (PFTs) are pivotal in diagnosing and managing a broad spectrum of respiratory disorders. These tests provide critical insights into lung health, guiding diagnoses, assessing disease severity, and shaping patient management strategies. This review addresses the complexities and nuances inherent in interpreting PFT data, particularly in light of recent updates from the European Respiratory Society (ERS) and American Thoracic Society (ATS). These updates have refined interpretive strategies, moving away from definitive diagnostic uses of spirometry to a more probabilistic approach that better accounts for individual variability through the use of Z-scores and lower limits of normal (LLNs). Significantly, this narrative review delves into the philosophical shift in spirometry interpretation, highlighting the transition from direct clinical diagnostics to a more nuanced evaluation geared towards determining the likelihood of disease. It critiques the reliance on fixed ratios and emphasizes the need for reference values that consider demographic variables such as age, sex, height, and ethnicity, in line with the latest Global Lung Function Initiative (GLI) equations. Despite these advances, challenges remain in ensuring uniformity across different predictive models and reference equations, which can affect the accuracy and consistency of interpretations. This paper proposes a streamlined three-step framework for interpreting PFTs, aiming to unify and simplify the process to enhance clarity and reliability across various medical specialties. This approach not only aids in accurate patient assessments but also mitigates the potential for misdiagnosis and ensures more effective patient management. By synthesizing contemporary guidelines and integrating robust physiological principles, this review fosters a standardized yet flexible approach to PFT interpretation that is both scientifically sound and practically feasible.

Drug-drug interactions and synergy: from pharmacological models to clinical application.

This review explores the concept of synergy in pharmacology, emphasizing its importance in optimizing treatment outcomes through the combination of drugs with different mechanisms of action. Synergy, defined as an effect greater than the expected additive effect elicited by individual agents according to specific predictive models, offers a promising approach to enhance therapeutic efficacy while minimizing adverse events. The historical evolution of synergy research, from ancient civilizations to modern pharmacology, highlights the ongoing quest to understand and harness synergistic interactions. Key concepts such as concentration-response curves, additive effects, and predictive models are discussed in detail, emphasizing the need for accurate assessment methods throughout translational drug development. While various mathematical models exist for synergy analysis, selecting the appropriate model and software tools remains a challenge, necessitating careful consideration of experimental design and data interpretation. Furthermore, this review addresses practical considerations in synergy assessment, including preclinical and clinical approaches, mechanism of action, and statistical analysis. Optimizing synergy requires attention to concentration/dose ratios, target site localization, and timing of drug administration, ensuring that the benefits of combination therapy detected at bench-side are translatable into clinical practice. Overall, the review advocates for a systematic approach to synergy assessment, incorporating robust statistical analysis, effective and simplified predictive models, and collaborative efforts across pivotal sectors such as academic institutions, pharmaceutical companies, and regulatory agencies. By overcoming critical challenges and maximizing therapeutic potential, effective synergy assessment in drug development holds promise for advancing patient care. Significance Statement Combining drugs with different mechanisms of action for synergistic interactions optimizes treatment efficacy and safety. Accurate interpretation of synergy requires the identification of the expected additive effect. Despite innovative models to predict the additive effect, consensus in drug interaction research is lacking, hindering the bench-to-bedside development of combination therapies. Collaboration among science, industry, and regulation is crucial for advancing combination therapy development, ensuring rigorous application of predictive models in clinical settings.

Asthma management with triple ICS/LABA/LAMA combination to reduce the risk of exacerbation: an umbrella review compliant with the PRIOR statement.

INTRODUCTION: According to Global Initiative for Asthma (GINA) guidelines, long-acting muscarinic antagonists (LAMAs) should be considered as add-on therapy in patients with asthma that remains uncontrolled, despite treatment with medium-dose (MD) or high-dose (HD) inhaled corticosteroids (ICS)/long-acting ß2-agonist (LABA) combinations. In patients ≥ 18 years, LAMA may be added in triple combination with an ICS and a LABA. To date, the precise efficacy of triple ICS/LABA/LAMA combination remains uncertain concerning the impact on exacerbation risk in patients with uncontrolled asthma. Therefore, an umbrella review was performed to systematically summarize available data on the effect of triple ICS/LABA/LAMA combination on the risk of asthma exacerbation. METHODS: An umbrella review has been performed according to the PRIOR statement. RESULTS: The overall results obtained from 5 systematic reviews and meta-analyses suggest that triple ICS/LABA/LAMA combination reduces the risk of asthma exacerbation. HD-ICS showed a greater effect particularly in reducing severe asthma exacerbation, especially in patients with evidence of type 2 inflammation biomarkers. CONCLUSIONS: The findings of this umbrella review suggest an optimization of ICS dose in triple ICS/LABA/LAMA combination, based on the severity of exacerbation and type 2 biomarkers expression.

Asthma remission one, none and one-hundred thousand: the relevance of the patient's view.

OBJECTIVE: Achieving remission in severe asthma holds paramount importance in elevating patient quality of life and reducing both individual and societal burdens associated with this chronic condition. This study centers on identifying pivotal patient-relevant endpoints through standardized, reproducible methods, while also developing a patient-centric definition of remission, essential for effective disease management. METHODS: A discrete choice experiment (DCE) was conducted to assess patients' perceptions on the four primary criteria for defining severe asthma remission, as outlined by the SANI survey. Additionally, it investigated the correlation between these perceptions and improvements in the doctor-patient therapeutic alliance during treatment decision-making. RESULTS: 249 patients (70% aged between 31-60, 59% women and 82% without other pathologies requiring corticosteroids) prioritize the use of oral corticosteroids (OCS, 48%) and the Asthma Control Test (ACT, 27%) in defining their condition, ranking these above lung function and exacerbations. This preference for OCS stems from its direct role in treatment, tangible tracking, immediate symptom relief, and being a concrete measure of disease severity compared to the less predictable and quantifiable exacerbations. CONCLUSIONS: This study explores severe asthma remission from patients' perspectives using clinician-evaluated parameters. The DCE revealed that most patients highly value OCS and the ACT, prefer moderate improvement, and avoid cortisone cycles. No definitive preference was found for lung function status. Integrating patient-reported information with professional insights is crucial for effective management and future research. Personalized treatment plans focusing on patient preferences, adherence, and alternative therapies aim to achieve remission and enhance quality of life.

Can glucagon-like peptide-1 receptor agonists induce asthma? An analysis of the FAERS database.

OBJECTIVE: Glucagon-like peptide-1 receptor agonists (GLP1RAs), originally developed for the treatment of type 2 diabetes mellitus, have attracted attention for their potential therapeutic benefits in asthma due to their anti-inflammatory properties and effects on airway smooth muscle function. However, concerns have been raised about the possibility of GLP1RAs inducing or exacerbating asthma symptoms. METHODS: We reviewed data from the US Food and Drug Administration's (FDA) adverse event (AE) reporting system (FAERS) to examine reports of cases of asthma observed in the real-world during treatment with GLP1RAs. RESULTS: Analysis of the FAERS reporting system database has shown that certain GLP1RAs, particularly exenatide, semaglutide and liraglutide, were associated with a higher proportion of respiratory AEs, particularly asthma or asthma-like events. This association was statistically significant at least for semaglutide and liraglutide. Serious asthma-related events and deaths were also reported, with exenatide having the highest proportion of deaths. CONCLUSIONS: The reasons for the observed differences in the AE profiles of the GLP1RAs remain unclear and may involve various factors such as pharmacological properties, patient characteristics and reporting biases. The complex interplay between the therapeutic benefits of GLP1RAs and the potential respiratory risks requires careful monitoring by clinicians, underpinned by ongoing research efforts to improve patient care and safety.

Cardiovascular events after exacerbations of chronic obstructive pulmonary disease: Results from the EXAcerbations of COPD and their OutcomeS in CardioVascular diseases study in Italy.

INTRODUCTION: Exacerbations of chronic obstructive pulmonary disease (COPD) can increase the risk of severe cardiovascular events. OBJECTIVE: Assess the crude incidence rates (IR) of cardiovascular events and the impact of exacerbations on the risk of cardiovascular events within different time periods following an exacerbation. METHODS: COPD patients aged ≥45 years between 01/01/2015 and 12/31/2018 were identified from the Fondazione Ricerca e Salute administrative database. IRs of severe non-fatal and fatal cardiovascular events were obtained for post-exacerbation time periods (1-7, 8-14, 15-30, 31-180, 181-365 days). Time-dependent Cox proportional hazard models compared cardiovascular risks between periods with and without exacerbations. RESULTS: Of 216,864 COPD patients, >55 % were male, mean age was 74 years, frequent comorbidities were cardiovascular, metabolic and psychiatric. During an average 34-month follow-up, 69,620 (32 %) patients had ≥1 exacerbation and 46,214 (21 %) experienced ≥1 cardiovascular event. During follow-up, 55,470 patients died; 4,661 were in-hospital cardiovascular-related deaths. Among 10,269 patients experiencing cardiovascular events within 365 days post-exacerbation, the IR was 15.8 per 100 person-years (95 %CI 15.5-16.1). Estimated hazard ratios (HR) for the cardiovascular event risk associated with periods post-exacerbation were highest within 7 days (HR: 34.3, 95 %CI: 33.1-35.6), especially for heart failure (HR 50.6; 95 %CI 48.6-52.7) and remained elevated throughout 365 days (HR 1.1, 95 %CI 1.02-1.13). CONCLUSIONS: COPD patients in Italy are at high risk of severe cardiovascular events following exacerbations, suggesting the need to prevent exacerbations and possible subsequent cardiovascular events through early interventions and treatment optimization.

An overview of the efficacy and safety of ß2-adrenoceptor antagonists for the treatment of chronic obstructive pulmonary disease.

INTRODUCTION: The safety of ß2-AR antagonists in the treatment of patients with COPD continues to be a topic of research and discussion within the medical community. Emerging evidence suggests potentially benefits in the management of this complex respiratory condition. However, antagonists that display a preference for ß2-AR over ß1-AR present a complex therapeutic challenge in COPD management, necessitating an understanding of differences in their pharmacological profiles and clinical implications. AREAS COVERED: An overview of the mechanisms of action of ß2-AR antagonists and their potential impact on respiratory function, their pharmacological interactions, clinical implications, and future perspectives in COPD. EXPERT OPINION: ß-Blockers have the potential to become a versatile class of therapeutic agents with benefits beyond their original cardiovascular use. However, the one-size-fits-all approach of prescribing ß-blockers regardless of their receptor selectivity to COPD patients with concomitant heart disease may not be appropriate. Instead, it is advisable to develop an individualized treatment strategy based on a thorough assessment of the patient's overall health. The use of non selective ß2-AR antagonists, functioning as inverse agonists at ß2-ARs, has garnered interest and debate, but further research efforts should focus on elucidating the optimal use of ß-AR antagonists in COPD, balancing cardiovascular benefits with potential respiratory risks to enhance outcomes and quality of life for individuals living with this debilitating respiratory condition.

Sustained Effectiveness of Benralizumab in Naïve and Biologics-Experienced Severe Eosinophilic Asthma Patients: Results from the ANANKE Study.

Purpose: Severe eosinophilic asthma (SEA) patients often present overlapping inflammatory features rendering them eligible for multiple biologic therapies; switching biologic treatment is a strategy adopted to optimize asthma control when patients show partial or no response to previous biologics. Patients and Methods: ANANKE is a retrospective, multicenter Italian study (NCT04272463). Here, we outline the characteristics and long-term clinical outcomes in naïve-to-biologics and biologics-experienced patients treated with benralizumab for up to 96 weeks. Bio-experienced patients were split into omalizumab and mepolizumab subsets according to the type of biologic previously used. Results: A total of 124 (76.5%) naïve and 38 (23.5%) bio-experienced patients were evaluated at index date; 13 patients (34.2%) switched from mepolizumab, 21 patients (55.3%) switched from omalizumab, and four patients (10.5%) received both biologics. The mepolizumab subset was characterized by the longest SEA duration (median of 4.6 years), the highest prevalence of chronic rhinosinusitis with nasal polyposis (CRSwNP) (76.5%), and the greatest oral corticosteroid (OCS) daily dosage (median of 25 mg prednisone equivalent). The omalizumab group showed the highest severe annual exacerbation rate (AER) (1.70). At 96 weeks, treatment with benralizumab reduced any and severe AER by more than 87% and 94%, respectively, across all groups. Lung function was overall preserved, with major improvements observed in the mepolizumab group, which also revealed a 100% drop of the median OCS dose. Asthma Control Test (ACT) score improved in the naïve group while its increment was more variable in bio-experienced patients; among these, a marked difference was noticed between omalizumab and mepolizumab subsets (median ACT score of 23.5 and 18, respectively). Conclusion: Benralizumab promotes durable and profound clinical benefits in naïve and bio-experienced groups, indicating that a nearly complete depletion of eosinophils is highly beneficial in the control of SEA, independently of previous biologic use.

Exacerbation Burden in COPD and Occurrence of Mortality in a Cohort of Italian Patients: Results of the Gulp Study.

Objective: To describe the burden of moderate to severe exacerbations and all-cause mortality; the secondary objectives were to analyze treatment patterns and changes over follow-up. Design: Observational, multicenter, retrospective, cohort study with a three year follow-up period. Setting: Ten Italian academic secondary- and tertiary-care centers. Participants: Patients with a confirmed diagnosis of COPD referring to the outpatient clinics of the participating centers were retrospectively recruited. Primary and Secondary Outcome Measures: Annualized frequency of moderate and severe exacerbations stratified by exacerbation history prior to study enrollment. Patients were classified according to airflow obstruction, GOLD risk categories, and divided in 4 groups: A = no exacerbations; B = 1 moderate exacerbation; C = 1 severe exacerbation; D = ≥2 moderate and/or severe exacerbations. Overall all-cause mortality stratified by age, COPD category, and COPD therapy. A logistic regression model assessed the association of clinical characteristics with mortality. Results: 1111 patients were included (73% males), of which 41.5% had a history of exacerbations. As expected, the proportion of patients experiencing ≥1 exacerbation during follow-up increased according to pre-defined study risk categories (B: 79%, C: 84%, D: 97.4%). Overall, by the end of follow-up, 45.5% of patients without a history of exacerbation experienced an exacerbation (31% of which severe), and 13% died. Deceased patients were significantly older, more obstructed and hyperinflated, and more frequently active smokers compared with survivors. Severe exacerbations were more frequent in patients that died (23.5%, vs 10.2%; p-value: 0.002). Chronic heart failure and ischemic heart disease were the only comorbidities associated with a higher odds ratio (OR) for death (OR: 2.2, p-value: 0.001; and OR: 1.9, p-value: 0.007). Treatment patterns were similar in patients that died and survivors. Conclusion: Patients with a low exacerbation risk are exposed to a significant future risk of moderate/severe exacerbations. Real life data confirm the strong association between mortality and cardiovascular comorbidities in COPD.

Systematic literature review of treatments used for refractory or unexplained chronic cough in adults.

BACKGROUND: Refractory or unexplained chronic cough (RCC or UCC) is difficult to manage and is usually treated by the off-label use of drugs approved for other indications. OBJECTIVE: The objectives of this systematic literature review (SLR) were to identify and characterize the current published body of evidence for the efficacy and safety of treatments for RCC or UCC. METHODS: The SLR was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The SLRs pre-defined population included patients ≥18 years of age who were diagnosed with chronic cough. The review was not restricted to any intervention type or study comparator, nor by timeframe. RESULTS: A total of 20 eligible publications from 19 unique trials were included. Seventeen of these trials were randomized controlled trials and most (14/17) were placebo-controlled. There was considerable variability between trials in the definition of RCC or UCC, participant exclusion and inclusion criteria, outcome measurement timepoints, and the safety and efficacy outcomes assessed. Several trials identified significant improvements in cough frequency, severity, or health-related quality of life measures while participants were on treatment, although these improvements did not persist in any of the studies that included a post-treatment follow-up timepoint. CONCLUSIONS: In the absence of an approved therapy, placebo remains the most common comparator in trials of potential RCC or UCC treatments. The between-study comparability of the published evidence is limited by heterogeneity of study design, study populations, and outcomes measures, as well as by concerns regarding study size and risk of bias.

Cardiovascular Events with the Use of Long-Acting Muscarinic Receptor Antagonists: An Analysis of the FAERS Database 2020-2023.

PURPOSE: This study aimed to examine reports of cardiovascular adverse events (CV AEs) observed in the real-world during treatment with aclidinium, tiotropium, glycopyrronium, and umeclidinium alone or in combination with a LABA and, in the context of triple therapy, with the addition of an ICS, and submitted to the food and drug administration adverse event reporting system (FAERS). METHODS: A retrospective disproportionality analysis was conducted utilizing CV AE reports submitted to the FAERS from January 2020 to 30 September 2023. Disproportionality was measured by calculating the reporting odds ratio. RESULTS: Compared with ipratropium, tiotropium was associated with fewer reports of CV AEs. Compared with tiotropium, other LAMAs were more likely to be associated with reports of CV AEs. Combinations of glycopyrronium with indacaterol or formoterol and umeclidinium with vilanterol significantly reduced reports of CV AEs compared with the respective LAMA. The addition of an ICS to these combinations further reduced the risk of CV AE reports. CONCLUSION: Our study suggests that inhaled LAMAs are not free from cardiac AE risks. This risk may be more evident when the newer LAMAs are used, but it is generally significantly reduced when COPD patients are treated with dual bronchodilators or triple therapy. However, these results do not prove that LAMAs cause CV AEs, as FAERS data alone are not indicative of a drug's safety profile. Given the frequency with which COPD and cardiovascular disease co-exist, a large study in the general population could shed light on this very important issue.

The Impact of Thermal Water in Asthma and COPD: A Systematic Review According to the PRISMA Statement.

BACKGROUND: Asthma and chronic obstructive pulmonary disease (COPD) are global health challenges leading to substantial morbidity and mortality. While existing guidelines emphasize evidence-based treatments, the potential therapeutic role of thermal water (TW) inhalation remains under-investigated. METHODS: This systematic review followed PRISMA-P guidelines and sought to evaluate the impact of TW in asthma and COPD. A thorough literature search, performed up to May 2023, encompassed in vitro, in vivo, randomized controlled trial (RCT), non-RCT, and observational studies. RESULTS: The review included 12 studies reporting different findings. In vitro studies suggested TW could enhance antioxidant capacity and cell proliferation. In a murine model of non-atopic asthma, TW inhalation reduced airway hyperresponsiveness and inflammation. RCTs in COPD patients indicated mixed effects, including improved quality of life, reduced airway oxidant stress, and enhanced exercise tolerance. Asthma patients exposed to water aerosols exhibited improved lung function and reduced airway inflammation. Non-RCTs showed improved lung function and antioxidant activity after TW therapy. Additionally, observational studies reported enhanced lung function and reduced airway inflammation. CONCLUSION: The current evidence suggests potential benefits of TW therapy in asthma and COPD. However, limited high-quality RCTs and concerns regarding occupational TW exposure necessitate further investigation. While TW therapy offers a non-invasive treatment, its therapeutic potential still needs definitive demonstration. Future research should therefore prioritize well-designed RCTs to thoroughly establish the efficacy and safety of TW as a potential therapeutic intervention for asthma and COPD.

Biologics for asthma and risk of pneumonia.

OBJECTIVE: Modification of the immune system with biologics raises theoretical concerns about the risk of infections but it is still unclear whether currently routinely used biologics in severe asthma may facilitate the development of pneumonia. Therefore, we aimed to determine whether omalizumab, mepolizumab, benralizumab, and dupilumab are associated with pneumonia in a real-world setting. METHODS: A retrospective disproportionality analysis was performed using adverse event (AE) reports submitted to FAERS from January 2020 to September 30, 2023. MedDRA was used to identify infections and infestations and then pneumonia cases. ROR and PRR were used to measure disproportionality. RESULTS: The percentage of reported cases of pneumonia compared to infections and infestations was highest for mepolizumab (36.8%), followed by omalizumab (32.6%), benralizumab (19.2%) and dupilumab (5.7%). We found a moderate or strong signal for increased risk of pneumonia with mepolizumab (ROR = 3.74, 95%CI 3.50-4.00), omalizumab (ROR = 3.26, 95%CI 3.06-3.49) and benralizumab (ROR = 2.65, 95%CI 2.49-2.83). CONCLUSIONS: Mepolizumab, omalizumab and benralizumab, but not dupilumab, were associated with high odds of reporting pneumonia. Our results represent only potential associations between these biologics and pneumonia but not causality. The nature of the FAERS database is such that the cause of the reported events is uncertain. Therefore, we can only roughly estimate the incidence of AEs by the signal strength (ROR value). Nevertheless, although causality could not be assessed, the signal from our study is interesting. We believe it deserves to be further substantiated by real-world studies with robust designs.

Investigational thymic stromal lymphopoietin inhibitors for the treatment of asthma: a systematic review.

INTRODUCTION: Severe asthma patients often remain uncontrolled despite high-intensity therapies. Biological therapies targeting thymic stromal lymphopoietin (TSLP), a key player in asthma pathogenesis, have emerged as potential options. Currently, the only TSLP inhibitor approved for the treatment of severe asthma is the immunoglobulin G (IgG) 2λ anti-TSLP monoclonal antibody (mAb) tezepelumab. AREAS COVERED: This systematic review assesses the efficacy and safety of investigational TSLP inhibitors across different stages of development for asthma treatment. EXPERT OPINION: TSLP contributes to airway inflammation, making it a pivotal therapeutic target. Ecleralimab, an inhaled antibody fragment antigen binding, shows promising evidence in enhancing efficacy and reducing systemic adverse events. SAR443765, with its NANOBODY® formulation and bispecific inhibition of TSLP and IL-13, offers improved tissue penetration and efficacy. The mAB TQC2731 exhibits high in vitro bioactivity, and the strength of the mAb UPB-101 is to act against the TSLP receptor. Some studies include mild and moderate asthma patients, suggesting the potential for extending biological therapy to non-severe patients. This systematic review highlights the potential of TSLP inhibitors as valuable additions to asthma treatment, even in milder forms of the disease. Future research and cost-reduction efforts are needed to expanding access to these promising therapies.

Spontaneous Ventilation Thoracoscopic Lung Biopsy in Undetermined Interstitial Lung Disease: Systematic Review and Meta-Analysis.

Thoracoscopic surgical biopsy has shown excellent histological characterization of undetermined interstitial lung diseases, although the morbidity rates reported are not negligible. In delicate patients, interstitial lung disease and restrictive ventilatory impairment morbidity are thought to be due at least in part to tracheal intubation with single-lung mechanical ventilation; therefore, spontaneous ventilation thoracoscopic lung biopsy (SVTLB) has been proposed as a potentially less invasive surgical option. This systematic review summarizes the results of SVTLB, focusing on diagnostic yield and operative morbidity. A systematic search for original studies regarding SVTLB published between 2010 to 2023 was performed. In addition, articles comparing SVTLB to mechanical ventilation thoracoscopic lung biopsy (MVTLB) were selected for a meta-analysis. Overall, 13 studies (two before 2017 and eleven between 2018 and 2023) entailing 675 patients were included. Diagnostic yield ranged from 84.6% to 100%. There were 64 (9.5%) complications, most of which were minor. There was no 30-day operative mortality. When comparing SVTLB to MVTLB, the former group showed a significantly lower risk of complications (p < 0.001), whereas no differences were found in diagnostic accuracy. The results of this review suggest that SVTLB is being increasingly adopted worldwide and has proven to be a safe procedure with excellent diagnostic accuracy.

Exercise-Induced Asthma: Managing Respiratory Issues in Athletes.

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.