Montelukast is a selective cysteinyl leukotriene receptor 1 antagonist with an established, though nuanced, role in the management of asthma and allergic rhinitis. By inhibiting leukotriene-mediated signaling, montelukast targets a pathway involved in bronchoconstriction, mucus secretion, vascular permeability, eosinophil recruitment, cytokine release, and airway remodeling. Available evidence indicates that montelukast may reduce several markers of allergic inflammation, including fractional exhaled nitric oxide, peripheral and tissue eosinophilia, eosinophil-derived mediators, adhesion molecules, selected cytokines, and markers related to airway remodeling. These effects are most consistently demonstrated in asthma and allergic rhinitis, while evidence in chronic urticaria, atopic dermatitis, and other inflammatory conditions remains limited or exploratory. Montelukast's once-daily oral administration and age-adjusted pediatric formulations make it a practical option in selected children, particularly when inhaled therapy is difficult or adherence is problematic. However, montelukast should not be regarded as a direct substitute for corticosteroid-based anti-inflammatory therapy. Current evidence and guideline positioning support its use mainly as an add-on controller, or an alternative when more efficacious treatment is contraindicated. The benefit-risk balance is further shaped by concerns regarding neuropsychiatric adverse events, especially in children, although evidence remains heterogeneous. Current data show no increased risk of severe, diagnostically coded neuropsychiatric events, yet milder sleep-related and behavioral symptoms are consistently reported, so that caution and active monitoring remain warranted. Overall, montelukast remains a biologically plausible and clinically useful therapy, but its value depends on appropriate patient selection and realistic expectations of its anti-inflammatory potential.

Exercise-induced bronchoconstriction (EIB) is a common cause of exercise-related respiratory symptoms in athletes and is traditionally diagnosed by demonstrating airway narrowing following exercise or surrogate bronchoprovocation testing. Whilst this provides objective evidence of bronchoconstriction, it offers limited insight into the underlying pathophysiology of airway dysfunction.

The Venegas-Winkler model is a seminal model in asthma pathophysiology, providing both a conceptual and quantitative framework for extending a posited bistability between open and closed states at the level of the individual, terminal airway to the lung as a whole. In doing so, it offers an explanation for the characteristic ventilation heterogeneity (or clustered ventilation defects) seen in asthma. The terminal airway bistability is based on the Anafi-Wilson model, and this is embedded and extended into a symmetric bifurcating airway tree, in which an enforced tidal volume target and an imposed degree of airway smooth-muscle activation interact to generate spatially structured ventilation patterns. Here, we provide the first open-source implementation of the Venegas-Winkler bronchoconstriction cascade model and use it to identify several previously undescribed properties: both the tree depth and wall thickness assumptions affect the bifurcation onset, tidal volume and acinar elastance assumptions require careful interpretation for a model at sub-lung scale and airway geometry assumptions strongly affect driving pressures and bifurcation cascade characteristics.

Asthma is a heterogeneous chronic airway disease in which exercise may act both as a trigger of respiratory symptoms and as a beneficial non-pharmacological intervention. Training responses vary across exercise modalities and asthma phenotypes; inconsistent findings for lung function, airway inflammation, bronchial hyperresponsiveness (BHR), and exercise-induced bronchoconstriction (EIB) highlight the need for a mechanism-oriented framework. This review synthesizes current evidence on moderate-intensity continuous aerobic training, high-intensity interval training, resistance training, combined aerobic-resistance training, breathing exercises, mind-body exercise, and aquatic exercise from the perspective of their dominant ventilatory, metabolic, mechanical-muscular, respiratory-behavioral, and neuropsychological loads. These load characteristics interact with different asthma phenotypes and clinical-mechanistic traits, including type 2-high eosinophilic asthma, obesity-related or non-type 2 asthma, EIB-dominant asthma, severe asthma with physical deconditioning, and dysfunctional breathing or anxiety-related symptoms. Four key mechanistic axes are examined: the ventilatory load-airway epithelium-EIB axis, immune inflammation-BHR axis, skeletal muscle-metabolic-systemic inflammation axis, and respiratory behavior-autonomic regulation-symptom perception axis. Structured exercise training provides the strongest and most consistent benefits for exercise capacity, asthma control, symptoms, and health-related quality of life.,whereas effects on airway inflammation, BHR, lung function, and EIB remain heterogeneous and appear to depend more on baseline phenotype, disease control, environmental exposure, and training protocol. The proposed mechanism-informed framework is intended to support individualized exercise selection, risk stratification, and outcome monitoring rather than serve as a fixed phenotype-specific prescription algorithm.

Background: Children born preterm may have persistent alterations in airway function that extend into school age; however, exercise-induced bronchoconstriction (EIB) in this population remains insufficiently characterized. This study aimed to determine the prevalence of EIB in school-aged children born at ≤32 weeks of gestation and to investigate associated clinical and neonatal factors. Methods: This single-center cross-sectional study included 42 children born at ≤32 weeks of gestation who were evaluated at 7-8 years of age. Perinatal, neonatal, respiratory, and atopic characteristics were obtained from medical records and parental reports. Baseline spirometry was performed before a standardized treadmill exercise challenge. Spirometry was repeated at 5, 10, 15, and 30 min after exercise. EIB was defined as a ≥10% decrease in forced expiratory volume in one second (FEV1) from baseline at any post-exercise time point. Results: The median gestational age was 29 (25-32) weeks, and 31% had a history of bronchopulmonary dysplasia. EIB was identified in 13 of 42 children (31%). Post-exercise EIB positivity was observed at 5, 10, 15, and 30 min in 9.5%, 16.7%, 11.9%, and 9.5% of participants, respectively. Dyspnea was the most frequent exercise-related symptom (38%). No significant differences were observed between EIB-positive and EIB-negative children regarding gestational age, birth weight, bronchopulmonary dysplasia, neonatal respiratory support, baseline pulmonary function, total IgE, or peripheral eosinophil count. Conclusions: EIB was detected in approximately one-third of school-aged children born at ≤32 weeks of gestation. These findings suggest that clinically relevant exercise-related airway hyperresponsiveness may persist into school age despite relatively preserved baseline spirometry.

Background/Objectives: Exercise-induced bronchoconstriction (EIB) may persist despite apparently adequate asthma control and may remain unrecognized in children without prominent exercise-related symptoms. This study aimed to determine the prevalence of objectively confirmed EIB in children with controlled asthma who did not report prominent exercise-related respiratory symptoms and to identify factors associated with EIB. Methods: This cross-sectional study included 67 children with controlled asthma who underwent standardized exercise challenge testing with serial spirometry. Demographic, environmental, allergic, laboratory, aeroallergen sensitization, and baseline pulmonary function characteristics were evaluated. Children were classified as EIB-positive or EIB-negative according to their post-exercise FEV1 response. Factors associated with EIB were assessed using univariate analyses and multivariable logistic regression. Results: EIB was identified in 24 of 67 children (35.8%). Baseline pulmonary function was generally preserved and did not differ significantly between EIB-positive and EIB-negative children. A history of atopic eczema was more frequent in the EIB-positive group (37.5% vs. 14.0%; p = 0.035). Allergic rhinitis, food allergy, total IgE, eosinophil percentage, and aeroallergen sensitization were not significantly associated with EIB. In multivariable logistic regression, a history of atopic eczema remained associated with EIB (adjusted odds ratio, 3.95; 95% CI, 1.08-14.41; p = 0.038), although the wide confidence interval indicates substantial uncertainty in the effect estimate. Conclusions: EIB was objectively detected in more than one-third of children with controlled asthma without prominent exercise-related symptoms despite preserved baseline pulmonary function. A history of atopic eczema may help identify children with persistent susceptibility to exercise-induced airway narrowing who might otherwise remain unrecognized.

Background: Gastroesophageal reflux and exercise-induced bronchoconstriction (EIB) commonly coexist with asthma, but the effect of exercise on reflux remains unclear. We aimed to assess the prevalence of abnormal impedance-detected acid exposure in children with partially controlled or uncontrolled asthma, its association with EIB, and changes in reflux parameters after an exercise challenge test (ECT). Methods: Thirty patients aged 7-18 years underwent spirometry, treadmill ECT, and 48 h multichannel intraluminal impedance-pH monitoring. EIB was defined as a ≥10% fall in FEV1, and abnormal acid exposure as impedance-detected acid reflux lasting ≥1.2% of recording time. Results: Abnormal acid exposure was identified in 14/30 patients (46.7%), whereas EIB occurred in 6/30 (20.0%), with no significant association between them. The absolute number of reflux episodes was higher after ECT in the count-based analysis (43.0 [35.2-69.8] vs. 33.5 [21.2-54.5], p = 0.006); however, this finding was not confirmed after normalization to analyzable recording time in a sensitivity analysis. Overweight or obesity was present in 9 patients (30.0%) and correlated positively with acid exposure. BMI-for-age z-score correlated positively with acid exposure (ρ = 0.41, p = 0.025), but these findings did not remain significant after correction for multiple testing. Conclusions: Using the prespecified acid-exposure criterion, abnormal acid exposure was frequently identified in this cohort. No statistically significant association with EIB was demonstrated; however, the small number of EIB events limits definitive conclusions. The higher absolute post-ECT reflux episode count was not confirmed in a rate-based sensitivity analysis, and a causal effect of exercise on reflux cannot be established.

Asthma is a chronic inflammatory respiratory disorder characterized by airway hyperresponsiveness, oxidative stress, and recurrent bronchoconstriction. Conventional treatment with β2- agonists such as salbutamol provides rapid symptomatic relief through bronchodilation; however, it does not adequately address the underlying inflammation and oxidative damage associated with disease progression. Spirulina, a nutrient-rich cyanobacterium, possesses significant antioxidant, antiinflammatory, and immunomodulatory properties that may complement the pharmacological effects of salbutamol. This review explores the potential of combining salbutamol and spirulina as a novel dual-acting therapeutic strategy for asthma management. The proposed synergistic mechanism involves immediate bronchodilation mediated through β2-adrenergic receptor stimulation by salbutamol, alongside spirulina-mediated modulation of inflammatory cytokines, inhibition of eosinophilic infiltration, and reduction of oxidative stress. Preclinical findings and limited clinical evidence suggest that spirulina supplementation may improve pulmonary function and decrease inflammatory biomarkers in individuals with asthma. In addition, the review discusses formulation and delivery considerations that may influence the therapeutic effectiveness of this combination approach. Although preliminary evidence supports the potential benefits of combining pharmacological and nutraceutical interventions, large-scale randomized clinical trials are required to establish efficacy, optimize dosing strategies, and evaluate long-term safety. Overall, the integration of spirulina with salbutamol may represent a promising adjunctive strategy and a potential paradigm shift in comprehensive asthma management.

Anaphylaxis is a severe systemic hypersensitivity reaction characterized by rapid onset, unpredictable clinical course, and potentially fatal outcomes. Although its diagnosis remains primarily clinical, the identification of biomarkers capable of improving risk stratification and understanding disease mechanisms remains an important unmet need. Among the mediators implicated in anaphylaxis, platelet-activating factor (PAF) has emerged as a key effector molecule involved in vascular permeability, bronchoconstriction, platelet activation, and cardiovascular dysfunction. The biological activity of PAF is tightly regulated by platelet-activating factor acetylhydrolase (PAF-AH), the enzyme responsible for its degradation, making the PAF-PAF-AH axis a potentially important determinant of reaction severity. OBJECTIVES: The present review summarizes current knowledge regarding the biology of PAF and PAF-AH and examines their role in the pathophysiology of anaphylaxis, with particular emphasis on Hymenoptera venom allergy (HVA). The therapeutic potential of targeting the PAF pathway is also discussed. Experimental and clinical evidence consistently suggests an association between increased PAF activity, reduced PAF-AH activity, and more severe anaphylactic reactions. However, methodological limitations, biological variability, and conflicting findings across studies currently limit the clinical applicability of these molecules as standalone biomarkers. Overall, the PAF-PAF-AH axis represents a biologically plausible link between molecular mechanisms and clinical severity in anaphylaxis. Further studies are required to standardize measurements, validate clinical utility, and define the role of this pathway as both a biomarker and therapeutic target; hence gaining insight into PAF's role in various biological processes is critical.

The parasympathetic efferent innervation to the respiratory airways controls bronchoconstriction and mucus secretion. It is known that the parasympathetic respiratory motoneurones (PRMNs) projecting to the airways are located in the nucleus ambiguus (NA) and dorsal motor nucleus of the vagus (DMV). Although NA PRMNs are known to regulate bronchoconstriction in both physiological and pathological conditions, the electrophysiological properties of DMV PRMNs and their functional role in regulating the airways are not entirely clear. Retrograde labelling, neuronal and ventilatory recordings, optogenetics, chemogenetics, and histological and molecular analyses in vitro and in vivo preparations of rats were performed to evaluate the electrophysiological characteristics controlling the activity of DMV PRMNs and their role in airway mucus secretion. DMV PRMNs present K[+]-dominated leak currents, mediated by two-pore domain TWIK-2 channels, which regulate their resting membrane potential, firing frequency and excitation by acidosis. Acidosis also reduces synaptic inhibition to these motoneurones and activates astrocytes in the DMV. Furthermore, optogenetic activation of astrocytes induced action potentials in DMV PRMNs, mediated by glutamatergic NMDA receptor excitation. Finally, chemogenetic activation of DMV PRMNs evoked mucus secretion in respiratory airways and increases sighing, without affecting inflammatory cell infiltration, pulmonary ventilation, oxygen consumption or heart rate. Therefore, our data demonstrate that TWIK-2 leak channels and astrocytes signalling regulate the activity of DMV PRMNs and their role in airway mucus secretion of rats. KEY POINTS: Parasympathetic respiratory motoneurones (PRMNs) of the dorsal motor nucleus of the vagus (DMV) present K+-dominated leak currents, mediated by TWIK-2 channels, regulating their resting membrane potential, firing frequency and excitation by acidosis. Acidosis also reduces synaptic inhibition to DMV PRMNs and activates astrocytes in the DMV. Activation of DMV astrocytes induced action potentials in PRMNs, mediated by glutamatergic NMDA receptor excitation. Activation of DMV PRMNs evoked mucus secretion in respiratory airways and increased sighing, without affecting pulmonary ventilation, oxygen consumption or heart rate. TWIK-2 leak channels and astrocytes signalling regulate the activity of DMV PRMNs and their role in airway mucus secretion of rats.