Search Results (20)

Introduction: Asthma is a chronic airway inflammatory disease characterized by variable airflow limitation and intermittent symptoms. In well-controlled asthma, auscultation and spirometry often appear normal, making diagnosis challenging. Moreover, bronchial provocation tests carry a risk of inducing acute bronchoconstriction. This study aimed to develop a non-invasive, objective, and reproducible diagnostic method using machine learning-based lung sound analysis for the early detection of asthma, even during stable periods. Methods: We designed a machine learning algorithm to classify controlled asthma patients and healthy individuals using respiratory sounds recorded with a digital stethoscope. We enrolled 120 participants (60 asthmatic, 60 healthy). Controlled asthma was defined according to Global Initiative for Asthma (GINA) criteria and was supported by normal spirometry, no pathological auscultation findings, and no exacerbations in the past three months. A total of 3600 respiratory sound segments (each 3 s long) were obtained by dividing 90 s recordings from 120 participants (60 asthmatic, 60 healthy) into non-overlapping clips. The samples were analyzed using Mel-Frequency Cepstral Coefficients (MFCCs) and Tunable Q-Factor Wavelet Transform (TQWT). Significant features selected with ReliefF were used to train Quadratic Support Vector Machine (SVM) and Narrow Neural Network (NNN) models. Results: In 120 participants, pulmonary function test (PFT) results in the asthma group showed lower FEV1 (86.9 ± 5.7%) and FEV1/FVC ratios (86.1 ± 8.8%) compared to controls, but remained within normal ranges. Quadratic SVM achieved 99.86% accuracy, correctly classifying 99.44% of controls and 99.89% of asthma cases. Narrow Neural Network achieved 99.63% accuracy. Sensitivity, specificity, and F1-scores exceeded 99%. Conclusion: This machine learning-based algorithm provides accurate asthma diagnosis, even in patients with normal spirometry and clinical findings, offering a non-invasive and efficient diagnostic tool. Full article

Background/Objectives: The methacholine bronchial provocation test (MBPT) is a diagnostic test frequently used to evaluate airway hyper-reactivity. MBPT is essential for diagnosing asthma; however, it can be time-consuming and resource-intensive. This study aimed to develop an artificial intelligence (AI) model to predict the MBPT results using forced expiratory volume in one second (FEV₁) and bronchodilator test measurements from spirometry. Methods: a dataset of spirometry measurements, including Pre- and Post-bronchodilator FEV₁, was used to train and validate the model. Results: Among the evaluated models, the multilayer perceptron (MLP) achieved the highest area under the curve (AUC) of 0.701 (95% CI: 0.676–0.725), accuracy of 0.758, and an F1-score of 0.853. Logistic regression (LR) and a support vector machine (SVM) demonstrated comparable performance with AUC values of 0.688, while random forest (RF) and extreme gradient boost (XGBoost) achieved slightly lower AUC values of 0.669 and 0.672, respectively. Feature importance analysis of the MLP model identified key contributing features, including Pre-FEF_25–75 (%), Pre-FVC (L), Post FEV₁/FVC, Change-FEV₁ (L), and Change-FEF_25–75 (%), providing insight into the interpretability and clinical applicability of the model. Conclusions: These results highlight the potential of the model to utilize readily available spirometry data, particularly FEV₁ and bronchodilator responses, to accurately predict MBPT results. Our findings suggest that AI-based prediction can improve asthma diagnostic workflows by minimizing the reliance on MBPT and enabling faster and more accessible assessments. Full article

In patients with aspirin-exacerbated respiratory disease (AERD), there is disparate regulation of prostaglandin E2 (PGE₂) and prostaglandin D₂ (PGD₂). Both prostanoids are synthesised by cyclooxygenase 1 (COX-1) and cyclooxygenase 2 (COX-2). However, while the basal synthesis of PGE₂ tends to decrease, that of PGD₂ increases in patients with AERD. Furthermore, both behave differently in response to the inhibitory action of NSAIDs on COX-1: PGE₂ levels decrease while PGD₂ increases. Increased PGD₂ release correlates with nasal, bronchial, and extra-pulmonary symptoms caused by aspirin in AERD. The proposed hypothesis establishes that the answer to this paradoxical dissociation can be found in the airway epithelium. This is based on the observation that reduced COX-2 mRNA and/or protein expression is associated with reduced PGE₂ synthesis in cultured fibroblast and epithelial cells from AERD compared to patients with asthma who are aspirin-tolerant and healthy subjects. The low production of PGE₂ by the airway epithelium in AERD results in an excessive release of alarmins (TSLP, IL-33), which in turn contributes to activating group 2 innate lymphoid cells (ILC2s) and PGD₂ synthesis by mast cells and eosinophils. Aspirin, by further increasing the diminished PGE₂ regulation capacity in AERD, leads to respiratory reactions associated with the surge in PGD₂ from mast cells and eosinophils. In summary, the downregulation of COX-2 and the subsequent low production of PGE₂ by airway cells account for the apparently paradoxical increased production of PGD₂ by mast cells and eosinophils at the baseline and after aspirin provocation in patients with AERD. A better understanding of the role of the airway epithelium would contribute to elucidating the mechanism of AERD. Full article

Background: Obesity is a multi-organ system disease, which is associated with, e.g., a higher prevalence of non-alcoholic fatty liver disease (NAFLD) and asthma. Little is known regarding the effect of obesity-related parameters (including liver integrity) and the respiratory phenotype after a combination of physical activity and diet. Methods: Thirty-two C57BL/6 mice were, after 27 weeks of a high fat diet (HFD), randomly assigned to two dietary interventions for three weeks: a HFD or a normal chow diet (NCD). In both dietary groups, half of the animals were subjected to a sub-maximal exercise protocol. Lung function, lung inflammation, liver histology, and metabolic profile were determined. Results: Mice with obesity did not show airway hyperreactivity after methacholine provocation. Sub-maximal exercise with diet (NCD/E) induced a significant reduction in forced expiratory volume in 0.1 s after methacholine provocation. NCD/E had significantly more neutrophils and inflammation (IFN-γ, TNF-α, IL-4, and IL-17F) in bronchoalveolar lavage compared to non-exercising mice on a HFD (HFD/NE). However, more epithelial injury (serum surfactant protein D and IL-33) was seen in HFD/NE. Additionally, hepatic steatosis and fibrosis were reduced by combined diet and sub-maximal exercise. Conclusions: Combining sub-maximal exercise with diet induced airway hyperreactivity and pulmonary inflammation, while body weight, hepatic steatosis, and fibrosis improved. Full article

A high proportion of house dust mite (HDM)-allergic asthmatics suffer from both an early asthmatic reaction (EAR) and a late asthmatic reaction (LAR) which follows it. In these patients, allergic inflammation is more relevant. MiRNAs have been shown to play an important role in the regulation of asthma’s pathology. The aim of this study was to analyze the miRNA profile in patients with mild asthma and an HDM allergy after bronchial allergen provocation (BAP). Seventeen patients with EAR/no LAR and 17 patients with EAR plus LAR, determined by a significant fall in FEV1 after BAP, were differentially analyzed. As expected, patients with EAR plus LAR showed a more pronounced allergic inflammation and FEV1 delta drop after 24 h. NGS-miRNA analysis identified the down-regulation of miR-15a-5p, miR-15b-5p, and miR-374a-5p after BAP with the highest significance in patients with EAR plus LAR, which were negatively correlated with eNO and the maximum decrease in FEV1. These miRNAs have shared targets like CCND1, VEGFA, and GSK3B, which are known to be involved in airway remodeling, basement membrane thickening, and Extracellular Matrix deposition. NGS-profiling identified miRNAs involved in the inflammatory response after BAP with HDM extract, which might be useful to predict a LAR. Full article

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. Full article

In the last decade, e-cigarette usage has increased, with an estimated 82 million e-cigarette users globally. This is, in part, due to the common opinion that they are “healthier” than tobacco cigarettes or simply “water vapour”. Third-hand e-vapour exposure is the chemical residue left behind from e-cigarette aerosols, which is of concern due to its invisible nature, especially among young children. However, there is limited information surrounding third-hand e-vapour exposure. This study aimed to investigate the pulmonary effects of sub-chronic third-hand e-vapour exposure in a murine model. BALB/c mice (4 weeks of age) were exposed to a towel containing nicotine free (0 mg) e-vapour, nicotine (18 mg) e-vapour, or no e-vapour (sham) and replaced daily for 4 weeks. At the endpoint, lung function was assessed, and bronchoalveolar lavage fluid and lungs were collected to measure inflammation and fibrosis. Mice exposed to third-hand e-vapour without nicotine had alveolar enlargement compared to sham exposed controls. Mice exposed to third-hand e-vapour with nicotine had reduced bronchial responsiveness to provocation, increased epithelial thickening in large airways, increased epithelial layers in small airways, alveolar enlargement, and increased small airway collagen deposition, compared to sham exposed controls. In conclusion, our study shows that third-hand e-vapour exposure, particularly in the presence of nicotine, negatively affects the lung health of mice and highlights the need for greater public awareness surrounding the dangers of third-hand exposure to e-cigarette vapour. Full article

Background: Gold nanoparticles (AuNPs) can inhibit pivotal pathological changes in experimental asthma, but their effect on steroid-insensitive asthma is unclear. The current study assessed the effectiveness of nebulized AuNPs in a murine model of glucocorticoid (GC)-resistant asthma. Methods: A/J mice were sensitized and subjected to intranasal instillations of ovalbumin (OVA) once a week for nine weeks. Two weeks after starting allergen stimulations, mice were subjected to Budesonide or AuNP nebulization 1 h before stimuli. Analyses were carried out 24 h after the last provocation. Results: We found that mice challenged with OVA had airway hyperreactivity, eosinophil, and neutrophil infiltrates in the lung, concomitantly with peribronchiolar fibrosis, mucus production, and pro-inflammatory cytokine generation compared to sham-challenged mice. These changes were inhibited in mice treated with AuNPs, but not Budesonide. In the GC-resistant asthmatic mice, oxidative stress was established, marked by a reduction in nuclear factor erythroid 2-related factor 2 (NRF2) levels and catalase activity, accompanied by elevated values of thiobarbituric acid reactive substances (TBARS), phosphoinositide 3-kinases δ (PI3Kδ) expression, as well as a reduction in the nuclear expression of histone deacetylase 2 (HDAC2) in the lung tissue, all of which sensitive to AuNPs but not Budesonide treatment. Conclusion: These findings suggest that AuNPs can improve GC-insensitive asthma by preserving HDAC2 and NRF2. Full article

Asthma is a chronic inflammatory airway disease characterized by reversible airway obstruction and airway hyperreactivity. We proposed a cold dry air (CDA) provocation test and investigated its application in pediatric patients with asthma. We enrolled 72 children and adolescents older than 5 years who presented to our hospital with chronic cough, shortness of breath, and wheezing. We analyzed the results of allergy, pulmonary function, methacholine provocation, and CDA provocation tests. The FEV1 change 5 min after the provocation was recorded as CDA5 dFEV1; that after 15 min was recorded as CDA15 dFEV1. PT10 was the provocation time causing a 10% decrease in FEV1; a decrease of >10% in dFEV1 was considered a positive CDA test. Among the 72 subjects, 51 were diagnosed with asthma. A positive CDA test in patients with asthma correlated with non-eosinophilic asthma. In patients with asthma, sputum eosinophils and eosinophil cationic protein (ECP) levels of the patients with a positive CDA test were significantly lower than those of patients with a negative test. CDA5 dFEV1 correlated with PC20 and total immunoglobulin E. CDA15 dFEV1 correlated with PC20, sputum eosinophils, and ECP. PT10 became shorter as the peripheral blood eosinophil, FVC, FEV1, FEV1/FVC, and FEF25-75 decreased. The CDA provocation test showed airway hyperreactivity to non-specific stimuli, a high correlation with non-eosinophilic asthma, and the possibility of assessing asthma severity via PT10. Full article

Asthma is a complex syndrome associated with episodic decompensations provoked by aeroallergen exposures. The underlying pathophysiological states driving exacerbations are latent in the resting state and do not adequately inform biomarker-driven therapy. A better understanding of the pathophysiological pathways driving allergic exacerbations is needed. We hypothesized that disease-associated pathways could be identified in humans by unbiased metabolomics of bronchoalveolar fluid (BALF) during the peak inflammatory response provoked by a bronchial allergen challenge. We analyzed BALF metabolites in samples from 12 volunteers who underwent segmental bronchial antigen provocation (SBP-Ag). Metabolites were quantified using liquid chromatography-tandem mass spectrometry (LC–MS/MS) followed by pathway analysis and correlation with airway inflammation. SBP-Ag induced statistically significant changes in 549 features that mapped to 72 uniquely identified metabolites. From these features, two distinct inducible metabolic phenotypes were identified by the principal component analysis, partitioning around medoids (PAM) and k-means clustering. Ten index metabolites were identified that informed the presence of asthma-relevant pathways, including unsaturated fatty acid production/metabolism, mitochondrial beta oxidation of unsaturated fatty acid, and bile acid metabolism. Pathways were validated using proteomics in eosinophils. A segmental bronchial allergen challenge induces distinct metabolic responses in humans, providing insight into pathogenic and protective endotypes in allergic asthma. Full article

Fractional exhaled nitric oxide (FeNO) is a non-invasive test for evaluating the degree of airway inflammation and for the diagnosis, evaluation, and treatment of asthma. We attempted to measure FeNO levels in Korean children with asthma and determine its cutoff value for diagnosing asthma. We enrolled 176 children and adolescents between the ages of 5 and 18 years, who visited for the evaluation of chronic cough, shortness of breath, and wheezing. Among them, 138 patients who underwent skin prick tests or inhalation Immuno CAP (UniCAP; Pharmacia, Uppsala, Sweden) tests for allergy testing together with a pulmonary function test were included. FeNO was measured using a NIOX MINO (Aerocrine AB, Solna, Sweden) instrument according to the American Thoracic Society/European Respiratory Society (ATS/ERS) guidelines. There were 29 patients with asthma, 43 with rhinitis, and 38 with asthma and allergic rhinitis. In the asthma group, FeNO levels significantly correlated with total immunoglobulin E (r = 0.572, p < 0.001), but did not show significant correlation with pulmonary function test parameters (forced vital capacity—FVC, forced expiratory volume in one second—FEV1, FEV1/FVC) or PC20 (provocative concentration of methacholine causing a 20% fall in FEV1). The FeNO cutoff values obtained in the asthma and asthma rhinitis groups were 16.5 ppb and 18.5 ppb, respectively. Hence, we provide a FeNO cutoff value according to the presence or absence of rhinitis in pediatric patients with asthma. Full article

House dust mites (HDMs) are the allergenic sources most frequently involved in airway allergy. Nevertheless, not every sensitized patient develops respiratory symptoms upon exposure to HDM, and there is a clinical need to differentiate allergic asthmatics (AAs) from atopic non-allergic asthmatics with HDM sensitization. This differentiation sometimes requires in vivo provocations like the bronchial allergen challenge (BAC). Interestingly, recent data demonstrate that non-atopic patients with asthma can also develop positive BAC results. This novel phenotype has been termed local allergic asthma (LAA). The interest in identifying the allergic triggers of asthma resides in the possibility of administering allergen immunotherapy (AIT). AIT is a disease-modifying intervention, the clinical benefit of which persists after therapy discontinuation. Recently, new modalities of sublingual tablets of HDM immunotherapy registered as pharmaceutical products (HDM-SLIT tablets) have become commercially available. HDM-SLIT tablets have demonstrated a robust effect over critical asthma parameters (dose of inhaled corticosteroids, exacerbations, and safety), thus being recommended by international guidelines for patients with HDM-driven AA. In this review, we will summarize the current knowledge on the phenotype and endotype of HDM-driven AA, and LAA, address the difficulties for BAC implementation in the clinic, and discuss the effects of AIT in AA and LAA. Full article

Research has shown that cold air exercise causes significant respiratory dysfunction, especially in female athletes. However, how female and male athletes respond to cold air exercise is not known. Thus, we aimed to compare acute respiratory responses (function, recovery and symptoms) in males and females after high-intensity cold air exercise. Eighteen (nine female) athletes completed two environmental chamber running trials at 0 °C and −20 °C (humidity 34 ± 5%) on different days in a randomized starting order. Spirometry was performed pre, 3, 6, 10, 15 and 20 min post. Respiratory symptoms were measured posttrial and heart rate and rating of perceived exertion were assessed during each trial. No significant differences in delta change (pre to post) were found at either temperature between sexes for FEV₁, FVC, FEF50% and FEF25–75%. At −20 °C, FEV₁ decreased similarly in both sexes (males: 7.5%, females: 6.3%) but not at 0 °C, p = 0.003. Postexertion respiratory function recovery and reported symptoms were not different between sexes at either temperature. These results indicate no sex-based differences in acute respiratory responses (function, recovery and symptoms) to cold air exercise. However, intense exercise at −20 °C is challenging to the respiratory system in both sexes and may lead to altered respiratory responses compared to mild winter conditions like 0 °C. Full article

Neurotensin (NT) demonstrates ambiguous activity on inflammatory processes. The present study was undertaken to test the potential anti-inflammatory activity of NT in a murine model of non-atopic asthma and to establish the contribution of NTR1 receptors. Asthma was induced in BALB/c mice by skin sensitization with dinitrofluorobenzene followed by intratracheal hapten provocation. The mice were treated intraperitoneally with NT, SR 142948 (NTR1 receptor antagonist) + NT or NaCl. Twenty-four hours after the challenge, airway responsiveness to nebulized methacholine was measured. Bronchoalveolar lavage fluid (BALF) and lungs were collected for biochemical and immunohistological analysis. NT alleviated airway hyperreactivity and reduced the number of inflammatory cells in BALF. These beneficial effects were inhibited by pretreatment with the NTR1 antagonist. Additionally, NT reduced levels of IL-13 and TNF-α in BALF and IL-17A, IL12p40, RANTES, mouse mast cell protease and malondialdehyde in lung homogenates. SR 142948 reverted only a post-NT TNF-α decrease. NT exhibited anti-inflammatory activity in the hapten-induced asthma. Reduced leukocyte accumulation and airway hyperresponsiveness indicate that this beneficial NT action is mediated through NTR1 receptors. A lack of effect by the NTR1 blockade on mast cell activation, oxidative stress marker and pro-inflammatory cytokine production suggests that other pathways can be involved, which requires further research. Full article

Chronic asthma is associated with progressive airway remodeling, which may contribute to declining lung function. An increase in matrix metalloproteinases-9 (MMP-9)/tissue inhibitor metalloproteinase-1 (TIMP-1) may indicate airway inflammation and bronchial injury. Bronchial biopsy specimens and alveolar macrophages (AMs) were obtained from patients with asthma under regular treatment with inhaled corticosteroids or combination therapy and normal subjects (n = 10). Asthmatics included those with a slow forced expiratory volume in one second (FEV₁) decline (<30 mL/year, n = 13) and those with a fast FEV₁ decline (≥30 mL/year, n = 8) in 5-year follow-up. Immunostaining expression of MMP-9 and TIMP-1 was detected in airway tissues. MMP-9 and TIMP-1 was measured from AMs cultured for 24 h. After the 5-year treatment, the methacholine airway hyperresponsiveness of the slow FEV₁ decline group was decreased, but that of the fast FEV₁ decline group was increased (PC₂₀, provocative concentration causing a 20% decrease in FEV₁, 3.12 ± 1.10 to 1.14 ± 0.34 mg/dL, p < 0.05). AMs of asthma with a fast FEV₁ decline released a higher level of MMP-9 (8.52 ± 3.53 pg/mL, p < 0.05) than those of a slow FEV₁ decline (0.99 ± 0.20 pg/mL). The MMP-9/TIMP ratio in the fast FEV₁ decline group (0.089 ± 0.032) was higher than that of the slow FEV₁ decline group (0.007 ± 0.001, p < 0.01). The annual FEV₁ decline in 5 years was proportional to the level of MMP-9 (r = 57, p < 0.01) and MMP-9/TIMP-1 ratio (r = 0.58, p < 0.01). The airways of asthma with greater yearly decline in FEV₁ showed an increased thickness of submucosa and strong expression of MMP-9. An increase in MMP-9 and MMP-9/TIMP-1 in airways or AMs could be indicators of chronic airway inflammation and contribute to a greater decline in lung function of patients with chronic asthma. Full article