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The Journal of Allergy and Clinical... Apr 2024Prevention of asthma exacerbations and reduction of systemic corticosteroid burden remain unmet needs in asthma. US asthma guidelines recommend concomitant short-acting...
Prevention of asthma exacerbations and reduction of systemic corticosteroid burden remain unmet needs in asthma. US asthma guidelines recommend concomitant short-acting β-agonist (SABA) and inhaled corticosteroid (ICS) as an alternative reliever at step 2. The Food and Drug Administration approved a pressurized metered-dose inhaler containing albuterol and budesonide for as-needed treatment or prevention of bronchoconstriction and for reducing exacerbation risk in patients with asthma aged ≥18 years. This combination is approved for use as a reliever with or without maintenance therapy, but it is not indicated for maintenance therapy (or for single maintenance and reliever therapy). Intervening with as-needed SABA-ICS during the window of opportunity to reduce inflammation during loss of asthma control can reduce exacerbation risk, by exerting both genomic and nongenomic anti-inflammatory effects. We propose that the use of albuterol-budesonide rather than albuterol as a reliever to manage episodic symptoms driven by acute bronchoconstriction and airway inflammation can improve outcomes. This combination approach, shown to decrease asthma exacerbations and oral corticosteroid burden in patients with moderate-to-severe asthma, represents a paradigm shift for asthma treatment in the United States. Further safety and efficacy studies should provide evidence that this type of reliever should be standard of care.
Topics: Humans; Adolescent; Adult; Budesonide; Albuterol; Anti-Asthmatic Agents; Ethanolamines; Asthma; Adrenal Cortex Hormones; Administration, Inhalation; Inflammation; Formoterol Fumarate; Bronchodilator Agents
PubMed: 38316182
DOI: 10.1016/j.jaip.2024.01.043 -
Scientific Reports Jan 2024Vilanterol is a once-daily dose inhaler prescribed for asthma and chronic obstructive pulmonary disease. This study involved an investigation of vilanterol stability...
Vilanterol is a once-daily dose inhaler prescribed for asthma and chronic obstructive pulmonary disease. This study involved an investigation of vilanterol stability under acidic, basic, oxidative, thermal, and photolytic stress conditions. UPLC method was developed and validated for the analysis of vilanterol with its degradants. The drug was stable under photolytic and thermal stress conditions and degraded under acidic, basic, and oxidative stress conditions. Degradation kinetics was performed for acidic, basic and oxidative stress conditions. Kinetics parameters, K, half-life time (t) and shelf-life time (t) were assessed, and the degradation followed first order reaction. The method was linear from 0.10 to 100.00 µg mL with accuracy, inter-day and intra-day precision from 99.45 to 100.02%, 0.391-0.694 and 0.041-0.345, respectively. Mass spectrometry was employed to elucidate the structure of the degradants, and the results revealed that certain degradation products were comparable to vilanterol metabolites. The World Anti-Doping Agency has prohibited the presence of vilanterol and its metabolites in athletes' urine except for exercise bronchoconstriction with limited dose. So, quantification of vilanterol in the presence of its degradants was performed in human urine. The results revealed that the method was linear in range of 1.00 to 100.00 µg mL. Samples collection and experimental protocol was performed according to the guidelines of the Research Ethics Committee of the Faculty of Pharmacy, the British University in Egypt with approval No. CH-2305.
Topics: Humans; Chromatography, High Pressure Liquid; Drug Stability; Mass Spectrometry; Benzyl Alcohols; Chlorobenzenes
PubMed: 38286793
DOI: 10.1038/s41598-024-52664-6 -
Frontiers in Pediatrics 2023Evaluating oscillometry parameters separately for the inspiratory and expiratory breath phases and their within-breath differences can help to identify exercise-induced...
BACKGROUND
Evaluating oscillometry parameters separately for the inspiratory and expiratory breath phases and their within-breath differences can help to identify exercise-induced bronchoconstriction (EIB) in pediatric outpatients disclosing exercise-induced symptoms (EIS).
AIMS
To assess the response in impedance parameters following an exercise challenge in patients reporting EIS.
METHODS
Sixty-eight patients reporting EIS (34 asthmatics and 34 suspected of asthma, age mean = 10.8 years, range = 6.0-16.0) underwent an incremental treadmill exercise test. Spirometry was performed at baseline and 1, 5-, 10-, 15-, and 20-min post exercise. Oscillometry was performed at baseline and at 3- and 18-min post exercise. Bronchodilator response to 200 µg albuterol was then assessed. EIB was defined as a forced expiratory volume in 1 s (FEV) fall ≥10% from baseline. Expiratory and inspiratory resistance (Rrs) and reactance (Xrs), their -score (Ducharme et al. 2022), and their mean within-breath differences (ΔRrs = Rrs-Rrs, ΔXrs =Xrs-Xrs) were calculated. Receiver operating characteristic (ROC) curves and their areas (AUCs) were used to evaluate impedance parameters' performances in classifying EIB.
RESULTS
Asthmatic patients developed EIB more frequently than those suspected of asthma [18/34 (52.9%) vs. 2/34 (5.9%), < 0.001]. In the 20 subjects with EIB, Rrs, Rrs, Xrs, and Xrs peaked early (3'), and remained steady except for Xrs which recovered faster afterward. ΔXrs widened 18 min following the exercise and reversed sharply after bronchodilation (BD) (-1.81 ± 1.60 vs. -0.52 ± 0.80 cmHO × s/L, < 0.001). Cutoffs for EIB leading to the highest AUCs were a rise of 0.41 in -score Rrs (Se: 90.0%, Sp: 66.7%), and a fall of -0.64 in -score Xrs (Se: 90.0%, Sp: 75.0%). Accepting as having "positive" postexercise oscillometry changes those subjects who had both -scores beyond respective cutoffs, sensitivity for EIB was 90.0% (18/20) and specificity, 83.3% (40/48).
CONCLUSION
Oscillometry parameters and their within-breath differences changed markedly in pediatric patients presenting EIB and were restored after the bronchodilator. Strong agreement between -scores of inspiratory oscillometry parameters and spirometry supports their clinical utility, though larger studies are required to validate these findings in a broader population.
PubMed: 38274467
DOI: 10.3389/fped.2023.1324413 -
Frontiers in Pharmacology 2023Over 20 million adults and 6 million children in the United States (US) have asthma, a chronic respiratory disease characterized by airway inflammation,... (Review)
Review
Over 20 million adults and 6 million children in the United States (US) have asthma, a chronic respiratory disease characterized by airway inflammation, bronchoconstriction, and mucus hypersecretion. Obesity, another highly prevalent disease in the US, is a major risk factor for asthma and a significant cause of diminished asthma control, increased submucosal eosinophilia, and reduced quality of life. A large subgroup of these patients experiences severe symptoms and recurrent exacerbations despite maximal dosage of standard asthma therapies. In the past two decades, the development of biological therapies has revolutionized the field and advanced our understanding of type 2 inflammatory biomarkers. However, patients with obesity and comorbid asthma are not principally considered in clinical trials of biologics. Large landmark cluster analyses of patients with asthma have consistently identified specific asthma phenotypes that associate with obesity but may be differentiated by age of asthma onset and inflammatory cell profiles in sputum. These patterns suggest that biologic processes driving asthma pathology are heterogenous among patients with obesity. The biological mechanisms driving pathology in patients with asthma and comorbid obesity are not well understood and likely multifactorial. Future research needs to be done to elicit the cellular and metabolic functions in the relationship of obesity and asthma to yield the best treatment options for this multiplex condition. In this review, we explore the key features of type 2 inflammation in asthma and discuss the effectiveness, safety profile, and research gaps regarding the currently approved biological therapies in asthma patients with obesity.
PubMed: 38259298
DOI: 10.3389/fphar.2023.1315540 -
Journal of Functional Morphology and... Jan 2024Asthma is a complex respiratory condition characterized by chronic airway inflammation and variable expiratory airflow limitation, affecting millions globally. Among... (Review)
Review
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.
PubMed: 38249092
DOI: 10.3390/jfmk9010015 -
BMC Pulmonary Medicine Jan 2024Pulmonary air embolism (AE) and thromboembolism lead to severe ventilation-perfusion defects. The spatial distribution of pulmonary perfusion dysfunctions differs...
BACKGROUND
Pulmonary air embolism (AE) and thromboembolism lead to severe ventilation-perfusion defects. The spatial distribution of pulmonary perfusion dysfunctions differs substantially in the two pulmonary embolism pathologies, and the effects on respiratory mechanics, gas exchange, and ventilation-perfusion match have not been compared within a study. Therefore, we compared changes in indices reflecting airway and respiratory tissue mechanics, gas exchange, and capnography when pulmonary embolism was induced by venous injection of air as a model of gas embolism or by clamping the main pulmonary artery to mimic severe thromboembolism.
METHODS
Anesthetized and mechanically ventilated rats (n = 9) were measured under baseline conditions after inducing pulmonary AE by injecting 0.1 mL air into the femoral vein and after occluding the left pulmonary artery (LPAO). Changes in mechanical parameters were assessed by forced oscillations to measure airway resistance, lung tissue damping, and elastance. The arterial partial pressures of oxygen (PaO) and carbon dioxide (PaCO) were determined by blood gas analyses. Gas exchange indices were also assessed by measuring end-tidal CO concentration (ETCO), shape factors, and dead space parameters by volumetric capnography.
RESULTS
In the presence of a uniform decrease in ETCO in the two embolism models, marked elevations in the bronchial tone and compromised lung tissue mechanics were noted after LPAO, whereas AE did not affect lung mechanics. Conversely, only AE deteriorated PaO, and PaCO, while LPAO did not affect these outcomes. Neither AE nor LPAO caused changes in the anatomical or physiological dead space, while both embolism models resulted in elevated alveolar dead space indices incorporating intrapulmonary shunting.
CONCLUSIONS
Our findings indicate that severe focal hypocapnia following LPAO triggers bronchoconstriction redirecting airflow to well-perfused lung areas, thereby maintaining normal oxygenation, and the CO elimination ability of the lungs. However, hypocapnia in diffuse pulmonary perfusion after AE may not reach the threshold level to induce lung mechanical changes; thus, the compensatory mechanisms to match ventilation to perfusion are activated less effectively.
Topics: Animals; Rats; Carbon Dioxide; Hypocapnia; Thromboembolism; Perfusion; Pulmonary Embolism; Bronchi; Embolism, Air; Bronchoconstriction
PubMed: 38200483
DOI: 10.1186/s12890-024-02842-z -
ERJ Open Research Nov 2023Many athletes use short-acting inhaled β-agonists multiple times weekly during training sessions to prevent exercise-induced bronchoconstriction, but it is unclear if...
INTRODUCTION
Many athletes use short-acting inhaled β-agonists multiple times weekly during training sessions to prevent exercise-induced bronchoconstriction, but it is unclear if treatment impairs training outcomes. Herein, we investigated performance adaptations in well-trained females and males training with prior inhalation of salbutamol.
METHODS
19 females and 21 males with maximal oxygen uptake (') of 50.5±3.3 and 57.9±4.9 mL·min·kg, respectively, participated in this double-blinded, placebo-controlled, parallel-group study. We randomised participants to placebo or salbutamol inhalation (800-1600 µg·training day) for 6 weeks of combined endurance (1× per week) and high-intensity interval training (2× per week). We assessed participants' body composition, ' and muscle contractile function, and collected vastus lateralis muscle biopsies.
RESULTS
Salbutamol induced a sex-specific loss of whole-body fat mass (sex×treatment: p=0.048) where only salbutamol-treated females had a fat mass reduction compared to placebo (-0.8 kg at 6 weeks; 95% CI: -0.5 to -1.6; p=0.039). Furthermore, salbutamol-treated females exhibited a repartitioning effect, lowering fat mass while gaining lean mass (p=0.011), which was not apparent for males (p=0.303). Salbutamol negatively impacted ' in both sexes (treatment main effect: p=0.014) due to a blunted increase in ' during the initial 4 weeks of the intervention. Quadriceps contractile strength was impaired in salbutamol-treated females (-39 N·m; 95% CI: -61 to -17; p=0.002) compared to placebo at 6 weeks. Muscle electron transport chain complex I-V abundance increased with salbutamol (treatment main effect: p=0.035), while content of SERCAI, β-adrenoceptor and desmin remained unchanged.
CONCLUSION
Inhaled salbutamol appears to be an effective repartitioning agent in females but may impair aerobic and strength-related training outcomes.
PubMed: 38152086
DOI: 10.1183/23120541.00657-2023 -
The Journal of International Medical... Dec 2023Foreign body aspiration is relatively common in children, especially in children younger than 3 years, and it is associated with a high incidence and mortality rate....
Foreign body aspiration is relatively common in children, especially in children younger than 3 years, and it is associated with a high incidence and mortality rate. Because of impairments in swallowing, speech, and vision, more caution regarding foreign body aspiration is required in children with abnormal nervous system development. This report describes a clinically rare case involving a 6-year-old patient with delayed brain development and epilepsy who was found to have a tooth in the bronchus of the left lung through fiberoptic bronchoscopy. The tooth was successfully removed by an extraction procedure. A follow-up examination showed that the patient had a sequela of left lower lobe atelectasis. This case indicates that greater caution is necessary regarding foreign body aspiration, including dental aspiration, in patients with abnormal development of the nervous system.
Topics: Humans; Child; Foreign Bodies; Bronchi; Lung; Bronchoscopy; Pulmonary Atelectasis
PubMed: 38041829
DOI: 10.1177/03000605231215220 -
Toxicology Dec 2023Particulate matter (PM) has been associated with adverse effects on human health, causing allergies, skin and eye irritation and corrosion, respiratory tract irritation,...
Particulate matter (PM) has been associated with adverse effects on human health, causing allergies, skin and eye irritation and corrosion, respiratory tract irritation, headaches, bronchoconstriction, cardiopulmonary diseases such as asthma, chronic obstructive pulmonary disease (COPD), lung cancer, reproductive problems, premature deaths, and epigenetic changes that lead to a wide variety of cancers, among other health conditions. The air quality in the Medellín - Colombia presents fluctuations that oscillate between the maximum permissible levels established at the national level and by the WHO, which represents a latent risk to people's health. Although important efforts have been made to quantify the different levels of pollution and administrative measures have been established to mitigate air pollution, little research work has been done to establish the relationship between these levels of pollutants and the effects on biological systems. The objective of the present research was to make a morphological and chemical characterization of particulate matter (PM) captured with a commercial air filter and a electrospun nanofiber membrane and evaluate the cytotoxicity of the each PM extracts in monolayer and co-culture models which recreate microphysiological systems of lung, skin and cornea and propose the possible cellular interactions that lead the cytotoxic response of the chemical compounds found in particulate matter in cities. The morphology and elemental chemical characterization were done with scanning electron microscopy coupled with energy dispersive X-ray spectroscopy (SEM - EDS). For the polycyclic aromatic hydrocarbons detection was made with a chromatographic method accoupled to mass spectrometer. Finally, the cytotoxicity was made in monolayers of A549, HEK001, and SIRC cell lines and microphysiological systems consisting of two-cell layer construct to resemble the interaction between fibroblast and epithelial cells that comprises naturally the corneal, skin and lung tissue. We performed three different cocultures models with BALB/3T3 clone A31 as a feeder layer, using porous Transwell® inserts in the in-contact and non-contact way. Monolayer and co-culture models were exposed to coarse and fine PM (1, 2, and 5 mg/mL) and the cell viability was evaluated at 24 h using an MTT assay. The electrospun nanofibers membranes demonstrates higher efficiency to capture PM with different sizes and high concentration of polycyclic aromatic hydrocarbons, heavy metals, and other chemical compounds responsible of many human diseases. Cytotoxic effects of MP were observed in all models at higher concentration; however, models exposed to fine PM exhibited a significant reduction in cell viability compared to those exposed to coarse PM. In addition, multilayer models are more resistant to PM exposure than monolayer models. Furthermore, the study indicated that, depending on the seeding strategy, different results might be observed: the non-contact model showed higher resistance to PM exposure than in-contact for SIRC and HEK001, but A549 monolayers showed the highest viability response. This study demonstrates the usefulness of applying co-culture models to assess environmental pollutant toxicity, in addition to being a potential alternative method to animal testing for risk assessment.
Topics: Animals; Humans; Particulate Matter; Air Pollutants; Microphysiological Systems; Lung; Environmental Pollutants; Cornea; Polycyclic Aromatic Hydrocarbons
PubMed: 38029955
DOI: 10.1016/j.tox.2023.153685