Airway Narrowing Research Articles

Systolic and global right ventricular functions of children with bronchial asthma as compared with those of healthy controls using echocardiography: a single-centre cross-sectional observational study from Nigeria

BackgroundAsthma is the most prevalent chronic airway condition in children. It is characterised by hyperresponsiveness of the small airways leading to airway narrowing, which is usually reversible, with or without treatment. Asthma is known to cause right ventricular dysfunction, but not much is known of this effect among children with highest burden of asthma. The aim of this study is to compare the right ventricular functions of children with asthma, aged 6– ≤ 13 years, with those of their age and sex-matched apparently healthy control using transthoracic echocardiography. The systolic and global right ventricular functions were assessed using Tricuspid Annular Plane Systolic Function (TAPSE) and Tei index, respectively.ResultsSeventy cases and 68 controls were included in the final analysis of the results. The male-to-female ratios are 1.9:1 and 2:1 for the cases and controls, respectively, and their mean age were 8.82 (± 2.28) and 9.05 (2.50) years. There was no statistically significant difference between their sex (X2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${X}^{2}$$\\end{document}/P = 0.810/0.85) and their mean age (P = 0.554). The mean TAPSE of the cases (20.16 ± 2.15 mm) and the controls (20.28 ± 2.71 mm) did not differ significantly (P = 0.74), but the mean Tei index of the cases (0.56 ± 0.16) was significantly higher than that of the control (0.50 ± 0.10) (P = 0.007). Among the asthmatics, 17.1% (12/70) and 2.9% (2/70) had global and systolic RV dysfunctions, respectively; 2.9% (2/70) of the controls had RV global dysfunctions, but none had RV systolic dysfunction. The global dysfunction among the asthmatics was significantly associated with their age range and frequency of hospitalisation (X2\\documentclass[12pt]{minimal} \\usepackage{amsmath} \\usepackage{wasysym} \\usepackage{amsfonts} \\usepackage{amssymb} \\usepackage{amsbsy} \\usepackage{mathrsfs} \\usepackage{upgreek} \\setlength{\\oddsidemargin}{-69pt} \\begin{document}$${X}^{2}$$\\end{document} /p of 6.051/0.014 and 7.209/0.021, respectively), and significantly correlates with their Body Mass Index, and peripheral oxygen saturation (r/P of −0.236/0.049 and − 2.490/0.038, respectively). None of the participants had right ventricular systolic dysfunction.ConclusionThis study shows that asthmatic patients have global RV dysfunction, and it is suggested that better control of asthma would preserve cardiac function.

Fatal Nocturnal Stridor after Tracheostomy Decannulation in a Patient with Medullary Infarction and Vocal Cord Palsy

Nocturnal stridor, a high-pitched breathing sound during sleep, is one of the respiratory signs indicating airway narrowing. A 70-year-old man experienced life-threatening nocturnal stridor following tracheostomy decannulation after medullary infarction and vocal cord paralysis. This rare case highlights the importance of evaluating risk of sleep apnea and vocal cord function pre-decannulation to prevent serious complications.

Pharyngeal airway dimensions and hyoid bone position in children with class II malocclusion and sleep problems: A cross sectional study

ObjectiveTo evaluate the pharyngeal airway width and hyoid bone position in children with class II malocclusion and a positive history of sleep problems. Methods60 children aged 8–12 years with skeletal class II malocclusion were segregated into two groups according to the existence of sleep problems: 30 participants with sleep disorders constituted the study group, while 30 participants without sleep disorders formed the control group. Pharyngeal airway space and hyoid bone position were evaluated via a clinical and radiographic examination. ResultsA significantly narrower upper pharyngeal airway width and decreased C3-H hyoid parameter was noted in children with sleep problems (p = 0.035, 0.012). ConclusionBoth pharyngeal airway parameters and the hyoid bone parameters could be potential risk indicators while screening for sleep-disordered breathing in children.

Fingolimod, a sphingosine-1-phosphate receptor modulator, prevents neonatal bronchopulmonary dysplasia and subsequent airway remodeling in a murine model.

Neonatal bronchopulmonary dysplasia (BPD) is associated with alveolar simplification and airway remodeling. Airway remodeling leads to deformation of airways characterized by peribronchial collagen deposition and hypertrophy of airway smooth muscle, which contribute to the narrowing of airways. Poorly developed lungs contribute to reduced lung function that deteriorates with the passage of time. We have earlier shown that sphingosine kinase 1 (SPHK 1)/sphingosine-1-phosphate (S1P)/S1P receptor1 (S1PR1) signaling plays a role in the pathogenesis of BPD. In this study, we investigated the role of fingolimod or FTY720, a known S1PR1 modulator approved for the treatment of multiple sclerosis in the treatment of BPD. Fingolimod promotes the degradation of S1PR1 by preventing its recycling, thus serving as the equivalent of an inhibitor. Exposure of neonatal mice to hyperoxia enhanced the expression of S1PR1 in both airways and alveoli as compared with normoxia. This increased expression of S1PR1 in the airways persisted into adulthood, accompanied by airway remodeling and airway hyperreactivity (AHR) after neonatal hyperoxia. Intranasal fingolimod at a much lower dose compared with the intraperitoneal route of administration during neonatal hyperoxia improved alveolarization in neonates and reduced airway remodeling and AHR in adult mice associated with improved lung function. The intranasal route was not associated with the lymphopenia seen with the intraperitoneal route of administration of the drug. An increase in S1PR1 expression in the airways was associated with an increase in the expression of enzyme lysyl oxidase (LOX) in the airways following hyperoxia, which was suppressed by fingolimod. This association warrants further investigation.NEW & NOTEWORTHY The role of the S1P receptor1 modulator, fingolimod, as an FDA-approved drug in preventing the recurrence of multiple sclerosis is established. Fingolimod prevented bronchopulmonary dysplasia (BPD) and its sequela of airway remodeling in a neonatal murine model. This protection was associated with the downregulation of lysyl oxidase signaling pathway. Fingolimod could be repurposed for the therapy of BPD.

Knowledge, attitude, and practice of asthma among the adults in Shendi locality, Sudan: A cross-sectional study.

Asthma is a chronic inflammatory condition leading to intermittent airway narrowing and obstruction. Although millions suffer from asthma globally, there is limited data from African countries, particularly Sudan. This study addresses the gap in research on asthma knowledge, attitudes, and practices among the adults in Shendi locality, Northern Sudan. This cross-sectional, community-based study was conducted in Kabushiya village, Shendi, Sudan, involving 148 participants selected through multistage random sampling. Data were collected via face-to-face interviews using a validated, structured questionnaire. Statistical analyses included Mann-Whitney, Kruskal-Wallis, Chi-square, Fisher exact tests, and multiple linear regression. Participants demonstrated high levels of knowledge, positive attitudes, and good practices regarding asthma. Knowledge scores were significantly associated with marital status, education, occupation, and income (P values: .040, .003, .000, and .006, respectively), with the highest medians among divorced individuals, those with higher education, professional workers, and people earning <50,000 SDGs (medians: 17, 16, 17, and 16, respectively). Attitude scores varied significantly by marital status, education, occupation, and family asthma history (P values: .001, .000, .003, and .016, respectively), with highest scores among divorced individuals, those with high school or higher education, professionals, and those with a first-degree relative with asthma (medians: 6, 5, 5, and 5, respectively). Patient practice scores differed by marital status and income (P values: .026 and .006, respectively), with higher scores among singles and those earning <50,000 SDGs. Co-patient practice scores were significantly influenced by occupation, personal or familial asthma experience, and family asthma status (P values: .026, .003, and .000, respectively). No significant differences were observed in co-patient practice scores between groups. The study highlights a generally good level of asthma knowledge and positive attitudes among participants, with some variability in practices based on socio-demographic factors. These findings emphasize the need for targeted education and intervention programs to improve asthma management in rural Sudan.

Integrative Cross-Talk in Asthma: Unraveling the Complex Interactions Between Eosinophils, Immune, and Structural Cells in the Airway Microenvironment.

Asthma is a chronic inflammatory process that leads to airway narrowing, causing breath loss followed by spasms, wheezing, and shortness of breath. Within the asthmatic lungs, interaction among various immune cells and structural cells plays a significant role in orchestrating an inflammatory response in which eosinophils hold central importance. In these settings, allergens or other environmental exposures commonly drive the immune response to recruit eosinophils to the airways. The appearance of eosinophils in the airways indicates a dynamic interplay of various cell types within lung tissue and does not represent a passive effect of inflammation. The cellular cross-talk causes the persistence of eosinophilic inflammation, and if left untreated, it results in long-term damage to the airway structure and function. Further exacerbation of the condition occurs because of this. We discuss how this complex interplay of eosinophils, immune, and structural cells within the airway microenvironment leads to the distinct pathophysiological features in asthma, the variability in disease severity, and the response to biological treatments.

Automated CT-based Decoupling of the Effects of Airway Narrowing and Wall Thinning on Airway Counts in Chronic Obstructive Pulmonary Disease.

We examine pathways of airway alteration due to wall thinning, narrowing, and obliteration at different COPD severity stages using CT-derived airway metrics. Ex-smokers (N = 649; age mean±std: 69 ± 6years; 52% male) from the COPDGene Iowa cohort (September 2013-July 2017) were studied. Total airway count (TAC), peripheral TAC beyond 7th generation (TACp), and airway wall thickness (WT) were computed from chest CT scans using previously validated automated methods. Causal relationships among demographic, smoking, spirometry, COPD severity, airway counts, WT, and scanner variables were analyzed using causal inference techniques including direct acyclic graphs (DAGs) to quantitatively assess multi-pathway alterations of airways in COPD. TAC, TACp, and WT were significantly lower (p < 0.0001) in mild, moderate, and severe COPD compared to the preserved lung function group. TAC (TACp) losses attributed to narrowing and obliteration of small airways were 4.59, 13.29, and 32.58% (4.64, 17.82, and 45.51%) in mild, moderate, and severe COPD, while the losses attributed to wall thinning were 8.24, 17.01, and 22.95% (12.79, 25.66, and 33.95%) in respective groups. Different pathways of airway alteration in COPD are observed using CT-derived automated airway metrics. Wall thinning is a dominant contributor to both TAC and TACp loss in mild and moderate COPD while narrowing and obliteration of small airways is dominant in severe COPD. This automated CT-based study shows that wall thinning dominates airway alteration in mild and moderate COPD while narrowing and obliteration of small airways leads the alteration process in severe COPD.

Atelectasis After Bilateral Costal Cartilage Ear Reconstruction.

This study, through the case analysis of 2 patients with congenital bilateral microtia, explores the causes and preventive strategies of atelectasis after bilateral rib cartilage extraction surgery. Although ear reconstruction technology is quite mature, it may lead to complications, such as atelectasis, due to thoracic surgery and general anesthesia. Pediatric patients are more prone to such complications due to narrower airways, less pulmonary surfactant, and difficulties in pain management. Therefore, for children undergoing bilateral rib cartilage extraction surgery, health care providers need to closely monitor their respiratory status, effectively manage postoperative pain, and encourage them to engage in deep breathing and coughing exercises as much as possible to prevent and improve atelectasis.

Phytotherapeutic BS012 and Its Active Component Ameliorate Allergic Asthma via Inhibition of Th2-Mediated Immune Response and Apoptosis.

Asthma is a chronic inflammatory disorder of the lungs that results in airway inflammation and narrowing. BS012 is an herbal remedy containing Asarum sieboldii, Platycodon grandiflorum, and Cinnamomum cassia extracts. To elucidate the anti-asthma effect of BS012, this study analyzed the immune response, respiratory protection, and changes in metabolic mechanisms in an ovalbumin-induced allergic asthma mouse model. Female BALB/c mice were exposed to ovalbumin to induce allergic asthma. Bronchoalveolar lavage fluid and plasma were analyzed for interleukin and immunoglobulin E levels. Histological analyses of the lungs were performed to measure morphological changes. Apoptosis-related mediators were assayed by western blotting. Plasma and lung tissue metabolomic analyses were performed to investigate the metabolic changes. A T-helper-2-like differentiated cell model was used to identify the active components of BS012. BS012 treatment improved inflammatory cell infiltration, mucus production, and goblet cell hyperplasia in lung tissues. BS012 also significantly downregulated ovalbumin-specific immunoglobulin E in plasma and T-helper-2-specific cytokines, interleukin-4 and -5, in bronchoalveolar lavage fluid. The lungs of ovalbumininhaled mice exhibited nerve growth factor-mediated apoptotic protein expression, which was significantly attenuated by BS012 treatment. Ovalbumin-induced abnormalities in amino acid and lipid metabolism were improved by BS012 in correlation with its anti-inflammatory properties and normalization of energy metabolism. Additionally, the differentiated cell model revealed that N-isobutyl-dodecatetraenamide is an active component that contributes to the anti-allergic properties of BS012. The current findings demonstrate the anti-allergic and respiratory protective functions of BS012 against allergic asthma, which can be considered a therapeutic candidate.

The airway smooth muscle and the pipe dream of better bronchodilators.

Research on airway smooth muscle has traditionally focused on its putative detrimental role in asthma, emphasizing on how its shortening narrows the airway lumen, without much consideration about its potential role in subserving the function of the entire respiratory system. New experimental evidence on mice suggests that not only the smooth muscle is required to sustain life postnatally, but its stiffening effect on the lung tissue also protects against excessive airway narrowing and, most importantly, against small airway narrowing heterogeneity and closure. These results suggest that the smooth muscle plays an vital role in the lung periphery, essentially safeguarding alveolar ventilation by preventing small airway closure. These results also shed light on perplexing clinical observations, such as the long-standing doubts about the safety of bronchodilators. Since there seems to be an optimal level of smooth muscle contraction, at least in small airways, the therapeutic goal of maximizing the relaxation of the smooth muscle in asthma needs to be revisited. A bronchodilator with an excessive potency for inhibiting smooth muscle contraction, and that is still potent at concentrations reaching the lung periphery, may foster airway closure and air trapping, resulting in no net gain or even a decline in lung function.

Risk of Narrow Upper Airway in Class II Children with Large Horizontal Maxillary Overjet Assessed By Acoustic Reflection: a Case-Control Study

Risk of Narrow Upper Airway in Class II Children with Large Horizontal Maxillary Overjet Assessed By Acoustic Reflection: a Case-Control Study

Case report on tracheo-bronchial Stenting: A Rare procedure

In the expanding era of interventional medicine, tracheo-bronchial stenting has emerged as an exigent procedure with new ray of hope. The most common indications for stenting are to minimise extrinsic airway compression from mass effect, maintain airway patency due to intrinsic obstruction or treat significant nonmalignant airway narrowing or fistula. It plays an important role as a bridge to additional tumor-specific therapies, especially in chemoradiotherapy-naïve patients. Our patient, a 66-year-old lady with history of recurrent oesphageal carcinoma treated with chemotherapy, was suffering from increasing breathlessness with presence of stridor. Tracheo-bronchial stenting (Y-stenting) was done successfully in this patient to relieve her tracheal stenosis as observed in bronchoscopy. We report this case as it highlights the first ever Y-stenting in Bangladesh, might cultivate more feasibilty towards such intervention in different centres. Bangladesh J Medicine 2024; 35: 218-220

Airway Tapering in Chronic Obstructive Pulmonary Disease.

Luminal narrowing is a hallmark feature of airway remodeling in COPD, but current measures focus on airway wall remodeling. Quantification of the natural increase in cumulative cross-sectional area along the length of the human airway tree can facilitate assessment of airway narrowing. We analysed the airway trees of 7641 subjects enrolled in the multicenter COPDGene cohort. Airway luminal tapering was assessed by estimating the slope of the change in cumulative cross-sectional area along the length of the airway tree over successive generations (T-Slope). We performed multivariable regression analyses to test the associations between T-Slope and lung function, St. George's Respiratory Questionnaire (SGRQ), modified Medical Research Council (mMRC) dyspnea score, 6-minute walk distance (6 MWD), FEV1 change, exacerbations, and all-cause mortality after adjusting for demographics, %CT emphysema, and total airway count. The T-Slope decreased with increasing COPD severity: 2.69 (0.70) in nonsmokers and 2.33 (0.70), 2.11 (0.65), 1.78 (0.58), 1.60 (0.53), and 1.57 (0.52) in GOLD stages 0 through 4 respectively (Jonckheere-Terpstra p=0.04). On multivariable analyses, the T-Slope was independently associated with FEV1 (β=0.13 L, 95% CI 0.10 to 0.15, p<0.001), 6MWD (β=15.0 m, 95%CI 10.8 to 19.2, p<0.001), change in FEV1 (β=-4.50 ml·year-1, 95% CI -7.32 to -1.67; p=0.001), exacerbations (IRR=0.78, 95% CI 0.73 to 0.83, p<0.001), and mortality (HR=0.79, 95% CI 0.72 to 0.86, p<0.001). T-Slope is a measure of airway luminal remodeling and is associated with respiratory morbidity and mortality.

Characteristics of lung resistance and elastance associated with tracheal stenosis and intrapulmonary airway narrowing in ex vivo sheep lungs

BackgroundUnderstanding the characteristics of pulmonary resistance and elastance in relation to the location of airway narrowing, e.g., tracheal stenosis vs. intrapulmonary airway obstruction, will help us understand lung function characteristics and mechanisms related to different airway diseases.MethodsIn this study, we used ex vivo sheep lungs as a model to measure lung resistance and elastance across a range of transpulmonary pressures (5–30 cmH2O) and ventilation frequencies (0.125–2 Hz). We established two tracheal stenosis models by inserting plastic tubes into the tracheas, representing mild (71.8% lumen area reduction) and severe (92.1%) obstructions. For intrapulmonary airway obstruction, we induced airway narrowing by challenging the lung with acetylcholine (ACh).ResultsWe found a pattern change in the lung resistance and apparent lung elastance as functions of ventilation frequency that depended on the transpulmonary pressure (or lung volume). At a transpulmonary pressure of 10 cmH2O, lung resistance increased with ventilation frequency in severe tracheal stenosis, whereas in ACh-induced airway narrowing the opposite occurred. Furthermore, apparent lung elastance at 10 cmH2O decreased with increasing ventilation frequency in severe tracheal stenosis whereas in ACh-induced airway narrowing the opposite occurred. Flow-volume analysis revealed that the flow amplitude was much sensitive to ventilation frequency in tracheal stenosis than it was in ACh induced airway constriction.ConclusionsResults from this study suggest that lung resistance and apparent elastance measured at 10 cmH2O over the frequency range of 0.125-2 Hz can differentiate tracheal stenosis vs. intrapulmonary airway narrowing in ex vivo sheep lungs.

Effects of different masks on diaphragm motion in OSAS patients undergoing CPAP: results from an ultrasound-based proof of concept study.

Obstructive sleep apnea (OSA) is characterized by recurrent upper airway narrowing or collapse during sleep. Continuous positive airway pressure (CPAP) remains the preferred treatment in selected patients and masks' choice plays an important role for subsequent respiratory events' reduction. It is known that oronasal masks are not as effective at opening the upper airway compared to nasal ones. Thus, the objective of this study was to investigate differences in US-assessed diaphragmatic excursion (DE) using oronasal vs. nasal CPAP masks. This observational study included 50 OSA patients presenting a moderate to severe apnea-hypopneaindex and requiring CPAP treatment. All participants received US evaluations on diaphragm motion during their oronasal and nasal CPAP trial at equal positive end-expiratory pressure level. The difference of DE switching mask during CPAP was assessed by using the non-parametric Wilcoxon signed-rank test. A statistically significant increase in US- assessed DE was found when shifting from oronasal to nasal mask (p-value < 0.01). Linear regression models revealed that increased neck circumference and more severe AHI were associated with decreased DE when shifting to an oronasal mask. This study evaluated the acute impact on US-assessed DE after changing CPAP route from oronasal to nasal mask. Our results suggest that the nasal type should be the more suitable option for most patients with OSA, especially those with higher nasal circumference. Diaphragmatic motion throughout US may become a practical tool to help in the choice of the fittest mask in patients undergoing CPAP.

Managing Exercise-Induced Bronchoconstriction: A Comprehensive Review of Strategies for Athletes to Maintain Fitness and Health

Exercise-induced bronchoconstriction (EIB) significantly impacts athletes by impairing their performance and overall health. Characterized by airway narrowing during or after physical activity, EIB affects the quality of training and competition. This study employs a qualitative descriptive research model based on a comprehensive literature review to evaluate EIB management strategies in athletes. We systematically collected data from trusted scientific databases—Scopus, Science Direct, and Google Scholar—using keywords such as "Exercise-Induced Asthma," "Athlete," and "Sport." Relevant articles were identified, and key terms related to EIB management were reviewed. The data, including study designs, research objectives, sample sizes, and findings, were compiled and analyzed to determine effective management approaches. Key findings indicate that accurate diagnosis using spirometry and bronchial provocation tests is essential. Pharmacological management primarily involves inhaled corticosteroids (ICS) to reduce inflammation and control EIB, while short-acting beta agonists (SABAs) offer only temporary relief. Non-pharmacological strategies include avoiding triggers, implementing proper warm-up routines, and using breathing techniques. Supervised aerobic exercise programs were shown to improve cardiovascular fitness without worsening EIB symptoms. The study also reviewed the impact of environmental factors, such as air pollution and post-COVID-19 conditions, on EIB. Recommendations include personalized asthma action plans, training for coaches on environmental triggers, and exercising in controlled conditions. This study highlights the need for a holistic approach combining pharmacological and non-pharmacological methods to manage EIB effectively and maintain athletic performance. Further research is warranted to develop tailored strategies for athletes with EIB.

Major clinical results of orthognatic surgery in obstructive sleep apnea syndrome: a systematic review

Introduction: Obstructive sleep apnea involves obstruction or narrowing of an individual's airways during sleep and is associated with several comorbidities. Management can be surgical or non-surgical, and Phase II of the Stanford Protocol for surgical management involves maxillomandibular advancement. Objective: To conduct a concise systematic review to present the main considerations and clinical results of orthognathic surgery in obstructive sleep apnea syndrome. Methods: The PRISMA Platform systematic review rules were followed. The search was carried out from April to June 2024 in the Scopus, PubMed, Science Direct, Scielo, and Google Scholar databases. The quality of the studies was based on the GRADE instrument and the risk of bias was analyzed according to the Cochrane instrument. Results and Conclusion: 110 articles were found, 41 articles were evaluated and 23 were included in this systematic review. Considering the Cochrane tool for risk of bias, the global assessment resulted in 28 studies with a high risk of bias and 28 studies that did not meet GRADE. Most studies showed homogeneity in their results, with X2 =88.5% &gt;50%. Maxillomandibular advancement surgery is a successful treatment for obstructive sleep apnea, but there are still concerns about cosmetic results due to the major advances involved. Bimaxillary advancement osteotomy significantly increases oropharyngeal volume and contracted superficial areas, which remain stable between 6 months and 1 year postoperatively.

Management of Bronchial Asthma Through Herbo-Mineral Drugs

Ayurveda is ancient system of medicine and a holistic approach to prevent and treat illness by maintaining balance in body and mind to improve your health and vitality. Ayurveda is one of alternative way of treating illness, prevention and management of respiratory disorders. Nowadays respiratory disorders are the major health issue resulting primary cause of death and disability in the world. Asthma is a common respiratory problem increasing globally and affecting approximately 339 million people worldwide and 17.23 million people with an overall prevalence of 2.05% in India. Bronchial asthma is a heterogeneous disease, usually characterized by chronic inflammatory disease of the airway. It is defined by chronic respiratory problem characterized by hyper-responsiveness, inflammation and narrowing of airway resulting in cardinal symptoms cough, chest tightness, dyspnea and wheeze. Tamak swasa closely resembles to bronchial asthma. Swasa roga is major health problem affecting the Pranavaha srotas. According to Acharya Charak tamak swasa is Vata-Kaphaja Vyadhi which is originated from Pithasthan (Amashaya). The treatment of this disease is still unsatisfactory in modern medicine as the use of corticosteroids have many side effects and may lead to medicine dependency. Ayurveda is proven to be a boon for management of asthmatic patients (Tamak swasa). Our Ayurveda classics have explained a lot about signs and symptoms of asthma that has a direct correlation with Tamak swasa. So this is the need of the time that a direct, safe and holistic approach should be established to treat the disease with specific herbomineral formulations as mentioned in our Ayurveda classics.

Does Cardiac Computed Tomography In Patients With A Vascular Ring Add Diagnostic Value? Correlation Of Airway Narrowing With Symptoms And Utility Of Tracheal Area Measurements

Does Cardiac Computed Tomography In Patients With A Vascular Ring Add Diagnostic Value? Correlation Of Airway Narrowing With Symptoms And Utility Of Tracheal Area Measurements

AdipoRon, an adiponectin receptor agonist, modulates AMPK signaling pathway and alleviates ovalbumin-induced airway inflammation in a murine model of asthma

Asthma is a long-term disease that causes airways swelling and inflammation and in turn airway narrowing. AdipoRonis an orally active synthetic small molecule that acts as a selective agonist at theadiponectin receptor 1 and 2. The aim of the current study is to delineate the protective effect and the potential underlying mechanism ofadipoRon inairway inflammationinduced byovalbumin (OVA) in comparison withdexamethasone. Adult maleSwiss Albino micewere sensitized to OVA on days 0 and 7, then challenged with OVA on days 14, 15 and 16. AdipoRon was administered orally for 6 days starting from the 11th day till the 16th and 1 h prior to OVA in the challenge days. Obtained results from asthmatic control group showed a significant decrease in serum adiponectin concentration, an increase in inflammatory cell counts inthe bronchoalveolar lavage fluid(BALF), CD68 protein expression, inflammatory cytokine concentration and oxidative stress as well. Administration of adipoRon enhanced antioxidant mechanisms limiting oxidative stress by significantly increasing reduced glutathione (GSH) pulmonary content, decreasing serum lactate dehydrogenase (LDH) together with malondialdehyde (MDA) significant reduction in lung tissue. In addition, it modulated the levels of serum immunoglobulin E (IgE), pro-inflammatory cytokines tumor necrosis factor (TNF)-α, interleukin (IL)-4, IL-13, nuclear factor kappa B (NF-κB) and the anti-inflammatory one IL-10 improving lung inflammation as revealed by histopathological evaluation. Furthermore, lung tissue expression of nuclear factor erythroid 2-related factor (Nrf2) and 5′AMP-activated protein kinase (AMPK) were significantly increased adipoRon. Notably, results of adipoRon received group were comparable to those of dexamethasone group. In conclusion, our study demonstrates that adipoRon can positively modulate adiponectin expression with activation of AMPK pathway and subsequent improvement in inflammatory and oxidative signaling.