Airway Collapse Research Articles

Preoperative Workup of Patients With Excessive Central Airway Collapse: Does Stent Evaluation Serve a Role?

Tracheobronchoplasty (TBP) is a definitive anatomic intervention for patients with severe symptomatic expiratory central airway collapse. Although stent evaluations have been described for surgical workup, current literature does not address if improvement during stent evaluation is sustained after TBP. We compared health-related quality of life (HRQOL) and functional status responses after airway stenting to those post-TBP. A retrospective review was performed in patients with severe expiratory central airway collapse who underwent stent evaluation followed by TBP from January 2004 to December 2019. Baseline, poststent, 3- and 12-month postoperative HRQOL scores, and functional status were analyzed with statistical tests as appropriate. One hundred twenty patients underwent a stent evaluation and TBP. Baseline and stent evaluation measurements were compared with statistically and clinically significant differences in the Cough Quality-of-life Questionnaire (CQLQ) (55 vs. 68, P <0.01), Modified Medical Research Council (mMRC) 0 to 2 (90% vs. 47%, P <0.01), 6-minute walk test (6MWT) (1301ft vs. 1138ft, P <0.01). Improvements in the HRQOL and functional status were maintained from stent evaluation to 3 months postoperatively [CQLQ 55 vs. 54, P =0.63; mMRC 0 to 2 (87% vs. 84%), P =0.39; 6MWT 1350ft vs. 1314ft, P =0.33], and 12 months postoperatively [CQLQ 54 vs. 54, P =0.91; mMRC 0 to 2 (95% vs. 86%), P =0.74; 6MWT 1409ft vs. 1328ft, P =0.13]. The magnitude of change between the data was not significantly different between the stent evaluation, 3-, and 12 months postoperative. Predicted forced expiratory volume in 1-second measurements at baseline, after stent placement, 3 months, and 12 months post-TBP were 74%, 79%, 73%, and 73%, respectively, and not clinically significant. Improvement after stent evaluation and the magnitude of improvement may be predictive of postoperative outcomes up to 1 year after surgery.

Indications for Dental Specialists for Treating Obstructive Sleep Apnea with Mandibular Advancement Devices: A Narrative Review.

Obstructive sleep apnea (OSA) syndrome is characterized by repeated airway collapse during sleep. It determines cardiovascular, pulmonary, and neurocognitive consequences and is associated with several daytime and nighttime symptoms that influence the patient's quality of life. The contribution of the dental specialist in the clinical management of OSA patients entails participating in the screening process as diagnostic sentinels and providing adequate treatment using mandibular advancement devices (MADs). Since the treatment of OSA requires a multidisciplinary approach, including different medical specialists, dentists should have a comprehensive understanding of medical and dental factors that influence the strategy and effectiveness of OSA treatment with MAD. Such expertise is crucial in determining the appropriate treatment indications and helps clinicians establish a consolidated position within the multidisciplinary OSA team. In this regard, this review summarizes the evidence of the clinical indications for MAD treatment and provides the dental specialist with helpful information about medical, functional, and other relevant factors that should be considered during diagnosis, treatment plan, and follow-up stages. Information retrieved was organized and discussed, generating specific domains/queries oriented to the clinical management of OSA patients from the clinical perspective of dental specialists.

Esophagus Dilation and Quality of Life in Adults with Scleroderma and Concomitant Obstructive Sleep Apnea.

(1) Background: Systemic sclerosis (SSc) is a rare systemic disease, which often affects the esophagus, leading to dilation and complications such as dysphagia and reflux. Obstructive sleep apnea (OSA) is a chronic condition with recurrent episodes of upper airway collapsibility and is known to impair quality of life (QoL). The primary aim of this study was to investigate the occurrence of esophagus dilation in patients with SSc and concomitant OSA and, further, to address the impact of these conditions on QoL. (2) Methods: In this cross-sectional cohort study, 62 consecutive patients with SSc underwent chest computer tomography (CT) and home sleep apnea testing. The OSA diagnosis was based on AHI ≥ 15 events/h. The QoL was quantified using the short-form (SF)-36 questionnaire. The patients were dichotomized as high- vs. low-esophageal-diameter groups, based on the median cut-off values. (3) Results: The mean age was 48 ± 11 years; 58 (93.5%) were female; the mean BMI was 26.7 ± 5.0 kg/m2. The median esophageal diameter was 17.47 mm. A larger esophageal diameter was more frequently associated with the diffuse cutaneous subtype of SSc (p = 0.002) and significantly higher Warrick scores (p < 0.001), indicating more severe pulmonary fibrosis. There was a significant linear correlation between the Warrick score and the esophageal diameter (standardized β coefficient 0.544 [%95 confidence interval 0.250-0.609]; p < 0.001). In the subgroup analysis, the patients with both OSA and enlarged esophageal diameter experienced a significant decline in QoL, particularly in the domains of physical functioning, role physical, general health, role emotional, and vitality. (4) Conclusions: While OSA was not directly associated with enlarged esophageal diameter in patients with SSc, those with both OSA and enlarged esophageal diameter exhibited a significant decline in QoL. These findings suggest that the presence of OSA may exacerbate the adverse effects of esophageal dilation on QoL in SSc patients. Our results underline the importance of considering both gastrointestinal and sleep-related aspects in SSc management to enhance patient QoL.

Orientin Promotes Antioxidant Capacity, Mitochondrial Biogenesis, and Fiber Transformation in Skeletal Muscles through the AMPK Pathway.

The sleep-breathing condition obstructive sleep apnea (OSA) is characterized by repetitive upper airway collapse, which can exacerbate oxidative stress and free radical generation, thereby detrimentally impacting both motor and sensory nerve function and inducing muscular damage. OSA development is promoted by increasing proportions of fast-twitch muscle fibers in the genioglossus. Orientin, a water-soluble dietary C-glycosyl flavonoid with antioxidant properties, increased the expression of slow myosin heavy chain (MyHC) and signaling factors associated with AMP-activated protein kinase (AMPK) activation both in vivo and in vitro. Inhibiting AMPK signaling diminished the effects of orientin on slow MyHC, fast MyHC, and Sirt1 expression. Overall, orientin enhanced type I muscle fibers in the genioglossus, enhanced antioxidant capacity, increased mitochondrial biogenesis through AMPK signaling, and ultimately improved fatigue resistance in C2C12 myotubes and mouse genioglossus. These findings suggest that orientin may contribute to upper airway stability in patients with OSA, potentially preventing airway collapse.

Relationship of ankyloglossia and obstructive sleep apnea: systematic review and meta-analysis.

Recent studies have highlighted the potential role of a short lingual frenulum as a risk factor for pediatric obstructive sleep apnea syndrome. A shortened frenulum may contribute to abnormal orofacial development, leading to increased upper airway resistance and susceptibility to upper airway collapsibility during sleep. Recognizing early indicators, such as a short lingual frenulum, is crucial for prompt intervention. This systematic review aims to evaluate the association between a short lingual frenulum and the risk of obstructive sleep apnea syndrome in children. This systematic review adheres to PRISMA criteria for a quantitative analysis. A comprehensive search was conducted on five databases until January 2024 to identify relevant studies. The selected articles underwent rigorous analysis, considering study design, sample characteristics, lingual frenulum characterization, sleep assessment methods, and key findings. A total of 239 references were initially identified. Finally, six studies were included in the qualitative synthesis, with four studies eligible for the quantitative synthesis. The Newcastle-Ottawa scale was employed to assess study quality. Meta-analysis, supported by a moderate evidence profile according to the GRADE scale, revealed statistically significant differences, with odds ratios of 3.051 (confidence interval: 1.939 to 4.801) for a short frenulum and 12.304 (confidence interval: 6.141 to 24.653) for a high-arched palate. This systematic review and meta-analysis provide evidence supporting the association between ankyloglossia and obstructive sleep apnea in children. Nevertheless, it is crucial to consider additional factors such as tongue mobility and the presence of a high-arched palate in further evaluations.

Obstructive sleep apnoea in obesity: A review.

Obstructive sleep apnea is a common comorbidity that occurs in individuals with obesity. It classically manifests with excessive daytime sleepiness, resulting in reduced quality of life, workplace productivity, and an increased risk of motor vehicle accidents. Weight gain plays an important role in its pathogenesis through worsening upper airway collapsibility, and current treatment options are targeted towards mechanically overcoming upper airway obstruction and weight loss. Continuous positive airway pressure therapy remains the most widely prescribed treatment for obstructive sleep apnea but poor tolerance is a common barrier to effective treatment. Sustainable weight loss is an important treatment option but can be difficult to achieve without bariatric surgery. The recent advances in incretin-based pharmacotherapies represent a promising avenue not only in achieving long-term weight loss but also in treating obstructive sleep apnoea and alleviating the burden of its symptoms and comorbidities.

The Effectiveness of Continuous Positive Airway Pressure for Treating Obstructive Sleep Apnoea in Pregnancy: A Systematic Review

(Aust N Z J Obstet Gynaecol 2023. 2023;63(3):290–300) Obstructive sleep apnea (OSA) is characterized by recurrent pauses in breathing during sleep due to upper airway collapse, resulting in decreased oxygen levels. OSA affects around 10.5% of parturients during early pregnancy and up to 30% at term. In pregnancy, OSA is associated with an increased risk for gestational hypertension, pre-eclampsia, and gestational diabetes. Infants born to mothers with OSA may have a lower birth weight and are at increased risk for premature delivery and neonatal intensive care unit admission. Baseline obesity increases the risk of OSA during pregnancy, with lifestyle modifications being the standard treatment, though their influence on maternal outcomes is limited. Continuous positive airway pressure (CPAP) is an effective OSA treatment; however, little research exists on the impact of CPAP on either maternal or fetal outcomes. This systematic review sought to investigate if the use of CPAP improved outcomes for pregnant women with or at risk of OSA.

Modifications in Upper Airway Collapsibility during Sleep Endoscopy with a Mandibular Positioner: Study in Snorers and Obstructive Sleep Apnea Patients.

Mandibular advancement devices (MADs) are an effective treatment for patients with sleep-related breathing disorders, with variable response. Increasingly more research points to the predictive value of Drug-Induced Sleep Endoscopy (DISE) in patient selection. This study aims to analyze the changes in upper airway collapsibility using a titratable MAD simulator during DISE. This study included 104 patients with simple snoring and obstructive sleep apnea (OSA). The VOTE scale was used to assess the presence of collapses during the DISE both without and with the MAD simulator. In snorers, there was a decrease in collapses at the level of the soft palate and oropharynx when the advancement was achieved. Patients with mild OSA also showed a decrease in collapses at the base of the tongue. Patients with moderate/severe OSA exhibited significant amelioration at all levels. The levels at which there were residual collapses despite the maneuver were, in order, the velopharynx, oropharynx, epiglottis, and tongue. The MAD simulator reduces collapsibility at all levels and in all severity groups. Residual collapses suitable for combined treatments were able to be identified. This highlights the need for individualized patient selection, as upper airway collapsibility exhibits variable improvement or worsening with the MAD simulator regardless of the severity of the condition.

Fluoroscopically measured bronchial collapse in healthy dogs during cough exceeds 25%, and a cutoff of 60% bronchial collapse can be used to distinguish healthy from chronically coughing dogs.

Bronchomalacia, the weakening of bronchial cartilage, is a common cause of cough in dogs. The gold standard for diagnosis of bronchomalacia is bronchoscopy; however, fluoroscopy is often used as a preliminary diagnostic test due to its noninvasiveness. The normal amount of bronchial collapse in healthy dogs using fluoroscopy has not been previously established, with some authors citing <25%. The aims of this prospective and retrospective analytical observational study were to determine the normal amount of airway collapse in healthy animals, the amount of airway collapse in dogs with chronic cough and presumed bronchomalacia, and cut-off values of airway collapse during expiration and cough to distinguish between the two groups. Thoracic fluoroscopy was performed in right and left lateral recumbency during inspiration, expiration, and cough to evaluate the percentage collapse of the trachea and lobar bronchi in 45 healthy and 76 chronically coughing dogs. The bronchi of chronically coughing dogs exhibited a significantly greater amount of collapse during both expiration and cough compared with healthy dogs. Chronically coughing dogs exhibited up to 31.7±26.6% collapse in expiration and 87.5±23.7% collapse during cough, whereas healthy dogs exhibited 14.9±6.1% collapse in expiration and 35.0±13.7% collapse during cough. Based on ROC curves, the authors suggest using cut-off values of 30% during expiration and 60% during cough to distinguish between healthy dogs and those with presumed bronchomalacia. Findings suggest that though healthy dogs can exhibit a greater degree of airway collapse than previously thought, fluoroscopy can be used to distinguish between healthy and presumed bronchomalacic dogs.

A Case of Excessive Dynamic Airway Collapse Caused by Deep Neck Abscess and Tracheostomy

A Case of Excessive Dynamic Airway Collapse Caused by Deep Neck Abscess and Tracheostomy

Risk factors associated with severe adverse events in patients with relapsing polychondritis undergoing flexible bronchoscopy

BackgroundPatients with relapsing polychondritis (RP) sometimes experience upper airway collapse or lower airway stenosis, and bronchoscopy may provide a valuable typical image to confirm the diagnosis. This study aimed to identify potential risk factors associated with severe adverse effects during bronchoscopy.MethodsWe performed a retrospective cohort study of 82 consecutive patients with RP hospitalized at Peking Union Medical College Hospital between January 1, 2012 and December 31, 2022. Clinical features and disease patterns were compared among patients with RP undergoing bronchoscopy with or without severe adverse effects. Binary logistic regression analysis was performed to identify the associated risk factors.ResultsFor patients with RP undergoing bronchoscopy with severe adverse effects, the forced vital capacity (FVC), forced vital capacity percent predicted values (FVC%), and peak expiratory flow were significantly lower (P = 0.001, P = 0.001, and P = 0.021, respectively) than those in the non-severe adverse effect subgroup. Binary logistic regression analysis revealed that low FVC% (odds ratio, 0.930; 95% confidence interval, 0.880–0.982; P = 0.009) was an independent risk factor for severe adverse events in patients undergoing bronchoscopy.ConclusionsLow FVC or FVC% suggests a high risk of severe adverse effects in patients with RP undergoing bronchoscopy. Patients with such risk factors should be carefully evaluated before bronchoscopy and adequately prepared for emergency tracheal intubation or tracheostomy.

Investigating Predictors of Decannulation Through Endoscopic Approach in Patients With Tracheostomy and Peristomal Subglottic Stenosis.

Peristomal subglottic stenosis (SGS) is a common sequela after tracheostomy, with severe cases precluding decannulation. Predictors of decannulation success in these patients following endoscopic intervention are not well studied. The aim of this study is to investigate predictors of successful decannulation and inform treatment decisions. This study is a retrospective case series of 22 adult patients presenting to the senior author with a tracheostomy and peristomal SGS precluding decannulation between 2018 and 2023. Department of Otolaryngology-Head & Neck Surgery, University of Arizona College of Medicine-Tucson. Patient demographics, relevant clinical factors, stenosis characteristics, and the number of endoscopic procedures performed were analyzed to identify predictors of successful decannulation. Endoscopic interventions were generally performed 3 months apart with CO2 laser debridement, balloon dilation, and intralesional injection of steroid, all done with a laser-safe endotracheal tube in place through the stoma. Out of the 22 patients in the study, 9 (40.9%) achieved decannulation, all through an endoscopic approach. Body mass index (BMI) and age were identified as significant negative predictors of decannulation success (P = .02; P = .05, respectively). Stenosis characteristics, such as the presence of tracheomalacia, excessive dynamic airway collapse, multilevel stenosis, posterior glottic stenosis, and anterior granulation tissue shelf did not significantly impact decannulation success. A 40.9% decannulation rate was achieved in our cohort. BMI and age were identified as negative predictors of decannulation success. Stenosis characteristics did not significantly affect decannulation outcomes. Further investigation is warranted to establish reliable predictors of decannulation.

Effects of TAK-925 (danavorexton) a selective orexin 2 receptor agonist on upper airway collapsibility and pharyngeal muscle activity in adults with obstructive sleep apnea

Effects of TAK-925 (danavorexton) a selective orexin 2 receptor agonist on upper airway collapsibility and pharyngeal muscle activity in adults with obstructive sleep apnea

Prevalence of Obstructive Sleep Apnea Among Atrial Fibrillation Patients: A Cross-Sectional Study from Jordan.

Obstructive Sleep Apnea (OSA) is a common respiratory disorder that causes intermittent upper airway collapse during sleep and can lead to various acute cardiovascular complications. Atrial Fibrillation (AF) is the most common sustained cardiac arrhythmia and is associated with an increased risk of cardiovascular hospitalization and all-cause mortality. Our study aimed to investigate the prevalence of individuals with AF and those considered at high risk for OSA. A cross-sectional study was conducted with a population comprising patients who had visited KAUH cardiology clinics between 2017-2019; subjects were categorized into AF patients and general cardiology patients. Patients were surveyed for OSA using the Berlin Questionnaire to assess the degree of OSA symptoms and to classify patients into high- or low-risk groups based on their responses. Of the 656 patients, 545 met our inclusion criteria, of whom 192 were diagnosed with AF. Comparable demographic characteristics were observed between the AF and non-AF groups, barring higher rates of obesity (p=0.001) and smoking (p=0.042) in the AF group. The prevalence of high-risk OSA was significantly higher in AF patients (68.2%) compared to non-AF patients (29.4%), with an adjusted odds ratio of 2.473 times (95% CI: 1.434 -4.266, p=0.001) greater for AF. The age, gender, and BMI categories did not differ significantly between the two groups. Binary logistic regression revealed significant associations between OSA and risk factors such as asthma (OR=4.408, 95% CI: 2.634-7.376, p=0.001). These results serve to display a statistically significant increase in high-risk OSA in existing AF patients, irrespective of the presence of conventional OSA risk factors; this could imply a more immediate and direct relationship between both diseases and calls to include routine screening for OSA in patients diagnosed, newly or otherwise, with AF.

Exploring the dynamics of snoring in relation to sleep stages: Implications for gender differences, sleep position, and upper airway collapsibility.

The purpose of this study was to determine the sleep stage during which isolated snoring occurs in children and adults, and to analyze changes after treatment of obstructive sleep apnea (OSA). This retrospective study examined duration of snoring time and respiratory events during each sleep stage in adults and children who underwent polysomnography, had an apnea-hypopnea index (AHI) < 15/h and had snoring time ≥ 10% of total sleep time. Changes in duration of snoring time were also examined in adult patients after treatment with an oral appliance (OA). Snoring time was shown to be predominant during N3 and N2 sleep and less dominant during REM sleep in both children (n = 47) and adults (n = 93). These results were seen even in children with REM dependency. The percentage of snoring time during N3 sleep was more pronounced in women than in men among young adult patients aged < 40 years but was not significantly different between men and women overall. There were no significant differences in the percentage of snoring time in each sleep stage between young women with mild OSA and non-OSA. In children, there were no significant differences between boys and girls in the percentage of snoring time in any sleep stage. The percentage of snoring time during N3 was significantly higher sleep in the non-supine position than in the supine position in children, whereas no significant differences were noted between the supine and non-supine positions in any sleep stage in adults. OA treatment for adult patients (n = 20) significantly increased the percentage of snoring time during N3 sleep, although it significantly decreased AHI, total snoring time, and snoring time during N1 sleep and REM sleep. Snoring presented exclusively during the N3 sleep stage, especially in young women with mild OSA, and in children with OSA, especially in the non-supine position. Snoring time during N3 sleep increased during OA treatment for OSA.

Comparison of airway collapsibility following single induction dose ketamine with propofol versus propofol sedation in children undergoing magnetic resonance imaging: A randomised controlled study.

Adequate sedation is essential for children undergoing magnetic resonance imaging (MRI) console. Propofol is commonly used for sedation, but it has the drawback of upper airway collapse at higher doses, which may be overcome by ketamine. This study was designed to evaluate the beneficial effect of ketamine on propofol in preventing airway collapse. Fifty-eight children undergoing MRI were randomised to Group P (propofol bolus dose followed by infusion or Group KP (bolus dose of ketamine and propofol followed by propofol infusion). The primary aim is to compare the upper airway cross-sectional area (CSA) and diameters (transverse diameter [TD] and anteroposterior diameter [APD]) obtained from MRI during inspiration and expiration. Upper airway collapse as measured by delta CSA in mean (SD) [95% confidence interval] was statistically more significant between the two groups [at the soft palate level, 16.9 mm2 (19.8) [9.3-24.4] versus 9.0 mm2 (5.50) [6.9-11.1] (P = 0.043); at the base of the tongue level, 15.4 mm2 (11.03) [11.2-19.6] versus 7.48 mm2 (4.83) [5.64-9.32] (P < 0.001); at the epiglottis level, 23.9 (26.05) [14.0-33.8] versus 10.9 mm2 (9.47) [7.35-14.5] (P = 0.014)]. A significant difference was obtained for TD at all levels and for APD at the soft palate and base of tongue level. Adding a single dose of ketamine to propofol reduced the upper airway collapse significantly, as evidenced by the MRI-based measurements of upper airway dimensions, compared to propofol alone.

Effect of pharyngeal wall compliance on passive collapsibility of retropalatal airway in patients with obstructive sleep apnea

AbstractObjectiveTo evaluate the pharyngeal compliance of patients with obstructive sleep apnea with complete muscle relaxation. And to study the relationship between the pharyngeal wall compliance and the mechanical load of the retropalatal airway.MethodsThe static mechanical load of the retropalatal pharynx was determined by critical closing pressure (Pcrit) of the segment during general anesthesia in 30 patients. The size/dimensions of the pharynx were measured while intraluminal pressure was controlled at 3–20 cmH2O.ResultsA total of 30 participants (age: 37.6 ± 7.6 years, 27 males) were studied. The mean apnea‐hypopnea index was 51.6 ± 23.9 events/h. The retropalatal mean Pcrit was 12.68 ± 4.13 cmH2O. There was a significant difference in the length of the obstruction segment (F = 26.028, p &lt; 0.001) among groups with different pharyngeal collapsibility. The correlation between the mechanical load of retropalatal airway and pharyngeal compliance in the level of the hard palate (r = −0.448, p = 0.015) and the uvula level (r = −0.462, p = 0.026) were significant.ConclusionsIncreased retropalatal mechanical loads were related to abnormal passive compliance of the pharyngeal wall. The contribution of each pharyngeal wall to airway collapse was varied.

Types of Epiglottic Collapse in Breathing Sleep Disorder and Their Impact in Clinical Practice.

Introduction Obstructive sleep apnea (OSA) is a severe form of sleep-disordered breathing (SDB) that is strongly correlated with comorbidities, in which epiglottic collapse (EC) and other contributing factors are involved. Objectives To evaluate the occurrence of EC in OSA patients through drug-induced sleep endoscopy (DISE) and to determine the factors contributing to EC. Methods A retrospective study of 37 adult patients using medical history. Patients were assessed for laryngopharyngeal reflux (LPR) and lingual tonsil hypertrophy (LTH) using reflux symptom index and reflux finding score (RFS); for OSA using polysomnography, and for airway collapse through DISE. An independent t -test was performed to evaluate risk factors, including the involvement of three other airway structures. Results Most EC patients exhibited trap door epiglottic collapse (TDEC) (56.8%) or pushed epiglottic collapse (PEC) (29.7%). Lingual tonsil hypertrophy, RFS, and respiratory effort-related arousal (RERA) were associated with epiglottic subtypes. Laryngopharyngeal reflux patients confirmed by RFS (t(25) = -1.32, p = 0.197) tended to suffer PEC; LTH was significantly associated (X2(1) = 2.5, p = 0.012) with PEC (odds ratio [OR] value = 44) in grades II and III LTH patients; 11 of 16 TDEC patients had grade I LTH. Pushed epiglottic collapse was more prevalent among multilevel airway obstruction patients. A single additional collapse site was found only in TDEC patients. Conclusion Laryngopharyngeal reflux causes repetitive acid stress toward lingual tonsils causing LTH, resulting in PEC with grade II or III LTH. Trap door epiglottic collapse requires one additional structural collapse, while at least two additional collapse sites were necessary to develop PEC. Respiratory effort-related arousal values may indicate EC.

A novel TASK channel antagonist nasal spray reduces sleep apnea severity in physiological responders: a randomized, blinded, trial.

Preclinical and human physiological studies indicate that topical, selective TASK 1/3 K+ channel antagonism increases upper airway dilator muscle activity and reduces pharyngeal collapsibility during anesthesia and nasal breathing during sleep. The primary aim of this study was to determine the effects of BAY2586116 nasal spray on obstructive sleep apnea (OSA) severity and whether individual responses vary according to differences in physiological responses and route of breathing. Ten people (5 females) with OSA [apnea-hypopnea index (AHI) = 47 ± 26 events/h (means ± SD)] who completed previous sleep physiology studies with BAY2586116 were invited to return for three polysomnography studies to quantify OSA severity. In random order, participants received either placebo nasal spray (saline), BAY2586116 nasal spray (160 µg), or BAY2586116 nasal spray (160 µg) restricted to nasal breathing (chinstrap or mouth tape). Physiological responders were defined a priori as those who had improved upper airway collapsibility (critical closing pressure ≥2 cmH2O) with BAY2586116 nasal spray (NCT04236440). There was no systematic change in apnea-hypopnea index (AHI3) from placebo versus BAY2586116 with either unrestricted or nasal-only breathing versus placebo (47 ± 26 vs. 43 ± 27 vs. 53 ± 33 events/h, P = 0.15). However, BAY2586116 (unrestricted breathing) reduced OSA severity in physiological responders compared with placebo (e.g., AHI3 = 28 ± 11 vs. 36 ± 12 events/h, P = 0.03 and ODI3 = 18 ± 10 vs. 28 ± 12 events/h, P = 0.02). Morning blood pressure was also lower in physiological responders after BAY2586116 versus placebo (e.g., systolic blood pressure = 137 ± 24 vs. 147 ± 21 mmHg, P < 0.01). In conclusion, BAY2586116 reduces OSA severity during sleep in people who demonstrate physiological improvement in upper airway collapsibility. These findings highlight the therapeutic potential of this novel pharmacotherapy target in selected individuals.NEW & NOTEWORTHY Preclinical findings in pigs and humans indicate that blocking potassium channels in the upper airway with topical nasal application increases pharyngeal dilator muscle activity and reduces upper airway collapsibility. In this study, BAY2586116 nasal spray (potassium channel blocker) reduced sleep apnea severity in those who had physiological improvement in upper airway collapsibility. BAY2586116 lowered the next morning's blood pressure. These findings highlight the potential for this novel therapeutic approach to improve sleep apnea in certain people.

Dexamethasone eluting polydopaminated polycaprolactone-poly (lactic-co-glycolic) acid for treatment of tracheal stenosis.

Tracheal stenosis is commonly caused by injury, resulting in inflammation and fibrosis. Inhibiting inflammation and promoting epithelization can reduce recurrence after initial successful treatment of tracheal stenosis. Steroids play an important role in tracheal stenosis management. This study in vitro evaluated effectiveness of a polydopaminated polycaprolactone stent coated with dexamethasone-eluting poly(lactic-co-glycolic) acid microparticles (μPLGA) for tracheal stenosis management. Polydopamination was characterized by Raman spectroscopy and promoted epithelialization while dexamethasone delivery reduced macrophage activity, assessed by individual cell area measurements and immunofluorescent staining for inducible nitric oxide synthase (iNOS). Dexamethasone release was quantified by high-performance liquid chromatography over 30 days. Activation-related increase in cell area and iNOS production by RAW 264.7 were both reduced significantly (p < .05) through dexamethasone release. Epithelial cell spreading was higher on polydopaminated polycaprolactone (PCL) than PCL-alone (p < .05). Force required for stent migration was measured by pullout tests of PCL-μPLGA stents from cadaveric rabbit and porcine tracheas (0.425 ± 0.068 N and 1.082 ± 0.064 N, respectively) were above forces estimated to occur during forced respiration. Biomechanical support provided by stents to prevent airway collapse was assessed by comparing compressive circumferential stiffness, and stiffness of the stent was about 1/10th of the rabbit trachea (0.156 ± 0.023 N/mm vs. 1.420 ± 0.194 N/mm, respectively). A dexamethasone-loaded PCL-μPLGA stent platform can deliver dexamethasone and exhibits sufficient mechanical properties to anchor within the trachea and polydopamination of PCL is conducive to epithelial layer formation. Therefore, a polydopaminated PCL-μPLGA stent is a promising candidate for in vivo evaluation for treatment of tracheal restenosis.