Airway Dilator Research Articles

O002 A novel, optogenetics based therapy for obstructive sleep apnea

Abstract INTRODUCTION Many obstructive sleep apnea (OSA) patients are sub-optimally treated due to poor tolerance or incomplete response to established therapies. We propose a novel stimulation therapy that sensitises the dilator muscles to light activation (‘optogenetics') and activates the muscles with light during sleep. This study aims to determine feasibility in a rodent model of OSA and identify effective optogenetic constructs. METHODS Rats received intramuscular injections of a viral vector encapsulating the opsin ChR2, driven by either a muscle-specific or non-specific promotor. Three weeks post-injection, opsin expression was quantified via confocal imaging. Light-induced tongue muscle activity afforded by the superior promotor was then measured in an acute model of OSA. The superior promotor was then combined with a novel muscle-targeted viral vector and, light-induced airway dilation was measured with ultrasound imaging. RESULTS With the muscle-specific promotor, opsin expression in the tongue was 470%(p=0.013, RM-ANOVA) greater, and brainstem expression was abolished. In the animals who received this superior promotor, light stimulation facilitated a 56% increase in muscle activity from that recorded during unstimulated breaths in an acute model of OSA(p<0.001, linear mixed model). Ultrasound imaging confirmed that light stimulation of the optogenetic construct with a muscle-specific promotor encapsulated in a muscle-targeted viral vector produced airway dilation in the same OSA model. DISCUSSION The combined muscle-specific promotor and muscle-specific viral vector resulted in a novel and highly effective method of inducing light-sensitivity in upper airway muscles and facilitating light-induced airway dilation. This study provides proof-of-concept for a non-invasive optogenetics-based OSA therapy.

O054 Genioglossus neural drive and upper airway dilation in people with obstructive sleep apnoea during wakefulness

Abstract Introduction Genioglossus neural drive and the ensuing tongue dilatory movement may be dissociated in obstructive sleep apnoea (OSA), but this has not been studied. This study aimed to investigate this relationship and its potential role in OSA pathophysiology. Methods During awake nasal breathing in the supine position, inspiratory tongue dilatory movement, quantified with tagged magnetic resonance imaging, and inspiratory peak genioglossus electromyography (EMG) normalised to the maximum voluntary contraction (tongue protrusion), were measured in 4 tongue neuromuscular compartments from 8 controls [apnea-hypopnea index (AHI)<5 events/h] and 34 patients with untreated OSA [AHI>10 events/h]. Results Although larger inspiratory dilatory movement was associated with increased drive to genioglossus (partial Spearman, r=0.23, p=0.016, n=115/68% of compartments), in 14% of the compartments (n=16), there was a large dilatory (>1mm) movement but minimal EMG (<4th percentile). This occurred only in the horizontal compartment. In another group of 18 compartments (16%), there was a large peak EMG (>4th percentile) but minimal dilatory movement (<1mm). This occurred more commonly in the oblique compartments. Dissociation between the amplitude of the peak EMG and inspiratory tongue dilatory movement was most commonly seen in severe OSA patients (AHI>30 events/h, Fisher's exact test, p=0.047). Conclusions Inspiratory tongue dilatory function generally remains closely linked to muscle drive during wakefulness, with larger movement associated with higher peak EMG. However, for approximately one-third of the neuromuscular tongue compartments, neural drive was dissociated from the dilatory motion in severe OSA patients. This may contribute to OSA pathogenesis and have implications for neural stimulation therapy targets.

RECANNULATION OF COMPLETELY OCCLUDED BRONCHUS INTERMEDIUS WITH A DIODE LASER

RECANNULATION OF COMPLETELY OCCLUDED BRONCHUS INTERMEDIUS WITH A DIODE LASER

UTILIZATION OF CONTINUOUS REMOTE MONITORING FOR A HIGH-RISK PATIENT REQUIRING INTERVAL TUMOR DEBULKING PALLIATIVE THERAPY

UTILIZATION OF CONTINUOUS REMOTE MONITORING FOR A HIGH-RISK PATIENT REQUIRING INTERVAL TUMOR DEBULKING PALLIATIVE THERAPY

Non-Cystic Fibrosis Bronchiectasis in Pediatric Age: A Case Series in a Metropolitan Area of Northern Italy.

Non-cystic fibrosis bronchiectasis is an emergent disease characterized by endobronchial suppuration, dilated airways with neutrophilic inflammation and chronic wet cough due to recurrent lower airway infections. A regular clinical follow-up and adequate management of exacerbations are essential to reduce symptoms and the worsening of lung injury. We report a retrospective study comprising 15 children and adolescents with NCFB followed in our hospital center of pediatric pulmonology. We retrospectively analyzed the main comorbidities associated with the presence of NCFB, the radiological aspect associated with the different etiologies and the therapeutic approach used. We also emphasized the importance of an effective preventive strategy to reduce and prevent pulmonary exacerbations.

Monitoring disease progression in childhood bronchiectasis.

Bronchiectasis (not related to cystic fibrosis) is a chronic lung disease caused by a range of etiologies but characterized by abnormal airway dilatation, recurrent respiratory symptoms, impaired quality of life and reduced life expectancy. Patients typically experience episodes of chronic wet cough and recurrent pulmonary exacerbations requiring hospitalization. Early diagnosis and management of childhood bronchiectasis are essential to prevent respiratory decline, optimize quality of life, minimize pulmonary exacerbations, and potentially reverse bronchial disease. Disease monitoring potentially allows for (1) the early detection of acute exacerbations, facilitating timely intervention, (2) tracking the rate of disease progression for prognostic purposes, and (3) quantifying the response to therapies. This narrative review article will discuss methods for monitoring disease progression in children with bronchiectasis, including lung imaging, respiratory function, patient-reported outcomes, respiratory exacerbations, sputum biomarkers, and nutritional outcomes.

Assessment of clinical signs of brachycephalic obstructive airway syndrome and other breed-specific diseases in pug dogs - an online survey

The aim of the study was to investigate the awareness for the breed-related brachycephalic obstructive airway syndrome (BOAS) and the occurrence of other breed-typical diseases within the framework of an online survey for pug owners. A digital questionnaire for owners was created, distributed via social media and subsequently evaluated. The questionnaire was completed by 1220 pug owners. According to the owners, 32 % (344/1073) of the animals that did not undergo airway dilatation surgery show slight and 3 % (34/1073) show distinct breathing sounds when at rest. 86 % (326/378) of the owners perceive these breathing sounds as "normal, breed-specific" and 14 % (51/378) consider them as sign of "disease". 20 % (210/1073) of the animals are considered "somewhat" and 5 % (57/1073) "frequently tired and quickly short of breath" after a small amount of time. 24 % (245/1220) of all animals suffer from ocular diseases, 10 % (122/1220) from skin diseases and 11 % (134/1220) from spinal diseases, among others. The survey shows that with 67 % (814/1220) more than half of the pug owners perceive clinical signs of BOAS and/or other breed-specific diseases in their animals, however, a large proportion consider these as being non-problematic. The present study reveals that the animals' clinical limitations associated with brachycephaly are oftentimes not perceived as being pathologic and are hence underestimated by the owners.

Med Check: Psilocybin for OCD, Nuplazid Vote, and More

Med Check: Psilocybin for OCD, Nuplazid Vote, and More

Bronchiectasis in African children: Challenges and barriers to care.

Bronchiectasis (BE) is a chronic condition affecting the bronchial tree. It is characterized by the dilatation of large and medium-sized airways, secondary to damage of the underlying bronchial wall structural elements and accompanied by the clinical picture of recurrent or persistent cough. Despite an increased awareness of childhood BE, there is still a paucity of data on the epidemiology, pathophysiological phenotypes, diagnosis, management, and outcomes in Africa where the prevalence is mostly unmeasured, and likely to be higher than high-income countries. Diagnostic pathways and management principles have largely been extrapolated from approaches in adults and children in high-income countries or from data in children with cystic fibrosis. Here we provide an overview of pediatric BE in Africa, highlighting risk factors, diagnostic and management challenges, need for a global approach to addressing key research gaps, and recommendations for practitioners working in Africa.

Severity of nasopharyngeal collapse before and after corrective upper airway surgery in brachycephalic dogs.

To determine the severity of nasopharyngeal collapse in brachycephalic dogs before and after corrective airway surgery. Twenty-three brachycephalic dogs (21 with clinical signs referrable to the upper airway) and nine clinically normal nonbrachycephalic dogs (controls). Dogs were evaluated with fluoroscopy awake and standing with the head in a neutral position. The magnitude of nasopharyngeal collapse was measured as the maximum reduction in the dorsoventral dimension of the nasopharynx during respiration and expressed as a percentage. Brachycephalic dogs were anesthetized, the airway evaluated, and corrective upper airway surgery (alaplasty, staphylectomy, sacculectomy, tonsillectomy) was performed. A cohort (n=11) of the surgically treated brachycephalic dogs had fluoroscopy repeated a minimum of 6 weeks after surgery. Median preoperative reduction in the dorsoventral dimensions of the nasopharynx was greater in brachycephalic dogs (65%; range: 8-100%) than in controls (10%; range: 1-24%, p=.0001). Surgery did not improve the reduction in dorsoventral diameter of the nasopharynx during respiration in brachycephalic dogs (n=11) postoperatively (p=.0505). Nasopharyngeal collapse was a common and sometimes severe component of brachycephalic airway obstruction syndrome in the cohort of dogs evaluated. The lack of significant postoperative improvement may represent a type II error, a failure to adequately address anatomical abnormalities that increase resistance to airflow, or inadequate upper airway dilator muscle function in some brachycephalic dogs.

The impact of daytime transoral neuromuscular stimulation on upper airway physiology - A mechanistic clinical investigation.

There is a need for alternatives to positive airway pressure for the treatment of obstructive sleep apnea and snoring. Improving upper airway dilator function might alleviate upper airway obstruction. We hypothesized that transoral neuromuscular stimulation would reduce upper airway collapse in concert with improvement in genioglossal muscle function. Subjects with simple snoring and mild OSA (AHI < 15/h on screening) underwent in‐laboratory polysomnography with concurrent genioglossal electromyography (EMGgg) before and after 4–6 weeks of twice‐daily transoral neuromuscular stimulation. Twenty patients completed the study: Sixteen males, mean ± SD age 40 ± 13 years, and BMI 26.3 ± 3.8 kg/m2. Although there was no change in non‐rapid eye movement EMGgg phasic (p = 0.66) or tonic activity (p = 0.83), and no decrease in snoring or flow limitation, treatment was associated with improvements in tongue endurance, sleep quality, and sleep efficiency. In this protocol, transoral neurostimulation did not result in changes in genioglossal activity or upper airway collapse, but other beneficial effects were noted suggesting a need for additional mechanistic investigation.

ROLE OF CHEST COMPUTED TOMOGRAPHY IN EVALUATION AND MANAGEMENT OF CHRONIC OBSTRUCTIVE PULMONARY DISEASE

Chronic obstructive pulmonary disease (COPD) exhibits significant heterogeneity in its clinical presentation and rate of disease progression among affected individuals, owing at least in part to differing pulmonary morphologic abnormalities. Symptom assessment, spirometric evaluation, and frequency of respiratory exacerbations have traditionally been used to determine disease severity and guide management. ChestComputed Tomography (CT) scanning provides clear and exact in vivo assessments of organs, and from these data, we can extract subjective and objective features such as parenchymal remodeling, airway dilatation, and vascular calcification. These features can be used to detect the extent of the disease, its severity and also predict its clinical course. However, despite the increasing use and widespread availability of chest CT scans, the wealth of information from Chest CT scans is not consistently used in routine practice and has not yet been incorporated into clinical guidelines for COPD diagnosis, management or prognosis.This article reviews the role of CT in differentiating different phenotypes of Chronic Obstructive Pulmonary Disease (COPD), its clinical implications of emphysema, airway disease, air trapping, and pulmonary vasculature and, highlight the potential value of assessing nonpulmonary structures such as coronary arteries and vertebral bone to provide better comprehensive care for patients with COPD.

Is Continuous Positive Airway Pressure All There Is? Alternative Perioperative Treatments for Obstructive Sleep Apnea

Is Continuous Positive Airway Pressure All There Is? Alternative Perioperative Treatments for Obstructive Sleep Apnea

0754 Effects of Atomoxetine plus a Hypnotic on Obstructive Sleep Apnea (OSA) Severity in Patients with a Moderately Collapsible Pharyngeal Airway

Abstract Introduction The combination of atomoxetine and oxybutynin has demonstrated efficacy in the treatment of OSA. Oxybutynin may play a role as an upper airway dilator muscle activator and/or a hypnotic to improve sleep quality. We assessed the effectiveness of atomoxetine when combined with one of two hypnotics. Trazodone is a known hypnotic with possible effects on pharyngeal muscle activity. The other is lemborexant, an orexin antagonist. The effects of both combinations were assessed in patients with OSA and a moderately collapsible pharyngeal airway. Methods Recruited patients were 18 – 65 years of age, with an AHI 4 (4% desaturation criteria) of 10 – 55 and a BMI &amp;lt; 40 kg/m2. Each had to have a moderately collapsible pharyngeal airway using previously defined criteria based on the average percent desaturation during obstructive events (&amp;lt; 8%) and the ratio of hypopneas to total events (&amp;gt; 50%). After a qualifying PSG, each patient spent three nights in the sleep laboratory with approximately one week between studies. Nights were randomized to placebo, atomoxetine 80 mg plus trazodone 100 mg, and atomoxetine 80 mg plus lemborexant 10 mg. Primary outcomes were AHI 4 and the sleep apnea specific hypoxic burden (HB), the area under the SpO2 curve associated with disordered breathing events. Results Fifteen patients completed the trial (median [interquartile range] age was 52 [48-55] and BMI was 33.6 [30 – 35.1] kg/m2. Atomoxetine plus trazodone showed a strong trend for AHI 4 reduction from placebo (from 18.2 [11.8 – 31.3] to 7.4 [5.4 – 16.1] events/h, p=0.064), a significant reduction in HB from placebo (from 48.2 [31.2 – 79.6] to 18.7 [14.9 – 43.5] % min/h) and a trend for a reduction in HB with atomoxetine plus lemborexant (from 34.1 [12.1 – 128.8] to 18.7 [14.9 – 43.5] % min/h, p=0.055). There was no change in total sleep time or arousal index between treatment arms. Mild adverse events were reported on atomoxetine plus trazodone (2/15 sinusitis, 1/15 heartburn). Conclusion In OSA patients with a moderately collapsible upper airway, the combination of atomoxetine plus trazodone yielded clinically meaningful improvements in measures of sleep disordered breathing and oxygenation while atomoxetine plus lemborexant produced smaller effects. Support (If Any) This study was supported by Apnimed.

332 Association of sphingolipid de novo synthesis with airway response to magnesium

OBJECTIVES/GOALS: MgSO4 is a frequently used to treat asthma exacerbations. Its role in the management of pediatric asthma remains controversial. Our objective is to demonstrate that the response of the small (peripheral) airways depends on airway de novo sphingolipid synthesis, clinically and experimentally. The small airways are the main site of asthma pathology. METHODS/STUDY POPULATION: We investigated airway reactivity in response to MgSO4 in murine small airways and children 1. Precision-cut lung slices (PCLS): Using heterozygous knockouts mice of one of the Sptlc2 subunit of the serine palmitoyl-CoA transferase (SPT) which results in reduced tissue sphingolipid levels compared to wild-type control littermates (Sptlc2+/+). We compared small airway dilation to MgSO4 in Sptlc2+/- and Sptlc2+/+ mice. This was assessed by directly visualization of small airway contractility in PCLS from Sptlc2+/- mice using video phase-contrast microscopy 2. Clinical response to MgSO4 in children by using a respiratory score before and after the treatment. The response to MgSO4 was the correlated to asthma-associated 17q21 specific single nucleotide polymorphisms (SNPs) from DNA isolated from buccal swabs RESULTS/ANTICIPATED RESULTS: Sphingolipid-mediated activity alters magnesium response in small airways. We assessed whether downregulation of SPT could lead to alterations in MgSO4-induced small airway dilation and in MgSO4 responsiveness in mouse tracheal rings and found that the magnesium-induced relaxation of airways pre-contracted with methacholine was impaired in Sptlc+/- mice compared to the control group (p=&lt;0.05) Clinical response to MgSO4 in children with status asthmaticus. A respiratory score was assessed in a cohort of 5 to 21-year-old who received IV MgSO4. An increase of 3 or more points was considered positive. Only 32% of the patients showed a favorable improvement to the medication, showing variability of response between individuals. The correlation of sphingolipid-deficient SNPs and MgSO4 responsiveness is ongoing DISCUSSION/SIGNIFICANCE: This suggest that decreased SPT activity in the respiratory track alters the response of the airways to magnesium. Connecting decreased de novo SL synthesis to alterations in cellular magnesium homeostasis provides a mechanistic link to differential airway reactivity to MgSO4 in pediatric asthma management.

Pulmonary MALT lymphoma: Imaging findings in 18 cases and the associated pathological correlations

BackgroundPulmonary MALT lymphoma is a rare disease that is easily misdiagnosed. The objective of this study was to improve the understanding of pulmonary MALT lymphoma for clinicians. MethodsThe computed tomography (CT) scans of 18 patients (13 males and 5 females), aged 41-70 years (mean=55.6 years), with histologically proven pulmonary MALT lymphoma were retrospectively reviewed by two radiologists, and pulmonary imaging findings were described. Correlations between the pulmonary abnormalities and histopathological findings in 13 patients were retrospectively reviewed. ResultsElementary lesions were characterized by masses or mass-like areas of consolidation (15/18), nodules (5/18), air bronchograms (16/18), airway dilatation (7/18), cavitation (5/18), airways passing through the lesion (8/18), CT angiogram signs (12/14) and vessels passing through the lesion (12/14). Additional findings included multiple cysts (n = 1), pleural effusion (n = 1) and atelectasis (n = 1). Pulmonary abnormalities were correlated with pathological appearance. Pathological examination confirmed lymphomatous infiltration with a bronchovascular distribution but no vessel or airway destruction, which appeared on CT as the vessels/airways passed through lesions naturally. ConclusionsWe herein demonstrated the imaging findings for 18 cases of pulmonary MALT lymphomas by analyzing the corresponding pathologies. We also discovered that vessels/airways could pass through pulmonary MALT lymphoma lesions, which may be helpful for diagnosis. This disease should be considered when chest CT imaging shows multiple/single masses or nodules or mass-like areas of consolidation together with vessels/airways passing through lesions.

Beyond Usual Care: A Multidisciplinary Approach Towards the Treatment of Obstructive Sleep Apnoea.

Obstructive Sleep Apnoea (OSA) is common and characterised by repeated apnoeas and hypopnoeas while asleep due to collapse of the upper airway. OSA can have a significant impact on physical and mental health and, when left untreated, is associated with increased risk of developing cardiovascular ill health. Besides cardiorespiratory implications excessive daytime sleepiness, morning headaches, limited memory function and lack of concentration are some further symptoms caused by OSA. Continuous Positive Airway Pressure (CPAP) therapy is the evidence-based treatment to maintain upper airway patency in patients with moderate to severe OSA. Proper adherence to CPAP therapy successfully abolishes nocturnal apnoeas and hypopnoeas, and diminishes consequences of uncontrolled OSA, such as treatment resistant hypertension. However, long term adherence to CPAP remains an unresolved limitation of this method. Although alternatives to CPAP therapy may be less efficacious, there is a variety of non-CPAP treatments that includes conventional lifestyle advice, postural advice, the use of mandibular advancement devices (MADs), surgical treatment options, such as uvulopalatopharyngoplasty, tonsillectomy, or maxillomandibular advancement, and the use of electrical stimulation of the upper airway dilator muscles. Hypoglossal Nerve Stimulation is available as an invasive (HNS) and a transcutaneous (TESLA) approach. For the management of “difficult-to-treat” patients with OSA, particularly in those in whom first line therapy proved to be unsuccessful, a multidisciplinary team approach may be helpful to incorporate the available options of non-CPAP therapy and provide appropriate choices. Symptom control, patient-related outcome measures and long-term cardiovascular health should be prioritised when choosing long-term therapies to treat OSA. The inclusion of patients in the choice of successful management options of their condition will facilitate better long-term adherence. Advancing clinical trials in the field will further help to resolve the relative lack of evidence for effective non-CPAP methods.

Sleep-Disordered Breathing - A Dental Perspective.

What is Sleep Disordered Breathing? What are the causes of Sleep Disordered Breathing? What role does an Orthodontist play? The article aims at answering such questions and spreading the ideology and seriousness of this disorder. Normal sleep involves air passing through and going directly down to the lungs. With an obstructed airway, the structures in the back of the throat occlude the airway due to an inadequate motor tone of the tongue and airway dilator muscles, and thus, prevent the air from passing.

Treatment with Oral Appliances in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is a disorder caused by a number of factors like an obstruction of the upper airway during sleep because of insufficient motor tone of the tongue and/or airway dilator muscles or inadequate growth of the maxillary jaw bone etc. Oral appliances (OAs) are commonly used as a non-invasive treatment for obstructive sleep apnea syndrome. The primary oral appliance (OA) used in obstructive sleep apnea (OSA) treatment is the mandibular advancement device (MAD). Tongue-retaining devices or tongue-stabilizing devices (TSDs) are a second type of OA, which displace the tongue anteriorly and may be customized or come in different stock sizes. This review article aims to examine the best in class on this particular subject of treatment of OSA with oral appliances, explaining acceptability of an appliance in patients on the basis of its construction and results, while providing enough cognizance regarding the diagnosis, management and causes of discontinuation.

Clinical characteristics of patients with bronchiectasis with nontuberculous mycobacterial disease in Mainland China: a single center cross-sectional study

BackgroundThe diagnosis and treatment of patients with bronchiectasis and nontuberculous mycobacterium (NTM) pulmonary disease are challenging issues and the treatment is also prolonged and depends on the species. There is limited information on patients with bronchiectasis and NTM pulmonary disease in Mainland China.MethodsThis cross-sectional study was conducted at the China–Japan Friendship Hospital, Beijing, China. Those adult patients who met the diagnostic criteria for bronchiectasis and obtained a culture result of mycobacteria from lower respiratory tract specimens or lung tissue were included in this study. A logistic regression model was used to identify the related factors in patients with NTM pulmonary disease.ResultsA total of 202 patients with bronchiectasis from 19 cities, 155 without and 47 (23.3%) with NTM pulmonary disease, were included. In all the 47 patients with NTM pulmonary disease, Mycobacterium avium complex was the most common species (66.0%), and 72.3% of them were initiated on standard anti-NTM treatment within 3 months after the diagnosis of NTM pulmonary disease. A larger proportion of patients with NTM pulmonary disease had acute exacerbations of ≥ 3 times within 1 year and were diagnosed bronchiectasis ≥ 50 years among patients with NTM pulmonary disease. The HRCT chest images revealed higher proportions of nodular shadow (100% vs. 35.3%), tree-in-bud sign (97.9% vs. 29.0%), cavities (29.8% vs. 5.8%), and airway dilation of the right middle lobe or the left lingular lobe (63.8% vs. 23.9%) in patients with NTM pulmonary disease than in those without NTM pulmonary disease (all P values = 0.001). The multivariable logistic regression model indicated that three and more abnormal features (OR 33.8; 95% CI 11.1–102.8) and main lesions of bronchial expansion in the middle or lingual lobe (OR 6.4; 95% CI 2.4–16.6) in HRCT chest images were independently associated with NTM pulmonary disease (P values = 0.001).ConclusionIn a single center of Mainland China, > 23% of patients with bronchiectasis had NTM pulmonary disease, and most patients were started on standard treatment within 3 months after the diagnosis of NTM pulmonary disease. These findings suggest that patients with bronchiectasis should be thoroughly examined for the presence of NTM pulmonary disease.Trial registrationNCT03594032.