P155 Effects of upper airway muscle training on upper airway physiology in people with obstructive sleep apnea

Introduction Previous studies demonstrate that oropharyngeal exercises can reduce obstructive sleep apnoea (OSA) severity. However, the physiological mechanisms underlying this improvement are unknown. Thus, this study aimed to evaluate the effects of a speech-pathology led, targeted upper airway muscle training protocol on upper airway physiology. Methods People with mild-moderate OSA (n=12 studied to date, 5 females, 7 males) completed 12 weeks of daily upper airway muscle training targeting the muscles of the tongue and soft palate. Pre- and post-training outcome measures included anterior and posterior tongue muscle strength and endurance and upper airway collapsibility via the upper airway collapsibility index. Results Preliminary findings indicate that 12 weeks of targeted exercise training improved anterior and posterior tongue muscle strength, respectively (54.3±12.7 vs. 61.5±7.7kPa, p<0.01, 50.1±8.5 vs. 58.0±8.5kPa, p<0.01), and anterior and posterior tongue muscle endurance, respectively (15.7±10.9 vs. 24.1±8s, p<0.01, 9.5±4.2 vs. 23.3±17.7s, p<0.01). The upper airway collapsibility index improved post-training (25.5±18.9 vs. 12.26±12.11 %, p=0.03). Conclusions Twelve weeks of upper airway muscle training improved tongue muscle strength, endurance and upper airway collapsibility in people with mild-moderate OSA. These physiological changes provide insight into the potential mechanisms mediating reductions in OSA severity with oropharyngeal exercises. This research was supported by the 2019 Phillips/ASA Sleep Research grant.

Different antimuscarinics when combined with atomoxetine have differential effects on obstructive sleep apnea severity

The combination of the noradrenergic agent atomoxetine plus the anti-muscarinic oxybutynin has recently been shown to improve upper airway physiology and reduce obstructive sleep apnea (OSA) severity. However, the effects of different anti-muscarinics when combined with atomoxetine is limited. This study aimed to determine the effects of atomoxetine combined with two different anti-muscarinics with varying M-subtype receptor selectivity on OSA severity and upper airway physiology.10 people with predominantly severe OSA completed a double-blind, randomised, placebo-controlled, cross-over trial. Participants completed 3 overnight in-laboratory sleep studies after either 80mg atomoxetine+5mg solifenacin succinate (ato-sol) or 80mg atomoxetine+2mg biperiden hydrochloride (ato-bip) or placebo. OSA severity, ventilatory stability (loop gain), respiratory-arousal threshold (via epiglottic manometry), next day subjective sleepiness (Karolinska Sleepiness Scale:KSS) and alertness were compared between conditions. Neither drug combination altered the apnea/hypopnoea index versus placebo (p=0.63). Ato-sol caused a shift towards milder respiratory events with reduced frequency of obstructive apneas (13±14vs. 22±17events/h; mean±SD, p=0.04) and increased hypopneas during NREM (38±21vs. 24±18events/h, p=0.006) with improved nadir oxygenation versus placebo (83±4vs. 80±8%, p=0.03). Both combinations reduced loop gain by ~10% versus placebo; sleep efficiency and arousal threshold were unaltered. Ato-bip reduced next-day sleepiness versus placebo (KSS=4.3±2.2vs. 5.6±1.6, p=0.03).Atomoxetine+biperiden hydrochloride reduces perceived sleepiness and atomoxetine+solifenacin modestly improves upper airway function in people with OSA but to a lesser extent versus recently published atomoxetine+oxybutynin (broad M-subtype receptor selectivity) findings. These results provide novel mechanistic insight into the role of noradrenergic and anti-muscarinic agents on sleep and breathing and are important for pharmacotherapy development for OSA.

Changes in the Cystic Fibrosis Airway Microbiome in Response to CFTR Modulator Therapy

The development of CFTR modulator therapies significantly changed the treatment scheme of people with cystic fibrosis. However, CFTR modulator therapy is still a life-long treatment, which is not able to correct the genetic defect and cure the disease. Therefore, it becomes crucial to understand the effects of such modulation of CFTR function on the airway physiology, especially on airway infections and inflammation that are currently the major life-limiting factors in people with cystic fibrosis. In this context, understanding the dynamics of airway microbiome changes in response to modulator therapy plays an essential role in developing strategies for managing airway infections. Whether and how the newly available therapies affect the airway microbiome is still at the beginning of being deciphered. We present here a brief review summarizing the latest information about microbiome alterations in light of modern cystic fibrosis modulator therapy.

Optimization of combined measures of airway physiology and cardiovascular hemodynamics in mice

Pulmonary hypertension may arise as a complication of chronic lung disease typically associated with tissue hypoxia, as well as infectious agents or injury eliciting a type 2 immune response. The onset of pulmonary hypertension in this setting (classified as Group 3) often complicates treatment and worsens prognosis of chronic lung disease. Chronic lung diseases such as chronic obstructive lung disease (COPD), emphysema, and interstitial lung fibrosis impair airflow and alter lung elastance in addition to affecting pulmonary vascular hemodynamics that may culminate in right ventricle dysfunction. To date, functional endpoints in murine models of chronic lung disease have typically been limited to separately measuring airway and lung parenchyma physiology. These approaches may be lengthy and require a large number of animals per experiment. Here, we provide a detailed protocol for combined assessment of airway physiology with cardiovascular hemodynamics in mice. Ultimately, a comprehensive overview of pulmonary function in murine models of injury and disease will facilitate the integration of studies of the airway and vascular biology necessary to understand underlying pathophysiology of Group 3 pulmonary hypertension.

Endocannabinoid System in the Airways

Cannabinoids and the mammalian endocannabinoid system is an important research area of interest and attracted many researchers because of their widespread biological effects. The significant immune-modulatory role of cannabinoids has suggested their therapeutic use in several inflammatory conditions. Airways are prone to environmental irritants and stimulants, and increased inflammation is an important process in most of the respiratory diseases. Therefore, the main strategies for treating airway diseases are suppression of inflammation and producing bronchodilation. The ability of cannabinoids to induce bronchodilation and modify inflammation indicates their importance for airway physiology and pathologies. In this review, the contribution of cannabinoids and the endocannabinoid system in the airways are discussed, and the existing data for their therapeutic use in airway diseases are presented.

Airway Physiology

An understanding of airway physiology is important for the anesthesiologist, tasked with supporting the patient's respiratory functions which are altered in the conduct of anesthesia and surgery, or which may be abnormal due to co-existing disease. Airflow and airway resistance, lung compliance, spirometric values, flow-volume measurements, work of breathing, ventilation-perfusion matching, and oxygen-carbon dioxide transport are some of the basic principles. Clinical application of physiology allows the anesthesiologist to anticipate and manage changes that may occur when anesthetizing the patient, altering position or manipulating the airway. This review contains 5 tables, and 25 references. Keywords: Ohm’s law, laminar vs turbulent flow, Reynold’s number, Heliox, Bernoulli’s principle, compliance vs elasticity, Law of Laplace, spirometry, dead space, hypoxic pulmonary vasoconstriction

Physiologic and Pathophysiologic Responses to Intubation

The placement of an endotracheal tube provides definitive airway control for the anesthesiologist and protects the patient from aspiration, hypoventilation and hypoxemia. Airway instrumentation and intubation, however, cause physiologic changes that may have negative effects especially in patients with systemic disease. An abundance of sensory receptors and nerve endings exist in the upper airway that respond to noxious stimulation by activation of the autonomic nervous system, which cause brief but profound cardiovascular and neurologic effects. Stimulation of upper airway receptors may elicit reflexes such as sneezing, coughing, gagging, swallowing, vomiting, laryngospasm and bronchospasm. The presence of the endotracheal tube also bypasses the normal conduit for air movement and changes the airway physiology. This review contains 4 figures, 3 tables, and 45 references. Keywords: intubation, sympathetic response, coronary artery disease, aortic dissection, aortic aneurysm, intracranial pressure, attenuating response, airway devices