Awake Abnormalities of Control of Breathing and of the Upper Airway

Introduction Breathing must be tightly regulated so that the amount of oxygen inhaled and carbon dioxide exhaled matches precisely the metabolic needs of the body. Acute malfunction of breathing control mechanisms, even for a few seconds, may lead rapidly to serious physiologic derangements, with death as the final outcome if the system fails to recover. Chronic malfunction of breathing control mechanisms may lead to chronically abnormal blood gases (eg, hypoxemia), with such consequent complications as developmental delay or cor pulmonale. Because the upper airway is shared for breathing, eating, drinking, and talking, control of breathing also encompasses coordination of these actions in such a way that all are carried out effectively. The upper airway also must be actively held open during sleep or it will collapse during the inspiratory phase of breathing. Tone and activity of the muscles that maintain upper airway patency are controlled, in part, by the respiratory control systems. Malfunction of upper airway control mechanisms may play a role in obstructive sleep apnea. Thus, respiratory control not only refers to the control of gas exchange, but encompasses breathing pattern, apnea, respiratory protective reflexes, and upper airway control—specifically, maintenance of upper airway patency. This review will cover infant apnea and home cardiorespiratory monitoring, apparent life-threatening events (ALTEs) and home monitoring, obstructive sleep apnea syndrome (OSAS) in children, central hypoventilation syndromes, and hyperventilation syndromes.

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003 Treatment of Sleep Disordered Breathing with Leptin Loaded Exosomes

SLEEP ◽

10.1093/sleep/zsab072.002 ◽

2021 ◽

Vol 44 (Supplement_2) ◽

pp. A1-A2

Author(s):

Carla Freire ◽

Huy Pho ◽

Jacob Ramsey ◽

Stone Streeter ◽

Ryo Kojima ◽

...

Keyword(s):

Sleep Apnea ◽

Sleep Disordered Breathing ◽

Imaging System ◽

Minute Ventilation ◽

Upper Airway ◽

Control Of Breathing ◽

Obstructive Sleep ◽

Hypoventilation Syndrome ◽

Disordered Breathing

Abstract Introduction Obstructive sleep apnea (OSA) is characterized by recurrent periods of upper airway obstruction. The prevalence of OSA exceeds 50% in obese individuals and in 10–20% of obese patients OSA coexists with obesity hypoventilation syndrome (OHS) defined as daytime hypercapnia and hypoventilation during sleep attributed to the depressed control of breathing. There is no effective pharmacotherapy for OSA and OHS. Leptin is a potent respiratory stimulant and a potential therapeutic candidate. However, diet-induced obesity (DIO) results in reduced permeability of the blood-brain barrier (BBB) for leptin. Previous studies have shown that the BBB can be penetrated by exosomes, natural nanoparticles that can be used as drug delivery vehicles. In this study, we aimed to determine if exosomes overcome the BBB and treat OSA and OHS in DIO mice. Methods o examine the ability of exosomes to cross the BBB, male, lean (n=5) and DIO (n=5) C57BL/6J mice were injected with fluorescent exosomes or saline into the lateral tail vein. After 4h fluorescent exosomes biodistribution was evaluated by an in vitro imaging system (IVIS). Saline injected mice images were used for background adjustment. A separate subgroup of male, DIO (n=10) and lean (n=10) mice were headmounted with EEG and nuchal EMG leads. Sleep studies were performed in a plethysmography chamber and mice received saline, empty exosomes, free leptin, or leptin-loaded exosomes in a crossover manner. Results Exosomes were successfully delivered to the brain and the transport across the BBB was more efficient in DIO mice with 2-times greater relative fluorescence units measured in DIO when compared to lean mice (p<0.005). In DIO mice, exosomal leptin induced dramatic 1.7-2.2-fold increases in minute ventilation and 1.5-2.0-fold increases in maximal inspiratory flow during both flow-limited (upper airway/sleep apnea) and non-flow limited breathing (control of breathing) (p<0.05). In contrast, free leptin had no effect. Lean mice did not present significant sleep disordered breathing and no differences were observed between groups. Conclusion We demonstrated that exosomes overcome the BBB and that leptin-loaded exosomes treat OSA and OHS in DIO mice. Support (if any) R01HL 128970, R01HL 138932, R61 HL156240, U18 DA052301, FAPESP 2018/08758-3

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Respiratory Physiology in Critical Illness

Mayo Clinic Critical and Neurocritical Care Board Review ◽

10.1093/med/9780190862923.003.0001 ◽

2019 ◽

pp. 3-9

Author(s):

Minkyung Kwon ◽

Jose L. Diaz-Gomez

Keyword(s):

Carbon Dioxide ◽

Upper Airway ◽

Control Of Breathing ◽

Respiratory Physiology ◽

Lung Mechanics ◽

Detailed Knowledge ◽

Small Airways ◽

Dense Network ◽

Gas Barrier ◽

Simple Diffusion

The practice of critical care medicine requires detailed knowledge of the practical aspects of respiratory physiology, including lung mechanics, the physiology of hypoxia, and the control of breathing. Before the lungs can enable gas exchange, air must move from the upper airway down a series of branching small airways and reach the alveoli. In the walls of the alveoli, capillaries form a dense network and receive blood flowing from the pulmonary artery before it flows to the pulmonary vein. Between the capillary network and the alveoli lies a thin blood-gas barrier through which oxygen and carbon dioxide move, chiefly by simple diffusion.

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Control of breathing during sleep assessed by proportional assist ventilation

Journal of Applied Physiology ◽

10.1152/jappl.1998.84.1.3 ◽

1998 ◽

Vol 84 (1) ◽

pp. 3-12 ◽

Cited By ~ 42

Author(s):

S. Meza ◽

E. Giannouli ◽

M. Younes

Keyword(s):

Rem Sleep ◽

Slow Wave Sleep ◽

Minute Ventilation ◽

Upper Airway ◽

Normal Subjects ◽

Progressive Increase ◽

Control Of Breathing ◽

Respiratory Drive ◽

Proportional Assist Ventilation ◽

End Tidal

Meza, S., E. Giannouli, and M. Younes. Control of breathing during sleep assessed by proportional assist ventilation. J. Appl. Physiol. 84(1): 3–12, 1998.—We used proportional assist ventilation (PAV) to evaluate the sources of respiratory drive during sleep. PAV increases the slope of the relation between tidal volume (Vt) and respiratory muscle pressure output (Pmus). We reasoned that if respiratory drive is dominated by chemical factors, progressive increase of PAV gain should result in only a small increase in Vt because Pmus would be downregulated substantially as a result of small decreases in[Formula: see text]. In the presence of substantial nonchemical sources of drive [believed to be the case in rapid-eye-movement (REM) sleep] PAV should result in a substantial increase in minute ventilation and reduction in [Formula: see text] as the output related to the chemically insensitive drive source is amplified severalfold. Twelve normal subjects underwent polysomnography while connected to a PAV ventilator. Continuous positive air pressure (5.2 ± 2.0 cmH2O) was administered to stabilize the upper airway. PAV was increased in 2-min steps from 0 to 20, 40, 60, 80, and 90% of the subject’s elastance and resistance. Vt, respiratory rate, minute ventilation, and end-tidal CO2pressure were measured at the different levels, and Pmus was calculated. Observations were obtained in stage 2 sleep ( n = 12), slow-wave sleep ( n = 11), and REM sleep ( n = 7). In all cases, Pmus was substantially downregulated with increase in assist so that the increase in Vt, although significant ( P < 0.05), was small (0.08 liter at the highest assist). There was no difference in response between REM and non-REM sleep. We conclude that respiratory drive during sleep is dominated by chemical control and that there is no fundamental difference between REM and non-REM sleep in this regard. REM sleep appears to simply add bidirectional noise to what is basically a chemically controlled respiratory output.

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Sensory information from the upper airway: Role in the control of breathing

Respiration Physiology ◽

10.1016/0034-5687(95)00048-i ◽

1995 ◽

Vol 102 (1) ◽

pp. 1-16 ◽

Cited By ~ 132

Author(s):

Giuseppe Sant'Ambrogio ◽

Hirokazu Tsubone ◽

Franca B. Sant'Ambrogio

Keyword(s):

Sensory Information ◽

Upper Airway ◽

Control Of Breathing

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Role of the Larynx and Upper Airway in Control of Breathing during Exercise

Clinical Science ◽

10.1042/cs070068pa ◽

1986 ◽

Vol 70 (s13) ◽

pp. 68P-68P

Author(s):

W.N. Gardner ◽

M.S. Meah

Keyword(s):

Upper Airway ◽

Control Of Breathing

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Unstable control of breathing can lead to ineffective noninvasive ventilation in amyotrophic lateral sclerosis

ERJ Open Research ◽

10.1183/23120541.00099-2019 ◽

2019 ◽

Vol 5 (3) ◽

pp. 00099-2019 ◽

Cited By ~ 2

Author(s):

Jesús Sancho ◽

Enric Burés ◽

Santos Ferrer ◽

Ana Ferrando ◽

Pilar Bañuls ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Motor Neuron ◽

Noninvasive Ventilation ◽

Upper Airway ◽

Control Of Breathing ◽

Controller Gain ◽

Central Origin ◽

Als Patients ◽

Bulbar Dysfunction ◽

Lateral Sclerosis

Upper airway obstruction with decreased central drive (ODCD) is one of the causes of ineffective noninvasive ventilation (NIV) in amyotrophic lateral sclerosis (ALS). The aim of this study is to determine the mechanism responsible for ODCD in ALS patients using NIV.This is a prospective study that included ALS patients with home NIV. Severity of bulbar dysfunction was assessed with the Norris scale bulbar subscore; data on upper or lower bulbar motor neuron predominant dysfunction on physical examination were collected. Polysomnography was performed on every patient while using NIV and the ODCD index (ODCDI: number of ODCD events/total sleep time) was calculated. To determine the possible central origin of ODCD, controller gain was measured by inducing a hypocapnic hyperventilation apnoea. Sonography of the upper airway during NIV was performed to determine the location of the ODCD.30 patients were enrolled; three (10%) had ODCDI >5 h−1. The vast majority of ODCD events were produced during non-rapid eye movement sleep stages and were a consequence of an adduction of the vocal folds. Patients with ODCDI >5 h−1 had upper motor neuron predominant dysfunction at the bulbar level, and had greater controller gain (1.97±0.33 versus 0.91±0.36 L·min−1·mmHg−1; p<0.001) and lower carbon dioxide (CO2) reserve (4.00±0.00 versus 10.37±5.13 mmHg; p=0.043). ODCDI was correlated with the severity of bulbar dysfunction (r= −0.37; p=0.044), controller gain (r=0.59; p=0.001) and CO2 reserve (r= −0.35; p=0.037).ODCD events in ALS patients using NIV have a central origin, and are associated with instability in the control of breathing and an upper motor neuron predominant dysfunction at the bulbar level.

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Laryngeal Manifestations of Autoimmune Diseases

Perspectives of the ASHA Special Interest Groups ◽

10.1044/2020_persp-19-00168 ◽

2020 ◽

Vol 5 (2) ◽

pp. 439-456

Author(s):

Jenny L. Pierce

Keyword(s):

Autoimmune Disease ◽

Autoimmune Diseases ◽

Patient Outcomes ◽

Correct Diagnosis ◽

Upper Airway ◽

Clinical Implications ◽

Laryngeal Function ◽

The Past ◽

Referral Practices ◽

Timely Referral

Purpose This review article provides an overview of autoimmune diseases and their effects on voice and laryngeal function. Method A literature review was conducted in PubMed. Combinations of the following keywords were used: “autoimmune disease and upper airway,” “larynx,” “cough,” “voice,” “dysphonia,” and “dyspnea.” Precedence was given to articles published in the past 10 years due to recent advances in this area and to review articles. Ultimately, 115 articles were included for review. Results Approximately 81 autoimmune diseases exist, with 18 of those highlighted in the literature as having laryngeal involvement. The general and laryngeal manifestations of these 18 are discussed in detail, in addition to the clinical implications for a laryngeal expert. Conclusions Voice, breathing, and cough symptoms may be an indication of underlying autoimmune disease. However, these symptoms are often similar to those in the general population. Appropriate differential diagnosis and timely referral practices maximize patient outcomes. Guidelines are provided to facilitate correct diagnosis when an autoimmune disease is suspected.

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Distraction Osteogenesis in the Treatment of Craniofacial Anomalies: Applications and Outcomes

Perspectives of the ASHA Special Interest Groups ◽

10.1044/2020_persp-20-00055 ◽

2020 ◽

Vol 5 (6) ◽

pp. 1469-1481 ◽

Cited By ~ 1

Author(s):

Joseph A. Napoli ◽

Carrie E. Zimmerman ◽

Linda D. Vallino

Keyword(s):

Distraction Osteogenesis ◽

Bone Growth ◽

Upper Airway ◽

Craniofacial Anomalies ◽

Craniofacial Skeleton ◽

Facial Skeleton ◽

Psychosocial Impairment ◽

And Function ◽

Correct Structure

Purpose Craniofacial anomalies (CFA) often result in growth abnormalities of the facial skeleton adversely affecting function and appearance. The functional problems caused by the structural anomalies include upper airway obstruction, speech abnormalities, feeding difficulty, hearing deficits, dental/occlusal defects, and cognitive and psychosocial impairment. Managing disorders of the craniofacial skeleton has been improved by the technique known as distraction osteogenesis (DO). In DO, new bone growth is stimulated allowing bones to be lengthened without need for bone graft. The purpose of this clinical focus article is to describe the technique and clinical applications and outcomes of DO in CFA. Conclusion Distraction can be applied to various regions of the craniofacial skeleton to correct structure and function. The benefits of this procedure include improved airway, feeding, occlusion, speech, and appearance, resulting in a better quality of life for patients with CFA.

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Swallow Pattern Generator Reconfiguration of the Respiratory Neural Network

Perspectives on Swallowing and Swallowing Disorders (Dysphagia) ◽

10.1044/sasd18.1.3 ◽

2009 ◽

Vol 18 (1) ◽

pp. 3-12

Author(s):

Andrea Vovka ◽

Paul W. Davenport ◽

Karen Wheeler-Hegland ◽

Kendall F. Morris ◽

Christine M. Sapienza ◽

...

Keyword(s):

Behavioral Control ◽

Upper Airway ◽

Pattern Generator ◽

Breathing Patterns ◽

Motor Patterns ◽

Control Assembly ◽

Pharyngeal Swallow ◽

Laryngeal Vestibule ◽

Lower Airways ◽

Swallow Apnea

Abstract When the nasal and oral passages converge and a bolus enters the pharynx, it is critical that breathing and swallow motor patterns become integrated to allow safe passage of the bolus through the pharynx. Breathing patterns must be reconfigured to inhibit inspiration, and upper airway muscle activity must be recruited and reconfigured to close the glottis and laryngeal vestibule, invert the epiglottis, and ultimately protect the lower airways. Failure to close and protect the glottal opening to the lower airways, or loss of the integration and coordination of swallow and breathing, increases the risk of penetration or aspiration. A neural swallow central pattern generator (CPG) controls the pharyngeal swallow phase and is located in the medulla. We propose that this swallow CPG is functionally organized in a holarchical behavioral control assembly (BCA) and is recruited with pharyngeal swallow. The swallow BCA holon reconfigures the respiratory CPG to produce the stereotypical swallow breathing pattern, consisting of swallow apnea during swallowing followed by prolongation of expiration following swallow. The timing of swallow apnea and the duration of expiration is a function of the presence of the bolus in the pharynx, size of the bolus, bolus consistency, breath cycle, ventilatory state and disease.

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