Teaching the distribution of pulmonary blood flow using a Starling resistor model and turbine flowmeters.

The distribution of pulmonary blood flow is uneven and can be described as a three-zone model, the West zones: zone 1 occurs whenever alveolar pressure exceeds arterial pressure; zone 2 when the arterial pressure is greater than alveolar but the alveolar pressure exceeds the venous pressure; and finally zone 3 when both arterial and venous pressures exceed alveolar pressure. Consequently, the blood flow is almost determined by the difference between the arterial and venous pressures in zone 3 and between arterial and alveolar pressures in zone 2 and ceases in zone 1. The understanding of this subject may be difficult to some medical students. Therefore, to improve the learning of this topic in our physiology course, we used a didactic model to demonstrate the core concept of flow down gradients and its application to pulmonary blood flow. We modeled a Starling resistor by placing a collapsible tube inside a hermetic chamber of variable pressure. Transparent turbine flowmeters were connected to the upstream and downstream extremities of the Starling resistor, and we generated a constant airflow with a brushless motor. By maintaining the input (arterial) pressure constant and varying the chamber (alveolar) pressure, we could simulate the three zones and demonstrate the resulting flow through the turbines. In conclusion, our demonstration using a Starling resistor model combined with visible turbine flowmeters can be used to facilitate comprehension of important concepts in physiology involving flow down gradients, such as pulmonary blood flow.NEW & NOTEWORTHY The understanding of respiratory physiology is a challenge to medical students. To improve the learning of pulmonary blood flow distribution through lung vessels in our physiology course, we modeled a Starling resistor model combined with visible turbine flowmeters. Our model can significantly improve the core concept of flow down gradients teaching and its application to West zones.

Headache in idiopathic intracranial hypertension. A CGRP-dependent head pain?

Headache is the most frequent and often the most severe symptom of idiopathic intracranial hypertension (IIH) clinical presentation, although pain characteristics are very variable among sufferers and the pain may even lack in some cases. Whatever the headache features, refractoriness to treatments, pain worsening in the recumbent position, and frequent awakenings with severe headache late in the night are the specific complains of such patients. However, a migraine or probable migraine headache, mostly with a chronic headache pattern, can be diagnosed in about 2/3 of the cases. In IIH cases without papilledema (IIHWOP), this leads to a high rate of misdiagnosis with primary chronic migraine (CM). Mechanisms responsible for the shared migrainous presentation of CM and IIH/IIHWOP may rely on a pathologic CGRP release from the rich trigemino-vascular innervated dural sinuses, congested in the course of raised intracranial pressure. The possible role of IIHWOP as a powerful and modifiable risk factor for migraine progression is discussed. Further studies investigating the possible efficacy of anti CGRP/receptor antibodies in IIH/IIHWOP headache treatment are needed.

Dural sinus collapsibility, idiopathic intracranial hypertension, and the pathogenesis of chronic migraine.

Available evidences suggest that a number of known assumption on idiopathic intracranial hypertension (IIH) with or without papilledema might be discussed. These include (1) the primary pathogenetic role of an excessive dural sinus collapsibility in IIH, allowing a new relatively stable intracranial fluids pressure balance at higher values; (2) the non-mandatory role of papilledema for a definite diagnosis; (3) the possibly much higher prevalence of IIH without papilledema than currently considered; (4) the crucial role of the cerebral compliance exhaustion that precede the raise in intracranial pressure and that may already be pathologic in cases showing a moderately elevated opening pressure; (5) the role as "intracranial pressure sensor" played by the trigeminovascular innervation of dural sinuses and cortical bridge veins, which could represent a major source of CGRP and may explain the high comorbidity and the emerging causative link between IIHWOP and chronic migraine (CM). Accordingly, the control of intracranial pressure is to be considered a promising new therapeutic target in CM.

Chronic overdrainage syndrome: pathophysiological insights based on ICP analysis: a case-based review.

INTRODUCTION: Chronic overdrainage affects shunted patients producing a variety of symptoms that may be misdiagnosed. The best known symptoms are so-called shunt-related headaches. There is mounting evidence that changes in cerebrospinal venous system dynamics are a key factor to the pathophysiology of chronic overdrainage syndrome. CLINICAL PRESENTATION: We report the case of a 29-year-old woman with a shunt since the postnatal period suffering from chronic but the most severe intermittent headache attacks, despite an open shunt and with unchanged ventricular width during attacks. Intracranial pressure (ICP) recordings were performed during headache attacks and thereafter. DIAGNOSIS AND MANAGMENT: Massively increased ICPs, a continuous B wave "storm," and severely compromised intracranial compliance despite an open shunt were found, a scenario that was always self-limiting with the resolution of symptoms after several hours. When mobilized to the upright position, her ICPs dropped to - 17 mm Hg, proving shunt overdrainage. OUTCOME AND CONCLUSIONS: Symptomatology can only be explained by sudden venous entrapment following chronic venous distention as a result of chronic overdrainage. Subsequent therapeutic management with an overdrainage preventing shunt and satisfying clinical outcome with complete ceasing of headache attacks adds insight into the pathophysiology of chronic overdrainage syndrome.

Computational micro-scale model of control of extravascular water and capillary perfusion in the air blood barrier.

A computational model of a morphologically-based alveolar capillary unit (ACU) in the rabbit is developed to relate lung fluid balance to mechanical forces between capillary surface and interstitium during development of interstitial edema. We hypothesize that positive values of interstitial liquid pressure Pliq impact on capillary transmural pressure and on blood flow. ACU blood flow, capillary recruitment and filtration are computed by modulating vascular and interstitial pressures. Model results are compared with experimental data of Pliq increasing from ~-10 (control) up to ~4cmH2O in two conditions, hypoxia and collagenase injection. For hypoxia exposure, fitting data requires a linear increase in hydraulic conductivity Lp and capillary pressure PC, that fulfils the need of increase in oxygen delivery. For severe fragmentation of capillary endothelial barrier (collagenase injection), fitting requires a rapid increase in both hydraulic and protein permeability, causing ACU de-recruitment, followed by an increase in PC as a late response to restore blood flow. In conclusion, the model allows to describe the lung adaptive response to edemagenic perturbations; the increase in Pliq, related to the low interstitial compliance, provides an efficient control of extravascular water, by limiting microvascular filtration.

The cerebral venous system and the postural regulation of intracranial pressure: implications in the management of patients with cerebrospinal fluid diversion.

Loss of cerebrospinal fluid (CSF) occurs commonly in daily neurosurgical practice. Understanding the altered physiology following CSF loss is important for optimization of patient care and avoidance of complications. There is overwhelming evidence now that the cerebral venous system plays a major role in intracranial pressure (ICP) dynamics especially when one takes into account the effects of postural changes, atmospheric pressure, and gravity on the craniospinal axis as a whole. The CSF and cerebral venous compartments are tightly coupled in two important ways. CSF is resorbed into the venous system, and there is also an evolved mechanism that prevents overdrainage of venous blood with upright positioning known as the Starling resistor. With loss of CSF pressure, this protective mechanism could become nonfunctional which may result in posture-related venous overdrainage through the cranial venous outflow tracts leading to pathologic states. This review article summarizes the relevant anatomic and physiologic basis of the relationship between the craniospinal venous and CSF compartments in the setting of CSF diversion. It is hoped that this article improves our understanding of ICP dynamics after CSF loss, adds a new dimension to our therapeutic methods, stimulates further research into this field, and ultimately improves our care of these patients.

Cerebral venous overdrainage: an under-recognized complication of cerebrospinal fluid diversion.

Understanding the altered physiology following cerebrospinal fluid (CSF) diversion in the setting of adult hydrocephalus is important for optimizing patient care and avoiding complications. There is mounting evidence that the cerebral venous system plays a major role in intracranial pressure (ICP) dynamics especially when one takes into account the effects of postural changes, atmospheric pressure, and gravity on the craniospinal axis as a whole. An evolved mechanism acting at the cortical bridging veins, known as the "Starling resistor," prevents overdrainage of cranial venous blood with upright positioning. This protective mechanism can become nonfunctional after CSF diversion, which can result in posture-related cerebral venous overdrainage through the cranial venous outflow tracts, leading to pathological states. This review article summarizes the relevant anatomical and physiological bases of the relationship between the craniospinal venous and CSF compartments and surveys complications that may be explained by the cerebral venous overdrainage phenomenon. It is hoped that this article adds a new dimension to our therapeutic methods, stimulates further research into this field, and ultimately improves our care of these patients.

Simulation using novel equipment designed to explain spirometric abnormalities in respiratory disease enhances learning in higher cognitive domains.

Simulation of disorders of respiratory mechanics shown by spirometry provides insight into the pathophysiology of disease but some clinically important disorders have not been simulated and none have been formally evaluated for education. We have designed simple mechanical devices which, along with existing simulators, enable all the main dysfunctions which have diagnostic value in spirometry to be simulated and clearly explained with visual and haptic feedback. We modelled the airways as Starling resistors by a clearly visible mechanical action to simulate intra- and extra-thoracic obstruction. A narrow tube was used to simulate fixed large airway obstruction and inelastic bands to simulate restriction. We hypothesized that using simulators whose action explains disease promotes learning especially in higher domain educational objectives. The main features of obstruction and restriction were correctly simulated. Simulation of variable extra-thoracic obstruction caused blunting and plateauing of inspiratory flow, and simulation of intra-thoracic obstruction caused limitation of expiratory flow with marked dynamic compression. Multiple choice tests were created with questions allocated to lower (remember and understand) or higher cognitive domains (apply, analyse and evaluate). In a cross-over design, overall mean scores increased after 1½ h simulation spirometry (43-68 %, effect size 1.06, P < 0.0001). In higher cognitive domains the mean score was lower before and increased further than lower domains (Δ 30 vs 20 %, higher vs lower effect size 0.22, P < 0.05). In conclusion, the devices successfully simulate various patterns of obstruction and restriction. Using these devices medical students achieved marked enhancement of learning especially in higher cognitive domains.

Phenotypes of Velopharyngeal Tube Law in Obstructive Sleep Apnea.

OBJECTIVE: The biomechanics of upper airway collapse in obstructive sleep apnea (OSA) remains poorly understood. The goal of this study is to compare the area-pressure relationship (tube law) of the velopharynx at peak inspiration and peak expiration. STUDY DESIGN: Cross-sectional. SETTING: Academic tertiary medical center. METHODS: The velopharyngeal tube law was quantified in a convenience sample of 20 OSA patients via step reductions in nasal mask pressure during drug induced sleep endoscopy (DISE). The velopharyngeal airspace cross-sectional area was estimated from endoscopy while luminal pressure was recorded with a catheter. The tube law was quantified for nasal mask pressures from 14 to 0 cmH2O at peak inspiration and at peak expiration in all patients. The tube law was also quantified during the breathing cycle at a constant nasal mask pressure of 4 cmH2O in 3 patients representing different phenotypes. RESULTS: Velopharyngeal compliance (the slope of the tube law) was not statistically different in the peak inspiration versus peak expiration tube laws. Three phenotypes were observed, namely inspiratory collapse (phenotype 1), expiratory collapse (phenotype 2 = palatal prolapse), and a mostly stable airway during inspiration and expiration that collapsed as CPAP was reduced (phenotype 3). CONCLUSION: Velopharyngeal compliance is not significantly different at peak inspiration and peak expiration, which suggests that muscle tone is low when luminal pressure is above the closing pressure. Additional studies are needed to investigate how different phenotypes of velopharyngeal collapse may affect therapeutic outcomes.

Mechanical mechanism to induce inspiratory flow limitation in obstructive sleep apnea patients revealed from in-vitro studies.

Inspiratory flow limitation means that when the flowrate reaches a certain value, it no longer increases, or even decreases, which is called negative effort dependence flow limitation, even if the inspiration effort is increased. This occurs often in obstructive sleep apnea patients, but its mechanism remains unclear. To reveal the mechanism of inspiratory flow limitation, we constructed a unique partially collapsible in-vitro upper airway model of obstructive sleep apnea patients to observe the change of airway resistance with inspiratory driving pressure. The important findings demonstrate that with the increase of inspiratory effort, the driving pressure increases faster than the airway resistance in the early stages, and then the reverse occurs as the airway becomes narrower. The airway collapse caused by the transmural pressure can lead to a rapid increase in downstream resistance with the increase of inspiratory effort, which is the key reason causing the flow reduction and the formation of typical negative effort dependence flow limitation. The mechanical mechanism revealed in this study will lead to fully new insights into the study and treatment of obstructive sleep apnea.

Anatomical determinants of upper airway collapsibility in obstructive sleep apnea: A systematic review and meta-analysis.

Upper airway (UA) collapsibility is one of the key factors that determine the severity of obstructive sleep apnea (OSA). Interventions for OSA are aimed at reducing UA collapsibility, but selecting the optimal alternative intervention for patients who fail CPAP is challenging because currently no validated method predicts how anatomical changes affect UA collapsibility. The gold standard objective measure of UA collapsibility is the pharyngeal critical pressure (Pcrit). A systematic literature review and meta-analysis were performed to identify the anatomical factors with the strongest correlation with Pcrit. A search using the PRISMA methodology was performed on PubMed for English language scientific papers that correlated Pcrit to anatomic variables and OSA severity as measured by the apnea-hypopnea index (AHI). A total of 29 papers that matched eligibility criteria were included in the quantitative synthesis. The meta-analysis suggested that AHI has only a moderate correlation with Pcrit (estimated Pearson correlation coefficient r = 0.46). The meta-analysis identified four key anatomical variables associated with UA collapsibility, namely hyoid position (r = 0.53), tongue volume (r = 0.51), pharyngeal length (r = 0.50), and waist circumference (r = 0.49). In the future, biomechanical models that quantify the relative importance of these anatomical factors in determining UA collapsibility may help identify the optimal intervention for each patient. Many anatomical and structural factors such as airspace cross-sectional areas, epiglottic collapse, and palatal prolapse have inadequate data and require further research.

Obstructive sleep apnea.

Obstructive sleep apnea (OSA) is a disease that results from loss of upper airway muscle tone leading to upper airway collapse during sleep in anatomically susceptible persons, leading to recurrent periods of hypoventilation, hypoxia, and arousals from sleep. Significant clinical consequences of the disorder cover a wide spectrum and include daytime hypersomnolence, neurocognitive dysfunction, cardiovascular disease, metabolic dysfunction, respiratory failure, and pulmonary hypertension. With escalating rates of obesity a major risk factor for OSA, the public health burden from OSA and its sequalae are expected to increase, as well. In this chapter, we review the mechanisms responsible for the development of OSA and associated neurocognitive and cardiometabolic comorbidities. Emphasis is placed on the neural control of the striated muscles that control the pharyngeal passages, especially regulation of hypoglossal motoneuron activity throughout the sleep/wake cycle, the neurocognitive complications of OSA, and the therapeutic options available to treat OSA including recent pharmacotherapeutic developments.

Venous overload choroidopathy: A hypothetical framework for central serous chorioretinopathy and allied disorders.

In central serous chorioretinopathy (CSC), the macula is detached because of fluid leakage at the level of the retinal pigment epithelium. The fluid appears to originate from choroidal vascular hyperpermeability, but the etiology for the fluid is controversial. The choroidal vascular findings as elucidated by recent optical coherence tomography (OCT) and wide-field indocyanine green (ICG) angiographic evaluation show eyes with CSC have many of the same venous patterns that are found in eyes following occlusion of the vortex veins or carotid cavernous sinus fistulas (CCSF). The eyes show delayed choroidal filling, dilated veins, intervortex venous anastomoses, and choroidal vascular hyperpermeability. While patients with occlusion of the vortex veins or CCSF have extraocular abnormalities accounting for the venous outflow problems, eyes with CSC appear to have venous outflow abnormalities as an intrinsic phenomenon. Control of venous outflow from the eye involves a Starling resistor effect, which appears to be abnormal in CSC. Similar choroidal vascular abnormalities have been found in peripapillary pachychoroid syndrome. However, peripapillary pachychoroid syndrome has intervortex venous anastomoses located in the peripapillary region while in CSC these are seen to be located in the macular region. Spaceflight associated neuro-ocular syndrome appears to share many of the pathophysiologic problems of abnormal venous outflow from the choroid along with a host of associated abnormalities. These diseases vary according to their underlying etiologies but are linked by the venous decompensation in the choroid that leads to significant vision loss. Choroidal venous overload provides a unifying concept and theory for an improved understanding of the pathophysiology and classification of a group of diseases to a greater extent than previous proposals.

An experimental investigation to model wheezing in lungs.

A quarter of the world's population experience wheezing. These sounds have been used for diagnosis since the time of the Ebers Papyrus (ca 1500 BC). We know that wheezing is a result of the oscillations of the airways that make up the lung. However, the physical mechanisms for the onset of wheezing remain poorly understood, and we do not have a quantitative model to predict when wheezing occurs. We address these issues in this paper. We model the airways of the lungs by a modified Starling resistor in which airflow is driven through thin, stretched elastic tubes. By completing systematic experiments, we find a generalized 'tube law' that describes how the cross-sectional area of the tubes change in response to the transmural pressure difference across them. We find the necessary conditions for the onset of oscillations that represent wheezing and propose a flutter-like instability model for it about a heavily deformed state of the tube. Our findings allow for a predictive tool for wheezing in lungs, which could lead to better diagnosis and treatment of lung diseases.

Effect of tube length on the buckling pressure of collapsible tubes.

BACKGROUND: The higher incidence of obstructive sleep apnea (OSA) in men than in women has been attributed to the upper airway being longer in men. The Starling resistor is the paradigm biomechanical model of upper airway collapse in OSA where a collapsible tube (representing the pharynx) is located between two rigid tubes (representing the nasal cavity and trachea). While the Starling resistor has been extensively studied due to its relevance to many physiological phenomena, the effect of tube length on tube collapsibility has not been quantified yet. METHODS: Finite element analysis of a 3-dimensional collapsible tube subjected to a transmural pressure was performed in ANSYS Workbench. The numerical methods were validated with in vitro experiments in a silicone tube whose modulus of elasticity (361 ± 28 kPa) and dimensions (length = 100 mm, diameter = 22.2 mm, and wall thickness = 1.59 mm) were selected so that tube compliance was similar to pharyngeal compliance in humans during sleep. The buckling pressure (transmural pressure at which the tube collapses) was quantified in tubes of three different diameters (10 mm, 16 mm, and 22.2 mm) and ten length-to-diameter ratios (L/D = 4 to 13), while keeping the wall-thickness-to-radius ratio constant at 0.143. RESULTS: The absolute value of the buckling pressure decreased from 4.7 to 3.3 cmH2O (461-324 Pa) when L/D increased from 4 to 13. The buckling pressure was nearly independent from tube length for L/D >10. CONCLUSIONS: Our finding that longer tubes are more collapsible than shorter tubes is consistent with the higher incidence of obstructive sleep apnea in males than females.

Much Ado about Sleep: Current Concepts on Mechanisms and Predisposition to Pediatric Obstructive Sleep Apnea.

Obstructive Sleep Apnea (OSA) is a form of sleep-disordered breathing characterized by upper airway collapse during sleep resulting in recurring arousals and desaturations. However, many aspects of this syndrome in children remain unclear. Understanding underlying pathogenic mechanisms of OSA is critical for the development of therapeutic strategies. In this article, we review current concepts surrounding the mechanism, pathogenesis, and predisposing factors of pediatric OSA. Specifically, we discuss the biomechanical properties of the upper airway that contribute to its primary role in OSA pathogenesis and examine the anatomical and neuromuscular factors that predispose to upper airway narrowing and collapsibility.

Remote Cerebellar Hemorrhage Following Surgery for Supratentorial Lesions.

BACKGROUND: Remote cerebellar hemorrhage (RCH) after intracranial surgery is a rare complication. Cerebellar hemorrhage is the most commonly described remote site hemorrhage after surgery for supratentorial pathologies. Although this is a rare complication 0.04% to 0.8%, it can be devastating in terms of patient outcome. There are various hypotheses to explain the occurrence of RCH. We report 6 cases of RCH after surgery for supratentorial lesions, discuss the pathophysiology, and review the pertinent literature. METHODS: We retrospectively analyzed data of patients who underwent surgery for supratentorial lesions at our center between 2015 and 2017. We identified 6 patients who developed RCH among 1200 patients who underwent surgery and reviewed the demographic data, diagnosis, surgical procedure, and final outcome. RESULTS: A total of 1200 patients underwent surgery for supratentorial pathologies between 2015 and 2017. Six patients developed RCH (incidence, 0.5%); 5 were male and 1 was female, with a mean age of 46.4 years. One patient underwent suboccipital decompression for RCH; the rest 5 were managed with close observation and serial imaging. The Glasgow outcome scale (GOS) of 5 was observed in 4 patients, GOS of 4 in 1 patient at discharge, and GOS of 1 in 1 patient who succumbed to severe pulmonary infection after surgery. CONCLUSIONS: RCH is a rare complication but can lead to catastrophic results. Loss of large volumes of cerebrospinal fluid or sudden alteration in intracranial pressure due to removal of a mass lesion is the likely etiology. Although majority of cases may be managed conservatively, in a subset of cases with neurologic deterioration, surgery may be required as a life-saving procedure.

Airflow limitation in a collapsible model of the human pharynx: physical mechanisms studied with fluid-structure interaction simulations and experiments.

The classical Starling Resistor model has been the paradigm of airway collapse in obstructive sleep apnea (OSA) for the last 30 years. Its theoretical framework is grounded on the wave-speed flow limitation (WSFL) theory. Recent observations of negative effort dependence in OSA patients violate the predictions of the WSFL theory. Fluid-structure interaction (FSI) simulations are emerging as a technique to quantify how the biomechanical properties of the upper airway determine the shape of the pressure-flow curve. This study aimed to test two predictions of the WSFL theory, namely (1) the pressure profile upstream from the choke point becomes independent of downstream pressure during flow limitation and (2) the maximum flowrate in a collapsible tube is VImax=A3/2(ρdA/dP)-1/2 , where ρ is air density and A and P are the cross-sectional area and pressure at the choke point respectively. FSI simulations were performed in a model of the human upper airway with a collapsible pharynx whose wall thickness varied from 2 to 8 mm and modulus of elasticity ranged from 2 to 30 kPa. Experimental measurements in an airway replica with a silicone pharynx validated the numerical methods. Good agreement was found between our FSI simulations and the WSFL theory. Other key findings include: (1) the pressure-flow curve is independent of breathing effort (downstream pressure vs. time profile); (2) the shape of the pressure-flow curve reflects the airway biomechanical properties, so that VImax is a surrogate measure of pharyngeal compliance.

Anatomic and Pathophysiologic Considerations in Surgical Treatment of Obstructive Sleep Apnea.

Evaluation of the upper airway is key for a successful surgical management. Proper evaluation can be done only with a good understanding of the anatomy and pathophysiology of the upper airway. The authors discuss surgical anatomy from a soft tissue and bony perspective in detail along with its clinical implications. The complex interaction among pharyngeal dilator tone, arousal threshold, respiratory control instability, and changes in lung volume during sleep play an important role in obstructive sleep apnea. Because all the anatomic and physiologic characteristics discussed have genetic predisposition, gene therapy may play a pivotal role in the future.

Mimicking a flow-limited human upper airway using a collapsible tube: relationships between flow patterns and pressures in a respiratory model.

The upper airway (UA) in humans is commonly modeled as a Starling resistor. However, negative effort dependence (NED) observed in some patients with obstructive sleep apnea (OSA) contradicts predictions based on the Starling resistor model in which inspiratory flow is independent of inspiratory driving pressure when flow is limited. In a respiratory bench model consisting of a collapsible tube and an active lung model (ASL5000), inspiratory flow characteristics were investigated in relation to upstream, downstream, and extra-luminal pressures (denoted as Pus, Pds, and Pout, respectively) by varying inspiratory effort (muscle pressure) from -1 to -20 cmH2O in the active lung. Pus was provided by a constant airway pressure device and varied from 4 to 20 cmH2O, and Pout was set at 10 and 15 cmH2O. Upstream resistance at onset of flow limitation and critical transmural pressure (Ptm) corresponding to opening of the UA were found to be independent of Pus, Pds, and Pout. With fixed Ptm, when Pds fell below a specific value (Pds'), inspiratory peak flow became constant and independent of Pds. NED plateau flow patterns at mid-inspiration (V̇n) were produced within the current bench setting when Pds fell below Pds'. V̇n was proportional to Pds, and the slope (ΔV̇n/ΔPds) increased linearly with Ptm. Ptm and Pds were the two final independent determinants of inspiratory flow. Our bench model closely mimics a flow-limited human UA, and the findings have implications for OSA treatment and research, especially for bench-testing auto-titrating devices in a more physiological way. NEW & NOTEWORTHY A respiratory model consisting of a collapsible tube was used to mimic a flow-limited human upper airway. Flow-limited breathing patterns including negative effort dependence were produced. Transmural and downstream pressures acting on the tube are the two independent determinants of the resulting inspiratory flow during flow limitation. The findings have implications for obstructive sleep apnea treatment and research, especially for bench-testing auto-titrating devices in a more physiological way.