Face mask application for calibration of respiratory inductive plethysmography in lambs

Respiratory inductive plethysmography is a non-invasive method of assessing breathing patterns that requires an airway connection for calibration. In previous studies an endotracheal tube was used to establish this connection. We employed a single position graphic calibration technique for gain calculation using a conical face mask in place of the endotracheal tube, thus eliminating the need for sedation and topical anaesthesia. Thirteen studies were completed on seven lambs. Validation of gains was performed by comparing volumes obtained simultaneously by respiratory inductive plethysmography and integrated pneumotachography. Total study time ranged between 5 and 10 min for each calibration procedure. Our results suggest that the conical mask can be used to perform accurate and time-efficient calibration of the respiratory inductive plethysmograph in the spontaneously breathing non-sedated lamb and eliminates the need for endotracheal intubation.     

Calibration of respiratory inductive plethysmography during quiet and active sleep in lambs

Respiratory inductive plethysmography provides a noninvasive method of measuring breathing patterns. Calibration of respiratory inductive plethysmography requires calculation of gain factors for ribcage and abdomen transducers utilizing 2 breathing patterns with different ribcage and abdomen contributions and tidal volume measured by either spirometry or integrated pneumotachography. The purpose of this study was to determine if respiratory inductive plethysmography can be calibrated to provide accurate measurements during quiet and active sleep in lambs. We used a least squares linear regression calibration technique with breaths selected from quiet sleep and active sleep to calculate gain factors in 6 tracheostomized lambs. Validation of gain factors was performed by comparing tidal volumes obtained simultaneously by respiratory inductive plethysmography and pneumotachography during quiet sleep and active sleep. Tidal volume differences between respiratory inductive plethysmography and pneumotachography on validation runs of 15 consecutive breaths each revealed 90% of validation breaths within +/- 20% during quiet sleep and 82% of validation breaths within +/- 20% during active sleep. These data provide evidence that respiratory inductive plethysmography can be calibrated to allow breathing pattern measurement during sleep.     

Mathematical assessment of qualitative diagnostic calibration for respiratory inductive plethysmography.

We present a critical assessment of qualitative diagnostic calibration (QDC), which claims to provide a relative calibration of respiratory inductive plethysmography during natural breathing (Sackner MA, Watson H, Belsito AS, Feinerman D, Suarez M, Gonzalez G, Bizousky F, and Krieger B. J Appl Physiol 66: 410-420, 1989). QDC computes the calibration factor (K) by considering breaths of constant tidal volume (VT) and provides a criterion to select breaths when VT is unknown. We applied QDC on uncalibrated data constructed from simulated sets of thoracic and abdominal volumes, with a predefined K. As expected, QDC yields a correct K when applied to breaths at constant VT. In breathing at quasi-constant VT, the criterion for breath selection is shown to bias the results toward K = 1. For spontaneous breathing, the calculated K deviates from its predefined value and depends heavily on the selection criterion. We conclude that QDC will only provide a correct calibration factor when applied to an entire set of breaths with constant or quasi-constant VT. More generally, physiological conclusions based on QDC should be critically evaluated on a case-by-case basis.     

Accuracy of the respiratory inductive plethysmograph during loaded breathing

Indirect methods of measuring ventilation, such as the respiratory inductive plethysmograph (RIP), operate on the assumption that the respiratory system possesses two degrees of freedom of motion: the rib cage and abdomen. Accurate measurements have been obtained in many patients with pulmonary disease who possess additional degrees of freedom. Since calibration and validation of the RIP was carried out during quiet breathing in these patients, the amount of asynchronous or paradoxic breathing was presumably similar during the calibration and validation runs. Conversely, accuracy might be lost if following the initial calibration procedure the magnitude of chest wall distortion increased during subsequent validation runs. We calibrated the RIP during quiet breathing and examined its accuracy while subsequently breathing against resistive loads that required the generation of 20-80% of the subject's maximum inspiratory mouth pressure (Pmmax). We compared the relative accuracy of three commonly employed calibration methods: isovolume technique, least-squares technique, and single position loop-area technique. Up to 60% of Pmmax, 89% of the RIP values with the least-squares technique were within +/- 10% of simultaneous spirometric (SP) measurements and 100% were within +/- 20% of SP, compared with 63 and 91%, respectively, for the loop-area technique and 19 and 54%, respectively, for the isovolume technique. At 70 and 80% of Pmmax accuracy deteriorated. Accuracy of respiratory timing was judged in terms of fractional inspiratory time (TI/TT).(ABSTRACT TRUNCATED AT 250 WORDS)     

Noninvasive ventilatory monitoring with bellows pneumographs in supine subjects

We compared simultaneous measurements of ventilatory movements obtained by a bellows pneumograph (BP) and a respiratory inductive plethysmograph (RIP) vs. integrated volume from a pneumotachograph in seven healthy volunteers during different respiratory patterns. The purpose of this study was to assess if a computer-aided calibration procedure could improve the accuracy of BP, a simple semiquantitative method for noninvasive ventilatory monitoring in supine subjects. Both devices were repeatedly calibrated against a pneumotachograph in the same posture with a computer-aided least-squares method. One calibration maneuver was sufficient to achieve a minimal relative difference in volume measurements between the RIP as well as the BP and the pneumotachograph of less than 1.2 +/- 4.5 (SD) %. The accuracy remained in this range during the subsequent calibrations with time (1 h) and after body movements. However, this difference increased significantly with both devices when the subjects were studied in the lateral decubitus position. The present study indicates that despite theoretical advantages of the RIP, the BP, when properly calibrated, has similar performances in supine subjects for monitoring ventilation; it is simpler and less expensive than the RIP and is devoid of electrical drift and artifacts.     

Respiratory volume perception through the nose and mouth determined noninvasively

The relative importance of the nose vs. the mouth in the perception of respiratory volumes has never been assessed, nor have previous respiratory perception studies been performed noninvasively. Using respiratory inductive plethysmography, we monitored 12 normal subjects noninvasively when breathing either exclusively through the nose or mouth. The sensation of inspired volume mouth breathing was compared with that of nose breathing over a wide range of the inspiratory capacity. The psychophysical techniques of tidal volume duplication, tidal volume doubling, and magnitude estimation were utilized. A just noticeable difference was calculated from the constant error of the tidal volume duplication trials. The exponents for magnitude estimation were 1.06 and 1.07 for nose and mouth breathing, respectively. The other psychophysical techniques also revealed no differences in nose and mouth volume perception. These results suggest that tidal volume changes are perceived equally well through the nose and mouth. Furthermore, the location of the receptors, important in volume perception, is probably at a distal point common to the nose and mouth.     

Transition from dynamically maintained to relaxed end-expiratory volume in human infants

Newborn infants, in contrast to adults, dynamically maintain end-expiratory lung volume (EEV) above relaxation volume. The purpose of this study was to determine at what age children develop a breathing strategy that is relaxed, i.e., determined by the mechanical characteristics of the lung and chest wall. Forty studies were performed in 27 healthy infants and children aged 1 mo to 8 yr during natural sleep. Volume changes were recorded with the use of respiratory inductance plethysmography (RIP). The volume signal was differentiated to yield flow. Flow-volume representations were generated for a random sample of the recorded breaths to determine the predominant breathing strategy utilized, i.e., relaxed, interrupted, or indeterminate. The respiratory pattern was predominantly interrupted below 6 mo of age and predominantly relaxed over 1 yr of age. Mixed patterns were observed in children 6-12 mo of age. The number of breaths that could not be classified (indeterminate) decreased with age. Respiratory frequency measured from the sample of breaths decreased with age and was accompanied by an increase in expiratory time. We conclude that a relaxed EEV develops at the end of the first year of life and may be related to changes in the mechanical properties of the chest wall associated with growth as well as changes in respiratory timing.     

Effect of changes in lung volume on respiratory system compliance in newborn infants

Total respiratory system compliance (Crs) at volumes above the tidal volume (VT) was studied by use of the expiratory volume clamping (EVC) technique in 10 healthy sleeping unsedated newborn infants. Flow was measured with a pneumotachograph attached to a face mask and integrated to yield volume. Volume changes were confirmed by respiratory inductance plethysmography. Crs measured by EVC was compared with Crs during tidal breathing determined by the passive flow-volume (PFV) technique. Volume increases of approximately 75% VT were achieved with three to eight inspiratory efforts during expiratory occlusions. Crs above VT was consistently greater than during tidal breathing (P less than 0.0005). This increase in Crs likely reflects recruitment of lung units that are closed or atelectatic in the VT range. Within the VT range, Crs measured by PFV was compared with that obtained by the multiple-occlusion method (MO). PFV yielded greater values of Crs than MO (P less than 0.01). This may be due to braking of expiratory airflow after the release of an occlusion or nonlinearity of Crs. Thus both volume recruitment and airflow retardation may affect the measurement of Crs in unsedated newborn infants.     

Spinal cord injury-induced changes in breathing are not due to supraspinal plasticity in turtles (Pseudemys scripta)

After occurrence of spinal cord injury, it is not known whether the respiratory rhythm generator undergoes plasticity to compensate for respiratory insufficiency. To test this hypothesis, respiratory variables were measured in adult semiaquatic turtles using a pneumotachograph attached to a breathing chamber on a water-filled tank. Turtles breathed room air (2 h) before being challenged with two consecutive 2-h bouts of hypercapnia (2 and 6% CO2 or 4 and 8% CO2). Turtles were spinalized at dorsal segments D8-D10 so that only pectoral girdle movement was used for breathing. Measurements were repeated at 4 and 8 wk postinjury. For turtles breathing room air, breathing frequency, tidal volume, and ventilation were not altered by spinalization; single-breath (singlet) frequency increased sevenfold. Spinalized turtles breathing 6-8% CO2 had lower ventilation due to decreased frequency and tidal volume, episodic breathing (breaths/episode) was reduced, and singlet breathing was increased sevenfold. Respiratory variables in sham-operated turtles were unaltered by surgery. Isolated brain stems from control, spinalized, and sham turtles produced similar respiratory motor output and responded the same to increased bath pH. Thus spinalized turtles compensated for pelvic girdle loss while breathing room air but were unable to compensate during hypercapnic challenges. Because isolated brain stems from control and spinalized turtles had similar respiratory motor output and chemosensitivity, breathing changes in spinalized turtles in vivo were probably not due to plasticity within the respiratory rhythm generator. Instead, caudal spinal cord damage probably disrupts spinobulbar pathways that are necessary for normal breathing.     

The breathing pattern and the ventilatory response to aquatic and aerial hypoxia and hypercarbia in the frog Pipa carvalhoi

Anuran amphibians are known to exhibit an intermittent pattern of pulmonary ventilation and to exhibit an increased ventilatory response to hypoxia and hypercarbia. However, only a few species have been studied to date. The aquatic frog Pipa carvalhoi inhabits lakes, ponds and marshes that are rich in nutrients but low in O(2). There are no studies of the respiratory pattern of this species and its ventilation during hypoxia or hypercarbia. Accordingly, the aim of the present study was to characterize the breathing pattern and the ventilatory response to aquatic and aerial hypoxia and hypercarbia in this species. With this purpose, pulmonary ventilation (V(I)) was directly measured by the pneumotachograph method during normocapnic normoxia to determine the basal respiratory pattern and during aerial and aquatic hypercarbia (5% CO(2)) and hypoxia (5% O(2)). Our data demonstrate that P. carvalhoi exhibits a periodic breathing pattern composed of single events (single breaths) of pulmonary ventilation separated by periods of apnea. The animals had an enhanced V(I) during aerial hypoxia, but not during aquatic hypoxia. This increase was strictly the result of an increase in the breathing frequency. A pronounced increase in V(I) was observed if the animals were simultaneously exposed to aerial and aquatic hypercarbia, whereas small or no ventilatory responses were observed during separately administered aerial or aquatic hypercarbia. P. carvalhoi primarily inhabits an aquatic environment. Nevertheless, it does not respond to low O(2) levels in water, although it does so in air. The observed ventilatory responses to hypercarbia may indicate that this species is similar to other anurans in possessing central chemoreceptors.     

Pneumotachograph calibration for inspiratory and expiratory flows during HeO2 breathing

Maximum expiratory flows during breathing of a 80% helium-20% oxygen mixture (HeO2) are commonly used to determine the site of airflow limitation. To do this test the flowmeter is usually calibrated with the inspired gases, and the airflows are measured during expiration. We tested the adequacy of such calibration maneuvers by using two identical flowmeters in series through a bag-in-box system. Different gases were flowed though the test pneumotachograph into a bag contained in a closed box connected to the second pneumotachograph. Distension of the bag caused air to flow from the box through this second pneumotachograph. Our results indicate that when breathing HeO2, the flowmeter correction for different gas viscosity, compared with air, should be 20% for inspired HeO2 and 12% for expired gases. Inspired gases therefore cannot be used to calibrate the flowmeters when assessing expiratory flows.     

Effects of positive-pressure ventilation on the spontaneous baroreflex in healthy subjects.

To determine the short-term effects of noninvasive positive-pressure ventilation (PPV) on spontaneous baroreflex sensitivity, we acquired time series of R-R interval and beat-to-beat blood pressure in 55 healthy volunteers (mean age 46.5 +/- 10.5 yr) who performed breathing on four occasions at frequencies of 12 and 15 breaths/min without positive pressure (control) and also using PPV of 5 mbar. By using spectral and cross-spectral analysis, R-R interval variability and systolic blood pressure variability as well as the gain (alpha-index) of the baroreceptor reflex were estimated for the low-frequency and high-frequency (HF) bands. Compared with control breathing, PPV at 12 breaths/min and 15 breaths/min led to an increase in mean R-R (P < 0.001) and blood pressure (P < 0.05). The alpha-index of the HF band increased significantly for both respiratory frequencies (P < 0.05) due to PPV. These results indicate that short-term administration of PPV in normal subjects elicits a significant enhancement in the HF index of the baroreflex gain. These findings may contribute to understanding the mechanisms, indications, and effectiveness of positive pressure breathing strategies in treating cardiorespiratory and other disease conditions.     

Short-term entrainment of ventilation to the walking cycle in humans

We describe a breath-by-breath method to test for entrainment of breathing and walking cycles. Thirty-eight normal subjects walked comfortably on a treadmill while breathing through a pneumotachograph. We analyzed the time intervals between heel strikes and the onset of inspiration (or expiration) for evidence of phase locking between steps and breaths, using Monte Carlo simulation to model the probability that n consecutive inspirations (or expirations) would begin at a constant time interval +/- 0.10 s from heel strikes by chance. We developed empirical criteria for rhythm synchronization during series of four or more breaths, while maintaining an estimated specificity of 95%. The majority of subjects showed some evidence of entrainment (29 +/- 23% of breaths on average), which occurred intermittently, usually lasting less than 10 breaths at a time. The precision of phase locking during spontaneous entrainment was similar to that in 10 subjects who attempted to maintain deliberate entrainment. The results suggest that the walking cadence provides a persuasive, but not dominant, input to the central breathing pattern generator. The present method can detect entrainment even when it occurs sporadically or with varying coupling pattern.     

Unrestrained video-assisted plethysmography: a noninvasive method for assessment of lung mechanical function in small animals.

The assessment of lung mechanical function in small animals, particularly mice, is essential for investigations into the pathophysiology of pulmonary disease. The most accurate and specific methods for making this assessment are highly invasive and so provide data of questionable relevance to normality. By contrast, present noninvasive methods based on unrestrained plethysmography have no direct link to the mechanical properties of the lung. There is thus a need for a completely noninvasive method for determining lung mechanical function in small animals. In the present study, we demonstrate an extension of unrestrained plethysmography in which changes in lung volume are estimated via orthogonal video imaging of the thorax. These estimates are combined with the pressure swings recorded as mice breathe inside a heated and humidified chamber to yield an estimate of specific airway resistance (sRaw). We used this new technique, which we term "unrestrained video-assisted plethysmography" (UVAP), to measure sRaw in 11 BALB/c mice exposed to aerosols of saline, methacholine, and albuterol and obtained mean values of 0.71, 1.23 and 1.10 cmH(2)O x s, respectively. Mean breathing frequency was 4.3, 3.4, and 3.6 breaths/s, respectively, while the corresponding mean tidal volumes were 0.36, 0.44 and 0.37 ml, respectively. We conclude that UVAP, a noninvasive method, is able to provide usefully accurate estimates of sRaw and breathing pattern parameters in mice.     

Cardiac output and O2 consumption during inspiratory threshold loaded breathing

In this study, noninvasive measurements of cardiac output and O2 consumption were performed to estimate the blood flow to and efficiency of the respiratory muscles that are used in elevated inspiratory work loads. Five subjects were studied for 4.5 min at a respiratory rate of 18 breaths/min and a duty cycle of 0.5. Studies were performed at rest without added respiratory loads and at elevated inspiratory work loads with the use of an inspiratory valve that permitted flow only when a threshold pressure was maintained. Cardiac output and O2 consumption were calculated using a rebreathing technique. Respiratory muscle blood flow and O2 consumption were estimated as the difference between resting and loaded breathing. Work of breathing was calculated by integrating the product of mouth pressure and volume. Increases in cardiac output and O2 consumption in response of 4.5 min loaded breathing averaged 1.84 l/min and 108 ml/min, respectively. No increases were seen in response to 20-s loaded breathing. In a separate series of experiments on four subjects, though, cardiac output increased for the first 2 min then leveled off. These results indicate that the increase in cardiac output was a metabolic effect of the increased work load and was not caused primarily by the influence of the highly negative intrathoracic pressure on venous return. Efficiency of the respiratory muscles during inspiratory threshold loading averaged 5.9%, which was similar to measurements of efficiency of respiratory muscles using whole-body O2 consumption that have been reported previously in humans and in dogs.     

Effect of ventilation rate on instilled surfactant distribution in the pulmonary airways of rats.

Liquid can be instilled into the pulmonary airways during medical procedures such as surfactant replacement therapy, partial liquid ventilation, and pulmonary drug delivery. For all cases, understanding the dynamics of liquid distribution in the lung will increase the efficacy of treatment. A recently developed imaging technique for the study of real-time liquid transport dynamics in the pulmonary airways was used to investigate the effect of respiratory rate on the distribution of an instilled liquid, surfactant, in a rat lung. Twelve excised rat lungs were suspended vertically, and a single bolus (0.05 ml) of exogenous surfactant (Survanta, Ross Laboratories, Columbus, OH) mixed with radiopaque tracer was instilled as a plug into the trachea. The lungs were ventilated with a 4-ml tidal volume for 20 breaths at one of two respiratory rates: 20 or 60 breaths/min. The motion of radiodense surfactant was imaged at 30 frames/s with a microfocal X-ray source and an image intensifier. Dynamics of surfactant distribution were quantified for each image by use of distribution statistics and a homogeneity index. We found that the liquid distribution depended on the time to liquid plug rupture, which depends on ventilation rate. At 20 breaths/min, liquid was localized in the gravity-dependent region of the lung. At 60 breaths/min, the liquid coated the airways, providing a more vertically uniform liquid distribution.     

A Simple Dynamic Model of Respiratory Pump

To study the interaction of forces that produce chest wall motion, we propose a model based on the lever system of Hillman and Finucane (J Appl Physiol 63(3):951–961, 1987) and introduce some dynamic properties of the respiratory system. The passive elements (rib cage and abdomen) are considered as elastic compartments linked to the open air via a resistive tube, an image of airways. The respiratory muscles (active) force is applied to both compartments. Parameters of the model are identified in using experimental data of airflow signal measured by pneumotachography and rib cage and abdomen signals measured by respiratory inductive plethysmography on eleven healthy volunteers in five conditions: at rest and with four level of added loads. A breath by breath analysis showed, whatever the individual and the condition are, that there are several breaths on which the airflow simulated by our model is well fitted to the airflow measured by pneumotachography as estimated by a determination coefficient R ² ≥ 0.70. This very simple model may well represent the behaviour of the chest wall and thus may be useful to interpret the relative motion of rib cage and abdomen during quiet breathing.     

Small reduction of neurokinin-1 receptor-expressing neurons in the pre-B?tzinger complex area induces abnormal breathing periods in awake goats.

In awake rats, >80% bilateral reduction of neurokinin-1 receptor (NK1R)-expressing neurons in the pre-B?tzinger complex (pre-B?tzC) resulted in hypoventilation and an "ataxic" breathing pattern (Gray PA, Rekling JC, Bocchiaro CM, Feldman JL, Science 286: 1566-1568, 1999). Accordingly, the present study was designed to gain further insight into the role of the pre-B?tzC area NK1R-expressing neurons in the control of breathing during physiological conditions. Microtubules were chronically implanted bilaterally into the medulla of adult goats. After recovery from surgery, the neurotoxin saporin conjugated to substance P, specific for NK1R-expressing neurons, was bilaterally injected (50 pM in 10 microl) into the pre-B?tzC area during the awake state (n = 8). In unoperated goats, 34 +/- 0.01% of the pre-B?tzC area neurons are immunoreactive for the NK1R, but, in goats after bilateral injection of SP-SAP into the pre-B?tzC area, NK1R immunoreactivity was reduced to 22.5 +/- 2.5% (29% decrease, P < 0.01). Ten to fourteen days after the injection, the frequency of abnormal breathing periods was sixfold greater than before injection (107.8 +/- 21.8/h, P < 0.001). Fifty-six percent of these periods were breaths of varying duration and volume with an altered respiratory muscle activation pattern, whereas the remaining were rapid, complete breaths with coordinated inspiratory-expiratory cycles. The rate of occurrence and characteristics of abnormal breathing periods were not altered during a CO2 inhalation-induced hyperpnea. Pathological breathing patterns were eliminated during non-rapid eye movement sleep in seven of eight goats, but they frequently occurred on arousal from non-rapid eye movement sleep. We conclude that a moderate reduction in pre-B?tzC NK1R-expressing neurons results in state-dependent transient changes in respiratory rhythm and/or eupneic respiratory muscle activation patterns.     

Respiratory chemosensitivity during wake and sleep in harbour seal pups (Phoca vitulina richardsii)

In this study, we examined the cardiorespiratory patterns of harbour seal pups under normoxic/normocarbic (air), hypoxic/normocarbic (15%, 12%, and 9% O2 in air), and normoxic/hypercarbic (2%, 4%, and 6% CO2 in air) conditions while awake and sleeping on land. Animals were chronically instrumented to record electroencephalogram (EEG), electromyogram (EMG), and electrocardiogram (EKG) signals, which, along with respiration (whole-body plethysmography) and oxygen consumption (VO2), were recorded from animals breathing each gas mixture for 2-4 h on separate days. Our results show that for animals breathing air, VO2 was not significantly lower during slow-wave sleep (SWS; 7.71 +/- 0.39 mL O2 min(-1) kg(-1); all measurements are mean +/- SEM) than during wakefulness (WAKE; 8.80 +/- 0.25 mL O2 min(-1) kg(-1)) and was unaffected by changes in respiratory drive. Although there was no significant fall in VO2 associated with a decrease in arousal state, breathing frequency (f(R)) did decrease (from 18.80 +/- 1.50 breaths min(-1) in WAKE to 10.40 +/- 0.49 breaths min(-1) in SWS), while the incidence of long apneas (>20 s) increased (12.76 +/- 4.06 apneas h(-1) in WAKE and 31.95 +/- 2.37 apneas h(-1) in SWS). Breathing was rarely seen during rapid eye movement (REM) sleep. Tachypnea was present at all levels of increased respiratory drive; however, hypoxia induced a dramatic bradycardia regardless of arousal state, while hypercarbia produced a tachycardia in SWS only. The hypoxic and hypercarbic chemosensitivities of harbour seal pups were similar to those of terrestrial mammals; however, unlike terrestrial mammals, where hypoxic and hypercarbic sensitivities are often reduced during SWS, the sensitivity of harbour seal pups to hypoxia and hypercarbia remained unchanged during the decrease in arousal state from WAKE to SWS.     

Upper airway collapsibility and patterns of flow limitation at constant end-expiratory lung volume

The passive pharyngeal critical closing pressure (Pcrit) is measured using a series of pressure drops. However, pressure drops also lower end-expiratory lung volume (EELV), which independently affects Pcrit. We describe a technique to measure Pcrit at a constant EELV. Continuous positive airway pressure (CPAP)-treated obstructive sleep apnea (OSA) patients and controls were instrumented with an epiglottic catheter, magnetometers (to measure change in EELV), and nasal mask/pneumotachograph and slept supine on nasal CPAP. Pcrit was measured in standard fashion and using our novel "biphasic technique" in which expiratory pressure only was lowered for 1 min before the inspiratory pressure was dropped; this allowed EELV to decrease to the drop level before performing the pressure drop. Seven OSA and three controls were studied. The biphasic technique successfully lowered EELV before the inspiratory pressure drop. Pcrit was similar between the standard and biphasic techniques (-0.4 ± 2.6 vs. -0.6 ± 2.3 cmH(2)O, respectively, P = 0.84). Interestingly, we noted three different patterns of flow limitation: 1) classic Starling resistor type: flow fixed and independent of downstream pressure; 2) negative effort dependence within breaths: substantial decrease in flow, sometimes with complete collapse, as downstream pressure decreased; and 3) and negative effort dependence across breaths: progressive reductions in peak flow as respiratory effort on successive breaths increased. Overall, EELV changes do not influence standard passive Pcrit measurements if breaths 3-5 of pressure drops are used. These results also highlight the importance of inspiratory collapse in OSA pathogenesis. The cause of negative effort dependence within and across breaths is not known and requires further study.