Influence of CPAP on reflex responses to tracheal irritation in anesthetized humans

We investigated the effects of lung inflation during continuous positive airway pressure breathing (CPAP) on airway defensive reflexes in 10 enflurane-anesthetized spontaneously breathing humans. The airway defensive reflexes were induced by instillation into the trachea of 0.5 ml of distilled water at two different levels of end-expiratory pressure (0 and 10 cmH2O CPAP). The tracheal irritation at an end-expiratory pressure of 0 cmH2O caused a variety of reflex responses including apnea, spasmodic panting, expiration reflex, cough reflex, an increase in heart rate, and an increase in blood pressure. Lung inflation during CPAP of 10 cmH2O did not exert any influence on these reflex responses in terms of the types, latencies, and durations of reflex responses although the intensity of the expiration reflex and cough reflex was augmented by lung inflation. Our results suggest that the pulmonary stretch receptors do not play an important role in the mechanisms of airway defensive reflexes in humans.     

Expiratory muscle activity in the awake and sleeping human during lung inflation and hypercapnia.

Expiratory muscle activity has been shown to occur in awake humans during lung inflation; however, whether this activity is dependent on consciousness is unclear. Therefore we measured abdominal muscle electromyograms (intramuscular electrodes) in 13 subjects studied in the supine position during wakefulness and non-rapid-eye-movement sleep. Lung inflation was produced by nasal continuous positive airway pressure (CPAP). CPAP at 10-15 cmH2O produced phasic expiratory activity in two subjects during wakefulness but produced no activity in any subject during sleep. During sleep, CPAP to 15 cmH2O increased lung volume by 1,260 +/- 215 (SE) ml, but there was no change in minute ventilation. The ventilatory threshold at which phasic abdominal muscle activity was first recorded during hypercapnia was 10.3 +/- 1.1 l/min while awake and 13.8 +/- 1 l/min while asleep (P less than 0.05). Higher lung volumes reduced the threshold for abdominal muscle recruitment during hypercapnia. We conclude that lung inflation alone over the range that we studied does not alter ventilation or produce recruitment of the abdominal muscles in sleeping humans. The internal oblique and transversus abdominis are activated at a lower ventilatory threshold during hypercapnia, and this activation is influenced by state and lung volume.     

Effects of lung inflation on nasal airway resistance in the anesthetized rat

Nasal airway resistance was assessed in halothane-anesthetized rats by measuring the transnasal pressure at constant airflow through both nasal cavities. Low inflation pressures (2.5-5 cmH2O) decreased nasal airway resistance, whereas higher inflation pressures (10-20 cmH2O) caused a biphasic response: an initial increase in resistance followed by a decrease in resistance. The nasal responses to all levels of inflation were completely abolished by hexamethonium, guanethidine, or bretylium pretreatment or cervical sympathectomy and greatly lessened by cervical vagotomy or phenoxybenzamine pretreatment. Atropine and propranolol pretreatments had no effect on the responses. These findings indicate that the nasal airway resistance is related to the level of inflation through pulmonary reflexes with afferents along the vagi and efferents via the alpha-adrenergic nervous system.     

Extrathoracic airway stability during resistive loading in preterm infants

Extrathoracic airway (ETA) stability was tested in 10 preterm infants during sleep with a drop in intraluminal pressure produced by the application of an external inspiratory flow-resistive load (IRL, 125 cmH2O.1-1.s at 1 l/min). An increase in total pulmonary resistance was sought as the measure of airway narrowing. The role of the ETA in the increased pulmonary resistance with loading was examined by testing the same infants while endotracheally intubated and after extubation. Total pulmonary resistance decreased with loading during the intubated studies (102.5 +/- 41.2 to 82.4 +/- 33.3 cmH2O.1-1.s, P less than 0.05), whereas a significant increase in pulmonary resistance was seen with loading in the extubated studies (101 +/- 58.1 to 128 +/- 68.6 cmH2O.1-1.s, P less than 0.01). Intraluminal pressure in the ETA, measured by the lowest proximal airway pressure, fell significantly with loading in both conditions, with values changing from -0.7 +/- 0.3 to -4.7 +/- 2.7 cmH2O in the intubated infants and from -0.9 +/- 0.3 to -4.6 +/- 0.9 cmH2O) in the extubated infants (P less than 0.01). The results suggest ETA narrowing with loading in extubated infants despite the absence of overt obstructive apnea. Measurements of total pulmonary resistance with IRL can be used as a simple test of ETA stability.     

Influence of passive changes of lung volume on upper airways

The total upper airway resistances are modified during active changes in lung volume. We studied nine normal subjects to assess the influence of passive thoracopulmonary inflation and deflation on nasal and pharyngeal resistances. With the subjects lying in an iron lung, lung volumes were changed by application of an extrathoracic pressure (Pet) from 0 to 20 (+Pet) or -20 cmH2O (-Pet) in 5-cmH2O steps. Upper airway pressures were measured with two low-bias flow catheters, one at the tip of the epiglottis and the other in the posterior nasopharynx. Breath-by-breath resistance measurements were made at an inspiratory flow rate of 300 ml/s at each Pet step. Total upper airway, nasal, and pharyngeal resistances increased with +Pet [i.e., nasal resistance = 139.6 +/- 14.4% (SE) of base-line and pharyngeal resistances = 189.7 +/- 21.1% at 10 cmH2O of +Pet]. During -Pet there were no significant changes in nasal resistance, whereas pharyngeal resistance decreased significantly (pharyngeal resistance = 73.4 +/- 7.4% at -10 cmH2O). We conclude that upper airway resistance, particularly the pharyngeal resistance, is influenced by passive changes in lung volumes, especially pulmonary deflation.     

Effects of topical anesthesia on upper airway resistance during wake-sleep transitions.

Deformation of the upper airway (UA) by negative transmural pressure alters the activity of UA mechanoreceptors, causing a reflex increase in UA muscle activity. Topical anesthesia of the UA mucosa, which greatly reduces this reflex response, causes an increase in UA resistance during stage 2 sleep. We hypothesized that topical anesthesia of the UA mucosa would predispose to UA instability at sleep onset and, therefore, examined the effect of UA anesthesia on pharyngeal resistance (Rph) in stage 1 sleep. Eleven normal, healthy volunteers were instrumented to record standard polysomnographic variables, respiratory airflow, and UA pressure at the nasal choanae and the epiglottis. Subjects were permitted to sleep until stable stage 2 sleep was reached and were then awoken. This procedure was repeated three times to obtain reproducible wake-sleep transitions. The UA mucosa was then anesthetized with 10% lidocaine to the oropharynx and laryngopharynx, and the pharyngeal mechanics were studied during the subsequent wake-sleep transition. Three subjects were excluded because of failure to resume sleep postanesthesia. Rph was significantly higher after anesthesia during stage 1 sleep [2.88 +/- 0.77 cmH(2)O.l(-1).s (mean +/- SE)] compared with control (0.95 +/- 0.35 cmH(2)O.l(-1).s; P < 0.05), but there was no difference during wakefulness. Furthermore, there was a significant rise in Rph at wake-to-sleep transitions and a significant fall in Rph at sleep-to-wake transitions after anesthesia (P < 0.05) but not in the control condition. We conclude that sensory receptors in the UA mucosa contribute to the maintenance of UA patency at wake-sleep transition in normal humans.     

Assessment of airway resistance in preterm infants during incremental inspiratory flow-resistive loading

Extrathoracic airway (ETA) stability was tested by inspiratory flow-resistive loading in 10 preterm infants to determine whether ETA collapsibility was directly related to the size of the added load. A fall in intraluminal pressure was produced by applying two inspiratory flow-resistive loads of lower (L1) and higher (L2) magnitudes. An increase in intrinsic resistance was used as an index of upper airway collapsibility. Total pulmonary resistance did not change from baseline with L1 (73 +/- 26 to 71 +/- 25 cmH2O.l-1.s) but increased significantly with L2 (72 +/- 21 to 99 +/- 34 cmH2O.l-1.s, P less than 0.02) secondary to a rise in inspiratory resistance (55 +/- 21 to 109 +/- 55 cmH2O.l-1.s, P less than 0.05). Expiratory resistance did not change significantly with either load. Proximal airway pressure was more negative with L2 than with L1 in every infant (mean -4.5 +/- 0.6 vs. -3.6 +/- 0.9 cmH2O, P less than 0.05). This study shows that the ETA of preterm infants is pressure passive at high but not at low collapsing pressures, and possible explanations include limited "active" compensation by upper airway dilator muscles and an overwhelming of the "passive" defense offered by the intrinsic rigidity of the ETA to large changes in transmural pressure.     

The acute impact of continuous positive airway pressure on nasal resistance: a randomized controlled comparison.

Subjective nasal obstruction is common among users of continuous positive airway pressure (CPAP). The aim of this study was to measure the acute effect of CPAP on nasal resistance and nasal symptoms in awake normal subjects. Twenty-four healthy CPAP-naive adults [8 men, 16 women; mean age 30 yr (SD 14)] underwent a randomized controlled crossover study comparing nasal CPAP (8 cmH(2)O) for 6 h on one occasion and the control condition (nasal mask without CPAP) on the other. Nasal resistance measurements (posterior active rhinometry) before and after the test exposure were similar on both test days. Nasal resistance during CPAP exposure [2.04 cmH(2)O.l(-1).s (SD 0.72)] was significantly lower than that of the control [2.67 cmH(2)O.l(-1).s (SD 1.07)]: mean difference 0.66 cmH(2)O.l(-1).s, 95% confidence interval 0.19-1.13 cmH(2)O.l(-1).s. The gradient in pressure from CPAP mask to posterior naris during CPAP exposure varied from 1.6 to 2 cmH(2)O but was not significantly different between time points. Subjective nasal symptom scores and peak nasal inspiratory flow rates did not change significantly on either test day. We conclude that in awake CPAP-naive normal subjects, acute CPAP exposure is associated with a reduction in nasal resistance compared with the control condition, but it is not associated with an immediate post-CPAP change in subjective or objective nasal resistance.     

Inspiratory and expiratory muscle function during continuous positive airway pressure in dogs

Continuous positive airway pressure (CPAP) is known to produce activation of the expiratory muscles. Several factors may determine whether this activation can assist inspiration. In this study we asked how and to what extent expiratory muscle contraction can assist inspiration during CPAP. Respiratory muscle response to CPAP was studied in eight supine anesthetized dogs. Lung volume and diaphragmatic initial length were defended by recruitment of the expiratory muscles. At the maximum CPAP of 18 cmH2O, diaphragmatic initial lengths were longer than predicted by the passive relationship by 52 and 46% in the costal and crural diaphragmatic segments, respectively. During tidal breathing after cessation of expiratory muscle activity, a component of passive inspiration occurred before the onset of inspiratory diaphragmatic electromyogram (EMG). At CPAP of 18 cmH2O, passive inspiration represented 24% of the tidal volume (VT) and tidal breathing was within the relaxation characteristic. Diaphragmatic EMG decreased at CPAP of 18 cmH2O; however, VT and tidal shortening were unchanged. We identified passive and active components of inspiration. Passive inspiration was limited by the time between the cessation of expiratory activity and the onset of inspiratory activity. We conclude that increased expiratory activity during CPAP defends diaphragmatic initial length, assists inspiration, and preserves VT. Even though breathing appeared to be an expiratory act, there remained a significant component of active inspiratory diaphragmatic shortening, and the major portion of VT was produced during active inspiration.     

Effect of maturation on the extrathoracic airway stability of infants.

The influence of maturation on extrathoracic airway (ETA) stability during quiet sleep was determined in 13 normal preterm infants of 1.41 +/- 0.14 (SD) kg birth weight and 32 +/- 2 wk estimated gestational age. Studies began in the first week of life and were performed three times at weekly intervals. A drop in intraluminal pressure within the ETA was produced by external inspiratory flow-resistive loading (60 cmH2O.l-1 x s at 1 l/min); an increase in intrinsic resistance, indicating airway narrowing, was sought as a measure of ETA instability. Baseline total pulmonary resistance was not significantly different between weeks 1, 2, and 3 (88 +/- 35, 65 +/- 24, and 61 +/- 17 cmH2O.l-1 x s, respectively) but increased markedly above baseline with loading to 144 +/- 45 cmH2O.l-1.s during week 1 (P < 0.001), 89 +/- 28 cmH2O.l-1 x s at week 2 (P < 0.01), and 74 +/- 25 cmH2O.l-1 x s at week 3 (n = 10). The increment with loading was significantly greater during week 1 than during weeks 2 or 3 (P < 0.02). Similar studies were also done in seven full-term infants in the first week of life to evaluate the influence of gestational maturity on ETA stability. Despite a relatively greater drop in intraluminal pressure within the ETA of term vs. preterm infants with loading (P < 0.001), total pulmonary resistance failed to increase (68 +/- 21 to 71 +/- 32 cmH2O.l-1.s). These data reveal that ETA instability is present in preterm infants at birth and decreases with increasing postnatal age. Full-term neonates, by comparison, display markedly greater ETA stability in the immediate neonatal period.     

Site of phrenic nerve stimulation-induced upper airway collapse: influence of expiratory time.

Electrical phrenic nerve stimulation (EPNS) applied at end expiration during exclusive nasal breathing can be used to characterize upper airway (UA) dynamics during wakefulness by dissociating phasic activation of UA and respiratory muscles. The UA level responsible for the EPNS-induced increase in UA resistance is unknown. The influence of the twitch expiratory timing (200 ms and 2 s) on UA resistance was studied in nine normal awake subjects by looking at instantaneous flow, esophageal and pharyngeal pressures, and genioglossal electromyogram (EMG) activity during EPNS at baseline and at -10 cmH(2)O. The majority of twitches had a flow-limited pattern. Twitches realized at 200 ms and 2 s did not differ in their maximum inspiratory flows, but esophageal pressure measured at maximum inspiratory flow was significantly less negative with late twitches (-6.6 +/- 2.7 and -5.0 +/- 3.0 cmH(2)O respectively, P = 0.04). Pharyngeal resistance was higher when twitches were realized at 2 s than at 200 ms (6.4 +/- 2.4 and 2.7 +/- 1.1 cmH(2)O x l(-1). s, respectively). EMG activity significant rose at peak esophageal pressure with a greater increase for late twitches. We conclude that twitch-induced UA collapse predominantly occurs at the pharyngeal level and that UA stability assessed by EPNS depends on the expiratory time at which twitches are performed.     

Effects of continuous positive airway pressure breathing on lung volume and distensibility

In this study the effects on lung elastic behavior of 10 min of breathing at a continuous positive airway pressure (CPAP) of 10 cmH2O were examined in 10 normal subjects. To investigate whether any changes were induced by release of prostaglandins, the subjects were also pretreated with the cyclooxygenase inhibitor indomethacin. CPAP produced a significant (P less than 0.001) upward shift of the pressure-volume (PV) curve [change in total lung capacity (delta TLC) 374 +/- 67 (SE) ml, mean delta volume at a transpulmonary pressure of 15 cmH2O (delta VL15) 279 +/- 31 ml] with no change in K, an index of lung distensibility. After CPAP the PV curves returned to normal base line within 20 min. The same pattern was observed after indomethacin, but the increase in TLC was significantly less (P less than 0.01) (mean delta TLC 206 +/- 42 ml) mainly because of a slight and not statistically significant increase in base-line TLC. In five subjects further PV curves with and without CPAP were obtained greater than or equal to 7 days after indomethacin. The responses were not significantly different from those obtained before indomethacin (mean delta TLC 366 +/- 89, mean delta VL15 296 +/- 42 ml). We conclude that CPAP produces an upward shift of the PV curve without a change in lung distensibility. In addition, there may be a small degree of resting alveolar duct tone that is influenced by indomethacin.     

Respiratory system responsiveness in rabbits in vivo is reduced by prolonged continuous positive airway pressure.

Active, nonanesthetized, tracheotomized rabbits were subjected to continuous positive airway pressure (CPAP) for 4 days to determine the effects of chronic mechanical strain on lung and airway function. Rabbits were maintained for 4 days at a CPAP of 6 cmH(2)O (high CPAP), at a CPAP of 0 cmH(2)O (low CPAP), or without tracheostomy (no CPAP). After treatment with CPAP, changes in respiratory resistance in response to increasing concentrations of inhaled ACh were measured during mechanical ventilation to evaluate respiratory system responsiveness in vivo. Intraparenchymal bronchial segments were isolated from the lungs of all animals to evaluate airway smooth muscle responsiveness and bronchial compliance in vitro. Rabbits maintained for 4 days at high CPAP demonstrated significantly lower responsiveness to ACh compared with rabbits that were maintained at low CPAP or with no CPAP. Airways isolated from the lungs of animals subjected to the chronic application of high CPAP were also less responsive to ACh in vitro than the airways isolated from animals subjected to low CPAP or no CPAP. The persistence of the decreased responsiveness in the excised airway tissues suggests that the decreased respiratory system responsiveness observed in vivo results primarily from direct effects on the airways. The results demonstrate that the application of prolonged mechanical strain in vivo can reduce airway reactivity.     

Influence of muscle activity on the elastance of the upper airway of rabbits

This study sought to assess the effect of variations in upper airway muscle activity on upper airway pressure-volume properties. Upper airway elastance, closing pressure, and reserve volume were measured in the isolated upper airways of anesthetized rabbits under control conditions and after administration of gallamine (2 mg/kg iv) or after 10 min of spontaneous respiration of 7% CO2 in O2. Administration of gallamine to seven animals was associated with a fall in reserve volume from 0.94 +/- 0.24 to 0.69 +/- 0.17 (95% confidence interval) ml (P less than 0.01) and of closing pressure from -7.53 +/- 0.23 to -5.75 +/- 1.05 cmH2O (P less than 0.01), but airway elastance did not change significantly. Hypercapnia in seven animals was associated with a rise in elastance from 7.06 +/- 0.91 to 7.67 +/- 0.86 cmH2O/ml (P less than 0.001) and in reserve volume from 0.68 +/- 0.06 to 0.86 +/- 0.13 ml (P less than 0.05). Closing pressure also changed from -5.88 +/- 0.94 to -7.92 +/- 1.85 cmH2O. This change was correlated with the change in reserve volume but not with the change in elastance. In three animals exposed to hypercapnia, return to room air breathing was associated with return of elastance, reserve volume, and closing pressure to control levels. It is concluded that muscle activity in the upper airway affects both the size and elastance of the airway, but the dominant mechanism by which upper airway muscles increase the resistance of the upper airway to collapse is by increasing airway volume.     

Comparison of upper and lower airway responses of two sensitized rat strains to inhaled antigen.

The purpose of the study was to investigate the relationships between upper airways responses and pulmonary responses of two strains of highly inbred rats to inhaled antigen. To do this we measured the upper and lower airways resistance for 60 min after challenge of Brown-Norway rats (BN; n = 13) and an inbred rat strain (MF; n = 11), derived from Sprague-Dawley, with aerosolized ovalbumin (OA). Rats were actively sensitized with OA (1 mg sc) using Bordetella pertussis as an adjuvant. Two weeks later the animals were anesthetized and challenged. Tracheal pressure, esophageal pressure, and airflow were measured, from which total pulmonary resistance was partitioned into upper airway and lower pulmonary resistance (RL). The peak upper airway response to inhaled OA was similar in BN (1.89 +/- 0.66 cmH2O.ml-1.s; n = 7) and MF (2.85 +/- 0.68 cmH2O.ml-1.s; n = 6). The lower airway response to OA challenge was substantially greater in BN, and RL changed from 0.07 +/- 0.01 to 0.34 +/- 0.13 (n = 6; P < 0.05). The MF did not have any significant increase in RL after challenge; the baseline RL was 0.12 +/- 0.02 and only reached a peak value of 0.15 +/- 0.05 (n = 5; P = NS). Lower airway responsiveness of BN (n = 10) to serotonin, an important mediator early allergic airway responses, was similar to MF (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)     

Pressure-volume properties of the upper airway of rabbits

In 10 anesthetized rabbits the upper airway cephalad of the vocal cords was isolated from the distal airway and sealed. Static deflation pressure-volume data were recorded from the isolated upper airway. The relationship between pressure and volume in the upper airway was a straight line; the correlation coefficient (r) ranged from 0.97 to 1.00. The following quantities were derived from the data: the pressure-volume ratio (upper airway elastance, cmH2O/ml), the pressure in the airway at airway closure (closing pressure, cmH2O), and the airway volume at zero airway pressure (reserve volume, ml). Mean upper airway elastance was 8.13 +/- 1.45 [95% confidence intervals (CI)] cmH2O/ml, closing pressure was -6.93 +/- 1.53 (95% CI) cmH2O, and reserve volume was 0.74 +/- 0.15 (95% CI) ml. There was no significant correlation between elastance and closing pressure (r = 0.47, P greater than 0.1), but closing pressure and reserve volume were significantly correlated (r = 0.77, P less than 0.01). Pressure-volume data recorded from newly dead animals exhibited the same linear relationship between pressure and volume observed in living animals. It is concluded that the pressure-volume properties of the isolated upper airway of the rabbit can be expressed as a single value for airway elastance, that estimation of pressure-volume properties over part of the volume range is representative of the whole volume range, and that pressure-volume properties are determined by passive elastic properties of the airway tissues. It appears that the resistance of the upper airway to collapse by negative intraluminal pressure is more dependent on the initial size of the airway than on its elastance.     

Production mechanism of crackles in excised normal canine lungs

Lung crackles may be produced by the opening of small airways or by the sudden expansion of alveoli. We studied the generation of crackles in excised canine lobes ventilated in an airtight box. Total airflow, transairway pressure (Pta), transpulmonary pressure (Ptp), and crackles were recorded simultaneously. Crackles were produced only during inflation and had high-peak frequencies (738 +/- 194 Hz, mean +/- SD). During inflation, crackles were produced from 111 +/- 83 ms (mean +/- SD) prior to the negative peak of Pta, presumably when small airways began to open. When end-expiratory Ptp was set constant between 15 and 20 cmH2O and end-expiratory Ptp was gradually reduced from 5 cmH2O to -15 or -20 cmH2O in a breath-by-breath manner, crackles were produced in the cycles in which end-expiratory Ptp fell below -1 to 1 cmH2O. This pressure was consistent with previously known airway closing pressures. When end-expiratory Ptp was set constant at -10 cmH2O and end inspiratory Ptp was gradually increased from -5 to 15 or 20 cmH2O, crackles were produced in inspiratory phase in which end-inspiratory Ptp exceeded 4-6 cmH2O. This pressure was consistent with previously known airway opening pressures. These results indicate that crackles in excised normal dog lungs are produced by opening of peripheral airways and are not generated by the sudden inflation of groups of alveoli.     

Measurement of interrupter resistance in rabbits exposed to methacholine aerosols.

We studied the effect of increasing airway resistance on equilibration of airway and alveolar pressure during passive expiratory airflow interruption. In 10 anesthetized and paralyzed rabbits, airway and alveolar pressures were compared before and after airway resistance was increased with methacholine. In all studies, airway pressure rose to equilibrate with alveolar pressure immediately after the interruption (delta Pinit) regardless of increases in airway resistance. The pressures then remained equal during the interruption while gradually increasing to plateau (delta Pdiff). Before methacholine exposure, delta Pdiff was small (0.6 +/- 0.3 cmH2O). Steady-state resistance calculated from the sum of delta Pinit and delta Pdiff was similar to airway resistance calculated from delta Pinit alone. After methacholine, increased airway resistance was accompanied by increased delta Pdiff (2.0 +/- 0.5 cmH2O), causing disproportionate increase in steady-state resistance. delta Pdiff increases were equal in the airway and alveoli, implying resistive changes distal to the sampled alveoli. Thus increasing airway resistance did not delay pressure equilibration across airways. However, increases in airway resistance were accompanied by tissue resistive changes that were greater than the increases in airway resistance.     

A plethysmographic technique for direct measurement of airway resistance in hamsters

We have developed a new technique to directly measure airway resistance (Raw) in small animals with a pressure-type body plethysmograph equipped with a hot-wire microflow sensor. Seventeen male golden hamsters weighing 70-84 g were studied. Change in alveolar pressure (delta PA) was calculated from total gas volume and the respired volume difference through the flow sensor between the midpoints of the tidal excursion curve, reflecting the thorax movement. The ratio of delta PA to the flow difference between those two midpoints gave Raw. Raw was compared with pulmonary resistance, and inspiratory and expiratory resistances were also compared. Raw was 0.44 +/- 0.06 (SE) cmH2O.ml-1.s. Mean of the coefficients of variation of Raw was 19.6 +/- 3.2% (SE). Raw was well correlated with pulmonary resistance (r = 0.93). We demonstrated that Raw could be directly measured in small animals with a hot-wire flow sensor and a plethysmographic technique, and the values were well correlated with previously reported pulmonary resistance.