Saliva production and surface tension: influences on patency of the passive upper airway.

Pharyngeal patency is influenced by the surface tension (gamma) of the upper airway lining liquid (UAL), of which saliva is a major component. We investigated the influences of saliva production on gamma of the UAL, and upper airway re-opening and closing pressures. In 10 supine, male, anaesthetized, tracheostomised, mechanically ventilated New Zealand White rabbits, we measured re-opening and closing of the passive isolated upper airway at baseline and following graded (cumulative) doses of methacholine or atropine. Upper airway liquid volume index (UALVI) was assessed using a standardized suction procedure (secretion weight obtained per second) expressed as the natural logarithm (LnUALVI). The gamma of UAL samples were measured using the 'pull-off' force technique. Across all animals, baseline values were: LnUALVI -6.2 (-8.6 to -5.4) median (interquartile range), gamma of UAL 58.9 (56.6-59.9) mN m(-1), re-opening 8.6 (6.9-11.1) cmH(2)O, and closing pressures 3.2 (1.8-5.7) cmH(2)O. LnUALVI increased by approximately 0.17 per microg kg(-1) methacholine and decreased by approximately 0.14 per 100 microg kg(-1) atropine (both P < 0.03, linear mixed effects modelling). Surface tension was unchanged by methacholine but increased by approximately 0.6 mN m(-1) per 100 microg kg(-1) atropine (P < 0.004). When data were analysed across all animals, both re-opening and closing pressures increased as surface tension increased (by approximately 0.4 cmH(2)O mN(-1) and by approximately 0.7 cmH(2)O mN(-1), respectively; both P < 0.05). We conclude that saliva production influences upper airway mechanical properties partly via alterations in gamma of UAL. We speculate that in obstructive sleep apnoea, altered autonomic activity may reduce saliva production and increase surface tension of the upper airway lining liquid, thus increasing the likelihood of upper airway obstruction.

Initiating oral breathing in response to nasal loading: asthmatics versus healthy subjects.

Factors influencing nasal versus oral breathing in asthmatics are not well understood. The current authors hypothesised that asthmatic subjects have enhanced perception of nasal threshold loads, and switch from nasal to oral breathing at a lower load than healthy subjects. In total, 15 mild asthmatic and 20 healthy control subjects breathed nasally via an inspiratory threshold loading device. Nasal loading was progressively increased until subjects switched to oral breathing. Load perception at switching was rated using a Borg scale. Nasal resistance was measured using posterior rhinomanometry. The protocol was repeated before and after nasal decongestant administration in subgroups of 10 healthy control and six asthmatic subjects. Inspiratory nasal resistance was within normal limits for most subjects and was not significantly different between asthmatics and healthy controls. Compared with controls, asthmatics switched to oral breathing at a significantly lower nasal load but rated "difficulty breathing in" at the same level. Decongestant significantly lowered nasal resistance but did not change the nasal load initiating switching in either subgroup. Enhanced perception of nasal loading may trigger increased oral breathing in asthmatics, potentially enhancing exposure to nonconditioned inhaled gas and contributing to the occurrence and/or severity of bronchoconstrictive exacerbations.

Route of breathing in patients with asthma.

STUDY OBJECTIVES: To measure route of breathing in chronic asthmatic patients during and after an acute severe exacerbation. PATIENTS OR PARTICIPANTS: Thirteen asthmatic patients were studied during hospital admission for acute asthma and, in 9 patients, again when asymptomatic. Nine healthy subjects were also studied. INTERVENTIONS: Spontaneous route of breathing was qualitatively assessed using oral and nasal thermistor probes, and was then quantified using a dual compartment face mask with attached pneumotachographs. MEASUREMENTS AND RESULTS: All asthmatic patients had severe bronchoconstriction initially (FEV(1), 46 +/- 3% of predicted) that had resolved at follow-up (FEV(1), 91 +/- 6% of predicted). No healthy subject had evidence of bronchoconstriction (FEV(1), 102 +/- 5% of predicted). During acute asthma, 11 asthmatics were spontaneously breathing oronasally, as assessed using thermistor probes, while all 13 breathed oronasally via face mask. When assessed using thermistor probes, seven of nine asymptomatic asthmatic patients studied were breathing exclusively via the nose; however, all breathed oronasally via face mask. In contrast, while eight of nine healthy subjects were also breathing exclusively via the nose when assessed using thermistor probes, all breathed nasally only via face mask. CONCLUSIONS: Thus, when asymptomatic and at rest, asthmatic patients breathe exclusively via the nose. However, during acute exacerbations of asthma, these patients switch to oronasal breathing. Unlike healthy subjects, chronic asthmatic patients also switch to oronasal breathing when wearing a face mask, irrespective of the degree of bronchoconstriction. We speculate that asthmatics may have an increased tendency to switch to oral breathing, a factor that may contribute to the pathogenesis of their asthma.

New nonionic triiodinated x-ray contrast media containing the N-(2-hydroxyethyl)aminopropane-2,3-diol side chain.

We have found the amino alcohol (HE)APD to be an effective solubilizing and detoxifying agent for triiodinated benzene XRCM. Most of the compounds containing the (HE)APD moiety displayed good solution properties (low osmolality and viscosity) and relatively low toxicities. A general trend was observed in which compounds with low hydrophilicity were more toxic. High hydrophilicity was found to be necessary for low intracisternal toxicity, but is not the only criterion. Use of the 5-glycolamido group provides compounds with high hydrophilicity. When all the properties were compared, the best compounds in this study were found to be the three asymmetrically substituted isophthalamides containing the (HE)APD and APD side chains (4a-c: MP-1556, MP-1683, and MP-1689). These compounds have excellent solution properties (low osmolality and viscosity) and low intravenous and intracisternal toxicities, and compare favorably to current clinical agents.

Influence of NREM sleep on respiratory-related cortical evoked potentials in normal humans.

Sleep substantially alters respiratory system responses to a variety of ventilatory stimuli. This could, to some extent, be a product of a sleep-induced decrement in respiratory afferent traffic to the cortex or cortical influences on central respiratory neurons. To investigate this, we determined the effect of non-rapid-eye-movement (NREM) sleep on cortical evoked potentials produced by rapid-onset inspiratory negative-pressure generations in the airway of seven normal subjects. Mean electroencephalographic activity at Cz-C3 and Cz-C4 for each subject was obtained by signal averaging. For Cz-C3, four respiratory-related cortical evoked potentials (P1, N1, P2, N2) occurred during wakefulness with latencies of 72 +/- 8, 128 +/- 9, 231 +/- 12, and 340 +/- 15 ms and amplitudes of 2.7 +/- 1.1, -3.2 +/- 1.1, 3.0 +/- 0.9, and -2.1 +/- 1.0 microV, respectively. During sleep, amplitudes of N1 and P2 were much greater (-9.4 +/- 1.3 and 14.1 +/- 1.7 microV, respectively; P < 0.05) and the latencies of P1, N1, and P2 (116 +/- 16, 244 +/- 24, and 664 +/- 75 ms, respectively) were substantially prolonged (P < 0.05). We conclude that respiratory-related cortical evoked potentials produced by negative-pressure generations in the airway during wakefulness are profoundly altered by NREM sleep. Their latencies are prolonged, magnitudes are increased, and the waveform is altered to resemble a K-complex. This altered sensory processing may impair respiratory responses during NREM sleep.

Respiratory-related activity of cricothyroid muscle in awake normal humans.

The role of the cricothyroid muscle (CT) in respiration is unclear. To examine the respiratory-related electrical activity of the CT, we measured its electromyogram (EMG) and compared it with that of the alae nasi (AN) in eight healthy subjects. During quiet breathing the CT EMG phasing was inspiratory in seven subjects. This pattern was similar to the AN with respect to phasing and shape of the integrated EMG. The onset of phasic CT and AN activity related to inspiration preceded flow by 173 +/- 39 and 570 +/- 76 (SE) ms, respectively (P less than 0.01). We measured the duration from onset of phasic activity to peak of the EMG (TA) and the total cycle duration (TT). TA/TT of the CT was 0.29 +/- 0.02, similar to that of the AN (0.28 +/- 0.03). Inspiratory resistive loading, panting, and voluntary hyperventilation increased CT activity above the peak level seen during tidal breathing. Voluntary glottic closure increased CT activity to a level above tonic but below peak tidal activity. The findings suggest that the phasic electrical activity of the CT simulates predominantly that of an upper airway dilator.

Cricothyroid muscle responses to increased chemical drive in awake normal humans.

To examine the response of the cricothyroid muscle (CT) to increased chemical drive, we measured its electromyogram simultaneously with that of the alae nasi (AN) in seven normal awake subjects. During both progressive hyperoxic hypercapnia and hypoxia, peak integrated inspiratory activity (moving time average, MTA) of the CT and AN increased as a power function of mean inspiratory flow (ratio of tidal volume to inspiratory time, VT/TI), given by MTA = a(VT/TI)b + c (where a, b, and c are constants). The exponent b varied from 0.009 to 3.4 among subjects but was correlated between CT and AN both during hypercapnia (r = 0.86) and hypoxia (r = 0.81). The onset of inspiratory activity of the CT and AN preceded that of inspiratory flow. Expressed as a percentage of expiratory time, the CT lead time rose from 7% at rest to 20% during hyperpnea. The corresponding values for the AN were from 22 to 52% (both P less than 0.03). Thus the pattern of response of the CT and AN is similar and related to that of the inspiratory muscles in a curvilinear manner. The findings suggest that during chemical stimulation the electrical activity of the CT is analogous to that of the AN, an upper airway dilator.

Effects of a synthetic lung surfactant on pharyngeal patency in awake human subjects.

We examined the effects of separate applications of saline and a synthetic lung surfactant preparation (Surf; Exosurf Neonatal) into the supraglottic airway (SA) on the anteroposterior pharyngeal diameter (Dap) and the airway pressures required to close (Pcl) and reopen (Pop) the SA in five awake normal supine subjects. Dap, Pcl, and P(op) were determined during lateral X-ray fluoroscopy and voluntary glottic closure when pressure applied to the SA lumen was decreased from 0 to -20 cmH2O and then increased to +20 cmH2O. After Surf application and relative to control, Dap was larger for most of the applied pressures, Pcl decreased (-12.3 +/- 1.9 to -18.7 +/- 0.9 cmH2O; P < 0.01), P(op) decreased (13.4 +/- 1.9 to -6.0 +/- 3.4 cmH2O; P < 0.01), and genioglossus electromyographic activity did not change (P > 0.05). Saline had no effect. These observations suggest that pharyngeal intraluminal surface properties are important in maintaining pharyngeal patency. We propose that surfactants enhance pharyngeal patency by reducing surface tension and adhesive forces acting on intraluminal SA surfaces.

Hysteresis of the nasal pressure-flow relationship during hyperpnea in normal subjects.

Hysteresis of the nasal airway pressure-flow relationship (PFR) is seen during hyperpnea, with lower nasal resistance during increasing inspiratory flow than during decreasing flow. We hypothesized that the nasal PFR hysteresis arose in the nasal vestibule airway because of progressive collapse during the inspiration. We measured the inspiratory transnasal and transvestibular PFR for one nasal passage in five normal subjects breathing via a nasal mask during voluntary hyperventilation, both with voluntary nostril flaring and without flaring. The inspiratory hysteresis (IH) was quantified as the ratio of the areas under the descending and ascending pressure-flow curves. Flaring reduced the vestibular IH from 1.96 +/- 0.06 to 1.15 +/- 0.06 and the nasal IH from 2.05 +/- 0.13 to 1.28 +/- 0.06 (both P < 0.01). Our results demonstrate that hysteresis arises in the compliant vestibule segment of the nasal airway, likely because of progressive collapse of the nasal vestibule during inspiration. The findings suggest that hysteresis is prevented by voluntary nostril flaring maintained throughout inspiration.

Alae nasi activation decreases nasal resistance during hyperoxic hypercapnia.

It has been proposed that decreases in nasal resistance (Rn) during hypercapnia are entirely due to vasoconstriction in the nasal cavity. We hypothesized that alae nasi (AN) muscle activity dilates the nasal vestibule and contributes to the decrease in Rn during hypercapnia. Nine normal subjects were studied during hyperoxic hypercapnia (HH). Rn and vestibular resistance (Rvest) for one nasal passage were measured simultaneously with the AN electromyogram before and after nasal decongestion. HH decreased Rvest from 1.6 +/- 0.6 to 0.8 +/- 0.9 cmH2O . l-1 . s (predecongestant) and from 1.3 +/- 0.8 to 0.6 +/- 0.7 cmH2O . l-1 . s (postdecongestant; both P < 0. 01). Nasal decongestant decreased Rn but not Rvest. Significant inverse linear relationships between Rvest and AN electromyogram were demonstrated for all subjects. We conclude that in normal subjects during HH 1) decreases in Rvest are predominantly due to increases in AN activity; and 2) decreases in Rn are due to a combination of mucosal vasoconstriction and AN activation.

Pressure-diameter relationships of the upper airway in awake supine subjects.

In awake supine normal subjects, dimensional changes of the oropharyngeal airway were measured during exposure to negative intraluminal pressures. The pressure was generated 1) "actively" by subjects inspiring against an externally occluded airway or 2) "passively" by external suction at the mouth during voluntary glottic closure with no inspiratory effort. Airway dimensions were imaged with X-ray fluoroscopy and anteroposterior diameters measured at levels corresponding to cervical vertebra 3 and 4 (C3 and C4). Cephalad axial displacement of the hyoid bone (CDHY) was also measured. During the "active" maneuver, airway diameters and position were maintained at resting levels despite airway pressure up to -15 cmH2O. In contrast, during the passive maneuver at -15 cmH2O, C3 was only 15 +/- 9% and C4 only 47 +/- 8% of control; CDHY was 5.6 +/- 1.8 mm. In three subjects airway wall apposition occurred and persisted until an active inspiratory effort. We conclude that, in the absence of inspiratory effort, negative oropharyngeal airway pressures result in marked narrowing and cephalad displacement of the upper airway, even during wakefulness. Therefore, our data suggest that the complex interaction of upper airway and thoracic muscle activity is critical in determining the effective compliance and patency of the upper airway, which is readily collapsible even in normal subjects.

Influence of nasal airflow temperature and pressure on alae nasi electrical activity.

The influence of nasal airflow, temperature, and pressure on upper airway muscle electromyogram (EMG) was studied during steady-state exercise in five normal subjects. Alae nasi (AN) and genioglossus EMG activity was recorded together with nasal and oral airflows and pressures measured simultaneously by use of a partitioned face mask. At constant ventilations between 30 and 50 l/min, peak inspiratory AN activity during nasal breathing (7.2 +/- 1.4 arbitrary units) was greater than that during oral breathing (1.0 +/- 0.3 arbitrary units; P less than 0.005). In addition, the onset of AN EMG activity preceded inspiratory flow by 0.38 +/- 0.03 s during nasal breathing but by only 0.17 +/- 0.04 s during oral breathing (P less than 0.04). When the subject changed from nasal to oral breathing, both these differences were apparent on the first breath. However, peak AN activity during nasal breathing was uninfluenced by inspiration of hot saturated air (greater than 40 degrees C), by external inspiratory nasal resistance, or by changes in the expiratory route. The genioglossus activity did not differ between nasal and oral breathing (n = 2). Our findings do not support reflex control of AN activity sensitive to nasal flow, temperature, or surface pressure. We propose a centrally controlled feedforward modulation of phasic inspiratory AN activity linked with the tonic drive to the muscles determining upper airway breathing route.

Nasal and oral airway pressure-flow relationships.

We examined the inspiratory and expiratory pressure-flow relationships of both the oral and nasal airways before and after exercise in normal upright subjects. With the use of a partitioned facemask, nasal resistance was measured using posterior rhinomanometry, and oral resistance was measured by recording transoral pressure during oral breathing. Both the nasal and oral pressure-flow relationships for inspiration and expiration were curvilinear and were well described by a power function of the form delta P = aVb (where P is pressure, V is flow, a and b are constants) (r2 = 0.96 +/- 0.01). The exponent b describes the curvilinearity of the pressure-flow curve and can be used to infer the flow regimen. At rest, the inspiratory nasal and oral curves suggested a similar degree of turbulence (b = 1.77 +/- 0.06 and 1.83 +/- 0.04, respectively). However, inspiratory flow regimens were inferred to be more turbulent than those during expiration both before and after exercise. After exercise, decreases in inspiratory nasal resistance at low flows were associated with a change in flow regimen from fully turbulent to orifice flow over the entire flow range. Thus the application of a power function to nasal and oral pressure-flow data permits representation of the whole relationship and allows insight into the nature of the flow regimens.

Oronasal partitioning of ventilation during exercise in humans.

The partitioning of oronasal breathing was studied in five normal subjects during progressive exercise. Subjects performed three to five identical runs, each consisting of four 1-min work periods at increments of 50 W. Nasal and oral airflow were measured simultaneously using a partitioned face mask both during and for 4 min after exercise. Total mean flows were the sum of nasal and oral flows. At a total mean inspiratory flow of 2 l/s, the nasal fraction of total flow was 0.36 +/- 0.04 (SE) and decreased by 6 +/- 3% between total flows of 1.5 and 2.5 l/s. Throughout exercise, the nasal fraction of total mean inspiratory flow did not differ from that of total expiratory flow and was similar to that of total mean inspiratory flow during the postexercise period at a corresponding total mean flow (both P greater than 0.02). The results show that oronasal flow partitioning is not directly due to the exercise itself but is related to the level of ventilation and is uninfluenced by the direction of upper airway flow (i.e., inspiratory vs. expiratory). These findings suggest tightly controlled modulation of the relative resistances of the oral and/or nasal pathways.

Relationship between alae nasi activation and breathing route during exercise in humans.

We studied the relationship between alae nasi muscle (AN) activation and breathing route in normal subjects during exercise. Nasal and oral airflow were measured simultaneously using a partitioned face mask and were recorded with the AN electromyogram. Subjects breathed via 1) the nose and mouth (NM) 2) the nose only (N), or 3) the mouth only (M). As ventilation (VE) rose progressively, the peak phasic inspiratory AN activity (IAAN) increased for all breathing routes. IAAN during N [11.8 +/- 2.0 arbitrary units (AU)] was greater than during NM (3.3 +/- 1.3 AU) and M (2.4 +/- 1.0 AU; P less than 0.01) measured at the highest common VE (over a 10-l/min range). At the highest 20% of IAAN recorded during NM, the total VE during N (24 +/- 5 l/min). However, for the same IAAN, nasal VE during NM (27 +/- 3 l/min) was similar to that during N. Thus, as ventilation increases during exercise, AN activity and nasal ventilation are tightly correlated, independently of flow through the mouth. This suggests either reflex modulation of AN activity by nasal flow or coordination of AN activation with the flow-partitioning mechanism of the upper airway.

Breathing route dependence of upper airway muscle activity during hyperpnea.

Exercise (Ex) and hypercapnia (HC) both lead to increases in ventilation and upper airway muscle (UAM) activity. To determine whether different breathing routes (nasal vs. oral) or stimuli produced differential UAM activation, electromyographic (EMG) activity of the alae nasi (AN) and genioglossus (GG) were measured in seven normal subjects seated on a bicycle ergometer. Subjects performed paired runs during both progressive Ex and HC while breathing through the nose alone (N) or the mouth alone (O). During hyperpnea, AN EMG was greater when the subjects were breathing via N [81 +/- 6% maximum (HC) and 69 +/- 7% maximum (Ex)] than when they were breathing via O [30 +/- 5% maximum (HC) and 27 +/- 5% maximum (Ex); both P < 0.01], whereas the GG EMG did not differ between N and O. Both AN and GG EMG were similar for Ex and HC when the subjects were breathing via the same route. We conclude that UAM activation was independent of the nature of the stimulus. However, the AN muscle but not the GG muscle demonstrated breathing-route dependence of activity.

Effect of upper airway negative pressure on proprioceptive afferents from the tongue.

We examined whether receptors in the tongue muscle respond to negative upper airway pressure (NUAP). In six cats, one hypoglossal nerve was cut and its distal end was prepared for single-fiber recording. Twelve afferent fibers were selected for study on the basis of their sensitivity to passive stretch (PS) of the tongue. Fiber discharge frequency was measured during PS of the tongue and after the rapid onset of constant NUAP. During PS of 1-3 cm, firing frequency increased from 17 +/- 7 to 40 +/- 11 (SE) Hz (P < 0.01). In addition, 8 of the 12 fibers responded to NUAP (-10 to -30 cmH2O), with firing frequency increasing from 23 +/- 9 to 41 +/- 9 Hz (P < 0.001). In two fibers tested, the increase in firing frequency in response to NUAP was not altered by topical anesthesia (10% lignocaine) applied liberally to the entire upper airway mucosa. Our results demonstrate that afferent discharges from the hypoglossal nerve are elicited by 1) stretching of the tongue and 2) NUAP before and after upper airway anesthesia. We speculate that activation of proprioceptive mechanoreceptors in the cat's tongue provides an additional pathway for the reflex activation of upper airway dilator muscles in response to NUAP, independent of superficially located mucosal mechanoreceptors.

Influence of sleep on alae nasi EMG and nasal resistance in normal men.

The influence of sleep on the upper airway musculature varies considerably, with some muscles maintaining their activity at waking levels and others falling substantially. The influence of sleep on the alae nasi (AN), a dilator muscle of the nasal airway, has been minimally studied to date. Thus we determined the effect of non-rapid-eye-movement (NREM) sleep on the AN electromyogram and its relationship to nasal resistance (Rn) in nine normal supine males. Phasic inspiratory AN activity decreased from 20 +/- 6 arbitrary units during wakefulness to 5 +/- 1 arbitrary units (P < 0.001) at the onset of stage 2 NREM sleep and remained unchanged for two subsequent hours of NREM sleep. However, the Rn at the onset of NREM sleep remained similar to awake values (5.7 +/- 0.9 cmH2O.l-1 x s) and increased only after 1 h of NREM sleep (8.6 +/- 1.7 cmH2O.l-1 x s, P < 0.05), thus demonstrating little relationship to AN activity. We conclude that Rn increases slightly after 1 h of sleep, whereas AN activity decreases at stage 2 sleep onset. Thus AN activity has little influence on Rn during sleep.

Nasal vestibule wall elasticity: interactions with a nasal dilator strip.

We studied the effect of an adhesive external nasal dilator strip (ENDS) on external nasal geometry in 20 healthy Caucasian adults (10 men, 10 women; age 21-45 yr). The recoil force exerted by ENDS was estimated by bending the device (n = 10) with known weights. In the horizontal direction, a small/medium-sized ENDS in situ exerted a unilateral recoil force of 21.4-22.6 g. Application of ENDS resulted in a displacement of the lateral nasal vestibule walls that had both anterosuperior and horizontal components and that was maintained over an 8-h period. The resultant unilateral nasal vestibule wall displacement at the tip of the device was at 47.6 +/- 2.0 degrees to the horizontal (as related to the plane of the device when in situ) and had a magnitude of 3.5 +/- 0.1 mm. ENDS increased external nasal cross-sectional area by 23.0-65.3 mm2. Nasal vestibule wall compliance was estimated at 0.05-0.16 mm/g. Thus ENDS applies a relatively constant abducting force irrespective of nasal width. Variable responsiveness to ENDS may be related to differences in elastic properties of the nasal vestibule wall.

Nasal resistance and flow resistive work of nasal breathing during exercise: effects of a nasal dilator strip.

Using posterior rhinomanometry, we measured nasal airflow resistance (Rn) and flow-resistive work of nasal breathing (WONB), with an external nasal dilator strip (ENDS) and without (control), in 15 healthy adults (6 men, 9 women) during exclusive nasal breathing and graded (50-230 W) exercise on a cycle ergometer. ENDS decreased resting inspiratory and/or expiratory Rn (at 0.4 l/s) by >0.5 cmH(2)O. l(-1). s in 11 subjects ("responders"). Inspired ventilation (VI) increased with external work rate, but tended to be greater with ENDS. Inspiratory and expiratory Rn (at 0.4 l/s) decreased as VI increased but, in responders, tended to remain lower with ENDS. Inspiratory (but not expiratory) Rn at peak nasal airflow (Vn) increased as VI increased but, again, was lower with ENDS. At a VI of approximately 35 l/min, ENDS decreased flow limitation and hysteresis of the inspiratory transnasal pressure-flow curve. In responders, ENDS reduced inspiratory WONB per breath and inspiratory nasal power values during exercise. We conclude that ENDS stiffens the lateral nasal vestibule walls and, in responders, may reduce the energy required for nasal ventilation during exercise.