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This study has evaluated the nasal response to exercise in patients with cystic fibrosis (CF), a genetic disease in which factors such as chronic lung disease and/or nasal polyposis might be anticipated to modify nasal function responses. Measurements of nasal resistance (NAR) by posterior rhinomanometry and specific airway resistance (sRAW) were made before and 1, 5, 10, and 30 min after a 4-min period of exhausting legwork exercise (50% predicted maximal) in 19 CF patients (aged 11-29 years) and 10 healthy subjects (aged 11-31 years). One minute after exercise, healthy subjects showed a 54 +/- 5% (mean +/- SEM; standard error of the mean) relative fall from baseline in NAR and CF patients showed a 31 +/- 8% relative fall from baseline (p < 0.05). There were no significant differences in the magnitude or pattern of recovery in NAR after exercise (1 to 30 min) between the groups, largely because of the variability in NAR responses in CF patients. Exercise did not result in significant changes in sRAW in either group. We also found that a history or presence of nasal polyposis does not significantly affect functional nasal responses to exercise. Our conclusion is that the CF genotype and its airway sequelae do not substantively affect the control of the nasal response to exercise.

Recent studies have suggested that the inhalation of cold air through the nose is associated with the subsequent release of mediators of immediate hypersensitivity. To determine if mucosal surface heat and water loss influence the nasal functional response to cold air, we measured nasal resistance by posterior rhinomanometry before and 1, 5, and 10 min after a 4-min period of isocapnic hyperventilation (30 l/min) through the nose in nine healthy subjects (5 males, 4 females; aged 25-39 yr) while they inhaled air at 0 degrees C. During the challenge period, the subjects breathed either in and out of the nose or in through the nose and out through the mouth. No changes in nasal resistance developed when subjects breathed exclusively through the nose; however, when subjects breathed in through the nose and out through the mouth, nasal resistance was increased 200% at 1 min (P less than 0.01) after the challenge and returned to baseline values by 10 min after cessation of the challenge. These data indicate that nasal functional responses to cold dry air are dependent on the pattern of the ventilatory challenge. If the heat given up from the nasal mucosa to the incoming air is not recovered during expiration (as is the case with inspiration through the nose and expiration through the mouth), nasal obstruction will occur. Hyperpnea of cold air, per se, does not influence nasal resistance.

Continuous positive pressure applied at the nose has been shown to cause a decrease in upper airway resistance. The present study was designed to determine whether a similar positive transmural pressure gradient, generated by applying a negative pressure at the body surface around the neck, altered upper airway patency. Studies were performed in nine spontaneously breathing anesthetized supine dogs. Airflow was measured with a pneumotachograph mounted on an airtight muzzle placed over the nose and mouth of each animal. Upper airway pressure was measured as the differential pressure between the extrathoracic trachea and the inside of the muzzle. Upper airway resistance was monitored as an index of airway patency. Negative pressure (-2 to -20 cmH2O) was applied around the neck by using a cuirass extending from the jaw to the thorax. In each animal, increasingly negative pressures were transmitted to the airway wall in a progressive, although not linear, fashion. Decreasing the pressure produced a progressive fall in upper airway resistance, without causing a significant change in respiratory drive or respiratory timing. At -5 cmH2O pressure, there occurred a significant fall in upper airway resistance, comparable with the response of a single, intravenous injection of sodium cyanide (0.5-3.0 mg), a respiratory stimulant that produces substantial increases in respiratory drive. We conclude that upper airway resistance is influenced by the transmural pressure across the airway wall and that such a gradient can be accomplished by making the extraluminal pressure more negative.(ABSTRACT TRUNCATED AT 250 WORDS)

The effects of continuous positive airway pressure (CPAP) on supraglottic and total pulmonary resistance were determined in 10 healthy premature infants (postconceptional age 34 +/- 2 wk, weight at study 1,628 +/- 250 g). Nasal airflow was measured with a mask pneumotachograph, and pressures in the esophagus and oropharynx were measured with a 5-Fr Millar or fluid-filled catheter. Nasal CPAP between 0 and 5 cmH2O correlated well with oropharyngeal pressure (r = 0.94). Total supraglottic resistance, total pulmonary resistance, and supraglottic resistance in inspiration and expiration were measured on increasing CPAP. Total supraglottic resistance decreased from 46 +/- 29 to 17 +/- 16 cmH2O.l-1.s (P less than 0.005) between 0 and 5 cmH2O CPAP, and a delay in return of resistance to control values was seen as CPAP was reciprocally decreased to 0. CPAP produced a decrease in supraglottic resistance in both inspiration and expiration, from 41 +/- 26 to 14 +/- 9 and from 33 +/- 17 to 10 +/- 6 cmH2O.l-1.s, respectively (P less than 0.01). Total pulmonary resistance also decreased from 161 +/- 40 to 95 +/- 24 cmH2O.l-1.s (P less than 0.01) between 0 and 5 cmH2O CPAP. The decrease in total supraglottic resistance in these infants accounted for 60% of the change in total pulmonary resistance, which occurred on CPAP of 5 cmH2O. We speculate that CPAP may decrease supraglottic resistance directly through mechanical splinting of the airway. This effect of CPAP may be the primary mechanism by which this form of therapy reduces apnea with an obstructive component in premature infants.

The effect of alae nasi activation on nasal resistance in a group of healthy preterm infants was measured. Alae nasi activity was determined via the alae nasi electromyogram obtained from skin surface electrodes during both active and quiet sleep. Nasal resistance was calculated from airflow measured with a mask pneumotachograph and transnasal pressure drop obtained by simultaneous measurement of nasal pressure via a catheter inserted in one nostril and mask pressure. The percentage of breaths accompanied by phasic alae nasi activity was higher during active sleep than during quiet sleep (43% +/- 10% v 14% +/- 6%; P less than .005), and hypercapnic stimulation (4% CO2 inhalation) significantly increased the incidence of phasic alae nasi activity to comparable levels in both sleep states (82% +/- 8% in active sleep and 82% +/- 9% in quiet sleep). Elevation of tonic alae nasi activity also occurred more frequently during active sleep (P less than .05). The presence of either phasic or elevated tonic alae nasi activity decreased nasal resistance by 23% +/- 4% during active sleep and 21% +/- 3% during quiet sleep. This reduction in nasal resistance resulted in either a lower transnasal pressure during inspiration, a higher peak inspiratory airflow, or a combination of the two. Alae nasi activity may be an important mechanism that facilitates ventilation by reducing nasal resistance, and it may help stabilize the upper airway by preventing the development of large negative pharyngeal pressure during inspiration.

In 8 anesthetized mongrel dogs, we studied the effects of carbachol-induced bronchoconstriction (BC) on the cardiovascular system. Inhalation of carbachol in an amount sufficient to produce at least a 50% decrease in lung conductance (GL) did not lead to significant changes in cardiac output, mean transmural left atrial (Pla) or right atrial pressure, end-diastolic left ventricular septal-lateral dimension, left ventricular apex to base dimension, or in end-diastolic right ventricular septal to lateral dimension during expiration. Mean transmural pulmonary arterial pressure rose and mean transmural aortic pressure (Pao) fell during BC. During inspiration, there were significant increases in transmural left atrial pressure, Pla, associated with decreases in end-diastolic left ventricular septal-lateral and apex-base dimensions. End-diastolic right ventricular septal-lateral dimension increased during inspiration. Beat-to-beat aortic flow (Qao) decreased during inspiration, while pulmonary arterial flow increased. There were no changes in transmural Pao during inspiration measured at the nadir of aortic flow. During BC, these changes were exaggerated, but remained qualitatively the same. The magnitude of the inspiratory decrease in pleural pressure (Ppl) was shown to be linearly related to the magnitude of the change in GL, and the magnitude of the inspiratory decrease in Pao and Qao (pulsus paradoxus) was shown to be linearly related to the magnitude of the inspiratory swing in Ppl. Although vagotomy significantly altered the pattern of respiration such that tidal volume increased and respiratory rate decreased, it did not substantially alter the responses of the cardiovascular system to breathing during BC. We conclude: the inspiratory decrease in Pao and Qao (pulsus paradoxus) is associated with a decrease in left ventricular end-diastolic filling, and a stiffening of the left ventricle; these changes are exaggerated during BC as a result of the exaggerated inspiratory swings in Ppl; the effects on left ventricular dynamics are mediated only in part through increases in right ventricular end-diastolic filling operating through the mechanism of ventricular interdependence; changes in left ventricular afterload appear to play little role in determining the responses seen.

Skeletal muscle activation is believed to be important in the maintenance of upper airway patency. To determine where and how muscles affect pharyngeal stability, we assessed in heavily anesthetized, ventilated dogs, the negative pressure required to close the nasopharynx and the passage from the oral to the pharyngeal airway before and after electrical stimulation of six pairs of upper airway muscles: the sternohyoid, sternothyroid, ceratohyoid, thyrohyoid, genioglossus, and geniohyoid. Before muscle stimulation, the pressures required to close the nasopharynx and the oral passage were -9.8 +/- 2.3 (mean +/- SEM) and -4.9 +/- 1.9 cm H2O, respectively. Submaximal electrical stimulation of each of the six muscle pairs caused consistent and substantial improvements in nasopharynx closing pressure. In contrast, the stabilizing actions of these muscles on the oral passage was less consistent and smaller in magnitude. Using pressure in the sealed upper airway as an index of forces acting on the airway, we found a strong association between the effect of muscle stimulation on the closing pressure and the effect of muscle stimulation on producing a dilating force on the airway. We conclude that muscles in the anterior and lateral pharyngeal wall improve nasopharynx stability to a greater extent than oral passage stability and that the action by any of these six muscle pairs improves airway stability through their ability to dilate the upper airway.

The purpose of this study was to determine whether pharmacologic interventions which increase respiratory drive could also reduce flow resistance in the upper airway. Studies were performed in twelve anesthetized supine dogs. In six animals breathing spontaneously through the intact upper airway, intravenous administration of respiratory stimulants (sodium cyanide and nicotine) produced a dose-related decrease in upper airway. In nine animals, upper airway resistance was measured across the isolated upper airway. The stimulants produced a dose-related decrease in upper airway resistance. In both preparations inspiratory resistance fell at lower doses than expiratory resistance. Eventually a dose could be given which resulted in comparable, minimal values of resistance during both inspiration and expiration. Mechanisms for changes in resistance were clarified using lateral radiographs of the neck and transbronchoscopic views of the upper airway. Pharmacologic challenge resulted in a change in the route of airflow (from nose only to nose-and-mouth breathing) as well as a change in caliber of the airway at the level of the naso-pharynx and hyoid apparatus. In anesthetized dogs, respiratory stimulants will decrease upper airway resistance by increasing activation of upper airway muscles which may enlarge the airway, change the route of flow, and thus overcoming collapsing forces produced by increased chest wall muscle activation.

The study was performed to investigate the relationship between force generation and upper airway expansion during respiratory efforts by upper airway muscles. In 11 anesthetized dogs we isolated the upper airway (nasal, oral, pharyngeal, and laryngeal regions) by transecting the cervical trachea and sealing the nasal and oral openings. During spontaneous respiratory efforts the pressure within the sealed upper airway, used as an index of dilating force, decreased during inspiration. On alternate breaths the upper airway was opened to a pneumotachograph, and an increase in volume occurred, also during inspiration. Progressive hyperoxic hypercapnia produced by rebreathing increased the magnitude of change in pressure and volume. At any level of drive, peak pressure or volume occurred at the same point during inspiration. At any level of drive, volume and pressure changes increased with end-expiratory occlusion of the trachea. The force-volume relationship determined from measurements during rebreathing was compared with pressure-volume curves performed by passive inflation of the airway while the animal was apneic. The relationship during apnea was 1.06 +/- 0.55 (SD) ml/cmH2O, while the force-volume relationship from rebreathing trials was -1.09 +/- 0.45 ml/cmH2O. We conclude that there is a correspondence between force production and volume expansion in the upper airway during active respiratory efforts.

We reasoned that in an isolated sealed upper airway a pressure change would be caused by a change in airway volume. In eight spontaneously breathing anesthetized dogs, we isolated the upper airway by transecting the cervical trachea and sealing it from the lung and from the atmosphere. Pressure changes in this isolated upper airway were studied in relation to respiratory phase as evidenced by alae nasi electromyographic (EMG) activation and tidal volume measured at the distal trachea. A fall in pressure, indicating airway dilation, occurred with each spontaneous respiratory effort. Like the moving average of the alae nasi EMG, the pressure drop reached a peak value early in inspiration, was inhibited by further lung inflation, and was absent during passive mechanical ventilation. End-expiratory tracheal occlusion or vagotomy prolonged and augmented EMG activity and also the inspiratory fall in upper airway pressure. Increased levels of CO2 increased the magnitude of change in pressure during inspiration. An inhibiting effect of lung inflation was present to an equal extent at low and high levels of chemical drive. We show that dilation of the airway is concurrent with upper airway muscle activation during early inspiration, that this dilation increases with increasing chemical drive, and that vagal reflexes during lung inflation inhibit this dilation during the latter half of inspiration.

Nasal resistance is known to be affected by changes in nasal blood volume and hence to depend on sympathetic discharge to nasal blood vessels. Structures located superficially near the ventrolateral surface of the medulla significantly affect respiratory and sympathetic activity and the tone of the trachea. To assess the importance of these structures on nasal patency, we measured transnasal pressure at a constant flow and examined the change in pressure produced by topically applied N-methyl-D-aspartic acid (NMDA). Experiments were performed in chloralose-anesthetized, paralyzed, and artificially ventilated cats. NMDA administered on the intermediate area of the ventral surface of the medulla decreased transnasal pressure and increased phrenic nerve activity. The response to NMDA could be diminished or abolished by application to the ventral medullary surface of the NMDA antagonist 2-amino-5-phosphonovalerate (2-APV) or the local anesthetic lidocaine. Carotid sinus denervation and posthypothalamic decerebration did not alter the nasal and phrenic nerve responses to NMDA; however, cervical sympathetic denervation decreased these responses, both in intact and in bilaterally adrenalectomized animals. Therefore, activation of NMDA receptors on structures near the ventral surface of the medulla increases tone in the nasal vasculature and leads to a response pattern that includes changes in not only phrenic nerve activity and blood pressure but also nasal patency.

Respiratory chemical and reflex interventions have been shown to affect nasal resistance or tracheal tone, respectively. In the present study, nasal caliber (assessed from pressure at a constant flow) and tracheal tone (assessed from pressure in a fluid-filled balloon within an isolated tracheal segment) were monitored simultaneously in anesthetized, paralyzed, artificially ventilated (inspired O2 fraction = 100%) cats. We examined the effect of CO2 inhalation and sciatic nerve stimulation as well as the application of nicotine (6 X 10(-4) mol/l) or lidocaine (2% solution) to the intermediate area of the ventral medullary surface (VMS). CO2 and VMS nicotine resulted in a significant increase in tracheal pressure [147 +/- 73 and 91 +/- 86% (SD), respectively]; and a significant reduction in nasal pressure (-35 +/- 10 and -20 +/- 13%, respectively). In contrast, sciatic nerve stimulation resulted in a significant fall in both tracheal (-50 +/- 36%) and nasal pressure (-21 +/- 13%). Application of 2 or 4% lidocaine to the VMS reduced tracheal pressure but did not significantly affect nasal pressure. After VMS lidocaine, nasal and tracheal responses to CO2, sciatic nerve stimulation, or VMS nicotine, when present, were negligible. These results suggest a role for the VMS in the regulation and coordination of nasal and tracheal caliber responses.

Two studies were carried out to test the hypothesis that the fall and recovery of nasal resistance after exercise in asthmatic and non-asthmatic subjects are related to the development of bronchoconstriction after exercise. In study 1 nasal resistance (posterior rhinomanometry) and specific airway resistance (sRaw) were measured before challenge and one, five, 10 and 30 minutes after four minutes of exhausting legwork exercise in nine asthmatic subjects and nine age matched healthy subjects. One minute after exercise there was a reduction in nasal resistance of 49% (SD 15%) from baseline in the healthy subjects and of 66% (17%) in the asthmatic subjects. This response and the subsequent return of nasal resistance to baseline values did not differ significantly between the two groups despite a substantial difference in the change in sRaw, an increase of 74% (45%) in the asthmatic subjects 10 minutes after exercise, and no change in the non-asthmatic subjects. In study 2, nasal and specific airway resistances were monitored according to the same measurement protocol in six subjects with increased airway reactivity. Subjects exercised on two occasions, wearing a noseclip, once while breathing cold, dry air and once while breathing warm, humid air. The fall in nasal resistance was similar under both conditions (to 47% and 39% of baseline), through sRaw rose only after cold air inhalation (to 172% of baseline). The results indicate that the nasal response to exercise is not related to bronchial obstruction in asthmatic subjects after exercise or to the temperature or humidity of the air inspired through the mouth during exercise.