Laryngeal afferents activated by phenyldiguanide and their response to cold air or helium-oxygen

In anesthetized cats, sensory neurons in the superior laryngeal nerves (SLN) were identified with respect to their response to (1) phenyldiguanide (PDG) i.v., (2) mechanical stimulation and (3) lowering temperature in an isolated tracheolaryngeal segment. The activity originating from 107 SLN afferent units activated by PDG was recorded using glass microelectrodes advanced in the nodose ganglion. All tested afferent units increased their discharge rate during direct touching of the airway mucosa. None showed flow or pressure related activity during abrupt changes in constant laryngeal flow or transmural pressure in the isolated segment. Fifteen units were inhibited by cold air. Sixty-two units significantly increased their firing rate when the temperature approached 18 degrees C, reached a peak discharge near 15 degrees C, then their activity decreased or stopped. The response to cold air was compared to cold heliox (79% He-21% O2), which enhanced the respiratory heat loss by conduction. The peak firing rate was significantly higher with heliox (+356% compared to +246% with air), the temperature threshold higher (25 degrees C +/- 1.0 degree C) and the temperature range broader (25-11.5 degrees C). Present results show that a large proportion (58%) of afferent SLN fibres activated by PDG are likely non-proprioceptive units, which are stimulated by cooling the inspired gas. Thermosensitive units in the upper airways may act as sensors of the thermal flux through the airway wall more than as detectors of the absolute value of temperature in the airway lumen.     

Reflex apnea induced by high-frequency oscillatory ventilation in rabbits

In rabbits with intact vagus nerves, HFOV applied for 10-20 s caused apnea (i.e., respiratory arrest for as long as HFOV lasted) accompanied by tonic discharges of the diaphragm. To identify the vagal mechanisms involved in this type of apnea, the vagus nerves of anaesthetized rabbits were gradually cooled from 37 degrees C to 0 degree C, i.e., the vagal fibres were, corresponding to their diameter, successively blocked. At each temperature, the effects of HFOV on spontaneous breathing were compared with those of static lung inflation and deflation: Between 20 degrees C and 14 degrees C, the lung inflation reflex (mediated by pulmonary slowly adapting stretch receptors = PSR) was weakened or abolished, whereas the lung deflation reflex (mediated by rapidly adapting stretch receptors = RAR) was reinforced; the HFOV-induced apnea occurred less frequently, however, the accompanying diaphragmatic activity was enhanced. Between 14 degrees C and 5 degrees C, both HFOV and large static inflation caused a slight increase of breathing frequency in the majority of animals. Some animals, however, responded even below 14 degrees C by apnea to both HFOV and inflation, and, under these conditions, both HFOV- and inflation-induced apnea were accompanied by a pronounced tonic diaphragmatic activity. At 5 degrees C, the effects of HFOV as well as of inflation (except in two animals) and deflation were abolished. From the results we conclude that in rabbits the apnea during HFOV is mainly mediated by stimulation of PSR, and the concomitant tonic activity of the diaphragm is mainly due to stimulation of RAR, as it is reinforced with gradual blockade of PSR fibres and abolished when only non-myelinated fibres are intact.     

Respiratory effects of cold-gas breathing in humans under hyperbaric environment

Changes in total lung resistance (RL) during inhalation of cold gas mixtures were measured in 4 human volunteers during an experimental dive at 46 ATA. The subjects breathed helium-nitrogen-oxygen mixtures during the decompression schedule, and measurements were performed at 46, 36, 21, 12.5, 6 and 2 ATA (1 ATA = 100 kPa). RL was measured during eupneic ventilation when individuals inhaled either ambient gas at +30 to +33 degrees C (control condition), or cooled gas at +7 to +18 degrees C. RL values measured in control conditions increased with gas density. Thus, the changes in RL induced by cold gas breathing were expressed in percent of the corresponding control values. No cold-induced bronchospasm occurred at low ambient pressure, even at the lowest inspired temperature, +7 degrees C. However, the airway response was present at pressure up to 21 ATA and then occurred at higher level of inspired gas temperature. The convective respiratory heat loss (Cr), calculated at each pressure level and experimental condition, was linearly related to cold-induced changes in RL; the value of Cr inducing 20% increase in RL was around 1.4 kcal.min-1. The bronchomotor response was related to the increase in respiratory heat loss induced by the high thermal capacity of the gas mixture used in hyperbaric environment. The present observations confirm previous data obtained under hyperbaric conditions (25 ATA) as well some experiments performed at sea level in normal individuals breathing very cold air.     

Reciprocal action of pulmonary vagal afferents on tracheal smooth muscle tension in dogs

Tracheal smooth muscle usually relaxes when the lungs are transiently inflated, an effect attributed to inhibitory input from pulmonary stretch receptors (PSRs). Relaxation is often followed by contraction, however, and occasionally contraction is the sole response. We attempted to identify the afferents responsible for this reflex contraction. In anesthetized, artificially ventilated dogs with open chest we recorded transverse tension in an upper tracheal segment innervated only by the superior laryngeal nerves and periodically hyperinflated the lungs as the cervical vagus nerves were cooled. Hyperinflation usually evoked tracheal relaxation when vagal temperature was 37 degrees C, but contraction became more frequent as temperature decreased and was the sole response below 8 degrees C. We hypothesise that above 6 degrees C contraction was triggered by rapidly adapting receptors and lung C fibers, whereas below 6 degrees C only C fibers were involved. Contraction, which appeared to represent the bronchomotor counterpart of Head's paradoxical reflex, was abolished below 2 degrees C. Cooling alone without periodic hyperinflation increased baseline tracheal tension to a maximum at 7-8 degrees C; further cooling often decreased tension, sometimes to control levels. Cutting the pulmonary vagal branches abolished these effects. Our results indicate that PSRs and C fibers act reciprocally, one causing bronchodilation, the other bronchoconstriction, and that background activity in C fibers may contribute to bronchomotor tone, an effect unmasked by selectively blocking A fibers.     

Effects of cooling on laryngeal reflexes in the dog

We investigated the reflex effects of laryngeal cooling on posterior cricoarytenoid (PCA) muscle activity, breathing pattern, arterial blood pressure and heart rate. We performed experiments on 9 anesthetized, spontaneously breathing dogs. Laryngeal temperature was decreased by passing cold air through the functionally isolated larynx while the dog was breathing through a tracheostomy. Inspiratory and expiratory durations, esophageal pressure, peak PCA activity, heart rate and blood pressure did not change significantly during laryngeal cooling. Upon interruption of cold airflow, while the laryngeal temperature was returning to control values, we assessed PCA response to upper airway occlusion. At laryngeal temperatures of 20-25 degrees C the peak PCA activity during upper airway occlusion was approximately 2/3 of that observed at control temperature (approximately equal to 33 degrees C). This difference was abolished by topically applied anesthetics or by superior laryngeal nerve section. In addition, we recorded from 4 laryngeal mechanoreceptors stimulated by negative pressure; their response to upper airway occlusion was reduced to 1/2 by laryngeal cooling. These results indicate that laryngeal cooling has a marked depressive effect on the PCA response to collapsing pressure in the larynx, thereby compromising the mechanism subserving upper airway patency.     

Cooling mediates the ventilatory depression associated with airflow through the larynx

Although constant airflow through the upper airway has been shown to induce ventilatory depression in anesthetized newborn animals, the role of laryngeal temperature in this response has not been studied. Experiments were performed in fourteen 1-5 day-old anesthetized puppies breathing through a tracheostomy. Tidal volume and laryngeal temperature were recorded while a constant stream of air (15-25 ml/sec) at room temperature was passed in the expiratory direction for 20 sec through the isolated upper airway. Warm (35-37 degrees C), humidified air at the same flow served as control. When laryngeal temperature was decreased by 7.5 +/- 0.9 degrees C, a marked change in breathing pattern was observed (VT = 54 +/- 5, TI = 187 +/- 33, TE = 636 +/- 179, VT/TI = 45 +/- 10% of control; n = 9). Warm air at the same flow induced no significant changes. Superior laryngeal nerve section abolished the effects of cooling on breathing pattern. In 5 puppies we compared the effect of 'fast' and 'slow' laryngeal cooling. Fast trials altered breathing pattern earlier than slow trials. We conclude that the depressant effect of airflow through the upper airway is entirely due to a decrease in laryngeal temperature and is mediated by superior laryngeal nerve afferents.     

Characteristics of laryngeal cold receptors

This study was designed to further characterize the properties of previously described laryngeal cold receptors (Respir. Physiol. 59:35, 1985). Single unit action potentials were recorded from the internal branch of the superior laryngeal nerve (SLN) in anesthetized, spontaneously breathing dogs. The nervous conduction of fibers originating from 12 laryngeal cold receptors was blocked at a mean (+/- SE) temperature of 18.8 +/- 0.7 degrees C. Twelve receptors were localized on the edge of the vocal folds in correspondence of the vocal process of the arytenoid cartilage. Topical anesthesia (2% lidocaine) blocked their activity within 4-18 sec, suggesting a superficial location. Paralysis of the vocal folds during spontaneous breathing through the upper airway did not alter the activity of 9 of 13 cold receptors. On the other hand, 7 of 12 cold receptors tested with constant flow showed respiratory modulation and laryngeal paralysis abolished the modulation of 3 of these tested with a constant flow of air. During progressive cooling in a stepwise fashion, as in frigid air breathing, laryngeal cold receptors maintained a phasic discharge. Our results indicate that these endings are particularly suited for detecting changes in temperature.     

Dynamic analysis of airway temperature in dogs breathing cold air]

Exercise in cold, dry air induces bronchoconstriction. However, the time course of airway cooling during the breathing of cold air has not been investigated. In this study in dogs, the temperatures of tracheal gas and the tracheal wall were measured continuously while the animal was breathing cold air at approximately 4.5 degrees C. The temperature of the tracheal gas decreased during the inspiratory phase, increase slightly early in the expiratory phase, and then decreased to the level at end-expiration. The lowest temperature of the tracheal gas decreased significantly, from 29.7 +/- 2.4 degrees C (mean +/- SD) to 25.7 +/- 2.8 degrees C. The highest temperature also changed significantly, but the decrease was less than 1 degree C. The lowest temperature of the tracheal wall decreased from 31.1 +/- 2.6 degrees C to 30.5 +/- 2.5 degrees C during cold-air breathing, but the difference was not significant. When a dog inspired deeply during a cough, the temperature of tracheal gas did not decrease linearly with the progression of inspiration. However, the decrease in the tracheal wall temperature was almost directly proportional to inspiratory volume. We concluded that both the tracheal gas and the tracheal wall temperatures were resistant to cooling with cold-air breathing. It remains uncertain whether rapid, deep breathing during exercise decreased the tracheal wall temperature.     

Effect of alpha-adrenergic blockade on exercise-induced asthma and conditioned cold air

Cooling and drying of the intrapulmonary airways have been shown to be important stimuli for the development of bronchospasm induced by exercise and isocapnic cold air hyperventilation. It has also been suggested that alpha-adrenergic receptor activity is increased at lower temperatures. To evaluate the role of alpha-adrenergic activity in the development of bronchoconstriction during airway cooling, we examined the effects of alpha-adrenergic blockade with phentolamine on bronchospasm induced by exercise and isocapnic cold air hyperventilation in 8 asthmatics. Exercise consisted of 6 min of steady-state exercise at 90% predicted maximal heart rate breathing compressed air at 0% humidity and 21 +/- 1 degrees C (mean +/- SD). During baseline exercise studies, FEV1 fell 41.6 +/- 15.8%, but only 12.8 +/- 8.5% during alpha-adrenergic blockade (p less than 0.001). Isocapnic cold air challenge consisted of breathing compressed cold air (0% humidity, -17 +/- 4 degrees C) for 3-min periods, with stepwise increases in minute ventilation (Ve) until the FEV1 fell at least 20%. During baseline cold air challenges, FEV1 fell 20% (PD20 FEV1) at a Ve of 48.8 +/- 21 L/min. However, during alpha-adrenergic blockade 6 asthmatics were able to achieve much higher levels of VE (86.6 +/- 22.7 L/min) before FEV1 fell 20% (p less than 0.01), and 2 asthmatics did not decrease their FEV1 by 20%, despite reaching maximal levels of ventilation of 132 and 108 L/min, respectively. Alpha-adrenergic blockade did not affect airways responses to histamine or ragweed antigen (p greater than 0.1).(ABSTRACT TRUNCATED AT 250 WORDS)     

The effects of electrical stimulation of myelinated and non-myelinated vagal motor fibres on airway tone in the rabbit and the cat

The bronchomotor effects of repetitive electrical stimulation of the peripheral end of the cervical vagus nerves were studied in anaesthetized and paralysed rabbits and cats. Stimulation of either myelinated or of all motor vagal fibres was obtained by varying the duration of electrical square pulses. In rabbits, selective stimulation of myelinated vagal fibres induced a bronchoconstriction, strongly potentiated by the recruitment of non-myelinated fibres. This potentiation was absent in cats. After ganglionic blockade with hexamethonium, the vagally mediated bronchoconstriction was abolished in rabbits, while a slight and transient effect persisted in cats. Propranolol did not modify the bronchoconstrictor response to vagal stimulation, which was abolished after further injection of atropine in both species. When propranolol plus atropine was administered and airway tone was increased by continuous i.v. injection of bronchoconstrictor agonists, the stimulation of vagal motor fibres was devoid of any bronchomotor effect in rabbits. However, in cats this resulted in a strong bronchodilation, which was doubled after recruitment of non-myelinated fibres. Thus, in the latter species preganglionic vagal motor fibres participate in the non-adrenergic-non-cholinergic vagal system. Amongst them, non-myelinated fibres play an important role.     

Effect of breathing dry warm air on respiratory water loss at rest and during exercise

The changes in respiratory water loss with time, expressed as the mass of water vapour lost per liter BTPS of ventilation (MH2O), and expired temperature (TE), used to calculate the relative humidity (ERH), were investigated in ten normal subjects while breathing warm dry air by mouth (PIH2O = 0 kPa; TI = 30 degrees C): at rest for a period of 35 min; during 15 min light muscular exercise (50 W); at increasing work load from 50 to 100 W between the 5th and 10th min of the exercise. The data collected were compared to those obtained in room air conditions (PIH2O = 0.68-1.3 kPa) and under conditions with slightly heated inspired air (TI = 28-30 degrees C). At rest, when breathing dry warm air MH2O and ERH fell during the first 15 min, while they recovered their initial values during the last 20 min. In contrast no differences in MH2O or ERH were observed when breathing ambient warm air. At constant and moderate work load for 15 min, the respiratory water loss fell significantly (compared to the 5th min) at the 10th and the 15th min when breathing warm dry air. The added hyperpnea which was obtained by increasing work load from 50 to 100 W between the 5th and 10th min of exercise did not further reduce MH2O and ERH. The transient fall in MH2O and ERH, which lasted at least 15 min either at rest or during muscular exercise, suggested that the mechanism underlying humidification of expired gas is overwhelmed by thermal stress. Since the upper airways mucosa is unable to saturate expired gas, this also suggested that the mucosa is dehydrated and probably hyperosmotic. The progressive recovery in MH2O and ERH after 15 min of warm dry air breathing at rest, suggest operation of a slow adaptive mechanism.     

Respiratory heat loss is not the sole stimulus for bronchoconstriction induced by isocapnic hyperpnea with dry air

It is uncertain if respiratory heat loss or respiratory water loss is the stimulus for bronchoconstriction induced by isocapnic hyperpnea or exercise with dry air in subjects with asthma. We partially separated these 2 stimuli by having 18 subjects with asthma breathe dry air (0 mg/L water content) at increasing ventilations by isocapnic hyperpnea while we measured the increase in specific airway resistance (SRaw). The study was divided into 2 phases. In Phase 1, we used an apparatus with a single respiratory valve and evaluated the subjects' responses at 3 different inspired temperatures (-8.4, 20.5, and 39.4 degrees C). Seven of the subjects had esophageal catheters with 2 thermocouples in place to measure retrocardiac and retrotracheal temperatures. In this phase, we found that there were no significant differences in the ventilation required to cause a 100% increase in SRaw among the 3 different inspired temperatures (48.4 L/min, cold; 47.5 L/min, room temperature; 44.2 L/min, hot), even though the retrotracheal temperature fell more when the subjects breathed cold air at 40 L/min (2.1 degrees C) than when they breathed hot air (1.2 degrees C), suggesting greater airway cooling with the cold air. In Phase 2, in order to accurately measure inspired and exhaled temperatures and exhaled water content, we used 2 separate systems for delivering the inspired air and collecting the exhaled air at 2 different inspired temperatures (-21.4 and 38.9 degrees C). Again, we found that there was no significant difference in the ventilation required to cause a 100% increase in SRaw between the 2 different inspired temperatures (28.3 L/min, cold; 33.6 L/min, hot). When the subjects inhaled cold air, exhaled temperature was warmer than previously reported.(ABSTRACT TRUNCATED AT 250 WORDS)     

Phrenic and hypoglossal neural responses to cold airflow in the upper airway.

Cold air flowing through the larynx is known to alter the activities of laryngeal receptors with afferents in the superior laryngeal nerves (SLNs) and to induce reflex apnea in neonatal mammals. To examine the ventilatory response in adult animals and to explore associated upper airway motor responses, we recorded phrenic and hypoglossal neural responses to cooling the isolated larynx with cold air in decerebrate, vagotomized, paralyzed, ventilated cats. The most consistent response was phrenic inhibition, which occurred in all animals tested. Either excitation or inhibition of hypoglossal activity was seen consistently in individual cats, with the result that the group response was not statistically significant. All responses to laryngeal cooling were abolished by section of the SLNs. The findings confirm that directing cold air through the larynx causes reflex inhibition of ventilatory (phrenic) activity, but raise new questions as to how the two, directionally opposite hypoglossal responses are mediated.     

Background activity in pulmonary vagal C-fibers and its effects on breathing

Vagal cooling experiments suggest that the deep slow breathing observed after vagotomy results not only from loss of pulmonary stretch receptor feedback, but also from loss of some unidentified vagal input. To investigate this possibility we cooled the vagus nerves in anesthetized dogs. In dogs breathing spontaneously, the Hering-Breuer reflex was abolished at 7 degrees C, but average expiratory time was unchanged and lengthened only on cooling below 3 degrees C. In artificially ventilated dogs the pulmonary vagus nerves were cooled in the chest and phrenic activity was recorded. Entrainment of phrenic bursts to the ventilator cycle ceased at 7 degrees C, and expiratory pauses shortened; they lengthened again on cooling below 3 degrees C. Cervical vagotomy did not change breathing pattern after the pulmonary vagus nerves were cut. Recording of afferent impulses during cooling showed that at 5 degrees C or less pulmonary vagal input was confined largely to nonmyelinated fibers; at 3 degrees C, background activity in pulmonary C-fibers was still 78% of control whereas myelinated afferents were virtually silent. We suggest that in eupnea low frequency, background activity in pulmonary afferent C-fibers shortens expiratory time.     

Cold-induced bronchospasm in normal and sensitized rabbits

In anesthetized, paralyzed and artificially ventilated rabbits, changes in lung resistance induced by cooling the inspired air were studied under dry air conditions. Airway response to cold was measured in normal animals and in rabbits sensitized to bovine serum albumin. The magnitude of cold-induced bronchospasm was significantly greater in sensitized than in normal rabbits but the time course for recovery of control lung resistance during rewarming was the same in both groups and lasted longer than 4 min. Inhalation of a nebulized aerosol of sodium cromoglycate (SCG) markedly reduced cold-induced bronchospasm and shortened the recovery period, which then lasted only 20 to 30 sec. Vagotomy abolished the airway response to cold air in all cases and this was observed whether the vagus nerves were cut before or after SCG inhalation. SCG or vagotomy exerted the same effect on the response to cold air in normal or sensitized rabbits. Sensitized animals showed an hyperresponsiveness to histamine as well as to cold air. These results suggest that cold-induced bronchospasm results from a vagally mediated reflex whose effects are only enhanced and prolonged by a local release of humoral factors, linked to the reflex path. The increased response to cold air in the sensitized rabbits seems to correspond to non-specific hyperresponsiveness of bronchial smooth muscle rather than to an increased local release of inflammatory mediators.     

Water vapour and temperature dynamics in the upper airways of normal and CF subjects

Water vapour partial pressure (PH2O) and temperature (T) were measured together, continuously, at the airway opening (either lips or nares) and at the oropharynx of human subjects with normal lungs or with cystic fibrosis (CF). No apparent differences in PH2O or T were found between normal and CF groups breathing ambient air (22 +/- 2 degrees C). During inspiration the relative humidity at the pharynx for nose breathing (95%) was higher than for mouth breathing (75%). For hot air breathing (48 +/- 2 degrees C), the PH2O and relative humidity of inspired gas at the pharynx was lower for the CF group than for the normal group. Also, the CF group had a higher airway surface temperature at the airway openings on inspiration. These data suggest that when the rate of evaporation is sufficiently high, the rate-limiting step may be water transport through the mucosal tissue and/or secretions. At least for the upper airways, this rate limitation is more evident for CF patients than for normal subjects.     

Effects of bronchoconstriction on breathing during normoxia and hypoxia in anesthetized cats

The effect of an increase in bronchomotor tone on control of breathing during both normoxia and hypoxia, and the role of vagal afferents in regulating these responses were studied in 15 anesthetized cats. Minute ventilation (VE) was measured with a pneumotachograph connected in series with a tracheal cannula. Total diaphragmatic EMG activity per minute (means p X f, peak EMG moving average X respiratory frequency) was measured to assess the central inspiratory drive. Bronchoconstriction was generated by inhalation of methacholine aerosol (10-30 breaths, 0.5% solution) which increased total lung resistance to approximately 400% of the control value. Transient hypoxia was induced by allowing the cats to rebreathe a hypoxic gas mixture (4.5% O2 balanced N2) for approximately 1 min. During normoxia, bronchoconstriction increased VE from a baseline of 100 to 129 +/- 7% (mean +/- SEM; P less than 0.05) and increased (means p X f) from 100 to 174 +/- 16% (P less than 0.01). During hypoxia, the response of (means p X f) to bronchoconstriction (404 +/- 40%) was still greater than without bronchoconstriction (306 +/- 35%; P less than 0.01), but the responses of VE were not significantly different between these two conditions (P greater than 0.05). After sectioning both vagus nerves the bronchoconstriction-induced increase in central inspiratory drive was either reduced (during normoxia) or abolished (during hypoxia). These results suggest that stimulation of vagal bronchopulmonary afferents are involved in regulating the ventilatory responses to bronchoconstriction. Other non-vagal factors, such as intrinsic properties and reflex responses of the respiratory muscles, may also contribute, in part, to the observed responses.     

Menthol in the upper airway depresses ventilation in newborn dogs.

Upper airway cooling depresses ventilation in the newborn dog. Since airway cooling stimulates laryngeal cold receptors and inhibits laryngeal mechanoreceptors, the type of afferent ending responsible for this reflex cannot be easily identified. l-menthol, a specific stimulant of cold receptors in the absence of any cooling, has been used to ascertain the discrete role of upper airway cold receptors in this ventilatory depression. Experiments were carried out in 8 anesthetized 7-14-day-old dogs breathing through a tracheostomy with the upper airway functionally isolated. Constant flows of warm air (37 degrees C), with and without addition of l-menthol, and cold air (25 degrees C) were delivered through the upper airway in the expiratory direction. As compared to warm air trials, cold air and warm air + l-menthol trials greatly reduced ventilation (57.5 +/- 10.7% and 52.8 +/- 11.7% of control, respectively; P less than 0.01) mostly due to a prolongation of Te (291.2 +/- 106.4% and 339.2 +/- 90.0%, respectively, P less than 0.01). Section of the superior laryngeal nerve abolished the response to cold air. However, a residual depressive effect of l-menthol was still present in 3 of 5 animals and was abolished by nasal anesthesia, suggesting the involvement of nasal cold receptors. The results suggest that in the newborn dog stimulation of laryngeal cold receptors, without any concurrent inhibition of laryngeal mechanoreceptors, is a sufficient stimulus to cause respiratory depression.     

Interaction between SO2 and cold-induced bronchospasm in anesthetized rabbits

In anesthetized, paralyzed and artificially ventilated rabbits, reflex changes in lung resistance induced by cooling the inspired air from 38 to 15 degrees C were studied before and after 45 min periods of SO2 exposure at two different concentrations (0.5 or 5 ppm). Both concentrations of SO2 induced significant increase in RL in intact animals (+16% and +50%, respectively). The effect of 5 ppm SO2 persisted after vagotomy. The cold-induced bronchospasm was halved after exposure to 0.5 ppm SO2 and was no longer significant after exposure to 5 ppm SO2. In both cases, RL recovered to control values 40 min after the end of SO2 exposure and then, the magnitude of cold-induced bronchospasm also recovered. The reflex bronchoconstrictor response to phenyldiguanide (PDG) i.v. disappeared after exposure to 5 ppm SO2. However, the bronchomotor response to histamine i.v., which involved both reflex and direct actions on airway smooth muscle, was not altered. These results show that (1) prolonged increase in RL measured after SO2 exposure does not result from a vagal reflex; (2) the cold-induced bronchospasm, as well as the bronchomotor response to PDG, are reduced or suppressed during the period where the effect of SO2 persisted. This suggests that 45 min exposure to SO2 induces transient alterations in tracheobronchial wall, which reduce the accessibility to nervous receptors in the airways.     

Temperature and humidity modify airway response to inhaled histamine in normal subjects

The airway response to inhaled histamine is known to be influenced by various stimuli (e.g., infection, ozone). Temperature (T) has been shown to affect it in vitro. We studied whether T and humidity (H) modify airway response to inhaled histamine in normal subjects. Twelve normal subjects 21 to 46 yr of age (mean age, 29 yr) performed two similar histamine inhalation tests, the only difference being the conditions of the inspired air. One test was done while breathing cold dry air (mean T +/- SEM, -17.3 +/- 1.8 degrees C; relative H, 0%), and the other while breathing warm humid air (mean T +/- SEM, 33.9 +/- 0.5 degrees C; relative H, 100%). Whereas the geometric mean histamine concentration required to produce a 15% fall in FEV1 in the warm humid tests was 22.7 mg/ml, it was 11.9 mg/ml in the cold dry test (p less than 0.01). It is concluded that the T and H of inspired air modify the airway response to inhaled histamine in normal subjects.