Inhaled furosemide attenuates hyperpnea-induced obstruction and intra-airway thermal gradients.

Inhaled furosemide attenuates exercise- and isocapnic hyperventilation-induced asthma; however, the mechanism for this phenomenon is unknown. Because the magnitude of the intra-airway thermal gradient that develops between the cooling of hyperpnea and the rewarming that occurs once hyperventilation ceases is directly related to the severity of thermally induced obstruction in humans, we wondered if furosemide blunted these temperature changes. To explore this issue, eight asthmatic subjects had tracheobronchial airstream temperature measures as they performed isocapnic hyperventilation with frigid air alone (HV) or with pretreatment with inhaled saline (S + HV) or 45 +/- 3 (SE) mg of furosemide (F + HV).

Acoustic rhinometry: effects of decongestants and posture on nasal patency.

To determine whether acoustic rhinometry can be used to detect changes in nasal patency caused by decongestants or posture, we studied 10 healthy volunteers. Maps of the effective cross-sectional area of the nasal cavity as a function of distance into the respiratory system were generated, and an index of nasal cavity volume was calculated in the right and left nostril of each subject. The volume index was reproducible in subjects.

Effects of ozone on lung mechanics and cyclooxygenase metabolites in dogs.

To determine if acute exposure to ozone can cause changes in the production of cyclooxygenase metabolites of arachidonic acid (AA) in the lung which are associated with changes in lung mechanics, we exposed mongrel dogs to 0.5 ppm ozone for two hours. We measured pulmonary resistance (RL) and dynamic compliance (Cdyn) and obtained methacholine dose response curves and bronchoalveolar lavagate (BAL) before and after the exposures.

Fast-responding automated airway temperature probe.

Rapid changes occur in the thermal profiles of asthmatic subjects following the cessation of hyperpnea, which include temperature increases of the order of 0.25 degrees C s-1 in the trachea. These thermal events could indicate abnormal blood flow in the airway wall of these patients, a factor which may be linked to the instability of their airway geometry.

Contribution of large airway to the input impedance of the respiratory system.

To evaluate the contribution of the large airway to total respiratory impedance, we develop a one-dimensional model of pressure and flow in these airways by coupling conservation of mass and momentum equations with the geometric information obtained by the acoustic reflection technique. We use this model to calculate the impedance of the respiratory system distal to the carina from impedance data estimated at the airway opening by the forced oscillation technique. Simulations show that the real part of the impedance distal to the carina is uniformly decreased from the impedance at the airway opening, indicating a resistive loss, while the imaginary part is increased as a function of frequency.

Proximal, tracheal, and alveolar pressures during high-frequency oscillatory ventilation in a normal rabbit model.

To study the effect of different high-frequency oscillatory ventilation parameters on airway pressure, we measured oscillatory pressure amplitude ([Paw[) and mean airway pressure (Paw) at three sites in open-chested normal rabbits: proximal, trachea, and alveolus. Five animals were studied to test a new pleural capsule design, which was then used in two groups of animals to measure right upper (n = 4) or middle (n = 5) lobe alveolar pressures. Animals were randomly sequenced through combinations of frequency (10, 15, and 20 Hz) and fractional inspiratory time (Ti) (0.

The effect of repetitive exercise on airway temperatures.

To determine if a relationship exists between intra-airway thermal events and the reduction in pulmonary mechanics that occur in asthmatics when they perform repetitive exercise, we recorded intrathoracic airstream temperatures in seven subjects during and after two identical bouts of cycle ergometry performed 30 min apart. From these data, global and regional thermal energy exchanges were calculated. Inspired air conditions, work loads, and minute ventilations were held constant for both trials.

Effect of facial cooling on mucosal blood flow in the mouth in humans.

1. To determine the effects of facial cooling on intraoral thermal events, we placed a thermal conductivity sensor on the buccal surface of the left cheek in six normal and six asthmatic subjects. Room temperature and cold stimuli were then applied to the integument surface of both sides of the face while mucosal surface temperature and thermal conductivity, as an index of blood flow, were recorded.

Radial heat and water transport across the airway wall.

The thermal profiles in the airways of healthy human volunteers and patients with asthma differ after cessation of hyperpnea. The asthmatic patients rewarm their airways more rapidly. To identify thermal properties and processes that could account for the difference between these populations, we developed a model describing the radial transport of heat and water across the trachea.

Effects of ozone on cyclooxygenase metabolites in the baboon tracheobronchial tree.

Short-term exposure to 0.5 parts per million (ppm) ozone has been shown to cause an increase in respiratory resistance in primates that can be diminished by 50% with pretreatment with cromolyn sodium. Because of the known membrane-stabilizing effects of cromolyn and the resultant inhibition of mediator production, we hypothesized a role for the products of arachidonic acid (AA) metabolism in these events.

A model of muscular control of upper airway geometry.

Some disorders of the upper airway in humans are marked by decreased cross-sectional area and increased airway wall compliance. Based on our observations from studies performed in the isolated upper airway of dogs, we hypothesized that the size, and perhaps the geometry, of the airway was altered by changes in the relative activation levels of various muscle pairs. This could be accomplished either by altering the intensity of the neuromuscular input, or by activating muscle pairs which have different geometric orientation to the airway.

Responses to negative pressure surrounding the neck in anesthetized animals.

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.

Reproducibility of measurements of upper airway area by acoustic reflection.

To evaluate the extent and nature of the variability of measurements of upper airway area by acoustic reflection (AAAR), we made repeated measures of pharyngeal AAAR in 10 normal adult volunteers. We selected mean pharyngeal area as a better index of upper airway size than peak pharyngeal area or pharyngeal volume. Within-run variability of this measure was 8 +/- 4% (SD) (coeff of variation).

Instrumentation for estimating pulmonary function in patients on positive end-expiratory pressure.

For patients requiring PEEP during ventilation, e.g., patients with respiratory distress syndrome, performing traditional tests of lung function is a complicated problem.

Elastic characteristics of the airway wall.

To examine the elastic behavior of the upper airway, we obtained pressure-area plots from data gathered from acoustic images of the airway and measurements of mouth pressure during tidal breathing in 10 adult human volunteers (dA/dP). These plots revealed both tidal hysteresis and a change in slope as a function of distance along the airway. The slope of the regression line of the dA/dP plots decreased from the pharyngeal region to the trachea and became 0 at the thoracic inlet, the location of which was independently assessed.

Intra-airway thermodynamics during exercise and hyperventilation in asthmatics.

To determine whether exercise and hyperventilation produce the same intrathoracic thermal events in asthmatics, we used a thermal probe to record airstream temperatures during both stimuli at multiple points within the tracheobronchial tree. From these data, the global and regionally distributed exchanges of water and heat that occurred throughout the respiratory tract were calculated. During each provocation, intra-airway temperatures fell equivalently, thereby producing similar intrathoracic water fluxes and heat transfers.

Relationship between lung volume and tracheal area as assessed by acoustic reflection.

To determine whether airway size correlates with measures of lung or body size, we used the acoustic reflection technique to calculate tracheal cross-sectional area in 103 healthy young adults. Men have significantly larger tracheas than women [2.48 +/- 0.

Airway response to ultra short-term exposure to ozone.

To determine whether acute short-term exposure to oxidant pollutants can cause changes in respiratory mechanics, we gave 0.5 ppm ozone for 5 min to 7 baboons. We measured pulmonary resistance (RL) and obtained dose response curves to methacholine before and after the exposures.

Heat and water flux in the intrathoracic airways and exercise-induced asthma.

To explore the relationship between the flux of heat and water within the respiratory tract during exercise and recovery to the development of exercise-induced asthma (EIA), we recorded airstream temperature at multiple points throughout the tracheobronchial tree in 10 normal and 10 asthmatic subjects before, during, and after cycle ergometry. In both groups, the intra-airway temperature fell progressively as ventilation increased, and there were no significant differences between the thermal profiles of the two populations at rest or during exercise. Calculation of water losses and the osmolality of the airway surface fluid failed to demonstrate significant airway drying in either group.

Phasic changes in upper airway impedance.

To identify within breath variations in the mechanical properties of the isolated upper airway, we examined changes in impedance spectra over the course of the respiratory cycle. Changes were evaluated with a modified forced oscillation technique applied to the isolated, sealed upper airways of nine anesthetized mongrel dogs. Upper airway impedance spectra were studied during sequential 350 msec epochs.

Assessment of muscle action on upper airway stability in anesthetized dogs.

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.

Effect of position and lung volume on upper airway geometry.

The occurrence of upper airway obstruction during sleep and with anesthesia suggests the possibility that upper airway size might be compromised by the gravitational effects of the supine position. We used an acoustic reflection technique to image airway geometry and made 180 estimates of effective cross-sectional area as a function of distance along the airway in 10 healthy volunteers while they were supine and also while they were seated upright. We calculated z-scores along the airway and found that pharyngeal cross-sectional area was smaller in the supine than in the upright position in 9 of the 10 subjects.

Comparison of volume changes in the upper airway and thorax.

To describe the mechanical cycles of the upper and lower portions of the respiratory system, we measured volume change in and out of the isolated upper airway in 13 anesthetized dogs and compared volume changes in the upper airway with tidal volume change during spontaneous respiratory efforts. During inspiration the onset and peak increase in volume into the upper airway preceded the onset and peak of inspiratory tidal volume by 84 +/- 8 and 638 +/- 47 ms, respectively. The volume cycle of the upper airway was nearly complete by the end of inspiratory airflow into the thorax.