Tidal breathing parameters in young children: comparison of measurement by respiratory inductance plethysmography to a facemask pneumotachograph system

The ratio of expiratory time at tidal peak flow to total expiratory time (t(ptef)/t(e)) correlates with conventional measures of airway obstruction. It is usually assessed using a facemask and pneumotachograph system which may be poorly tolerated in young children and hence limits the usefulness of this technique. We therefore determined in young asthmatic children the accuracy of t(ptef)/t(e), using an uncalibrated respiratory inductance plethysmograph (RIP), and compared the results with those from a facemask-pneumotachograph system. We also assessed whether age influenced the agreement between measurements using the two devices. Forty-seven children aged between 1 month and 12 years were recruited: 39 were inpatients recovering from an acute wheezy episode, and 8 were recruited from the asthma clinic. All were receiving bronchodilators. Tidal breathing parameters t(ptef)/t(e), the duty cycle (t(i)/t(tot)), and respiratory rate were initially measured using the Respitrace alone and then simultaneously with both the Respitrace and the facemask-pneumotachograph system. Eight children did not tolerate the facemask, and in two others it was impossible to analyze the Respitrace trace due to artefacts. In the remaining 37 children, the reliability coefficients and coefficients of variation of the two techniques were similar. Similar values of t(i)/t(tot) and respiratory rate were obtained using the two devices. The mean t(ptef)/t(e) obtained using the Respitrace was lower than with the facemask-pneumotachograph system (P < 0.01), although this was age group-dependent (P < 0.05), as the difference was less apparent in the 1 to 2-year-old children than in other age groups. Application of the facemask-pneumotachograph system did not significantly influence the results obtained using the Respitrace. We conclude that uncalibrated respiratory inductance plethysmography can measure tidal breathing parameters as reliably as a facemask-pneumotachograph system in young asthmatic children, and is better tolerated than the pneumotachograph system. The results obtained using the two devices are not interchangeable.     

Measuring tidal breathing parameters using a volumetric vest in neonates with and without lung disease

Lung function measurement is difficult in unsedated infants; tidal breathing parameters are a useful non‐invasive surrogate, but even these measurements cause disturbance from applying a facemask. We investigated a novel volumetric vest system (FloRight), which measures volume changes of the respiratory system from changes in the magnetic fields induced by current‐carrying coils around the entire chest and abdomen. Using a facemask and ultrasonic flowmeter as comparator, we assessed the validity and repeatability of tidal breathing parameters measured by FloRight in 10 healthy newborn infants during natural sleep. We also assessed the effect of a facemask on tidal volume and tidal expiratory flow parameters. To assess the ability of the FloRight system to detect disease, we compared the healthy infants with 11 infants suffering from bronchopulmonary dysplasia. Tidal parameters with the FloRight vest corresponded closely with facemask measurements. Mean difference, mask minus vest, for tidal volume was 0.096 ml (P < 0.05), with limits of agreement +4.5 to ?4.3 ml. Coefficient of repeatability was similar for mask and vest measurements. Tidal volume measured by FloRight with mask in place (20.6 ml) was significantly higher than without mask (16.1 ml), but tidal expiratory flow parameters were not altered. FloRight measurements of tidal parameters were markedly different between the two groups of infants, with tidal volume per Kg significantly higher and tidal expiratory flow parameters significantly lower. Our findings suggest that the FloRight system is able to measure tidal breathing parameters accurately, in healthy newborn infants, without prior calibration on the infant. It appears to have at least sufficient sensitivity to detect severe respiratory disease. Pediatr Pulmonol. 2010;45:1070–1075. © 2010 Wiley‐Liss, Inc.     

Effect of respiratory apparatus on timing and depth of breathing in man

The effects on breathing of (1) nose-clips, with and without mouthpieces, (2) tube breathing with incremental dead spaces up to 600 ml, and (3) a Venturi mask with a high air inflow reducing the effective dead space to zero were measured with respiratory inductance plethysmography. The effective dead spaces of the lengths of tubing were 25% smaller than their water-displacement volumes. The principal response to the increase in dead space was an increase in VT without any change in frequency or timing. The increase in VE was 16% greater than the ventilation of the effective dead space. The facemask with a high flow of air did not affect the pattern of breathing. External devices alone (nose-clips, mouthpieces) by themselves brought about a significant increase in VT (+10%, P less than 0.05) and a small drop in frequency, which in the case of a nose-clip alone was large enough to be significant (-15%, P less than 0.05). The increase in DS with the change from nasal to oral breathing may have contributed to the accompanying increase in VT; the fall in frequency with the nose-clip alone might have been caused by stimulation of receptors in the trigeminal area.     

Effects of a face mask and pneumotachograph on breathing in sleeping infants

The effect of facial attachments on breathing was measured by respiratory induction plethysmography (RIP) during quiet sleep in 32 studies in 18 infants. The addition of a face mask plus pneumotachograph led to an increase in tidal volume (VT) (22.0 +/- 13.5%, p less than 0.01) during 5-min sleep studies when compared to measurements using RIP alone. Applying only the mask rim also led to an increase in VT (14.6 +/- 3.1%, p less than 0.05). A significant increase in VT was noted in 3 of 6 infants studied when a lightweight cardboard ring was in place perinasally. Respiratory frequency fell significantly in the mask/pneumotachograph group (-5.9 +/- 10.0%, p less than 0.05) and with the mask rim (-7.4 +/- 8.8%, p less than 0.01), but there was individual infant variation. Minute ventilation rose significantly (19.1 +/- 16.9%, p less than 0.01) only with the addition of the mask and pneumotachograph. Instrument deadspace can account for some of the increase in VT noted, but in its absence, sensory stimulation of the trigeminal area can augment tidal breathing.     

Effect of exercise rate and route of inhalation on sulfur-dioxide-induced bronchoconstriction in asthmatic subjects

Nine asthmatic subjects exercised at low, moderate, and high work rates on a cycle ergometer while breathing filtered, humidified air with or without 0.5 ppm of sulfur dioxide (SO2) in a double-blind study. Subjects first performed these experiments breathing through a mouthpiece while wearing a noseclip (oral breathing) and then repeated the experiments breathing through a facemask that separated and permitted independent measurement of oral and nasal air flow (oronasal breathing). We determined specific airway resistance before and after exercise by body plethysmography. Inhaled by mouthpiece, 0.5 ppm So2 caused bronchoconstriction at moderate and high but not at low work rates. There was a dose-response relationship between the work rate performed and the degree of bronchoconstriction induced. Inhaled oronasally, 0.5 ppm SO2 caused bronchoconstriction only at the high work rate. These findings demonstrate that So2-induced bronchoconstriction is dependent on the work rate of exercise during exposure, that oronasal breathing is only partially effective in preventing the bronchoconstriction observed with oral breathing, and that oronasal breathing is less effective in preventing bronchoconstriction with high than with moderate exercise at this concentration of SO2.     

The breathing patterns of identical twins

The resting breathing patterns of healthy adult identical twins were compared to see if there was any possible genetic component in the determination of this pattern. From breath-by-breath analysis of airflow, measured with a pneumotachometer (9 pairs of twins), the pattern of breathing was quantified in terms of individual respiratory variables; inspiratory time (TI), expiratory time (TE), total breath duration (TTOT), VT/TI, TI/TTOT, and by taking TI, TE and VT all together (TRIAD). Also, the airflow shape was quantified by harmonic analysis (ASTER). A second study was performed under more strictly defined conditions of rest and where the respiratory variables were estimated with respiratory inductance plethysmography to eliminate the possible effect of a facemask (5 pairs of twins). In each study, for each variable, the differences within twin-pairs were compared to the differences within random-pairs from the same subject population. In both studies, there were highly significant similarities within twin-pairs in the pattern of breathing, being best demonstrated when the entire 'shape' of the pneumotachogram (ASTER) or the spirogram (TRIAD) was considered.     

Evaluation of the interrupter technique in healthy, unsedated infants.

The interrupter technique may be used to monitor respiratory resistance and does not require active patient cooperation, but has yet to be applied in unsedated, spontaneously breathing infants. The aim of this study was to determine if the interrupter technique is feasible in spontaneously breathing infants and to investigate the influence of facemask types and analysis techniques on the interrupter resistance (Rint). Rint was measured in 14 healthy, unsedated, sleeping infants (aged 38.4 (31-56) days (mean (range)). Paired measurements were made using large volume, compliant (Mcomp) and small volume, rigid (Mrigid) facemasks. Flow and pressure were measured at the airway opening prior to- and following a brief airway occlusion (500 ms). Rint was calculated using four previously reported analysis techniques. Rint could be measured in all infants. Mcomp, independent of the analysis method significantly underestimated Rint (p<0.001). The variability and magnitude of Rint were significantly influenced by the choice of analysis method. The conclusion is that the interrupter technique is feasible in spontaneously breathing, unsedated infants. Equipment design and analysis method significantly influences interrupter resistance. Studies standardizing equipment and identifying the most appropriate analysis technique in this age group are needed.     

Valved holding chambers (VHCs) for use with pressurised metered-dose inhalers (pMDIs): a review of causes of inconsistent medication delivery.

BACKGROUND: Valved holding chambers (VHCs) are prescribed with pressurised metered dose inhalers (pMDIs) to improve medication delivery for the treatment of respiratory diseases because they reduce the need for the patient to co-ordinate inhaler actuation with the onset of inhalation. Although mechanically robust and clinically effective if properly designed and pre-conditioned, there are several causes of inconsistent medication delivery if this is not the case. These include: electrostatic charge; incorrect operation of inhalation and exhalation valves; and the fit of the facemask - where present - to the face. In addition, behavioral factors, such as not following patient instructions for use and maintenance, and imperfect breathing technique, amplify overall variability. Aids such as valve movement indicators that provide patient feedback are helpful in order to minimise these factors. METHODS: This article reviews recent literature concerning the causes of inconsistent drug delivery and the improvements that have been made by manufacturers to VHC devices, and assesses the clinical implications. The attributes of a well-designed VHC are summarised.     

Effect of continuous positive airway pressure on the measurement of thoracoabdominal asynchrony and minute ventilation in children anesthetized with sevoflurane and nitrous oxide

STUDY OBJECTIVE:s: To quantify thoracoabdominal asynchrony (TAA) in children during anesthesia, and to measure the effect of continuous positive airway pressure (CPAP) on TAA, tidal volume (VT), and minute ventilation (E). DESIGN: Prospective, nonrandomized, controlled study. SETTING: Operating room of a university children's hospital. PARTICIPANTS: Ninety children aged 2 to 9 years scheduled for elective outpatient day surgery who were enrolled prospectively. METHODS: Each subject was anesthetized with sevoflurane 3% in equal parts O2 and N2O while breathing spontaneously through a facemask. Respiratory impedance plethysmography was used to calculate TAA indexes (phase angle [PA], phase relation in inspiration [PhRIB], phase relation in expiration, phase relation in total breath [PhRTB], and ratio of the inspiratory time to the total duration of the respiratory cycle [TI/TTOT]), VT, and E. Tidal gas flows were measured with a dual-hotwire anemometer with the sensor inserted between the facemask and the Y-piece of the anesthetic breathing circuit. This enabled the volume calibration of the respiratory impedance plethysmography equipment. The following conditions were compared: (1) no CPAP, (2) CPAP of 5 cm H2O, and (3) CPAP of 10 cm H2O. RESULTS: Eighty-one children completed the study protocol. All measurements of TAA with an inspiratory component (PA, PhRIB, PhRTB, and TI/TTOT) decreased significantly from baseline with the addition of CPAP to the circuit. Application of CPAP of 10 cm H2O decreased significantly mean VTs and Es compared with CPAP of 5 cm H2O and no CPAP. There were no differences in TAA for all conditions when comparing children scheduled for adenoidectomy with other surgical procedures. CONCLUSIONS: With spontaneously breathing anesthetized children, TAA decreases with the application of CPAP. CPAP of 5 cm H2O was as effective as CPAP of 10 cm H2O in reducing PA, PhRIB, PhRTB, and TI/TTOT. However, CPAP of 10 cm H2O also caused a significant decrease in VT and E.     

Effect on breathing of raising end-expiratory lung volume in sleeping laryngectomized man

In animals, tonic vagal activity from lung receptors provides a means by which changes in end-expiratory lung volume can influence respiratory timing. We wished to examine whether increasing the end-expiratory lung volume within the tidal volume range had a similar effect in man. In order to minimize behavioral influences on breathing, the study was performed in subjects during deep non-rapid eye movement sleep. Five laryngectomized subjects were chosen for the study since their permanent tracheal stomata allow simple, airtight connection to respiratory apparatus and avoided problems with glottic closure. During EEG-documented sleep, end-expiratory volume was increased by up to 350 ml with the addition of expiratory threshold loads of 1 to 10 cm H2O. End-expiratory volume increased linearly with expiratory pressure. Inspiratory and expiratory times (TI and TE) were not affected by increases in end-expiratory volume. Tidal volume (VT) was decreased such that end-inspiratory volume remained unchanged. The decrease in VT may result from a reduction in inspiratory muscle efficiency at a higher lung volume. The results of the study provide no evidence that tonic vagal afferent information from the lungs is important in controlling respiratory rhythm within the tidal volume range in man when behavioral control of breathing is minimized.     

Efficiency of the respiratory muscles in healthy individuals

We evaluated respiratory muscle performance by determining the energy cost of breathing against incremental threshold loads and calculating the efficiency of the respiratory apparatus for handling the added work. In five subjects, the energy cost of breathing against the loads, and thus the calculated efficiency of the respiratory muscles, was reproducible on repeated measurements. In all subjects, the calculated efficiency varied while breathing with low loads but was relatively constant at loads that resulted in a mouth pressure of 20 to 60% of the subjects' maximal static inspiratory pressure (PImax). The mean efficiency calculated between 20 to 60% of PImax in 30 normal subjects (15 males and 15 females) ranged between 1.54 and 7.98%. It was significantly greater in males (5.41 +/- 0.43%) (mean +/- SEM) than in females (2.41 +/- 0.17%). There was no relationship between efficiency and body size, but the efficiency correlated with inspiratory muscle strength (PImax). We suggest that measurement of the efficiency of the respiratory muscles over a spectrum of incremental threshold loads is a simple, noninvasive, and reproducible method of assessing respiratory muscle performance and may have clinical application.     

Effect of naloxone on breathing pattern in patients with chronic obstructive pulmonary disease with and without hypercapnia

Recent reports suggest that endogenously released endorphins may exert a modifying influence on respiratory center drive in patients with respiratory disease. In this report, we employed respiratory inductive plethysmography to noninvasively assess breathing patterns with particular attention to respiratory center drive as reflected by mean inspiratory flow. We studied 10 patients with documented chronic obstructive pulmonary disease (6 with hypercapnia and 4 with normocapnia) after treatment with placebo and the opiate antagonist, naloxone. No significant change in breathing pattern was observed in either patient group after treatment with placebo or naloxone, although individual patients displayed greater respiratory drive after naloxone than placebo. Therefore, endorphins do not exert a consistent influence on respiratory center output in patients with chronic obstructive pulmonary disease.     

Characterization and validation of forced input method for respiratory impedance measurement

We have studied the effect of spontaneous breathing on the measurement of total respiratory impedance by the oscillation method, that is using forced random pressure input. Free breathing of the subject induces parasite signals on the pressure and flow measured at the mouth. These induced random signals are correlated through a loudspeaker box with side tubing and flowmeter impedance. The respiratory impedance of the subject, calculated by the cross-power spectrum method, is shown to be systematically biased. This bias is obvious in a calculation model, experimentally verified by an analogue electrical experiment. The validity of the method depends on the respiratory noise level which affects the correlation between the forced pressure input and related flow output. The impedance of the apparatus should thus be minimized in order to decrease the respiratory noise. In this manner, the bias would be shifted to lower frequencies and the accuracy of the measurement near the resonant frequency of the respiratory system would be improved.     

Effects of imposed pursed-lips breathing on respiratory mechanics and dyspnea at rest and during exercise in COPD

STUDY OBJECTIVES: To investigate the effect of volitional pursed-lips breathing (PLB) on breathing pattern, respiratory mechanics, operational lung volumes, and dyspnea in patients with COPD. SUBJECTS: Eight COPD patients (6 male and 2 female) with a mean (+/-SD) age of 58 +/- 11 years and a mean FEV1 of 1.34 +/- 0.44 L (50 +/- 21% predicted). METHODS: Wearing a tight-fitting transparent facemask, patients breathed for 8 min each, with and without PLB at rest and during constant-work-rate bicycle exercise (60% of maximum). RESULTS: PLB promoted a slower and deeper breathing pattern both at rest and during exercise. Whereas patients had no dyspnea with or without PLB at rest, during exercise dyspnea was variably affected by PLB across patients. Changes in the individual dyspnea scores with PLB during exercise were significantly correlated with changes in the end-expiratory lung volume (EELV) values estimated from inspiratory capacity maneuvers (as a percentage of total lung capacity; r2 = 0.82, p = 0.002) and with changes in the mean inspiratory ratio of pleural pressure to the maximal static inspiratory pressure-generating capacity (PcapI) [r2 = 0.84; p = 0.001], measured using an esophageal balloon, where PcapI was determined over the range of inspiratory lung volumes and adjusted for flow. CONCLUSION: PLB can have a variable effect on dyspnea when performed volitionally during exercise by patients with COPD. The effect of PLB on dyspnea is related to the combined change that it promotes in the tidal volume and EELV and their impact on the available capacity of the respiratory muscles to meet the demands placed on them in terms of pressure generation.     

Esophageal-directed pressure support ventilation in normal volunteers

STUDY OBJECTIVES: To ascertain whether inspiratory pressure support (IPS) can be triggered reliably from and targeted at esophageal pressures (Pes), and to compare the work of breathing and time delay to initiation of inspiratory flow between conventional pressure support and esophageal-directed pressure support (EDPS). DESIGN: Prospective laboratory study. SETTING: University medical school. PATIENTS OR PARTICIPANTS: Five normal volunteers. INTERVENTIONS: IPS at a level to achieve tidal volume of 10 mL/kg, and EDPS with a target Pes of 0 cm H2O via full facemask. MEASUREMENTS AND RESULTS: Pes, airway pressure, and inspiratory flow were measured during spontaneous breathing. Peak Pes and pressure time product (PTP) of Pes were calculated during spontaneous breathing and through linear resistances. Measurements were repeated during IPS and EDPS ventilation. At rest, PTP was 7.56 (+/- 3.6) and peak Pes was -5.8 cm H2O (+/- 1.44). When subjects were breathing through the resistors, PTP increased to 12.4 (+/- 8.1) and 30.3 (+/- 8.9) and peak Pes decreased to -7.2 and -15.3 cm H2O respectively. With facemask IPS, unloaded PTP fell to 1.7 (+/- 1.3) and peak Pes fell to -3.3 cm H2O (+/- 1.3). When ventilated through the highest resistance with IPS, mean PTP increased to 21.9 and peak Pes increased to -11.9 (+/- 4.2) cm H2O relative to baseline. During EDPS with the resistor, PTP fell to 1.5+/-1.1 (p < 0.007) and peak Pes fell to -1.9+/-1.1 cm H2O (p < 0.0001). CONCLUSIONS: It was possible to initiate supported breathing from Pes values. The work performed, as measured by PTP, was lower during EDPS than during either unsupported breathing or conventional IPS.     

Continuous positive airway pressure by face mask in acute cardiogenic pulmonary edema

The therapeutic efficacy of continuous positive airway pressure (CPAP) administered by face mask was studied in 40 patients with acute cardiogenic pulmonary edema and respiratory failure. Arterial blood gas values and pH, systemic arterial pressure, heart rate and respiratory rate were measured during administration of 30% oxygen with a high-flow face mask apparatus at ambient airway pressure. Twenty patients were then randomly chosen to continue ambient airway pressure breathing and 20 received 10 cm H2O of CPAP. The measurements were repeated 10, 60 and 180 minutes after therapy was initiated. During the first 10 minutes of CPAP treatment, arterial blood oxygen partial pressure increased 8 +/- 9 mm Hg (mean +/- 1 standard deviation), (p less than 0.01) and respiratory rate decreased 5 +/- 5 breaths/min (p less than 0.001). Systolic arterial pressure decreased 12 +/- 21 mm Hg (p less than 0.05), and heart rate by 10 +/- 11 beats/min (p less than 0.001). A decrease in respiratory rate by 2 +/- 5 breaths/min (p less than 0.05) was the only change that occurred in the control group. The improvement in arterial blood oxygenation persisted throughout the investigation period (p less than 0.05). Thirteen patients (65%) in the control group and 7 patients (35%) in the CPAP group met our criteria for treatment failure during the study (p = 0.068). Thus, CPAP administered by face mask improves gas exchange, decreases respiratory work, unloads circulatory stress, and may reduce the need for ventilator treatment in acute cardiogenic pulmonary edema.     

Nasal airflow and thoracoabdominal motion in children using infrared thermographic video processing

The assessment of apnea and asynchronous breathing requires the application of a facemask connected to a pneumotachograph and inductive transducer bands placed around the chest wall. These contact devices may alter the breathing pattern and are difficult to implement, especially in infants and children. This study validates a contactless image‐processing system that simultaneously retrieves breath‐related thermal variations from nasal, ribcage, and abdomen regions of interest (ROI) from infrared thermographic video recordings of children. Thermographic videos were obtained in 17 supine, spontaneously breathing unsedated children (0.33–13.75 years), including 8 patients with respiratory pathology. Representative thermographic signals were obtained from each ROI on a frame‐by‐frame basis. Cronbach's Alpha reliability coefficient assessed the correlation between control nasal pressure period, the visually scored respiratory rate and the fundamental period in the frequency domain of thermographic signals. A cross‐correlation function calculated the time delay and the phase angle between ribcage and abdomen variability. A Cronbach's Alpha value of 0.976 (0.992–0.944 95% CI) suggests a small‐scale measurement error between thermographic and control periods. The ribcage‐abdomen time delay in children with respiratory disease (?0.42 ± 0.707 sec) significantly differed from healthy children (0.22 ± 0.426 sec, P = 0.0125). This novel system reliably acquired time‐aligned nasal airflow and thoracoabdominal motion estimates without relying on attached sensor performance and detected asynchronous breathing in pediatric patients. Pediatr Pulmonol. 2012; 47:476–486. © 2011 Wiley Periodicals, Inc.     

Influence of naloxone on fetal breathing and the respiratory response to hypercapnia

The effect of naloxone on fetal breathing and the respiratory sensitivity to CO2 was tested on chronically prepared fetal lambs on days one and four post-surgery. After a control period the fetus was challenged with hypercapnia for 10 min and after another control period 9 mg naloxone was administered to the fetus followed by another CO2 test 15 min later. An index of fetal breathing (Veq), tidal volume (VT) and frequency of breathing (f) was determined from tracheal pressure deflections and from the integrated diaphragmatic EMG, expressed as power of diaphragmatic activity per min. Naloxone consistently caused fetal arousal but the duration was variable. The respiratory response to naloxone was also variable and not statistically different from control. The respiratory sensitivity to CO2 (% delta Veq/Torr delta PaCO2 or % delta Diaph. Power/min/Torr delta PaCO2) was not changed by naloxone on either day. We conclude that endorphins do not have a significant direct role in the fetal respiratory response to CO2 but may be involved in the control of state.     

Sleep abnormalities associated with neuromuscular disease: pathophysiology and evaluation

The development of respiratory failure is common in patients with neuromuscular disorders that involve the respiratory muscles. However, the high incidence of sleep-related breathing problems in this population is less well known. In patients with neuromuscular disease, nocturnal breathing abnormalities frequently precede respiratory failure during wakefulness by months or even years. These nocturnal breathing problems are caused by multiple factors, including diaphragm and upper airway muscle weakness, scoliosis, obesity, and central respiratory control problems. Advances in the understanding of the links between sleep-disordered breathing and the development of daytime dysfunction and respiratory failure has revolutionized the management of these individuals. Mask positive pressure therapy is now available to improve both quality of life and longevity for these individuals. The lack of correlation between daytime testing and the severity of nocturnal breathing abnormalities makes it difficult to predict the presence of sleep-disordered breathing. Further, patients may not always be aware of symptoms associated with sleep-disordered breathing, even if specifically questioned. However, simple bedside measurements of vital capacity and inspiratory muscle strength can provide useful guides for when nocturnal respiratory monitoring is indicated.     

Effects of sodium cyanide and nicotine on upper airway resistance in anesthetized dogs

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.