Respiratory System Conductance Research Articles

Assessment of Airway Distensibility by the Forced Oscillation Technique: Reproducible and Potentially Simplifiable.

A non-invasive index of airway distensibility is required to track airway remodeling over time. The forced oscillation technique (FOT) provides such an index by measuring the change in respiratory system conductance at 5 Hz over the corresponding change in lung volume (ΔGrs5/ΔVL). To become useful clinically, this method has to be reproducible and easy to perform. The series of breathing maneuvers required to measure distensibility would be greatly facilitated if the difficulty of breathing below functional residual capacity (FRC) could be precluded and the number of maneuvers could be reduced. The distensibility at lung volumes below FRC is also reduced by several confounders, suggesting that excluding data points below FRC should provide a better surrogate for airway remodeling. The objectives of this study were to investigate the reproducibility of airway distensibility measured by FOT and to assess whether the method could be simplified to increase feasibility. Distensibility was measured at three separate occasions in 13 healthy volunteers. At each visit, three deflationary maneuvers were performed, each consisting of tidal breathing from total lung capacity (TLC) to residual volume by slowly decreasing the end-expiratory volume on each subsequent breath. Distensibility was calculated by using either all data points from TLC to residual volume (RV) or only data points from TLC to FRC for either all three or only the first two deflationary maneuvers. Intra-class correlation coefficients (ICC) were used to assess reproducibility and Bland-Altman analyses were used to assess the level of agreement between the differently calculated values of distensibility. The results indicate that distensibility calculated using all data points is reproducible (ICC = 0.64). Using data points from TLC to FRC slightly improved reproducibility (ICC = 0.68) and increased distensibility by 19.4%, which was expected as distensibility above FRC should not be affected by confounders. Using only data points within the first two maneuvers did not affect reproducibility when tested between TLC and FRC (ICC = 0.66). We conclude that a valuable measure of airway distensibility could potentially be obtained with only two deflationary maneuvers that do not require breathing below FRC. This simplified method would increase feasibility without compromising reproducibility.

Airway distensibility with lung inflation after allogeneic haematopoietic stem-cell transplantation

The ability to reverse induced-bronchoconstriction by deep-inhalation increases after allogeneic haematopoietic stem-cell transplantation (HSCT), despite a decreased total lung capacity (TLC). We hypothesized that this effect may be due to an increased airway distensibility with lung inflation, likely related to an increment in lung stiffness. We studied 28 subjects, 2 weeks before and 2 months after HSCT. Within-breath respiratory system conductance (Grs) at 5, 11 and 19Hz was measured by forced oscillation technique (FOT) at functional residual capacity (FRC) and TLC. Changes in conductance at 5Hz (Grs5) were related to changes in lung volume (ΔGrs5/ΔVL) to estimate airway distensibility. Grs at FRC showed a slight but significant increase at all forcing frequencies by approximately 12–16%. TLC decreased after HSCT whereas the ΔGrs5/ΔVL ratio became higher after than before HSCT and was positively correlated (R2=0.87) with lung tissue density determined by quantitative CT scanning.We conclude that airway caliber and distensibility with lung inflation are increased after HSCT. This effect seems to be related to an increase in lung stiffness and must be taken into account when interpreting lung function changes after HSCT.

Effect of airway smooth muscle tone on airway distensibility measured by the forced oscillation technique in adults with asthma

Airway distensibility appears to be unaffected by airway smooth muscle (ASM) tone, despite the influence of ASM tone on the airway diameter-pressure relationship. This discrepancy may be because the greatest effect of ASM tone on airway diameter-pressure behavior occurs at low transpulmonary pressures, i.e., low lung volumes, which has not been investigated. Our study aimed to determine the contribution of ASM tone to airway distensibility, as assessed via the forced oscillation technique (FOT), across all lung volumes with a specific focus on low lung volumes. We also investigated the accompanying influence of ASM tone on peripheral airway closure and heterogeneity inferred from the reactance versus lung volume relationship. Respiratory system conductance and reactance were measured using FOT across the entire lung volume range in 22 asthma subjects and 19 healthy controls before and after bronchodilator. Airway distensibility (slope of conductance vs. lung volume) was calculated at residual volume (RV), functional residual capacity (FRC), and total lung capacity. At baseline, airway distensibility was significantly lower in subjects with asthma at all lung volumes. After bronchodilator, distensibility significantly increased at RV (64.8%, P < 0.001) and at FRC (61.8%, P < 0.01) in subjects with asthma but not in control subjects. The increased distensibility at RV and FRC in asthma were not associated with the accompanying changes in the reactance versus lung volume relationship. Our findings demonstrate that, at low lung volumes, ASM tone reduces airway distensibility in adults with asthma, independent of changes in airway closure and heterogeneity.

Improved respiratory system conductance following bronchodilator predicts reduced exertional dyspnoea

In COPD, improvements in lung mechanics following bronchodilator, measured using the forced oscillation technique (FOT), are more sensitive than spirometry at detecting improvement in lung function following bronchodilator. The relationship between these improvements in lung mechanics and improvements in functional outcomes, such as exertional dyspnoea, following bronchodilator, in COPD is unknown. 17 COPD subjects were recruited into a double blind placebo controlled randomised cross over study. Dyspnoea was induced using a standardised six-minute walk test (6 MWT), and measured by borg score throughout the test. Measurement of respiratory system conductance (Grs), respiratory system reactance (Xrs), inspiratory capacity (IC) and spirometry were made at baseline and 1 h after a single dose of either 18 μg of tiotropium bromide plus 200 μg salbutamol, or placebo. Subjects had a mean baseline FEV(1) of 45.5 ± 11.0% predicted. The bronchodilator induced reduction in exertional dyspnoea correlated significantly with the increase in Grs (r(s) = 0.59, p = 0.01) and approached significance with FEV(1) (r(s) = 0.45, p = 0.07) but not with FVC (r(s) = 0.30, p = 0.24), Xrs (r(s) = 0.19, p = 0.47) or IC (r(s) = -0.08, p = 0.78). Increase in Grs was the best and sole predictor of reduction in exertional dyspnoea, explaining 41% of the variance. There was no additional contribution to the model from the increase in FEV(1) or IC. Bronchodilator induced improvements in exertional dyspnoea in moderate to severe COPD are predicted by improvements in Grs, measured by FOT, independent of improvements in spirometry or hyperinflation. The findings suggest that FOT may be useful for measuring response to bronchodilator in COPD.

Cut-points for response to mannitol challenges using the forced oscillation technique

The forced oscillation technique (FOT) can be used to determine airway hyperresponsiveness, but the cut-points for changes in respiratory system conductance (Grs) and reactance (Xrs) that define a positive mannitol challenge are not known. Furthermore, the effects of changes in lung volume on these cut-points or on the repeatability of the test are unknown. In 15 non-asthmatic and 52 asthmatic subjects, response to mannitol challenge was measured by Grs and Xrs, using FOT, and by FEV(1). The FOT variables were adjusted for inspiratory capacity (IC) at each dose. Dose response slope (DRS) was used in receiver operator characteristic (ROC) analysis to compare the ability of adjusted and unadjusted DRSGrs and DRSXrs to detect a positive challenge, defined as PD(15)FEV(1) ≤635 mg mannitol. Mannitol challenges were positive in 32 asthmatic and 2 non-asthmatic subjects. Both DRSGrs and DRSXrs detected positive challenges (p < 0.0001 for both), and this was not altered by adjustment for IC for either DRSGrs (p = 0.21) or DRSXrs (p = 0.90). FOT cut-points for a positive challenge were 27% fall in Grs or 0.93 cm H(2)O/L/s decrease in Xrs at 635 mg. Repeatability of DRSGrs (±2.01 doubling doses) and DRSXrs (±1.95dd) was comparable with DRSFEV(1) (±1.67dd) and was not improved by adjustment for IC. Grs and Xrs, measured by FOT, provide a sensitive, repeatable measure of response to mannitol challenge. Adjusting for lung volume does not alter the ability of these variables to detect a positive response or the repeatability of the measurement.

Differences in the time course of proximal and distal airway response to inhaled histamine studied by synchrotron radiation CT

We studied the kinetics of proximal and distal bronchial response to histamine aerosol in healthy anesthetized and mechanically ventilated rabbits up to 60 min after histamine administration using a novel xenon-enhanced synchrotron radiation computed tomography imaging technique. Individual proximal airway constriction was assessed by measuring the luminal cross-sectional area. Distal airway obstruction was estimated by measuring the ventilated alveolar area after inhaled xenon administration. Respiratory system conductance was assessed continuously. Proximal airway cross-sectional area decreased by 57% of the baseline value by 20 min and recovered gradually but incompletely within 60 min. The ventilated alveolar area decreased immediately after histamine inhalation by 55% of baseline value and recovered rapidly thereafter. The results indicate that the airway reaction to inhaled histamine and the subsequent recovery are significantly slower in proximal than in distal bronchi in healthy rabbit. The findings suggest that physiological reaction mechanisms to inhaled histamine in the airway walls of large and small bronchi are not similar.

Changes in respiratory mechanics with increasing degrees of airway obstruction in COPD: Detection by forced oscillation technique

The Forced Oscillation Technique (FOT) is a method for non-invasively assessing respiratory mechanics during spontaneous breathing, demanding little cooperation. The aim of this study was to test the ability of FOT to describe the changes in respiratory mechanics in progressive COPD. The study was performed in a control group formed by 21 healthy subjects and 79 outpatients with COPD, which were classified by spirometry, according to the degree of airway obstruction, in mild, moderate and severe groups. Resistive impedance data were submitted to linear regression analysis over the 4-16 Hz frequency range, which yielded the total respiratory system resistance extrapolated at 0 Hz (R0), the respiratory system conductance (Grs), mean respiratory resistance (Rm), and the resistance/frequency slope (S). Reactance data were interpreted using the mean values (Xm) over the 4-32 Hz frequency range, the dynamic compliance (Crs,dyn), the dynamic elastance (E(rs,dyn)), and the resonant frequency (fr) data. Considering the control and mild groups, the increase of airway obstruction resulted in a significant increase of R0 (P<0.008), Rm (P<0.001), and a significant reduction in Grs (P<0.002). Reactive parameters, Crs, dyn and Ers,dyn also presented significant modifications. The subsequent increase (mild to moderate) showed a significant raise of R(0) (P<0.007), S (P<0.001), and a reduction in Grs (P<0.015), while significant increases in Xrs (P<0.001), and Ers,dyn (P<0.02), and also a reduction in Crs, dyn (P<0.02) were also observed. In contrast to earlier stages, in the late stage of the airway obstruction increase (moderate to severe obstruction), resistive parameters did not present statistically significant modifications, while significant modifications were observed in Xrs (P<0.02), Crs, dyn (P<0.003) and Ers,dyn (P<0.003). The results of this study demonstrated that the FOT is useful for detecting the respiratory mechanics modifications in COPD patients. The initial phases of airway obstruction in COPD can be described mainly by resistive parameters, while in more advanced phases, reactive parameters seem to be more useful. Since the FOT has the advantage of being a simple method, such a technique may give a significant clinical contribution, representing an alternative and/or complement to the evaluation of respiratory mechanics by means of forced expiration.

BCG modulation of anaphylactic antibody response, airway inflammation and lung hyperreactivity in genetically selected mouse strains (Selection IV-A)

The effect of Bacillus Calmette–Guérin (BCG) treatment in allergic pulmonary reaction was studied in mice genetically selected accordingly to a High (H-IVA) or Low (L-IVA) antibody responsiveness. Mice were immunized with ovalbumin (OVA) or OVA plus BCG. Two days after nasal antigenic challenge, seric IgE and IgG1 anti-OVA, eosinophils in pulmonary tissue, inflammatory cells in bronchoalveolar lavage and the compliance and conductance of respiratory system were evaluated. H-IVA mice were found more susceptible than L-IVA, and BCG was able to inhibit simultaneously the production of IgE, the bronchopulmonary inflammation and bronchial hyperresponsiveness in these genetically selected mice.

Effects of methacholine on small airway function measured by forced oscillation technique and multiple breath nitrogen washout in normal subjects

The multiple breath nitrogen washout (MBNW) can be analysed to produce the parameters Scond and Sacin as measures of ventilation heterogeneity in conductive and acinar airways, respectively. The derivation of these parameters is based on a model of pulmonary ventilation and results of similar modelling suggest that respiratory system conductance (Grs) measured by forced oscillation technique (FOT) is also sensitive to heterogeneity and to airway closure. Therefore, Scond, the volume of gas trapping at FRC (VtrappedFRC) and Grs may be inter-related parameters. These relationships were examined in 12 normals under baseline and bronchoconstricted states. Specific Grs was measured at 5Hz (sGrs5=Grs5/FRC) and Scond, Sacin and VtrappedFRC by MBNW, before and after methacholine challenge. Scond was independently predicted by VtrappedFRC and FRC in a multivariate model (R2=0.68, p=0.002). Post methacholine challenge, Scond related only to VtrappedFRC (R2=0.79, p<0.0001). The absolute change in Scond induced by methacholine challenge were predicted by the changes in VtrappedFRC and sGrs5 in a multivariate model (R2=0.82, p=0.0002). Sacin was unrelated to VtrappedFRC and sGrs5 before and after methacholine challenge. In conclusion, Scond and sGrs5 are measurements that are sensitive to changes occurring to the function of peripheral conducting airways, in particular heterogeneity and airway closure, while Sacin and presumably heterogeneity in terminal airways, are independent of these. Scond is also related to lung size. We review the current state of knowledge of FOT and MBNW in obstructive lung diseases and discuss future research directions.

A comparison of two methods for measuring airway distensibility: nitrogen washout and the forced oscillation technique

The measurement of airway stiffness is an important tool for studying airway remodelling in asthma. The relationship between airway calibre and lung volume (airway distensibility) was measured by forced oscillation technique (FOT) and compared with that measured by single-breath nitrogen washout (SBNW). In four non-asthmatic healthy subjects and three asthmatics, anatomical dead space (VDF) was measured by SBNW and respiratory system conductance (Grs) was measured by FOT at 6 Hz. During SBNW testing, 0.5 l oxygen boluses were inhaled from three different lung volumes: functional residual capacity (FRC), 1 l above FRC and near total lung capacity (TLC). Following inhalation of the oxygen bolus subjects exhaled to residual volume and then inhaled to TLC. During FOT, subjects breathed 0.5–1.0 l tidal volumes but with gradually increasing end-expiratory lung volume until close to TLC, then returned to normal breathing before inhaling to TLC. This was also repeated but with reducing lung volume from TLC. Absolute lung volumes were measured by body plethysmography and related to volumes during FOT and SBNW by reference to TLC obtained at the end of each SBNW or FOT test manoeuvre. Distensibility was calculated as the linear regression slopes of VDF or Grs versus lung volume. Distensibility measured by VDF ranged 16–37 ml l−1 lung volume and by Grs it ranged 0.06–0.19 l s−1 cmH2O−1 l−1 lung volume. Both distensibility measurements were correlated (Pearson's R2 = 0.91, p = 0.001). The SBNW and FOT are comparable methods for measuring airway distensibility and may have similar clinical usefulness. However, further studies are required to make any specific inferences about the relationship between airway distensibility by FOT and airway remodelling.

Effects of smoking in pregnancy on neonatal lung function

AIMSTo assess the effects of smoking during pregnancy on lung mechanics and lung volumes in the immediate neonatal period, before infants are exposed to passive smoking.METHODSLung function tests were carried...

Effects of airway parasympathetic tone on responses to intravenous bronchoconstrictor agonists in rats

To test the hypothesis that parasympathetic airway tone may affect airway responsiveness, we measured bronchoconstrictor responses to intravenous bethanechol (BCh) in anesthetized vagotomized rats with and without background vagal nerve stimulation and developed a predictive model based on pharmacological additivity between endogenous and intravenous agonists. A high degree of agreement (r2 = 0.93) between the measured and predicted responses indicated that intravenous BCh and parasympathetic tone had bronchoconstrictor effects that were pharmacologically additive. An expansion of the additive model was used to determine that the percentage of decrease in respiratory system conductance (Grs) would be a measure of airway response independent of background parasympathetic tone. As predicted, the percentage of decrease in Grs after intravenous BCh was minimally affected by background vagal stimulation. However, the percentage of decrease in Grs was augmented by vagal stimulation for intravenous 5-hydroxytryptamine hydrochloride, a known parasympathetic neuromodulator, and for methacholine, an agonist with nicotinic as well as muscarinic activity (P < 0.02 for each agonist). We conclude that airway parasympathetic tone can be a source of variability for airway responsiveness when substances having neuromodulatory activity are involved in the provocative challenge.

Quantification of nasal involvement in a guinea pig plethysmograph.

We have developed a technique for measuring lung function in conscious guinea pigs using a whole body plethysmograph. Because guinea pigs breathe through the nose, a technique was also developed to measure nasal and lower respiratory system conductance simultaneously in anesthetized animals. The upper and the lower airways could be challenged separately and studied in a manner similar to the conditions in the plethysmograph. Aerosols of histamine, carbachol, or ovalbumin delivered to the nose in sensitized animals had no effect on nasal conductance, even in doses 100 times higher than that required to reduce lower respiratory system conductance. However, intravenous histamine increased nasal conductance. Thus, although nasal resistance constitutes the majority of the total respiratory system resistance measured in the plethysmograph, nasal resistance is unaffected by the aerosol drugs studied. We therefore consider changes in resistance measured in the plethysmograph to originate at or below the larynx. The plethysmographic technique described here is a reliable, reproducible, and rapid technique that enables repeated measurement in animals and minimizes animal trauma.

Effects of neuraminidase on airway reactivity in the guinea pig.

We investigated the effects of neuraminidase, a viral enzyme that cleaves alpha ketosidic cell-bound sialic acids, to see if it accounts for parainfluenza and influenza virus-induced airway hyperreactivity. Accordingly, Vibrio cholerae neuraminidase was administered intratracheally in guinea pigs, and airway reactivity was assessed 3 h later. Removal of sialic acid residues was evaluated by histologic studies. Airway responsiveness was determined in anesthetized, tracheotomized, and mechanically ventilated guinea pigs by exposing them to increasing concentrations of aerosolized bronchoconstrictor agents. Respiratory system conductance was measured by the occlusion method. Neuraminidase injected intratracheally did not change airway reactivity to 10(-4) to 10(-2) M acetylcholine or 10(-4) to 2.5 x 10(-3) M histamine; nor did it prevent aerosolized albuterol from inhibiting histamine-induced bronchoconstriction. Substance P (10(-6) to 5 x 10(-5) M) had no significant bronchoconstrictor effect on guinea pigs pretreated with saline or neuraminidase. In guinea pigs pretreated with aerosols of the neutral endopeptidase inhibitor phosphoramidon (10(-4) M) before the concentration curve to aerosolized substance P was recorded, neuraminidase significantly reduced substance P-induced bronchoconstriction. When bronchoconstriction was induced by the 4-11 fragment of substance P (10(-5) to 10(-2) M), which is devoid of positive charges, it did not differ significantly in guinea pigs pretreated with saline and those pretreated with neuraminidase. These results indicate that in the guinea pig, neuraminidase injected intratracheally does not induce non-specific airway hyperreactivity and may alter the binding of substance P to its receptors.

Birthweight, early passive respiratory system mechanics, and ventilator requirements as predictors of outcome in premature infants with respiratory failure

Early respiratory mechanics have been reported to predict outcome in newborns with respiratory failure. However, it remains unknown whether measurements of pulmonary function add significantly to the predictive value of more readily available variables The present study was designed to answer this question. Passive respiratory system mechanics were measured by an airway occlusion technique in 104 ventilator-dependent premature infants between 6 and 48 hours of life and corrected for infant size. A ventilation index [FiO2 x mean airway pressure (MAP)] was calculated at the time of pulmonary function testing. Poor outcome was defined as death from respiratory failure or need for supplemental oxygen at 28 days. Stepwise logistic function regression examined whether ventilation index and respiratory mechanics added predictive power over and above birthweight. Five infants died, and 45 patients required supplemental oxygen at 28 days. Birthweight was a strong predictor and would have entered the logistic model first in any case. Ventilation index added significantly to the predictive model (P = 0.038). Respiratory system conductance (P = 0.15) and compliance (P = 0.93) entered on the third and last step, respectively. We conclude that in premature infants with respiratory failure, birthweight is a strong predictor of outcome. Early ventilator requirements but not respiratory system mechanics, add significantly to this predictive model.

Expiratory volume clamping: a new method to assess respiratory mechanics in sedated infants.

During breathing under sedation via a two-way valve, airflow (V), volume (delta V), and airway pressure (P) were recorded in eight normal (N) infants, seven with reversible obstructive airway disease (ROAD), and seven with chronic lung disease (CLD). Intermittently, expiratory volume clamping (EVC) was applied, involving selective occlusion of the expiratory valve for three to five breaths. The latter produced cumulative increases in delta V that, due to progressive recruitment of the Hering-Breuer reflex, were accompanied by increasing expiratory plateaus in P (i.e., apneas). The resultant passive inflation delta V-P relationships were closely approximated by the expression: delta V = aP2 + bP + c, wherein a represented the pressure-related changes in chord compliance (Crs), b the Crs at P = 0, and c the difference between the dynamic end-expiratory and relaxation volumes of the respiratory system. Relative to N, the ROAD and CLD infants had significantly reduced weight-specific values of a/kg, their b/kg values were increased, whereas the c/kg measurements did not significantly vary. Moreover, for each subject we determined the net Crs/kg obtaining at P = 20 cmH2O (i.e., Crs20/kg), an estimate of the net deflation compliance; the passive respiratory time constant (tau rs) based on the slope of the expired delta V/V relationship; and the respiratory system conductance (Grs/kg). Relative to N, the mean Crs20/kg was significantly reduced only in the infants with CLD and, due to increases in tau rs, both patient groups depicted significantly diminished values of Grs/kg, suggesting the presence of airways obstruction.(ABSTRACT TRUNCATED AT 250 WORDS)

Failure of hypoxic pulmonary vasoconstriction in the canine asthma model. Effect of prostaglandin inhibitors.

Measurements of respiratory mechanics, arterial blood gases, and pulmonary vascular resistance were made before and 15 min after inhalation challenge with Ascaris suum extract in dogs with natural sensitivity to this antigen. 25 of 47 dogs were treated before inhalation challenge with a prostaglandin inhibitor (90 mg/kg of aspirin or 2 mg/kg of indomethacin by intravenous infusion). In response to the challenge, bronchospasm developed in approximately half (responders) of each group reflected by decreases in mean specific respiratory system conductance and arterial oxygen tension. While the dogs were breathing room air, pulmonary vascular resistance remained unchanged after antigen challenge in the responders not given aspirin or indomethacin, but increased significantly and was associated with a lesser degree of arterial hypoxemia in the responders pretreated with either of the prostaglandin inhibitors. Prevention of arterial hypoxemia by oxygen breathing blocked an increase in pulmonary vascular resistance in four pretreated responders. No changes in respiratory mechanics, pulmonary hemodynamics, or arterial blood gases were noted in the 21 dogs who did not develop bronchospasm regardless of whether or not they were pretreated. 12 additional dogs in whom arterial hypoxemia was produced by 10% oxygen breathing, showed an increase in pulmonary vascular resistance that was not potentiated by pretreatment with aspirin in 6. We conclude that in acute experimental canine asthma, vasodilator prostaglandins appear to blunt the hypoxic pulmonary vasoconstrictor response, thereby further compromising gas exchange but preventing the development of pulmonary hypertension.

The lung following repair of congenital diaphragmatic hernia

To determine the effects of the pulmonary hypoplasia present at birth in infants with congenital diaphragmatic hernia upon subsequent development of the lung, 19 patients who had undergone surgical repair before the age of one year were studied at ages 6 to 18 years. Total lung capacity and vital capacity averaged 99% of predicted value. Diffusing capacity for carbon monoxide was normal. Forced expiratory volume in one second averaged 89% of predicted value and 80% of vital capacity. Total respiratory system conductance and maximum expiratory flow volume curves obtained during air and helium-oxygen breathing were normal. Xenon 133 radiospirometry performed in nine patients revealed equal distribution of lung volumes on the two sides. Ventilation to the hernia side was reduced in only two patients. Blood flow to the hernia side was reduced in all nine patients. Chest radiographs supported the physiologic observations. These findings are consistent with the persistence of a reduction in the number of branches or generations of pulmonary arteries and bronchi on the side of the hernia. Since a substantial part of the vascular resistance resides in peripheral vessels, this developmental abnormality influences the distribution of pulmonary blood flow, although it has little effect on tests reflecting airway resistance or the distribution of ventilation.

Study of the pulmonary circulation in a canine asthma model.

Measurements of respiratory mechanics, gas exchange, and pulmonary hemodynamics were made before and serially for 2 hours after inhalation challenge with Ascaris suum extract in dogs with natural sensitivity to this antigen. Nine of 14 dogs randomly exposed to an inspired oxygen fraction of 0.21 or 0.60 to 0.70, responded to the challenge with bronchospasm reflected by a transient decrease of mean specific respiratory system conductance to 50 per cent of baseline after 5 to 15 min. This was accompanied by a decrease in alveolar ventilation in all and acidosis in some animals. No changes were observed in transmural pulmonary arterial pressure, cardiac output, pulmonary vascular resistance, and pulmonary blood volume in all 9 dogs who responded with bronchospasm, whether or not arterial hypoxemia was allowed to develop. In contrast, a significant increase in pulmonary vascular resistance occurred in control dogs in whom comparable degrees of arterial hypoxemia were produced by 10 per cent oxygen breathing or mechanical bronchial obstruction by placing beads in lobar and segmental airways. No changes in any parameter measured occurred in the 5 dogs who did not develop bronchospasm after antigen challenge. The results indicated that moderately severe, antigen-induced bronchospasm in anesthetized dogs has no effect on the pulmonary circulation even when associated with arterial hypoxemia. Because nonuniformity of alveolar hypoxia allowing redistribution of blood flow is probably not responsible for this failure to develop increases in pulmonary vascular resistance in induced asthma, it is suggested that the elaboration of chemical mediators may have interfered with the hypoxic pulmonary vasoconstrictor response.

Tracheal mucous transport in experimental canine asthma.

Tracheal mucous velocity (TMV) was measured in experimental canine asthma. All 10 sensitive dogs exposed to an aerosol of Ascaris suum extract showed a decrease in TMV to about one-third of base-line values within 45 min whereas only half of them (reactors) responded with bronchospasm as measured by a significant reduction in specific respiratory system conductance (SGrs). Mean TMV remained decreased at the end of the 2-h observation period when mean SGrs had returned to base-line values in the reactors. Neither TMV nor SGrs changed in nonsensitive animals who inhaled ragweed antigen. Aerosols of acetylcholine and histamine increased TMV thereby excluding these mediators as responsible for the impairment of mucous transport in asthma. Nebulization of A. suum antigen together with a selective antagonist of slow reacting substance of anaphylaxis (srs-a) produced a marked increase of TMV in all dogs regardless of whether or not bronchospasm was elicited. This suggests that the observed decrease in TMV may be related to the release of SRS-A during the immunologic reaction.