O.35 ppm O3 exposure induces hyperresponsiveness on 24-h reexposure to 0.20 ppm O3

Pulmonary function hyperresponsiveness, defined as enhanced response on reexposure to O3, compared with initial O3 exposure, has been previously noted in consecutive day exposures to high ambient O3 concentrations (i.e., 0.32-0.42 ppm). Effects of consecutive-day exposure to lower O3 concentrations (0.20-0.25 ppm) have yielded equivocal results. To examine the occurrence of hyperresponsiveness at two levels of O3 exposure, 15 aerobically trained males completed seven 1-h exposures of continuous exercise at work rates eliciting a mean minute ventilation of 60 1/min. Three sets of consecutive-day exposures, involving day 1/day 2 exposures to 0.20/0.20 ppm O3, 0.35/0.20 ppm O3, and 0.35/0.35 ppm O3, were randomly delivered via an obligatory mouthpiece inhalation system. A filtered-air exposure was randomly placed 24 h before one of the three sets. Treatment effects were assessed by standard pulmonary function tests, exercise ventilatory pattern (i.e., respiratory frequency, f; and tidal volume, VT) changes and subjective symptom (SS) response. Initial O3 exposures to 0.35 and 0.20 ppm had a statistically significant effect, compared with filtered air, on all measurements. On reexposure to 0.35 ppm O3 24 h after an initial 0.35 ppm O3 exposure, significant hyperresponsiveness was demonstrated for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1), f, VT, and total SS score. Exposure to 0.20 ppm O3 24 h after 0.35 ppm O3 exposure, however, resulted in significantly enhanced responses (compared with initial 0.20 ppm O3 exposure) only for FEV1, f, and VT.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ozone inhalation effects consequent to continuous exercise in females: comparison to males

Exposure to ozone (O3) at ambient photochemical smog alert levels has been shown to cause alteration in pulmonary function and exercise response in humans, but there is a paucity of data on females. The initial purpose of the present investigation was to study the effects of O3 inhalation on pulmonary function and selected exercise respiratory metabolism and breathing pattern responses in young adult females. Six female subjects exercised continuously on a bicycle ergometer for 1 h on 10 occasions at one of three intensities, while exposed to 0.0, 0.20, 0.30, or 0.40 ppm O3. Forced expiratory volume and flow rates and residual volume (RV) were measured before and immediately following each protocol. During exercise, expired minute ventilation (VE), respiratory frequency (fR), tidal volume, O2 uptake (VO2), and heart rate (HR) were measured every 10 min. O3 dose-dependent decrements were observed for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), and forced expiratory flow rate during the middle half of FVC, coupled with an increase in RV and altered exercise ventilatory pattern. There was also an increased VE but no significant O3 effect on VO2 or HR. Comparison of the females' responses to those of a group of young adult males (previously studied) at the same total O3 effective dose (i.e., expressed as the simple product of O3 concentration, VE, and exposure time) revealed significantly greater effects on FVC, FEV1.0, and fR for the females. With VE reduced for females as a function of exercise intensity at the same percent of maximum VO2, these differences were considerably attenuated, although not negated.(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of ozone on peripheral lung reactivity

In previous studies, we demonstrated that local exposures to the lung periphery to 0.1 ppm ozone (O3) produce increases in resistance to flow through the collateral system (Rcs) which are prevented by vagotomy, and the local exposures to 1.0 ppm O3 produces increases in Rcs which are only partially mediated by the parasympathetic system. In the present studies, we evaluated the effects of short exposures to O3 on reactions to H2O and histamine in anesthetized male dogs when no residual effects of the O3 exposures could be detected. For this purpose a fiber-optic bronchoscope was wedged in a segmental airway of anesthetized dogs and was used to deliver O3, aerosols of H2O, histamine (1.5 X 10(-4) mg), and atropine (0.1 mg). Measurements of Rcs were used to monitor responses to these agents. Responses to three successive challenges with H2O and with histamine were not different from each other. A 30-min exposure to 0.1 ppm O3 between the first and second challenge did not alter responses to histamine or H2O. However, a 10-min exposure to 1.0 ppm O3 resulted in a significant increase in responses to both H2O and histamine. No correlation was noted between the magnitude of response to O3 and the increase in response to histamine or H2O following O3 exposure. Parasympathetic blockade (atropine or bilateral cervical vagotomy) abolished the increase in response to H2O but not the increase in response to histamine following exposure to 1.0 ppm O3.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ozone inhalation effects in females varying widely in lung size: comparison with males

It has been suggested that lung size accounts for observed gender differences in responsiveness to the same total inhaled dose of O3. To test the hypothesis that lung size is a determinant of magnitude of response within a gender, two groups of 14 healthy young adult females differing significantly in forced vital capacity [FVC; i.e., small-lung group mean = 3.74 liters (range 3.2-4.0) and large-lung group mean = 5.11 liters (range 4.5-6.2] were exposed for 1 h to filtered air (FA) and to 0.18 and 0.30 ppm O3. On each occasion, subjects exercised continuously on a cycle ergometer at a work rate that elicited a mean minute ventilation of approximately 47 l/min. For the small-lung group [mean total lung capacity (TLC) = 4.52 liters] exercise O2 uptake was 67% of maximal O2 uptake (VO2max), and that for the large-lung group (TLC 6.37 liters) was 61% of VO2max. Statistical analysis revealed significant decrements for both groups in FVC, forced expiratory volume in 1 s (FEV1.0), and forced expiratory flow rate in the middle half of FVC on exposure to 0.18 and 0.30 ppm O3. Exercise respiratory frequency increased, and tidal volume decreased significantly in both groups in response to 0.18 and 0.30 ppm O3 exposure. On exposure to 0.30 ppm O3, the number of individual subjective symptoms reported and their severity were significantly greater for both groups than those reported for the FA and 0.18 ppm O3 exposures. Both groups evidenced similar percent changes in pulmonary function and exercise ventilation response, and in subjective symptom response.(ABSTRACT TRUNCATED AT 250 WORDS)     

Pulmonary response to threshold levels of sulfur dioxide (1.0 ppm) and ozone (0.3 ppm)

We exposed 22 healthy adult nonsmoking male subjects for 2 h to filtered air, 1.0 ppm sulfur dioxide (SO2), 0.3 ppm ozone (O3), or the combination of 1.0 ppm SO2 + 0.3 ppm O3. We hypothesized that exposure to near-threshold concentrations of these pollutants would allow us to observe any interaction between the two pollutants that might have been masked by the more obvious response to the higher concentrations of O3 used in previous studies. Each subject alternated 30-min treadmill exercise with 10-min rest periods for the 2 h. The average exercise ventilation measured during the last 5 min of exercise was 38 1/min (BTPS). Forced expiratory maneuvers were performed before exposure and 5 min after each of the three exercise periods. Maximum voluntary ventilation, He dilution functional residual capacity, thoracic gas volume, and airway resistance were measured before and after the exposure. After O3 exposure alone, forced expiratory measurements (FVC, FEV1.0, and FEF25-75%) were significantly decreased. The combined exposure to SO2 + O3 produced similar but smaller decreases in these measures. There were small but significant differences between the O3 and the O3 + SO2 exposure for FVC, FEV1.0, FEV2.0, FEV3.0, and FEF25-75% at the end of the 2-h exposure. We conclude that, with these pollutant concentrations, there is no additive or synergistic effect of the two pollutants on pulmonary function.     

Mechanism of action of ozone on the human lung

Fourteen healthy normal volunteers were randomly exposed to air and 0.5 ppm of ozone (O3) in a controlled exposure chamber for a 2-h period during which 15 min of treadmill exercise sufficient to produce a ventilation of approximately 40 l/min was alternated with 15-min rest periods. Before testing an esophageal balloon was inserted, and lung volumes, flow rates, maximal inspiratory (at residual volume and functional residual capacity) and expiratory (at total lung capacity and functional residual capacity) mouth pressures, and pulmonary mechanics (static and dynamic compliance and airway resistance) were measured before and immediately after the exposure period. After the postexposure measurements had been completed, the subjects inhaled an aerosol of 20% lidocaine until response to citric acid aerosol inhalation was abolished. All of the measurements were immediately repeated. We found that the O3 exposure 1) induced a significant mean decrement of 17.8% in vital capacity (this change was the result of a marked fall in inspiratory capacity without significant increase in residual volume), 2) significantly increased mean airway resistance and specific airway resistance but did not change dynamic or static pulmonary compliance or viscous or elastic work, 3) significantly reduced maximal transpulmonary pressure (by 19%) but produced no changes in inspiratory or expiratory maximal mouth pressures, and 4) significantly increased respiratory rate (in 5 subjects by more than 6 breaths/min) and decreased tidal volume.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ventilatory behavior after hypoxia in C57BL/6J and A/J mice.

Given the environmental forcing by extremes in hypoxia-reoxygenation, there might be no genetic effect on posthypoxic short-term potentiation of ventilation. Minute ventilation (VE), respiratory frequency (f), tidal volume (VT), and the airway resistance during chemical loading were assessed in unanesthetized unrestrained C57BL/6J (B6) and A/J mice using whole body plethysmography. Static pressure-volume curves were also performed. In 12 males for each strain, after 5 min of 8% O2 exposure, B6 mice had a prominent decrease in VE on reoxygenation with either air (-11%) or 100% O2 (-20%), due to the decline of f. In contrast, A/J animals had no ventilatory undershoot or f decline. After 5 min of 3% CO2-10% O2 exposure, B6 exhibited significant decrease in VE (-28.4 vs. -38.7%, air vs. 100% O2) and f (-13.8 vs. -22.3%, air vs. 100% O2) during reoxygenation with both air and 100% O2; however, A/J mice showed significant increase in VE (+116%) and f (+62.2%) during air reoxygenation and significant increase in VE (+68.2%) during 100% O2 reoxygenation. There were no strain differences in dynamic airway resistance during gas challenges or in steady-state total respiratory compliance measured postmortem. Strain differences in ventilatory responses to reoxygenation indicate that genetic mechanisms strongly influence posthypoxic ventilatory behavior.     

Combined effects of ozone exposure and ambient heat on exercising females

Ten aerobically trained young adult females exercised continuously at 66% of maximum O2 uptake for 1 h while exposed orally to filtered air and 0.15 and 0.30 parts per million (ppm) ozone (O3) in both moderate (24 degrees C) and hot (35 degrees C) ambient conditions. Exposure to 0.30 ppm O3 induced significant impairment in forced vital capacity (FVC), forced expiratory volume in 1 s (FEV1.0), and other pulmonary function variables. Exercise respiratory frequency (fR) increased, whereas tidal volume and alveolar volume (VA) decreased with 0.30 ppm O3 exposure. Significant interactions of O3 and ambient heat were obtained for fR and VA, whereas FVC and FEV1.0 displayed a trend toward an O3-temperature interaction. Although expired ventilation increased, the interactions could not be ascribed to a greater O3 effective dose in the 35 degrees C exposures. However, subjective discomfort increased with both O3 and heat exposure such that three subjects ceased exercise prematurely when O3 and ambient heat were combined. We conclude that accentuation of subjective limitations and certain physiological alterations by ambient heat coinciding with photochemical oxidant episodes is likely to result in more severe impairment of exercise performance, although the mechanisms remain unclear.     

Ozone exposure decreases the effect of a deep inhalation on forced expiratory flow in normal subjects.

Sixteen healthy nonsmoking subjects (7 women), 21-49 yr old, were exposed in a climate chamber to either clean air or 300 parts/billion ozone on 4 days for 5 h each day. Before each exposure, the subjects had been pretreated with either oxidants (fish oil) or antioxidants (multivitamins). The study design was double-blind crossover with randomized allocation to the exposure regime. Full and partial flow-volume curves were recorded in the morning and before and during a histamine provocation at the end of the day. Nasal cavity volume and inflammatory markers in nasal lavage fluid were also measured. Compared with air, ozone exposure decreased peak expiratory flow, forced expiratory volume in 1 s, and forced vital capacity (FVC), with no significant effect from the pretreatment regimens. Ozone decreased the ratio of maximal to partial flow at 40% FVC by 0.08 +/- 0.03 (mean +/- SE, analysis of variance: P = 0.018) and at 30% FVC by 0.10 +/- 0.05 (P = 0.070). Ozone exposure did not significantly increase bronchial responsiveness, but, after treatment with fish oil, partial flows decreased more than after vitamins during the histamine test, without changing the maximal-to-partial flow ratio. The decreased effect of a deep inhalation after ozone exposure can be explained by changes in airway hysteresis relative to parenchymal hysteresis, due either to ozone-induced airway inflammation or to less deep inspiration after ozone, not significantly influenced by multivitamins or fish oil.     

Density dependence of forced expiratory flows in healthy infants and toddlers.

In older children and adults, density dependence (DD) of forced expiratory flow is present over the majority of the full flow-volume curve. In healthy subjects, DD occurs because the pressure drop from peripheral to central airways is primarily dependent on turbulence and convective acceleration rather than laminar resistance; however, an increase in peripheral resistance reduces DD. We measured DD of forced expiratory flow in 22 healthy infants to evaluate whether infants have low DD. Full forced expiratory maneuvers were obtained while the subjects breathed room air and then a mixture of 80% helium-20% oxygen. Flows at 50 and 75% of expired forced vital capacity (FVC) were measured, and the ratio of helium-oxygen to air flow was calculated (DD at 50 and 75% FVC). The mean (range) of DD at 50 and 75% FVC was 1.37 (1.22-1.54) and 1.23 (1.02-1.65), respectively, values similar to those reported in older children and adults. There were no significant relationships between DD and age. Our results suggest that infants, compared with older children and adults, have similar DD, a finding that suggests that infants do not have a greater ratio of peripheral-to-central airway resistance.     

Atropine pretreatment enhances airway hyperreactivity in antigen-challenged guinea pigs through an eosinophil-dependent mechanism

Airway hyperreactivity in antigen-challenged animals is mediated by eosinophil major basic protein (MBP) that blocks inhibitory M(2) muscarinic receptors on parasympathetic nerves, increasing acetylcholine release onto M(3) muscarinic receptors on airway smooth muscle. Acutely, anticholinergics block hyperreactivity in antigen-challenged animals and reverse asthma exacerbations in the human, but are less effective in chronic asthma. We tested whether atropine, given before antigen challenge, affected hyperreactivity, M(2) receptor function, eosinophil accumulation, and activation. Sensitized guinea pigs received atropine (1 mg/kg ip) 1 h before challenge and 6 h later. Twenty-four hours after challenge, animals were anesthetized, vagotomized, paralyzed, and ventilated. Airway reactivity to electrical stimulation of the vagi and to intravenous acetylcholine was not altered by atropine pretreatment in nonsensitized animals, indicating that atropine was no longer blocking postjunctional muscarinic receptors. Antigen challenge induced airway hyperreactivity to vagal stimulation that was significantly potentiated by atropine pretreatment. Bronchoconstriction induced by acetylcholine was not changed by antigen challenge or by atropine pretreatment. M(2) receptor function was lost in challenged animals but protected by atropine pretreatment. Eosinophils in bronchoalveolar lavage and within airway tissues were significantly increased by challenge but significantly reduced by atropine pretreatment. However, extracellular MBP in challenged airways was significantly increased by atropine pretreatment, which may account for reduced eosinophils. Depleting eosinophils with antibody to IL-5 before challenge prevented hyperreactivity and significantly reduced MBP in airways of atropine-pretreated animals. Thus atropine pretreatment potentiated airway hyperreactivity by increasing eosinophil activation and degranulation. These data suggest that anticholinergics enhance eosinophil interactions with airway nerves.     

Effects of NO2 alone and in combination with O3 on young men and women

Previous studies of 2 h of exposure to NO2 at high urban atmospheric levels (i.e., 0.50-1.0 ppm), utilizing light-to-moderate exercise for up to 1 h have failed to demonstrate significant pulmonary dysfunction in healthy humans. To test the hypothesis that heavy sustained exercise would elicit pulmonary dysfunction on exposure to 0.60 ppm NO2 and/or enhance the effects of exposure to 0.30 ppm O3, 40 aerobically trained young adults (20 males and 20 females) completed 1 h of continuous exercise at work rates eliciting a mean minute ventilation of 70 and 50 l/min for the males and females, respectively. Exposures to filtered air, 0.60 ppm NO2, 0.30 ppm O3, and 0.60 ppm NO2 plus 0.30 ppm O3 were randomly delivered via an obligatory mouthpiece inhalation system. Treatment effects were assessed by standard pulmonary function tests and exercise ventilatory and subjective symptoms response. Two-way analysis of variance with repeated measures and post hoc analyses revealed a statistically significant (P less than 0.05) effect of O3 on forced expiratory parameters, specific airway resistance, exercise ventilatory response, and reported subjective symptoms of respiratory discomfort. In contrast, no significant effect of NO2 was observed nor was there any significant interaction of NO2 and O3 in combination. There were no significant differences between male and female responses to gas mixture treatments. It was concluded that inhalation of 0.60 ppm NO2 for 1 h while engaged in heavy sustained exercise does not elicit effects evidenced by measurement techniques used in this study nor evoke additive effects beyond those induced by 0.30 ppm O3 in healthy young adults.     

Pulmonary function in men after oxygen breathing at 3.0 ATA for 3.5 h.

As a pulmonary component of Predictive Studies V, designed to determine O2 tolerance of multiple organs and systems in humans at 3.0-1.5 ATA, pulmonary function was evaluated at 1.0 ATA in 13 healthy men before and after O2 exposure at 3.0 ATA for 3.5 h. Measurements included flow-volume loops, spirometry, and airway resistance (Raw) (n = 12); CO diffusing capacity (n = 11); closing volumes (n = 6); and air vs. HeO2 forced vital capacity maneuvers (n = 5). Chest discomfort, cough, and dyspnea were experienced during exposure in mild degree by most subjects. Mean forced expiratory volume in 1 s (FEV1) and forced expiratory flow at 25-75% of vital capacity (FEF25-75) were significantly reduced postexposure by 5.9 and 11.8%, respectively, whereas forced vital capacity was not significantly changed. The average difference in maximum midexpiratory flow rates at 50% vital capacity on air and HeO2 was significantly reduced postexposure by 18%. Raw and CO diffusing capacity were not changed postexposure. The relatively large change in FEF25-75 compared with FEV1, the reduction in density dependence of flow, and the normal Raw postexposure are all consistent with flow limitation in peripheral airways as a major cause of the observed reduction in expiratory flow. Postexposure pulmonary function changes in one subject who convulsed at 3.0 h of exposure are compared with corresponding average changes in 12 subjects who did not convulse.     

Physiological characterization of variability in response to lung volume reduction surgery.

This paper examines potential physiological mechanisms responsible for improvement after lung volume reduction surgery (LVRS). In 25 patients (63 +/- 9 yr; 11 men, 14 women), spirometry [forced expiratory volume in 1 s (FEV(1)) and forced vital capacity (FVC)], lung volumes [residual volume (RV) and total lung capacity (TLC)], small airway resistance, recoil pressures, and respiratory muscle contractility (RMC) were measured before and 4-6 mo after LVRS. Data were interpreted to assess how changes in each component of lung mechanics affect overall function. Among responders (DeltaFEV(1) > or = 12%; 150 ml), improvement was primarily due to an increase in FVC, not to FEV(1)-to-FVC ratio. Among nonresponders, FEV(1), FVC, and RV/TLC did not change after surgery, although recoil pressure increased in both groups. Both groups experienced a reduction in RMC after LVRS. In conclusion, LVRS improves function in emphysema by resizing the lung relative to the chest wall by reducing RV. LVRS does not change airway resistance but decreases RMC, which attenuates the potential benefits of LVRS that are generated by reducing RV/TLC. Among nonresponders, recoil pressure increased out of proportion to reduced volume, such that no increase in vital capacity or improvement in FEV(1) occurred.     

Small airway morphology and lung function in the transition from normality to chronic airway obstruction.

This study investigated the relationships between pathological changes in small airways (<6 mm perimeter) and lung function in 22 nonasthmatic subjects (20 smokers) undergoing lung resection for peripheral lesions. Preoperative pulmonary function tests revealed airway obstruction [ratio of forced expiratory volume in 1 s to forced vital capacity (FEV1/FVC) < 70%] in 12 subjects and normal lung function in 10. When all subjects were considered together, total airway wall thickness was significantly correlated with FEV1/FVC (r2 = 0.25), reactivity to methacholine (r2 = 0.26), and slope of linear regression of FVC against FEV1 values recorded during the methacholine challenge (r2 = 0.56). Loss of peribronchiolar alveolar attachments was significantly associated (r2 = 0.25) with a bronchoconstrictor effect of deep inhalation, as assessed from a maximal-to-partial expiratory flow ratio <1, but not with airway responses to methacholine. No significant correlation was found between airway smooth muscle thickness and lung function measurements. In conclusion, this study suggests that thickening of the airway wall is a major mechanism for airway closure, whereas loss of airway-to-lung interdependence may contribute to the bronchoconstrictor effect of deep inhalation in the transition from normal lung function to airway obstruction in nonasthmatic smokers.     

Inspiratory-to-expiratory time ratio and alveolar ventilation during high-frequency ventilation in dogs

It has been suggested that the increase in inspiratory flow rate caused by a decrease in the inspiratory-to-expiratory time ratio (I:E) at a constant tidal volume (VT) could increase the efficiency of ventilation in high-frequency ventilation (HFV). To test this hypothesis, we studied the effect of changing I:E from 1:1 to 1:4 on steady-state alveolar ventilation (VA) at a given VT and frequency (f) and at a constant mean lung volume (VL). In nine anesthetized, paralyzed, supine dogs, HFV was performed at 3, 6, and 9 Hz with a ventilator that delivered constant inspiratory and expiratory flow rates. Mean airway pressure was adjusted so that VL was maintained at a level equivalent to that of resting FRC. At each f and one of the I:E chosen at random, VT was adjusted to obtain a eucapnic steady state [arterial pressure of CO2 (PaCO2) = 37 +/- 3 Torr]. After 10 min of each HFV, PaCO2, arterial pressure of O2 (PaO2), and CO2 production (VCO2) were measured, and I:E was changed before repeating the run with the same f and VT. VA was calculated from the ratio of VCO2 and PaCO2. We found that the change of I:E from 1:1 to 1:4 had no significant effects on PaCO2, PaO2, and VA at any of the frequencies studied. We conclude, therefore, that the mechanism or mechanisms responsible for gas transport during HFV must be insensitive to the changes in inspiratory and expiratory flow rates over the VT-f range covered in our experiments.     

Airway obstruction during periodic breathing in premature infants

To characterize changes in pulmonary resistance, timing, and respiratory drive during periodic breathing, we studied 10 healthy preterm infants (body wt 1,340 +/- 240 g, postconceptional age 35 +/- 2 wk). Periodic breathing in these infants was defined by characteristic cycles of ventilation with intervening respiratory pauses greater than or equal to 2 s. Nasal airflow was recorded with a pneumotachometer, and esophageal or pharyngeal pressure was recorded with a fluid-filled catheter. Pulmonary resistance at half-maximal tidal volume, inspiratory time (TI), expiratory time (TE), and mean inspiratory flow (VT/TI) were derived from computer analysis of five cycles of periodic breathing per infant. In 80% of infants periodic breathing was accompanied by completely obstructed breaths at the onset of ventilatory cycles; the site of airway obstruction occurred within the pharynx. The first one-third of the ventilatory phase of each cycle was accompanied by the highest airway resistance of the entire cycle (168 +/- 98 cmH2O.l-1.s). In all infants TI was greatest at the onset of the ventilatory cycle, VT/TI was maximal at the midpoint of the cycle, and TE was longest in the latter two-thirds of each cycle. A characteristic increase and subsequent decrease of 4.5 +/- 1.9 ml in end-expiratory volume also occurred within each cycle. These results demonstrate that partial or complete airway obstruction occurs during periodic breathing. Both apnea and periodic breathing share the element of upper airway instability common to premature infants.     

Airway mechanics, gas exchange, and blood flow in a nonlinear model of the normal human lung

Amodel integrating airway/lung mechanics, pulmonary blood flow, and gasexchange for a normal human subject executing the forced vital capacity(FVC) maneuver is presented. It requires as input the intrapleuralpressure measured during the maneuver. Selected model-generated outputvariables are compared against measured data (flow at the mouth, changein lung volume, and expired O₂ and CO₂concentrations at the mouth). A nonlinear parameter-estimation algorithm is employed to vary selected sensitive model parameters toobtain reasonable least squares fits to the data. This study indicatesthat 1) all three components of the respiratory model arenecessary to characterize the FVC maneuver; 2) changes in pulmonary blood flow rate are associated with changes in alveolar andintrapleural pressures and affect gas exchange and the time course ofexpired gas concentrations; and 3) a collapsible midairway segment must be included to match airflow during a forced expiration. Model simulations suggest that the resistances to airflow offered bythe collapsible segment and the small airways are significant throughout forced expiration; their combined effect is needed toadequately match the inspiratory and expiratory flow-volume loops.Despite the limitations of this lumped single-compartment model, aremarkable agreement with airflow and expired gas concentration measurements is obtained for normal subjects. Furthermore, the modelprovides insight into the important dynamic interactions betweenventilation and perfusion during the FVC maneuver.

     

Respiratory mechanics and maximal expiratory flow in the anesthetized mouse.

Mice have been widely used in immunologic and other research to study the influence of different diseases on the lungs. However, the respiratory mechanical properties of the mouse are not clear. This study extended the methodology of measuring respiratory mechanics of anesthetized rats and guinea pigs and applied it to the mouse. First, we performed static pressure-volume and maximal expiratory flow-volume curves in 10 anesthetized paralyzed C57BL/6 mice. Second, in 10 mice, we measured dynamic respiratory compliance, forced expiratory volume in 0.1 s, and maximal expiratory flow before and after methacholine challenge. Averaged total lung capacity and functional residual capacity were 1.05 +/- 0.04 and 0.25 +/- 0.01 ml, respectively, in 20 mice weighing 22.2 +/- 0.4 g. The chest wall was very compliant. In terms of vital capacity (VC) per second, maximal expiratory flow values were 13.5, 8.0, and 2.8 VC/s at 75, 50, and 25% VC, respectively. Maximal flow-static pressure curves were relatively linear up to pressure equal to 9 cm H(2)O. In addition, methacholine challenge caused significant decreases in respiratory compliance, forced expiratory volume in 0.1 s, and maximal expiratory flow, indicating marked airway constriction. We conclude that respiratory mechanical parameters of mice (after normalization with body weight) are similar to those of guinea pigs and rats and that forced expiratory maneuver is a useful technique to detect airway constriction in this species.     

Effects of rapid saline infusion on lung mechanics and airway responsiveness in humans.

Lung mechanics and airway responsiveness to methacholine (MCh) were studied in seven volunteers before and after a 20-min intravenous infusion of saline. Data were compared with those of a time point-matched control study. The following parameters were measured: 1-s forced expiratory volume, forced vital capacity, flows at 40% of control forced vital capacity on maximal (Vm(40)) and partial (Vp(40)) forced expiratory maneuvers, lung volumes, lung elastic recoil, lung resistance (Rl), dynamic elastance (Edyn), and within-breath resistance of respiratory system (Rrs). Rl and Edyn were measured during tidal breathing before and for 2 min after a deep inhalation and also at different lung volumes above and below functional residual capacity. Rrs was measured at functional residual capacity and at total lung capacity. Before MCh, saline infusion caused significant decrements of forced expiratory volume in 1 s, Vm(40), and Vp(40), but insignificantly affected lung volumes, elastic recoil, Rl, Edyn, and Rrs at any lung volume. Furthermore, saline infusion was associated with an increased response to MCh, which was not associated with significant changes in the ratio of Vm(40) to Vp(40). In conclusion, mild airflow obstruction and enhanced airway responsiveness were observed after saline, but this was not apparently due to altered elastic properties of the lung or inability of the airways to dilate with deep inhalation. It is speculated that it was likely the result of airway wall edema encroaching on the bronchial lumen.