Effect Of Volume History Research Articles

Pressure–Volume Curve Does Not Predict Steady-State Lung Volume in Canine Lavage Lung Injury

To better understand strategies for recruiting and maintaining lung volume in acute lung injury, we examined relationships between steady-state lung volume and cumulative cyclic recruitment/derecruitment volume history and the quasi-static pressure-volume curve, in an animal saline lavage lung injury model. Small-volume tidal pressure-volume loops performed after inflation from functional residual capacity demonstrated incremental, cyclic recruitment only if the peak pressure achieved exceeded the pressure at which the compliance increased (Pflex) on the pressure-volume curve, whereas loops performed after deflation from total lung capacity remained close to the envelope deflation curve. Recruitment continued to occur up to and beyond a peak inspiratory airway pressure of 40 cm H(2)O, as demonstrated by both the tidal loops and by computed tomography-derived lung volume data. Tidal-specific compliance was relatively constant across positive end-expiratory pressure levels after inflation from functional residual capacity, but peaked at moderate positive end-expiratory pressure after deflation from total lung capacity, further demonstrating the effects of volume history and providing experimental validation of the recruitment models of Hickling (AJRCCM 2001;163:69-78). These results support the interpretation of Pflex as pressure threshold for recruitment, but otherwise do not suggest a role for the pressure-volume curve in predicting steady-state lung volume.

Maximal and partial expiratory flow rates in a population sample of 10- to 11-yr-old schoolchildren. Effect of volume history and relation to asthma and maternal smoking.

The effect of volume history on forced expiratory flow rates has been reported to differ between patients with asthma and healthy persons, and it has been hypothesized that the peripheral airway inflammation of patients with asthma may underlie this difference. There are no published data, however, on the distribution of such volume history effects or the relation of these effects to airways disease in children. We obtained combined partial and maximal forced expiratory flow-volume curves on 1,834 children, age 10-11 yr, in eight communities in the United States and Canada. The effect of a deep inhalation on forced expiratory flow rates at low lung volumes was quantitated by the ratio of V (30) during a maximal expiratory maneuver (V (30M)) to V (30) during a partial expiratory maneuver (V (30P)). The V (30M)/V (30P) ratio was slightly higher among girls than boys (1.26 versus 1.18, p = 0.0001) indicating that a deep inhalation increased V (30) slightly more among girls than among boys. The V (30M)/V (30P) ratio was related to neither history of asthma nor to maternal smoking. In contrast, most spirometric indices from either the maximal or the partial expiratory flow-volume curve were lower in association with a history of asthma or a report of maternal smoking. The ratio of FEF(25-75)/FVC was particularly consistent as a measurement that discriminated both of these effects in boys and girls. These results suggest that the measurement of volume history effects offers no benefits for epidemiological studies of childhood respiratory disease whereas spirometric indices such as the FEF(25-75)/FVC ratio are quite sensitive to the effects of asthma and environmental tobacco smoke exposure on the airways.

Reduction in bronchodilation following a deep inhalation is poorly related to airway inflammation in asthma.

In patients with bronchial asthma, forced expiratory flows are differently sensitive to a previous volume history. A reduced ability of a deep inhalation (DI) to dilate obstructed airways has been hypothesized to be a physiological marker for the degree of airway responsiveness and to relate to the presence and magnitude of inflammation in the lung, even in mild stable asthma. However, there are at present doubts as to whether functional changes could be used as a substitute for airway inflammation studies. In order to investigate the interrelations among airway inflammation, bronchial hyperresponsiveness and effects of volume history, 58 consecutive asthmatics with mild to moderate asthma were studied. The effects of DI were assessed as the isovolumic ratio of flows from forced expiratory manoeuvres started from maximal (M) or partial (P) lung inflation. Airway inflammation was assessed by using induced sputum. Sputum was analysed for total and differential cell counts, and levels of eosinophil cationic protein (ECP) which reflects eosinophil activation. Airway responsiveness was assessed as the provocative concentration of histamine which caused a 20% fall in forced expiratory volume in one second (FEV1) from control (PC20). The M/P ratio was significantly related to ECP (r=-0.31, p<0.03) and eosinophils (r=-0.29, p<0.03), FEV1/vital capacity (VC) (r=0.32; p<0.01), clinical score (r=-0.33; p<0.03) and age (r=-0.41; p<0.0001). In a stepwise multiple regression analysis including age, score, baseline lung function, ECP, number of eosinophils and the response to beta2-agonist, age (p<0.037) predicted a small amount of the variance in M/P ratio (r2=0.12). It is concluded that volume history response is substantially independent of both sputum outcomes (inflammatory cell number and eosinophil cationic protein) and bronchial hyperresponsiveness; rather it seems to be associated with anthropometric characteristics. Functional aspects do not provide information on eosinophilic, probably central, airway inflammation.

Volume history effects and airway responsiveness in middle-aged and older men. The Normative Aging Study.

In persons with asthma, a deep inhalation (DI) to total lung capacity may lead to bronchoconstriction. The intensity of this effect has been shown to correlate positively with the severity of inflammatory airflow obstruction and the level of methacholine airway responsiveness. The correlates of lung volume history effects in the general population, however, are unknown. We analyzed combined maximal and partial expiratory flow-volume data, pre- and postbronchodilator spirometry data, and methacholine challenge data from 89 middle-aged and older men participating in the Normative Aging Study. The ratio of maximal to partial expiratory flow rates (VM/VP) was significantly correlated with methacholine airway responsiveness, even after adjustment for age and baseline FEV1. The direction of this correlation indicated that men with higher VM/VP ratios (i.e., greater dilator effect of a DI) tended to have greater methacholine airway responsiveness. Subjects with a higher VM/VP ratio also tended to have a greater response to a bronchodilator. These results suggest that, in the general population, airway responsiveness relates in part to airway smooth muscle tone. The correlations suggest that this relatively simple maneuver might play a role in future epidemiologic studies.

The severity of breathlessness during challenges with inhaled methacholine and hypertonic saline in atopic asthmatic subjects. The relationship with deep breath-induced bronchodilation.

The severity of breathlessness at given degrees of airway obstruction varies between patients with asthma. It has been postulated that the symptoms during bronchoconstriction are determined in part by involvement of airway inflammation. We compared the severity of breathlessness at various degrees of acute airway obstruction between a direct stimulus of airway smooth muscle, methacholine, and an indirectly acting stimulus, hypertonic saline. Twelve atopic asthmatic adults (mean +/- SD; age 25.3 +/- 3.4 yr; baseline FEV1 91.2 +/- 10.4% pred; PC20 1.0 mg/ml methacholine +/- 1.7 doubling dose) entered a methacholine and a hypertonic saline period in random order. In each period doubling doses of either methacholine (0.03 to 256 mg/ml) or hypertonic saline (0.9 to 14.4% NaCl) were inhaled on two occasions 7 d apart, using standardized tidal breathing methods. The response was obtained by FEV1 and, in order to assess volume history effects on airway caliber, by the ratio of flows obtained from volume history standardized maximal and partial expiratory flow-volume curves (M/P ratio). Breathlessness was measured by a visual analogue scale (VAS), which ranged from 0 (none) to 100% (most severe experienced). The subjects were blinded to the response in lung function. The changes from baseline in VAS scores at intervals of 5% fall in FEV1 (delta VAS) and the changes in M/P ratios (delta M/P ratio) were calculated by linear interpolation. The results were analyzed by MANOVA. There were no differences in baseline FEV1 or baseline VAS scores between the methacholine and hypertonic saline periods (p > 0.40).(ABSTRACT TRUNCATED AT 250 WORDS)

Airway and tissue responses during hyperpnea-induced constriction in guinea pigs.

It has been reported that hyperpnea-induced bronchoconstriction in guinea pigs is a potential model for exercise-induced asthma in humans. On the basis of recent studies that show increases in tissue resistance after allergen exposure in sensitized rats, we hypothesized that lung tissues might also be involved in the pathophysiology in this asthma model. We measured tracheal pressure (Ptr) and alveolar pressure (PA) using alveolar capsules in open-chested, mechanically ventilated (respiratory frequency [f] = 1 Hz, tidal volume [VT] = 9 ml/kg, positive end-expiratory pressure [PEEP] = 4 cm H2O) guinea pigs under control conditions (regular breathing of warm, humidified air) and after dry gas hyperpnea challenge (HC, mixture of 95% O2 and 5% CO2, 150 breaths/min, 7 min). We calculated lung elastance (EL) and resistance of lung (RL), tissue (Rti), and airway (Raw) by fitting the equation of motion to changes in Ptr and PA. To assess the effects of volume history, we applied a single deep inflation (three times VT) in five HC animals. We performed morphometric analysis in five control and five HC animals, freezing the lungs with liquid nitrogen and processing the tissues via freeze substitution. HC significantly increased RL, Rti, Raw, and EL (424 +/- 62, 771 +/- 230, 287 +/- 33, 259 +/- 31% baseline, respectively). A deep inflation reduced RL, Rti, Raw, and EL by 30 +/- 4, 31 +/- 4, 29 +/- 6, 23 +/- 5%, respectively. In HC animals, the degree of airway constriction was most prominent in the larger airways; extensive tissue distortion was also observed.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of volume history on measurements of respiratory mechanics using the interrupter technique.

The importance of the viscoelastic properties of the tissues of the respiratory system has recently been recognized, and lung models have been produced to describe the resistive and viscoelastic properties of the lung. The pulmonary mechanics of 10 rabbits were studied using the interrupter technique to assess the effect of volume history on the resistive and viscoelastic elements of the respiratory system. The influence of the tone of the muscles of respiration was also studied. In healthy lungs, the resistive and viscoelastic elements of the lung are dependent on the volume history of the respiratory system and are significantly lower if these elements do not reach a resting position before expiration. The chest wall made a significant contribution to the resistive and viscoelastic elements of the respiratory system, which was also dependent on the lung volume history. The tone of the muscles of respiration had no effect on the resistive or viscoelastic elements of the respiratory system.

Heterogeneous airway tone in asthmatic subjects

We examined the effect of volume history on the dynamic relationship between airways and lung parenchyma (relative hysteresis) in 20 asthmatic subjects. The acoustic reflection technique was employed to evaluate changes in airway cross-sectional areas during a slow continuous expiration from total lung capacity to residual volume and inspiration back to total lung capacity. Lung volume was measured continuously during this quasi-static maneuver. We studied three anatomic airway segments: extra- and intrathoracic tracheal and main bronchial segments. Plots of airway area vs. lung volume were obtained for each segment to assess the relative magnitude and direction of the airway and parenchymal hysteresis. We also performed maximal expiratory flow-volume and partial expiratory flow-volume curves and calculated the ratio of maximal to partial flow rates (M/P) at 30% of the vital capacity. We found that 10 subjects (group I) showed a significant predominance of airway over parenchymal hysteresis (P < 0.005) at the extra- and intrathoracic tracheal and main bronchial segments; these subjects had high M/P ratios [1.53 +/- 0.27 (SD)]. The other 10 subjects (group II) showed similar airway and parenchymal hysteresis for all three segments and significantly lower M/P ratios (1.16 +/- 0.20, P < 0.01). We conclude that the effect of volume history on the relative hysteresis of airway and lung parenchyma and M/P ratio at 30% of vital capacity in nonprovoked asthmatic subjects is variable. We suggest that our findings may result from heterogeneous airway tone in asthmatic subjects.

Effect of volume history on changes in DLcoSB-3EQ with lung volume in normal subjects.

The purpose of this study was to determine the relationship between the three-equation diffusing capacity for carbon monoxide (DLcoSB-3EQ) and lung volume and to determine how this relationship was altered when maneuvers were immediately preceded by a deep breath. DLcoSB-3EQ maneuvers were performed in nine healthy subjects either immediately after a deep breath or after tidal breathing for 10 min. The maneuvers consisted of slow inhalation of test gas from functional residual capacity to 25, 50, 75, or 100% of the inspiratory capacity and, without breath holding, slow exhalation to residual volume. After either a deep breath or tidal breathing, we found that DLcoSB-3EQ decreased nonlinearly with decreasing lung volume. At all lung volumes, DLcoSB-3EQ was significantly greater when measured after a deep breath than after tidal breathing. This effect increased as lung volume decreased, so that the greatest difference between DLcoSB-3EQ after a deep breath and that after tidal breathing occurred at the lowest lung volume. We conclude that a deep breath or spontaneous sigh has a role in reestablishing the pathway for gas exchange during tidal breathing.

Effects of volume history and vagotomy on pulmonary and chest wall mechanics in cats

Using the technique of rapid airway occlusion during constant-flow inflation, we studied the effects of inflation volume, different baseline tidal volumes (10, 20, and 30 ml/kg), and vagotomy on the resistive and elastic properties of the lungs and chest wall in six anesthetized tracheotomized paralyzed mechanically ventilated cats. Before vagotomy, airway resistance decreased significantly with increasing inflation volume at all baseline tidal volumes. At any given inflation volume, airway resistance decreased with increasing baseline tidal volume. After vagotomy, airway resistance decreased markedly and was no longer affected by baseline tidal volume. Prevagotomy, pulmonary tissue resistance increased progressively with increasing lung volume and was not affected by baseline tidal volume. Pulmonary tissue resistance decreased postvagotomy. Chest wall tissue resistance increased during lung inflation but was not affected by either baseline tidal volume or vagotomy. The static volume-pressure relationships of the lungs and chest wall were not affected by either baseline tidal volume or vagotomy. The data were interpreted in terms of a linear viscoelastic model of the respiratory system (J. Appl. Physiol. 67: 2276-2285, 1989).

Nonhomogeneous Lung Emptying in Cystic Fibrosis Patients: Volume History and Bronchodilator Effects

In spontaneous asthma after a deep inhalation (DI) obstruction occurs in direct proportion to disease severity. Since this has been associated with peripheral inflammation, which is present in cystic fibrosis (CF), we tested whether worsening obstruction after DI also occurs in CF in 12 patients. We assessed volume history effects by comparing isovolumic expiratory flows (Vmax) during forced exhalation begun at the end of tidal inspiration (partial P) with those begun at TLC (maximal M) to obtain M/P. As in asthma there was a correlation between M/P and FEV1 (% predicted; r = 0.64, p less than or equal to 0.03, n = 12). To control for a time dependency effect due to preferential emptying of fast compartments early in both the P and M maneuvers, we compared Vmax obtained from a first partial (P1) with a second (P2) obtained after inspiration to TLC and slow exhalation to the same starting volume as P1 (P2/P1). In contrast to asthma the P2/P1 was greater than the M/P and not related to disease severity. A further index of nonhomogeneous lung emptying was the relationship between M/P and the slope ratio at 70% TLC (r = -0.67, p less than or equal to 0.03). After isoetharine inhalation the M/P decreased (-0.12 +/- 0.12, p less than or equal to 0.01) but no change was apparent in P2/P1, indicating further increases in the degree of nonhomogeneity. We conclude that although volume history effects on M/P are similar in asthma and CF, this is due to a predominance of parenchymal hysteresis in the former and nonhomogeneity in the latter, which worsens with bronchodilator use.

Effects of increasing doses of beta-agonists on airway and parenchymal hysteresis

We examined the effects of a deep inhalation on airway caliber before and after increasing doses of a beta-agonist in eight subjects, including one former and two current but mild asthmatics. With bronchodilation the increase in maximal flow on the partial flow-volume curve (P), initiated from functional residual capacity, exceeded that seen on the maximal curve (M), initiated from total lung capacity, such that isovolumic maximal flows diminished after a deep inhalation; i.e., M/P ratios fell with bronchodilation, as we and others have found. Five of eight reversed this downward trend in M/P ratios at higher cumulative doses. Quasistatic pressure-volume curves (QSPV) were simultaneously performed on two of these five and demonstrated a decrease in pressure-volume hysteresis (PVH) at the higher doses associated with a rising M/P ratio. Three of eight had continuing low and diminishing M/P ratio up to the highest dose given. QSPV were performed in two of these three and indicated no change in PVH at any of the doses. One of these two had a repeat study using a subcutaneous beta-agonist after the inhaled drug was given, and the M/P ratio rose as QSPV PVH fell. These data support the relative hysteresis analysis of airway and parenchyma as an explanation for volume history effects on airway caliber.

Effects of Volume History During Spontaneous and Acutely Induced Air-Flow Obstruction in Asthma

We examined the volume history effect on maximal expiratory flow (Vmax) in patients with asthma by comparing Vmax at 60% of VC from forced exhalation maneuvers begun just above FRC (partial, P) with those begun from TLC (maximal, M) and expressed the results as M-P ratios. In a clinic population with varying degrees of obstruction, we found that M-P ratios varied inversely with the severity of the obstructive process, i.e., the more severely obstructed patients had a fall in Vmax after a deep inhalation (DI). By contrast, equally severe obstruction acutely induced in subjects with mild asthma was associated with an increase in Vmax after a DI. There was no difference between the spontaneous versus the induced groups in degree of nonhomogeneity as assessed by single-breath nitrogen tests. Changes in specific airway conductance after a DI during spontaneous obstruction were in the same direction as the changes in Vmax, and the time course for restitution of airway caliber in subjects who showed bronchoconstriction after a DI was significantly longer than for those subjects who showed bronchodilatation. We conclude that in severe bronchial asthma with spontaneous obstruction, a DI produces an increase in severity that is opposite to the results found in acutely induced obstruction, and the time course for reestablishing baseline airway caliber is more prolonged. We suggest that mechanisms for and sites of obstruction vary between the 2 groups.

Effect of volume history on distribution of inspired gas in asthmatics.

Twelve stable adult asthmatics slowly inhaled boluses of He at 20, 40, or 60% vital capacity (VC); these volumes were achieved either by expiring from total lung capacity (TLC) or by inspiring from residual volume (RV). Inspirations were continued to TLC and then were followed by slow expirations to RV while expired He was measured as a function of expired volume. At 20% VC slopes of alveolar plateaus (phase III) were positive, at 40% VC they were flat, and at 60% VC they were negative; at 20 and 60% VC the slopes were steeper than those in normals. When boluses were administered at 40 and 60% VC, He washout curves were independent of lung volume history. However at 20% VC the slope of phase III was significantly less positive when boluses were given after inspiration from RV than after expiration from TLC. In eight subjects, who were given inhaled beta-agonists, slopes of all He washouts decreased and became independent of volume history at 20% VC. We conclude that in asthmatics at low lung volumes the airways that determine ventilation distribution behave as though they have less hysteresis than the lung parenchyma probably due to increased airway tone.

Effects of airway tone and volume history on maximal expiratory flow in asthma.

We assessed the difference between isovolumic maximal expiratory flows (Vmax) using maneuvers begun at mid-lung volumes, so-called partial expiratory flow-volume curves (P), vs. those begun at full inflation, so-called maximal expiratory flow-volume curves (M), in 10 asthmatic subjects before and following obstruction induced by isocapnic hyperpnea with cold air and before and after bronchodilation with a beta-agonist or antimuscarinic agent. Volume history effects were quantitated as an M-to-P ratio of Vmax at 30% vital capacity (M/P V30). Although M/P V30 was variable among patients at base line, there was a uniform increase in M/P V30 during constriction and a consistent decrease below base line after dilation. Blunting of induced obstruction with beta-agonists also diminished the increase in M/P V30. Antimuscarinics, despite equivalent bronchodilation, failed to alter the degree of obstruction induced by cold air or the increase in M/P V30 seen during obstruction. The level of airway tone, as indicated by specific resistance, related directly to the M/P V30. We conclude that the response of the asthmatic lung to a deep inhalation is relatively predictable when acute changes in airway tone are produced.

Partitioning of pulmonary resistance during constriction in the dog: effects of volume history.

We assessed the relative changes in airways and lung tissue with bronchoconstriction, and the changes in each during and following a deep inhalation (DI). We partitioned pulmonary resistance (RL) into airway (Raw) and tissue (Vtis) components using alveolar capsules in 10 anesthetized, paralyzed, and open-chested dogs ventilated sinusoidally with 350-ml breaths at 1 Hz. We made measurements before and during bronchoconstriction induced by vagal stimulation or inhalation of histamine or prostaglandin F2 alpha (PGF2 alpha), each of which decreased dynamic compliance by approximately 40%. With histamine and PGF2 alpha the rise in RL was predominantly due to Vtis. With vagal stimulation there was a relatively greater increase in Raw than Vtis. At higher lung volumes, Vtis increases offset falls in Raw, producing higher RL at these volumes before and during constriction with PGF2 alpha and histamine. During constriction with vagal stimulation, the fall in Raw with inflation overrode the rise in Vtis, resulting in a lower RL at the higher compared with the lower lung volume. The changes seen after a DI in the control and constricted states were due to alterations in tissue properties, both viscous and elastic. However, the relative hysteresis of the airways and parenchyma were equal, since Raw, our index of airway size, was unchanged after a DI.

Effect of previous volume history on airway closure.

We studied the effect of volume history on airway closure in six healthy males ranging from 32 to 67 yr of age. The method used was to compare the regional distribution of 133Xe boluses distributed according to N2O uptake during open-glottis breath-hold maneuvers with the regional distribution of boluses of intravenously injected 133Xe. Measurements were made at two lung volumes, one close to residual volume (RV) and the other just below closing volume. The required volume was reached either by expiring from total lung capacity or by inspiring from RV. Although there was considerable airway closure in the basal regions of the lungs at both lung volumes studied, the degree of airway closure was not dependent on the previous volume history. We conclude that the airways concerned with closure have a volume-pressure hysteresis similar to that of the lung parenchyma. Furthermore in normal humans the volume-pressure hysteresis of the lung is not secondary to airway closure.

End-expiratory volume in the rat: effects of consciousness and body position.

Functional residual capacity (FRC), tidal volume (VT), and frequency (f) were compared in 23 rats while either awake and unrestrained or anesthetized. FRC was determined from gas compression with closed airway inside a cone-shaped body plethysmograph. In the awake state (mean +/- SD), FRC was 1.02 +/- 0.22 ml/100 g, VT was 0.38 +/- 0.06 ml/100 g, and f was 142 +/- 22 breaths/min. During anesthesia, FRC decreased (P less than 0.01) to 52.9% of awake values, VT increased (P less than 0.01) to 147.4%, and f decreased (P less than 0.01) to 71.8%, leaving minute ventilation almost unchanged. An additional seven rats were used to examine postural effects on FRC during anesthesia, and in another seven animals pleural pressure changes were monitored. Dynamic lung compliance (0.80 ml . kg-1 X cmH2O-1) was not altered by anesthesia, but the pressure-volume curve was shifted 6 cmH2O higher. Thoracic compression, followed by a time-dependent effect of volume history, may account for the major change in FRC. The remainder of the decrease in FRC may be due to lower breathing frequency, loss of inspiratory muscle activity, and/or less airway resistance after anesthesia. Peak diaphragmatic electromyogram per unit VT was shown to increase almost linearly with FRC, indicating that diaphragmatic efficiency was decreased as lung volume was elevated.

Effects of volume history and time dependence of flow-volume curves on assessment of bronchial response to inhaled methacholine in normals.

The behavior of maximum expiratory flow-volume curves and partial expiratory flow-volume curves with and without volume history of total lung capacity was studied in 11 healthy subjects before and after methacholine inhalation challenge. Flow-volume curves were superimposed at absolute lung volumes by measuring thoracic gas volumes at which inspiratory maneuvers began. The results show that maximum inspiratory effort reduced significantly residual volume, either before or after challenge, while flow rates at 40% of control total lung capacity achieved with partial expiratory flow-volume curves with history of total lung capacity were significantly greater than those without history of maximal inflation. These findings are explained by the stress relaxation as an effect of volume history ot total lung capacity and by the appearance of time dependence as an index of inhomogeneity of lung emptying. After methacholine the effects of volume history on maximum flows and residual volume were increased. In conclusion, the results of this study emphasize the probability of errors when only maximum expiratory flow-volume curve are used in assessment of bronchial responses.

Airways response to inhaled tobacco smoke: time course, dose dependence and effect of volume history.

We have measured puff by puff the effect of smoking three brands of cigarettes with different composition on airways resistance (Raw) thoracic gas volume (TGV) and the maximal expiratory flow volume (MEFV) curve. Raw increased significantly with all three brands of cigarettes after one puff. The maximum effect was reached after three puffs. Instantaneous flow at 50% of vital capacity (FEF50) decreased significantly with cigarettes high in nicotine content, but not so after smoking a low nicotine (0.31 mg) cigarette. Instantaneous flow at 75% of vital capacity out (FEF75) increased significantly 30 min after the low nicotine cigarette was smoked. A deep inspiration prior to Raw determination reduced by approximately one third the bronchoconstrictor effect of cigarette smoke. All effects were reversible within 30 min, except the delayed effect of the low nicotine cigarette on the FEF75. We conclude that the probable site of action of tobacco smoke is in the large and central airways. The bronchoconstrictor effect rapidly reaches a plateau. A delayed bronchodilation of the small airways observed after smoking the low nicotine cigarette might represent a response usually masked by other long-acting components in smoke. We suggest that the airway response to tobacco smoke is complex and probably a result of several components present in smoke which still have to be identified.