Tracheal dimensions at full inflation and deflation in adolescent twins

Tracheal dimensions at total lung capacity (TLC) and residual volume (RV) were analyzed roentgenographically in 17 pairs of male adolescent twins (mean age 16.3 yr; 12 monozygotic pairs and 5 dizygotic pairs). Genetic factors dominated environmental traits in intra- as well as extrathoracic tracheal width at RV. Extrathoracic tracheal width at TLC was also governed by genetic components. Intrathoracic tracheal depth (anteroposterior diameter), length, and cross-sectional area did not seem to be genetically controlled at TLC and RV. Intrathoracic tracheal cross-sectional area increased by 14.4% and became more elliptical from RV to TLC, owing mainly to an increase in tracheal depth (16.7%). Increments from RV to TLC in tracheal depth but not width correlated with increases in lung width, depth, and height. Intrathoracic trachea was elongated 14% in association with increase in lung height from RV to TLC. At TLC, extrathoracic tracheal width was larger than intrathoracic tracheal width, but this dimension did not differ at RV. These results indicate that genetic factors influence, at least at RV, the tracheal rings more strongly than membranous parts. Intrathoracic tracheal depth but not width increases during inspiration in accordance with increase in lung volume. Extrathoracic tracheal width widens more than intrathoracic trachea from RV to TLC.     

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.     

Gravity effects on regional lung ventilation determined by functional EIT during parabolic flights.

Gravity-dependent changes of regional lung function were studied during normogravity, hypergravity, and microgravity induced by parabolic flights. Seven healthy subjects were followed in the right lateral and supine postures during tidal breathing, forced vital capacity, and slow expiratory vital capacity maneuvers. Regional 1) lung ventilation, 2) lung volumes, and 3) lung emptying behavior were studied in a transverse thoracic plane by functional electrical impedance tomography (EIT). The results showed gravity-dependent changes of regional lung ventilation parameters. A significant effect of gravity on regional functional residual capacity with a rapid lung volume redistribution during the gravity transition phases was established. The most homogeneous functional residual capacity distribution was found at microgravity. During vital capacity and forced vital capacity in the right lateral posture, the decrease in lung volume on expiration was larger in the right lung region at all gravity phases. During tidal breathing, the differences in ventilation magnitudes between the right and left lung regions were not significant in either posture or gravity phase. A significant nonlinearity of lung emptying was determined at normogravity and hypergravity. The pattern of lung emptying was homogeneous during microgravity.     

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.     

Dose response relation to oral theophylline in severe chronic obstructive airways disease.

OBJECTIVE--To evaluate measurement of the trapped gas volume as a measure of respiratory function in patients with chronic obstructive airways disease and their response to treatment with theophylline. DESIGN--Patients able to produce consistent results on testing of respiratory function spent two weeks having dosage of theophylline adjusted to give individual pharmacokinetic data. This was followed by random assignment to four consecutive two month treatment periods--placebo and low, medium, and high dose, as assessed by serum concentrations of theophylline. Respiratory function and exercise performance was assessed at the end of each two month period. SETTING--Chest unit in district hospital. PATIENTS--Thirty eight patients with chronic bronchitis and moderate to severe chronic obstruction to airflow were recruited; 33 aged 53-73 years completed the study. INTERVENTIONS--Dosage of oral theophylline increased during two week optimisation period to 800 mg daily unless toxicity was predicted, when 400 mg was given. Targets for the steady state serum theophylline concentrations were 5-10 mg/l in the low dose period, 10-15 mg/l in the medium dose, and 15-20 mg/l in the high dose period. ENDPOINTS--Respiratory function as measured by forced expiratory volume in one second, forced vital capacity, peak expiratory flow rate, slow vital capacity, and static lung volumes using helium dilution and body plethysmography from which trapped gas volume was derived. Exercise performance assessed by six minute walking test and diary cards using visual analogue scale. MEASUREMENTS AND MAIN RESULTS--The forced expiratory volume in one second, forced vital capacity, and peak expiratory flow rate changed only slightly (about 13%) over the range of doses. There was a linear dose dependent fall of trapped gas volume from 1.84 l (SE 0.157) to 1.42 l (0.152), 1.05 l (0.128), and 0.67 l (0.102) during the placebo and low, medium, and high dose treatment periods. Mean walking distance increased by up to 55.6 m (20%). There was a modest improvement in dyspnoea as the dose of theophylline was increased. Side effects were mostly minor but they became more frequent as the dose was increased. CONCLUSION--The fall in trapped gas volume may reflect an improvement in peripheral ventilation (associated with treatment with theophylline) which is less apparent in the more common tests of lung function used in patients with chronic obstructive airways disease.     

Respiratory morbidity 10 years after the Union Carbide gas leak at Bhopal: a cross sectional survey. The International Medical Commission on Bhopal.

OBJECTIVE: To examine the role of exposure to the 1984 Bhopal gas leak in the development of persistent obstructive airways disease. DESIGN: Cross sectional survey. SETTING: Bhopal, India. SUBJECTS: Random sample of 454 adults stratified by distance of residence from the Union Carbide plant. MAIN OUTCOME MEASURES: Self reported respiratory symptoms; indices of lung function measured by simple spirometry and adjusted for age, sex, and height according to Indian derived regression equations. RESULTS: Respiratory symptoms were significantly more common and lung function (percentage predicted forced expiratory volume in one second (FEV1), forced vital capacity (FVC), forced expiratory flow between 25% and 75% of vital capacity (FEF25-75), and FEV1/FVC ratio) was reduced among those reporting exposure to the gas leak. The frequency of symptoms fell as exposure decreased (as estimated by distance lived from the plant), and lung function measurements displayed similar trends. These findings were not wholly accounted for by confounding by smoking or literacy, a measure of socioeconomic status. Lung function measurements were consistently lower in those reporting symptoms. CONCLUSION: Our results suggest that persistent small airways obstruction among survivors of the 1984 disaster may be attributed to gas exposure.     

Bronchoconstrictor and antibronchoconstrictor properties of inhaled prostacyclin in asthma

Prostacyclin (PGI2) is generated in appreciable amounts during allergic reactions in human lung tissue. To define its activity on human airways we have studied the effects of doubling concentrations of inhaled PGI2 and its hydrolysis product 6-oxoprostaglandin F1 alpha (6-oxo-PGF1 alpha) on specific airway conductance (sGaw), maximum expiratory flow at 30% vital capacity (Vmax30), forced expiratory volume in 1 s (FEV1), and static lung volumes in subjects with mild allergic asthma. In a second study the effect of inhaled PGI2 on bronchoconstriction provoked by increasing concentrations of inhaled prostaglandin (PG) D2 and methacholine was observed. Inhalation of PGI2 up to a concentration of 500 micrograms/ml had no significant effect on sGaw but produced a concentration-related decrease in FEV1 and Vmax30 in all subjects. In two of four subjects inhalation of PGI2 also increased residual volume and decreased vital capacity but had no effect on total lung capacity. PGI2, but not 6-oxo-PGF1 alpha, protected against bronchoconstriction provoked by either PGD2 or methacholine whether airway caliber was measured as sGaw, FEV1, or Vmax30. The apparent disparity between the bronchoconstrictor and antibronchoconstrictor effects of PGI2 might be explained by its potent vasodilator effect in causing airway narrowing through mucosal engorgement and reducing the spasmogenic effects of other inhaled mediators by increasing their clearance from the airways.     

Exercise-induced bronchodilation in natural and induced asthma: effects on ventilatory response and performance.

We studied whether bronchodilatation occurs with exercise during the late asthmatic reaction (LAR) to allergen (group 1, n = 13) or natural asthma (NA; group 2, n = 8) and whether this is sufficient to preserve maximum ventilation (VE(max)), oxygen consumption (VO(2 max)), and exercise performance (W(max)). In group 1, partial forced expiratory flow at 30% of resting forced vital capacity increased during exercise, both at control and LAR. W(max) was slightly reduced at LAR, whereas VE(max), tidal volume, breathing frequency, and VO(2 max) were preserved. Functional residual capacity and end-inspiratory lung volume were significantly larger at LAR than at control. In group 2, partial forced expiratory flow at 30% of resting forced vital capacity increased greatly with exercise during NA but did not attain control values after appropriate therapy. Compared with control, W(max) was slightly less during NA, whereas VO(2 max) and VE(max) were similar. Functional residual capacity, but not end-inspiratory lung volume at maximum load, was significantly greater than at control, whereas tidal volume decreased and breathing frequency increased. In conclusion, remarkable exercise bronchodilation occurs during either LAR or NA and allows VE(max) and VO(2 max) to be preserved with small changes in breathing pattern and a slight reduction in W(max).     

Relationship of tracheal size to maximal expiratory airflow and density dependence

Wave-speed theory predicts that maximal expiratory flow (MEF) at high lung volumes depends strongly on size of central airways. We tested this prediction by correlating MEF and tracheal cross-section area (T-XSA) in 15 (11 males, 4 females) healthy never-smoking volunteers. T-XSA was determined by planimetric analysis of contiguous 1-cm computerized tomographic scans of the intrathoracic trachea. We found a significant correlation between T-XSA at total lung capacity (TLC) and flow at 75% of vital capacity (V75) (r = 0.88, P less than 0.001). This contrasted to the correlation found between lung volume at TLC and V75 (r = 0.60). Density dependence of airflow (percent increase in V75 in air) was 35 +/- 17% and showed a significant inverse relationship to T-XSA (r = 0.70). These results confirm predictions of wave-speed theory and demonstrate the importance of cross-sectional area of central airways in determining MEF at high lung volumes. The large variability of MEF in normal individuals partly represents variations in tracheal size. Poor correlation between lung size and airway size suggests only a loose coupling between airways and lung parenchyma consistent with dysanaptic growth. Our findings indicate that changes in density dependence of airflow are not solely determined by the status of small airways and that differences in tracheal size contribute to its variability.     

The airway response to deep inspirations decreases with COPD severity and is associated with airway distensibility assessed by computed tomography.

In patients with mild chronic obstructive pulmonary disease (COPD), the effect of deep inspirations (DIs) to reverse methacholine-induced bronchoconstriction is largely attenuated. In this study, we tested the hypothesis that the effectiveness of DI is reduced with increasing disease severity and that this is associated with a reduction in the ability of DI to distend the airways. Fifteen subjects [Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage I-II: n = 7; GOLD stage III-IV: n = 8] underwent methacholine bronchoprovocation in the absence of DI, followed by DI. The effectiveness of DI was assessed by their ability to improve inspiratory vital capacity and forced expiratory volume in 1 s (FEV(1)). To evaluate airway distensibility, two sets of high-resolution computed tomography scans [at residual volume (RV) and at total lung capacity] were obtained before the challenge. In addition, mean parenchymal density was calculated on the high-resolution computed tomography scans. We found a strong correlation between the response to DI and baseline FEV(1) %predicted (r(2) = 0.70, P < 0.0001) or baseline FEV(1)/forced vital capacity (r(2) = 0.57, P = 0.001). RV %predicted and functional residual capacity %predicted correlated inversely (r(2) = 0.33, P = 0.02 and r(2) = 0.32, P = 0.03, respectively), and parenchymal density at RV correlated directly (r(2) = 0.30, P = 0.03), with the response to DI. Finally, the effect of DI correlated to the change in large airway area from RV to total lung capacity (r(2) = 0.44, P = 0.01). We conclude that loss of the effects of DI is strongly associated with COPD severity and speculate that the reduction in the effectiveness of DI is due to the failure to expand the lungs because of the hyperinflated state and/or the parenchymal damage that prevents distension of the airways with lung inflation.     

Respiratory effects of non-tobacco cigarettes.

Data from the Tucson epidemiological study of airways obstructive disease on smoking of non-tobacco cigarettes such as marijuana were analysed to determine the effect of such smoking on respiratory symptoms and pulmonary function. Among adults aged under 40, 14% had smoked non-tobacco cigarettes at some time and 9% were current users. The prevalence of respiratory symptoms was increased in smokers of non-tobacco cigarettes. After tobacco smoking had been controlled for men who smoked non-tobacco cigarettes showed significant decreases in expiratory flow rates at low lung volumes and in the ratio of the forced expiratory volume in one second to the vital capacity. This effect on pulmonary function in male non-tobacco cigarette smokers was greater than the effect of tobacco cigarette smoking. These data suggest that non-tobacco cigarette smoking may be an important risk factor in young adults with respiratory symptoms or evidence of airways obstruction.     

Acoustic and spirometry parameters of forced expiratory sounds during a five-day dry immersion

The dynamic studies of the parameters of forced expiration under the conditions of a five-day dry immersion involved seven healthy male subjects aged 20 to 25 years. During forced expiration, spirometry tests were performed simultaneously with tracheal sounds being recorded by a microphone. A number of parameters, including the acoustic duration of the forced-expiration tracheal sounds, the lungs’ forced vital capacity, the 1-s forced expiration volume, the peak expiratory flow, and time of achieving the peak expiratory flow, were recorded before dry immersion, on days 1 and 4 of immersion, and the next day after the termination of immersion. There was a significant decrease (by 8.4%) in the peak expiratory flow on day 1 of immersion; however, by day 4 of immersion, the peak expiratory flow increased by 8.9%, reaching its baseline values. The lungs’ forced vital capacity and the forced expiration volume during 1 second, on the average, did not change throughout the experiment. There was a significant increase (by 17%) in the duration of the forced expiration tracheal sounds after the immersion, which suggests an increase in respiratory resistance and needs further studies. A moderate negative correlation between the duration of the forced expiration tracheal sounds and Gensler’s index (r = ?0.63) was found, whereas the correlation with other spirometry parameters was weak or absent.     

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.     

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.     

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.     

Deep breaths, methacholine, and airway narrowing in healthy and mild asthmatic subjects.

Deep breaths taken before inhalation of methacholine attenuate the decrease in forced expiratory volume in 1 s and forced vital capacity in healthy but not in asthmatic subjects. We investigated whether this difference also exists by using measurements not preceded by full inflation, i.e., airway conductance, functional residual capacity, as well as flow and residual volume from partial forced expiration. We found that five deep breaths preceding a single dose of methacholine 1) transiently attenuated the decrements in forced expiratory volume in 1 s and forced vital capacity in healthy (n = 8) but not in mild asthmatic (n = 10) subjects and 2) increased the areas under the curve of changes in parameters not preceded by a full inflation over 40 min, during which further deep breaths were prohibited, without significant difference between healthy (n = 6) and mild asthmatic (n = 16) subjects. In conclusion, a series of deep breaths preceding methacholine inhalation significantly enhances bronchoconstrictor response similarly in mild asthmatic and healthy subjects but facilitates bronchodilatation on further full inflation in the latter.     

Model of forced expiratory flows and airway geometry in infants.

Early measurements of autopsied lungs from infants, children, and adults suggested that the ratio of peripheral to central airway resistance was higher in infants than older children and adults. Recent measurements of forced expiration suggest that infants have high flows relative to lung volume. We employed a computational model of forced expiratory flow along with physiological and anatomic data to evaluate whether the infant lung is a uniformly scaled-down version of the adult lung. First, we uniformly scaled an existing computational model of adult forced expiration to estimate forced expiratory flows (FEF) and density dependence for an 18-mo-old infant. The values obtained for FEF and density dependence were significantly lower than those reported for healthy 18-mo-old infants. Next, we modified the model for the infant lung to reproduce standard indexes of expiratory flow [forced expiratory volume in 0.5 s (FEV(0.5)), FEFs after exhalation of 50 and 75% forced vital capacity, FEF between 25 and 75% expired volume] for this age group. The airway sizes obtained for the infant lung model that produced accurate physiological measurements were similar to anatomic data available for this age and larger than those in the scaled model. Our findings indicate that the airways in the infant lung model differ from those in the scaled model, i.e., middle and peripheral airway sizes are larger than result from uniform downscaling of the adult lung model. We show that the infant lung model can be made to reproduce individual flow-volume curves by adjusting lumen area generation by generation.     

Wistar大鼠肺功能参考值范围测定

目的建立Wistar大鼠肺功能各项指标的参考值。方法用创体描法小动物肺功能检测仪检测大鼠肺功能各项指标,根据肺功能指标检测结果,通过统计分析,确定其参考值范围。结果 Ri（吸气阻力）为1.81（0.94~4.10）cm H2O/（mL·s）,Re（呼气阻力）为1.83（0.71~3.57）cm H2O/（mL·s）,Cl（肺顺应性）为0.15（0.05~0.29）mL/cm H2O,MVV（最大通气量）为144.65（77.28~256.20）mL/min,FVC（用力肺活量）为8.49（5.82~12.70）mL,Fev0.2（第0.2秒用力呼气容积）为5.72（3.62~7.01）mL,Fev0.2/FVC（第0.2秒用力呼出容积占用力肺活量百分比）为8.12（39.14~85.28）%,FEF（25~75）%（用力中期呼气流速）为34.11（28.25~46.87）mL/min。PEF（用力最大呼气流速）为38.28（30.75~50.25）mL/min。结论 Wistar大鼠肺功能指标的参考值范围可为临床和科研工作以及未来制定国家标准和规范提供参考依据。     

Ventilatory Tests and Pulmonary Conductance in Hospitalized Patients

In a series of 49 patients, including individuals with varying lung pathology and some older patients with no lung disease, the usual excellent correlation between first-second forced expiratory volume and maximum breathing capacity was found (coefficient of correlation=0.88). The first-second forced expiratory volume and maximum mid-expiratory flow rate were also seen to be closely related (coefficient of correlation=0.87). The relationship between these ventilatory tests and direct mechanical measurements of pulmonary resistance, however, was not as striking. Reduction in pulmonary compliance not due to loss or removal of pulmonary tissue did not affect the interrelationships between these tests. First-second forced expiratory volume, expressed as a percentage of the predicted vital capacity, was more closely related to the expression “% of predicted maximum breathing capacity” than the first-second forced expiratory volume, expressed as a percentage of the actual vital capacity (p<.05).     

Bronchial hyperreactivity to leucotriene D4 and histamine in exogenous asthma.

Reactivity of the small and large airways to inhaled leucotriene D4, one of the leucotrienes that constitute slow reacting substance of anaphylaxis, was studied in eight patients with exogenous asthma and nine healthy subjects with no history of atopy. Non-cumulative dose response relations were constructed for leucotriene D4 in a randomised, double blind set up. Reactivity to the leucotriene was compared with reactivity to histamine in the two groups. Both groups reacted to leucotriene D4 with significant airway obstruction evident in forced expiratory volume in one second (FEV1), peak expiratory flow rate, maximal expiratory flow rate at 30% of forced vital capacity estimated from a partial flow volume curve initiated at 50% of vital capacity (V30), and an increase in volume of trapped gas. The airways of the patients were significantly (p less than 0.01) more reactive to leucotriene D4 than those of the controls. The differences were in order of magnitude, 10(2)-10(3) for FEV1 but only about 15 for V30 (p less than 0.05). The hyperreactivity of the airways of the asthmatic subjects to leucotriene D4 was comparable to that to histamine. Inhalation of leucotriene D4 caused pronounced dyspnoea only among the patients. The findings suggest a role for leucotriene D4 in human bronchial asthma.