Forced Expiratory Flow-volume Research Articles

Die Spirometrie in der ärztlichen Praxis – Teil 1: Die Messung

Spirometry in the Medical Practice - Part 1: Measuring Abstract. Today, every practitioner, as well as every hospital emergency, should be able to perform spirometry. However, the measurement requires solid basic knowledge as well as a certain amount of experience so that consistent and reproducible measurements are possible. Since the measurement depends heavily on the cooperation of the patient, typical errors must be recognised and corrected immediately. A rounded forced expiratory flow volume curve, or a sudden drop of the curve towards zero at the end of exhalation as well as clearly deviating curves or values in the minimum required three measurement manoeuvres are clear hints for an insufficiently forced expiration or an expiration that was stopped too early. Pulmonary function assistants need instructions as to when application of a rapid acting beta agonist with repeated spirometry to detect possible reversibility is necessary. This includes knowing how long therapeutic bronchodilators must be stopped prior to the test.

The effect of Tai Chi on the pulmonary rehabilitation of chronic obstructive pulmonary disease: a systematic review and meta-analysis.

The effectiveness of Tai Chi for chronic obstructive pulmonary disease (COPD) so far is unclear. The present systematic review aimed to determine the influence of Tai Chi among people with COPD. We searched six electronic databases for relevant studies in September, 2019. The methods of standard meta-analysis were used for identifying relevant studies, quality appraisal, and synthesis. The primary outcomes were six-minute walking distance (6MWD), percentage predicted forced expiratory flow volume in the first second (%PredFEV1), and St. George's Respiratory Questionnaire (SGRQ) score. A total of 23 studies including 1663 participants were included in the meta-analysis. The pooled data showed that the Tai Chi group was associated with a significant improvement in 6MWD [mean difference (MD) 40.83 m, 95% CI: 32.47 to 49.19], %PredFEV1 (MD 1.67%, 95% CI: 0.41 to 2.93), SGRQ score (MD -6.57, 95% CI: -10.17 to -2.98), and Chronic Respiratory Disease Questionnaire (CRQ) (MD 1.60, 95% CI: 0.89 to 2.30) relative to the blank control population. When compared with breathing exercises, the 6MWD was significantly enhanced with Tai Chi (MD 14.15 m, 95% CI: 3.76 to 24.53). Finally, when compared with breathing and walking exercises, Tai Chi was associated with a significant improvement in 6MWD (MD 7.68 m, 95% CI: 2.28 to 13.09 m) and SGRQ score (MD -6.31, 95% CI: -9.13 to -1.48). Tai Chi may have the potential to reduce dyspnoea, enhance exercise capacity, and improve the quality of life in COPD patients. People with COPD may obtain benefit from practicing Tai Chi.

Forced expiratory time: a composite of airway narrowing and airway closure.

Forced expiratory time (FET) is a spirometrically derived variable thought to reflect lung function, but its physiological basis remains poorly understood. We developed a mathematical theory of FET assuming a linear forced expiratory flow-volume profile that terminates when expiratory flow falls below a defined detection threshold. FET is predicted to correlate negatively with both FEV1 and FVC if variations in the rate of lung emptying (relative to normal) among individuals in a population exceed variations in the amount of lung emptying. We retrospectively determined FET pre- and postmethacholine challenge in 1,241 patients (818 had normal lung function, 137 were obstructed, and 229 were restricted) and examined its relationships to spirometric and demographic variables in both hyperresponsive and normoresponsive individuals. Mean FET was 9.6 ± 2.2 s in the normal group, 12.3 ± 3.0 s in those with obstruction, and 8.8 ± 1.9 s in those with restriction. FET was inversely related to FEV1/FVC in all groups, negatively related to FEV1 in the obstructed patients, and positively related to FVC in both the normal and restricted patients. There was no relationship with methacholine responsiveness. Overall, our theory of the relationship between FET to the spirometric indices is supported by these findings and potentially explains how FET is affected by sex, age, smoking status, and possibly body mass index.NEW & NOTEWORTHY Forced expiratory time (FET) has long been felt to reflect important physiological information about lung function but exactly how has never been clear. Here, we use a model analysis to assess the contributions of airway narrowing versus airway closure to FET in a population of individuals and find support for the theory that FET correlates positively with FEV1 if the amounts of lung emptying over a forced expiration vary from predicted values more than variations in the rates of lung emptying, whereas the correlation is negative in the opposite case.

Raised-Volume Forced Expiratory Flow-Volume Curve in Healthy Taiwanese Infants

The raised-volume rapid thoracoabdominal compression (RVRTC) manoeuvre has been applied to obtain full forced expiratory flow-volume curves in infants. No reference data are available for Asian populations. This study was conducted to establish predictive reference equations for Taiwanese infants. Full-term infants without any chronic disease or major anomaly were enrolled from this cohort study. Full forced expiratory flow-volume curves were acquired using RVRTC manoeuvres through Jaeger’s system. Tidal breath analysis, passive respiratory mechanics, and tidal forced expiratory flow-volume curves were performed and collected at the same measurement. Multiple linear analyses were used to model the variables. We performed 117 tests of RVRTC flow-volume curves in 97 infants. The results revealed that all parameters, except for FEV0.5 /FVC, correlated highly and positively with body length. These parameters correlated significantly with other parameters of passive respiratory mechanics and tidal forced expiratory flow-volume curves. This is the first study to establish equipment-specific reference data of full forced expiration using RVRTC manoeuvres in Asian infants. The results revealed that parameters of RVRTC manoeuvres are moderately related to other parameters of infant lung function. These race-specific reference data can be used to more precisely and efficiently diagnose respiratory diseases in infants of Chinese ethnicity.

GLCCI1 variant accelerates pulmonary function decline in patients with asthma receiving inhaled corticosteroids

In steroid-naive patients with asthma, several gene variants are associated with a short-term response to inhaled corticosteroid (ICS) treatment; this has mostly been observed in Caucasians. However, not many studies have been conducted for other ethnicities. Here, we aimed to determine the relationship between the annual decline in forced expiratory flow volume in one second (FEV1 ) and the variant of the glucocorticoid-induced transcript 1 gene (GLCCI1) in Japanese patients with asthma receiving long-term ICS treatment, taking into account the effect of high serum periostin levels, a known association factor of pulmonary function decline and a marker of refractory eosinophilic/Th2 inflammation. In this study, 224 patients with asthma receiving ICS treatment for at least 4years were enrolled. The effects of single-nucleotide polymorphisms (SNPs) in GLCCI1, stress-induced phosphoprotein 1 (STIP1), and T gene on the decline in FEV1 of 30ml/year or greater were determined. Besides the known contributing factors, that is, the most intensive treatment step, ex-smoking, and high serum periostin levels (≥95ng/ml), the GG genotype of GLCCI1 rs37973, and not other SNPs, was independently associated with a decline in FEV1 of 30ml/year or greater. When patients were stratified according to their serum periostin levels, the GG genotype of rs37973 was significantly associated with blood eosinophilia (≥250/μl) in the high serum periostin group. A GLCCI1 variant is a risk factor of pulmonary function decline in Japanese patients with asthma receiving long-term ICS treatment. Thus, GLCCI1 may be associated with response to ICS across ethnicities.

Thoracic gas compression during forced expiration in patients with emphysema, interstitial lung disease and obesity

BackgroundDynamic gas compression during forced expiration has an influence on conventional flow-volume spirometry results. The extent of gas compression in different pulmonary disorders remains obscure. Utilizing a flow plethysmograph we determined the difference between thoracic and mouth flows during forced expiration as an indication of thoracic gas compression in subjects with different pulmonary diseases characterized by limitations in pulmonary mechanics.MethodsPatients with emphysema (N = 16), interstitial lung disease (ILD) (N = 15), obesity (N = 15) and healthy controls (N = 16) were included. Compressed expiratory flow-volume curves (at mouth) and corresponding compression-free curves (thoracic) were recorded. Peak flow (PEF) and maximal flows at 75%, 50% and 25% of remaining forced vital capacity (MEF75, MEF50 and MEF25) were derived from both recordings. Their respective difference was assessed as an indicator of gas compression.ResultsIn all groups, significant differences between thoracic and mouth flows were found at MEF50 (p < 0.01). In controls, a significant difference was also measured at MEF75 (p <0.005), in emphysema subjects, at PEF and MEF75 (p < 0.05, p < 0.005) and in obese subjects at MEF75 (p <0.005) and MEF25 (p < 0.01). ILD patients showed the lowest difference between thoracic and mouth flows at MEF75 relative to controls and emphysema patients (p < 0.005, p < 0.001). Obese subjects did not differ from controls, however, the difference between thoracic and mouth flows was significantly higher than in patients with emphysema at MEF50 (p < 0.001) and MEF25 (p < 0.005).ConclusionsAlveolar gas compression distorts the forced expiratory flow volume curve in all studied groups at the middle fraction of forced expiratory flow. Consequently, mouth flows are underestimated and the reduction of flow measured at 75% and 50% of vital capacity is often considerable. However, gas compression profiles in stiff lungs, in patients with decreased elastic recoil in emphysema and in obesity differ; the difference between thoracic and mouth flows in forced expiration was minimal in ILD at the first part of forced expiration and was higher in obesity than in emphysema at the middle and last parts of forced expiration.

Factors associated with aerobic fitness in adolescents with asthma

In adolescents with asthma, information on factors associated with cardiorespiratory fitness levels is limited. The present study aimed to determine if objectively measured physical activity as well as potential relevant factors such as lung function, asthma exacerbations, use of inhaled corticosteroids or skin fold thickness are associated with direct measurements of peak oxygen uptake (V˙O2peak) in adolescents with asthma. From a nested case-control study at 13-years in the Environment and Childhood Asthma birth cohort study in Oslo, Norway, 86 13-years old adolescents with and 76 without asthma performed maximal running on a treadmill with V˙O2peak measured. The sum of four skin fold thicknesses was recorded, followed by wearing an activity monitor for four consecutive days. Lung function was measured by maximum forced expiratory flow-volume curves and body plethysmography. Asthma exacerbations and use of medication were registered by parental structured interview. Data were analysed using multiple regression analysis. Vigorous physical activity (coefficients with 95% confidence intervals; 1.73 (0.32, 3.14)) and skin fold thickness -0.35 (-0.41, -0.28)) were significantly associated with V˙O2peak in adolescents with asthma. Neither use of inhaled corticosteroids, lung function nor number of asthma exacerbations was associated with V˙O2peak when taking physical activity and skin fold thickness into account. In the adolescents without asthma only skin fold thicknesses was negatively associated with V˙O2peak -3.5 (-4.1, -2.8). V˙O2peak appears to be determined by vigorous physical activity level in Norwegian adolescents with asthma and not by asthma-related factors such as use of inhaled corticosteroids, lung function nor number of asthma exacerbations.

Effects of posture on lung function in obese children

Forced expiratory manoeuvres are recommended performed in sitting posture; however, standing posture has been reported to be usually more advantageous since any diaphragmatic restriction associated with obesity is reduced. Information on the effect of posture on forced expiratory manoeuvres in obese children is lacking. To determine whether lung function measured in standing compared with sitting posture is increased in overweight and obese children. One hundred fifteen overweight (n = 23) and obese (n = 92) children (7-17 years old) performed forced expiratory flow-volume manoeuvres in sitting and standing posture in random order. Forced expiratory volume in 1 s (FEV(1) ), forced vital capacity (FVC) and forced expiratory flow after 50% of FVC (FEF(50) ) was significantly higher in sitting compared with standing posture [0.8, 1.1 and 2.2 percentage change in absolute values (all with P < 0.05)]. FEV(1) /FVC and peak expiratory flow were not significantly different measured in sitting and standing posture; 95%-99% of the variance were explained by differences among individuals (all with P < 0.0001). In conclusion, FEV(1) , FVC and FEF(50) were all significantly higher when measured in sitting compared with standing posture; however, the improvements were of little clinical significance. These findings confirm that sitting posture is appropriate in obese children when performing forced expiratory flow-volume manoeuvres.

Potential misinterpretation of infant lung function unless prospective healthy controls are studied

SUMMARY RATIONALE: Reliable interpretation of pulmonary function tests relies on appropriate reference data, which remain very limited for infants. This study aimed to assess the validity of published reference equations for forced expiratory flow-volume (FEFV) data in infants when using current, commercially available equipment, and how this could impact on interpretation of results from infants with lung disease. The Jaeger Masterscreen BabyBody (v4.67) equipment was used to perform partial and raised volume FEFV maneuvers in healthy infants and those with cystic fibrosis (CF). Results were initially expressed as Z-scores using published reference equations. Multilevel modeling was used to calculate differences, if any, from predicted scores in healthy infants. Data were available from 66 healthy full term infants on 89 test occasions; [median (range) postnatal age 49.4 (12-101) weeks. All FEFV outcomes were significantly lower than predicted, with mean (SD) Z-score differences of -0.4 (1.1) for FVC; -0.6 (1.0) for FEV(0.5); -1.0 (1.0) for FEF(25-75) and -1.4 (1.1) for V'(maxFRC). After adjustments using multilevel modeling, mean Z-scores were within 0.1 (SD approximately 1.0) predicted for all outcomes in healthy infants. Among 50 infants with CF, studied on 85 test occasions, results were "abnormal" (<-1.96 Z-scores) on 35 (41%) and 37 (45%) test occasions for FEV(0.5) and FEF(25-75), respectively, when using published equations. This fell to 24 (28%) and 20 (24%), respectively, after adjustment. Dependence on published equations for interpreting FEFV data in infants may lead to misinterpretation of lung function status, which could impact adversely both in the research setting and on clinical management. Use of a contemporary control group or establishment of equipment-specific reference data is essential for meaningful interpretation of infant lung function data.

Asthma symptoms in rural living Tanzanian children; prevalence and the relation to aerobic fitness and body fat

To determine the prevalence of asthma symptoms in children from a rural district in North-Tanzania, and their relationship to aerobic fitness and body fat. In Manyara region in Tanzania, children (aged 9-10 years) were randomly selected to participate in the present cross-sectional study. Hundred and seventy two participants completed a video questionnaire showing the symptoms and signs of asthma. Lung function was measured by maximum forced expiratory flow-volume curves. Aerobic fitness was estimated from a standardized indirect maximal cycle ergometer test and sum of three skinfolds reflected body fat. Twenty four per cent reported asthma symptoms last year. Severe wheezing attacks last year were reported in 5% of the participants. Thirty seven per cent of the participants were underweight. Underweight children had significantly lower (P < 0.02) lung function (per cent of predicted). Lower body fat was associated with higher occurrence of asthma symptoms (odds ratio and 95% CI; 0.45 (0.22-0.95; P = 0.04). Aerobic fitness was not associated with asthma symptoms. More than every fifth 9-10 year old child from a rural district in North-Tanzania reported asthma symptoms. Lower body fat was associated with higher occurrence of asthma symptoms, but aerobic fitness was not associated with asthma symptoms.

Non-invasive forced expiratory flow–volume curves to measure lung function in cats

Forced expiratory flow-volume curves were performed in 15 cats using the non-invasive thoracic compression techniques developed for use in human infants. Cats breathed through a face mask and pneumotachygraph from which flow and volume were obtained. Thoracic compression was applied from an inflatable bag in a non-expandable jacket surrounding the animal. Bag inflation at end inspiration was initiated by a computer pulse to a pressurized chamber. Processed signals from the pneumotachygraph determined maximum-forced expiratory flow at lung volume equivalent to functional residual capacity (FRC), termed V'maxFRC. Different compression pressures were used, and the highest value from a technically satisfactory flow-volume loop was taken as the result. Mean (+/- 95% CI) V'maxFRC was 422 (369-475) ml/s. Compared with infants of similar weight (V'maxFRC approximately 180 ml/s), cats had a much higher V'maxFRC. Tests repeated another day showed a mean (+/-95% CI) percentage difference between paired tests to be 2.8 (-12.6, +18.3)%. Non-invasive forced expiratory flow-volume measurements can be reliably obtained in sedated cats.

SENSITIVITY OF SPIROMETRIC MEASUREMENTS TO DETECT AIRWAY OBSTRUCTION IN INFANTS

Jones MH, Howard J, Davis S, Kisling J, Tepper R. Am J Respir Crit Care Med . 2003;167:1283–1286 To demonstrate the ability of forced expiratory flow (FEF) volume curves from increased lung volumes to discriminate among infants with differing severities of respiratory symptoms and to compare the ability of variables used to quantify the flow volume curves to detect airway obstruction. Infants referred to a pediatric pulmonary clinic were classified into 2 groups. Group 1 patients had previous respiratory symptoms but …

Effects of paternal tobacco smoking on children's pulmonary function

Rationale Since studies on the effects of paternal smoking on children's pulmonary function have yielded inconsistent result, we conducted a cross-sectional study to investigate the effects of paternal smoking on children's pulmonary function in urban communities of Seoul, Korea. Methods Our analysis included 1,005 children 6 to 12 years of age whose mothers were never-smokers. At study enrollment, parents or guardians of each subject completed a questionnaire, and lung function was measured spirometrically with maximum forced expiratory flow-volume maneuvers. Results Children whose fathers smoked ≥30 cigarettes/day showed deficits in maximum midexpiratory flow (MMEF, −141 ml, 5.9% reduction, p=0.038). Conclusions Paternal smoking is associated with small but statistically significant deficits in MMEF in school aged children in this urban Korean population.

Sensitivity of spirometric measurements to detect airway obstruction in infants.

We evaluated the ability of forced expiratory flow volume curves from raised lung volumes to assess airway function among infants with differing severities of respiratory symptoms. Group 1 (n = 33) had previous respiratory symptoms but were currently asymptomatic; group 2 (n = 36) was symptomatic at the time of evaluation. As a control group, we used our previously published sample of 155 healthy infants. Flow volume curves were quantified by FVC, FEF50, FEF75, FEF25-75, FEV0.5, and FEV0.5/FVC, which were expressed as Z scores. All variables except FVC had Z scores that were significantly less than zero and distinguished groups 1 and 2 with progressively lower Z scores. The mean Z scores of the flow variables (FEF50%, FEF75%, and FEF25-75%) were more negative than the Z scores for the timed expired volumes (FEV0.5 or FEV0.5/FVC) for both groups. In general, measures of flow identified a greater number of infants with abnormal lung function than measures of timed volume; FEF50 had the highest performance in detecting abnormal lung function. In summary, forced expiratory maneuvers obtained by the raised volume rapid compression technique can discriminate among groups of infants with differing severity of respiratory symptoms, and measures of forced expiratory flows were better than timed expiratory volume in detecting abnormal airway function.

Effects ofIn Uteroand Environmental Tobacco Smoke Exposure on Lung Function in Boys and Girls with and without Asthma

To investigate whether the effects of in utero exposure to maternal smoking and environmental tobacco smoke (ETS) exposure on lung function vary by sex or asthma status, we examined medical history and tobacco smoke exposure data for 5,263 participants in the Children's Health Study. At study enrollment, parents or guardians of each subject completed a questionnaire, and lung function was measured spirometrically with maximum forced expiratory flow-volume maneuvers. To assess the in utero effects of maternal smoking and ETS exposure on lung function, we used regression splines that accounted for the nonlinear relationship between pulmonary function, height, and age. In utero exposure to maternal smoking was independently associated with deficits in lung function that were larger for children with asthma. Boys and girls with a history of in utero exposure to maternal smoking showed deficits in maximum midexpiratory flow (MMEF) and a decrease in the FEV(1)/FVC ratio. As compared with children without asthma, boys with asthma had significantly larger deficits from in utero exposure in FVC, MMEF, and FEV(1)/FVC, and girls with asthma had larger decreases in FEV(1)/FVC. The effect of ETS exposure varied by children's gender and asthma status. Deficits in flows associated with current ETS exposure were present in children with and without asthma but were significant only among children without asthma. Past ETS exposure was associated with reduced FEV(1), MMEF, and FEV(1)/FVC among boys with asthma. In contrast, past ETS exposure was associated with decreased flow rates in girls without asthma. In summary, both in utero exposure to maternal smoking and ETS exposure were associated with persistent deficits in lung function. The effects of in utero exposure were greatest among children with asthma.

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.

Crying significantly reduces absorption of aerosolised drug in infants

AIMTherapeutic aerosols are routinely used in the management of infant obstructive airways disease. Infants often become distressed during administration. The aim of this study was to determine the influence of...

Is ventilation during maximal exercise limited by dynamic airway closure?

A study was undertaken to find if the reason why horses hypoventilate when running is that they experience expiratory flow limitation due to dynamic airway closure. To test this hypothesis, we measured peak expiratory flows on a Thoroughbred galloping on a treadmill and hypoventilating and compared those flows with the peak dynamically-limited flow that the same horse could achieve during a forced expiratory flow-volume manoeuvre. At the approximate lung volumes at which the horse was ventilating while running, it did not appear to be mechanically limited and appeared to have reserve capacity available potentially to increase its expiratory flow.

Expiratory Flow Limitation During Spontaneous Breathing: Comparison of Patients With Restrictive and Obstructive Respiratory Disorders

Comparison of tidal and forced expiratory flow-volume (V-V) curves has inherent technical problems in the characterization of expiratory flow limitation. In addition, patients with neuromuscular disorders may be unable to perform forced expiratory maneuvers because of muscle weakness or poor coordination. A recently developed simple, noninvasive technique that avoids these problems was used to detect expiratory flow limitation at rest in 19 seated patients with restrictive respiratory (13 with musculoskeletal) disorders (RD) and 20 with chronic obstructive airway disease (COAD). A large rehabilitation hospital for the care of patients with chronic musculoskeletal and respiratory disorders. The method consisted of applying negative pressure of about 5 cm H2O at the airway opening during expiration and comparing the ensuing V-V curve to the preceding tidal V-V curve. While nine patients with COAD demonstrated flow limitation, only one patient with RD did so. Patients with expiratory flow limitation exhibited various contours of the control tidal expiratory V-V curve. Thus, inspection of the tidal V-V curve is not a reliable means of detecting expiratory flow limitation. We conclude that expiratory flow limitation during resting breathing is common in patients with COAD but not in patients with RD.

Shape and position of the complete dose-response curve for inhaled methacholine in normal subjects.

Plateaus on the inhalation concentration-response curve have been described in normal subjects and patients with mild asthma. To determine the prevalence of plateaus on inhalation concentration-response curves, and the position of the curves in normal subjects, we measured complete dose-response curves for methacholine (1 mg/ml to 256 mg/ml) in 73 nonatopic, nonsmoking, nonasthmatic normal subjects between the ages of 20 and 76 yr. Measurements included FEV1, maximal expiratory flow at 50% and 30% of vital capacity on partial and complete forced expiratory flow-volume curves (Vmax50p, Vmax50c, Vmax30p, Vmax30c) and pulmonary resistance (RL). Plateau responses, EC50 values and slopes were measured. Plateaus were present in 25, 27, 24, 34, 35, and 16 subjects for FEV1, Vmax50c, Vmax30c, Vmax50p, Vmax30p, and RL, respectively. In those who achieved a plateau, the mean maximal decrease in FEV1 (+/- SD) was 21 +/- 8%, in Vmax50c it was 46 +/- 16%, in Vmax50p it was 67 +/- 12%, in Vmax30c it was 58 +/- 21%, and in Vmax30p it was 75 +/- 15%, and the increase in RL was 213 +/- 89%. In summary, the results of this study showed that easily identifiable plateaus develop on the inhalation concentration-response curves of approximately 40% of normal subjects after only moderate decreases in maximum flow and increases in RL. Maximal response at the plateau was greater on partial flow-volume curves and at lower lung volumes (30% versus 50% of VC). Comparison of these data with data from patients at risk for airway hyperresponsiveness will allow definition of the mechanisms leading to airway hyperresponsiveness.