Single-breath Nitrogen Test Research Articles

Single breath nitrogen test as predictor of lung function decline and COPD over an 8-year follow-up

BackgroundThe single breath nitrogen (SBN2) test was proposed for early detection of “small airways disease” in the seventies. Few longitudinal studies have subsequently evaluated the relationships between SBN2 test measurements and lung function decline or COPD incidence. AimThis study evaluates whether SBN2 test abnormalities may be significant predictors of lung function decline and COPD incidence over an 8-year follow-up. Study Design and MethodsIn this longitudinal study, 907 adults (20+ years old; 56% males) from the prospective Po River Delta epidemiological study underwent SBN2 test at baseline and spirometry testing at both baseline and follow-up 8-year apart. Multinomial and multiple regression models were used to assess associations of SBN2 indexes and rates of FEV1 decline or risk of COPD incidence over time, after adjusting for sex, height and baseline age, FEV1 and smoking status. COPD was defined according to either GOLD or ATS-ERS criteria. ResultsAmong SBN2 indexes, only the slope of alveolar plateau (N2-slope) was significantly associated with rates of FEV1 decline (7.93 mL/year for a one-unit change in N2-slope, p<0.0001), and with an increased risk of developing COPD as defined by GOLD (RR 1.81, 95%CI 1.29-2.52, mild; RR 2.78, 95%CI 1.70-4.53, moderate or severe obstruction) and ATS-ERS criteria (RR 1.62, 95%CI 1.14-2.29, mild; RR 3.40, 95%CI 1.72-6.73, moderate or severe obstruction). ConclusionIn this population-based study, N2-slope from SBN2 test is a significant predictor of lung function decline and COPD incidence over an 8-year follow-up, confirming the role of the “small airways disease” in the natural history of COPD.

Prediction of COPD by the single-breath nitrogen test and various respiratory symptoms.

Early identification of subjects running an increased risk of contracting COPD enables focus on individual preventive measures. The slope of the alveolar plateau of the single-breath nitrogen washout test (N2-slope) is a sensitive measure of small-airway dysfunction. However, its role remains unexplored in predicting hospital admission or death related to COPD, i.e. incident COPD events, in relation to the presence of various respiratory symptoms.A random population sample of 625 men, aged 50 (n=218) or 60 years (n=407), was followed for 38 years for incident COPD events. At baseline, a questionnaire on respiratory symptoms and smoking habits was collected, spirometry and the single-breath nitrogen test were performed, and the N2-slope was determined. Proportional hazard regression (Cox regression) analysis was used for the prediction model.The N2-slope improved the prediction of COPD events significantly beyond that of respiratory symptoms weighted all together and other covariates (hazard ratio 1.63, 95% CI 1.20–2.22; p<0.005), a prediction applicable to subjects without (p=0.001) and with (p<0.05) airway obstruction. Dyspnoea and wheezing were the most predictive symptoms. The combination of the N2-slope and number of respiratory symptoms notably resulted in an effective prediction of incident COPD events even in nonobstructive subjects, as evidenced by a predicted incidence of ∼70% and ∼90% for a very steep N2-slope combined with many respiratory symptoms in subject without and with airway obstruction, respectively.The alveolar N2-slope should be considered in the critical need for further research on early diagnosis of COPD.

Prediction of COPD and Related Events Improves by Combining Spirometry and the Single Breath Nitrogen Test

Chronic obstructive pulmonary disease (COPD) develops in small airways. Severity of small airway pathology relates to progression and mortality. The present study evaluated the prediction of COPD of a validated test for small airway disease, i.e. a slope of the alveolar plateau of the single breath nitrogen test (N2-slope). The N2-slope, spirometry, age, smoking habits, and anthropometric variables at baseline were obtained in a population-based sample (n = 592). The cohort was followed for first COPD events (first hospital admission of COPD or related conditions or death from COPD) during 38 years. During follow-up, 52 subjects (8.8%) had a first COPD event, of which 18 (3.0%) died with a first COPD diagnosis. In the proportional hazard regression analysis adjusted for age and smoking habits, the cumulative COPD event incidence increased from 5% among those with high forced expired volume in one second (FEV1) to 25% among those with low FEV1, while increasing from 4% among those with the lowest N2-slope to 26% among those with the highest. However, combining the N2-slope and FEV1 resulted in considerable synergy in the prediction of first COPD event and even more so when taking account of smoking habits. The cumulative COPD event incidence rate was 75% among heavy smokers with the highest N2-slope and lowest FEV1, and less than 1% among never smokers with the lowest N2-slope and highest FEV1. Thus, combining the results of the single breath N2-slope and FEV1 considerably improved the prediction of COPD events as compared to either test alone.

Airway occlusion assessed by single breath N2 test and lung P-V curve in healthy subjects and COPD patients

PurposeTo determine whether the analysis of the slow expiratory transpulmonary pressure–volume (PL-V) curve provides an alternative to the single-breath nitrogen test (SBN) for the assessment of the closing volume (CV). MethodsSBN test and slow deflation PL-V curve were simultaneously recorded in 40 healthy subjects and 43 COPD patients. Onset of phase IV identified CV in SBN test (CVSBN), whereas in the PL-V curve CV was identified by: a) deviation from the exponential fit (CVexp), and b) inflection point of the interpolating sigmoid function (CVsig). ResultsIn the absence of phase IV, COPD patients exhibited a clearly discernible inflection in the PL-V curve. In the presence of phase IV, CVSBN and CVexp coincided (CVSBN/CVexp=1.04±0.04 SD), whereas CVsig was systematically larger (CVsig/CVexp=2.1±0.86). ConclusionThe coincidence between CVSBN and CVexp, and the presence of the inflection in the absence of phase IV indicate that the deviation of the PL-V curve from the exponential fit reliably assesses CV.

The single breath nitrogen test and mortality – A 38 years follow up

BackgroundSpirometry data predict mortality, but are less sensitive to detect dysfunction in small airways as compared to the slope of phase III (the N2 slope) of the single breath nitrogen test. The association between the N2 slope and mortality has been studied with conflicting results. In the present study the prognostic importance of the N2 slope was tested taking spirometry variables into account. MethodsA systematic general population sample of 595 middle-aged men had a baseline investigation with lung function tests including spirometry and the N2 slope. Age, smoking, and anthropometry variables were registered. The cohort was followed up regarding survival for 38 years. ResultsThe sample was subdivided by tertiles of the N2 slope. A proportional hazards regression analysis was performed for each group of covariates: anthropometric, smoking variables, and spirometry variables, after accounting for age. Covariates with significant impact on mortality and the highest chi-square levels were smoking habit score and forced expired volume in 1 s corrected for height. These variables, in addition to age and the N2 tertiles were entered into a final proportional hazards regression analysis. In this multivariate model, mortality was significantly related to age (p < .0001), smoking habit score (p < .0001) and the N2 tertiles (p = .0004), but not to FEV1 when N2 slope was allowed for in the model. ConclusionsDysfunction in small airways as measured by the N2 slope is significantly associated with overall mortality in middle-aged men, and outrivals spirometry as a predictor in multivariate analysis.

Closing volume and flow volume abnormalities in alpha(1)-antitrypsin phenotype groups in a community population.

Alpha1-antitrypsin phenotype groups, found in a community population studied in Tucson, were compared by using the maximum expiratory flow volume curve and the single-breath nitrogen test, alone and in combination. Subjects 25 to 54 years of age were used for the comparison, among whom there were 728 Pi M, 29 Pi MZ, and 62 Pi MS phenotypes. None of the flow volume parameters or closing volume parameters was able to differentiate among the phenotype groups; subjects in groups heterozygous for alpha1-antitrypsin did not differ from individuals homozygous for Pi M with regard to any or all flow volume or closing volume parameters.

Relationship between CT air trapping criteria and lung function in small airway impairment quantification

BackgroundSmall airways are regarded as the elective anatomic site of obstruction in most chronic airway diseases. Expiratory computed tomography (CT) is increasingly used to assess obstruction at this level but there is no consensus regarding the best quantification method. We aimed to evaluate software-assisted CT quantification of air trapping for assessing small airway obstruction and determine which CT criteria better predict small airway obstruction on single breath nitrogen test (SBNT).MethodsEighty-nine healthy volunteers age from 60 to 90 years old, underwent spirometrically-gated inspiratory (I) and expiratory (E) CT and pulmonary function tests (PFTs) using SBNT, performed on the same day. Air trapping was estimated using dedicated software measuring on inspiratory and expiratory CT low attenuation area (LAA) lung proportion and mean lung density (MLD). CT indexes were compared to SBNT results using the Spearman correlation coefficient and hierarchical dendrogram analysis. In addition, receiver operating characteristic (ROC) curve analysis was performed to determine the optimal CT air-trapping criterion.Results43 of 89 subjects (48,3%) had dN2 value above the threshold defining small airway obstruction (i.e. 2.5% N2/l). Expiratory to inspiratory MLD ratio (r = 0.40) and LAA for the range −850 -1024 HU (r = 0.29) and for the range −850 -910 HU (r = 0.37) were positively correlated with SBNT results. E/I MLD was the most suitable criterion for its expression. Expiratory to inspiratory MLD ratio (E/I MLD) showed the highest AUC value (0.733) for small airway obstruction assessment.ConclusionAmong all CT criteria, all correlating with small airway obstruction on SBNT, E/I MLD was the most suitable criterion for its expression in asymptomatic subjects with mild small airway obstructionTrial registrationRegistered at Clinicaltrials.gov, identifier: NCT01230879.

Impact of hemodialysis on dyspnea and lung function in end stage kidney disease patients.

Background. Respiratory symptoms are usually underestimated in patients with chronic kidney disease undergoing maintenance hemodialysis. Therefore, we set out to investigate the prevalence of patients chronic dyspnea and the relationship of the symptom to lung function indices. Methods. Twenty-five clinically stable hemodialysis patients were included. The mMRC dyspnea scale was applied before and after hemodialysis. Spirometry, single breath nitrogen test, arterial blood gases, static maximum inspiratory (P imax⁡) and expiratory (P emax⁡) muscle pressures, and mouth occlusion pressure (P 0.1) were also measured. Results. Despite normal spirometry, all patients (100%) reported mild to moderate degree of chronic dyspnea pre which was reduced after hemodialysis. The sole predictor of (Δ) mMRC was the (Δ) P 0.1 (r = 0.71, P < 0.001). The P imax⁡ was reduced before and correlated with the duration of hemodialysis (r = 0.614, P < 0.001), whilst after the session it was significantly increased (P < 0.001). Finally (Δ) weight was correlated with the (Δ) P imax⁡ %pred (r = 0.533, P = 0,006) and with the (Δ) CV (%pred) (r = 0.65, P < 0.001). Conclusion. We conclude that dyspnea is the major symptom among the CKD patients that improves after hemodialysis. The neuromechanical dissociation observed probably is one of the major pathophysiologic mechanisms of dyspnea.

Small-airways dysfunction associates with respiratory symptoms and clinical features of asthma: A systematic review

Traditionally, asthma has been considered a disease that predominantly involves the large airways. Today, this concept is being challenged, and increasing evidence has become available showing that abnormalities in the small airways also contribute to the clinical expression of asthma. The small airways can be affected by inflammation, remodeling, and changes in the surrounding tissue, all contributing to small-airways dysfunction. In this article we have performed a systematic review of the literature on the association between small-airways dysfunction and clinical signs and symptoms of asthma. This review shows that small-airways dysfunction associates with worse control of asthma, higher numbers of exacerbations, the presence of nocturnal asthma, more severe bronchial hyperresponsiveness, exercise-induced asthma, and the late-phase allergic response. Importantly, small-airways dysfunction can already be present in patients with mild asthma. Our review provides suggestive evidence that a better response of the small airways to inhaled steroids or montelukast associates with better asthma control. For this reason, an early recognition of small-airways dysfunction is important because it enables the physician to start timely treatment to target the small airways. It is important to develop simpler and more reliable tools (eg, questionnaires or bronchial provocation tests with small-particle stimuli) to assess the presence and extent of small-airways dysfunction in daily clinical practice.

Respiratory symptoms and peripheral airways disease in a cross-sectional study on a random population sample

ObjectivesRespiratory symptoms are associated with spirometry results but more strongly with smoking history, suggesting that alterations in the lung other than those revealed by spirometry contribute to cause symptoms. Smoking...

Prediction of BOS by the single-breath nitrogen test in double lung transplant recipients

BackgroundThe present study analyses the ability of the alveolar slope of the single-breath nitrogen washout test (N2-slope) to diagnose and predict the development of the bronchiolitis obliterans syndrome (BOS).MethodsWe present a retrospective analysis of 61 consecutive bilateral lung or heart-lung transplant recipients who were followed at regular control visits during a three year follow-up. The operating characteristics of the N2-slope to diagnose BOS and potential BOS (BOS 0-p) and to predict BOS were determined based on cut off values of 95% specificity.ResultsThe sensitivity of the N2-slope to identify BOS was 96%, and BOS 0-p 100%. The predictive ability to predict BOS with a N2-slope > 478% of the predicted normal was 56%, and if combined with a coincident FEV1 < 90% of the basal value, the predictive ability was 75%.ConclusionsThe predictive ability of either the N2-slope or of FEV1 to diagnose BOS is limited but the combination of the two appears useful. Follow-up protocols of bilateral lung and heart-lung transplant recipients should consider including tests sensitive to obstruction of the peripheral airways.

Pathophysiology of Evolution of Small Airways Disease to Overt COPD

ABSTRACTBackground: The slope of phase III (single breath nitrogen test), an index of ventilation inhomogeneity, has been used for early detection of COPD. Tidal airway closure (cyclic opening and closure of the peripheral airways during tidal breathing; ACT) and expiratory flow limitation (attainment of maximal expiratory flow during tidal expiration; EFLT) cause small airways disease (SAD). The relationships of these indices with COPD severity may reflect the progress from SAD to overt COPD. Methods: In this cross-sectional study we have assessed for the first time the phase III slope, ACT and EFLT in 10 smokers with normal spirometry (group O) and 40 COPD patients with GOLD scores from I to IV. Results: In most group O smokers the phase III slope was increased, and further increased with GOLD severity (up to 800%pred in GOLD IV). A close correlation was found of slope with GOLD (r = 0.77). ACT was absent in smokers with normal spirometry and in most patients with mild COPD. EFLT first appeared in GOLD II patients and its prevalence progressively increased in GOLD III and IV patients. Conclusions: Most group O smokers exhibit increased phase III. With overt COPD there is a progressive increase in phase III and reduction of FEV1/FVC ratio from GOLD I to IV. A reduction of FEV1 occurs from GOLD stage II. As the disease progresses from moderate to severe, there is an increasing presence of ACT. Tidal EFL, with dynamic hyperinflation and severe dyspnea is present only in GOLD III and IV.

Effects of extra‐fine inhaled beclomethasone/formoterol on both large and small airways in asthma

Airway inflammation in asthma involves both large and small airways, and the combination of inhaled corticosteroids (ICS) and long acting beta-2 agonists (LABA) is the mainstay of therapy. Available inhaled combinations differ in terms of drug delivery to the lung and the ability to reach small airways. To evaluate whether treatment with an extra-fine inhaled combination provides additional effects vs a nonextra-fine combination on airway function. After a 1- to 4-week run-in period, patients with asthma were randomized to a double blind, double dummy, 12-week treatment with either extra-fine beclomethasone/formoterol (BDP/F) 400/24 microg daily or fluticasone propionate/salmeterol (FP/S) 500/100 microg daily. Methacholine (Mch) bronchoprovocation challenge and single breath nitrogen (sbN2) test were performed. Thirty patients with asthma (15 men), mean age 43, mean forced expiratory volume in the first second (FEV(1)) 71.4% of predicted, were included. A significant increase (P < 0.01) versus baseline was observed in predose FEV(1) in both BDP/F and FP/S groups (0.37 +/- 0.13 l and 0.36 +/- 0.12 l, respectively). PD(20)FEV(1) Mch improved significantly from 90.42 (+/-30.08) microg to 432.41 (+/-122.71) microg in the BDP/F group (P = 0.01) but not in the FP/S group. A trend toward improvement vs baseline was observed for BDP/F in closing capacity (CC), whereas no differences were recorded in other sbN(2) test parameters. The findings of this pilot study suggest that an extra-fine inhaled combination for the treatment of asthma has beneficial effects on both large and small airways function as expressed by Mch and sbN(2) tests.

HUMAN TRACHEOBRONCHIAL DEPOSITION AND EFFECT OF A HISTAMINE AEROSOL INHALED BY EXTREMELY SLOW INHALATIONS

Twelve subjects inhaled the same amounts of histamine aerosol in both a normal provocation test and in a test with extremely slow inhalations (ESI), a method which gives deposition in small airways. The purpose was to compare dose-effect relationships in large (diameter >1 mm) and small (diameter <1 mm) ciliated airways. The effect on large airways was estimated by measurement of airway resistance ( R aw), and the effect on small airways was measured by the single-breath nitrogen test phase III slope (N 2-delta). Mouth and throat deposition of the histamine aerosol was calculated from human experimental data, and deposition in the lower airways was calculated using a computerised model for particle deposition in the lungs. The study showed that only half the dose inhaled with ESI (0.65 mg) of that inhaled with normal inhalations (1.3 mg), was needed to obtain the same degree of obstruction for large airways in spite of that the calculated deposition in large airways was 40% higher for normal inhalations than for ESI. The threefold stronger effect in large airways was probably caused by a more uniform distribution of particles within each generation with ESI compared to normal inhalations with particle deposition near the bifurcation. There was slightly higher N 2-delta with ESI, and the calculated dose to the smaller airways for the same inhaled dose was 10 times higher with ESI than with normal inhalations.

HUMAN TRACHEOBRONCHIAL DEPOSITION AND EFFECT OF A CHOLINERGIC AEROSOL INHALED BY EXTREMELY SLOW INHALATIONS

Ten subjects inhaled the same amounts of cholinergic aerosol of a mass median diameter (MMD) of 7.7 mum in a normal provocation test and in a test with extremely slow inhalations (ESI). This new technique using ESI and large droplets/particles gives a high degree of deposition in small ciliated airways which cannot be obtained by using small particles. The purpose was to compare measured effects with calculated doses of the aerosol in large and small ciliated airways. The effect on large airways was measured by airway resistance (Raw), and the effect on small airways was measured by the phase III slope of single breath nitrogen test (N2-delta). Mouth and throat deposition was calculated from human experimental data, and deposition of the cholinergic aerosol into large and small airways was calculated, using a computerized lung model. The study showed that the extremely slow inhalation caused a larger effect on Raw and tendency to a larger effect on N2-delta compared to the effect in the normal provocation. Deposited dose in the large airways, in percent of inhaled dose, was calculated to be 25-33% for normal inhalation and 20-24% for ESI. Calculated deposited dose in the small airways (bronchioles; generations 12-16) was 1.8-3.4% for normal inhalation and 18-25% for ESI. For large airways a stronger effect was induced by ESI, perhaps by the more uniform distribution of particles within each generation, compared to normal inhalations when particles deposit near the bifurcations. Concerning the small airways, N2-delta did not differ significantly between normal and ESI provocations, indicating that they did not react much on cholinergic exposure. We believe that our approach using ESI for small airway deposition of a nebulized aerosol can be of value for estimating the effects of various substances on large and small airways.

Altered lung mechanics after double-lung transplantation.

We studied lung mechanics and small airways function in 15 patients after double-lung (DL) transplantation. Patients were classified as stable (DL-S, n = 11), or having obliterative bronchiolitis syndrome (DL-OBS, n = 4). We performed pulmonary function tests (PFT), measured slope of phase 3 of the single-breath nitrogen test (N2SP3), and obtained pressure-volume curves and values: chord compliance (Cst,L), specific chord compliance (SCst,L), and elastic recoil pressure at 90% TLC. PFT showed mild restrictive pattern in DL-S and severe obstructive lung disease in DL-OBS. The N2SP3 measurement indicated small airways dysfunction in 82% of DL-S and in all DL-OBS patients. The Cst,L was 0.24 +/- 0.08 L/cm H2O in DL-S and 0.16 +/- 0.05 L/cm H2O in DL-OBS, both lower than control subjects 0.34 +/- 0. 09 L/cm H2O (p < 0.01; p < 0.001). Moreover, SCst,L was 0.09 +/- 0. 03 cm H2O-1 in DL-S, and 0.05 +/- 0.02 cm H2O-1 in DL-OBS, significantly lower than control subjects 0.12 +/- 0.02 cm H2O-1 (p < 0.05; p < 0.001). Elastic recoil at 90% TLC was normal in 14 of 15 patients. We found a linear correlation between N2SP3 and FEV1, and between FEV1 and Cst,L and SCst,L for combined DL-S and DL-OBS. Reduced compliance near FRC with normal elastic recoil at high lung volumes does not suggest changes in lung parenchyma. We speculate that structural or functional alterations in small airways may have contributed to low compliance measurements. Of special concern are our findings that DL-S had significant small airways dysfunction and reduced compliance in a pattern similar to the DL-OBS, only smaller in magnitude.

The single-breath nitrogen test in coal miners: factors associated with failure to perform

The single-breath nitrogen washout (SBN 2) test was used, along with spirometry, in the baseline examination of a longitudinal study in a cohort of active coal miners from North-eastern France. The procedure was computerized, allowing the technician to coach and encourage the subject, and excluding computation errors. While all miners performed satisfactory spirometry, a significant number were unable to meet the National Heart and Lung Institute recommendation concerning a 10% agreement of vital capacities. When the limits were set at ± 12%, 57 miners (24·2%) were still classified as failing to perform. When compared to those who succeeded, those failing proved to be significantly older, had more cumulated dust exposure, a higher prevalence of chronic cough and sputum, and a trend for more micronodulation on the chest radiographs. The ventilatory function did not differ between the two groups. These results confirm previous data on spirometric test failure concerning older age and respiratory symptoms, extending them to the SBN 2 test. The present study further indicates that dust exposure and roentgenologic pneumoconiosis nodulation are associated with failure to perform the SBN 2 test.

Airway closure measured by a technegas bolus and SPECT.

Absence of a maximal dose-response plateau and mathematical modeling suggest that asthmatic airways close during bronchoconstriction. Finding segmental areas affected by closure would be important in understanding asthmatic airway function. The aim of this study was to evaluate single-photon emission computed tomography (SPECT) as a method of investigating airway closure. Simultaneous SPECT transmission and emission studies were performed on a thoracic phantom to develop analysis methodology, and on 13 normal subjects after they inhaled a Technegas bolus from residual volume (RV), to measure airway closure. Single-breath nitrogen test values and lung volumes were measured. Airway closure was defined as the percent of Technegas-free lung volume (LVclosed). The mean error +/- 95% CI of the error, as determined by transmission scan, was 1.1 ml +/- 165 ml (0.8% +/- 15% lung volume) in the phantom studies, and 112 ml +/- 419 ml (4% +/- 31% of supine functional residual capacity [FRC]) in the human studies. LVclosed correlated with closing capacity (r = 0.86, p < 0.01 ) and closing volume (r = 0.86, p < 0.01), but not with RV/total lung capacity (TLC). This study indicates that simultaneous SPECT emission and transmission scans, using a Technegas bolus, are a valid method of measuring airway closure in vivo, with the added advantage of providing three-dimensional data that allow the detection of small, discrete areas of airway closure and determination of their volumes and shapes.

Detection of small airway dysfunction in asymptomatic smokers using aerosol bolus behavior.

Tests using inhaled particles assess ventilatory nonuniformities and may be sensitive to early changes in the small airways of cigarette smokers. We measured aerosol bolus behavior in 20 asymptomatic smokers and 20 age- and sex-matched nonsmokers for comparison with pulmonary function parameters including the single-breath nitrogen test. Narrow boluses containing 1-micron particles were introduced into 1-I breaths and inhaled to varying lung depths. We examined changes in bolus shape between inhalation and exhalation using plots of aerosol concentration versus respired volume for measurement of bolus dispersion, volumetric change in mean location (mean shift), and quantitative particle deposition. We found exhaled bolus dispersion to be significantly increased in smokers compared with nonsmokers. Volumetric mean shift was significantly different in smokers at shallow lung depths, with the center of bolus mass occurring later in exhalation. FEV1/FVC in smokers was significantly inversely correlated with dispersion at deeper lung depths and with mean shift at all lung depths. Smokers with abnormal spirometry (n = 4) or an abnormal single-breath nitrogen test (n = 7) had significantly increased dispersion compared with smokers with normal pulmonary function tests. We conclude that aerosol bolus dispersion is a useful tool for examination of small airway function in asymptomatic smokers.

Variability of the computerized single-breath nitrogen washout test in healthy adults. Results from a field survey in a French rural area.

Within-subject (difference between paired tests, or coefficient of variation [c. var.] of three consecutive measurements) and between-subjects (standard deviation of the mean group) variability were assessed for the variables derived from the single-breath nitrogen (SBN2) test in a group of healthy, asymptomatic subjects (n = 289) aged 20-64 years, from a rural area in North-East France. Duplicate measurements in 99 subjects showed excellent agreement between the two attempts (correlation coefficients between 0.94 and 0.98) for static lung volumes and the alveolar N2 slope (PIII); closing volumes (CV) were more variable (r = 0.77 for absolute value, 0.79 for % VC) while closing capacities (CC) were in intermediate position (r = 0.86 for absolute value, and 0.88 for % TLC). The variability of three consecutive measures in 190 subjects showed the coefficients of variation to be low for static volumes and closing capacity (2.4-7.4%) and higher for PIII (15.1%) and CV or CV/VC (18.2 and 17.8%). The analysis of variance did not detect significant differences between the three sets of measurements, with the exception of a progressive increase of vital capacity (VC), and decrease in residual volume (RV) from test 1 to test 3, the total lung capacity being the same. Variability was uninfluenced by age or sex, except a higher c. var. for female VC as compared to males (2.8 vs. 2.2%, P = 0.02) and a higher variability of TLC (2.9 vs. 2.3%, P = 0.03) and VC (2.8 vs. 1.9%, P = 0.003) in people older than 40 years as opposed to those younger than 40 years.