INTRODUCTION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Keywords: asthma; lung function; resistance

The detection of airflow obstruction and its reversibility is a routine procedure in pediatric pulmonary function laboratories. Measurement of forced expiratory volume in 1 s (FEV₁) is considered to be the basic test for the assessment of airway obstruction and its reversibility after bronchodilation (1). However, forced expiratory maneuvers are usually difficult in children younger than 6 yr of age because they require active cooperation from the patient. Because noninvasive techniques such as the forced oscillation technique (FOT) and the interrupter technique are performed during tidal volume breathing and require minimal cooperation, they appear more suitable for young children. Comparative evaluations of these methods in children are limited. We have previously defined useful criteria for FOT measurements, permitting reliable evaluation of bronchial obstruction and its reversibility in children as young as 3 yr (2). The interrupter technique has also been proposed by many authors as a promising method for young children. In particular, significant reversibility in resistance measured by the interrupter technique was reported in young children with asthma (3). However, no comparison between FOT and the interrupter technique in children with airway obstruction is available with reference to children without bronchial obstruction.

In this investigation we first compared the FOT and interrupter technique in children able to perform forced expiratory maneuvers, in order to evaluate the respective capacities of the two methods to identify children with an abnormal flow- volume curve and to detect a response to a bronchodilator in terms of changes in FEV₁. We then studied the respective usefulness of the FOT and interrupter technique for assessing bronchial obstruction and its reversibility in a population of young children unable to perform forced expiratory maneuvers.

	METHODS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Population

One hundred and eighteen children were addressed to our pulmonary function laboratory for evaluation of bronchial disease. The clinical diagnoses were asthma (n = 107) and chronic nocturnal cough (n = 11). The present study describes results of routine examinations performed for these children: spirometry and resistance measurements.

Ninety-three children (51 boys and 42 girls) aged from 5.0 to 15.8 yr (9.5 ± 0.3 yr) were able to perform forced expiratory maneuvers and underwent measurements of resistance with both the interrupter (Rint) and FOT methods (Group 1).

Twenty-five children (17 boys and 8 girls) aged from 3.3 to 7.3 yr (4.7 ± 0.2 yr) were unable to perform forced expiratory maneuvers but had acceptable Rint and FOT measurements (Group 2).

Study Design

Baseline measurements were obtained in all the children. A bronchodilator (200 µg of salbutamol) was administered with a metered-dose spacer device to 71 children in Group 1 and 23 children in Group 2. Postbronchodilator measurements were made after 15 min.

Measurement of Forced Expiratory Volumes and Flows

Flow-volume curves were recorded with a MedGraphics PF/Dx (Medical Graphics, St. Paul, MN) to determine FEV₁ and maximal expiratory flow at 50% of forced vital capacity (MEF₅₀). Acceptance of flow-volume curves was subject to international criteria (8). Results were expressed as the percentage of predicted values (9). As forced expiratory maneuvers might induce changes in bronchial motor tone, all resistance measurements were performed first.

Measurement of Respiratory Resistance

Respiratory impedance was determined by means of the standard forced oscillation technique as previously described (2, 10, 11). The child was equipped with a mouthpiece and nose-clip, and was comfortably seated with the head in the neutral position, and the cheeks firmly held by a parent. The child was asked to breathe quietly and to avoid swallowing. A pseudorandom noise signal mixing integer frequencies between 4 and 30 Hz was generated by a loudspeaker (Oscilink; Datalink-MSR, Rungis, France) and superimposed on the subject's spontaneous breathing. Mouth flow was sensed by a pneumotachograph (4700; Hans Rudolph, Kansas City, MO) connected to a differential pressure transducer (DP45 ± 2 cm H₂O; Validyne, Northridge, CA). Both signals were low-pass filtered and sampled at 128 Hz for measurement periods of 16 s. The time course of pressure and flow was monitored, and data associated with glottic closure, swallowing, or episodes of irregular breathing were discarded. Auto- and cross-spectra of flow and pressure were estimated for adjacent 4-s blocks and averaged over each 16-s period to yield a mean estimate of impedance (Zrs) and coherence function (²) for each frequency component. A measurement period was considered acceptable if ² was higher than 0.9 for more than 80% of the frequency components, which ensures in practice that at least one frequency between 4 and 6 Hz has a coherence above the 90% threshold. The real component of Zrs (Rrs), which is related to the resistive properties of the respiratory system, was submitted to linear regression analysis over the 4- to 16-Hz frequency range to obtain the intercept (R₀, resistance extrapolated to 0 Hz) and the slope of the linear relationship between Rrs and frequency (Slope) (Figure 1). Resistance at 16 Hz (R₁₆) was estimated by the equation: R₁₆ = slope × 16 + R₀. At least three acceptable 16-s measurement periods were averaged to yield the final value of the parameters. R₀ and R₁₆ do not have the same physiological interpretation. In children, Rrs displays a marked negative frequency dependence up to about 16 Hz. R₀ is thought to reflect airway and tissue Newtonian resistance plus the delayed airway resistance resulting from gas redistribution, whereas R₁₆ is thought to reflect only airway and tissue Newtonian resistance (12).

View larger version (14K): [in this window] [in a new window]   Figure 1.   Output of the forced oscillation and interruption devices. (A) Forced oscillation technique; the real component of Zrs (Rrs) was submitted to linear regression analysis over the 4-16-Hz frequency range to obtain the intercept (R0, resistance extrapolated to 0 Hz) and the slope of the linear relationship between Rrs and frequency (Slope). (B) Interrupter technique; mouth pressure was estimated from the pressure-time curve by two methods; first, Pint was obtained by back-extrapolating a linear regression of the postocclusion signal to an arbitrary time (T) after airway occlusion (see text for details); second, PintE was calculated as the postocclusion pressure occurring 100 ms after valve closure (T100).

The respiratory system resistance measured by the interrupter method (Rint) is known to reflect airway resistance down to the point where gas redistribution, when present, occurs (13). It was calculated as the ratio of alveolar pressure (estimated from mouth pressure during occlusion) to flow before interruption. As in the FOT, the child was equipped with a mouthpiece and nose clip and was comfortably seated with the head in the neutral position and the cheeks firmly held by a parent. Children breathed through the interrupter valve (Spiroteq; Dyn'R, Les Mureaux, France) and a Lilly pneumotachograph placed in series. During quiet tidal breathing, airflow was interrupted for 100 ms at a predetermined volume during the early phase of expiration. The occluding valve was actuated at 87.5% of the tidal volume calculated from the preceding respiratory cycle. The pneumotachograph was connected to a differential pressure transducer (Validyne) with a range of ± 2.5 kPa. Pressure and flow were sampled at a rate of 512 Hz. Interruptions were not performed during consecutive respiratory cycles but were each preceded by at least two regular breathing cycles. At least 10 occlusions were performed for each condition tested. Mouth pressure was estimated by two methods (14). The first method measured mouth pressure by back-extrapolating a linear regression of the postocclusion signal to an arbitrary time after airway occlusion. The mean pressure values for two 10-ms portions of the data centered on times 30 and 70 ms after valve closure were then linearly back-extrapolated to the time taken at 25% of the peak value of the first oscillation upstroke. P was the difference between the baseline and the back-extrapolated pressure (Figure 1). Rint was given by the equation: Rint = P/V', where V' is the flow measured at the mouth before interruption. The second method measured mouth pressure as the value at the postocclusion pressure occurring 100 ms after the onset of valve closure, that is, at the end of the alveolar pressure plateau. With this second method, the pressure-flow relationship was abbreviated as Rint_E.

The linear regression of the pressure-flow relationships obtained for consecutive measurements, including the 0-0 intercept, had a correlation coefficient independent of age (data not shown).

Data Analysis

Data are expressed as means ± SEM, unless otherwise indicated.

Agreement between evaluation of resistance by R₀, R₁₆, or Rint was determined on baseline measurements, using the methods of Bland and Altman (15). A paired t test was first used to compare the means of two data sets. The differences between R₀, R₁₆, and Rint for each subject were then calculated and plotted against their mean values. The limits of agreement were estimated by d ± 2s, where d represents the mean difference between two resistance parameters and s is the standard deviation.

Because there are no appropriate predicted values for the Rint and FOT variables (R₀ and R₁₆), predictive equations were established for our subjects by using multiple linear regression taking into account age, height, weight, and sex (described by a bimodal distribution: 1 = male, 2 = female). Variables that did not significantly reduce the total variance were discarded. A fitted value was then computed for each of the subjects as the ratio of the difference between the observed and predicted values to the standard deviation of the residuals: R₀(SD), R₁₆(SD), and Rint(SD), for R₀, R₁₆, and Rint, respectively. Thus, a resistance measurement expressed as the SD score represents a relatively high or low resistance value for a given sex, height, and weight. The SD score reflects, therefore, only the disease severity. Baseline resistance measurements were compared with baseline FEV₁ and MEF₅₀ values in Group 1, using univariate and multivariate regression analysis.

Children in Group 1 were then divided into subgroups according to whether significant parameters of the forced expiratory curve were < 80 or  80% of the predicted value. Comparisons between subgroups of children were made by analysis of variance (ANOVA). The sensitivity and specificity of possible cutoff points for R₀(SD), R₁₆(SD), and Rint(SD) in discriminating between children with lung function parameters < 80 or  80% of the predicted value were determined with receiver operator characteristic (ROC) curves (16). The ROC curves plot all possible combinations between the true-positive ratio (sensitivity; y axis) and the false-positive ratio (1  specificity; x axis) as one varies the definition of positivity. Different points were therefore obtained by varying R₀(SD), R₁₆(SD), and Rint(SD), values taken as the criterion for positivity. The best compromise between sensitivity and specificity was defined as the point of the curve closest to the upper left-hand corner.

After bronchodilator inhalation, changes in variables derived from the flow-volume curve were expressed as the ratio of the difference between postbronchodilator and baseline values over the predicted value (FEV₁ and MEF₅₀). Changes in FOT parameters were expressed as the difference between postbronchodilator and baseline fitted values [R₀(SD), R₁₆(SD), and Rint(SD)]. The sensitivity and specificity of R₀(SD), R₁₆(SD), and Rint(SD) values after bronchodilator inhalation were examined by using ROC curves according to the presence of significant reversibility, defined by FEV₁  10% (17).

	RESULTS

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

Comparison of Resistance Measurements

The acceptability of resistance measurements was excellent with the FOT and the interrupter method. The mean coefficients of variation of R₀ and R₁₆ were significantly lower than those of Rint: 7.9 ± 0.4, 8.8 ± 0.5, and 11.4 ± 0.6%, respectively (p < 0.0001), and were not influenced by age. Mean R₀ was significantly higher than mean Rint, and the difference was significantly more pronounced in younger children (Group 2) (Table 1). Mean R₁₆ was slightly but significantly lower than mean Rint.

The two methods used for estimating mouth pressure with the interrupter technique gave very close resistance values. The mean difference (standard deviation) between Rint_E and Rint was 0.3 (0.2) hPa · s · L¹, giving limits of agreement for Rint_E in relation to Rint of 0.1 to 0.7 hPa · s · L¹. Because of these small limits of agreement, and to simplify our results, only Rint results are presented in the following sections.

Comparison between individual FOT and Rint measurements showed that Rint gave lower resistance values, compared with R₀, especially in children with high baseline values (Figure 2). The mean difference (standard deviation) between R₀ and Rint was 2.1 (2.0) hPa · s · L¹, and was independently correlated with height (cm) (p = 0.0001) and MEF₅₀ (% predicted) (p = 0.0002), but not with FEV₁ (% predicted). Individual Rint values were closer to R₁₆ than to R₀. The mean difference (standard deviation) between R₁₆ and Rint was 0.4 (2.2) hPa · s · L¹, giving limits of agreement for R₁₆ in relation to Rint of 4.8 to 4.0 hPa · s · L¹.

View larger version (26K): [in this window] [in a new window]   Figure 2.   Agreement between FOT and Rint parameters measured at baseline. R0 (top) and R16 (bottom) are compared with Rint. The difference between the parameters (y axis) is plotted against the average value of the two parameters (x axis). Dashed lines represent the mean difference between two resistance parameters and the limits of agreement (2 standard deviations).

In the whole study population, multiple regression analysis of R₀ to anthropometric data showed a negative correlation of R₀ with height (p < 0.0001) and weight (p < 0.02), but not with age or sex, according to the following equation:

R₀ predicted (hPa · s · L¹) = 30.187  0.193 × height (cm)  0.115 × weight (kg)

The standard deviation of the residual was 2.48. Accordingly, R₀(SD) was computed as:

R₀(SD) (hPa · s · L¹) = (R₀ observed  R₀ predicted)/2.48

R₁₆ also correlated with height (p < 0.0001) and weight (p < 0.03), according to the following equation:

R₁₆ predicted (hPa · s · L¹) = 19.356  0.116 × height(cm) + 0.059 × weight (kg)

The standard deviation of the residual was 1.41. Rint correlated only with height (p < 0.0001), according to the following equation:

Rint predicted (hPa · s · L¹) = 16.145  0.074 × Height (cm)

The standard deviation of the residual was 1.39.

Comparison of Resistance and Spirometry Measurements

Baseline Measurements. Univariate linear regression showed that R₀(SD), R₁₆(SD), and Rint(SD), all correlated negatively with FEV₁ (% predicted) (p = 0.0005, p < 0.01, and p < 0.0001, respectively) and with MEF₅₀ (% predicted) (p < 0.0001, p < 0.002, and p < 0.0001, respectively). However, multivariate regression analysis with R₀(SD), R₁₆(SD), or Rint(SD) as the dependent variable and FEV₁ (% predicted) and MEF₅₀ (% predicted) as the independent variables showed that R₀(SD) correlated only with MEF₅₀ (p < 0.002), whereas Rint(SD) correlated only with FEV₁ (p < 0.03). R₁₆(SD) correlated preferentially, although not significantly, with MEF₅₀ (p < 0.06). Group 1 children were divided into three subgroups according to their baseline FEV₁ and MEF₅₀ values. Anthropometric data and pulmonary function test results are summarized in Table 2.

Taking the subgroup of children with both FEV₁ and MEF₅₀  80% of predicted values as reference, there was a gradual and significant increase in R₀(SD), R₁₆(SD), and Rint(SD) in children with low lung function parameter values, showing that children with decreased lung function parameters are also those with increased resistance values (Figure 3).

View larger version (17K): [in this window] [in a new window]   Figure 3.   FOT and Rint baseline parameters: Rint(SD), open columns; R0(SD) gray columns; R16(SD), solid columns. Children were divided into three subgroups according to their baseline FEV1 and MEF50 values: (A) children with both FEV1 and MEF50  80% of predicted values; (B) children with FEV1  80% but MEF50 < 80% of predicted values; (C) children with both FEV1 and MEF50 < 80% of predicted values.

Figure 4 shows ROC curves corresponding to the sensitivity and specificity of possible cutoff points for R₀(SD), R₁₆(SD), and Rint(SD) to discriminate between children with lung function parameters < 80 or  80% of predicted values. The best results were obtained for R₀(SD). At a given specificity, R₀(SD) always had the highest sensitivity for children with low spirometric parameters. To discriminate between children with MEF₅₀ < 80 or  80% of predicted values, the cutoff point of R₀(SD) was 0.10, corresponding to 63% sensitivity and 80% specificity for the identification of children with MEF₅₀ < 80%. To discriminate between children with FEV₁ < 80 and  80% of predicted values, the cutoff point of R₀(SD) was 0.30, corresponding to 67% sensitivity and 79% specificity. With the 0.10 cutoff, 80% of children with FEV₁ < 80% of predicted values were identified.

Changes after bronchodilator inhalation. Seventy-one children received 200 µg of inhaled salbutamol and underwent flow-volume curve, FOT, and Rint measurements 15 min later. Nineteen children were considered to have significant reversibility, defined by FEV₁  10%. The characteristics of these children are summarized in Table 3. Examples of measurements obtained in children with or without reversibility are presented in Figure 5. At baseline, responding children had higher R₀(SD) and R₁₆(SD) values than children with no significant response to salbutamol. No significant difference was observed for Rint(SD) measurements. After salbutamol inhalation the decrease in R₀(SD) and R₁₆(SD) was significantly more marked in children with a significant increase in FEV₁, so that the difference in postbronchodilator R₀(SD) and R₁₆(SD) values between the two groups disappeared (Table 3). Rint(SD) was also significantly more marked in children with a significant increase in FEV₁. There was a strong correlation, both for FOT and Rint measurements, between baseline values and changes with bronchodilator [r = 0.77, p < 0.0001; r = 0.62, p < 0.0001; and r = 0.60, p < 0.0001 for R₀(SD), R₁₆(SD), and Rint(SD), respectively], showing that high baseline resistance values are associated with significant reversibility toward lower values after salbutamol inhalation in this population.

View larger version (16K): [in this window] [in a new window]   Figure 5.   Examples of changes induced by bronchodilator inhalation in FOT measurements. Slopes calculated on the 4 to 16 Hz range and extrapolated to 0 Hz (R0) are represented. Four children with significant reversibility (A) and four children without significant reversibility (B) are presented before (left) and after (right) bronchodilator inhalation. Each child is represented either by a circle, a triangle, a square, or a diamond.

Figure 6 shows the ROC curves corresponding to the sensitivity and specificity of possible cutoff points for R₀(SD), R₁₆(SD) and Rint(SD), to discriminate between children with significant reversibility (defined by FEV₁  10%) and those with no significant reversibility. At a given specificity, changes in R₀(SD) always identified responder children with the highest sensitivity. A decrease in R₀(SD) of one or more [R₀(SD)  1] yielded 79% sensitivity and 71% specificity. Rint(SD) was less useful for discriminating between the two subgroups: a decrease of one or more [Rint(SD)  1] had 58% sensitivity and 79% specificity. As regards R₁₆(SD), the point of the curve closest to the upper left-hand corner corresponded to R₁₆(SD)  0.75 and yielded 63% sensitivity and 77% specificity.

View larger version (21K): [in this window] [in a new window]   Figure 6.   ROC curve corresponding to the sensitivity and specificity of possible cutoff points for R0(SD), Rint(SD), and R16(SD) for discriminating between children with significant reversibility (defined by an improvement of 10% or more in FEV1) and those with no significant reversibility. Squares = R0(SD); diamonds = Rint(SD); circles = R16(SD).

Comparison of FOT and Rint Measurements in the Youngest Children (Group 2)

Twenty-five children were unable to perform forced expiratory maneuvers. All but one were preschool children under 6 yr of age. As in Group 1, higher baseline FOT and Rint values were significantly associated with larger decreases after bronchodilation, suggesting basal airway obstruction. However, the best correlation between baseline values and changes after salbutamol inhalation (n = 23) was clearly obtained for R₀ measurements (Figure 7).

View larger version (23K): [in this window] [in a new window]   Figure 7.   Correlations between baseline R0(SD), Rint(SD), and R16(SD) values and changes after bronchodilator inhalation [R0(SD), Rint(SD), and R16(SD), respectively] in children unable to perform forced expiratory maneuvers (Group 2).

Significant reversibility in Group 1 children was best reflected by R₀(SD)  1. We thus tested the relevance of this R₀ cutoff to Group 2 children. When comparing Group 2 with Group 1 children according to their response to the bronchodilator, mean R₀(SD), R₁₆(SD), and Rint(SD) values were similar in the two groups (Table 4). No significant difference in Rint(SD) between children with and without significant reversibility was found in Group 2. Group 2 children with R₀(SD)  1 had significantly higher baseline R₀(SD), and R₁₆(SD) values than Group 2 children with R₀(SD) > 1, but, after salbutamol inhalation, R₀(SD) and R₁₆(SD) returned to values similar to postsalbutamol values in Group 2 children without significant reversibility (Figure 8). Baseline Rint(SD) values were not significantly different between the two subgroups.

View larger version (14K): [in this window] [in a new window]   Figure 8.   Individual R0(SD), Rint(SD), and R16(SD) values in children unable to perform forced expiratory maneuvers (Group 2), at baseline and after bronchodilator inhalation. The children were divided into two subgroups according to the R0(SD) cutoff defined in Group 1: open circles, R0(SD)  1; closed circles, R0(SD) > 1. Asterisks indicate significant differences (p < 0.05) between the two subgroups.

	DISCUSSION

TOP ABSTRACT INTRODUCTION METHODS RESULTS DISCUSSION REFERENCES

We compared the interrupter technique and the FOT method for detecting airway obstruction and its reversibility in the pediatric setting. We showed that the FOT permits a reliable evaluation of bronchial obstruction and its reversibility in children as young as 3 yr (2). In particular, it was possible to define useful criteria for FOT measurements. The interrupter technique is another simple method for evaluating respiratory system resistance in children. However, the sensitivity and specificity of this method for assessing airway obstruction and its reversibility have rarely been investigated. The aims of our study were therefore to compare FOT results with resistance measurements obtained by the interrupter technique.

Our results confirm our previous results with the FOT in a new pediatric population, and demonstrate that the interrupter method underestimates resistance in children relative to R₀ obtained with the FOT, especially in the youngest children. Furthermore, we show that, at a given specificity, R₀ yields the highest sensitivity for identifying children with low lung function parameters or with a significant improvement after bronchodilator inhalation.

Differences in Resistance Measurements between FOT and Rint

R₀ was higher than R₁₆ and Rint in almost all the children. The difference between R₀ and R₁₆ or Rint gradually increased with increasing baseline values. Underestimation of resistance by Rint has previously been reported in children, in comparison with plethysmographic methods (20). This latter work suggested that the criteria used to estimate alveolar pressure from mouth pressure during occlusion could influence this underestimation. In particular, the underestimation could be increased by taking into account only the first part of the alveolar pressure plateau during occlusion, because of insufficient time for equilibration between alveolar pressure and mouth pressure. However, this possibility does not seem to be relevant to the present study as our results were not modified when we used the pressure value at the end of the occlusion time (Rint_E). Furthermore, the similar underestimation observed with Rint obtained by the interrupter technique, and R₁₆ obtained by the FOT, argue for a common explanation, which could be the low capacity of R₁₆ and Rint to reflect peripheral resistance. The difference between R₀ and R₁₆ reflects the frequency dependence of resistance in children. We estimated the frequency dependence of resistance by the slope of the 4- to 16-Hz regression equation and by its intercept at zero frequency. R₀ is a purely empirical intercept and is not an estimate of respiratory resistance measured at frequencies approaching 0 Hz. Younger children had higher R₀ values at baseline and a larger difference between R₀ and R₁₆, reflecting a more pronounced frequency dependence of resistance. This pattern has already been described in children (21) and may be related to differences in tissue viscoelastic properties or greater ventilation inhomogeneity, but has been explained mainly on the basis of increased peripheral resistance, which produces an asynchronous distribution of tidal volume between the airways and lung parenchyma (26). Indeed, young children have high peripheral resistance, which represents a higher fraction of total resistance than in adults (27), and total respiratory resistance becomes more frequency dependent as peripheral resistance increases (28). Thus, the higher peripheral resistance in younger children in comparison with older children and adolescents would directly explain the more pronounced frequency dependence of their total resistance (26). We have previously shown that R₀ measurement is strongly influenced by the peripheral airway resistance level in children (2). The present study confirms the significant contribution of the peripheral airways to R₀ but not to R₁₆ or Rint. Indeed, multiple regression analysis showed that MEF₅₀ was a highly significant determinant of the correlation between spirometric and resistance parameters at baseline for R₀ but not for R₁₆ or Rint. Furthermore, the difference between R₀ and Rint correlated with MEF₅₀ but not with FEV₁. Assuming that MEF₅₀ reflects small-airway caliber, it appears from our results that R₀, but not R₁₆ or Rint, might be a sensitive parameter for early identification of small-airway abnormalities in children. This is in agreement with previous physiological interpretations of these different parameters. R₀ was shown to reflect instantaneous airway and tissue Newtonian resistance plus the delayed airway resistance resulting from gas redistribution (12). This latter resistance characterizes the frequency dependence of resistive impedance. In contrast, R₁₆ and Rint would reflect only airway and tissue Newtonian resistance, without taking into account the delayed airway resistance resulting from gas redistribution (12, 13).

Identification of Baseline Airway Obstruction

Both FOT and interrupter measurements correlated with spirometric indices of bronchial obstruction such as FEV₁ and MEF₅₀. Children with FEV₁ or MEF₅₀ < 80% of predicted had higher mean R₀, R₁₆, and Rint values than children with spirometric parameters  80% of predicted. This increase was related to the degree of lung function abnormalities, the largest increase being observed in children with both low FEV₁ and MEF₅₀ values, and intermediate values being obtained in children with only a low MEF₅₀ value. This good correlation between resistance and spirometric parameters in children has previously been reported with FOT by ourselves (2) and others (24, 29). Data on the interrupter method are more controversial. Carter and coworkers demonstrated a good correlation between conductance and FEV₁ (5), whereas Oswald-Mammosser and coworkers found no difference in Rint between obstructed and nonobstructed children (20). Our data support R₀ as a more reliable indicator of baseline lung function than Rint. We tested R₀(SD) and Rint(SD) cutoffs to identify children with low lung function parameters. However, at a given specificity, R₀(SD) cutoff values always yielded higher sensitivity. For example, to discriminate between children with FEV₁ < 80 or  80% of predicted values with a chosen specificity of 80%, R₀(SD) yielded 66% sensitivity whereas Rint(SD) yielded only 33% sensitivity. Similarly, to discriminate between children with MEF₅₀ < 80 and  80% of predicted values with a chosen specificity of 80%, R₀(SD) yielded 64% sensitivity, whereas Rint(SD) yielded only 46% sensitivity.

Postbronchodilator Changes in FOT and Rint Measurements

Salbutamol inhalation induced a decrease in FOT and Rint values that correlated strongly with the degree of basal airway obstruction. In routine procedures, the aim of testing a bronchodilator response is to identify subjects with significant reversibility of an airway obstruction attributable to asthma. A significant improvement in FEV₁ was defined in our study by FEV₁  10%. This index is more suitable than the percentage change in FEV₁ in showing the reversibility of airway obstruction due to asthma, both in adults (17, 18) and in children (19). We found that children with a significant improvement in FEV₁ after salbutamol inhalation were better identified by changes in R₀ values than by changes in R₁₆ or Rint. The R₀(SD) cutoff value defined by ROC curve analysis for the identification of children with a significant FEV₁ improvement after bronchodilator inhalation was close to our previous results (2). At a specificity of 80%, the R₀(SD) cutoff yielded 69% sensitivity in our first study and 67% in this study. The best compromise between sensitivity and specificity corresponded to a decrease in R₀ of 2.3 hPa · s · L¹ or more in our previous study and 2.5 hPa · s · L¹ or more (i.e., the standard deviation of the residual) in the present study. Results with Rint(SD) were less favorable. Rint(SD)  1, corresponding to a decrease in Rint of 1.4 hPa · s · L¹ or more, had 79% specificity and 58% sensitivity. As in our study, it has been reported that bronchodilator inhalation induces a significant decrease in Rint values in children with asthma (4, 6, 7). In particular, McKenzie and coworkers showed that preschool children with wheezing could be usefully identified by changes in Rint induced by a bronchodilator, but not by basal Rint values (6). However, none of these previous studies evaluating changes in Rint induced by bronchodilator inhalation have specifically defined criteria for the identification of children with significant reversibility. The lower performance we observed in our study with Rint measurements than with the FOT could first be explained by the low capacity of Rint to identify basal obstruction. Underestimation of high basal resistance values with Rint will limit the decrease after bronchodilator inhalation. The absence of a significant difference in basal Rint values between children with and without significant reversibility strongly supports this explanation. Furthermore, the relatively high coefficient of variation of Rint measurements, and the low-decrease cutoff value defining significant reversibility (1.4 hPa · s · L¹ or more), would favor greater overlap between changes in Rint values in children with and without significant reversibility.

FOT and Rint Measurements in Preschool Children

Because the FOT and interrupter technique are easily performed during normal, quiet breathing, they appeared ideally suited to young children. Although many studies have evaluated these two techniques in preschool children (3, 4, 6, 7, 29- 31), few have compared their respective usefulness in this age range. Bisgaard and Klug found that the oscillation technique was significantly more sensitive than the interrupter technique to assess methacholine-induced changes in lung function (3). The few data available about the reversibility of bronchial obstruction suggest a greater sensitivity of the oscillation technique (3, 30). Our data highlight the limitations of Rint measurements in preschool children. In this age range, baseline resistance values are higher, and the underestimation of these values by Rint is larger. After bronchodilator inhalation, the correlation between baseline values and bronchodilator-induced changes was clearly better for R₀ than for Rint. Furthermore, the use of cutoffs defined with reference to spirometric parameters in older children allowed us to clearly identify subgroups of young children according to their variations in R₀ after bronchodilator inhalation. Children with large changes in R₀ values after bronchodilation [R₀(SD)  1] had high R₀ values at baseline that returned to normal after bronchodilation. Such results were not obtained for Rint values. Our results therefore suggest that, in preschool children, R₀ is more useful than Rint for detecting reversible basal airway obstruction. This is probably because R₀ can reflect changes in the frequency dependence of resistance, whereas R₁₆ and Rint are only a single measurement of resistance.

In conclusion, we demonstrate, in children as young as 3 yr, that FOT provides a more reliable evaluation of bronchial obstruction and its reversibility than does the interrupter technique. The usefulness of Rint measurements may be limited by the underestimation of resistance and by their poor assessment of peripheral airway resistance.