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American Journal of Respiratory and Critical Care Medicine Vol 165. pp. 1388-1394, (2002)
© 2002 American Thoracic Society

Original Article

Pre/Postbronchodilator Interrupter Resistance Values in Healthy Young Children

Nicole Beydon, Francis Amsallem, Michèle Bellet, Michèle Boule, Michèle Chaussain, André Denjean, Régis Matran, Bernard Wuyam, Corinne Alberti and Claude Gaultier the French Pediatric Programme Hospitalier de Recherche Clinique Group

Physiology Departments of the Robert Debré Teaching Hospital, Saint-Vincent-de-Paul Teaching Hospital, and Trousseau Teaching Hospital, Paris; Public Health Department of the Robert Debré Teaching Hospital, Paris; Pediatric Department, Arnaud de Villeneuve Teaching Hospital, Montpellier; Physiology Departments, Morvan Teaching Hospital, Brest; Poitiers Teaching Hospital, Poitiers; Calmette Teaching Hospital, Lille; and Grenoble Teaching Hospital, Grenoble, France

Correspondence should be addressed to Claude Gaultier, Service de Physiologie, Hôpital Robert Debré, 48 Bd Serurier, 75019, Paris, France. E-mail: claude.gaultier{at}rdb.ap-hop-paris.fr


   ABSTRACT
TOP
 ABSTRACT
INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The interrupter technique estimates flow resistance. It entails occlusion of the airways during tidal breathing while flow and mouth pressure are recorded. This noninvasive technique is easy to use in young children. The aim of the present study was to measure inspiratory and expiratory interrupter resistance (Rintinsp, Rintexp) before and after bronchodilator administration in young healthy white children. We designed a multicenter study using a standardized procedure for Rint measurements. Centers in five French cities studied 91 children (48 boys and 43 girls; height, 92 to 129 cm; mean age 5.3 ± 1.4 years). Mean values were not significantly different for Rintinsp and Rintexp (0.78 ± 0.21 versus 0.78 ± 0.20 KPa · L-1 · second). However, the difference between Rintinsp and Rintexp decreased significantly with age and being positive before 5 years and negative later on (p < 0.02). Rintinsp and Rintexp decreased significantly with height (Rintinsp [KPa · L-1 · second] = 2.289 - 1.37 . 10-2 · H [cm], Rintexp [KPa · L-1 · second] = 2.021 - 1.12.10-2 · H [cm]; p < 0.001). Bronchodilator (salbutamol) administration significantly decreased Rintinsp and Rintexp (p < 0.001). Bronchodilator-induced changes (% of predicted values) in mean Rintinsp and mean Rintexp were -15% (95% confidence interval, -46 to +15%) and -12% (95% confidence interval, -46 to +22%), respectively. Sex did not affect pre- or postbronchodilator values. Data from the present study may prove useful for testing lung function in young children with respiratory disorders who failed to cooperate with forced expiratory maneuvers.

Key Words: inspiratory and expiratory interrupter resistance • reference values • preschool children


   INTRODUCTION
TOP
 ABSTRACT
 INTRODUCTION
METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 
The interrupter technique is a noninvasive technique for estimating flow resistance, an important determinant of lung function, especially in children too young to accomplish forced respiratory maneuvers in a reproducible manner. The interrupter technique is easy to use in young children. Several recent studies used interrupter resistance (Rint) measurements in wheezy and/or asthmatic young children, particularly for testing bronchoreactivity (1–5).

The interrupter technique entails rapid and complete occlusion of the airways during a normal breathing cycle while flow and airway opening (or mouth) pressure (Pm) are recorded (6–9). The method is based on the assumption that alveolar pressure (PA) and Pm equilibrate at airway occlusion. Flow resistance is considered equal to Pm divided by the flow immediately before the interruption. Several methods have been suggested for estimating PA from the analysis of post-occlusion Pm curves, which comprise an initial, rapidly changing phase with rapid damped oscillations, followed by a second, slowly changing phase (6). Early studies using Pm measurement at the breakpoint between these two phases found that Rint overestimated plethysmographic airway resistance (Raw) in healthy human adults (6). Recent advances in equipment and computer analysis techniques have allowed a reappraisal of the interrupter method (8, 9). Curvilinear back-extrapolation of Pm back to the time of occlusion has been shown to improve PA estimates derived from the Pm curve and the correlation between Rint and Raw in healthy adults (8). Subsequent studies reported linear back-extrapolation methods (1–5, 9–15). Compliance of the upper airways may be responsible for lack of Pm-to-PA equilibration during airway occlusion, resulting in underestimation of flow resistance (9). However, studies performed using the Bates model suggest that as much as a 10-fold increase in airway resistance is measured correctly by the interrupter technique, provided upper airway compliance is not excessively high (16). This has been verified in adults with severe obstruction (9). Finally, Rint was higher during expiration than during inspiration in adults and school-age children (8, 10, 11), which can be explained by a diminished glottis opening during expiration (17).

Normative data for Rint measured during inspiration (Rintinsp) and/or expiration (Rintexp) in young children have been published recently (4, 11, 14, 15). However, no previous studies determined both Rintinsp and Rintexp before and after bronchodilator inhalation in healthy young children. The response to a bronchodilator in young children with respiratory disorders, however, has been examined in previous studies (1–5). Our aim was to measure Rintinsp and Rintexp before and after bronchodilator administration in young, healthy white children. We designed a multicenter study using a standardized procedure for Rint measurements. Linear back-extrapolation of Pm was used to estimate PA for Rint calculation.


   METHODS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
RESULTS
 DISCUSSION
 REFERENCES
 
Subjects
We conducted a multicenter study including children from eight pediatric lung function testing centers in hospitals in five French cities. One of the centers (Physiology Department, Robert Debré Teaching Hospital, Paris, France) coordinated the study, with the help of a local study coordinator in each of the other centers.

White children, 90 to 130 cm in height, were recruited. Criteria for healthiness were those recommended by international consensus (18). Children were eligible if they had none of the following exclusion criteria: premature birth, intrauterine growth retardation, chronic respiratory disease, cardiac disease, neurological disability, or a respiratory infection during the last 4 weeks. Children exposed to passive smoke were not excluded. Between April 1998 and December 1999, 101 children were recruited in the eight centers. The study coordinator performed a physical examination on each child on the day of the study, including height and weight measurements. All measurements were performed at the lung function testing laboratories of the study centers. The study was approved by the local ethics committee, and written informed consent was obtained from both parents of each child.

Equipment
All centers used a Spiroteq apparatus (Dyn'R Ltd, Toulouse, France) and the Programme Hospitalier de Recherche Clinique 2.55 computer program. The computer sent a digital signal to an analog converter, which controlled a motor-driven revolving disc that occluded the airways within 6 milliseconds and for 100 milliseconds. Each occlusion was triggered manually by the investigator and took place between 20% and 80% of the following tidal volume. Pm was sampled at 500 Hz. PA was estimated from the Pm pressure curve by performing linear back extrapolation of two mean points located at 30 and 70 milliseconds from a vertical line 15 milliseconds after occlusion onset (2, 3). The interrupter was connected to a heated pneumotachograph (Fleish 1, Lausanne, Switzerland). Flow calibration was performed once a day, with a precision of ± 1%. The flow signal used to calculate Rint was obtained just before the interruption.

Rint Measurement Procedure
A standardized procedure for Rint measurement and validation of Rint data was established and set up in all centers. Each child was first familiarized with the measuring equipment. He or she was seated comfortably, wore a noseclip, and breathed through a mouthpiece (dead space, 30 ml). An adult supported the child's jaw and cheeks, taking care to keep the child's neck straight. The child was asked to breathe as calmly as possible. The first occlusion was released after at least three respiratory cycles with a regular tidal volume and respiratory cycle duration.

As measurements proceeded, a computer displayed (1) the tidal volume, the volume at interruption, the preinterruption flow, the Pm curve, and the back-extrapolated Pm value for each interruption; and (2) an x/y graph of Pm values versus flow values for a series of interruption. The procedure for validating Rint measurements was the same in all eight centers and involved two steps performed by the investigators, based on a visual examination, and a third step performed by the computer, based on automated calculations. First, the investigators were asked to discard immediately all Rint values measured during breathing cycles disturbed by a respiratory pause, swallowing, speaking, moving, or coughing; or accompanied with a flagrant Pm curve error (blunted initial rapid changing phase, lack of oscillations, or aberrant second changing phase). Second, the investigators were asked to examine the x/y graph of Pm and flow and to delete Rint data for which the Pm values were aberrant relative to flow, i.e., too low, indicating a mouth leak, or too high either during inspiration, presumably because of inspiratory muscle activity, or during expiration, suggesting closure of the glottis. Third, the software automatically calculated the mean flow from the remaining Rint data and selected Rint values obtained within this mean flow ± 1 SD. At least seven validated Rint measurements with a coefficient of variation (CV) 20% or less were required for calculation of mean Rint values. The 20% limit for CV acceptance was chosen based on unpublished preliminary data showing that mean CV + 2 SD was equal to 20%.

Measurements were performed between 9 A.M. and 3 P.M. Rint was measured in all children, first during expiration (Rintexp), then during inspiration (Rintinsp), immediately before and 10 minutes after bronchodilator inhalation of 200 µg of salbutamol, administered using a metered-dose inhaler and a spacer (Volumatic, Bad Oldesloe, Germany) in all children.

Data Collection
The following data were collected: coded patient identifiers (study center and subject number); anthropomorphic data; clinical history and physical examination findings; printed tidal volume; volume at interruption; flow; Pm values for each Rint measurement; and x/y Pm versus flow graphs, saved on diskettes. All data were forwarded to the coordinating center, which performed detailed reviews of inclusion criteria. In addition, validity of the Rint measurements done in each study center were checked based on the following criteria: absence of aberrant pressure values on the x/y Pm versus flow graph, presence of at least seven measurements per series, and a CV of 20% or less at baseline.

Statistical Analysis
Continuous variables were expressed as medians (first quartile–third quartile) for each center, or means (± SD) when all centers were combined. Categorical variables were expressed as numbers. Between-centers comparisons used the Kruskal-Wallis test for continuous variables and Fisher's exact test for categorical variables. Linear relationships linking the volume at interruption, expressed as the percent of tidal volume attributed to Rintinsp and Rintexp, were tested using 120 Rintinsp and 120 Rintexp measurements, obtained before and after bronchodilator administration (480 measurements in all). Comparisons between Rint values and CV measured at inspiration and at expiration before and after bronchodilator administration were performed using paired t tests.

Stepwise multiple linear regression was used to determine which of the following variables (standing height, weight, age, sex, and numbers of cigarettes smoked per day by mothers and the fathers) correlated significantly with prebronchodilator Rintinsp and Rintexp and with the difference between Rintinsp and Rintexp. To take a possible center effect into account, we performed a statistical adjustment assuming a random effect, i.e., using a mixed linear model (SAS MIXED procedure; SAS Institute, Cary, NC). The residual standard deviation of the best equation was calculated and used to compute the confidence interval of the study population. All tests were two-tailed and p-values less than 0.05 were considered statistically significant. All statistical analyses were performed using SAS version 6.12 (SAS Institute).


   RESULTS
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
DISCUSSION
 REFERENCES
 
Subjects
Of the 101 children recruited in the eight centers, 10 were excluded from the analysis. Six were excluded when the coordinating center found that they had noninclusion criteria: one had a history of asthma during infancy and another during childhood, one had a chronic cough, one had a history of intrauterine growth retardation, and two were taller than 130 cm. Baseline measurements were incomplete in two children. Finally, the coordinating center excluded two children because they had fewer than seven validated Rint measurements at baseline. The remaining 91 children had a mean age of 5.3 ± 1.4 years (2.9 to 7.9 years), a mean height of 112 ± 9.2 cm (92 to 129 cm), and a mean weight of 19.5 ± 3.6 kg (12 to 29 kg). Table 1 shows the anthropomorphic data in each age group. Thirty percent of the children were exposed to passive smoke by their parents (mean ± SD numbers of cigarettes smoked per day by the mothers and fathers were 6.7 ± 7.6 and 10.7 ± 11.9, respectively). Table 2 shows the numbers, age and sex distributions, heights, and weights of the study children in each center. Ages, heights, and weights were significantly different among centers.


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  		TABLE 1. Anthropometric characteristics by age group inthe 91 study children

 

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  		TABLE 2. Anthropometric characteristics by study center in the 91 study children

 
Prebronchodilator Rint Values
The mean number of measurements validated by the investigators was 11.1 ± 2.4 for Rintinsp and 11.7 ± 2.4 for Rintexp. Of these measurements, 7.8 ± 1.2 for Rintinsp and 7.8 ± 1.2 for Rintexp were selected by the computer within the mean flow ± 1 SD. Median volumes at interruption, expressed as percent of tidal volume, were 52% (25th–75th percentiles: 42–67%) for Rintinsp and 48% (25th–75th percentiles: 33–65%) for Rintexp. No linear relationships were found between volumes at interruption and Rintinsp or Rintexp. Median Rintinsp and Rintexp values were significantly different across centers (p < 0.01, p < 0.03, respectively) (Table 2). The intrasubject CV of Rintinsp was slightly but significantly lower than that of Rintexp (p < 0.02) (Table 3). Rintinsp and Rintexp CV did not change significantly with age or across centers (Table 2).


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  		TABLE 3. Pre- and postbronchodilator inspiratory and expiratory interrupter resistance values

 
Mean values for the 91 study children were not significantly different for Rintinsp and Rintexp (Table 3). However, the difference between Rintinsp and Rintexp decreased significantly with age, being positive in children younger than 5 years and negative in those older than 5 years (p < 0.02) (Figure 1) .



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  		Figure 1. Relationship between age (years) and the difference between prebronchodilator Rintinsp and Rintexp (KPa · L-1 · second). The solid circles indicate boys and the open circles girls. The solid line is the regression line. y = -0.025x + 0.123; p < 0.02.

 
Rintinsp and Rintexp decreased significantly with height (p < 0.001) (Table 4, Figure 2) . The regression coefficients did not differ significantly when age, weight, sex, and/or parental smoking (total number of cigarettes smoked per day by both parents) were taken into account.


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  		TABLE 4. Regression of inspiratory and expiratory interrupter resistance on height

 


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  		Figure 2. Relationships between height (cm) and prebronchodilator Rintinsp (KPa · L- 1 · second) (top panel) and between height and prebronchodilator Rintexp (bottom panel). The solid lines are regression lines and the dotted lines 95% confidence interval limits. The solid circles indicate boys and the open circles girls. (See regression equations in Table 4.)

 
Postbronchodilator Rint Values
Median volumes at interruption expressed as percent of tidal volume were not significantly different before and after bronchodilator for Rintinsp and for Rintexp (median [25th–75th percentiles]: 52% [42–67%] versus 50% [42–65%] and 48% [33–65%] versus 50% [35–65%], respectively). No linear relationships were found between volumes at interruption and Rintinsp or Rintexp after bronchodilator administration. The CV of Rintexp was significantly larger after than before bronchodilator administration (p < 0.03) and significantly greater than CV Rintinsp (p < 0.02) (Table 3).

Rintinsp and Rintexp decreased significantly after bronchodilator administration (p < 0.001) (Table 3). Mean Rintinsp was significantly lower than mean Rintexp after bronchodilator administration (p < 0.01) (Table 3). The mean bronchodilator-induced change expressed as the percentage of the predicted value was -15% for Rintinsp (95% confidence interval, -46 to +15%) and -12% for Rintexp (95% confidence interval, -46 to +22%). Height, age, sex, and/or passive smoking had no effect on bronchodilator-induced changes in Rintinsp or Rintexp expressed as the absolute value or as the percentage of the prebronchodilator value or predicted value.


   DISCUSSION
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
REFERENCES
 
The present multicenter study in healthy young white children confirms that (1) Rint could be measured easily in young children; and (2) Rintinsp and Rintexp decreases linearly with height and is independent of sex. The new finding of this study is that the difference between Rintinsp and Rintexp decreased significantly with age, being positive in children younger than 5 years and negative in older children. Furthermore, changes in Rintinsp and Rintexp after bronchodilator administration are reported here for the first time in healthy young children. No differences in Rintinsp and Rintexp decreases after bronchodilator administration were observed between boys and girls.

Subjects
Only white children were studied because of the differences in airway growth reported between black and white children (19). Abnormalities in airway growth and dynamics have been found in children with a history of premature birth and/or intrauterine growth retardation (20), and children with either or both characteristics were consequently excluded. Exposure to passive smoke by the parents was not selected as an exclusion criteria because as many as 38% of French adults smoke (21). Thirty percent of our children were exposed to passive smoke by their parents. However, the number of cigarettes smoked by the parents included as an independent variable in the stepwise multiple regression analysis did not significantly modify the equations between Rintinsp and Rintexp and height. Our study did not include air quality controls in the five cities. Therefore, we cannot rule out the possibility that differences in exposure to air pollutants across the five cities may have resulted in differences in airway growth (22).

Acceptability of the interrupter technique was excellent: complete measurement sets were obtained in all but two children.

Rint Measurements
Similar interrupter and software were used for Rint measurements in all eight centers. The closing speed of the interrupter device was within the range recommended by Bates and colleagues (23). PA was estimated from Pm curves using linear back extrapolation (1–5, 9–15), a procedure that shares similarities with that described by Jackson and colleagues (8). Phagoo and coworkers compared Rint values using curvilinear and linear back-extrapolation methods and found less variability with linear back-extrapolation (12, 13). The Rint measurement procedure included careful support of the checks and floor of the mouth, aimed at reducing the compliance of this section of the extrathoracic airways. Such support has been shown to improve Rint measurement significantly in healthy school-aged children (11), but not in healthy younger children (15) or in healthy adults (9).

Previous studies of Rint measurement in children did not provide a detailed description of the criteria used to validate Rint measurements (1–4, 10, 11, 14, 15). We carefully standardized the Rint measurement validation. The interruptions were performed between 20 and 80% of tidal volumes. No linear relationships were found between the volume at interruption and Rint, confirming previous data in children (11). Our device was not preprogrammed to activate occlusion at a particular flow (1–4, 10, 12–15). However, Rint data were selected by the computer within a narrow range of flows. Mean Rint was the average of seven validated measurements. Previous data (unpublished) from our laboratory showed that the CV of Rint in young children was not changed by using more than seven validated Rint measurements. The CV of Rintexp was slightly but significantly higher than that of Rintinsp, a difference possibly ascribable to changes in glottal opening during expiration (17). Neither age nor center influenced the CV of Rintinsp or Rintexp.

Prebronchodilator Rint Values
Normative data for Rintinsp and/or Rintexp in young children have been collected recently in single-center studies (4, 11, 14, 15, 24). This study provides the first multicenter normative data for Rintinsp and Rintexp obtained using a statistical model that integrates center-to-center variability, thus allowing extrapolation of our findings to the general population of children of similar age. We found that height was the most significant predictor of Rint, in keeping with all earlier studies but one (4). One study reported Rint values according to height in a group of children, from early childhood to adolescence (11); few young children were included, however, so that the results cannot be compared with our data. Lombardi and colleagues recently reported the regression equations of Rintinsp and Rintexp on height determined from a single-center study of 284 healthy young children (15). Our regression equations for Rintinsp and Rintexp on height (Table 4) are not significantly different from theirs (Student's test on regression coefficients) (15), indicating that our multicenter study encountered similar variability in Rintinsp and Rintexp measurements as the large, single-center study of Lombardi and coworkers (15). Merkus and colleagues reported Rintinsp and Rintexp data in 59 healthy young children from a single center. They did not report the variability of the regression coefficients and, consequently, statistical comparisons with our model cannot be made (14). Nevertheless, the intercept and the slope of the relationship linking Rintinsp and Rintexp to height were apparently higher than in the present study (14). These differences may be ascribable to the smaller number of study children shorter than 110 cm in height as compared with our study (16 versus 39) (18). Rintexp values presented according to subject age have been reported in 2– to 5–year-old children with no history of respiratory symptoms (4). These values were within the range of those obtained in the 4–year-olds in our study, i.e., 0.85 kPa/L/second and 0.86 kPa/L/second. Finally, Klug and Bisgaard (24) reported Rintinsp values in a large group of young children, but used the opening interrupter method, in which the pressure used for Rint calculation was measured at the end of an 80-millisecond occlusion and the flow shortly after airway reopening. Rint measured by this method is thought to represent flow resistance plus the tissue viscoelastic component of the respiratory system (7). Lanteri and Sly reported an increase in the tissue viscoelastic component beyond 2 years of age (25). Consistent with this finding, Rintinsp values measured using the opening interrupter method were higher than those obtained in the present study (24).

In previous studies of either Rint or resistance measured using the oscillation technique, values were slightly but significantly higher during expiration than during inspiration in both school-age children and adults (8, 10, 11, 26). This difference can be explained by diminished glottal opening during expiration (17). No significant differences between mean Rintinsp and Rintexp were observed in this study of young children, as reported by Lombardi and colleagues (15). However, we found that the difference between Rintinsp and Rintexp decreased significantly with age, being positive in children under 5 years of age and negative in older children. Jeans and colleagues (27) reported that the size of the nasopharyngeal airway decreased between 3 and 5 years of age because the surface area of the soft tissues grew faster than that of the nasopharyngeal airway. At the oropharyngeal level, a faster increase in the surface area of soft tissues as compared with that of the pharyngeal airway may result in an increase in upper airway resistance. If this is the case, the reduction in glottal opening during expiration may not exceed that of the pharyngeal lumen, explaining the lower Rintexp than Rintinsp in very young children. Flow resistance may become higher during expiration than during inspiration when the surface area of the oropharyngeal soft tissues remains relatively constant, while the area of the oropharyngeal airway increases. Our data, demonstrating that the difference between Rintinsp and Rintexp changes with age and are relevant to clinical practice: Rintinsp data and Rintexp data should be reported separately in young children.

Measurements of maximal expiratory flows at low lung volumes (28) suggest that sex may influence airway growth and dynamics. Girls have been reported to have higher flows than boys during early and late childhood (28, 29). Since maximal expiratory flows at low lung volumes are believed to reflect small airway geometry, girls may have larger peripheral airways than boys. The central airways contribute most of the resistance to airflow. Conflicting data have been reported on the effect of sex on resistance to airflow. An early study found higher values in boys than in girls (30). However, in a recent study, sex had no effect on Rint in paralyzed, mechanically ventilated children of whom the youngest were a few weeks old and the oldest were adolescents (25). Our data are in agreement with these results and with reports of resistance measured in young children using the interrupter techniques and forced oscillations (14, 15, 31).

Postbronchodilator Rint Values
Early studies found a significant increase in airway conductance or a significant decrease in total pulmonary resistance after ß-adrenoceptor agonist inhalation in healthy adults and older children (32, 33). No previous studies have provided data for both Rintinsp and Rintexp before and after bronchodilator administration in healthy young children. However, the response to a bronchodilator has been tested using the interrupter technique: Rintinsp (1, 5) or Rintexp (2–4) decreased after bronchodilator administration in young children with respiratory disorders. In our study of healthy young children, both Rintinsp and Rintexp decreased significantly after salbutamol administration. The mean Rint decrease expressed as the percent of predicted values was within the range reported for resistance measured in young children using the forced oscillations technique (34). Salbutamol had a slightly but significantly larger effect on Rintinsp than on Rintexp. To the best of our knowledge, no previous studies have examined the effects of ß-adrenoceptor agonist inhalation on both upper and lower airway resistance during inspiration and expiration in healthy adults or children.

The Rint decrease after salbutamol inhalation was neither significantly different between the boys and girls in our study nor between those in a previous study of resistances, measured using the forced oscillations technique (34). In contrast, a study involving expiratory maneuvers found evidence of sex-related differences in airway muscle tone (35), suggesting that the muscle tone of the peripheral airway at rest may be less responsive to ß-adrenoceptor agonists in boys than in girls.

In line with a previous report on the effect of bronchodilator administration on resistance, measured using the forced oscillations technique (34), the salbutamol-induced Rint decrease varied widely across individuals in our study. This variability in the response to a bronchodilator across healthy children may be due to differences in environmental conditions and genetic makeup (36).

Conclusion
The present multicenter study of Rint measurements obtained using a standardized procedure provides Rint values according to height during both inspiration and expiration in healthy young white children, before and after bronchodilator. Acceptability of the technique was excellent, confirming previous reports of ease of use in young children. We show that the difference between Rintinsp and Rintexp decreased with age, being positive in children younger than 5 years and negative in older children. This indicates that Rintinsp data and Rintexp data should be reported separately in young children. The present Rint values may prove useful for testing lung function in young children with respiratory disorders who fail to cooperate with forced expiratory maneuvers. However, the large interindividual variability in the postbronchodilator Rint decrease in healthy children complicates determination of the optimal cut-off for defining a positive bronchodilator response in children with respiratory disorders.


   Acknowledgments
 
The authors are grateful to the physicians who participated in the study: H. Trang and A. Bernard (Robert Debré Teaching Hospital, Paris); M. Voisin and F. Couwil (Arnaud de Villeneuve Teaching Hospital, Montpellier); Y. Grossi and D. Sarni (Morvan Teaching Hospital, Brest); JL. Iniguez (Saint-Vincent-de-Paul Teaching Hospital, Paris); V. Diaz (Poitiers Teaching Hospital, Poitiers); E. Cixous (Calmette Teaching Hospital, Lille); and I. Pin, C. Pilenko-Mc Guigan, and H. Bensaïdane (Grenoble Teaching Hospital, Grenoble). For their technical assistance, the authors thank S Benjamaa, C. Foucard, M. Pisca, F. Dubois, and JC. Sismeiro (Robert Debré Teaching Hospital, Paris); V. Alibert (Arnaud de Villeneuve Teaching Hospital, Montpellier); MN. Guiffaut (Morvan Teaching Hospital, Brest); C. Lebeau and A. Roche (Saint-Vincent-de-Paul Teaching Hospital, Paris); MC. Mathlin (Calmette Teaching Hospital, Lille); M. Guyard, B. Julien, and M. Trochu (Grenoble Teaching Hospital, Grenoble). The authors are thankful to P. Le Corre (Dyn'R Ltd, Toulouse) for assistance with the computer program, to F. Zerah and A. Harf (Henri Mondor Teaching Hospital, Créteil) for their advice during the preparation of the grant, and to S. England (New Brunswick University, Piscataway, New Jersey) for her helpful comments. The authors are especially indebted to the parents and the children who participated in the study.

Supported by a grant from the Programme Hospitalier de Recherche Clinique AOM 96.


   FOOTNOTES
 
Requests for reprints to: Nicole Beydon, Service de Physiologie, Hôpital Robert Debré, 48 Boulevard Sérurier, 75019 Paris, France. E-mail: nicole.beydon{at}rdb.ap-hop-paris.fr

Received in original form November 27, 2000; accepted in final form November 14, 2001


   REFERENCES
TOP
 ABSTRACT
 INTRODUCTION
 METHODS
 RESULTS
 DISCUSSION
 REFERENCES
 

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