Can bronchodilator response predict bronchial response to methacholine in preschool coughers?

The aim of the present study was to determine the relationship between bronchodilator response, assessed by interrupter resistance (Rint), and bronchial reactivity in preschool children with chronic cough. Thirty-eight children coughers (median age 5.0 years, range 2.8-6.4) were tested. Bronchodilator response was recorded within 4 months before methacholine challenge. Response to the latter was assessed using transcutaneous partial pressure of oxygen and Rint. Children were considered responders if a 20% fall in transcutaneous partial pressure of oxygen occurred during the bronchial challenge. Bronchodilator response was not different between responders (n = 24) and nonresponders (n = 14) [median (range) -0.11 (-0.44-0.09) vs. -0.08 (-0.21-0.10) kPa L(-1) sec; respectively]. However, none of the nonresponders had a bronchodilator response larger than -0.21 kPa L(-1) sec, this cutoff had a 100% positive and a 44% negative predictive value to predict a positive methacholine challenge. The relationship between bronchodilator response and bronchial methacholine responsiveness reached the limit of significance (P = 0.048). Furthermore, the magnitude of the bronchodilator response was correlated to the level of methacholine-induced level of bronchoconstriction (P = 0.01), and to the postchallenge bronchodilation (P = 0.04), all values expressed as % predicted. Moreover, the postbronchodilator Rint value obtained with preceding methacholine challenge was lower than the postbronchodilator value without preceding methacholine challenge in 71.4% (10/14) of the nonresponders and in only 33.3% (8/24) of the responders. Conclusions in preschool coughers bronchodilator response, assessed by the interrupter technique, was correlated to the bronchial responsiveness to methacholine. Non responders had a bronchodilator response not larger than -0.21 kPa L(-1) sec.     

Airway resistance and atopy in preschool children with wheeze and cough.

The extent to which the measurement of airways resistance by the interrupter technique (Rint) distinguishes preschool children with previous wheeze from those with no respiratory symptoms and helps to classify subjects with persistent cough, was investigated. Rint was measured before and after salbutamol treatment in 82 children with recurrent wheeze, 58 with isolated cough and 48 with no symptoms (control subjects). Their mean age (range) was 3.7 yrs (2-<5 yrs). Median baseline Rint was higher (p<0.0001) in wheezers than in either coughers or control subjects (1.16, 0.94 and 0.88 kPa x L(-1) x s(-1) respectively); coughers did not differ significantly from control subjects (p=0.14). The median ratios of baseline to post-salbutamol measurements (bronchodilator response (BDR)) in the groups differed significantly (1.40, 1.27 and 1.07, p< or =0.01 for all), suggesting that coughers occupy an intermediate position. A BDR ratio of >1.22 had a specificity and sensitivity for wheeze of 80% and 76% respectively. Twenty-eight coughers had a BDR ratio >1.22. Wheezers' immunoglobulin E was inversely related to baseline Rint. It is concluded that measurements of airway resistance by the interrupter technique are useful for classifying preschool children with respiratory symptoms and could be used to monitor the effect of interventions. The relation between atopy and airways resistance suggests that they have separate roles in preschool wheezing. Coughers with a high bronchodilator response could represent "cough-variant" asthma in children who have baseline airway resistance by the interrupter technique measurements similar to control subjects. Whether these children develop classical asthma will only be known at follow-up later in childhood.     

Airway resistance by the interrupter technique: Which algorithm for measuring pressure?

Airway resistance using the interrupter technique (Rint) can be measured using commercial devices which employ different algorithms for estimating pressure change. We aim to describe differences in Rint due to algorithm. We compared Rint and change in Rint after bronchodilator, using four algorithms to estimate pressure change following interruption: 1) two-point back-extrapolation to interruption from points 70 msec and 30 msec from interruption, and similarly 2) to 15 msec from interruption, 3) at two-thirds from interruption, and 4) near end-interruption. Flow was measured immediately before interruption. Our subjects were 39 asymptomatic children 2-5 years old with previous intermittent wheeze. Rint differed significantly with algorithm. Geometric mean Rint (95% confidence interval (CI)) for algorithms 1-4 were 1.21 kPa x l(-1) x sec (1.18-1.24 kPa x l(-1) x sec), 1.31 kPa x l(-1) x sec (1.28-1.34 kPa x l(-1) x sec), 1.57 kPa x l(-1) x sec (1.54-1.61 kPa x l(-1) x sec) and 1.71 kPa x l(-1) x sec (1.67-1.75 kPa x l(-1) x sec), respectively. Measurement of change in R(int) following bronchodilator (BDR) did not differ on average with algorithm. Geometric means (95% CI) for BDR measurements for algorithms 1-4 were 29.9% (26.0-34.0%), 30.4% (26.4-34.5%), 32.9% (28.8-37.1%), and 31.7% (27.6-35.8%), respectively. However, measurement of change in individuals could differ by up to 40%, depending on algorithm. In conclusion, there are significant differences in Rint, depending on algorithm used to estimate pressure change. Measurement of change in Rint is unaffected on average, although in individuals there could be significant differences. Each laboratory should state its method and use the same algorithm for longitudinal and group data.     

Pre/postbronchodilator interrupter resistance values in healthy young children

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 (Rint(insp), Rint(exp)) 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 Rint(insp) and Rint(exp) (0.78 +/- 0.21 versus 0.78 +/- 0.20 KPa x L(-1) x second). However, the difference between Rint(insp) and Rint(exp) decreased significantly with age and being positive before 5 years and negative later on (p < 0.02). Rint(insp) and Rint(exp) decreased significantly with height (Rint(insp) [KPa x L(-1) x second] = 2.289 - 1.37. 10(-2) x H [cm], Rint(exp) [KPa. L(-1) x second] = 2.021 - 1.12.10(-2) x H [cm]; p < 0.001). Bronchodilator (salbutamol) administration significantly decreased Rint(insp) and Rint(exp) (p < 0.001). Bronchodilator-induced changes (% of predicted values) in mean Rint(insp) and mean Rint(exp) 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.     

How should airways resistance be measured in young children: mask or mouthpiece?

The reproducibility and acceptability of airways resistance measurements using the interrupter technique (MicroRint) obtained using a mouthpiece were compared with those using a face mask. Fifty children aged 4-7 yrs performed four sets of six Rint measurements; two using a mouthpiece and two using a face mask with integral mouthpiece. Complete data were obtained from 45 (90%) children using the mouthpiece and 43 (86%) children using the mask. The two methods were equally repeatable with comparable intraclass correlation coefficients (ICC) and coefficients of variation. Mean Rint values obtained using the mouthpiece were significantly lower than those using the face mask ((mean+/-SD) mouthpiece=0.81+/-0.18 kPa x L(-1) x s, mask=0.88+/-0.24 kPa x L(-1) x s p=0.0002). Although the mean paired differences between the two methods were small (0.07 kPa x L(-1) x s), the ICC and limits of agreement confirmed that the two methods could not be used interchangeably. Sixty-seven per cent of children preferred the face mask but this was more time-consuming (p = 0.03). Children did not produce more repeatable results using their preferred method, nor did they improve with practice. Repeatable airway resistance measurements using the interrupter technique can be obtained from young children using either a mouthpiece or a face mask, but there are significant clinical and statistical differences between the results obtained.     

Pulmonary function tests in preschool children with cystic fibrosis

Pulmonary function tests have rarely been assessed in preschool children with cystic fibrosis (CF). The objective of this multicenter study was to compare pulmonary function in 39 preschool children with CF (height, 90-130 cm; 16 homozygous Delta F508) and in 79 healthy control children. Functional residual capacity (helium dilution technique) and expiratory interrupter resistance (Rint(exp)) (interrupter technique) were measured. As compared with control children, children with CF had significantly higher Rint(exp), expressed as absolute values and as Z-scores (1.05 +/- 0.36 versus 0.80 +/- 0.20 kPa.L(-1). second, p < 0.0001; and 1.31 +/- 1.72 versus 0.19 +/- 0.97, p < 0.0001), and significantly lower specific expiratory interrupter conductance (1.29 +/- 0.34 versus 1.63 +/- 0.43 kPa(-1). second, p < 0.0001). The effect of the bronchodilator salbutamol on Rint(exp) was not significantly different between children with CF and control children. Rint(exp) Z-scores were significantly higher in children with CF who were exposed to passive smoke (n = 8) (p < 0.03). Children with CF and with a history of respiratory symptoms (n = 31) had significantly higher functional residual capacity Z-scores (p < 0.02) and lower specific expiratory interrupter conductance Z-scores (p < 0.04). Genotype did not influence the data. We conclude that Rint(exp) and functional residual capacity measurements may help to follow young children with CF who are unable to perform reproducible forced expiratory maneuvers.     

The opening interrupter technique for respiratory resistance measurements in children

Background and objective: The interrupter resistance (Rint) can be calculated from various estimates of alveolar pressure based on mouth pressure during occlusion. We compared Rint, as measured by the opening interrupter technique (Rint1), and the linear back‐extrapolation method (Rint2), with the ‘gold standard’ airway resistance measured by plethysmography (Raw). Methods: The study included 32 asthmatic children and 11 children with cystic fibrosis, aged 5 to 18 years, who were categorized into non‐obstructed (NObs) (n = 27) and obstructed (Obs) (n = 16) groups. Spirometry and the three different resistance measurements were performed on all children. Rint1 and Raw were assessed after a bronchodilator (BD) test in 16 and nine children, respectively, in the Obs group. Results: Raw (0.48 ± 0.20 kPa.s/L) was lower than Rint1 (1.04 ± 0.34 kPa.s/L) and Rint2 (0.63 ± 0.18 kPa.s/L) (P < 0.001). Raw, but neither Rint1 nor Rint2, was significantly higher in the Obs group than in the NObs group (0.57 ± 0.23 vs 0.42 ± 0.16 kPa.s/L, P < 0.05). The differences Rint1‐Raw and Rint2‐Raw were correlated with FEV₁/VC (P < 0.01 and P < 0.001), and Rint1‐Raw was correlated with height (P < 0.001). After BD significant changes in Rint1 and Raw were observed in 5/9 and 7/9 children, respectively. Conclusions: Rint2, as well as Rint1, may be underestimated in the most Obs children and may therefore fail to detect severe obstruction. Rint1 is likely to include a non‐negligible contribution from the tissue component, especially in the youngest children. Although not different between Obs and NObs children at baseline, Rint1 did detect bronchodilation in some Obs children.     

Bronchodilator responsiveness and atopy in 5-10-yr-old coughers.

Cough-variant asthma is considered by some to be an asthma phenotype. Bronchodilator responsiveness (BDR) is an undisputed feature of asthma. Of school-aged wheezers, 90% are atopic. Are school-aged coughers who demonstrate BDR also atopic? If so, then it would be reasonable to reserve the diagnosis cough-variant asthma for this particular group. Airway resistance was measured by the interrupter technique (Rint) before and after salbutamol in controls (n=73), coughers (n=63) and previous wheezers (n=63) aged 5-10 yrs. Immunoglobulin (Ig)-E was measured in coughers and wheezers. BDR was expressed as the ratio baseline:post-salbutamol Rint. Groups were of similar age (mean 6.7, range 5-9.9 yrs). Geometric mean baseline Rint was similar in controls and coughers (0.66 and 0.68 kPa x L(-1) x s), but the baseline Rint for wheezers (0.73 kPa x L(-1) s) was greater than that for controls (p=0.05) but not significantly different from coughers (p=0.17). Geometric mean BDR in coughers was 1.22, controls 1.13 and wheezers 1.30 (p=0.01 for coughers and controls; p=0.08 for coughers and wheezers; p<0.001 for controls and wheezers). IgE was lower in coughers than wheezers (geometric means 36 and 364 International Units (IU) x L(-1), p<0.001) and was unrelated to BDR in both groups. In summary, atopy, and not bronchodilator responsiveness, distinguishes groups of coughers from groups of wheezers. A diagnosis of cough-variant asthma cannot be reserved for even those school-aged coughers, who demonstrate bronchodilator responsiveness.     

Comparison of the forced oscillation technique and the interrupter technique for assessing airway obstruction and its reversibility in children

The forced oscillation technique (FOT) and interrupter technique are particularly attractive for pediatric use as they require only passive cooperation from the patient. We compared the sensitivity and specificity of these methods for detecting airway obstruction and its reversibility in 118 children (3-16 yr) with asthma or chronic nocturnal cough. FOT (R(0) and R(16)) and interruption (Rint) parameters were measured at baseline and after bronchodilator inhalation (n = 94). Rint was significantly lower than R(0), especially in children with high baseline values. Baseline parameters were normalized for height and weight [R(SD)]. In children able to perform forced expiratory maneuvers (n = 93), the best discrimination between those with baseline FEV(1) < 80% or > or = 80% of predicted values was obtained with R(0)(SD). At a specificity of 80%, R(0)(SD) yielded 66% sensitivity, whereas Rint(SD) yielded only 33% sensitivity. Similarly, postbronchodilator changes in R(0)(SD) [DeltaR(0)(SD)] yielded the best discrimination between children with and without significant reversibility in FEV(1). At a specificity of 80%, DeltaR(0)(SD) yielded 67% sensitivity and DeltaRint(SD) yielded 58% sensitivity. In children unable to perform forced expiratory maneuvers (n = 25), FOT, contrary to the interrupter technique, clearly identified a subgroup of young children with high resistance values at baseline, which returned to normal after bronchodilation. We conclude that, in asthmatic children over 3 yr old, FOT measurements provide a more reliable evaluation of bronchial obstruction and its reversibility compared with the interrupter technique, especially in young children with high baseline values.     

Interrupter resistance short-term repeatability and bronchodilator response in preschool children

Interrupter resistance (Rint) technique can be easily and successfully performed in preschool children. The establishment of Rint short-term repeatability is essential to interpret any Rint change after a pharmacological intervention. AIMS OF THE STUDY: In preschool children with asthma or chronic cough: (1) to assess two indices of short-term repeatability: (a) intra-measurement and (b) within-occasion between-test repeatability; (2) to study the relationship between short-term repeatability and bronchodilator response (BDR). RESULTS: Rint intra-measurement repeatability assessed by the coefficient of variation was similar at baseline and after bronchodilator in asthmatics and in coughers (median 10% and 12%, respectively). There was no significant difference between asthmatics and coughers for both coefficient of repeatability (CR) (0.25 kPa L(-1)s and 32% of predicted vs 0.16 kPa L(-1) s and 21% of predicted, respectively) and BDR (median -14.7% vs -21.1% of predicted, respectively). However, in 20% of the study children, baseline variability of Rint modified the significance of the BDR. CONCLUSION: In the present study, Rint short-term repeatability was similar to that of previous studies. Similar Rint repeatability in coughers and in asthmatic children favored the use of asthmatic CR for both populations, and a -35% cut-off as a positive BDR. In 20% of study children, baseline Rint variability could influence the significance of the BDR. In order to improve assessment of BDR using Rint, further studies are needed (1) to compare the variability of Rint to other resistance measurement techniques and (2) to define the best method for Rint calculation and for expression of BDR.     

Effects of respiratory timing and cheek support on resistance measurements, before and after bronchodilation in asthmatic children using the interrupter technique

The interrupter technique (Rint) is a noninvasive method for assessing respiratory resistance. The aims of this study were to assess whether upper airway support affects the measurement of Rint, if inspiratory or expiratory Rint were most reproducible, and which method of assessing Rint correlated best with spirometry results and was the most sensitive for identifying bronchodilator response. Twenty-four asthmatic children with a mean age of 10.3 years (range, 7-16 years) were included in the study. Rint measurements were obtained in inspiration and expiration with cheeks supported and unsupported. Spirometry was then performed. Rint and spirometry measurements were repeated after the inhalation of 600 mcg of salbutamol. The mean Rint supported inspiratory (0.708 KPa/l/sec) and expiratory (0.729 KPa/l/sec) values were significantly higher than the unsupported values (inspiratory, 0.622 KPa/l/sec; expiratory, 0.584 KPa/l/sec), P < 0.05 and P < 0.001, respectively. The reproducibility of Rint was not different whether cheeks were supported or not, or whether the measurements were carried out during inspiration or expiration. Cheek support improved the correlation with all the lung function results, both in inspiratory and expiratory measurements. The best correlations, however, were found for the inspiratory supported Rint results. The most sensitive method to ascertain bronchodilator response (BD) was the inspiratory supported Rint measurement, as 83.3% of children were identified as having a positive response to bronchodilator therapy as defined by a reduction of twice the coefficient of variation of the measurement. In conclusion, cheek support increases Rint but does not impact on reproducibility, though it improves the correlation with spirometric indices. Rint with cheek support on inspiration correlates best with spirometric indices and appears to be the most sensitive measure of response to bronchodilators.     

Discriminative capacity of bronchodilator response measured with three different lung function techniques in asthmatic and healthy children aged 2 to 5 years

The primary aim of this study was to quantify and compare bronchodilator responsiveness in healthy and asthmatic children aged 2 to 5 yr. The secondary aim of the study was to compare discriminative capacity (i.e., sensitivity, specificity, and predictive values of the reversibility test for the diagnosis of asthma) for each of the lung function tests applied in the study. Specific airway resistance (sRaw) as measured by whole-body plethysmography, respiratory resistance as measured with the interrupter technique (Rint), and respiratory resistance and reactance at 5 Hz (Rrs5, Xrs5, respectively) as measured with the impulse oscillation technique were assessed before and 20 min after inhalation of terbutaline from a pressurized metered-dose inhaler via a metal spacer by 92 children (37 healthy controls and 55 asthmatic subjects). The study of healthy children followed a randomized, double-blind, crossover design, whereas the study of asthmatic children was open. Baseline lung function was significantly decreased in asthmatic children as compared with healthy control subjects as reflected by all techniques used in the study. sRaw, Rint, and Rrs5, but not Xrs5, improved significantly with terbutaline as compared with placebo in healthy control subjects. Lung function improved to a significantly greater extent in asthmatic children than in control subjects as reflected by all methods. sRaw provided the best discriminative power of such a bronchodilator response, with a sensitivity of 66% and specificity of 81% at the cutoff level of a 25% decrease in sRaw after bronchodilator administration. In conclusion, bronchodilator response measured by sRaw allows a separation of asthmatic from healthy young children. This may help define asthma in this clinically difficult-to-manage group of young wheezy children. The sensitivity and specificity of the other methods used in the study were less than those of sRaw.     

The interrupter technique to assess airway responsiveness in children with cystic fibrosis

The aim of this study was to assess the validity of the interrupter technique (Rint) in measuring airway responsiveness in children with cystic fibrosis. Fifty children (aged 6-16 years) with cystic fibrosis performed six Rint measurements followed by three acceptable forced expiratory maneuvers. Each child then inhaled 5 mg of nebulized salbutamol by facemask. After 20 min the Rint and forced expiratory measurements were repeated. In the population as a whole a moderate but significant correlation between inverse Rint and FEV1 values was observed, both before and after inhaled bronchodilator (r=0.71 and 0.72, respectively, P < 0.001). However, when changes in Rint and FEV1 readings following inhaled bronchodilator were examined, no relationship was seen. Indeed, the two methods identified completely different subsets of children as being bronchodilator responsive. These results indicate that although a relationship exists between Rint and FEV1 in the whole population, this is not the case in individual children. Rint and FEV1 reflect different aspects of lung function. It is not appropriate to use Rint as a simple alternative for FEV1 in children with cystic fibrosis when assessing airway responsiveness.     

Applicability of interrupter resistance measurements for evaluation of exercise-induced bronchoconstriction in children

The interrupter technique is a noninvasive method for measuring air-flow resistance during tidal breathing. This method requires minimal cooperation, and is therefore promising for use in uncooperative children. The aim of this study was to evaluate applicability interrupter resistance (Rint) measurements in the assessment of exercise-induced bronchoconstriction (EIB). Fifty children aged 5-12 years with mild to moderate asthma were tested by exercise challenge, consisting of free outdoor running for 6 min at 80-90% of maximal predicted heart rate for age. Rint, forced expiratory volume in 1 sec (FEV1), and peak expiratory flow (PEF) were measured before and 10 min after exercise. EIB was defined as a fall of 10% or more in FEV1 after exercise. The repeatability of Rint was assessed, and its response to exercise challenge was compared with current standardized methods. The mean intermeasurement coefficient of variation was 4.6% (SD, +/- 3.0%), and the repeatability coefficient was 0.056 kPa/l/sec. Eighteen (36%) of the 50 children had EIB after exercise challenge test. The area under the receiver-operating characteristic (ROC) curve was 0.953 (95% confidence interval, 0.853-0.992; P < 0.001), and the optimal Rint cutoff value was 15.2%, producing a sensitivity of 88.9% and a specificity of 96.9%. The positive and negative predictive values were 94.1% and 93.9%, respectively. The kappa value between FEV1 and Rint was 0.83. The repeatability of Rint measurements was good, and the results of exercise challenge tests using Rint measurements have excellent agreement with the current standardized methods to detect EIB. Considering that only minimal comprehension and coordination are needed without forced breathing technique, the Rint measurement can provide a useful alternative for assessment of EIB in children unable to perform reliable spirometry.     

Pressure oscillation amplitude after interruption of tidal breathing as an index of change in airway mechanics in preschool children

Bronchodilator reversibility testing using change in airway resistance during interruption (Rint) is feasible in preschool children. Analysis of postocclusion oscillations of the mouth pressure-time transient (Pmo(t)), recorded during airflow interruption, may offer an alternative index of change in airway mechanics. We analyzed Pmo(t) oscillation amplitude in three different ways: 1) difference between the first relative maximum and minimum (AMxMn); 2) detection of the dominant frequency using Fourier analysis (AFS); and 3) curve-fitting based on a mathematical model (ACurv). In 25 asymptomatic asthmatic children, aged 2.5-5.6 years, who had undertaken reversibility testing, the correlation coefficients between baseline Rint and amplitude were: AMxMn r = -0.84, AFS r = -0.82, ACurv r = -0.84. The coefficient of variation (CoV) of readings contributing to baseline Rint measurement, as median (range), was 12% (5-24%), which was not significantly different from AFS or ACurv (P > 0.05). All parameters were significantly different postbronchodilator (P < 0.001). Using the sensitivity index, i.e., the change after intervention divided by the baseline standard deviation, ACurv was the most sensitive and Rint the least sensitive, with median (range) at 2.72 (-0.84 to 12.10) and 1.91 (-1.17 to 9.50), respectively (P = 0.005). Our results suggest that oscillation amplitude analysis may provide a sensitive index of change in airway mechanics in preschool children undertaking bronchodilator reversibility testing.     

Measurements of resistance by the interrupter technique and of transcutaneous partial pressure of oxygen in young children during methacholine challenge

Measurement of bronchial airway responsiveness requires noninvasive techniques in young children. The study was designed to examine the changes in resistance as measured using the interrupter technique (Rint) at the dose of methacholine (M) that induced a fall in transcutaneous partial pressure in O2 (P(tc)O2) > or = 20% (PD(20)P(tc)O2) in young children. Rint was calculated using the linear back-extrapolation method (Rint(L)) and the end-interrupter method (Rint(EI)). Twenty-two children (mean age, 5.2 +/- 1.1 years; range, 3.4 - 7.1 years) with nonspecific respiratory symptoms (mainly chronic cough, n = 17) were tested. P(tc)O2, Rint(L), and Rint(EI) were measured before the test, after saline challenge (baseline (B)), after each dose of M delivered by a dosimeter, and after bronchodilator (BD) inhalation. P(tc)O2 decreased significantly during M challenge, from 85 +/- 6 mmHg (B) to 62 +/- 9 mmHg (P < 0.05), and increased after BD inhalation, to 82 +/- 8 mmHg. Rint(L) and Rint(EI) increased significantly during M challenge, from 0.94 +/- 0.2 KPa/L/s and 1.11 +/- 0.19 KPa/L/s (B) to 1.27 +/- 0.35 KPa/L/s and 1.47 +/- 0.37 KPa/L/s, respectively (P < 0.05), and decreased after BD inhalation to 0.80 +/- 0.17 KPa/L/s and 0.95 +/- 0.18 KPa/L/s, respectively. Nineteen of 22 children reached the PD(20)P(tc)O2 at a dose of M ranging from 50-400 microg. At the PD(20)P(tc)O2, significant changes in Rint(L) and Rint(EI) (sensitivity index (SI) > or = 2) were found in 79% and 63% of children, respectively. We conclude that: 1) M challenge using P(tc)O2 is safe in young children; and 2) our findings are not in favor of the use of Rint as the only indicator of bronchial reaction in young children during M challenge.     

Airway challenge testing - accuracy of the interrupter technique

According to national and international recommendations the bronchial sensitivity should be determined based on the decrease of the FEV1 by 20 % (FEV1 - 20) or the increase of the airway resistance by means of body plethysmography by 100 % (Raw + 100). Measurement of airway resistance by interrupter technique (Rint) is a simple method and needs no active cooperation of the patient, but is not recommended in airway challenge testing. We investigated the role of the increase of Rint by 100 % (Rint + 100) compared to Raw + 100 and FEV1 - 20 during carbachol airway challenge testing by means of dosimetry. We examined 123 patients with following symptoms: 85 x coughing, 31 x coughing and dyspnea, 7 x medical opinion. Significant correlations between Rint and Raw were found before and after the challenge tests (Rint before/after 0,3 +/- 0,13/0,36 +/- 0,25 kPa*s/l; Raw before/after 0,24 +/- 0,09/0,50 +/- 0,41 kPa*s/l; r = 0,504/0,672; p < 0,001 [Pearson]). The median values of Rint and Raw were significantly different (p < 0,001 [Wilcoxon]). Moreover Rint systematically overestimated airway resistance in the normal range and underestimated the increase of airway resistance during challenge testing (r = 0,783; p < 0,001 [Pearson]). In 58 patients an increased airway responsiveness was found. In 21 oft these patients there was no increase of Rint above the initial value. Sensitivity/specificity/positive predictive value/negative predictive value in % to the detection of airway hyperresponsiveness were in Rint + 100 9/95/63/54, in FEV1 - 20 61/100/100/66 and in Raw + 100 98/100/100/98. In conclusion we found significant correlations between Rint and Raw, but the median values were systematically and significantly different. Rint + 100 had a low sensitivity to detect airway hyperresponsiveness and is not comparable with FEV1 - 20 or Raw + 100.     

Interrupter technique for evaluation of exercise-induced bronchospasm in children

The free running test is a useful method for evaluation of exercise-induced bronchospasm in children. In young children this test simulates real-life circumstances and can be done more easily than histamine or methacholine challenges. The interrupter technique is a noninvasive method for measuring airflow resistance during tidal breathing. This approach requires minimal cooperation, and is therefore promising for use in young children. Fifty children aged 5-15 years with asthma symptoms were tested by exercise challenge consisting of free outdoor running for 8 min at 85% of maximal predicted heart rate for age. Pulmonary function was measured by using the interrupter technique (IR), with a Wright's peak flow meter (WPEF), and by flow-volume spirometry (FVS). The measurements were done before and 10 min after exercise. In addition, WPEF was measured at 5, 15, and 20 min after exercise. A fall of 15% or more in WPEF associated with wheezing or cough symptoms was considered a positive test. The exercise challenge was positive in 16 (32%) of the 50 children. Measurements at 10 min by WPEF identified 9 positive cases. At the same time point the IR identified 10 positive cases; a rise in resistance of 15% or more was considered positive, giving it 80% sensitivity and 93% specificity. The repeatability coefficient (CoR) for the interrupter technique was 0.06 kPa x L(-1) x s (13%) before and 0.07 kPa x L(-1) x s (14%) after exercise. The IR provides a useful alternative for estimation of airway obstruction in children following exercise challenge. The results were comparable with the current reference methods of forced expiratory volume in 1 s and peak flow measurements.     

Reference values for airway resistance in newborns, infants and preschoolers from a Latin American population

Background and objective: Several studies have determined reference values for airway resistance measured by the interrupter technique (Rint) in paediatric populations, but only one has been done on Latin American children, and no studies have been performed on Mexican children. Moreover, these previous studies mostly included children aged 3 years and older; therefore, information regarding Rint reference values for newborns and infants is scarce. Methods: Rint measurements were performed on preschool children attending eight kindergartens (Group 1) and also on sedated newborns, infants and preschool children admitted to a tertiary‐level paediatric hospital due to non‐cardiopulmonary disorders (Group 2). Results: In both groups, Rint values were inversely associated with age, weight and height, but the strongest association was with height. The linear regression equation for Group 1 (n = 209, height 86–129 cm) was Rint = 2.153 ? 0.012 × height (cm) (standard deviation of residuals 0.181 kPa/L/s). The linear regression equation for Group 2 (n = 55, height 52–113 cm) was Rint = 4.575 ? 0.035 × height (cm) (standard deviation of residuals 0.567 kPa/L/s). Girls tended to have slightly higher Rint values than boys, a difference that diminished with increasing height. Conclusions: In this study, Rint reference values applicable to Mexican children were determined, and these values are probably also applicable to other paediatric populations with similar Spanish‐Amerindian ancestries. There was an inverse relationship between Rint and height, with relatively large between‐subject variability.     

Measurement of lung function in awake 2–4-year-old asthmatic children during methacholine challenge and acute asthma: A comparison of the impulse oscillation technique,the interrupter technique,and transcutaneous measurement of oxygen versus whole-body plethysmography

This study evaluated three techniques for testing of lung function in young awake children. We compared measurements by the forced or impulse oscillation technique (IOS), the interrupter technique (IT), and transcutaneous measurements of oxygen (tcPO₂) with concomitant measurements of specific airway resistance (sRaw) during methacholine challenge in 20 stable asthmatic children, 2–4 years old. Measurements were performed with all techniques after each dose of methacholine and after inhalation of a bronchodilator. Measurements were carried out during tidal breathing using a face-mask with a built-in mouthpiece. The ranking of sensitivity was as follows: sRaw > IOS, respiratory reactance at 5 Hz (Xrs5) > tcPO₂ > interrupter resistance (Rint) > IOS, respiratory resistance at 5 Hz (Rrs5). The sensitivity of sRaw and Xrs5 was not significantly different, but both were significantly more sensitive than Rint and Rrs5; the sensitivity of tcPO₂, Rint, and Rrs5 was not significantly different. Measurements in eight of the subjects performed during an episode of acute asthma yielded comparable results in regard to the sensitivity of the techniques. Measurements improved significantly after bronchodilator administration; however, the response to bronchodilator tended to be less during acute asthma and was best demonstrated by a deterioration of tcPO₂. All the evaluated techniques reliably reflect short-term changes in respiratory function and can provide clinically useful estimates of airway function. The techniques are non-invasive, are not dependent on the active co-operation or sedation of the subjects, and therefore are well suited for routine use in young children. Pediatr Pulmonol. 1996; 21:290–300. © 1996 Wiley-Liss, Inc.