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.     

Interrupter technique versus plethysmography for measurement of respiratory resistance in children with asthma or cystic fibrosis

The purpose of the present study was to compare measurements of respiratory system resistance by the interrupter method (Rrsint) with those of airway resistance by plethysmography (Raw) in nonobstructed children with asthma or cystic fibrosis (ratio of forced expiratory volume in 1 sec to vital capacity, FEV(1)/VC >/=80% with a forced expiratory flow rate between 25-75% of forced vital capacity, FEF(25-75) >/=75% of normal values) and in obstructed children with the same diseases (FEV(1)/VC <80% and/or FEF(25-75) <75% of normal values). Eighty-one children (47 asthmatics and 34 suffering from cystic fibrosis) aged 5-18 years (mean 11.2 +/- SD 3.4 years) were included in the study. For the overall group, we observed generally lower values for Raw (4.7 +/- 2. 8 cmH(2)O.L(-).s) than for Rrsint20 (extrapolation of the mouth pressure during occlusion to 40 ms after interruption) (5.6 +/- 1.7 cmH(2)O.L(-1).s) (P < 0.02), or for Rrsint40 (extrapolation of the mouth pressure during occlusion to 60 ms after interruption) (6.6 +/- 2.2 cmH(2)O.L(-1).s) (P < 0.001), but there was no difference between Rrsint20 and Raw in the obstructed subgroup. Moreover, we observed a correlation between the difference (Rrsint20 - Raw) expressed in percentage of predicted values and the degree of obstruction estimated by FEV(1)/VC (r = 0.56, P < 0.001). The differences between the specific resistances (sRrsint20 - sRaw, sRrsint40 - sRaw) were also correlated with the severity of the obstruction (r = 0.65, P < 0.001 and r = 0.57, P < 0.001, respectively). We observed also that the tendency to underestimate resistance by Rrsint in obstructed children was not the same in children with asthma and cystic fibrosis. We conclude that the tendency of Rrsint, as measured with our method, to underestimate airway obstruction appears to increase in proportion to the severity of the airway obstruction.     

Spirometric reference values in Tunisian children

BACKGROUND: In Tunisia, there are no normal values of pulmonary function for healthy Tunisian children. OBJECTIVES: The purpose of this study was to set reference values for spirometric lung function in Tunisian children and to compare these results with other data sets. METHODS: Spirometric values were measured with a Minato portable spirometer in 1,114 asymptomatic, nonsmoking Tunisian children (581 boys and 533 girls) 6-16 years of age. Natural logarithmic values of lung function and standing height were used in the final regression model. RESULTS: Prediction equations for forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)), FEV(1)/FVC x 100, maximum mid expiratory flow (MMEF 25-75%) and peak expiratory flow (PEF) for both sexes are presented with standing height as the dependent variable. Our data show a significant increase in lung function with standing height in both sexes. Comparing our results with recent data, values of FVC and FEV(1) in both sexes in the present study are close to those in European, white US and Asian children, whereas our values are higher than the Libyan ones. CONCLUSIONS: Healthy Tunisian children showed similar spirometric reference values compared to European, white US and Asian children. Thus, these standards of lung function could also be used in Tunisia.     

Measurements of interrupter resistance: reference values for children 3-13 yrs of age.

The interrupter technique is a convenient and sensitive technique for studying airway function in subjects who cannot actively participate in (forced) ventilatory function tests. Reference values for preschool children exist but are lacking for children >7 yrs. Reference values were obtained for expiratory interrupter resistance (R(int,e)) in 208 healthy Dutch Caucasian children 3-13 yrs of age. A curvilinear relationship between R(int,e) and height was observed, similar to published airways resistance data measured by plethysmography. No significant differences in cross-sectional trend or level of R(int,e) were observed according to sex. It was found that Z-scores could be used to express individual R(int,e) values and to describe intra- and interindividual differences based on the reference equation: 10logR(int,e)=0.645-0.00668x standing height (cm) kPa x L(-1) x s(-1) and residual SD (0.093 kPa x L(-1) x s(-1)). Expiratory interrupter resistance provides a tool for clinical and epidemiological assessment of airway function in a large age range.     

Static lung volumes and airway resistance reference values in healthy adults

Background and objective: The assessment of static lung volumes and airway resistance is a frequently performed diagnostic procedure and considered as an important tool in medical surveillance to detect pulmonary diseases. The objectives of the study are to establish reference equations for body plethysmographic parameters in a representative adult population across a wide age range and to compare the normative values from this sample with previous ones. Methods: Body plethysmography was applied in 1809 participants (885 males) of a cross‐sectional, population‐based survey (Study of Health in Pomerania). Individuals with cardiopulmonary disorders and/or a pack‐year smoking history >10 years and participants with a body mass index >30 kg/m² were excluded. In total, 686 healthy individuals (275 males) aged 25–85 years were assessed. Results: Prediction equations for both genders were established by quantile regression analysis taking into account the influence of age, height and weight. Conclusions: The study provides a novel set of prediction equations for static lung volumes and airway resistance obtained using body plethysmography. Compared with our findings, existing equations underestimated some normal values. The results emphasize the need for up‐to‐date reference equations.     

Normal spirometric reference values for Omani children and adolescents

OBJECTIVES: Normal lung function has been shown to be population specific. The aim of this study was to derive normal reference spirometric values for Omani children and adolescents. METHODOLOGY: Forced vital capacity (FVC), forced expiratory volume in 1 s (FEV(1)), peak expiratory flow and forced mid-expiratory flow were measured in 837 healthy Omani school children aged 6-19 years. Multiple linear regression analysis was performed for each spirometric parameter against age, height and weight for boys and girls separately. RESULTS: All measured spirometric parameters increased with age and height and were significantly higher in boys than girls. Height explained the maximum variance for all parameters. After accounting for height in the prediction equations, the contribution of age and weight was minimal. The expiratory ratio (FEV(1)%FVC) was independent of age and height and its mean values (+/- standard deviation) were slightly higher in girls (91.1 +/- 6.1%) than boys (86.5 +/- 7.1%; P < 0.001). The predicted normal values of the subjects using the derived equations were between 5 and 10% lower than the respective values for subjects in Caucasian sample groups. CONCLUSION: The developed prediction equations can be used in clinical practice in Oman and can be considered for use in neighbouring Arab countries.     

Hematologic reference values for African American children and adolescents

Anemia is prevalent among African American children. When evaluating pediatric patients for anemia, clinicians refer to the normative hematological reference values in reference textbooks. These reference values are used in spite of evidence that healthy African American people of all ages have average hemoglobin concentrations from 0.5 to 0.73 g/dl below those of Whites. In an earlier study, using samples from 2,161 healthy African American children from 2 to 18 years old, we found a statistically significant difference (P < 0.0001) in the mean hemoglobin value for each age group as compared to reference normative mean hemoglobin values. Here we present the results of a comparative analysis of the data set from our previous study and the data set from the National Health and Nutrition Examination Surveys III (NHANES III) 1988-1994. We found no statistically significant difference between these data sets with respect to the hemoglobin values for any age or sex group, confirming that African American children and adolescents have lower mean hemoglobin values than do Whites. Use of the reference hemoglobin values presented here will help prevent the misdiagnosis of anemia in African American children and thereby minimize unnecessary hematological workups and treatment.     

Spirometric reference values for white European children and adolescents: Polgar revisited

We analyzed six spirometric data sets collected in the Netherlands, Austria, the United Kingdom, Spain, and Italy. The objectives were to establish whether (1) it was possible to describe spirometric indices from childhood to adulthood, taking into account the adolescent growth spurt, and (2) there are systematic differences in ventilatory function between children and adolescents in different parts of Western Europe. The study comprised 2,269 girls and 3,592 boys, aged 6–21 years. The range in standing height was 110–185 in girls, 110–205 in boys. The model applicable to all data sets was In FVC or In FEV₁ = a + (b + c · A)· H, where H = standing height and A = age; this model prevents the phase shift between the adolescent growth spurt in length and lung volume from leading to an age-dependent bias in predicted values. There was surprising agreement between most of the data sets; systematic differences are probably due to technical factors arising from ATPS-BTPS corrections and from defining the end of breath with pneumotachometer systems. Taking those into account, prediction equations for FVC, FEV₁, and FEV₁%FVC were developed with “lower limits of normal” which should be applicable to children and adolescents of European descent. It is proposed that the approach of analyzing available data sets should also be applied to other ventilatory indices, data collected in adults and elderly subjects, or in other ethnic groups, and that an international data base be set up to that end. © 1995 Wiley-Liss, Inc.     

Exhaled nitric oxide in healthy nonatopic school-age children: determinants and height-adjusted reference values

Exhaled nitric oxide (FENO) was proposed as a marker of airway inflammation, but data about FENO in healthy children measured with standardized methods are so far limited. In order to assess the determinants of FENO in healthy children, we investigated a population-based sample of school-age children (n = 276) with a questionnaire, skin-prick tests, spirometry, and the measurement of FENO. The FENO of 114 nonatopic and nonsmoking children considered healthy were analyzed with stepwise multiple regression analysis, which showed significant associations with age, standing height, weight, and body surface area, but not with gender. Height was found to be the best independent variable for the regression equation for FENO, which on average showed an increase in the height range of 120-180 cm from 7 to 14 ppb. In the random sample of children, increased FENO was associated with atopy (odds ratio, 9.0; 95% confidence interval, 3.9-21.1; P < 0.0001), and significantly with allergic rhinitis and atopic dermatitis, but not with asthma. Respiratory symptom-free children with skin-prick test positivity had significantly higher FENO than healthy nonatopic subjects. We conclude that height is the best determinant of FENO in healthy children. Due to the strong effect of atopy, FENO data should not be interpreted without knowing the atopic status of the child. The present reference values of FENO may serve in clinical assessments for measuring airway inflammation in children.     

Methacholine-induced volume dependence of respiratory resistance in preschool children.

Enhanced negative volume dependence of airway resistance is associated with bronchoconstriction in tracheostomized paralysed open-chest animals. Significant upper airways responses may be associated with bronchoconstriction and could thereby alter the pattern of volume dependence in spontaneously breathing subjects. The aim of the study was to test whether volume dependence of respiratory resistance (Rrs) could be demonstrated in preschool children undergoing routine methacholine challenge. The volume dependence of respiratory oscillation resistance at 12 and 20 Hz (Rrs,12 and Rrs,20) was examined in eight 4-5.5-yr-old children showing a positive response to methacholine. Multiple linear regression analysis was also used to account for flow dependence during tidal breathing (Rrs,12 or Rrs,20=K1+K2?V'?+K3V). Rrs,12 and Rrs,20 yielded similar results. Negative volume dependence was present at baseline and significantly enhanced by methacholine (p<0.01). For instance, the mean+/-SD inspiratory K3 at 20 Hz was 4.1+/-1.3 hPa x s x L(-2) at baseline and -15.0+/-4.3 hPa x s x L(-2) after methacholine, in which case it was also larger on expiration than on inspiration (p<0.05), possibly as a result of upper airway responses. A significant increase in the negative volume dependence of respiratory resistance may thus be shown in preschool children in response to methacholine. The volume dependence (K3) during inspiration may be particularly useful in detecting bronchoconstriction, because it is less likely to be affected by upper airway mechanisms than during expiration.     

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.     

Normal values for forced oscillatory respiratory resistance in children

Forced oscillatory respiratory resistance was measured in 138 healthy children aged 2- to 16-years-old using a commercial unit. Regression analysis was performed using the resistance measurements obtained at frequencies of 6 Hz and 26 Hz and averages of measurements obtained at frequencies of from 6-26 Hz, 6-10 Hz, and 22-26 Hz. The analysis suggested that regression curves and 95% confidence intervals obtained using a quadratic model with height as the independent variable provided the best prediction of normal values and their ranges. Three independent sets of resistance measurements, which were obtained for all 138 subjects, were used to calculate the average individual coefficients of variation (CV) for the five resistance parameters noted above; these ranged from 9 to 13%. This analysis suggested that the expected CV of repeated measurements would be about 10%. Finally, values from 13 children who had asthma with mild bronchial obstruction (FEV1 less than 80% of predicted) were compared with the normal values derived from the regression curves. Values from all but two of the children fell within the reference intervals, suggesting that FEV1 may be a more sensitive measure of obstruction than forced oscillatory resistance. The main applications of this new approach may be in the evaluation of young children, in following individual patients, and in bronchodilation and bronchial challenge tests.     

Interrupter resistance and wheezing phenotypes at 4 years of age

It is difficult to distinguish young children with respiratory symptoms who will develop asthma from those with transient symptoms only. Measurement of interrupter resistance may help to identify children at high risk of asthma. The aim of this study is to compare interrupter resistance in 4-year-old children with different wheezing phenotypes. All children participated in the Prevention and Incidence of Asthma and Mite Allergy cohort, a prospective birth cohort of more than 4,000 children. At 4 years of age, data on interrupter resistance plus wheezing phenotype were available for 838 children. Mean interrupter resistance values (95% confidence interval) were 0.95 (0.93, 0.97), 0.95 (0.92, 0.98), 0.96 (0.87, 1.05), and 1.08 (1.02, 1.14) kPa.L(-1).second for never (n = 482), early transient (n = 236), late-onset (n = 22), and persistent (n = 98) wheezing phenotypes, respectively. Additional analyses were performed for children with atopic and nonatopic mothers separately. Both in children with atopic and nonatopic mothers, children with persistent wheeze had significantly higher interrupter resistance values than children with never and early wheeze. In conclusion, mean interrupter resistance values were higher in children with persistent wheeze as compared with children with never and early transient wheezing phenotypes.     

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.     

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.     

Establishment of haematological and immunological reference values for healthy Tanzanian children in Kilimanjaro Region

Objective To determine the normal haematological and immunological reference intervals for healthy Tanzanian children. Methods We analysed data from 655 HIV‐seronegative, healthy children from 1 month to 18 years of age from the Kilimanjaro Region of Tanzania for this cross‐sectional study. Median and 95% reference ranges were determined for haematological and immunological parameters and analysed by age cohorts, and by gender for adolescents. Results Median haemoglobin (Hb) and haematocrit (Hct) for all age groups were higher than established East African reference intervals. Compared to U.S. intervals, reference ranges encompassed lower values for Hb, Hct, mean corpuscular volume, and platelets. Applying the U.S. National Institute of Health Division of AIDS (DAIDS) adverse event grading criteria commonly used in clinical trials to the reference range participants, 128 (21%) of 619 children would be classified as having an adverse event related to Hb level. CD4‐positive T‐lymphocyte absolute counts declined significantly with increasing age (P < 0.0001). For those aged under five years, CD4‐positive T‐lymphocyte percentages are lower than established developed country medians. Conclusions Country‐specific reference ranges are needed for defining normal laboratory parameters among children in Africa. Knowledge of appropriate reference intervals is critical not only for providing optimal clinical care, but also for enrolling children in medical research. Knowledge of normal CD4‐positive T‐lymphocyte parameters in this population is especially important for guiding the practice of HIV medicine in Tanzania.