The general purpose of this study was to determine the utility of IOS and spirometry in the evaluation of children in a general pediatric allergy clinic with well-controlled asthma in comparison to children who did not have asthma. This study showed overall that IOS was more sensitive and specific in identifying children with reversible obstruction than spirometry. When analyzing independent IOS lung parameters and comparing them to FEV1, R10 best differentiated those with asthma and non-asthmatics. Using objective cut-off points for lung parameter responses to bronchodilator, the consideration of CV did not contribute significantly to interpreting the results of the response. Additionally, the action of performing forced expiratory maneuvers in spirometry may cause a decrement in lung function detected by IOS. Thus, when both tests are performed sequentially, the data support the recommendation to perform IOS before spirometry.
The demographic data () indicate, based on a questionnaire, that parental assessment of asthma correctly identified 78% of patients diagnosed with asthma. This finding is remarkably consistent with an International Study of Asthma and Allergies in Childhood (ISAAC)-based questionnaire administered to parents of 6,295 children aged 1–6 whereupon 77% of the children parentally assessed to have asthma were diagnosed as such in their medical record,16
thus highlighting the important consideration of parental appraisal of childhood asthma.
When comparing pre- and post-bronchodilator responses in all 117 patients we found a statistically significant difference in R5, R10, X5, and AX, with R10 most remarkable (P
= 0.0008). This is consistent with other studies of IOS bronchodilator responses that found R5 and R10 to best differentiate between asthmatic and non-asthmatic children.10,17
Although others have found R5–R20, frequency dependance of resistance, to be highly correlated with AX and a sensitive measure of bronchomotor tone,18,19
our analysis did not reveal this correlation, nor did this parameter significantly distinguish between the asthmatics and nonasthmatics at baseline, or following administration of bronchodilator ( and ). This may be due to the greater variability in age, larger number of subjects or differences in severity of asthma in our disease population in comparison to other studies. ROC curve comparisons in also displays R10 with the best profile of sensitivity (77%) and specificity (76%) at a cut-off point of –8.6%. This suggests that an 8.6% or greater decrease in post-bronchodilator airway resistance at 10 Hz distinguishes between those with and without asthma. Similarly, cut-off points for R5 were –11.2%, and –29.1% for AX (). Previous studies in children and adults have suggested higher cut-off values for a “positive bronchodilator response,” such as 20–40%, 15–20%, and 50% for R5, R10, and AX, respectively.14,20,21
The lower cut-off values determined herein may be a reflection of the methodology used to determine these cut-offs, the age of our patients and/or study selection of well-maintained asthmatic children.
We used the CV to assist in the interpretation of response to bronchodilator. The mean CV in our total study group (n = 117) ranged from 6.6% for R10 to 21.4% for X5 and was generally lower in those without asthma, although the difference between groups did not reach significance (). This range is consistent with one study that found day-to-day measurements of CV using forced oscillation technique in healthy adults to be 7%.22
To determine the relevance of using the CV in the interpretation of a response to bronchodilator we employed the criteria as others have suggested8
to require a percentage improvement in IOS lung parameters following bronchodilator that is at least twice the preor post-CV, whichever is higher. This is formulated by the CV index (percent change in R or X following bronchodialator/2CV). A CV index ≥1 indicates a positive response to bronchodilator and may include patients with lower bronchodilator responses and lower variability, whereas a CV index <1 suggests too much variability and may exclude patients that met objective criteria (i.e., 20% for R10) for a positive response. Although the consideration of using the CV index to refine the interpretation of response to bronchodilator is reasonable, when factored into the ROC curves and replotted there was no significant improvement in sensitivity and specificity profiles ().
Based on the bronchodilator response in those patients that were able to perform spirometry (asthmatics, n = 66; non-asthmatics, n = 16) and IOS, we have shown that IOS is better than spirometry at identifying children with asthma () and the ROC comparison of FEV1
to other IOS parameters suggests it is a more sensitive and specific tool for distinguishing between these groups (). The advantages of IOS over spirometry gleaned from this study are supported by others.10,17,19,23–26
Our data are consistent with an earlier report which showed that significant differences in IOS-assessed bronchodilator responses distinguished between young Korean asthmatics and non-asthmatics, which was not detected by spirometry.17
In another study, when 24 clinically stable adolescent asthmatics were assessed with pulmonary function testing over 3 consecutive days, significant differences in reactance and resistance was detected by IOS but not by spirometry.19
Others have reported that in long-term studies of lung function in children treated with inhaled corticosteroids, IOS (specifically AX) may be more informative in determining lung function than spirometry.27
Other limitations of spirometry include effort dependency, which may preclude accurate testing in younger children and those mentally or physically compromised. Due to these factors, the failure rate in children under 4 years old was 100% (11/11) and overall, 25% (33/117) of our patients were unable to perform spirometry. A 17-year-old subject in our study with recurrent pneumothoraces and pulmonary fibrosis secondary to chemotherapy was prohibited from performing spirometry because of the risk inducing a pneumothorax. However, his pulmonary status was assessed repeatedly and un-eventfully over years using IOS. We successfully performed IOS down to 2 years old, while we found that spirometry was not useful for those ≤5. Others have shown that IOS can be performed successfully in 3- to 6-year-old asthmatics, and showed reproducible and sensitive indices of lung function.10,17,24,26,28,29
In a 2-year study to determine the effects of inhaled corticosteroids on the development of asthma in pre-school children, IOS was exclusively used to assess lung function because only 56% of the participants were able to perform spirometry.30
Our data support the conclusion that when IOS and spirometry are performed sequentially, IOS should be performed first (). Performing forced expiration during spirometry for multiple trials may cause bronchospasm detected by IOS (). As our data suggest, patients with atopic asthma on controller medications with active chest symptoms are more likely to experience a decrease in lung function following spirometry.
In summary, this study supports the objective utility of IOS in the evaluation of children with asthma. Current guidelines for pediatric asthma in terms of the establishment of a diagnosis, classification of severity, assessment of impairment and response to therapy recommend lung function testing with spirometry. The greater sensitivity and specificity of IOS shown in this study in addition to its broader application in younger or physically compromised children merits the consideration to incorporate IOS into future standard guidelines for the treatment of children with asthma.