Early diagnosis and good control of asthma is expected to improve the course of the disease, the most common chronic respiratory illness in children [1]. According to the current guidelines, treatment of asthma should aim at achieving and maintaining asthma control [2]. However, assessing control of childhood asthma is challenging and subjective as there is discordance in the perception of severity of symptoms between children and their parents. Various non-invasive techniques to objectively measure the lung functions in children have been developed which include spirometry, impulse oscillometry, body plethysmography, multiple breath washout test, forced oscillation techniques [3-6].

Conventional spirometry is considered as the gold standard test for assessment of airflow obstruction; however, it has certain shortcomings. Firstly, it is an effort-dependent test, younger children and those with acute exacerbation are generally unable to perform the test; hence, there is a poor correlation between symptoms and test results. Secondly, spirometry cannot properly differentiate between distal and peripheral airways. The forced expiratory volume in one second (FEV1) and the mid-forced expiratory flow (FEF25-75) mainly represents the large and small airways, respectively [7]. Thirdly, the effort dependent nature of the test interferes with the reproducibility of the test [8].

Children aged 5-15 years, attending Pediatric Chest Clinic and Pediatrics OPD of the All India Institute of Medical Sciences, New Delhi, between 2010 to 2016, were eligible for screening. Inclusion criteria were physician-diagnosed asthma and the ability to perform spirometry. Patients were excluded from the study if they had interstitial lung disease, congenital heart disease, tuberculosis, cystic fibrosis, bronchomalacia/laryngo-malacia, tracheaesophageal fistula, vocal cord dys-function, hypersensitivity pneumonitis, chronic liver/renal disease, took medications that could induce chronic cough such as ACE inhibitors/a blockers, or residing outside Delhi or were unlikely to follow-up. Written informed consent was taken from the parent/guardian of the study participants. The study was approved by the Ethics Committee of the institution. Children were followed up regularly at an interval of three months.

All study procedures were performed using MasterScreen IOS (CareFusion, Germany 234 GmbH) and Spirolab III. Spirometry and IOS were performed and anthropometric measurements taken by trained research officer and technician at each visit. Patients were explained about the procedure and were then allowed to perform the test. The best among three readings was taken in spirometry to ensure reproducibility of the test. FEV1 value was taken as a measure of airflow obstruction.

Statistical analysis: All statistical analyses were performed using STATA version 13 (StataCorp, College Station, TX, US). IOS parameters (percentage predicted of Z5, R5, X5, R5-20, and actual values of AX) and FEV1 (percentage predicted) were compared by Pearson correlation coefficient. The above mentioned parameters were individually compared in controlled and uncontrolled state of asthma by t test or rank-sum test as appropriate. The receiver operating characteristic (ROC) curves were used to evaluate the discriminatory powers of FEV1 and the IOS parameters in assessing control of asthma. Generalized estimating equation (GEE) was used to evaluate the association between controlled state and FEV1 and IOS parameters over time.

TABLE I Baseline Demographics and Pulmonary Function Test of Children with Asthma (N=256)

FEV1 and the IOS parameters Z5, R5, X5, R5-20 and AX were all significantly correlated with each other in both controlled and uncontrolled state (data not shown). FEV1 and all the IOS parameters were significantly different in the controlled and uncontrolled state (Table II). The areas under the ROC curve (95% CI) for discriminating the controlled and uncontrolled state were comparable (Table III).

TABLE II Comparison of Impulse Oscillometry and Spirometry Parameters in Controlled vs Uncontrolled Asthma

TABLE III IOS and Spirometry Parameters in Assessing Control of Asthma

GEE showed a significant association of FEV1 and AX measured over the duration of follow-up with the controlled state of asthma. For each unit change (increase) in FEV1 over time, the odds of control of asthma was 1.02 (95% CI: 1.01-1.03). For each unit of increase of AX over time, the odds of control of asthma was 0.88 (95% CI: 0.81-0.97).

Our study demonstrated that IOS and spirometry have comparable ability to detect the control state of asthma in children. Both IOS and spirometry yielded similar results in differentiating children with controlled and uncontrolled state of asthma. There was a significant association of increase in FEV1 and AX measured over the duration of follow-up, with the controlled and uncontrolled state of asthma, respectively. The FEV1 values were statistically different in the controlled versus uncontrolled groups; however, the uncontrolled group too had a fairly good lung function.

IOS is a form of forced oscillation technique which is based on the physiologic concepts originally described in 1956 [10], and can measure the mechanical properties of lung [11-13]. Spirometry, being effort dependent is difficult to perform in younger children, particularly those who present with uncontrolled or acute exacerbation of asthma. There are limited numbers of studies in children which have observed the utility of IOS in assessing long term control of asthmatic children [5,9]. IOS is especially important in determining the status of smaller airways and studies have also inferred that AX, which is a parameter representing the smaller airways, is the best indicator of long-term control and treatment response in childhood asthma [4,9,14]. A recent trial found that assessment of pulmonary function over time with IOS might offer additional insights into the response of asthmatic patients to therapy, and might detect alterations in airway mechanics not reflected by spirometry [4]. Over a prolonged period in their study, the area of reactance (AX) showed continued improvement compared to spirometry parameters [4].

In our study, a significant difference in R5-20 and AX in controlled and uncontrolled state was observed. Similar findings were demonstrated prior to bronchodilator therapy in asthmatic children where both IOS and spirometry were performed, and small airway measurements by IOS in uncontrolled asthma were significantly different from those of controlled asthma [14]. IOS parameters that reflect smaller airways like the difference in resistance between 5　Hz and 20　Hz　(R5-R20) and the area under the reactance curve (AX), are more closely related to asthma control [15]. The assessment of asthma control over a period of time in our cohort showed that both IOS and spirometry measurements were equally useful in the assessment of asthma control, as concluded in a study in adults with persistent asthma [16].