Reference values are essential for interpreting IOS even by ATS and ERS. However, there are a few studies to determine the prediction equation of IOS parameters in the world. Most of the existing predictive equations are based on the data of white children of European origin. As the differences of race, region, geographical location, and environment, if the interpretation is based on unsuitable reference values, it will cause incorrect result and mislead the clinical. Therefore, it is urgent to establish the reference values of children's IOS parameters in China, to provide the basis for the rational application of IOS.
In the principle of forced oscillation, rectangular electric pulse is generated by pulse generator and superimposed on the resting breath of the subject. Through Fourier transform and spectrum analysis, different respiratory impedance values (viscous resistance, elastic resistance, and inertial resistance) at different frequencies can be calculated. The impulse oscillation method (IOS) can detect airway resistance and calculate compliance by using sound waves with frequencies from 5 to 35 Hz. Compared with PFT, IOS is a simple, no special cooperation lung function test method, easy to use, more suitable for the elderly, critically ill patients and children who are not easy to cooperate, especially 3–5 young children [18–20]. IOS can measure the resistance and reactance at different frequencies, so it can provide important information of different areas of the lung. According to the frequency dependence and reactance of resistance, it can determine the location and severity of airway obstruction, and can be used to monitor the pathophysiological changes of the respiratory system and patients with asthma and chronic obstructive pulmonary disease, it can replace the PFT to assist the diagnosis and follow-up of asthma [21–23].
Totally 6270 healthy children enrolled in this research, aged 4–17 years old and 100-180cm in height from 20 regions and 24 research centers in China. The results showed that age, height, and weight were closely related to IOS values, among which height was the most important. The second is age, and weight has the weakest effect. With the increase of age and height, the total respiratory impedance and airway resistance gradually decreased, while the elastic resistance decreased (negative value increased).
With the increase of age and height, the total respiratory impedance and airway resistance decreased gradually, while the negative value of elastic resistance decreased (the value increased), and showed the frequency dependence of airway resistance. In healthy children, airway resistance is mainly affected by airway diameter, which is inversely proportional to the fourth power of airway radius. Due to the narrow airway diameter, the resistance of young children is greater than that of older children. With the increase of age, the diameter becomes widen and the resistance decreases. In particular, the reduction of peripheral resistance is more significant .
For children in the process of growth and development, their height and weight increase significantly, especially the growth rate of height is ahead of their weight. Take 2-year-old children as an example: according to the WHO standard, the height of 2-year-old children increases by 5-7cm and the weight increases by 2kg every year. The growth of height reflects the growth of bones. With the development of whole-body bones, the thorax increases, and the lung volume, airway diameter and airway surface area increase rapidly. Therefore, the airway resistance of older children is significantly lower than that of younger children. On the other hand, with the increase of age, the development of bronchial smooth muscle gradually improves, which increases the elastic retraction force of the lung. Therefore, the lung compliance gradually increases, and the negative value of X5 decreases with the increase of age. In conclusion, height is the most important factor affecting respiratory impedance, followed by age and weight. The results are similar to those reported by Zheng Jinping [25,26].
The difference of airway diameter between different sexes is small, especially in young children, so there is no significant difference in the specific parameter value of airway resistance. Many articles show that even in different ways of pulmonary function examination, there are little gender differences in parameters [15–17], but there are significant differences in older children. Our result also found that as for gender, at different ages, has different effects on IOS. For younger children that gender had no statistically significant influence on the IOS parameters. However, IOS values are different in different gender in older children, the values of Zrs, Fres, R5 and R20 of boys were lower than girls, while X5 values was higher. The main reason may be that the height and weight of older children are very different at the same age, and height and weight, especially height, will significantly affect the results of IOS parameters.
Fres is the oscillation frequency when the reactance is zero, and the respiratory impedance is equal to the viscous resistance. It is a sign of the transition from low frequency dominated by elastic resistance to high frequency dominated by inertial resistance. It is a sensitive index reflecting the increase of respiratory tract viscosity resistance. In children with mild peripheral respiratory tract obstruction, Fres will increase even when R5 has no significant change. The fluctuation range is large. It reaches as high as 24Hz at the age of 4 years, and decreases to 14Hz at the age of 17 years, which tends to be about 10Hz in adults. It indicates that Fres decreases dynamically with age, and this result was and this result was similar to the result of Zheng Jinping's [25,26].
The European lechtenboerger prediction is widely used in China. The lechtenboerger prediction equation was derived from 506 healthy German adults aged 18–69 years in 1990, without excluding smokers, and with an uneven number of age and sex groups. It is found that the correlation between the respiratory function parameters and ethnic differences is obvious, so the equation is not suitable for the evaluation of healthy people in China, especially children. The results of this study suggest that height is the most important factor for IOS parameters, followed by age and weight. With the increase of age, height and body mass, airway resistance (Rrs) gradually decreases, Fres, which represents lung compliance, and electrical resistance (Xrs) increases gradually. In this study, the actual measured values are compared with the predicted values of the equations in Tables 4 and 5 and the predicted values of the foreign lechtenboerger equation. The results show that the correlation coefficient of the series of equations for children in China is significantly greater than that of the foreign lechtenboerger equation. The differences between the two groups of equations and the measured values of respiratory impedance in different height segments are small and similar. However, the differences of lechtenboerger equation in Zrs, R5 and R20 are significant, indicating that our predicted values are more suitable for Chinese children.
This study had several limitations. First, like other PFT references study, this cross-sectional study had limited interpretation of longitudinal changes in lung function. In addition, IOS measurements did not include area of reactance (AX), which is considered as a useful parameter in the evaluation of children with asthma [27,28]. Finally, the healthy children in this study only passed the questionnaire survey and did not carry out blood IgE screening and chest X-ray, which could not completely exclude the children with allergic diseases and lung disease. Therefore, these issues should be concerned in future studies.