4.Discussion
To our knowledge, this is the first systematic review and meta-analysis of IOS parameters to identify the risk of acute attack or loss of control in children with asthma. Our research involved a total of 615 cases from 6 studies. We selected common IOS parameters and analyzed them. The results showed that R5, X5, AX, and Fres may better predict asthma exacerbations or loss of control.
Asthma is a common disease in pediatrics. The goal of care is to maximize the safety of treatment by achieving and maintaining the control of disease at the lowest level and dose of inhaled corticosteroids (ICS). Studies have shown that childhood asthma control is closely related to adult asthma control, lung function, and chronic obstructive pulmonary disease (COPD)[21]. An acute attack of asthma refers to the sudden occurrence of symptoms such as wheezing, coughing, shortness of breath, chest tightness, or the acute exacerbation of the original symptoms, which can even lead to dyspnea, asphyxia and life-threatening. Therefore, timely and objective indicators are needed for early identification and prevention. Pulmonary ventilation function monitoring is an important means for future risk assessment of asthma, but it has certain limitations. IOS has been widely clinically studied because of its simple operation and its ability to measure the impedance of the respiratory system, which consists of reactance and resistance. Previous trials suggested that IOS may be a reliable non-invasive method to assess asthma control in children[22, 23].
Resistance can be conceptualized as the energy required for sound waves to pass through the airways and inflate the lung. R5 represents the total airway resistance. The included five trials found that R5 increased in asthma exacerbations[14-17, 19]. Only Smith et al did not report the difference in R5 between the two groups[17, 19]. Our study showed that R5 had a good correlation with the acute attack of asthma. Besides, Galant et al held that R5 increased significantly when peripheral airway obstruction occurred[24]. The reactance of the respiratory system, expressed in Xrs, consists of the inert and elastic properties of the respiratory system. X5 is defined as the peripheral elastic resistance, providing important information about the peripheral respiratory tract. When small airway obstruction and lung compliance decrease, the negative value will increase significantly[25]. Our study found a good correlation between X5 and asthma loss of control. Schulze et al found that X5 represents hyperinflation[16]. Tirakitsoontorn et al also reported X5 may be well suited to identify peripheral airway impairment phenotype in the clinical setting[18]. Galant et al further confirmed that X5 decreased significantly in the uncontrolled asthma group[26]. Fres also known as resonant frequency refers to the frequency when the elastic recoil of the airways and lungs is equal and opposite to the inertance of the system, that is, the reactance is zero. Moreover, based on the mechanical properties of airways, Fres is the dividing point between large and small airways[24]. Our result revealed that Fres had a certain significance in predicting the acute attack of asthma, but there was large heterogeneity (I2=85.1%,p=0.000). This may be contributed to the small number of trials and the large age span between the trials. AX means the area under the reactance curve between 5 Hz (X5) and the Fres value, similar to X5, which also can provide information about distal airway obstruction[27]. Our research found a significant correlation between AX and acute asthma.
Peripheral airways have much smaller lumina than central (large) airways, and inflammation/edema in the walls of peripheral airways can be expected to have a proportionately larger effect on lumen size than inflammation/edema in larger airways. The above indicators reveal that peripheral airway impairment may be associated with uncontrolled asthma. Besides, previous studies have also reported that peripheral airway impairment is clinically related to asthma exacerbation, uncontrolled asthma, loss of control, and asthma severity[22, 23]. However, our study did not find the role of the R5-20 indicator in predicting the loss of asthma control.R5-20 refers to the resistance of the peripheral airways, which was also inconsistent with previous research. This may be related to the age and height of the population included in the study. When the peripheral airway was obstructed, R5 was significantly elevated and R20 was not changed. However, R5 decreased linearly with the growth of height[28].
Our meta-analysis had some limits. First, the severity of asthma
exacerbations or uncontrolled asthma and baseline treatment varied from study to study, which may affect the results. In addition, other factors like race, age, sex, height can also bring out the heterogeneity. These indicate that a large number of randomized trials are still needed to confirm the potential relationship between IOS parameters and acute attack of asthma. Our research also had some advantages. For instance, it is the first systematic review and meta-analysis about the predictive value of the IOS common parameter in asthma exacerbations. And all trials were of high quality.