Discussion
We described, for first time, the prevalence of an inversion of the reactance curve and the X5 approx. correction in asthmatic children. We found that these phenomena occurred in 65.5% of the cases, and this high prevalence is perhaps because the majority of our population had moderately or severely persistent asthma, so even in an asymptomatic period they could persist in showing a small-airway obstruction with IOS but with normal spirometry. Other studies have shown the presence of a small-airway obstruction in the IOS but with normal spirometry.19,20
In our study, the X5 approx. correction was needed in more than 80% of preschoolers, 67% of schoolchildren, and 36.5% of adolescents (p for trend < 0.001), indicating that this phenomenon is related to age. Several factors could explain why the reversal of reactance is more frequent in preschoolers, e.g. the smaller caliber of the airway, which makes the parallel resonance more visible, and the fact that the site of obstruction is predominantly the small airway, which makes it more severe. In addition, the lung function deficits that these children can carry even from birth and changes in the structure of the lung such as hypertrophy of the bronchial smooth muscle that has been found in biopsies are factors that could also have an influence.21-25
The adolescents that needed X5 approx. correction had significantly higher abnormal values of D5-20 in the IOS. There was clear evidence suggesting that the higher abnormal D5-20 values were associated with peripheral airway dysfunction in children and adolescents.26,27 This phenomenon was not found for other IOS parameters, maybe due to the cutoff used for adolescents’ being too high; therefore, it would perhaps be better to use an adult cutoff for determining peripheral airway obstruction.28,29
Among schoolchildren and preschoolers needing X5 approx. correction, the mean values of R5, Fres, AX, and D5-20 were significantly higher. The alterations of these IOS parameters were associated with peripheral airway dysfunction and with an asthma phenotype characterized by inadequate control, normal FEV1, alteration in FEF25-75%, air trapping, and higher AX and D5-20. For these patients, the use of ultrafine inhaled corticosteroids (ICS) that can reach small airways <2 mm in diameter was suggested.6,8,26,29,30 Therefore, it could be hypothesized that the inversion of the reactance curve and the X5 approx. correction could be useful for identifying this asthma phenotype.
Among schoolchildren and adolescents, the mean FEF25-75% value was significantly lower in the group that required X5 approx. correction, and this confirmed that these patients had alterations in the small airways manifested by spirometry. Previous studies31,32 have shown the association between lower values of FEF25-75% and asthma severity, ICS use, exacerbations, and bronchodilator response in children with normal FEV1; therefore, the presence of X5 approx. may have similar implications.
Compared to X5, X5 approx. exhibited closer correlation with other IOS parameters and FEF25-75%. This finding, together with the abnormal results and means in the IOS, suggests that X5 approx. is a better parameter for measuring small airway alteration than X5. This is especially important in preschoolers, since this is the age where morbidity and hospitalizations for asthma occur more frequently than in other childhood ages.33,34 Therefore, having an objective parameter (X5 approx.) could be useful for improving their asthma management.
Is important to mention that this inversion of the reactance curve was anecdotally reported in cystic fibrosis, 35 a disease characterized by small-airway dysfunction, the presence of different time constant units, and inhomogeneity ventilation, which can also occur in asthma, as was shown in the present study.
Our study has some limitations. First, we did not know the asthma control level of each patient, and it would be ideal to know if this new parameter (X5 approx.) is associated with uncontrolled asthma. Second, we were not be able to follow up with these patients, and it would be of interest to know if patients who required X5 correction had worse asthma evolution or more persistent symptoms than those who did not require X5 correction. Therefore, future studies that take these considerations into account are needed.
In conclusion, this study showed that inversion of the reactance curve is exhibited in a high percentage of asthmatic children, that it significantly decreases with age, and that it has a close association with IOS parameter alterations that measure small-airway dysfunction. Compared to X5, X5 approx. correlated better with other IOS parameters and with FEF2575, suggesting that it is a good indicator for asthma management in children.