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.