DISCUSSION
In this prospective study, the compatibility of the tools such as PACT,
ACT, FeNO, PALQLQ and lung function with GINA criteria were evaluated in
children. According to GINA criteria, 84.2% of the patients had
“well-controlled” asthma.
FeNO and lung function were unsuccessful at revealing control status
according to GINA criteria(Table 1, 2). PACT/ACT and PAQLQ were
demonstrated to be able to determine “well controlled asthma” to some
extent of consistency with GINA criteria(Table 2). The best consistency
with the highest sum of sensitivity and specifity were obtained with the
cut-off levels of 22 for PACT, 21 for ACT and 5.9 for PAQLQ(Table 2).
Neverthless, there were only fair agreement with the kappa value of
0.221 and 0.150 for PACT and PAQLQ, respectively(p<0.001).
Besides, moderate agreement was obtained between ACT and GINA(κ=0.473,
p<0.001). Correctly classified patients with PACT, ACT and
PALQLQ according to GINA were 93(64.1%), 63(75.9%) and 139(62.9%),
respectively. Ultimately, ACT gives the best result for assessing asthma
control in children > 12 year-old. Also, PAQLQ gives
better compatibility for asthma control in children> 12 years old than those younger <12 years
old.
In our study, girls with older age have more frequently “not
well-controlled” asthma. This may be due to the adverse impact of sex
hormones on the control status of asthma which is a particular problem
for female adult patients. Frequency of allergic sensitisation is also
lower in the group of “not well-controlled” asthma. All these may be a
suggestion of the hypothesis that gender disparity in asthma control
starts at puberty approximately at the age of 10
years.24
Although there is no approved or validated gold standard for determining
asthma control, GINA criteria are accepted to be used such as worldwide
in daily practice.5, 25 PACT and ACT are some of the
tools validated and mostly used in clinical practice to assess asthma
control in children. Although the studies comparing the compatibility of
them and GINA criteria for the assessment of asthma control had
challenging results.6-10
In the study of Koolen et al, they compared PACT and ACT with GINA
criteria in assessing asthma control of children with similar study
design.10 They found an AUC of ROC curve analyses for
PACT 0.89 and ACT 0.92 which were higher than our study(0.79 and 0.86 in
our study, respectively). In their study, the cut-off value with the
highest sum of sensitivity and specifity for ACT was< 20
for uncontrolled asthma, which is the same as our study. The cut-off
value for PACT in their study was< 22, which is one
point higher than that in our study(< 21). The
sensitivity and specifity of both PACT and ACT(sensitivity 82% and
76%; specifity 85% and 96%, respectively) with the calculated cut-off
values were higher than our study(sensitivity 60.9% and 71.9%;
specifity 88.2% and 89.5%, respectively). This may be due to that
Koolen et al(n=145) had more patients with uncontrolled(13.1%) and
partly controlled asthma(33.8%) than those in our study(6.1% and
9.6%, respectively). Another reason may be patients with uncontrolled
and partly controlled asthma were evaluated together in the “not-well
controlled” asthma group in our study.
In another study with similar design, Voorend-van Bergen et al(n=228)
found the same best cut-off value for PACT(> 22) for
“well-controlled” asthma with respect to GINA
criteria.8 They proposed to determine
“well-controlled” asthma which is the primary goal of clinical asthma
management according to GINA criteria. Their AUC for PACT(0.81) was also
similar to our results(0.79). On the other hand, their best cut-off
value for ACT(> 23, AUC=0.91) was higher than
ours(> 21, AUC=0.86).
In a recent study, Deschildre et al compared PACT performance of
assessing asthma control with respect to GINA
crtieria.7 Also, they grouped asthma level of patients
as well controlled and not controlled(partially controlled or
uncontrolled), as we did in our study. Using ROC curve analyses, they
found the same cut-off value for PACT(< 21, for “not
controlled” asthma) with a higher sensitivity(76%), but lower
specifity(81.5%) than those found in our study(60.9% and 88.2%,
respectively). However, the most important difference from our study is
that the rate of “not controlled” asthma in their study (76.5%) was
much higher than that in our study(15.7%).7
As in the study of Voorend-van Bergen et al, FeNO was not difference
between the control groups of asthma as in our study.8As similar to earlier studies, we found no correlation between asthma
control scores, GINA criteria and FeNO or
FEV126-28. Symptoms,
lung function and airway inflammation represent different domains of
asthma phenotype and show poor agreement8. Many
children with uncontrolled asthma have normal lung functions between
exacerbations1. A low FEV1 percent
predicted, particularly if it is<60%, identifies patients at
risk of future asthma exacerbations independent of symptom
levels1. If symptoms are few despite low
FEV1 %predicted, limitation of lifestyle or poor
perception of airflow limitation should be considered that would be a
marker of untreated airway inflammation.29, 30 In our
study, none of the participants had FEV1<60%.
Besides, there were no difference for FEV1(expected %),
FEV1/FVC(ratio) and FEF25-75(expected
%) between control groups and no compatibility with GINA criteria(Tabel
1 and 2).
In our study, ACT had better results for agreement and compatibility
with GINA criteria than PACT. This may be due to that older children
replies ACT and they had better perception of symptoms and longer recall
period than children younger than 12 years old who replies PACT with
their parents. Parents have a longer recall period than children, who
may recall only the last few days1. The fact that
younger children would be more frequently asymptomatic except
exacerbations may have an additional contribution to this result. In
accordance, the correlation of PAQLQ and ACT was stronger than that of
PAQLQ and PACT in our study. Voorend-van Bergen et al had similar
results for this correlation8. Additionally, PAQLQ had
higher agreement with GINA criteria in children > 12
years old than those of younger ones in our study (κ=0.326,
p<0.001 and κ=0.151, p=0.014, respectively). There are several
studies demonstrated the correlation between PAQLQ and
ACT/PACT31-34. However, to the best of our knowledge,
this is the first study to achieve a cut-off value for PAQLQ that has
fair compatibility with GINA criteria.
The most important limitation of our study was lower number of patients
with uncontrolled and partly controlled asthma. This may be a
consequence of the study design that firstly the control status of
asthma was evaluated, treatment adherence and inhaler technique were
adjusted if needed. Four weeks later, patients were called for the main
visit at which the adherence and technique of treatment was better than
the first visit(data not shown). As a natural consequence, asthma
control was better at the main visit. Besides, this was a real-world
study which would provide more true information from daily clinical
practice. Real-world studies presently start to become cause of choice
because randomised controlled trials include selected patients
populations that rarely represent the real
situation35.
In conclusion, ACT seems to be better than PACT for compatibility with
GINA in assessing control status in children. Probably, it is because
older children have a longer recall period than younger
ones(<12 yrs). The better correlation of PAQLQ and ACT and
better compability of PAQLQ and GINA in older children may also be
related to this reason. Neverthless, the cut-off levels for PACT and ACT
differ from study to study. This may be because diffent study
populations, varying study designs, care settings and rate of patients
with uncontrolled asthma. So, it would be better to use these tools for
individual patients by comparing their own tests, instead of determining
control status according to cut-off values, until large scale studies
are performed to determine cut-off values of the tools for each
population individually.