DISCUSSION
In this prospective birth cohort
of 307 children followed through 30 months of age, API+ children showed
5.7-fold higher odds of physician-diagnosed asthma (independent of prior
respiratory infections and other potential confounders); as well as
higher odds of OCS and ICS use, ED visits, and hospitalizations for
wheezing than those who were API-.
Recently, a cross-sectional study in the US demonstrated that the
application of the API to a retrospective study for ascertaining asthma
status is suitable8. The same group demonstrated that
using natural language processing (NLP) mining of electronic health
records for API criteria allowed for the ascertainment of asthma in
children9; the NLP-API predicted asthma with
sensitivity 86%, specificity 98%, PPV 88%, and NPV
98%9. Similarly, a cross-sectional study in 916
Korean preschoolers showed that questionnaire-defined asthma was
associated with stringent API+ (sensitivity 72.2%, specificity 82%,
PPV 14.1%, NPV 98.6%, and 77% accuracy), but not with spirometry,
airway hyperreactivity, exhaled nitric oxide, or atopic
sensitization6. The authors speculated that the API
may serve as a more reliable tool than those tests for the diagnosis of
asthma in preschoolers; they also compared the API to other predictive
models for asthma, and the API had higher LR+ and lower
LR-6. Consistent with those results, we did not find
an association between atopic biomarkers and API+, although the
Phadiatop was performed only in a subsample in our study. Unfortunately,
we did not perform infant lung function tests.
Given the difficulties with diagnosing asthma in preschool children, the
high specificity, NPV, likelihood ratios, and diagnostic accuracy of the
stringent API in both our cohort and the Korean study6suggest that the API can provide a simple, non-invasive, and
easy-to-implement tool for asthma diagnosis in preschoolers with high
confidence. This is important, since for example a recent retrospective
study in the Netherlands done in 656 children age 6-18 years who
received the diagnosis of asthma by an international code for primary
care showed that 53.5% had overdiagnosis of asthma.10
A timely asthma diagnosis is important and it should be done as early as
possible; often the onset of symptoms happens within the first year of
life, and 70% have symptoms by age 3.11 Despite this,
asthma tends to be underdiagnosis in very young children, particularly
those who wheeze only with upper respiratory
infections.12 Such patients may be diagnosed with
other conditions such a “wheezy bronchitis”, “asthma bronchitis”,
“recurrent pneumonia”, “recurrent
bronchiolitis”.13 Preschool age is a critical time
for intervention since long cohort studies have found that lung function
trajectory is established at this time,14 also
inflammation and remodeling have already been found at this
age.15
There are three primary clinical reasons for making a diagnosis of
asthma in young children: to identify the most effective treatment in an
effort to alleviate symptoms and possibly prevent morbidity and
mortality; to educate the parents or primary caregiver to manage the
symptoms and avoid triggers; and to estimate and hopefully modify the
prognosis over time.16 Treatment of asthma aims to
reduce symptoms and the risk of future complications, both of which are
important motivators for patients and families to seek
treatment.16 However, when asthma symptoms are not
present, patients and their families may not be sufficiently motivated
to continue treatment unless symptoms recur when the treatment stops.
The present study had limitations. Because the asthma diagnosis was made
by independent physicians, we cannot completely rule out an incorrect
diagnosis. However, the API was also strongly associated with objective
measures such as oral steroids, ED visits, and hospitalizations. Due to
the age of the cohort, we did not have lung function studies; further
follow-up will allow us to perform spirometry and bronchodilator
response when participants are older. Lastly, our findings will need to
be replicated in other cohorts, and other biomarkers for asthma
diagnosis will need to be tested in future studies.
Conclusions: This longitudinal birth cohort study suggests, for first
time, that API+ can act as a proxy for the diagnosis of asthma in the
first three years of life.
Therefore, the API could be used
as a diagnostic tool (not only as a prognosis tool), but more studies
are needed to replicate these findings.