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.