The Asthma Predictive Index: A very useful tool for predicting asthma in young children

doi:10.1016/j.jaci.2010.06.032

Journal of Allergy and Clinical Immunology

Volume 126, Issue 2, August 2010, Pages 212-216

https://doi.org/10.1016/j.jaci.2010.06.032 Get rights and content

Recurrent wheezing is a common problem in young children: approximately 40% of children wheeze in their first year of life. However, only 30% of preschoolers with recurrent wheezing still have asthma at the age of 6 years. Nevertheless, asthma, the most prevalent chronic disease in children, is difficult to diagnose in infants and preschoolers. This article reviews the importance of determining at an early age which infants/preschoolers will have asthma later in life, analyzes the pros and cons of different predictive indices, and discusses the efficacy of the Asthma Predictive Index.

Section snippets

Background

Unfortunately, infants who wheeze and eventually have asthma coexist with a large group of infants with recurrent wheezing whose symptoms are transient and usually subside during early years of school. It is a challenge to distinguish between these groups during infancy and early childhood simply on the basis of clinical presentation. No accurate screening tests (using genetic or single biochemical markers) have been developed to determine which young children with recurrent wheezing will have

API and other indices

The API was developed 10 years ago by using data from 1246 children in the Tucson Children's Respiratory Study birth cohort. It was based on factors that were found during the first 3 years of life to predict continued wheezing at school age.¹⁵ A positive API score requires recurrent episodes of wheezing during the first 3 years of life and 1 of 2 major criteria (physician-diagnosed eczema or parental asthma) or 2 of 3 minor criteria (physician-diagnosis allergic rhinitis, wheezing without

Applications

Among the 3 asthma predictive indices discussed, the API is the only one tested in different populations and in independent studies, such as randomized clinical trials (RCTs).32, 33 The API is also the only index used in studies to determine relationships between biomarkers, such as comparing fraction of exhaled nitric oxide (FeNO)25, 34 or early lung function (Garcia-Marcos, personal communication). Recently, a prospective cohort study of 391 young children (age, 3-47 months) showed that

Conclusions

The most impressive aspect of the API is its ability to rule out the likelihood of asthma by school age in young children with wheezing.³⁹ For children who are “early wheezers during the first 3 years of life,” API negative predictive values ranged from 93.9% at 6 years of age to 86.5% at 13 years of age. For children who are “early frequent wheezers during the first 3 years of life,” the negative predictive values were 91.6% and 84.2% for 6 and 13 years of age, respectively. Considering the

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Common respiratory disorders in children
2023, Encyclopedia of Child and Adolescent Health, First Edition
Unconjugated bilirubin is associated with protection from early-life wheeze and childhood asthma
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Citation Excerpt :
Children who did not wheeze in the previous 12 months were considered nonwheezers. Those who wheezed were categorized as follows on the basis of standard International Study of Asthma and Allergies in Childhood categorical responses: 1 to 3 wheezing episodes in the previous 12 months, and 4+ wheezing episodes in the previous 12 months.16 Allergic sensitization (yes/no) to common aeroallergens (cat, dog, mold mix, and house dust mite mix) and food allergens (egg, milk, peanut) was defined on the basis of positive specific IgE testing of plasma (>0.1 kUA/L) at age 1 year.
Wheeze and allergic sensitization are the strongest early-life predictors of childhood asthma development; the molecular origins of these early-life phenotypes are poorly understood.
We sought to identify metabolites associated with early-life wheeze, allergic sensitization, and childhood asthma.
We conducted a nested case-control study using Environmental influences on Child Health Outcomes Program cohorts for discovery and independent replication. Wheeze and allergic sensitization were defined by number of wheeze episodes and positive specific IgE at age 1 year, respectively. Asthma was defined as physician diagnosis of asthma at age 5 or 6 years. We used untargeted metabolomics, controlling for observed and latent confounding factors, to assess associations between the plasma metabolome and early-life wheeze, allergy, and childhood asthma.
Eighteen plasma metabolites were associated with first-year wheeze in the discovery cohort (n = 338). Z,Z unconjugated bilirubin (UCB) and its related metabolites exhibited a dose-response relationship with wheeze frequency; UCB levels were 13% (β = 0.87; 95% CI, 0.74-1.02) and 22% (β = 0.78; 95% CI, 0.68-0.91) lower in children with 1 to 3 and 4+ wheeze episodes compared with those who never wheezed, respectively. UCB levels were also associated with childhood asthma (β = 0.82; 95% CI, 0.68-0.98). Similar trends were observed in 2 independent cohorts. UCB was significantly negatively correlated with eicosanoid- and oxidative stress–related metabolites. There were no significant associations between metabolites and allergic sensitization.
We identified a novel inverse, dose-dependent association between UCB and recurrent wheeze and childhood asthma. Inflammatory lipid mediators and oxidative stress byproducts inversely correlated with UCB, suggesting that UCB modulates pathways critical to the development of early-life recurrent wheeze and childhood asthma.
ORMDL3 modulates airway epithelial cell repair in children with asthma under glucocorticoid treatment via regulating IL-33
2020, Pulmonary Pharmacology and Therapeutics
Study found that glucocorticoids, as first-line treatments for asthma, fails to prevent asthma recurrence. Orosomucoid-like (ORMDL) 3 is associated to childhood asthma onset and involved in the inflammation and repair of airway epithelium. We explored the functional role of ORMDL3 in glucocorticoid treatment for childhood asthma.
Mice were sensitized with Ovalbumin (OVA) and treated with Dexamethasone (Dex), followed by OVA challenge to establish a mouse model of asthma. Histopathological changes in lung tissues were observed by hematoxylin-eosin and masson staining. Human bronchial epithelial (16HBE-14°) cells were transfected with ORMDL3 overexpression plasmid and siRNA-interleukin (IL)-33 alone or in combination, followed by Dex. Cell viability was measured by MTT assay. Cell migration was evaluated by wound healing assay. The expressions of E-cadherin and Vimentin and the activation of NF-κB and MAPK/ERK in 16HBE-14° cells were assessed by Western blot. The expressions of ORMDL3 and IL-33 in lung tissues and 16HBE-14° cells were analyzed by qRT-PCR or Western blot.
Dex treatment alleviated the histopathological abnormality and reversed the overexpressions of ORMDL3 and IL-33 in the lung tissues of asthmatic mice. Overexpressed ORMDL3 enhanced migration and viability, decreased E-cadherin level, increased the levels of IL-33 and Vimentin, and promoted the phosphorylation of NF-κB and MAPK/ERK in Dex-treated 16HBE-14° cells, thus reversing the effect of Dex treatment. However, siRNA-IL-33 inhibited viability and migration, increased E-cadherin level, decreased Vimentin level, and suppressed the phosphorylation of NF-κB and MAPK/ERK, thus reversing the effect of overexpressed ORMDL3 in Dex-treated 16HBE-14° cells.
ORMDL3 overexpression helped airway epithelial cellrepairin asthma via regulating IL-33 expression.
Barrier dysfunction in the atopic march—how does atopic dermatitis lead to asthma in children?
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Variability in Diagnosed Asthma in Young Children in a Large Pediatric Primary Care Network
2020, Academic Pediatrics
Our objectives were to 1) quantify the frequency of wheezing episodes and asthma diagnosis in young children in a large pediatric primary care network and 2) assess the variability in practice-level asthma diagnosis, accounting for common asthma risk factors and comorbidities. We hypothesized that significant variability in practice-level asthma diagnosis rates would remain after adjusting for associated predictors.
We generated a retrospective longitudinal birth cohort of children who visited 1 of 31 pediatric primary care practices within the first 6 months of life from 1/2005 to 12/2016. Children were observed for up to 8 years or until the end of the observation window. We used multivariable discrete time survival models to evaluate predictors of asthma diagnosis by 3-month age intervals. We compared unadjusted and adjusted proportions of children diagnosed with asthma by practice.
Of the 161,502 children in the cohort, 34,578 children (21%) received at least 1 asthma diagnosis. In multivariable modeling, male gender, minority race/ethnicity, gestational age <34 weeks, allergic rhinitis, food allergy, and prior wheezing episodes were associated with asthma diagnosis. After adjusting for variation in these predictors across practices, the cumulative incidence of asthma diagnosis by practice by age 6 years ranged from 11% to 47% (interquartile range: 24%–29%).
Across pediatric primary care practices, adjusted incidence of asthma diagnosis by age 6 years ranged widely, though variation gauged by the interquartile range was more modest. Potential sources of practice-level variation, such as differing diagnosis thresholds and labeling of different wheezing phenotypes as “asthma,” should be further investigated.
Association of Early Childhood Wheeze and Asthma Diagnosis Documentation by Race, Ethnicity, and Language in Children
2024, Journal of the American Board of Family Medicine

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: Disclosure of potential conflict of interest: J. A. Castro-Rodriguez has declared that he has no conflict of interest.

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Reviews and feature articleThe Asthma Predictive Index: A very useful tool for predicting asthma in young children

Section snippets

Background

API and other indices

Applications

Conclusions

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

J Allergy Clin Immunol

Ann Allergy Asthma Immunol

Ann Allergy Asthma Immunol

J Allergy Clin Immunol

Asthma and wheezing in the first six years of life

N Engl J Med

Use of inhaled corticosteroids in pediatric asthma

Pediatr Pulmonol

A community-based study of the epidemiology of asthma. Incidence rates, 1964-1983

Am Rev Respir Dis

Status of childhood asthma in the United States, 1980-2007

Pediatrics

Age-related differences in perceived asthma control in childhood: guidelines and reality

Eur Respir J

Recognizing early asthma

Allergy

Early diagnosis of asthma in young children by using non-invasive biomarkers of airway inflammation and early lung function measurements: study protocol of a case-control study

BMC Public Health

Airway responsiveness in early infancy predicts asthma, lung function, and respiratory symptoms by school age

Am J Respir Crit Care Med

Relationship between bronchial hyperresponsiveness and impaired lung function after infantile asthma

PLoS One

Reviews and feature article
The Asthma Predictive Index: A very useful tool for predicting asthma in young children