The potential to predict the course of childhood asthma

Abstract

Many children experience pre-school or early childhood wheezing. In a significant proportion symptoms disappear as the child grows, but others have persistent and troublesome asthma which can be life-long. Tools to predict course of disease in young children are a priority for families and clinicians. This review summarizes evidence from several longitudinal population-based birth-cohort studies that have identified risk factors for persistence and remission of childhood asthma. These factors include clinical characteristics, environmental and other exposures, familial factors, biomarkers of allergic inflammation, measurements of lung function and airway responsiveness, and genetic variants. This review also introduces the concept of polygenic risk and genetic risk scores, and describes results from a recent study that suggests promise for the use of genetic information in predicting the course of childhood asthma. We conclude with a discussion of implications and future directions.

Keywords::

• asthma
• atopy
• birth cohort
• children
• genetic risk score
• longitudinal studies
• persistence
• severity

Financial & competing interests disclosure

DW Belsky was supported in part by the US National Institute on Aging grant T32 AG000029. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript other than those disclosed.

No writing assistance was utilized in the production of this manuscript.

Key issues

• Childhood asthma is common. For many children, asthma is a childhood-limited problem, but for others, symptoms persist across the life course.

• Risk factors for persistent asthma have been identified from birth cohort studies that follow unselected samples of children over time and track the onset and course of asthma.

• Risk factors for persistent asthma include young age at onset, manifestation of severe symptoms including airway hyperresponsiveness and airflow obstruction in early childhood, rhinoconjunctivitis and eczema, childhood allergic sensitization, respiratory infections and family history of asthma.

• Genome-wide association studies have discovered asthma-associated genetic variants and revealed that most of the population carries some degree of genetic risk for asthma, while smaller groups are at especially low or especially high risk.

• Children with asthma who carry higher levels of genetic risk may be predisposed to a persistent course of disease, according to one birth cohort study, although genetic predictions have low sensitivity and specificity.

• Despite efforts to combine information across risk factors, it is not yet possible to predict the course of childhood onset asthma with accuracy, and existing predictive algorithms often yield conflicting results.

• More precise definitions of risk factors and standardized approaches to phenotyping asthma are needed to improve accuracy of predictive algorithms.

• Integrating genomic information into prediction algorithms may also improve accuracy, especially if interactions among genomic, phenotypic and environmental factors can be quantified.