Wheezing is often an early indicator of childhood asthma. While there are several studies looking at patterns of childhood wheezing as well as studies investigating the association between genetic variants and childhood asthma, research is lacking on the direct association between wheezing patterns and genetic variants. To fill this gap, members of ECHO Children’s Respiratory Research and Environment Workgroup (CREW) explored the effect of chromosome 17q12-21 variants, which have been previously linked to childhood asthma, on patterns of wheezing in African American and European American children across the US.

Data collection lasted several years as ECHO CREW sites used questionnaires and interviews to collect information from children and their parents. The researchers harmonized data from the different sites in order to group children based on when and how often they wheezed from birth to 11 years old. Sites also collected DNA samples from most of the children, and researchers analyzed those samples for the presence of nine different small gene changes, also known as single nucleotide polymorphisms (SNPs), at the 17q12-21 chromosome locus. Using statistical techniques, the team then identified different wheezing patterns and measured their association with each of the genetic variants.

Overall, four wheezing patterns were identified among participants:

1. Infrequent—few wheezing episodes only in the first three years
2. Transient—some wheezing in first three years, then less, and gone by around six years
3. Late-onset—little wheezing in the first few years and then gradually occurs more often
4. Persistent—many wheezing episodes over the first 11 years of life.

These patterns are similar to with the wheezing patterns identified in previous studies that used data collected from other birth cohorts.

Researchers also found that a little more than half of the children experienced wheezing before three years old, and 62% wheezed within the first 10 years of life. Early childhood wheezing often starts due to a viral infection, such as the common cold. Additionally, some children who are diagnosed with asthma may experience transient wheezing patterns that will not last beyond pre-school.

This study was also the first to investigate how genetic variation relates to wheezing patterns in African American children. African American children were statistically more likely than European American children to experience persistent wheezing. While most of the SNPs were associated with transient, late-onset, and persistent wheezing patterns in European American children, only two SNPs were associated with these wheezing patterns in both European American and African American children. One of these SNPs interrupts production of a protein that may be involved in protecting the body from viral infection in the upper airways.

“Asthma is complicated, and susceptible children exposed to hazards such as viruses, allergens, and pollution have more risk of having episodes of wheeze in the preschool years,” said lead author Brian Hallmark, PhD, from the University of Arizona. “Some genetic variations put children at higher risk. The more we understand how asthma develops, the better we can identify and help children at risk and find ways to prevent asthma.”

Not only is this study the first to examine genetic variation and wheezing patterns in African American children, it is also the first to find evidence that genetic variants associated with childhood asthma are also associated with all early life wheezing patterns. These results are found consistently in children from different cities and those born in different decades. In the future, the team will focus on possible associations between children’s insulin levels, genetic variations, and the development of asthma in childhood.

Read the research summary.