Viral infections, family history drive trajectories of pediatric wheeze development

Key takeaways:

• Early-onset wheeze was associated with nonallergic rhinitis and respiratory infections before age 6 months.
• Family history of allergy was associated with higher odds for late-onset and persistent wheeze.

Wheeze may follow one of four distinct trajectories with different risk factors as it develops in children, possibly determined by the timing of viral infection, according to a study published in Annals of Allergy, Asthma & Immunology.

For example, persistent wheeze was associated with higher risks for atopic diseases, Hui Xing Lau, BSc, research officer at Singapore Institute for Clinical Sciences, Agency for Science, Technology and Research in Singapore, and colleagues wrote.

The study comprised 974 children (52.4% boys) from the multi-ethnic mother-offspring Growing Up in Singapore Towards healthy Outcomes — or GUSTO — cohort, including 557 (57.3%) of Chinese ethnicity and 479 (54.6%) with a family history of allergy. Researchers assessed wheeze and allergic comorbidities in the cohort through age 8 years using modified International Study of Asthma and Allergies in Childhood questionnaires and skin prick tests.

Overall, 234 (30.5%) children in the cohort had at least one occurrence of wheezing during their first 8 years of life.

Using group-based trajectory modeling, the researchers classified childhood wheezing into four categories:

• early onset with rapid remission from age 3 years (n = 44; 4.5%);
• late onset peaking at age 3 years and rapid remission from age 4 years (n = 79; 8.1%);
• persistent with a steady increase through age 5 years and high wheeze occurrence until age 8 years (n = 39; 4%); and
• no or low wheeze (n = 812; 83.4%).

Compared with the no or low-wheeze group, which had less than 1% probability of wheeze development through age 8 years, odds for early-onset wheeze were higher with maternal tobacco exposure during pregnancy (adjusted OR = 3.78; 95% CI, 1.05-13.61), childcare attendance during infancy (aOR = 5.39; 95% CI, 1.66-17.54), and rhinitis (aOR = 3.39; 95% CI, 1.06-10.8) and respiratory infections (aOR = 11.72; 95% CI, 3.16-43.43) before age 6 months.

Also, odds for late-onset wheeze increased with mixed feeding vs. mainly breastfeeding (aOR = 4.89; 95% CI, 1.27-18.83), whereas odds for persistent wheeze increased for infants with eczema before age 6 months (aOR = 5.98; 95% CI, 1.72-20.77). Family history of allergy increased the odds for late-onset (aOR = 5.9; 95% CI, 2.12-16.46) and persistent wheeze (aOR = 6.5; 95% CI, 1.31-32.08) alike.

Similarly compared with the no or low-wheeze group, the early transient wheeze group had more pneumonia infections before age 2 years (11.8% vs. 1.7%; P = .005).

Viral and respiratory infections were associated with higher odds for late-onset and persistent wheeze as well. These associations were stronger for persistent wheeze than late-onset wheeze through age 8 years, the researchers found, and early-onset wheeze only had these associations for children aged 0 to 2 years and 2 to 4 years.

The early-onset group had higher likelihood for rhinitis at all time points (by age 8 years, aOR = 1.27; 95% CI, 1.07-1.52) and the late-onset group had higher odds for eczema (aOR = 1.7; 95% CI, 1.31-2.19), atopic eczema (aOR = 1.75; 95% CI, 1.14-2.68) and eczema with steroids use (aOR = 1.7; 95% CI, 1.15-2.5) through age 8 years as well as allergic sensitization through age 5 years (aOR = 1.34; 95% CI, 1.07-1.67), compared with the no or low-wheeze group.

When comparing the late-onset and persistent wheeze groups, researchers found the latter had higher proportions of early food and mite sensitization (39.5% vs. 30.8%; P = .03), late mite sensitization (39.5% vs. 23.1%; P = .03) and family history of allergy (82.9% vs. 73%; P = .02).

Based on these findings, the researchers said that early-onset wheeze probably was nonallergenic and linked to early respiratory infections and other environmental risk factors associated with viral infections such as childcare attendance.

The association between early-onset disease with higher odds for rhinitis but not with atopic rhinitis later in childhood may indicate a shared pathology with nonallergenic rhinitis, the researchers continued, adding that this sometimes is called united airway disease.

Although viral infections later in childhood also may trigger late-onset and persistent wheeze, these trajectories were associated with eczema and allergic sensitization as well, unlike early-onset wheeze, indicating atopy and following the classic atopic march model, the researchers wrote.

Overall, the researchers wrote, these findings show that the timing of viral infections impacts the trajectory of wheeze development, as infections during infancy increase susceptibility to early-onset wheeze and later infections driving late-onset or persistent wheeze, differentiated by genetic risk for allergy, eczema and family history.