Clinically significant respiratory disease associated with childhood wheeze

Key takeaways:

• 67.7% of children had clinically significant respiratory disease during the first 2 years of life.
• Recurrent wheeze affected 10.6%, 11.3% and 3.3% of children at age 3, 5 and 8 years.

Clinically significant respiratory disease was significantly associated with childhood wheeze in a low-resource, nonindustrialized setting, according to a study published in Clinical and Translational Allergy.

These associations were stronger for children who also had tested positive for rhinovirus (RHV) with positive skin prick testing for atopy and soil-transmitted helminths (STH) infection, Jessica E. Atwell, PhD, MPH, assistant scientist at Johns Hopkins Bloomberg School of Public Health, and colleagues wrote.

The study included 426 children from the ECUAVIDA birth cohort born between late 2008 and the end of 2009 in Quinindé, Esmeraldas Province, a rural tropical coastal region in Ecuador. Infections with STH parasites are endemic in this district, the researchers noted.

Respiratory diseases and wheeze

Based on nasopharyngeal swabs collected whenever children had symptomatic respiratory illness, viral infections through age 2 years included RHV (41%), bocavirus (10%), adenovirus (9%) and respiratory syncytial virus (RSV; 7%).

Also, 5% of swabs were negative for all pathogens, 23% were positive for one pathogen, 38% were positive for two, 24% were positive for three, and 10% were positive for four or more of the seven pathogens that were assessed.

RHV was detected year-round, but RSV was seasonal, from January to July. With only 42% of children aged 6 months and younger under surveillance while RSV was circulating, the researchers wrote, these findings may be missing RSV cases in early infancy for those children born during the 2009 RSV season.

Clinically significant respiratory disease (CSRD) affected 67.7% of the children through age 2 years, including 7.5% whose CSRD was associated with both RSV and RHV, 4.3% with RSV alone and 28% with RHV alone.

The researchers called these associations between CSRD and RSV (OR = 4.53; 95% CI, 2.1-11.3) and RHV (OR = 2.46; 95% CI, 1.77-3.42) significant. Also, 2.4% of children were hospitalized for respiratory illnesses before age 2 years.

Further, 18% of children aged 3 years, 18.6% of children aged 5 years and 6.3% of children aged 8 years experienced wheeze during the previous 12 months. Proportions for recurrent wheeze at these time points included 10.6%, 11.3% and 3.3%.

Researchers found significant associations between all-cause CSRD and recent wheeze at age 3 years (adjusted OR = 2.33; 95% CI, 1.23-4.4) and at age 5 years (aOR = 2.12; 95% CI, 1.12-4.01).

RHV-associated CSRD was associated with recent wheeze at age 3 years (aOR = 2.44; 95% CI, 1.19-5). Also, CSRD with both RSV and RHV was associated with recent wheeze at age 3 years (aOR = 3.49; 95% CI, 1.31-9.33) and at age 5 years (aOR = 3.32; 95% CI, 1.25-8.78).

The researchers found similar associations between CSRD and recurrent wheeze.

The 210 children born after July 2009 who were aged 3 to 6 months during the 2010 RSV season also displayed comparable associations between CSRD with RSV and wheeze at age 3 years (aOR = 1.62; 95% CI, 0.27-9.73), age 5 years (aOR = 4.94; 95% CI, 0.37-66.3) and age 8 years (aOR = 4.76; 95% CI, 0.31-73.69).

Additional findings

With nine allergens tested at age 2 years, 17.9% of children had SPT reactivity.

Additionally, 43.9% of the mothers had STH infections, including 26% with Ascaris lumbricoides and 25.1% with Trichuris trichiura. Through age 2 years, 21% of children had an STH infection, including 16% with A. lumbricoides and 8.6% with T. trichiura.

None of the children who were considered atopic or who had been infected with STH had wheeze-associated CSRD with RSV.

But the researchers found some evidence for stronger associations between CSRD with RHV (aOR = 9.42; 95% CI, 1.88-47.15) among the atopic children compared with nonatopic children (aOR = 1.92; 95% CI, 0.84-4.38).

Children infected with STH had stronger associations between CSRD with RHV and wheeze (OR = 13.41; 95% CI, 1.56–115.64) compared with children not infected with STH (OR = 1.68, 95% CI, 0.73–3.84) as well, the researchers found.

Based on these findings, the researchers said that CSRD was associated with wheezing at age 3 and 5 years in this low-resource, nonindustrialized setting, especially with RHV and mixed RHV and RSV infections. The researchers also said that early childhood atopy and postnatal STH infections may enhance the effects of RHV on wheeze.

Because atopy and STH infections cause Th2-mediated inflammation, the researchers wrote, this may contribute to the severity of lower respiratory infections associated with RHV. These findings are likely generalizable to similar populations, the researchers continued, although they also called for larger studies in similar settings for a better understanding of these interactions.