Infections early in life increase risks for childhood asthma

Key takeaways:

• Asthma was 4.02 times more likely in children above the median of 16 infections before age 3 years.
• Children with colds and allergic rhinitis had higher risks for asthma.

Young children who experience more infections such as colds and pneumonia face greater risk for developing asthma later in childhood, according to a study published in The Journal of Allergy, Asthma and Clinical Immunology: In Practice.

Reducing the burden of these common infections may prevent childhood asthma, Julie Nyholm Kyvsgaard, MD, PhD, postdoctoral researcher, Copenhagen Prospective Studies on Asthma in Childhood, department of pediatrics, Herlev and Gentofte Hospital, University of Copenhagen, and colleagues wrote.

The prospective, population-based, clinical mother-child cohort study comprised 700 children born between 2008 and 2011 who attended clinical visits at age 1 week; 1, 3, 6, 12 and 18 months; and 2, 2.5, 3, 4, 5, 6, 8 and 10 years. The researchers also obtained diary data about infections through age 3 years for 662 (95%) of the children.

Among the 556 children (79%) who had more than 90% of a diary completed, median infection totals included 16 (interquartile range [IQR] = 12-23) at age 0 to 3 years, with five infection episodes (IQR = 3-8) through age 1 year, seven (IQR = 4-10) between age 1 and 2 years, and four (IQR = 2-6) between age 2 and 3 years.

Colds were the most common type of infection, with a median of 12 episodes (IQR = 7-18) through age 3 years.

Asthma prevalence peaked at 16.7% at age 3 years before decreasing to 9.5% at age 5 years, 6.6% at age 6 years and 5.5% at age 8 years and then increasing to 7.2% at age 10 years.

The cohort also included 112 children (23.8%) with a sensitization to at least one allergen and 43 (6.8%) who had been diagnosed with allergic rhinitis at age 6 years.

Risks for asthma

Children who had more than 16 infection episodes before age 3 years, which was above the median, had a 4.02 times greater risk for developing asthma between ages 3 and 10 years (95% CI, 2.68-6.04).

Adjustments for potential confounders and interventions during pregnancy did not impact the significance of these results, the researchers said, adding that there was no interaction with the age of asthma onset either (P > .05).

Risks for asthma between ages 3 and 10 years also increased with more than 12 episodes of colds, at least one episode of pneumonia and more than five episodes of fever before age 3 years. However, risks for asthma did not increase with at least one episode of acute tonsilitis or more than one episode of acute otitis media (AOM).

Adjustments for potential confounders did not impact the significance of these risks either, but the association between fever and risk for later asthma was no longer significant after adjusting for interventions during pregnancy.

Decreasing the sample size from 647 to 545 children did not impact the directional trends of the estimates despite the reduced statistical power, the researchers noted, adding that results also were similar when the sample only included children with diaries that were more than 90% complete.

Associations persisted between asthma and colds (aOR = 3.02; 95% CI, 2.03-4.49) and pneumonia (aOR = 2.24; 95% CI, 1.52-3.3) but not for gastroenteritis (aOR = 1.27; 95% CI, 0.86-1.87) with mutual adjustments for a high burden of these illnesses.

Specifically, more than five episodes in the first year, more than seven episodes in the second year and more than four episodes in the third year each had a significant association with increased risk for asthma between age 3 and 10 years (P < .05).

The second year had the highest risk estimate, and increased estimates for colds increased with age as well, the researchers added.

Using infection episodes as a continuous measure, sensitivity analyses indicated that each doubling in the number of infections increased risk for asthma between age 3 and 10 years by a factor of 3.44 (95% CI, 2.35-5.04).

Adjustments for possible confounders did not impact the significance of these results, the researchers said, with similar results found for infection subtypes.

Other risks

High burdens of common infections, defined as totals above their respective medians, were not associated with any of the lung function measurements taken at age 10 years.

High burdens of pneumonia, or at least one episode before age 3 years, were associated with lower FEV₁ (–50 mL; 95% CI, –100 to –10) and maximal midexpiratory flow (–120 mL/s; 95% CI, –220 to –10).

The researchers also noted an association between a high burden of AOM and a lower FEV₁/FVC ratio (–0.01; 95% CI, –0.02 to –0.09). However, associations between burdens of pneumonia, FEV₁ and midexpiratory flow were insignificant when children with current or former asthma were excluded.

There also were no associations between burdens of common infections and increased risks for allergic rhinitis or aeroallergen sensitization at age 6 years, the researchers said.

But there were associations between allergic rhinitis (OR = 4.91; 955 CI, 2.56-9.43) and sensitization (OR = 2.27; 95% CI, 1.24-4.15) and increased risks for asthma at age 6 to 10 years.

The interaction between the burden of common infections and allergic rhinitis in risks for asthma in children aged 3 and 10 years was borderline significant, the researchers continued. Also, interactions between allergic rhinitis and a high burden of colds were significant (P interaction = .032), but there were no interactions with other subtypes of infections (P interactions > .05).

Children with allergic rhinitis at age 6 years and a high burden of common infections were 14.4 times more likely to develop asthma between ages 3 and 10 years (95% CI, 4.15-50.17).

Children with a high burden of common infections but no allergic rhinitis were 3.62 times more likely to develop asthma between ages 3 and 10 years (95% CI, 2.34-5.61).

Similarly, children with allergic rhinitis at age 6 years and a high burden of colds were 9.41 times more likely to develop asthma between ages 3 and 10 years (95% CI, 2.87-30.85), but those who did not have allergic rhinitis with a high burden of colds were 3.17 times more likely to develop asthma between ages 3 and 10 years (95% CI, 2.09-4.79).

There was no interaction between aeroallergen sensitization at age 6 years and the burden of common infections (P interaction = .1) or of colds (P interaction = .33) in risks for asthma later.

The increased risk for asthma with a high burden of common colds among children with allergic rhinitis at age 6 years indicated an interaction with sensitization to mold (P interaction = .041) and house dust mites (P interaction = .037).

These children also saw a trend of interaction with sensitization to pollen (P interaction = .077) but not with sensitization to furred animals.

Another trend toward interaction included allergic rhinitis and risk for asthma at age 6 to 10 years (P interaction = .094).

When children had a high burden of infection in early life as well as allergic rhinitis (n = 42), the risk for asthma from age 6 to 10 years increased by a factor of 12 (95% CI, 3.22-44.7). But when children had a high burden of infection but no allergic rhinitis (n = 580), the risk for asthma increased by a factor of 3.19 (95% CI, 1.69-6.038).

Risks for asthma determined by a yes/no question at any time point between ages 3 and 10 years (n = 608) increased by a factor of 3.8 when children had a high burden of infection (95% CI, 2.55-5.67; P < .001).

But the researchers did not consider the interaction with allergic rhinitis to be significant when they analyzed asthma as a dichotomous end point, or a yes/no question (P interaction = .12).

Risks for asthma increased by a factor of 12.5 when children had allergic rhinitis and a high burden of infection (n = 39; 95% CI, 2.63-59.47) and by 3.43 when children had a high burden of infection without allergic rhinitis (n = 559; 95% CI, 2.24-5.25).

Conclusions

Driven by colds, pneumonia, gastroenteritis and fever, risks for asthma increased for children age 3 to 10 years with high burdens of common infections in early childhood, the researchers concluded.

The researchers also called for randomized controlled trials of maternal and child vaccinations, antibody administration, bacterial lysate treatment, vitamin D supplementation and other interventions designed to prevent infections to see if these strategies prevent asthma as well, especially in children with allergic rhinitis.