Rhinovirus infections associated with severe recurrent wheeze among children

Key takeaways:

• Rhinovirus was the most common virus (29%).
• Treatment with high-dose corticosteroids increased odds for bronchoalveolar lavage rhinovirus.
• Children with rhinovirus also had earlier onset of wheeze.

Asymptomatic rhinovirus lung infections may accompany severe recurrent wheeze in children, with granulocytic bronchoalveolitis and elevated inflammation, according to a study published in The Journal of Allergy and Clinical Immunology.

This syndrome is more predominant among younger children, W. Gerald Teague, MD, Ivy Foundation Distinguished Professor of Pediatrics, Child Health Research Center, University of Virginia College of Medicine, and colleagues wrote.

The prospective, observational study included 468 children aged 2 to 18 years who had bronchoscopies for treatment-refractory recurrent wheeze, including 341 (median age, 6.2 years; 66.3% boys; 20.5% Black) who had no bronchoalveolar lavage (BAL) pathogens and 127 (median age, 3.2 years; 70.9% boys; 19.7% Black) who were infected with rhinovirus alone, although they displayed no cold symptoms.

The researchers characterized rhinovirus as the dominant category of BAL pathogen, found in 29.7% of the cohort, adding that proportions of children with BAL free of pathogens increased with age.

Proportions of children who only had rhinovirus peaked in preschool and then fell. Additionally, the researchers noted that 75% of the children in the rhinovirus group also had BAL granulocytosis.

Other common pathogens included adenovirus (1.7%) and human metapneumovirus (1.7%). Moraxella catarrhalis (6.5%), Hemophilus influenzae (5.7%) and Streptococcus pneumoniae (4.7%) were among the most common bacteria. As children grew older, potential bacterial pathogens also decreased in prevalence.

Compared with the group that had no BAL pathogens, the group with rhinovirus alone had significantly higher blood neutrophil totals and high-sensitivity C-reactive protein. The rhinovirus group also was younger and had earlier onset of wheeze, along with greater prevalence of high-dose corticosteroid treatment.

Further, the rhinovirus group had greater tracheomalacia and mucosal edema even though both groups had similar prevalence of comorbid conditions and lung function variables, the researchers said.

An adjusted model indicated lower odds for BAL rhinovirus with older age (OR = 0.82; Q1-Q3 95% CI, 0.76-0.88; P < .001) and higher odds for BAL rhinovirus with high-dose corticosteroid treatment (OR = 1.58; Q1-Q3 95% CI, 1-2.51; P = .04).

Although the rhinovirus group had higher isolated neutrophilia (43% vs. 16%; P < .05) and mixed eosinophilia/neutrophilia (26% vs. 11%; P < .05), the researchers continued, it also had lower pauci-granulocytic BAL granulocyte categories (27% vs. 61%; P < .05).

The rhinovirus group additionally had higher total cell counts, total eosinophil counts, neutrophil percentage, total neutrophil counts and total lymphocyte counts than the group with no BAL pathogens.

Corrections for total cell count indicated that the rhinovirus group had higher BAL total macrophages despite lower BAL macrophage percentages as well.

Rhinovirus status was the only factor that was significant for BAL total neutrophils, whereas rhinovirus status and advancing age both were significant for BAL total eosinophils in generalized models. Advancing age was a significant covariate for BAL total macrophages, but rhinovirus status was not.

Both groups had similar blood markers of type 2 inflammation and blood total eosinophils, but the rhinovirus group had higher BAL total eosinophils.

Also, nearly half of the cohort had one or more detectable allergen, but the total IgE, number of allergens and sensitization to four or more allergens were similar in comparisons based on BAL rhinovirus status.

Adverse events related to bronchoscopy had low prevalence, with 27.6% of the rhinovirus group and 18.5% of the group with no pathogens experiencing events that were minor and expected.

Major unexpected adverse events requiring prolonged observation or unplanned ED visits were experienced by 1.5% (n = 7) of the full cohort. Two patients had laryngospasms requiring acute intubation during the procedure, two had fever and three had post-procedure respiratory distress and needed supplemental oxygen therapy during recovery.

Based on these findings, the researchers called these associations between silent granulocytic bronchoalveolitis and lung rhinovirus infection in children who have recurrent wheeze that is refractory to treatment a novel syndrome.

The researchers also said that these findings indicate that rhinovirus has a dominant role in determining lung inflammation among children with recurrent wheeze who are clinically stable.

Next, the researchers said that the mechanisms behind these silent infections should be characterized since these associations have implications for clinical practice while opening new research questions.