Indolent rhinovirus infections may predict asthma development in children with wheeze
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Key takeaways:
- More than a quarter of children with refractory wheeze were positive for rhinovirus despite a lack of symptoms.
- Children with indolent rhinovirus did not have any evidence for systemic type 2 disease.
BOSTON — Rhinovirus infections in children with a nascent type 2 inflammatory signature may be at greater risk for asthma, according to an abstract presented at the American College of Allergy, Asthma & Immunology Annual Scientific Meeting.
Many infants with treatment-refractory recurrent wheezing illnesses have indolent rhinovirus infections, Thomas L. Offerle, MD, a fellow in the division of asthma, allergy and immunology at the University of Virginia School of Medicine, said in his presentation.
Offerle told Healio that the study is one of many offshoots from the “excellent” work conducted by W. Gerald Teague, MD, Larry Borish, MD, and their colleagues at the University of Virginia over the past decade.
“While we are investigating recurrent, treatment refractory wheeze, the primary work of the lab has sought to answer one important question: which infants and toddlers who wheeze will go on to be children with asthma?” Offerle said.
The researchers speculated that the presence of eosinophilic inflammation in the airway would predict asthma development.
“With this in mind, we began asking questions about eosinophils, their innate, anti-viral properties and the connections to immunologic mechanisms which may predispose to asthma,” Offerle said.
The cohort included 468 children aged 5 years and younger with wheeze that was refractory to treatment. Bronchoalveolar lavage indicated that 27.1% of the children were positive for rhinovirus infection even though they had no clinical symptoms.
Researchers also conducted phlebotomies to examine granulocyte counts and inflammation markers as well as quantitative polymerase chain reaction tests to examine eosinophilic activation and chemoattraction markers.
There was no evidence of a systemic type 2 inflammatory disease among the children with indolent rhinovirus infections, Offerle said, with no differences in blood eosinophil count, total IgE or presence of atopy.
Blood eosinophil counts included 280 ± 370 cells/µL for those positive for rhinovirus and 210 ± 340 cells/µl for those who were negative for rhinovirus.
Total IgE included 46 ± 219 kU/L in the positive rhinovirus group and 51 ± 228 kU/L in the negative rhinovirus group.
Percentages of children with atopy included 48.8% among those positive for rhinovirus and 51.8% among those who were negative for rhinovirus.
However, 30% of the children who were positive for rhinovirus and 23.2% of those who were negative demonstrated eosinophilic inflammation in their airways.
Offerle noted associations between this eosinophilia and a nearly four-fold increase in CCL5 (RANTES), CCL11 (Eotaxin), CCL24 (Eotaxin-2) and IL-25 mRNA transcript expression but not with IL-33 or TSLP.
Even though these children did not have a systemic type 2 inflammatory signature, Offerle said, many of them had increased airway eosinophilia and transcripts that were associated with a developing type 2 inflammatory response.
“As with any project, the answer to one question simply prompts two more,” Offerle said.
Since this study, the researchers have performed additional ELISA testing on the bronchoalveolar lavage fluids of these patients for eosinophil-derived neurotoxin (EDN).
“One interesting outcome was that EDN may be a better marker of eosinopihlic inflammation than identification of intact eosinophils,” Offerle said.
Offerle also called the marked elevation in EDN levels in children with rhinovirus in their airways “intriguing.”
“Our results may suggest that a susceptibility to rhinovirus may precede the development of the T2 high/asthmatic state, contrary to what we previously believed,” he said.
Based on these findings, Offerle concluded that indolent rhinovirus infections can predict asthma development.
Offerle noted, though, that the full implications of this silent rhinovirus-associated bronchalveolitis are not completely known, since this research is currently ongoing.
“However, we are developing a clear story that some children may, in fact, not benefit from increasing doses of inhaled corticosteroids, as the current standard of care suggests,” Offerle explained, “and that this use of corticosteroids may predispose these infants to [rhinovirus] and worsen their inflammatory state.”
Instead, Offerle said, Teague is now increasingly using medications with antimicrobial and anti-inflammatory effects, such as macrolides antibiotics.
“As always, our research suggests that if there is a patient who is not responding as expected to standard therapy, it is important to reconsider the case to ensure the correct diagnosis,” Offerle said.