Charlottesville, VA—Would many children with recurrent wheezing be better treated with antiviral medications than commonly prescribed steroids? A new study proposes that the answer is “yes.”

A report published in the Journal of Allergy and Clinical Immunology suggested that nearly one-quarter of children with recurrent wheezing have “silent” lung infections that would be better treated with antiviral medications than commonly prescribed steroids, which can carry lifelong side effects.

“While steroids can help some children with wheeze, many children in the study showed no patterns of inflammation that would improve with steroids,” said W. Gerald Teague, MD, a clinician-scientist at the University of Virginia School of Medicine’s Child Health Research Center. “I advise the parents of my patients that wheeze episodes that are triggered by colds should be treated with anti-inflammatory medications that build immunity to viruses, such as azithromycin. They look surprised that we would use an antibiotic for a viral infection, but, in fact, azithromycin bolsters the immune response to viruses in a positive way.”

Dr. Teague and his colleagues sought to determine any between recurrent wheezing in children and so-called indolent lung infections—infections that can carry no symptoms and persist for long periods. After screening more than 800 children and teens with severe wheezing, the study team determined that 22% had undetected lung infections that did not display typical cold symptoms.

“Rhinovirus (RV) infections trigger wheeze episodes in children,” the authors wrote. “Thus, understanding of the lung inflammatory response to RV in children with wheeze is important.”

Their study examined the associations of RV on bronchoalveolar lavage (BAL) granulocyte patterns and biomarkers of inflammation with age in 616 children with treatment-refractory, recurrent wheeze. The researchers analyzed viral nucleic acid sequences, bacterial cultures, granulocyte counts, and phlebotomy for both general and type 2 inflammatory markers to reach their conclusion.

The results indicated that, despite the absence of cold symptoms, RV was the most common pathogen detected (30%), and when present, was accompanied by BAL granulocytosis in 75% of children.

The researchers reported that compared with children with no BAL pathogens (n = 341), those with RV alone (n = 127) had greater (P <.05) isolated neutrophilia (43% vs. 16%), mixed eosinophils and neutrophils (26% vs. 11%), and less pauci-granulocytic (27% vs. 61%) BAL. Furthermore, the authors wrote, children with RV alone had biomarkers of active infection with higher total blood neutrophils and serum C-reactive protein but no differences in blood eosinophils or total immunoglobulin E. With advancing age, the log odds of BAL RV alone were lower (0.82; 5th-95th percentile CI, 0.76-0.88; P <.001), but higher (1.58; 5th-95th percentile CI; 1.01-2.51; P = .04) with high-dose daily corticosteroid treatment.

The authors pointed out that the RV infections do not respond to corticosteroids commonly used to treat wheezing. In fact, they found that higher doses of the steroids may put children at increased risk for lingering lung inflammation, in addition to known side effects such as irritable behavior, reduced bone density, and suppressed growth.

“Children with severe recurrent wheeze often (22%) have a silent syndrome of lung RV infection with granulocytic bronchoalveolitis and elevated systemic markers of inflammation,” the study team concluded. “The syndrome is less prevalent by school age and is not informed by markers of type-2 inflammation.

The authors speculated that dysregulated mucosal innate antiviral immunity is a responsible mechanism.

While further research is needed, Dr. Teague suggested some rethinking on how wheezing is necessary.

“Viral infections are the most important trigger of acute wheeze episodes in children and, in some cases, lead to respiratory distress and hospital care,” Dr. Teague explained. “We hope this discovery will stimulate further work in the treatment of recurrent wheeze and viral infections in children. The field has to get to away from overuse of potentially toxic steroids for the treatment of acute wheeze to include novel therapies which target specific patterns of inflammation.”

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