New research at UVA Health Children’s, led by W. Gerald Teague, MD, Ivy Foundation Distinguished Professor in the department of pediatrics, shows that up to 25% of children with recurrent wheeze have a silent lung infection.
While the standard of care has been steroids, Teague’s research shows that antivirals promise to be a more effective therapy.
Viral respiratory infections in children can have debilitating effects over time, including inflammation that can cause loss of symptom control. Diagnosis and treatment of the underlying, infectious cause of chronic wheeze is critical to reducing symptoms in young children.
A New Treatment for a Revised Diagnosis
In a cross-sectional study of more than 800 children who underwent diagnostic bronchoscopy for severe respiratory symptoms, Teague and his research team found around 25% of children with recurrent wheeze had a silent rhinovirus infection. This infection led to lung and systemic inflammation.
Preliminary evidence suggests that many of these children have a reduced immune response to rhinovirus. This allows it to persist in the lung after infection and leads to further inflammation.
This research also demonstrates that antiviral therapies could be more helpful than corticosteroids for the treatment of wheezing. In fact, the study found that children treated with higher doses of corticosteroids may be at greater risk of silent rhinovirus infection and smoldering lung inflammation.
“Traditionally, we’ve poured steroids on these wheezy children,” says Teague. “But this research suggests that’s not what we should be doing, which is at odds with current guidelines. Before, we were missing the answer that it’s not just steroid-responsive inflammation that is causing wheeze. Instead, these children have lung inflammation from infection with the common cold virus which has not been cleared by an effective immune response. It is important to point out that other respiratory viruses are not identified as often as the cold virus in wheezy children."
Teague was motivated to study this topic because of the significant volume of children with asthma and wheezing coming through the emergency department. He recognized the fact that rhinovirus infection is the most important trigger of asthma episodes in children around the world. Looking ahead, Teague plans to research if these abnormal antiviral defenses are a risk factor for developing asthma.
In the clinic, the results of this research could lead to the treatment of acute and persistent wheeze with antiviral medications in children who demonstrate none of the traditional markers such as allergy that are known to respond to corticosteroids. This could have a huge impact on children, often preschoolers, most affected by recurrent wheeze episodes.
Translating Chronic Wheeze Research into Practice
This clinical care requires collaborative, personalized care from physicians, including:
- Pulmonologists
- Pediatricians
- Family medicine providers
- Nurses
- Respiratory therapists
- Pharmacists
- Nurse practitioners
- Physician assistants
“We don’t take care of guidelines or algorithms: We take care of children, and every child is unique,” says Teague. “We need to look at every child as being special and needing precise treatment that fits their pattern of inflammation. Those that don’t fit the guidelines are the orphans of the healthcare system. It’s these outliers that brought to light this new diagnosis.”
With this knowledge, Teague shifted his practice to investigate the cause of wheezing in children rather than immediately pushing steroids. This includes simple tests to look for steroid-responsive pathways, like blood eosinophilia and allergy tests. If these tests are negative or there is poor response to standard treatment, Teague considers bronchoscopy or a course of azithromycin therapy.
Continuing to Improve on Treatments for Children with Chronic Wheeze
“We want to confirm in future studies that the reduced innate immune response starts before the inception of asthma,” says Teague. “Once the developing lung barrier cells change their properties as a result of viral infections and genetic factors, it becomes a significant risk factor for established asthma.”
"Another impact of this study is to consider maintenance azithromycin therapy during the peak viral seasons in children who have failed standard corticosteroid therapy and have persistent wheeze. Azithromycin can be given every other day over 2-4 months with careful monitoring to facilitate weaning from corticosteroids and improve symptom control. This practice needs a controlled clinical trial to confirm its safety and efficacy. The concern of course is to select for azithromycin-resistant bacteria, but in work to date we have not found this to be the case."
UVA Health Children’s has a strong referral network across the commonwealth that ensures the sickest children with recurrent wheeze can get care from pediatric pulmonary specialists and allergists. Additionally, the Department of Pediatrics has an NIH-funded research program dedicated to the immune response to viruses in wheezing children that is advancing clinicians’ ability to care for young children.
“We offer excellence in clinical care and research, including basic sciences, and share the grounds with world-class immunologists who can analyze fresh samples on-site for quick results for our patients,” says Teague. “As part of a public university, UVA Health Children’s has a public health spirit about it that respects all children so they can access the care they need from skilled specialists.”
