By Philip R. Fischer, MD, DTM&H

Professor of Pediatrics, Department of Pediatric and Adolescent Medicine, Mayo Clinic, Rochester, MN

Dr. Fischer reports no financial relationships relevant to this field of study.

SYNOPSIS: Infants with severe bronchiolitis sometimes develop subsequent recurrent wheeze and asthma. Among infants hospitalized with bronchiolitis, the risk of developing asthma is greatest in those with rhinovirus C infection, especially if they also are sensitized with IgE against foods.

SOURCE: Hasegawa K, Mansbach JM, Bochkov YA, et al. Association of rhinovirus C bronchiolitis and immunoglobulin E sensitization during infancy with development of recurrent wheeze. JAMA Pediatr 2019; April 1. doi:10.1001/jamapediatrics.2019.0384. [Epub ahead of print].

Bronchiolitis accounts for 130,000 hospitalizations each year in the United States. Approximately one-third of infants sick enough to be hospitalized with bronchiolitis go on to develop recurrent episodes of wheezing and asthma. After respiratory syncytial virus, rhinovirus is the next most common cause of bronchiolitis.

A study of children in Australia revealed that those with atopic dermatitis who became ill with bronchiolitis C were more likely than other children to have further episodes of respiratory illness with wheezing.

With that background, Hasegawa and colleagues at 17 United States medical centers evaluated 716 children hospitalized during the first year of life with bronchiolitis to see if the risk of subsequent wheezing illness depended on the specific viral etiology of the initial bout of illness. They also performed immunoglobulin E (IgE) tests during the initial admission to determine if pre-illness allergic sensitization (to food and/or aeroallergens) altered the risk of subsequent asthma. The study covered three bronchiolitis seasons (November 2011 to April 2014).

The median age of study subjects was 2.9 months. Seventy-six percent of patients had respiratory syncytial virus bronchiolitis; the others had rhinovirus A (12%), B (2%), or C (11%). Overall, 32% developed recurrent wheeze by 3 years of age. Rhinovirus C-infected infants had a 1.58-fold higher risk of developing recurrent wheeze. Those with rhinovirus C who also had IgE sensitization at the time of their initial hospitalization were at greatest risk (3.03-fold risk) of developing recurrent wheeze.

COMMENTARY

Several key lessons emerge from this study. Rhinovirus is not merely a cause of runny nose and “colds.” After respiratory syncytial virus, rhinovirus is the second most common cause of bronchiolitis, a common infection that accounts for the more than 100,000 infant hospitalizations in the United States each year. In addition, not all rhinoviruses are equal. The rhinovirus family includes viruses with 170 different genotypes, and these viruses are classified into three species, grouped as A, B, and C. Rhinovirus C, identified in 2006, now is known to be the rhinovirus most responsible for severe infant illness and is linked the most to the development of subsequent respiratory difficulties.

The development of recurrent wheeze is multi-factorial. Many of us have long believed that some of the children who get sick enough with bronchiolitis to be hospitalized are more genetically predisposed to develop subsequent wheeze and asthma compared to those children who do not require hospitalization. Approximately one-third of subjects in this study had a parent with asthma, thus suggesting a genetic risk for the child to develop asthma as well. However, beyond host-specific genetic risks, this study informs us that the development of childhood asthma also relates to infant infection (with rhinovirus C being more dangerous than rhinovirus A, rhinovirus B, or respiratory syncytial virus) and concurrent infantile hypersensitivity to food. Personal genetics, specific viruses, and food sensitization combine to increase the risk of a young child developing recurrent wheeze and asthma.

Previous efforts to vaccinate children for respiratory syncytial virus caused vaccine recipients to mount more aggressive immune responses to subsequent infection and, thus, to become more ill than non-vaccinated individuals. To date, no good active immunization exists for respiratory syncytial virus or rhinovirus. Of course, high-risk children such as babies born very prematurely and those with chronic cardiopulmonary disease (who were not included in the current study) can benefit from passive respiratory syncytial virus infection.