Wheezing With Rhinovirus Infection in Early Life a Predictor of Asthma

Becky McCall

December 14, 2010

December 14, 2010 (Dubai, United Arab Emirates) — Children 3 years and younger who experience wheezing with rhinovirus (RV) respiratory infection are more likely to develop asthma by the age of 6, the ongoing Childhood Origins of Asthma (COAST) trial continues to show.

Robert Lemanske, MD, professor of pediatrics and medicine at the University of Wisconsin, Madison, discussed the recent findings from COAST on the link between wheezing, respiratory illnesses due to RV, and asthma here at the World Allergy Organization 2010 International Scientific Conference.

Most recently, the identification of human rhinovirus (HRV) C and its potential association with more severe asthma offers new insight, although detailed information is currently restricted pending publication, Dr. Lemanske acknowledged.

He and his colleagues carried out research into the RV–wheezing–asthma association with their high-risk cohort of children in COAST. They found that the combination of allergic sensitization and wheezing with viral illnesses were very significant.

"If a child wheezes with RV but is RAST [radioallergosorbent test]-negative, then there is a near 30-fold increased chance of asthma, but if the child is RAST-positive with a wheezing history with RV, then the chance asthma rises to nearly 80-fold," he reported.

They tracked the timing, severity, and cause of respiratory illness throughout childhood in 285 high-risk children. In the first year of life, nasal washes were collected at 2, 4, 6, 9, 12, 18, and 24 months to look at the background carriage rate of various viruses in the community. Persistent wheezing was assessed at 3 years, and the presence of asthma at 6 years. Nasal swabs were taken if the children experienced significant respiratory tract illnesses.

Risk factors related to persistent wheezing at 3 years were passive smoke during the first year (odds ratio [OR], 0.21), the presence of older siblings (OR, 2.5), allergic sensitization to food protein at 1 year (OR, 2.0), any moderate to severe respiratory illness without wheezing during infancy (OR, 3.6), and at least 1 wheezing illness during infancy with respiratory syncytial virus (RSV) (OR, 3.0), non-RV/RSV pathogens (OR, 3.9), or RV (OR, 10). These all increased the risk for persistent wheezing.

"Rhinovirus was found to be the strongest single predictor of persistent wheezing at 3 years. If [children] wheezed with rhinovirus infection, then their risk of persistent wheezing at year 3 was significantly enhanced. Notably, first-year illnesses caused by rhinovirus infection were the strongest single predictor of subsequent year 3 wheezing" (OR, 6.6; P = .0001), said Dr. Lemanske.

The researchers then investigated whether RV or RSV wheezing illnesses between 1 and 3 years of age affected the risk for asthma at age 6.

They found that children who wheeze with RSV had a significant 3-fold risk of developing asthma, but if they wheezed with RV only or with RV and RSV together, their chances of developing asthma were substantially increased. In addition, the combination of allergic sensitization and wheezing with viral illnesses appeared to be very significant. Children who wheezed with RV and who were RAST-positive had an 80-fold chance of developing asthma at age 6. Evidence for these findings were first published 2 years ago (Am J Respir Crit Care Med. 2008;178:667-672), Dr. Lemanske said.

The COAST investigators also found a link between asthma and viral load. "Another striking finding was that children who go on to get asthma have a higher respiratory tract burden of all respiratory pathogens at age 1 to 3 than those who don't get asthma," added Dr. Lemanske.

He continued his discussion with a brief overview of other work in the field. He explained that data from the past 5 to 10 years link RV to wheezing in early life and the expression of the asthmatic phenotype.

Scandinavian scientists found that RV infections requiring hospitalization during infancy were an early predictor of the subsequent development of asthma (J Allergy Clin Immunol. 2003;111:66-71). Australian researchers demonstrated significant associations between wheezing in outpatients with RV and RSV in infancy and the development of persistent wheezing at 5 years of age. They found that wheezing and persistent wheezing were restricted to children who had sensitization at less than 2 years of age (J Allergy Clin Immunol. 2007;119:1105-1110).

Recently, a new group of human RVs was identified, bringing to 3 the number of identified strains: HRV A, HRV B, and HRV C. The virulence patterns of these viruses continue to be investigated.

Dr. Lemanske drew attention to a study that assessed preschool children who entered hospital with fever and acute respiratory infection and found that upon discharge, of the children diagnosed with asthma, HRV C and HRV A were found in 55% and 36% of cases, respectively (J Allergy Clin Immunol. 2009;123:98-104). "This suggests something different about the host response or how the virus makes the host respond differently in HRV C than in HRV A," he said.

When Dr. Lemanske looked at the HRV A, B, and C split among the children in the COAST cohort, he found that in the first year of life, HRV A was present in 50%, HRV C levels were close to those of HRV A, and HRV B was uncommon.

"We also looked at the probability of [RV] inducing moderate to severe illness and found it to be similar for HRV A and C infections, but higher than B. A and C seem to produce more severe lower respiratory tract illness than B," he noted.

Dr. Lemanske said that he and his colleagues hope to conduct more sophisticated analyses to determine which viruses produce which clinical end points.

Louis-Philippe Boulet, MD, FCCP, from the Centre de pneumologie de l'Hôpital Laval, in Sainte-Foy, Québec, Canada, commented on the findings.

"HRV C has only recently been discovered because of new and improved technologies and methods. It seems to be involved in the development of asthma. There's more work to do, of course, but this is probably a risk factor for the development of asthma in the future if a child has infection with this rhinovirus."

Dr. Boulet speculated on possible advances in the treatment of RV illnesses with the discovery of HRV C. "If we could find a vaccine to prevent the infection, then we might have some solution to preventing the disease. This is probably the outcome being sought ultimately, but it isn't easy to develop a vaccine for the virus."

Dr. Lemanske reports current financial relationships with UpToDate and Elsevier. Dr. Boulet has disclosed no relevant financial relationships.

World Allergy Organization (WAO) 2010 International Scientific Conference: Presented December 8, 2010.

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