SAN DIEGO -- A wheezing illness before the age of three years signals the likelihood of asthma by age six, and frequent rhinoviral infections in infancy may have something to do with it, according to investigators here.
SAN DIEGO, Feb. 26 -- More than 75% of children who develop a wheezing illness before the age of three years will go on to have asthma by age six, reported investigators here.
In addition, children with rhinoviral infections who developed wheeze before age one had a threefold risk for developing asthma later on, reported the Childhood Origins of Asthma (COAST) investigators at the American Academy of Allergy, Asthma, & Immunology meeting here.
"We geared the project to convince ourselves as well as the rest of the scientific community that respiratory syncytial virus, a common virus that causes wheezing in children, was the dominant driving force in leading to the development of persistent respiratory illness at age of three to four years, and ultimately asthma," said Robert F. Lemanske, Jr., M.D., of the University of Wisconsin Medical School in Madison.
"What we found to our surprise was that it wasn't RSV that was doing it," he continued. "It was the common cold virus, the rhinovirus. There are more than 100 different strains of rhinovirus, so this is a common infection that we get, and the relationship of this to the development of these outcomes was a big surprise to us."
The investigators followed a birth cohort of 287 children for nearly eight years, and found that as the children reached age three, more than 75% who developed a wheezing illness, regardless of the viral etiology, would go on to develop asthma by their kindergarten or first-grade years.
"Rhinovirus continues to be the most striking relationship," said Kathleen A. Roberg, R.N., M.S., also of the University of Wisconsin, "However, respiratory syncytial virus and parainfluenza virus illnesses are similarly related to the diagnosis of asthma. These data would suggest that there is a time between the age of one and three that is critical in the development of persistent wheezing in children."
In two other presentations, COAST investigators reported that frequent respiratory illnesses during infancy were also associated with the development of asthma in early childhood, but not with immunologic or clinical markers of atopy, and that asthma at age six was associated with an early and variable pattern of allergic sensitization in childhood.
The COAST study is an NIH-funded longitudinal, epidemiologic study following a cohort of high-risk children from before birth. The study is designed to evaluate genetic and environmental factors that may play a role in the development of asthma.
To be eligible for the study, participants had to have at least one parent with asthma and/or confirmed sensitization to aeroallergens. Cord blood samples were collected at birth, and additional samples were taken annually to evaluate cytokine response profiles.
The investigators also collected nasal lavage samples from the children at scheduled study visits and whenever they had significant respiratory illness, in order to determine whether the illness was viral or bacterial in origin.
They found that the 41 children who had a wheezing rhinoviral illness during infancy were significantly more likely to be diagnosed with asthma at age six than the 241 children who did not (asthma incidence 54% for the children who developed wheeze by age 1, vs. 23% for all other, P=0.0002).
In addition, non-wheezing rhinoviral infections predicted risk of recurrent wheeze at age three years (29% vs. 15%, P=0.01), but did not predict asthma at age six years (24% vs. 22%, P=0.75).
In contrast, the occurrence of an RSV wheezing illness during infancy, which was seen in 47 children, was not significantly associated with asthma diagnosis at age six (38% for children who wheezed with RSV illnesses, compared with 26% of other P=0.13). There was a trend toward an association between non-rhinoviral, non-RSV wheezing illnesses in infancy and asthma, but this trend was not statistically significant (P=0.13).
"In this high-risk cohort, outpatient wheezing illnesses with rhinovirus, but not RSV or parainfluenza virus, during the first year of lifer are associated with asthma at age six years," Roberg said. "But viral wheezing illnesses during the third year of life, regardless of etiology was significant for the development of asthma in nearly 75% of children."
In a second presentation, Rochelle Grabher, B.S., a senior clinical nurse specialist at the University of Wisconsin, and clinical research coordinator with the COAST study, reported that children who had frequent respiratory illnesses during infancy had a significantly higher incidence of asthma at six compared with children who had no significant respiratory illnesses.
In this substudy, the investigators prospectively examined the influence of the frequency of viral respiratory illness during infancy on the development of asthma and other markers of atopy.
In addition to having the lavage samples taken, the children had skin prick tests at age five, and were evaluated for atopic dermatitis and asthma with radioallergosorbent testing (RAST).
They divided the children into those who had no significant respiratory illness during infancy, those with one to four illnesses, and those with five or more respiratory illnesses during infancy.
They then compared the frequency of illness to the results of the various outcomes, and found that there were no significant differences between the children with frequent colds and those with no colds in regard to either skin prick test (52% versus, 45%, respectively, P=0.62), RAST results (58% versus, 36%, P=0.14), or the diagnosis of active atopic dermatitis (38% versus, 23%, P=0.22).
"However, the results demonstrated that children who had frequent respiratory illnesses during infancy had a higher incidence of asthma at age six year relative to those who had no respiratory illnesses in infancy," Grabher said.
In the third presentation by the COAST researchers, Christopher J. Tisler, M.T., also of the University of Wisconsin, reported on a study of the associations of allergic sensitization and the diagnosis of asthma at six years.
They evaluated allergen-specific immunoglobulin E results at ages one, three, and five years, looking for allergic antibody responses to common foods and aeroallergens, include dust mite, Alternaria mold, dog and cat dander, ragweed, silver birch, timothy grass, cockroach, milk, egg and peanut.
They found that sensitization to any allergen at the three time points was associated with increased rate of asthma at age six, and that sensitization to all three food allergens at age one, and to egg and peanut at age five were significantly associated with an increased rate of asthma at age six.
Among the aeroallergens, however, sensitization only to dog and cat dander at age one was associated with an increased rate of asthma at age six. But by age five, children with sensitization to any aeroallergen were more likely to be diagnosed with asthma within a year.
"Allergic sensitization to foods and/or aeroallergens in early life is associated with the development of asthma by six years of age," Tisler said. "The pattern of this sensitization process varies depending on the antigens evaluated, Associations with milk, egg and peanut sensitization begin during infancy and persist into childhood. Associations with cat and dog sensitization also develop during infancy, whereas associations with mite and Alternaria sensitization do not occur until later childhood."
Dr. Lemanske said the next phase of COAST research will involve emerging viral molecular biology analysis techniques to try to tease out which strains of rhinovirus may be most strongly associated with asthma risk, with the ultimate goal being to develop, if possible, a prophylactic vaccine.