German study: atopy is key in asthma's origin.

KEYSTONE, COLO. -- Recurrent wheezing illnesses affect 35%-70% of children in the first 4 years of life, yet only about 10% of school-age children have active asthma with airway hyperresponsiveness and impaired lung function. What distinguishes preschoolers whose wheezing is self-limited from those who will go on to develop asthma?

Some of the most valuable insights regarding this key issue have come from the landmark German Multicenter Allergy Study (MAS), Dr. Joseph D. Spahn noted at a meeting on allergy and respiratory diseases.

In brief, MAS has shown there are two phenotypes of early childhood wheezers. Those without atopy typically outgrow their wheezing symptoms. They have normal lung function at puberty. In contrast, the majority of those who display sensitization to indoor perennial aeroallergens on skin testing at age 3 years will go on to have active asthma at age 13--and their risk is boosted further if they also have a high level of exposure to the allergens. These are the children who need to be on a controller medication, explained Dr. Spahn of the University of Colorado at Denver.

"If you're able to do RAST or skin testing and you only have one period of time to do it, I would say do it at age 3, because that's the cut point," he continued at the meeting, which was sponsored by the National Jewish Medical and Research Center, which is also in Denver. "If you're negative at 3 [years], chances are you're going to outgrow this thing, and if you're positive at 3 [years], chances are you're not. That's what this study has taught us."

The MAS study, funded by the German Federal Ministry of Education and Research, prospectively followed 1,314 children in five cities from birth to age 13 years. Allergic sensitization to house dust mites, cat and dog hair, and other perennial allergens was assessed six times during ages 1-10 years. Lung function was measured at 7, 10, and 13 years. Environmental exposure to allergens was evaluated via home visits at ages 6 months and 18 months, and at 3, 4, and 5 years.

"The exposure assessment is what makes this study so great. They went to the homes to see whether it was just sensitization in children or sensitization plus exposure that drives the development of asthma," he observed.

Nine of every 10 young children with recurrent wheezing but no atopy on skin testing at age 3 years lost their respiratory symptoms by school age and continued to have normal lung function by age 13 years.

In contrast, 56% of atopic wheezers had asthma by age 13 years. Impairment of small-airway function at age 7 years as assessed by maximum expiratory flow at 50% was greater in children sensitized to allergens by age 3 years than in those sensitized by age 5 years, and greater in those with high rather than low home exposure (Lancet 2006;368:763-70).

The MAS study also answered another key question: Do preschoolers with atopic dermatitis but no wheezing face an in creased risk of asthma later? The answer is no. The great majority of children with atopic dermatitis in the first 2 years of life outgrew it; indeed, only 18% had active atopic dermatitis at age 7 years. And those without concomitant early wheezing weren't at increased risk of asthma by age 7 years, compared with nonwheezers without eczema (J. Allergy Clin. Immunol. 2004; 113:925-31).

That finding throws a hitch into the atopic march theory.

"It's not that there's a progression from atopic dermatitis to asthma, which the atopic march would have us believe; but that there are two distinct phenotypes of eczema early in life: eczema by itself, and eczema plus recurrent wheezing," said Dr. Spahn, who also is director of the pediatric allergy/immunology fellowship program at the medical center. "The two have to be together early in life--atopic dermatitis and wheezing--for atopic dermatitis to have a bad outcome."

BY BRUCE JANCIN

Denver Bureau