SAN ANTONIO, TEX—Among preschoolers who wheeze, distinguishing those with asthma from those with other disorders is difficult because the presentation of asthma is so heterogeneous in young children. “Some may only have cough; others have cough, wheeze, and symptoms on exertion,” explained David P. Skoner, MD, at the annual meeting of the American College of Allergy, Asthma and Immunology (ACAAI).[1] “Some have [symptoms] at night; others may not,” added Dr. Skoner, Associate Professor of Pediatrics/Otolaryngology at the University of Pittsburgh.

Also, parents tend to underreport asthma symptoms in their children. For example, some parents may describe their child’s symptoms as mild even if bronchodilators are needed five or six times a week.

So, how should asthma be diagnosed in preschoolers? Dr. Skoner shared his views on these topics during a symposium on childhood asthma at the ACAAI meeting. During the same symposium, Jaime E. Alvarez, MD, Assistant Professor of Pediatrics at the University of Miami School of Medicine, described how to assess the response to asthma therapy in preschoolers.

CLINICAL DIAGNOSIS

Because spirometry is generally not used in children younger than 5 or 6, a diagnosis of asthma in preschoolers is usually based on clinical judgment. It is important to ask about a family history of atopy and asthma and, of course, wheeze, cough, dyspnea, and other symptoms associated with asthma.

In the office setting, physical examination often yields little evidence of asthma in preschoolers; results of a chest evaluation in pediatric outpatients are usually normal. Thus, assessment of risk factors may provide further clues.

“The single strongest predictor for wheezing that eventually develops into asthma is atopy,” stressed Dr. Skoner. “About 70% to 90% of children with asthma are atopic.” Maternal smoking, persistent wheeze, and viral respiratory infection are also important risk factors for childhood asthma.

However, most physicians will not diagnose asthma unless a child has had at least three episodes of reversible airway obstruction, said Dr. Skoner. In asthma, the obstruction should worsen with exercise, viral respiratory infection, or exposure to smoke or allergens. A foreign body in the airway, vascular rings around the airway, bronchiolitis, fistulas, cystic fibrosis, immunodeficiency, and laryngo-, tracheo-, or bronchomalacia can all mimic asthma.

In 2000, Castro-Rodríguez et al[2] tested the ability of “stringent” and “loose” clinical indexes to predict a subsequent diagnosis of asthma in children who wheezed in the first three years of life. The stringent index required frequent wheezing plus either one of two major risk factors (eczema and parental history of asthma) or two of three minor risk factors (eosinophilia, wheezing without colds, and allergic rhinitis). The loose index replaced “frequent wheezing” with “any wheezing” but otherwise required the same combinations of risk factors as in the stringent index.

Children who met the loose index criteria during their first three years of life were 2.6 to 5.5 times more likely to be given a diagnosis of active asthma between the ages of 6 and 13 than were those who did not meet these criteria. A positive stringent index was associated with a 4.3- to 9.8-fold increase in the risk of subsequent asthma. Furthermore, more than 95% of the children with a negative stringent index never received a diagnosis of asthma between the ages of 6 and 13. The National Heart, Lung, and Blood Institute used the study findings to formulate its latest recommendations on starting controller therapy for asthma in preschoolers, Dr. Skoner noted.

ASSESSING THE THERAPEUTIC RESPONSE

Asthmatic children must be identified and started on treatment between the ages of 1 and 6, stressed Dr. Alvarez. “After that time, whatever damage was going to occur in the airway will have taken place,” he pointed out.

However, skin tests for common allergens are recommended before inhaled corticosteroid therapy is initiated. The response to such therapy tends to be better among children with positive results to skin tests, Dr. Alvarez said.

In the absence of spirometry, physicians often use questionnaires (completed by parents) to follow up on very young children with asthma. Studies have shown that the questionnaire responses accurately reflect treatment-related changes in these children’s symptoms and quality of life.

Follow-up of asthmatic preschoolers may also be possible through measurement of inflammatory markers. For example, triamcinolone and montelukast have both been associated with increased levels of the inhibitory cytokine interleukin 10 (IL-10) in asthmatic children.[3] These children’s IL-10 levels appear to be strongly, albeit inversely, correlated with their eosinophil cationic protein (ECP) concentrations during montelukast and triamcinolone therapy. “The higher the levels of IL-10 in these patients, the lower the levels of ECP,” Dr. Alvarez reported. Nitric oxide concentrations have also been shown to decline in asthmatic children during montelukast administration.

Research involving adult asthma patients suggests that airway hyperreactivity to methacholine may also be useful in gauging the response to treatment; this may also prove true for childhood asthma. Treatment was more effective when medication adjustments were based on airway hyperreactivity rather than on forced expiratory volume in one second. Moreover, patients evaluated according to airway hyperreactivity showed larger declines in the thickness of their reticular basement membranes after 24 months of follow-up.

What is still unclear, remarked Dr. Alvarez, is whether anti-inflammatory therapy actually alters the natural course of asthma or only temporarily suppresses the disease, as some data suggest. “If that is the case, then we have a real problem,” he concluded.

—Timothy Begany