KEYSTONE, COLO. — Failure to appreciate the key differences between childhood asthma and the adult version of the disease has led to widespread underdiagnosis of young asthmatics.
“Many of us grew up with a whole list of synonyms—reactive airway disease, wheezing bronchitis—that we used without saying a child has asthma …which leads to underdiagnosis and undertreatment. We still see a large body of physicians not using controller medications when there is persistent wheezing and instead giving a 3- to 5-day burst of oral steroids to the kids. That's something we have to change,” Dr. Erwin W. Gelfand declared at a meeting on allergy and respiratory disease sponsored by National Jewish Health, Denver.
The Centers for Disease Control and Prevention statistics are revealing. During 2003–2005, the prevalence of asthma among children up to 4 years of age was 6.2%, well below the 9.3% figure for 5- to 10-year-olds and the 10.0% rate in 11- to 17-year-olds. Yet the rate of emergency department visits for asthma in 2003–2004 was 164/10,000 people among the under-5 set, markedly greater than the 83/10,000 for children aged 5–10 years and the 69/10,000 for those aged 11–17 years.
Moreover, the hospital admission rate for asthma was 61/10,000 in children through age 4 years, compared to just 24/10,000 in 5- to 10-years olds and 12/10,000 in 11- to 17-year-olds.
The rate of ambulatory visits for asthma was more than 50% higher in children younger than age 5 years than in older pediatric cohorts, added Dr. Gelfand, chairman of the department of pediatrics at National Jewish Health and professor of pediatrics and immunology at the University of Colorado.
Childhood asthma is more likely to be episodic, especially in younger children. Also, children tend to have greater involvement of the peripheral, airways, so larger particle size inhaled medications may never reach the hyperresponsive portion of their airways.
Also, many children with asthma have normal-range forced expiratory volume in 1 second (FEV1) values when stable because they can hyperinflate and increase their total lung capacity with less airway resistance to airflow; that feature has led to many missed pediatric asthma diagnoses. In children, the forced expiratory flow over the middle half of forced vital capacity, or FEF25%-75%, is a more sensitive indicator of airflow obstruction than is FEV1, he said.
The Childhood Asthma Management Program Research Group (CAMP) study (N. Engl. J. Med. 2000;343:1054–63) provided the first signal of the limitations—or as Dr. Gelfand put it, the failures—of long-term corticosteroid therapy in children with asthma. While aggressive therapy with oral and high-dose inhaled corticosteroids often improve symptoms as long as the child is using them, they are not disease modifying and don't prevent severe airway remodeling.
“The Achilles heel of corticosteroid therapy is that it doesn't inhibit increased reticular basement membrane thickness. Basically, all we have for childhood asthma are bronchodilators and anti-inflammatory therapies. We don't have a cure, and we certainly don't have good drugs to target airway remodeling,” Dr. Gelfand noted.
New and better drugs, and perhaps combination therapies, are clearly needed in childhood asthma. More comprehensive targeting of the leukotriene pathway may be beneficial. Montelukast and the other current-generation leukotriene receptor antagonists target leukotriene C4 and D4, but not E4, which recent studies from Children's Hospital of Boston suggest is another important pathway in asthma. And then there is leukotriene B4, which increasingly looks to be a major player in asthma pathogenesis but also is not addressed by the leukotriene modifiers now on the market.
Another priority is developing alternatives to spirometry for monitoring lung function and inflammation in young children. The Asthma Predictive Index hinges on the finding of one major criterion—either a parent with asthma, early sensitization to an aeroallergen, or concurrent atopic dermatitis—or two minor criteria in the form of wheezing apart from colds, food sensitization, or eosinophilia.
An ongoing initiative, especially in Europe, is to try to prevent the induction phase of asthma and the so-called “atopic march” through interventions during the narrow window of opportunity thought to exist antenatally and in the first few years of life. Ongoing clinical trials toward this end variously involve immunotherapy in infancy, early pharmacotherapy, allergen avoidance, and paradoxically, allergen exposure. “The idea is that, while one cat is bad for an infant, having seven cats could be good.”
Dr. Gelfand disclosed serving on advisory boards for Merck & Co., Sanofi-Aventis, and Schering-Plough Corp.
The Achilles heel of steroid therapy is that it doesn't inhibit reticular basement membrane thicknesss.
Source DR. GELFAND