Studies: Determining asthma's origin and treatment

Investigators designed a three-part, genomewide study to elucidate whether variations in genes that affect serum levels of the protein YKL-40, which has been implicated in inflammation and tissue remodeling, influence the risk of asthma and bronchial hyperresponsiveness and are associated with reduced lung function.

In the first phase of the study, YKL-40 levels were determined in a 3,000-person population of Hutterites, who were related to each other in multiple lines of descent in an isolated community in South Dakota that had 62 founders and a 13-generation pedigree. Seventy-six (11.7%) of the Hutterites had asthma, 80 (12.3%) others had only bronchial hyperresponsiveness, and 423 (64.9%) did not have bronchial hyperresponsiveness and were not symptomatic.

Hutterites with asthma, bronchial hyperresponsiveness, or reduced lung function had higher mean YKL-40 levels than those without these conditions. Among the birth-cohort group, serum YKL-40 levels at each age were not significant predictors of asthma diagnosis at 6 years, though the association at 3 years approached statistical significance. A genetic variation in CHI3L1, a gene that encodes YKL-40 and was associated with elevated serum YKL-40 levels in the Hutterites, also predicted the presence of asthma in the two case-control populations and serum YKL-40 levels at birth (in cord-blood specimens) through 5 years in the birth cohort. Investigators therefore concluded that CHI3L1 is a susceptibility gene for asthma, bronchial hyperresponsiveness, and reduced lung function, and that elevated circulating YKL-40 levels are a biomarker for asthma (Ober C et al: N Engl J Med 2008;358:1682).

Black and Latino children with asthma have worse morbidity and receive less controller medication than their white peers. Because of this, investigators examined whether parental expectations and concerns vary among different racial and ethnic groups.

The study was based on telephone interviews in English or Spanish with parents of children with asthma who were served by two health care systems in the Boston area: a large Medicaid managed care plan and a multispecialty provider group that serves privately insured patients as well as Medicaid patients.

The interviews with more than 700 families (43% white, 24% black, 21% Latino, and 12% other) addressed four issues: expectations for functioning with asthma, concerns about medications, interactions with providers, and worries about asthma and competing family priorities. The interviews, which lasted about 30 minutes, relied on statements to which parents were asked to express their level of agreement or disagreement (such as "strongly agree" or "strongly disagree").

Parents of black and Latino children had lower expectations for their children's asthma than parents of white children. For example, 84% of parents of black children, 75% of parents of Latino children, and 89% of parents of white children believed that their offspring could be symptom free most of the time. Similarly, 44% of parents of black children, 43% of parents of Latino children, and 55% of parents of white children expected that their children should have no asthma-related emergency department visits or hospitalizations. Latino children's parents also were more likely to consider their children in good control if they had more than two days each week that were symptom free.

Compared with white children's parents, parents of black and Latino children had more medication concerns. Parents of minority children were more likely to believe that their children would become dependent on medication if they received them every day. Thirty-two percent of parents of black children and 38% of parents of Latino children, compared with 23% of parents of white children, agreed with a statement that their children did not need as much medicine as the doctor prescribed.

In one area of agreement, black, Latino, and white children's parents were equally satisfied with interactions with health-care providers. Not only were 91% of parents overall highly satisfied with communication with their children's providers, but 93% were satisfied with providers' knowledge of their children and their history.

Compared with parents of white children, parents of black and Latino children were far more worried about their children's asthma-as well as housing, home and neighborhood safety, job, personal and family relationships, income, and personal or family health. Minority parents were also more likely to have competing family priorities "all of the time" or "most of the time" (Wu AC et al: Ambul Pediatr 2008;8:89).

Commentary

It's good to look at these first two articles together: The first describes a specific gene mutation that increases an inflammatory protein associated with asthma. One day soon, this gene and this protein may be used as markers for asthma risk, measures of asthma control, or targets for pharmaceutical intervention in asthma. The second article describes how parents perceive their children's asthma, and the social environment in which they deal with their child's disease. As with all chronic diseases in pediatrics, real progress depends on translating the complex advances in the first study into the complex environment of the second.

DR. BURKE, section editor for Journal Club, is chairman of the department of pediatrics at Saint Agnes Hospital, Baltimore. He is a contributing editor for Contemporary Pediatrics. He has nothing to disclose in regard to affiliations with, or financial interests in, any organization that may have an interest in any part of this article.