CHICAGO—Genetic research aimed at understanding the relationship between parents’ allergic sensitization and the allergic susceptibility of their offspring was presented at the Third Triennial World Asthma Meeting. Also discussed were two discoveries that could lead to new therapies for allergic rhinosinusitis and asthma: One uses short pieces of artificial DNA; the other involves interruption of transcription factor 6 function.

Other sessions focused on the treatment of asthma among disadvantaged inner-city and minority populations. Researchers also demonstrated that the use of a clearly defined care plan for the treatment of hospitalized patients with asthma can reduce the rate of additional hospitalizations and exacerbations.

PARENTAL INFLUENCES

Investigators from the Lovelace Respiratory Research Institute in Albuquerque have used a beagle dog model to evaluate the relationship between allergic sensitization of mothers and the allergic susceptibility of their offspring. Karen Rudolph, MS, and coworkers produced groups of puppies from females who had high levels of immunoglobulin (Ig) E but who were not sensitized to ragweed, and others who had been sensitized to ragweed through injection. Beginning 24 hours after birth and continuing through 22 weeks of age, all puppies were sensitized to ragweed. During sensitization and at ages 12 and 15 months, total IgE, ragweed-specific IgE, and IgG levels were assessed. Between 12 and 15 months, airway hyperresponsiveness to ragweed or histamine challenge was also examined.

Compared with the puppies from non-sensitized mothers, those puppies from sensitized dogs showed significantly higher levels of ragweed-specific IgE, but their ragweed-specific serum IgG levels were lower. In addition, the ragweed or histamine challenges produced more serious changes in airway resistance in the puppies from sensitized mothers.

The conclusion drawn by the researchers was that although the allergic sensitivity of the mothers influenced the allergic sensitivity of their young, it was still not clear whether allergen T cells, allergen-specific antibodies, or both from the pregnant females were most important in determining the next generation’s sensitivity.

“ARTIFICIAL” INTELLIGENCE

In a search for new approaches to the treatment of allergic rhinosinusitis, researchers have found an apparent means of blocking the malady’s TH2 (T-helper 2 cell) cytokine-mediated eosinophilic inflammation.

Iftikhar Hussain, MD, and his colleagues at the University of Iowa have observed the efficacy of CpG oligodeoxynucleotides (ODN), short strands of artificial DNA, in this capacity. Knowing that mammalian cells respond to stimulation from bacterial DNA with the release of inflammatory mediators in a TH1 response, they observed the effects of CpG ODN when it was used to mimic bacterial DNA at the time of mouse sensitization to aerosolized ovalbumin (OVA). They expected enhancement of the TH1 response and suppression of the TH2 response.

CpG ODN demonstrated an ability to reduce eosinophilic upper airway inflammation; no such reaction was seen in mice treated with non-CpG ODN, which served as a control. Levels of the TH2 cytokines interleukin (IL) 4 and IL-5 were suppressed in CpG-treated mice. There was no change in IL-2 levels, and interferon-g concentrations were increased in both the experimental and the control groups.

The conclusion drawn by the investigators was that when administered at the time of sensitization to an allergen, CpG ODN did suppress TH2 cytokine release and block the development of allergic rhinosinusitis.

ASTHMA TREATMENT: STAT?

Another approach to modulating the TH2 response involves interruption of Stat6 (signal transducer and activation of transcription factor 6). Anuja Mathew, PhD, and colleagues from the Division of Rheumatology, Allergy, and Immunology at Massachusetts General Hospital in Boston hypothesized that Stat6 may be involved in the trafficking and effector functions of TH2 cells. (It is already known to have a role in TH2 cell differentiation.)

After generating OVA-specific Stat6 TH2 cells from mice in vitro, these researchers transferred them into two sets of mice. One set was Stat6-positive; the other was Stat6-negative. Following OVA challenge, all of the features of asthma (eg, TH2 cell accumulation, chemokine production, airway eosinophilia, mucus production, and hyperresponsiveness) were found in the Stat6-positive mice, but they were “dramatically absent” in the Stat6-negative mice. Thus, the investigators believe that interruption of Stat6 signaling may prove an effective approach to asthma management.

MINORITIES’ UNDIAGNOSED ASTHMA

While working with the American Lung Association of Santa Clara and San Bernardino counties in California, Sulochina Lulla, MD, sent surveys to 1,755 students in three of Santa Clara’s elementary schools to help identify previously undiagnosed asthma cases in minority communities. A total of 883 surveys were returned. Most of the respondents were members of minority communities: 41% were Hispanic; 30%, Asian/Pacific Islander; 3%, African-American; and 1%, Native-American. One hundred of the respondents already had a diagnosis of asthma, and in 536 others, results suggested that no further evaluation was required. Of the remaining 247 students, 218 could be examined using spirometry both before and after bronchodilator administration. A diagnosis of asthma was made in 85 of these students after two independent physicians interpreted the spirometric results. The conclusion reached was that asthma incidence in this culturally and ethnically diverse community was 21%, compared with the national incidence of 8%, and that asthma cases in such communities are often undiagnosed.

PLANS REDUCE HOSPITALIZATIONS

The combination of an in-hospital care plan and good patient education can reduce subsequent utilization of medical resources.

Nina Zimmermann, RN, BSN, and colleagues performed a retrospective randomized review of patients admitted to Barnes Jewish Hospital, St. Louis, for asthma-related problems. During the six-month study, 42% of all asthma patients were treated using the care plan; 75% of these patients were at high risk for asthma morbidity.

Patients administered the care plan were more likely than were other asthma patients to receive in-hospital education and to be discharged with a prescription for inhaled corticosteroids. Use of the care plan appeared to significantly reduce the rate of subsequent hospitalizations, including emergency department visits.

—Owen McCarthy