Larry W. Williams

Obesity, inflammation, and asthma severity in childhood: data from the National Health and Nutrition Examination Survey 2001-2004

BACKGROUNDnThe prevalences of asthma and obesity in children have increased significantly during the past 2 decades. The basis for the relationship between pediatric asthma and obesity is not well established.nnnOBJECTIVESnTo explore the association between obesity and asthma severity in children and adolescents and to test whether obesity-induced inflammation, as characterized by serum C-reactive protein (CRP), is associated with increased severity of asthma.nnnMETHODSnRetrospective cohort analysis of interview, physical examination, and laboratory test data from participants younger than 20 years in 2 rounds of the National Health and Nutrition Examination Survey (2001-2002 and 2003-2004). We also performed generalized ordered logistic regression to evaluate the effect of body mass index (BMI) z score and CRP level on asthma severity, controlling for the impact of age, sex, race, income, insurance, and tobacco smoke exposure.nnnRESULTSnOf the 77 million individuals younger than 20 years represented by this weighted sample, 19% met the study-defined criteria for asthma; most cases were defined as mild (11%) or moderate (6%); 2% had severe asthma. In multivariable models, elevated BMI z scores (odds ratio, 1.12; 95% confidence interval, 1.05-1.21) were associated with worse asthma severity. Elevated CRP level was associated with obesity (P < .001) and asthma severity (odds ratio, 1.33; 95% confidence interval, 1.16-1.52).nnnCONCLUSIONSnHigher BMI z scores and elevated serum CRP levels are associated with increased asthma severity. These findings highlight the importance of controlling for inflammation when considering the role of obesity and provide support for the hypothesis that obesity-induced inflammation may contribute to greater asthma severity.

Clinical Characteristics of Peanut-Allergic Children: Recent Changes

OBJECTIVE. The goal was to determine whether patients seen in a referral clinic are experiencing initial allergic reactions to peanuts earlier, compared with a similar population profiled at a different medical center 10 years ago, and to investigate other changes in clinical characteristics of the patients between the 2 groups. METHODS. We reviewed the medical charts of peanut-allergic patients seen in the Duke University pediatric allergy and immunology clinic between July 2000 and April 2006. RESULTS. The median ages of first peanut exposure and reaction were 14 and 18 months, respectively; the respective ages in a similar population profiled between 1995 and 1997 were 22 and 24 months. Within our patient group, those born before 2000 were first exposed to peanuts at a median age of 19 months and reacted at a median age of 21 months, compared with first exposure at 12 months and first reaction at 14 months for those born in or after 2000. Most patients (68%) demonstrated sensitization or clinical allergy to other foods (53% to eggs, 26% to cows milk, 20% to tree nuts, 11% to fish, 9% to shellfish, 7% to soy, 6% to wheat, and 6% to sesame seeds). CONCLUSIONS. In the past decade, the ages of first peanut exposure and reaction have declined among peanut-allergic children seen in a referral clinic. Egg allergy is very common in peanut-allergic patients, and sesame seeds should perhaps be considered one of the major food allergens. The decline in the age of first peanut reaction seems to be attributable to earlier exposure.

Dietary Intake of Soy Genistein is Associated with Lung Function in Patients with Asthma

To determine if micronutrient intake is associated with asthma severity, we administered the Block food frequency questionnaire to participants in a randomized clinical trial of the safety of influenza vaccine for asthmatics. The nutrition substudy included 1033 participants, aged 12–75. Intake of antioxidant vitamins, soy isoflavones, total fruits and vegetables, fats, and fiber was compared with asthma severity at baseline [forced expiratory volume in 1 second (FEV1), peak expiratory flow rate (PEF), asthma symptoms] and the rate of asthma exacerbations during the 2 weeks following influenza vaccination. The only nutrient that had a consistent association with asthma severity was genistein, a soy isoflavone. None of the nutrients evaluated were related to asthma exacerbation rate when adjusted for known confounders. The FEV1 in genistein consumers of at least 250 µg/1000 Kcal/day was 82.1% predicted, 79.9% predicted for those who consumed between 1 and 249 µg/1000 kcal, and 76.2% predicted in genistein nonconsumers (p = 0.006); the PEF was 82.7% predicted, 80.8% predicted, and 78.3% predicted, respectively (p = 0.009). There were no differences in the Asthma Symptom Utility Index (ASUI). We could not account for these results based on differences in demographics, body mass index, or consumption of other nutrients. Thus, increasing consumption of genistein is associated with better lung function in patients with asthma. Further studies are needed to determine whether dietary supplementation with genistein can reduce asthma severity.

Safety of open food challenges in the office setting

BACKGROUNDnOpen food challenges are a practical alternative to double-blind, placebo-controlled food challenges in confirming clinical sensitivity or tolerance to a food, and the risks associated with open challenges are unknown.nnnOBJECTIVEnTo examine the safety of open food challenges administered in an office setting.nnnMETHODSnA retrospective medical record review of open food challenges, administered in a university-based pediatric allergy-immunology clinic during a 3-year period, was performed.nnnRESULTSnA total of 109 patients (69% male) underwent 150 open food challenges, most of which were to milk (n = 39), peanut (n = 37), and egg (n = 29). There were 40 positive challenges (27% of all challenges) in 33 patients. Reactions were mild to moderate in 92% of positive challenges. Cutaneous reactions occurred in 68% of positive challenges, followed by gastrointestinal tract reactions (45%) and upper respiratory tract reactions (38%), excluding laryngeal symptoms. No patient had cardiovascular involvement. Food specific IgE values did not correlate with reaction severity. Interventions included observation or antihistamine only in 92% of positive challenges. No patient received epinephrine or required hospitalization. For negative challenges to milk, peanut, and egg, median prechallenge food specific IgE approached previously published negative predictive values for these foods. Negative challenges in patients allowed the introduction of 19 different foods into the diet of 88 patients.nnnCONCLUSIONnOpen food challenges are a safe procedure in the office setting for patients selected based on history and food specific IgE approaching negative predictive values.

Burkholderia glumae Infection in an Infant with Chronic Granulomatous Disease

ABSTRACT An 8-month-old boy developed a necrotic lung mass from which Burkholderia glumae was recovered, leading to the diagnosis of chronic granulomatous disease (CGD). While other Burkholderia species have been identified as important pathogens in persons with CGD, B. glumae has not been previously reported to cause human infection.

Skin testing and food challenges in allergy and immunology practice

SummarySkin tests by prick technique offer considerable guidance in the diagnosis of food allergy. Negative prick skin tests are powerful evidence against food allergy. Positive food skin tests are slightly to moderately predictive of reaction to a food on DBPCFC. Oral food challenge is necessary for confirmation of food allergy, except where the history is overwhelmingly convincing. Open, incremental food challenge as described is diagnostic if negative, but only 50% of all positive open challenges are confirmed on blinded challenge. DBPCFC can be designed for any food with simple blinding techniques. The technique of DBPCFC can be modified for investigation of atypical symptoms.

PERSISTENT ANTIBODY DEPLETION AFTER RITUXIMAB IN THREE CHILDREN WITH AUTOIMMUNE CYTOPENIAS

We report 3 children who developed persistent antibody depletion and abnormal response to bacteriophage after rituximab treatment for autoimmune cytopenias. Whether these patients have developed immunodeficiency secondary to an underlying disease process, to rituximab, or both, is not understood. Rituximab is an efficacious drug for a number of pediatric conditions. However, some patients who receive the drug have prolonged suppression or absence of B-cell function. Families should be counseled of this possibility prior to therapy. Patients should have baseline measurement of quantitative immunoglobulins and specific antibody levels and should be monitored for long term changes in immune function after rituximab.

Isolation of the 36-kD German (Blattella germanica) cockroach allergen using fast protein liquid chromatography.

Cockroach allergens have been established as important sensitizing agents in the induction of asthma. In the present investigation, we identified a 36-kD allergen from German cockroach (Blattella germanica) using fast protein liquid chromatography that reacted in the Bla g II monoclonal assay developed by Pollart et al. Defatted whole body German cockroaches were extracted in phosphate-buffered saline and fractionated using gel filtration (Superdex 75) and anion exchange (MonoQ) chromatography. The 36-kD allergen was isolated from this enriched allergen preparation by excision from modified preparative sodium dodecyl sulfate polyacrylamide gel electrophoresis (SDS-PAGE) gels, electroelution, dialysis and lyophilization. SDS-PAGE/Western immunoblot analysis using a serum pool of cockroach-sensitive individuals revealed a single band. The lyophilized 36-kD allergen was then analyzed for amino acid composition and digested for peptide amino acid sequencing.

Identification of Cockroach Aeroallergens from Living Cultures of German or American Cockroaches

The Air Sentinel and polytetrafluoroethylene (PTFE) membranes were used to capture airborne particles over living colonies of German or American cockroaches. Silver-stained SDS-PAGE gels revealed protein bands at 80, 55, 36, and several bands below the 33-kD marker. SDS-PAGE/immunoblots of PTFE eluates from German cockroach colonies incubated with serum from cockroach-sensitive individuals revealed IgE-binding bands with apparent molecular weights of 36 and 80 kD. Only the 36-kD allergen and allergens below the 33-kD marker were evident in the American PTFE eluate. ELISA analysis with a monoclonal antibody assay identified the presence of both Bla g I and Bla g II in the German PTFE eluate. No Bla g I or Bla g II could be identified in the American PTFE eluate. These studies demonstrate that in addition to Bla g I and Bla g II, several other aerosolized allergens become airborne over cockroach colonies and may be important in the environment where cockroaches are abundant.

SKIN TESTING AND FOOD CHALLENGES FOR EVALUATION OF FOOD ALLERGY

Skin testing by prick technique has an excellent safety record in the evaluation of food hypersensitivity. Skin prick tests for the common food allergens are excellent tools for identifying those at very low risk of reaction on eating the food but are of variable value in identifying patients who will be positive on challenge. Intradermal skin tests to foods are less safe and appear to add no predictive information. Skin tests to less common food allergens, especially fruits, are less well characterized and may require use of the food item itself as the source of allergen rather than a commercial extract. For a few foods, the CAP system fluorescent enzyme immunoassay (Pharmacia, Peapack, NJ) recently has been shown to have good ability to identify patients at very high probability of reaction on oral challenge. Oral challenge remains the definitive method of demonstrating sensitivity or tolerance to a food. The double-blind, placebo-controlled food challenge is the gold standard of diagnosis, but in many situations, simpler open or single-blind challenge procedures may be substituted. With careful, incremental dosing and a low starting dose, oral challenges for food hypersensitivity have an excellent safety record. Skin prick tests are of little value in the evaluation of adverse food reactions not mediated by IgE. Oral challenge is relied upon in this situation for definitive diagnosis, but challenges may be cumbersome if the time course of the presumed reaction is not rapid.