Question

2.3. Assessment of infant allergies and infections

Infant allergies and infectious diseases that developed during the first 18 months of life were assessed based on mothers' self-administered questionnaire at 18 months post-delivery. Food allergy was defined as a positive response to the following question: “Has your child ever had symptoms such as hives, swelling of the lip, emesis, diarrhea, or respiratory distress when they ate food allergens including milk, egg rice gruel, egg-drop, shrimp, or other foods?” Eczema was defined using a modified part of the Japanese version of the International Study of Asthma and Allergies in Childhood (ISAAC) phase-I questionnaire (ISAAC Steering Committee, 1998). The part contained six questions: “(1) Has your child ever had an eczema in the past? If yes; (2) Has your child ever had an itchy rash, which was coming and going for at least 6 months? If yes; (3) Has this itchy rash at any time affected any of the following places: the folds of the elbows, behind the knees, in front of the ankles, under the buttocks, or around the neck, ears, or eyes?; (4) Has your child ever had dry skin in the past?; (5) Has your child ever had a doctor's diagnosis or diagnostic possibility for an eczema in the past?; (6) Does an itchy rash at any time affect any of the following places: the folds of the elbows, behind the knees, in front of the ankles, under the buttocks, or around the neck, ears, or eyes at present?” Wheezing was defined using a modified part of the Japanese version of the American Thoracic Society—Division of Lung Diseases (ATS—DLD) questionnaire (Nishima et al., 2009). The part contained five questions: “(1) Has your child ever had an attack of wheezing and/or shortness of breath in the past?; (2) Has your child ever had twice or more attacks in the past?; (3) Has your child ever had a doctor's diagnosis possibility for a bronchial asthma, asthmatic, or pediatric asthma in the past?; (4) Could wheezing be heard during an attack?; (5) Has your child ever had shortness of breath and wheezing during an attack?” To estimate the proportion of allergies or infectious diseases, we defined an outcome based on the following criteria: if infants had a positive response to the following medical question: “Has your child ever had a doctor's diagnosis, hospitalization, or medical treatment for the following diseases: asthma, eczema, other allergic diseases, otitis media, febrile convulsion, RSV diseases or other diseases, including chicken pox, bronchitis, rhinitis, pneumonia, skin infection and other viral infections?”

Are there any concerns about measurement error of the outcome factor in this study (both advantage(s) and disadvantage(s))? Give reasons for your answer.

Answer 1

#£ Wheeze in Infants: Correction for Bias Due to Exposure Measurement Error

--Exposure to elevated levels of endotoxin in family-room dust was previously observed to be significantly associated with increased wheeze in the first year of life among a cohort of 404 children in the Boston, Massachusetts, metropolitan area. However, it is likely that family-room dust endotoxin was a surrogate for airborne endotoxin exposure. Therefore, a related substudy characterized the relationship between levels of airborne household endotoxin and the level of endotoxin present in house dust, in addition to identifying other significant predictors of airborne endotoxin in the home. We now reexamine the relationship between endotoxin exposure and wheeze under the assumption that the level of airborne endotoxin in the home is the exposure of interest and that the amount of endotoxin in household dust is a surrogate for this exposure. We applied a measurement error correction technique, using all available data to estimate the effect of endotoxin exposure in terms of airborne concentration and accounting for the measurement error induced by using house-dust endotoxin as a surrogate measure in the portion of the data in which airborne endotoxin could not be directly measured. After adjusting for confounding by lower respiratory infection status and race/ethnicity, endotoxin exposure was found to be significantly associated with a nearly 6-fold increase in prevalence of wheeze for a one interquartile range increase in airborne endotoxin (95% confidence interval, 1.2–26) among the 360 children in households with dust endotoxin levels between the 5th and 95th percentiles.

¥ Bacterial endotoxin is a lipopolysaccharide found in the outer cell membrane of gram-negative bacteria (GNB). Among its many known biologic activities, endotoxin is a cause of airway inflammation when inhaled. Exposure to endotoxin is associated with increased risk of nonatopic wheeze and with reduced prevalence of inhalant allergy, eczema, and atopic wheezing. Given the pervasive presence of GNB in household dust and air, everyone is exposed to at least low levels of environmental endotoxin

# Eosinophilic esophagitis (EE) is an increasingly recognized disorder characterized by an abnormal accumulation of eosinophils in the esophageal mucosa in patients with symptoms of refractory gastroesophageal reflux and dysphagia.1 While the pathogenesis remains unknown, initial studies in mice exposed to the aeroallergen Aspergillus fumigatus suggested a role for T cells and IL-5.2,3 Recent studies of RNA in human biopsy specimens have suggested a role for IL-13 and eotaxin-3 in recruitment of eosinophils.4 Once present, eosinophils may act in an autocrine fashion to perpetuate inflammation and decrease epithelial barrier function.5 An allergic trigger for this inflammation is suspected since a large proportion of patients have identifiable allergic sensitivities. 6,7 In spite of the high prevalence of specific allergic sensitivities and associated atopic diagnoses frequently found among EE patients, the relationship between EE and allergic sensitization is not straightforward.