THE ROLE OF INDOOR ALLERGEN SENSITIZATION AND EXPOSURE IN CAUSING MORBIDITY IN WOMEN WITH ASTHMA
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1 Online Supplement for: THE ROLE OF INDOOR ALLERGEN SENSITIZATION AND EXPOSURE IN CAUSING MORBIDITY IN WOMEN WITH ASTHMA METHODS More Complete Description of Study Subjects This study involves the mothers of children in the Epidemiology of Home Allergens and Asthma Study, an ongoing longitudinal birth and family cohort study. Between September 1994 and June 1996, 499 families with a history of asthma or allergy in at least one parent were enrolled in a birth cohort study designed to examine the effects of early life allergen exposure on the development of childhood asthma. On weekdays, all mothers who delivered their babies at a large Boston hospital were approached for screening 24 to 48 hours after delivery if they lived within Route 128 (which roughly encircles the greater metropolitan area), were 18 years old or older, and were able to speak English or Spanish. Families were not screened if they were identified by the floor nurse as unlikely to be comfortable with an interview or if the index child was premature (under 36 weeks), had a major congenital abnormality, or was in the neonatal intensive care unit. Mothers were asked the following simple screening question: Have you ever had a doctor s diagnosis of asthma, hay fever, or allergies? Has the biological father of your child ever had a doctor s diagnosis of asthma, hay fever, or allergies? If the mother answered yes to one or both of these questions, they were asked to complete a more detailed screening questionnaire. E1
2 Over the enrolment period, we identified 7,657 women who lived within the Route 128 area and were 18 years of age or older; 5,973 were approached and asked about maternal or paternal history of asthma or allergy. Most of the mothers (5,904) agreed to answer the simple screening questions. Of these, 1,539 had a maternal or paternal history of asthma or allergy, and 1,405 families agreed to complete a more detailed screening questionnaire. Of the 1,405, 906 were excluded from the study before measurement of home allergen. The reasons for exclusion included plans to move within the next year (45%), loss-to-follow-up (14%), and other (2%). More Complete Description of Questionnaire At the screening interview the mother completed a detailed respiratory history that included the following questions. 1. Has a doctor ever said that you had asthma? IF YES: 2. Have you been ill with asthma at any time in the past 12 months? IF YES: 3. What was the longest amount of time you were ill with asthma in the past 12 months? (Under 1 week; 1 3 weeks; more than 3 weeks; don t know) 4. Did you take any of the following medications when you were ill with asthma in the past 12 months? (If you had more than one bout of asthma, answer for the WORST bout.) Included: Inhaled steroids (e.g., Vanceril, Azmacort, Becotide inhalers). Steroid by pill or by intravenous (e.g., prednisolone). 5. During the past 12 months, have you been treated in a hospital emergency room (ER) for your asthma? 6. Has you chest ever sounded wheezy or whistling, including when you had a cold? E2
3 IF YES: 7. Within the past 12 months, did you chest ever sound wheezy or whistling when you did not have a cold? Follow-up Questionnaires at 12-month Interviews Virtually identical questions were asked at each 12-month telephone interview for the following 4 years. At 4 years, the question on ER attendance was substantially altered, and we have therefore restricted our analysis of this end point to 3 years of follow-up. Derived Variables The following derived indicators of asthma morbidity were applied. Doctor diagnosed asthma. A positive response to: has a doctor ever said that you have asthma. Prolonged illness. Ill will asthma in the past 12 months and for 1-3 weeks or for more than 3 weeks. Use of steroid. Use of inhaled or pill steroids during the worst bout of asthma in the last 12 months. Use of a hospital ER. Positive response to: have you been treated in a hospital ER for your asthma. Wheeze without a cold. Positive response to question 7. E3
4 Overall asthma morbidity. A positive response to any one of the indicators (prolonged illness, use of steroid, use of a hospital ER, or wheeze without a cold) in the whole group and in the asthmatic subgroup was defined as overall asthma morbidity. Measurement of Cockroach, Mite, and Cat Allergen At the home visit, dust samples were collected in standardized fashion by vacuuming from the kitchen, living room, the index baby s bed and bedroom floor, and, if the baby shared a bedroom with the parents, also from the parent s bed. Methods used in collecting the dust samples, the array of allergens measured, and the processing and assay of each allergen have been detailed elsewhere (10;12). Each sample was analyzed for allergens from a dust mite (Der f 1) and cat (Fel d 1), recorded in units of µg per gram of dust, and cockroach (Bla g 1, and if sufficient dust was available, Bla g 2), recorded in units per gram (U/g) of dust. For analysis, we categorized Bla g 1 and Bla g 2 separately using the following cut-offs: 2 U/g (including concentrations exceeding the detectable limits), 0.05 to < 2 U/g, and < 0.05 U/g (including concentrations below the detection limit). We defined a further variable indicating the maximum of these categories for either Bla g 1 or Bla g 2, and we combined the lower two categories of this variable to provide a binary indicator of high ( 2 U/g) and low (< 2 U/g) levels. Levels of Der f 1 were categorized as: 10 µg/g, 2 to 10 µg/g, and < 2 µg/g or as high ( 10 µg/g) and low (< 10 µg/g) levels; and levels of Fel d 1 were categorized as < 1 µg/g, 1 to 8 µg/g, and 8 µg/g or as high ( 8 µg/g) and low (< 8 µg/g) levels. Levels of allergen in the bedroom were available for only those women who shared a bedroom with their baby and were derived as the E4
5 maximum of the measured level for the parent s bed, the child s bed, and the bedroom floor. Statistical Analysis Statistical analyses were performed using SAS statistical software (SAS Institute Inc., Cary, NC). We first analyzed the relation of measured allergen concentrations (on three levels) with specific sensitization and with the level of specific IgE, with and without adjustment for race/ethnicity and for poverty, and within the whole group and the allergic subgroup, using multiple logistic regression. Taking doctor-diagnosed asthma and overall asthma morbidity as two indicators of asthma status, we then analyzed the three-way relation of allergen level (binary) and sensitization to the risk of asthma and to measures of morbidity (steroid use, use of hospital ER, wheeze without a cold, prolonged illness) at screening and during follow-up in diagnosed asthmatics, using multiple logistic regression. Evidence of interaction between sensitization and allergen level on these outcomes was assessed using the likelihood ratio test. Numbers of doctor-diagnosed asthmatics were small, and we therefore also compared the sensitized women with high allergen levels to the remainder. We added each of age (in quartiles), race, and poverty in turn and simultaneously to the model to assess confounding. To analyze the longitudinal data, we computed the person years of follow-up for each individual and computed an estimate of the annual proportion with each measure of morbidity. In the logistic regression, we accounted for correlations between repeated observations on the same individual using generalized estimating equations (13). The GENMOD procedure in SAS deals with missing values by estimating the working correlation by the all-available pairs E5
6 method, where all nonmissing pairs of data were used in the moment estimators of the working correlation parameters. References E1. Kitch BT, Chew G, Burge HA, Muilenberg ML, Weiss ST, Platts-Mills TA, O Connor G, Gold DR. Socioeconomic predictors of high allergen levels in homes in the greater Boston area. Environ Health Perspect 2000;108: E2. Gold GR, Burge HA, Carey V, Milton DK, Platts-Mills T, Weiss ST. Predictors of repeated wheeze in the first year of life: the relative roles of cockroach, birth weight, acute lower respiratory illness, and maternal smoking. Am J Respir Crit Care Med 1999;160: E3. Zeger SL, Liang KY. Longitudinal data analysis for discrete and continuous outcomes. Biometrics 1986;42: E6
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