Marks et al. errors and missing information. Families were then telephoned to attempt to correct the mis- takes or to fill in the missing information. Research; Clayton South, Victoria, Australia). Formaldehyde samples were collected using UMEx 100 (SKC Inc., Eighty Four, PA, Once each week, on Thursday or Friday, USA) passive sampling badges. we recorded PEF and FEV1 using the child’s own MWD device. This served as an in- school measurement of lung function and also provided an opportunity to check their tech- nique and correct it if needed. In addition at these school visits, we also recorded exhaled nitric oxide (eNO), using the offline method (Salome et al. 1999). Measurement of indoor NO2 and formal- dehyde concentrations. Airborne NO2 concen- trations in school classrooms were measured using passive diffusion badge monitors sup- plied by the CSIRO Division of Atmospheric Table 1. Baseline characteristics of the study population that completed at least one diary card. na (%) or Characteristic mean ± SD Total subjects with diary cards 400 (100) Females 220 (55) Atopicb Yes 152 (44) No 192 (56) Missing 56 Wheeze ever 168 (42) Wheeze in the last 12 months 84 (21) Doctor-diagnosed asthma 108 (27) Positive bronchodilator testc Yes 39 (10) No 337 (90) Missing 24 Current asthmad 60 (15) Use of any medicines for asthma 81 (21) Smoking inside the house 28 (7) Gas heating at homee Flued 66 (17) [9 missing] Unflued 89 (23) [11 missing] Gas for cooking at home 202 (51) Age (years) 10.6 ± 0.9 Height (cm) 143.7 ± 8.8 [10 missing] Weight (kg) 39.8 ± 10.4 [10 missing] FEV1 (L) 2.02 ± 0.39 [12 missing] FEV1 (% predicted) 90.8 ± 10.2 [16 missing] Forced vital capacity (L) 2.39 ± 0.47 [12 missing] Forced vital capacity (% predicted) 94.6 ± 10.5 [16 missing] eNO (ppb)f 8.04 (2.3–27.7) [56 missing] aComplete data or missing four or fewer subjects unless otherwise indicated. bSensitized to one or more of the test allergens. cIncrease in FEV1 after bronchodilator ≥ 12% of baseline value. dCurrent asthma defined as wheeze in the last 12 months and either doctor-diag- nosed asthma or a positive bronchodilator test. eSubjects who indicated they had no heating or had another type of heating at home but who did not answer the ques- tion about gas heating were assumed not to have a gas heater. Subjects who had a flued gas heater were assumed not to have an unflued gas heater. fGeometric mean and geometric 95% range are shown. 1478 On Thursday and Friday of every week during the study period, two NO2 samplers were exposed at two different locations in each classroom. One formaldehyde sampler was co-located at one of these sites on both occasions. Further details about the placement of the samplers and their chemical analysis are provided in the Supplemental Material (doi:10.1289/ehp.1002186). Study power and sample size estimates. On the basis of previous data from our research group, we estimated that the within-subject SD in FEV1 was 200 mL. On this basis, using a simple crossover paired t-test analysis, 43 subjects would be sufficient to give 90% power to detect difference in FEV1 between the two exposures of ≥ 100 mL. We expected to have an average of 15 student participants in each class. If the intraclass correlation coefficient for classrooms was as high as 0.2, then the design effect would be 3.8 and the required sample size increased to 164 subjects in 11 classrooms. To contend with potential nonparticipation and dropout among subjects and to facilitate the subgroup analyses proposed in the second hypothesis, we intended to recruit an average of 20 students from each of 20 classrooms, for a total of 400 children. Statistical analysis. Analysis was con- ducted in SAS 9.2 (SAS Institute Inc., Cary, NC, USA). A p-value (alpha) < 0.05 was regarded as statistically significant. A mean morning symptom score and a mean evening symptom score (excluding “sore teeth or gums” and “stomachache”) was calculated for each subject for each day. PEF and FEV1 recordings made between midnight and 1200 hours were designated as morning values, and those made between 1200 hours and midnight were designated as evening val- ues. We limited the data analyzed to those relevant to a period within 24 hr after the last exposure to heaters in schools. Hence, analyses of morning symptoms and lung function data excluded observations made on Sunday and Monday mornings, and analyses of evening reports of symptoms and records of lung function excluded observations made on Saturday and Sunday evenings. The effect of randomized heater type allo- cation (that is, exposure to flued vs. unflued gas heaters) was estimated using hierarchi- cal or mixed-model regression. Fixed effects were the heater type allocation, study period (first, second, or third pair of weeks), and day of the week. In a preliminary analysis we also included heater type randomization order (that is, flued heater in the first week of a pair vs. unflued heater in the first week of a pair) and the heater type by heater type order interaction to test for order effects. Subjects were included as random intercept assuming an unstructured (variance components) cor- relation matrix for the outcomes measured on individuals (diary card and lung function outcomes). Mixed models treat missing values as missing at random, which is a less-rigorous assumption than missing completely at ran- dom. School was included as either a random effect or a fixed effect, as described below. In a planned subsidiary analysis, we tested for current asthma status by heater type and atopic status by heater type interactions; where these interactions were significant, we fitted separately the models described above for the subgroup with current asthma or the subgroup with atopy. The primary analysis used all data in an intention-to-treat (ITT) analysis. However, we also fitted a per-protocol model in which the analysis was limited to schools and days for which heater use was estimated as ≥ 30%. We also tested the effect of three time-variable confounders—use of gas heaters at home, use of an open fire at home, and exposure to ETS at home—on the effect of the randomized Table 2. Concentrations of NO2 and formaldehyde measured by badges, by treatment group. Gas (ppb) NO2a Formaldehyde 23.5 28.6 Mean 95% Geometric range Mean 95% Geometric range Mean 95% Geometric range Overall 4.6–121.4 1.8–55.4 17.5 24.7 Flued 3.5–88.4 3.3–46.1 Unflued 31.6 32.6 7.4–135.2 3.1–62.1 aValues for NO2 are geometric mean and geometric 95% range. Table 3. Effect of heater type on NO2 and formaldehyde levels, measured by badges. NO2 Formaldehyde (absolute difference: (relative difference: unflued/flued) unflued – flued ppb) Population ITT analysisa Per protocolb (weeks when heater use is ≥ 30%) n 248 51 Mean ratio 95% CI p-Value n Mean difference 95% CI p-Value 1.80 2.33 1.55–2.10 < 0.0001 1.53–3.55 0.0002 167 44 9.6 20.1 5.9–13.3 < 0.0001 10.6–29.6 0.0001 The ratios and differences and their 95% CIs are derived from a mixed-model regression. Fixed effects were the heater type allocation, study period (first, second, or third pair of weeks), and day of the week. Schools were treated as random intercept, and a variance components correlation structure was assumed. aAll observations are analyzed according to the heater type exposure to which they were assigned. bThe analysis was limited to schools and days for which heater use was estimated as ≥ 30%. ovlume 118 | number 10 | October 2010 • Environmental Health Perspectives