heater–type exposure on symptoms. Each of these three confounding factors was measured daily using the diary. For normally distributed continuous out- comes (FEV1, PEF, exhaled NO, and in-class formaldehyde), we used Proc Mixed (version 9.2; SAS Institute Inc., Cary, NC, USA) to fit the model assuming a normal error distribu- tion. School was included as an additional ran- dom-intercept term in these models. We used a similar model for the log10-transformed val- ues of in-class NO2 concentrations. The effect of heater type on the outcome was estimated as a difference with its 95% confidence inter- val (CI). The difference in log-transformed NO2 concentrations was raised to the power of 10 (anti-logged) to yield a ratio. Symptoms were treated as both a binary variable (present or absent) and a continu- ous score variable (0–3) and analyzed using Proc GLIMMIX with the Laplace estimation routine (SAS Institute Inc.). For binary out- comes, we used a logistic link and binary error structure and estimated odds ratios (ORs). For score variables, we used a log link and Poisson error structure. In some cases it was not possible to fit the model when school was included as a second random intercept. Therefore, for all logistic and Poisson models, school was included as an additional fixed effect rather than a random effect. Results Study participants. Twenty-two schools par- ticipated in the project. Overall, 418 subjects participated in at least one part of the study, representing 77% of the 543 students in the selected classes. Three students did not submit a baseline questionnaire. At least one diary was received for 400 participants (74% of eli- gible students). These participants formed the study population. In any given week, average participation rates ranged from 64% to 73%. Slightly over half the participants were girls, and their mean age was 10.6 years Health effects of low-NOx unflued gas heaters (Table 1). Nearly half were atopic, including 34% who were sensitized to house dust mite allergen. Approximately 15% had current asthma, but 21% were using some asthma- related medication. Unflued gas heaters were used in nearly one quarter of all participants’ homes and half used gas for cooking. Use of heaters in schools. Heater use was monitored during weeks 3–6 and was quantified as the proportion of time between 0900 and 1500 hours that the heaters were in operation. Across the 22 schools, median (interquartile range) daily heater use during weeks 3–6 was 25.7% (0–47.2%), 30.4% (6.9–47.8%), 16.7% (0–41.7%), and 0% (0–9.7%) of the school day, respectively. Heater use was recorded as ≥ 30% on 157 school days. Mean daily in-class temperature between 0900 and 1500 hours was 20.9°C on days when the unflued gas heater was operating and 20.5°C on days when the flued gas heater was operating (difference adjusted for random effects 0.4°C; 95% CI, 0.0–0.8, p = 0.07). When the analysis was limited to days when the heaters were operating for at least 30% of the day, the mean temperatures were slightly higher during the period of operation of the unflued gas heater (19.6°C) than during the periods of operation of the flued gas heater (18.6°C). The mean difference was 1.0°C (95% CI, 0.5–1.5). Effect of heater type on NO2 and formal- dehyde concentrations in the classroom. The overall geometric mean NO2 concentration in classrooms was 32 ppb (60.2 µg/m3), and the overall mean concentration of formaldehyde was 29 ppb (35.6 µg/m3) during school hours on the days of measurement. There was a significant order by heater type interaction in the effect on NO2 concen- trations (p = 0.01). However, as both order sequences showed an increase in NO2 levels when the unflued gas heater was operating, order effects were not considered further. The order by heater type interaction was not sig- nificant for formaldehyde. There were highly significant effects of heater type on concentrations of NO2 and formaldehyde in the classrooms (Tables 2 and 3). The effect was larger in magnitude when the analysis was limited to weeks and class- rooms in which heaters were used for ≥ 30% of the time. Estimated effects of heater type on lung function and airway inflammation (eNO). The randomized order in which classrooms were exposed to the two types of heaters (unflued gas heaters and flued gas heaters) had no significant influence on the effects of the heater type on lung function or airway inflammation (p > 0.2 for all heater type by order interactions). However, the estimated effect of heater type on PEF measured in the evening differed between people with and without asthma (p = 0.01). Atopic status did not influence the effect of heater type on lung function or eNO concentrations (all p > 0.1). In the ITT analysis for the whole study population, heater type did not have any significant effect on any of the lung func- tion measures after adjustment for day of the week, study week, and clustering by subject and school (Table 4). However, when the analysis was limited to days and schools in which heater use was ≥ 30%, morning FEV1 was 0.03 L (95% CI, 0.003–0.057, p = 0.03) higher during the period of exposure to the unflued gas heater. Similarly, in this sub- group, evening PEF was 5.2 L/min (95% CI, 1.0–9.3, p = 0.01) higher during operation of the unflued gas heater. Evening PEF was 7.3 L/min (95% CI, 0.6–13.7) higher dur- ing the operation of the unflued gas heater in the ITT analysis in the asthma subgroup but not in the nonasthma subgroup (difference = –0.1 L/min; 95% CI, –2.2 to 1.9). In the per-protocol analysis (when heater use was ≥ 30%) for the asthma subgroup, the asso- ciation of unflued gas heater exposure with higher evening PEF was similar but was not statistically significant. Table 4. Effect of heater type (unflued gas heater – flued gas heater) on lung function.a FEV1 morning (L) FEV1 evening (L) PEF morning (L/min) PEF evening (L/min) Population Unflued Flued Diff 95% CI p-Value Unflued Flued Diff 95% CI p-Value Unflued Flued Diff 95% CI p-Value Unflued Flued Diff 95% CI p-Value ITT analysisb 1.95 1.95 0.004 –0.009 to 0.55 1.96 1.96 0.000 –0.014 to 0.99 271 270 0.719 –1.239 to 0.47 279 278 0.994 –0.995 to 0.33 0.017 0.014 2.677 2.983 Per protocol: days 1.91 1.88 0.030 0.003 to 0.03 1.91 1.91 0.008 –0.021 to 0.59 269 268 0.832 –3.505 to 0.71 277 272 5.185 1.032 to 0.01 with heater use 0.057 0.037 5.168 9.338 ≥ 30%c Asthma subgroup, 1.84 1.84 0.001 –0.038 to 0.95 1.84 1.85 –0.017 –0.061 to 0.45 253 250 2.285 –4.954 to 0.54 260 253 7.130 0.578 to 0.03 ITT analysisd 0.041 0.027 9.524 13.682 Asthma subgroup, 1.84 1.79 0.056 –0.027 to 0.19 1.74 1.80 –0.059 –0.174 to 0.31 255 255 0.021 –11.637 to 1.00 260 251 8.910 –7.543 to 0.29 per-protocol 0.139 0.056 11.679 25.362 analysise Diff, difference. aThe means and differences and the 95% CIs for the differences are derived from 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 and subjects within schools were both treated as random intercepts, and a variance components correlation structure was assumed. bAll observations were analyzed according to the heater type exposure to which they were assigned. There were 6,776 observations for FEV1 morning and PEF morning and 6,504 observations for FEV1 evening and PEF evening cThe analysis was limited to schools and days for which heater use was estimated as ≥ 30%. There were 1,249 observations for FEV1 morning and PEF morning and 1,441 observations for FEV1 evening and PEF evening. dAll observations in subjects with current asthma at baseline were analyzed according to the heater type exposure to which they were assigned. There were 982 observations for FEV1 morning and PEF morning and 987 observations for FEV1 evening and PEF evening. eThe analysis was limited to schools and days for which heater use was estimated as ≥ 30% in subjects with asthma. There were 169 observations for FEV1 morning and PEF morning and 213 observations for FEV1 evening and PEF evening. Environmental Health Perspectives • volume 118 | number 10 | October 2010 1479