Marks et al. The findings on lung function were not substantially different when data were excluded for subject days on which the sub- ject used a bronchodilator in the morning or the evening [Supplemental Material, Table E1 (doi:10.1289/ehp.1002186)]. There was no evidence of any decrement in lung function attributable to unflued gas heater exposure when the analysis was restricted in this way. Analysis of lung function measures recorded during in-school testing on Thursday or Friday of each study week revealed that the unflued gas heater was associated with a small increase in FEV1 [0.03 L (95% CI, 0.01–0.05), p = 0.01] compared with the flued gas heater. The magnitude and direction of the estimated effect on FEV1 was similar in the per-protocol analysis [0.03 L (95% CI, –0.01 to 0.08), p = 0.14]. There were no sig- nificant effects on PEF measured at the same time, although the trend was in the same direction (data not shown). Overall, eNO levels, which were measured at the same time as the in-school lung function measurements, did not differ between periods of exposure to the two heater types in either the ITT or per-protocol analysis. However, there was a significant interaction with current asthma status in the per-protocol analysis (p = 0.002). In the subgroup with current asthma, eNO concentrations were 3.7 ppb higher dur- ing exposure to the unflued gas heater than during exposure to the flued gas heater (95% CI, –0.5 to 7.9, p = 0.08). However, in the subgroup without asthma, the effect of flued versus unflued gas heater exposure on eNO concentrations was close to zero [0.03 ppb (95% CI, –0.68 to 0.74), p = 0.93]. Effect of heater type on respiratory symp- in the morning was 4.9% during periods of exposure to the low-NOx unflued gas heater and 4.4% during exposure to flued gas heater (Table 5). For wheeze reported in the eve- ning, the overall prevalence was 5.7% and 5.2% respectively. The prevalence of cough reported in the morning was 14.2% during both exposure periods, and the prevalence of cough reported in the evening was 21.6% and 20.6%, respectively. Treatment order did not influence the effect of heater type on symptoms except in relation to symptoms recorded in the eve- ning (p = 0.02). However, no separate analy- sis by treatment order was undertaken. The estimated effect of heater type on symptoms did not differ significantly by current asthma status, but did according to atopic status, par- ticularly in relation to wheeze recorded in the morning (p = 0.0009) and in the evening (p = 0.01) and the use of bronchodilators to relieve symptoms (p = 0.002). In the ITT analysis, exposure to the unflued gas heater was associated with an increase in cough reported in the evening and wheeze reported in the morning (Table 6). When the analysis was restricted to days when heater use was ≥ 30%, the findings were gen- erally similar, although no significant differ- ences were found. After adjustment for use of unflued gas heaters or open fires at home and exposure to ETS at home, the associa- tion of heater type with wheeze reported in morning was stronger (OR = 1.60; 95% CI, 1.17–2.19, p = 0.003) than without adjust- ment (OR = 1.38; 95% CI, 1.04–1.83, p = 0.03). However, the association with cough reported in the evening was weaker and no longer significant after adjusting for these The association with morning wheeze was evident in atopic subjects in the ITT analysis (OR = 1.85; 95% CI, 1.26–2.72, p = 0.002) and was particularly strong in this subgroup when the analysis was limited to days when heater use was ≥ 30% (OR = 7.72; 95% CI, 1.55–38.43, p = 0.01). The evidence of an association with wheeze in atopic subjects was strengthened by the finding of an increased use of bronchodilators for relief of symptoms with exposure to the unflued gas heater in this subgroup (OR = 1.87; 95% CI, 1.08–3.25, p = 0.03). In the nonatopic subgroup, these adverse effects were not observed. In the ITT analysis in nonatopic subjects, there was no sig- nificant association with wheeze reported in the morning (OR = 0.63; 95% CI, 0.39–1.02, p = 0.06). There was a significant protective asso- ciation with wheeze reported in the evening (OR = 0.50; 95% CI, 0.30–0.84, p = 0.009) and with the use of bronchodilator for relief of symptoms (OR = 0.45; 95% CI, 0.23–0.91, p = 0.03). The atopic subgroup was slightly less likely to report cough in the morning when exposed to the unflued gas heaters (OR = 0.77; 95% CI, 0.60–0.98, p = 0.03). There was no consistent evidence of an association between heater type and reporting of sore teeth or stomachache, although the lat- ter was associated with exposure to unflued gas heaters in the atopic subgroup in the ITT analy- sis (OR = 1.63; 95% CI, 1.06–2.49, p = 0.02). The findings when symptoms were ana- lyzed based on symptom scores (0–3) were broadly similar to those observed when symp- toms were treated as simply present or absent (data not shown). The association between heater type and wheeze score differed signifi- cantly between atopic and nonatopic subjects, with more adverse associations in the atopic toms. The overall daily prevalence of wheeze confounders. Table 5. Prevalence of wheeze and cough by gas heater (flued or unflued) type and population subgroup. Morning cough Evening cough Morning wheeze Evening wheeze Population Flued Unflued Flued Unflued Flued Unflued Flued Unflued ITT analysisa 14.2 14.2 20.6 21.6 4.4 4.9 5.2 5.7 Per-protocol analysisb 16.8 15.9 23.2 23.2 5.4 4.4 5.3 5.6 Atopic subgroup, ITT samplea 16.3 14.6 21.0 21.9 4.9 6.5 6.9 8.1 Atopic subgroup, per-protocol sampleb 21.7 17.7 24.9 24.0 5.3 6.8 6.6 9.4 aAll observations were 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 esti- mated as ≥ 30%. Table 6. Effect of heater type (unflued gas heater/flued gas heater) on symptoms. Morning symptomsa Evening symptomsb Morning cough Evening cough Population ORc (95% CI) p-Value ORc (95% CI) p-Value ORc (95% CI) p-Value ORc (95% CI) p-Value ITT analysisd 0.931 (0.810–1.071) 0.32 0.962 (0.859–1.076) 0.49 0.994 (0.850–1.162) 0.94 1.161 (1.008–1.336) 0.04 Per-protocol analysise 0.737 (0.512–1.060) 0.10 0.888 (0.671–1.176) 0.41 0.872 (0.574–1.325) 0.52 1.192 (0.842 –1.686) 0.32 ITT analysis, adjusted for home use 0.938 (0.801–1.098) 0.43 0.963 (0.852–1.089) 0.55 1.006 (0.844–1.200) 0.94 1.103 (0.949–1.283) 0.20 of gas, open fire for heating, and exposure to ETSf Atopic subgroup, ITT sampleg 0.805 (0.650–0.997) 0.05 0.920 (0.764–1.107) 0.38 0.769 (0.604–0.979) 0.03 1.156 (0.923–1.448) 0.21 Atopic subgroup, per-protocol sampleh 0.843 (0.498–1.427) 0.52 0.958 (0.594–1.544) 0.86 0.722 (0.399–1.306) 0.28 1.256 (0.718–2.197) 0.42 aReported either cough or wheeze in the morning. bReported cough, wheeze or chest tightness, fever, sore throat, runny or blocked nose, eye irritation, sore teeth or gums, or stom- achache in the evening. cORs > 1 indicate that exposure to the unflued gas heater, compared with the flued gas heater, is associated with an increased risk of symptoms. The model used to estimate these ORs is described in “Methods.” dAll observations were analyzed according to the heater type exposure to which they were assigned. There were 9,079 obser- vations for morning wheeze and 8,858 observations for evening wheeze. eThe analysis was limited to schools and days for which heater use was estimated as ≥ 30%. There were 1480 ovlume 118 | number 10 | October 2010 • Environmental Health Perspectives