Dales et al. measurement and symptom assessment. We would assume that a true causal association would remain stable or weaken over time. If the association increased or fluctuated ran- domly with time of follow-up, this would reduce the probability of a causal association. We measured the results from 90-, 180-, 270-, 360-, 450-, 540-, 630-, and 720-day windows around the time of endotoxin sampling. The regression model obtained previously for a 2-year period was applied to each of these windows. The β-coefﬁcient for the effect of the natural logarithm of endotoxin on illness episodes and total illness days along with its 95% conﬁdence interval were graphed against the size of the window. Results The characteristics of the 332 children, overall and stratiﬁed by bedroom airborne endotoxin level, are presented in Tables 1 and 2. Of the categorical variables (Table 1), only year of testing was signiﬁcantly associated with endo- toxin, with no secular trends (p < 0.0001). The pets variable was not associated with endotoxin concentrations. For dogs, the geometric mean and geometric standard deviation (GSD) were 0.46 ± 3.82 if dogs were never reported present in the home and 0.54 ± 3.15 if ever reported to be in the home (p = 0.22). There was also no significant difference in endotoxin values between homes where dogs were reported in < 50% of interviews compared with at least 50% of interviews (p = 0.12). Similarly, there Variable Children Age (days) Mean hours/week child care Percent postnatal interviews where breast-feeding reported Environment Endotoxin (EU/m3) Living room ergosterol (ng/m3) Bedroom ergosterol (ng/m3) Temperature (°C) Relative humidity (%) Interior wood storage (m3) Mold area rank (%) Variable No. of episodes of any illnessb per year No. of illness days per year No. of days with cough per year No. of days with wheeze per year No. of days with SOB per year No. of days with stuffy nose per year was no significant association between cats and endotoxin. Of the continuous variables (Table 2), only indoor relative humidity was positively related to endotoxin (p = 0.01). Illness episodes correlated best with the individual symptoms of cough and stuffy nose; Pearson correlation coefﬁcients were 0.69 and 0.76, respectively, both at p < 0.01. For illness days, respective values were 0.83 and 0.95. Wheeze was also significant for both illness episodes and illness days at 0.37 and 0.41, respectively (p < 0.01). The annualized num- ber of respiratory illness episodes and total days of illness episodes were positively related to endotoxin at p = 0.13 and p = 0.07, respec- tively (Table 3). All of the individual respira- tory symptoms were greater in the higher compared with the lower endotoxin group, but only the incidence of wheeze reached statistical signiﬁcance, being a relative 248% greater in the higher compared with the lower endotoxin group (p = 0.01). The unadjusted Pearson correlation coefﬁ- cients between log-transformed endotoxin and illness episodes and illness days were 0.105 (p = 0.056) and 0.106 (p = 0.053), respectively. The association for number of days with wheeze was 0.271 (p < 0.0001), but other indi- vidual variables were not significant at p = 0.05. The adjusted associations for illness episodes and total illness days were highly sig- niﬁcant (Tables 4 and 5). The multiple linear regression model for illness episodes resulted in a β-coefﬁcient of 0.46 (SE 0.13) for the natural logarithm of endotoxin (p = 0.0003), which means that each 1.0 unit increase in the natural logarithm of airborne endotoxin concentration was associated with 0.46 more illness episodes per year. An alternative expression of the rela- tion would be that a doubling of air endotoxin concentration was associated with an increase of 0.32 illness episodes per year (p = 0.0003), adjusted for age, year of study, breast-feeding, environmental tobacco smoke, child care atten- dance, indoor temperature, and income. Also, starting from the geometric mean (0.49) and increasing endotoxin by its geometric mean resulted in 4.7% excess illnesses per year. Similarly, doubling air endotoxin was associ- ated with an increase of 3.25 illness days per year (p = 0.005), adjusted for age, year of study, breast-feeding, child care attendance, indoor temperature, and sex. Starting from the geometric mean (0.49) and increasing endo- toxin by its geometric mean resulted in 5.5% excess illness days per year. Signiﬁcant covariates in the regression of illness episodes were year of testing, indoor temperature, age, child care, environmental tobacco smoke, and income (all p < 0.05). Similar results were found with illness days with a β-coefﬁcient of 4.68 (SE 1.66, p = 0.005). In Figure 1, the β-coefﬁcient for the effect of the natural logarithm of endotoxin on ill- ness episodes and total illness days is graphed against the size of the window. The magnitude of the association between illness episodes and endotoxin levels was almost linearly decreasing 2nd tercile Mean ± SD 3rd tercile Mean ± SD p-Valuea Table 2. Characteristics of children’s home environments overall and stratiﬁed by terciles of endotoxin. ap-Value of the Fisher test for a linear trend for the terciles of endotoxin. bGeometric mean. cGeometric SD. dp-Value of the Fisher test for a linear trend for the terciles of endotoxin using the natural logarithm of the variable. Table 3. Incidence of children’s illness overall and stratiﬁed by terciles of endotoxin concentrations. SOB, shortness of breath. ap-Value of the Fisher test for a linear trend for the terciles of endotoxin. bIllnesses are cough, wheeze, shortness of breath, and stuffy nose. See “Materials and Methods” for details on how we deﬁned illness episodes. 612 VOLUME 114 | NUMBER 4 | April 2006 • Environmental Health Perspectives No. 332 332 332 332 319 319 332 332 332 332 No. 332 332 332 332 332 332 Overall Mean ± SD 351 ± 42.1 7.89 ± 8.97 30.1 ± 26.7 0.49b ± 3.49c 0.15b ± 4.12c 0.14b ± 4.24c 20.9 ± 2.32 31.5 ± 6.24 1.54 ± 4.39 51.3 ± 29.3 Overall Mean ± SD 6.83 ± 2.80 58.5 ± 36.4 33.0 ± 25.3 4.06 ± 9.66 0.41 ± 1.20 48.7 ± 31.2 No. 111 111 111 111 107 106 111 111 111 111 No. 111 111 111 111 111 111 1st tercile Mean ± SD 355 ± 34.9 8.43 ± 9.18 31.0 ± 25.4 0.14b ± 2.32c 0.16b ± 3.94c 0.14b ± 4.14c 20.9 ± 2.24 30.8 ± 5.74 1.12 ± 3.82 50.3 ± 29.1 1st tercile Mean ± SD 6.66 ± 2.86 54.6 ± 34.4 31.9 ± 23.8 2.28 ± 4.55 0.30 ± 0.99 46.1 ± 29.7 No. 110 110 110 110 105 105 110 110 110 110 No. 110 110 110 110 110 110 337 ± 59.0 7.65 ± 8.48 29.2 ± 29.5 0.50b ± 1.32c 0.16b ± 3.84c 0.15b ± 3.93c 20.7 ± 2.15 31.5 ± 5.80 1.81 ± 5.01 51.4 ± 30.5 2nd tercile Mean ± SD 6.60 ± 2.65 57.5 ± 36.4 31.0 ± 24.4 4.26 ± 10.1 0.48 ± 1.25 48.1 ± 31.3 No. 111 111 111 111 107 108 111 111 111 111 No. 111 111 111 111 111 111 360 ± 19.6 7.60 ± 9.28 29.9 ± 25.1 1.80b ± 2.10c 0.14b ± 4.63c 0.14b ± 4.71c 21.0 ± 2.33 33.0 ± 6.52 1.70 ± 4.26 50.7 ± 28.2 0.38 0.49 0.78 — 0.40d 0.81d 0.97 0.01 0.33 0.93 3rd tercile Mean ± SD 7.22 ± 2.85 63.5 ± 38.0 36.1 ± 27.6 5.66 ± 12.4 0.46 ± 1.33 51.9 ± 32.7 p-Valuea 0.13 0.07 0.21 0.01 0.30 0.17