Table 1 shows population demographics. Age ranges and gender distribution were statistically equivalent across countries. However, mean ages differed and were highest in Italy and Japan, followed by the US, Mexico, and then India, which had the lowest mean age.
Table 1
Age and Gender by Country
| Age Range, years** | Mean Ages, years (Std Dev) * | Percent Female** |
India | 18–99 | 38.07 (14.12) a | 48.50 |
Italy | 18–88 | 48.14 (16.46) b | 51.90 |
Japan | 18–89 | 48.07 (16.65) b | 51.80 |
Mexico | 18–90 | 39.56 (15.44) a | 51.70 |
United States1 | 18–88 | 45.76 (16.87) c | 51.00 |
*Values with different letters indicate statistical differences at p < .05 |
**No statistical difference by country Mantel Hanzel Chi-sqaure p = .13 |
N = 1000 per country. |
Figure 1 shows the average and the range of Chemical Exposures and Symptom Severity Scale scores for each country. Note that average scale scores for both scales exceed 40 for India. Italy and Japan both have average scores ≥ 40 on the Chemical Exposures Scale, but scores < 40 on the Symptom Severity Scale. Mexico and the U.S. averaged scores below 40 on both scales.
Figure 2 shows the prevalence of CI by country (“very suggestive” = scores ≥ 40 on both the Chemical Exposures and Symptom Severity Scales). India had the highest prevalence of CI (54.7%, 95% CI = 52–58) followed by Japan 40.3%, 95% CI = 40–77), Italy (34.3%, 95% CI = 32–37), U.S. (31.2%, 95% CI = 28–34), and Mexico (26.0%, 95% CI = 23–29), which had the lowest compared to other countries. On Fig. 2, letters indicate significant mean differences at < .05. Countries with the same letters are not significantly different from one another. Overall, all five countries’ average scores indicate a potentially high prevalence of CI.
The metrics in Table 2 indicate how well the BREESI correctly categorizes those with and without chemical intolerance as measured by the QEESI. We compared BREESI scores to the QEESI category of “very suggestive” as a positive case and to the QEESI category of “not suggestive” as a negative case. Sensitivity indicates how well a test predicts true positive cases. Specificity indicates how well a test predicts true negative cases. Sensitivity ranged from 79–93% for all countries except Japan, which had 17% sensitivity due to the high number of false negatives. Specificity across countries ranged from 79% (India) to 99% (Japan, which has a low number of false positive cases).
Table 2
Performance metrics for BREESI by country
| Value | 95% Confidence Intervals |
India | | |
Sensitivity | 91.58% | 88.38–94.13% |
Specificity | 92.21% | 83.81–97.09% |
Positive Likelihood Ratio | 11.75 | 5.45 to 25.36 |
Negative Likelihood Ratio | 0.09 | 0.07 to 0.13 |
Positive Predictive Value | 93.49% | 86.94–96.87% |
Negative Predictive Value | 89.96% | 86.53–92.59% |
Accuracy | 91.86% | 89.01–94.17% |
Italy | | |
Sensitivity | 80.75% | 74.36–86.14% |
Specificity | 96.97% | 91.40–99.37% |
Positive Likelihood Ratio | 26.65 | 8.72 to 81.39 |
Negative Likelihood Ratio | 0.2 | 0.15 to 0.27 |
Positive Predictive Value | 93.21% | 81.80–97.67% |
Negative Predictive Value | 90.72% | 87.92–92.93% |
Accuracy | 91.45% | 87.59–94.42% |
Japan | | |
Sensitivity | 17.22% | 12.37–23.04% |
Specificity | 99.57% | 97.65–99.99% |
Positive Likelihood Ratio | 40.48 | 5.60 to 292.67 |
Negative Likelihood Ratio | 0.83 | 0.78 to 0.88 |
Positive Predictive Value | 96.43% | 78.87–99.49% |
Negative Predictive Value | 64.34% | 62.90–65.76% |
Accuracy | 66.63% | 62.04–71.01% |
Mexico | | |
Sensitivity | 92.50% | 86.24–96.51% |
Specificity | 93.53% | 88.06–97.00% |
Positive Likelihood Ratio | 14.29 | 7.58 to 26.93 |
Negative Likelihood Ratio | 0.08 | 0.04 to 0.15 |
Positive Predictive Value | 97.26% | 94.98–98.52% |
Negative Predictive Value | 93.26% | 89.49–95.99% |
Accuracy | 92.50% | 86.24–96.51% |
United States | | |
Sensitivity | 78.71% | 71.42–84.87% |
Specificity | 97.28% | 93.18–99.25% |
Positive Likelihood Ratio | 28.93 | 10.96 to 76.31 |
Negative Likelihood Ratio | 0.22 | 0.16 to 0.30 |
Positive Predictive Value | 92.85% | 83.13–97.17% |
Negative Predictive Value | 91.05% | 88.24–93.23% |
Accuracy | 91.52% | 87.79–94.41% |
Positive predictive value (PPV) is the probability that subjects with a positive screening test truly have the disease. Negative predictive value (NPV) is the probability that subjects with a negative screening test truly do not have the disease. The PPV (probability of true positive cases) of the BREESI was between 75% (Mexico) and 97% (India). The NPV (percentage of true negative cases) for USA, Mexico, India, and Italy ranged from 79–96%. These ranges indicate that in these countries the BREESI correctly classifies those without chemical intolerance. Japan’s high number of false negatives is reflected in a low NPV of 57%.
Specificity, sensitivity, PPV, and NPV are measures that depend upon the prevalence of the clinical event in the population under study (Altman and Bland, 1994). In contrast, positive likelihood ratios and negative likelihood ratios do not depend on disease prevalence and are therefore preferred and considered more accurate than NPV and PPV (Heston, 2011). Since prevalence estimates will vary in the sampling frame for these countries, we calculated likelihood ratios (see Table 2). The likelihood ratios are used to express the change in the odds that a person does or does not have a condition given a positive or negative result (Sedighi, 2013). For example, the positive likelihood ratio gives the change in the odds of having the condition among persons with a positive screen (Glenn, 2021).
Responses on individual BREESI items by country appear in Table 3. The outliers were India and Japan. In India, 44% endorsed all three BREESI items (chemicals, foods, and drugs). In contrast, in Japan, only 5% endorsed all three.
Table 3
Responses for individual BREESI items by country (N = 1000 for each country)
| Country |
Number of BREESI Items chosen | India % (95% CI) | Italy % (95% CI) | Japan % (95% CI) | Mexico % (95% CI) | USA % (95% CI) |
0 | 19.6 (17.2 – 22.2) | 33.3 (30.3 – 36.3) | 59.4 (56.2 – 62.5) | 23.4 (20.8 – 26.1) | 32.3 (29.4 – 35.3) |
1 | 18.3 (15.9 – 20.8) | 26.7 (23.9 – 29.6) | 27.1 (24.4 – 29.9) | 29.4 (26.6 – 32.3) | 29.5 (26.7 – 32.4) |
2 | 17.9 (15.6 – 20.4) | 18.7 (16.3 – 21.3) | 8.9 (7.2 – 10.8) | 26.4 (23.7 – 29.3) | 19.1 (16.7 – 21.7) |
3 | 44.2 (41.1 – 47.3) | 21.3 (18.8 – 24.0) | 4.6 (3.3 – 6.1) | 20.8 (18.3 – 23.5) | 19.1 (16.7 – 21.7) |
Single BREESI Item * | % | % | % | % | % |
None | 19.6 a (17.2 – 22.2) | 33.3 b (30.3 – 36.3) | 59.4 c (56.2 – 62.5) | 23.4 a (20.8 – 26.1) | 32.3 b (29.4 – 35.3) |
Chemicals | 71.4 a (68.5 – 74.2) | 57.7 d (54.6 – 60.8) | 35.7 b (32.7 – 38.7) | 66.2 c (63.2 – 69.1) | 56.5 d (53.3– 59.6) |
Foods | 55.3 a (52.2 – 58.4) | 34.2 d (31.3 – 37.2) | 9.2 b (7.5 – 11.2) | 39.5 c (36.4 – 42.6) | 32.9 d (29.2 – 35.9) |
Drugs | 60.0 a (49.7 – 69.6) | 36.1 c (33.1 – 39.1) | 13.8 b (11.7 – 19.1) | 38.9 c (35.8 – 42.0) | 35.6 c 32.6 – 38.6) |
Note: Superscripted letters are statistical comparisons of BREESI categories across countries. Countries with the same letters are not statistically different. Those with different letters are statistically different at p < .05.
*N and percentages exceed 1,000 or 100% due to respondents choosing multiple BREESI items. See Venn diagrams (Figs. 3b-7b) for overlap percentages.
Table 4 shows the odds of CI with each additional BREESI item chosen. The logistic regression probability graphs are shown in Fig. 3. The predicted probabilities of CI increase sharply with increasing BREESI items chosen. Each country shows a similar increase in the odds of CI with increasing number of BREESI items. The odds of CI increase are 4- to 5-fold with each additional BREESI item. Consistent with NPV for Japan, note that with 0 items on the BREESI, the predicted probability of CI is still 50%, yet increases with each additional BREESI item.
Table 4
Logistic regression of BREESI predicting chemical intolerance
| Estimate (SE) | Odds Ratio1 | 95% CI |
India | 1.62 (0.14) | 5.05 | 3.86–6.57 |
Italy | 1.64 (0.16) | 5.16 | 3.81–7.01 |
Japan | 1.65 (0.14) | 4.39 | 2.87–6.71 |
Mexico | 1.64 (0.13) | 5.21 | 3.97–6.82 |
USA | 1.45 (0.22) | 5.22 | 3.93–6.92 |
| Estimate (SE) | Odds Ratio2 | 95% CI |
India | 0.86 (0.13) | 2.387 | 1.82–3.12 |
Italy | 0.84 (0.14) | 2.320 | 1.76–3.05 |
Japan | 0.84 (0.21) | 2.334 | 1.53–3.54 |
Mexico | 1.01 (0.11) | 2.736 | 2.23–3.36 |
USA | 1.10 (0.13) | 3.006 | 2.33–3.87 |
1Odds ratio for each one unit increase of BREESI comparing Very Suggestive of CI to Not Suggestive of CI |
2 Odds ratio for each one unit increase of BREESI comparing Suggestive of CI to Not Suggestive of CI |