Hong et al. examined the combined effects of 4 air pollutants (particulate matter<10 μm (PM10), nitrogen dioxide (NO2), sulfur dioxide (SO2), and ozone) by summing each pollutant concentration divided by its mean (i.e., relative concentrations) and then fitting this index as an independent variable [47]. They found that the combined index had a stronger association with mortality than individual pollutants. In a study of indoor exposure to volatile organic compounds (VOCs) and respiratory health, Billionnet et al. computed a global VOC score of 20 VOCs by dichotomizing individual VOC as 1 if greater than the 75th percentile and otherwise 0 and then summing the 20 dichotomous VOCs, which indicates the number of VOCs whose concentrations were relatively high within the study population (range 0–17) [43]. Each additional VOC with a concentration higher than the 75th percentile was associated with 7% (95% CI, 1.00–1.13) and 4% (95% CI, 1.00–1.08) higher odds of asthma and rhinitis, respectively. Although these studies evaluated the combined effects of multi-pollutants, their approaches did not account for the relative effects of individual pollutants on the phenotype of
