Respiratory Inflammation and Short-Term Ambient Air Pollution Exposures in Adult Beijing Residents with and without Prediabetes: A Panel Study

Background: Accumulating evidence suggests that individuals with glucose metabolism disorders are susceptible to mortality associated with fine particles. However, the mechanisms remain largely unknown. Objectives: We examined whether particle-associated respiratory inflammation differed between individuals with prediabetes and healthy control participants. Methods: Based on a panel study [A prospective Study COmparing the cardiometabolic and respiratory effects of air Pollution Exposure on healthy and prediabetic individuals (SCOPE)] conducted in Beijing between August 2013 and February 2015, fractional exhaled nitric oxide (FeNO) was measured from 112 participants at two to seven visits to indicate respiratory inflammation. Particulate pollutants—including particulate matter with an aerodynamic diameter of ≤2.5μm (PM2.5), black carbon (BC), ultrafine particles (UFPs), and accumulated-mode particles—were monitored continuously at a single central monitoring site. Linear mixed-effects models were used to estimate associations between ln-FeNO with pollutant concentrations at individual 1-h lags (up to 24 h) and with average concentrations at 8 and 24 h before the clinical visit. We evaluated glucose metabolism disorders as a potential modifier by comparing associations between participants with high vs. low average fasting blood glucose (FBG) and homeostasis model assessment insulin resistance (HOMA-IR) levels. Results: FeNO was positively associated with all pollutants, with the strongest associations for an interquartile range increase in 1-h lagged exposures (ranging from 21.3% for PM2.5 to 74.7% for BC). Associations differed significantly according to average HOMA-IR values when lagged 6–18 h for PM2.5, 15–19 h for BC, and 6–15 h for UFPs, with positive associations among those with HOMA-IR≥1.6 while associations were closer to the null or inverse among those with HOMA-IR<1.6. Associations between PM2.5 and FeNO were consistently higher among individuals with average FBG≥6.1 mmol/L vs. low FBG, with significant differences for multiple hourly lags. Discussion: Glucose metabolism disorders may aggravate respiratory inflammation following exposure to ambient particulate matter. https://doi.org/10.1289/EHP4906


Table of Contents
Table S1.Participant distribution in different subgroups.
Table S2.Variation of FBG and HOMA-IR in different subgroups.
Table S3.Spearman correlation coefficients matrix of preceding 24 h average of exposure to ambient pollutants.Table S4.Hourly pollutant concentrations in the proceeding 24 h and estimated percent differences in FeNO (95% CI) per IQR increase in each exposure.
Table S5.Estimated percent differences in FeNO (95% CI) per IQR increase in PM 2.5 , BC, UFPs, and Acc concentrations 8 h and 24 h prior to the starting time of visits.
Table S6.Estimated percent differences in FeNO (95% CI) per IQR increases in 1-24 h lagged particle concentrations stratified by high or low average FBG.
Table S7.Estimated percent differences in FeNO (95% CI) per IQR increases in average particle concentrations 8 h and 24 h prior to the starting time of visits stratified by low or high average FBG and IR.
Table S8.Estimated percent differences in FeNO (95% CI) per IQR increases in 1-24 h lagged particle concentrations stratified by high or low average HOMA-IR.
Table S9.Estimated percent differences in FeNO (95% CI) per IQR increase in 1 h lagged particle concentrations in the two-pollutant models in all participants and different subgroups.
Table S10.Estimated percent differences in FeNO (95% CI) per IQR increases in average particle concentrations 1 h, 8 h, and 24 h prior to the starting time of visits, with further adjustment for multiple confounders (Model 1-4), and when limited to visits with complete data for all pollutants (Model 5), and in subgroups of participants with ≥ 3 study visits (Model 6).
Table S11.Relative risk per IQR increase in lag 1-24 h concentrations of fine particles based on DLM.
Table S12.Associations between FeNO and short-term exposures to PM 2.5 , BC, UFPs, and Acc exposures in previous studies.All models were single-pollutant linear mixed-effects models of ln-FeNO with random participant-specific intercepts, adjusted for ambient temperature on the previous day, average relative humidity during 7 days before the visit, day of the week, age (continuous), sex, and smoking history (nonsmoker versus former smoker).Low-FBG group, high-FBG group, low-IR group, high-IR group referred to participants with average level of FBG < 6.1 mmol/L, FBG ≥ 6.1 mmol/L, HOMA-IR < 1.6 and HOMA-IR ≥ 1.6, respectively.See Table S7 for corresponding numeric data and interaction p-value for all pairs of estimates according to IR and FBG.The IQRs for each pollutant are provided in Table S5.Abbreviations: FBG, fasting blood glucose; HOMA-IR, homeostasis model assessment insulin resistance; IQR, interquartile range; FeNO, fractional exhaled nitric oxide; BC, black carbon; UFPs, ultrafine particles; Acc, accumulated-mode particles.
Model 3 denoted the model 2 with further adjustment for income (< 2000 vesus 2000-5000 versus 5000-8000 versus > 8000 RMB), education (at least senior versus no more than junior high school degree), sleeping hours at night, and commuting habits (walking or bicycle vs. car or public transit), alcohol and irritating food (barbecue, pickled food, seafood, hotpot, and preservative-containing food) intake, passive smoke exposure (> 0.5 h versus ≤ 0.5 h), chronic (asthma and chronic obstructive pulmonary disease) and acute (flue, cold, acute laryngopharyngitis, and acute bronchitis) respiratory disease.Model 4 denoted the model 1 with further adjustment for distance from home to the monitor (continuous).The IQRs for each pollutant and lag period are provided in Table S4 and S5. a number of the participants (left) and visits completed by participants (right).01 (0.99, 1.03) 1.00 (0.98, 1.02) 1.02 (1.01, 1.03) 1.01 (0.99, 1.03)  16 h 1.03 (1.00, 1.05) 0.98 (0.96, 1.00) 1.01 (1.00, 1.03) 0.99 (0.97, 1.01) 21 h 1.00 (0.98, 1.02) 0.98 (0.96, 1.00) 0.99 (0.98, 1.00) 0.99 (0.97, 1.00) Note: BC, black carbon; UFPs, ultrafine particles; Acc, accumulated-mode particles; DLM, distributed lag linear; FeNO, fractional exhaled nitric oxide; IQR, interquartile range.All models were DLM models, and adjusted for ambient temperature on the previous day, average relative humidity during the 7 days before the visit, day of the week, age (continuous), sex, and smoking history (nonsmoker versus former smoker).Distributed lag 1-24 h effects were specified with a 3rd degree polynomial function.For each pollutant, we used the lowest concentration measured during the study period as the reference (threshold) value.The dependent variable, FeNO level, was transformed logarithmically.The IQRs for each pollutant and lag period are provided in Table S4.a relative risk with 95% confidential intervals.Notes: BC, black carbon; UFPs, ultrafine particles; Acc, accumulated-mode particles; 24 h ACPV, average concentration of 24 h prior to the starting time of visits; FeNO, fractional exhaled nitric oxide.Reference listed at the end of supplementary material, and only included literatures discussing the particle-associated FeNO differences in individuals with diabetes, or associated with BC, UFPs, or Acc exposure.a estimated difference with 95% confidence intervals.All models were single-pollutant linear mixed-effects models of ln-FeNO with random participant-specific intercepts, adjusted for ambient temperature on the previous day, average relative humidity during 7 days before the visit, day of the week, age (continuous), sex, and smoking history (nonsmoker versus former smoker).Low-FBG group, high-FBG group, low-IR group, high-IR group referred to participants with average level of FBG < 6.1 mmol/L, FBG ≥ 6.1 mmol/L, HOMA-IR < 1.6 and HOMA-IR ≥ 1.6, respectively.See Table S7 for corresponding numeric data and interaction p-value for all pairs of estimates according to IR and FBG.The IQRs for each pollutant are provided in Table S5.Abbreviations: FBG, fasting blood glucose; HOMA-IR, homeostasis model assessment insulin resistance; IQR, interquartile range; FeNO, fractional exhaled nitric oxide; BC, black carbon; UFPs, ultrafine particles; Acc, accumulated-mode particles.The black curves and the gray areas were the mean relative risks and their 95% confidence intervals, respectively.All models were DLM models, and adjusted for ambient temperature on the previous day, average relative humidity during 7 days before the visit, day of the week, age (continuous), sex, and smoking history (nonsmoker versus former smoker).
Distributed lag 1-24 h effects were specified with a 3rd degree polynomial function.
For each pollutant, we used the lowest concentration measured during the study period as the reference (threshold) value.The dependent variable, FeNO level, was transformed logarithmically.See Table S11 for corresponding numeric data.The IQRs for each pollutant and lag period are provided in Table S4.Abbreviations: BC, black carbon; UFPs, ultrafine particles; Acc, accumulated-mode particles; DLM, distributed lag linear; FeNO, fractional exhaled nitric oxide; IQR, interquartile range.

Figure S1 .
Figure S1.Daily variation of PM2.5 concentrations in PKU site and Wan Liu state-control monitoring station nearby, during the study period (from August 1st 2013 to February 5 2015).The concentration in each hour was presented as mean with standard deviation.

Figure S2 .
Figure S2.Estimated percent differences in FeNO (95% CI) per IQR increases in average particle concentrations 8 h and 24 h prior to starting time of visits according to high and low FBG (left 4 panels) and HOMA-IR (right 4 panels) based on average values over all study visits.All models were single-pollutant linear mixed-effects models of ln-FeNO with random participant-specific intercepts, adjusted for ambient temperature on the previous day, average relative humidity during 7 days before the visit, day of the week, age (continuous), sex, and smoking history (nonsmoker versus former smoker).Low-FBG group, high-FBG group, low-IR group, high-IR group referred to participants with average level of FBG < 6.1 mmol/L, FBG ≥ 6.1 mmol/L, HOMA-IR < 1.6 and HOMA-IR ≥ 1.6, respectively.See TableS7for corresponding numeric data and interaction p-value for all pairs of estimates according to IR and FBG.The IQRs for each pollutant are provided in TableS5.Abbreviations: FBG, fasting blood glucose; HOMA-IR, homeostasis model assessment insulin resistance; IQR, interquartile range; FeNO, fractional exhaled nitric oxide; BC, black carbon; UFPs, ultrafine particles; Acc, accumulated-mode particles.

Figure S1 .
Figure S1.Daily variation of PM 2.5 concentrations in PKU site and Wan Liu state-control monitoring station nearby, during the study period (from August 1st 2013 to February 5 2015).The concentration in each hour was presented as mean with standard deviation.

Figure S2 .
Figure S2.Estimated percent differences in FeNO (95% CI) per IQR increases in average particle concentrations 8 h and 24 h prior to starting time of visits according to high and low FBG (left 4 panels) and HOMA-IR (right 4 panels) based on average values over all study visits.All models were single-pollutant linear mixed-effects models of ln-FeNO with random participant-specific intercepts, adjusted for ambient temperature on the previous day, average relative humidity during 7 days before the visit, day of the week, age (continuous), sex, and smoking history (nonsmoker versus former smoker).Low-FBG group, high-FBG group, low-IR group, high-IR group referred to participants with average level of FBG < 6.1 mmol/L, FBG ≥ 6.1 mmol/L, HOMA-IR < 1.6 and HOMA-IR ≥ 1.6, respectively.See TableS7for corresponding numeric data and interaction p-value for all pairs of estimates according to IR and FBG.The IQRs for each pollutant are provided in TableS5.Abbreviations: FBG, fasting blood glucose; HOMA-IR, homeostasis model assessment insulin resistance; IQR, interquartile range; FeNO, fractional exhaled nitric oxide; BC, black carbon; UFPs, ultrafine particles; Acc, accumulated-mode particles.

Figure S3 .
Figure S3.Relative risk per IQR increase in lag 1-24 h concentrations of PM 2.5 (A), BC (B), UFPs (C), and Acc (D) based on DLM.The black curves and the gray areas were the mean relative risks and their 95% confidence intervals, respectively.All models were DLM models, and adjusted for ambient temperature on the previous day, average relative humidity during 7 days before the visit, day of the week, age (continuous), sex, and smoking history (nonsmoker versus former smoker).Distributed lag 1-24 h effects were specified with a 3rd degree polynomial function.For each pollutant, we used the lowest concentration measured during the study period as the reference (threshold) value.The dependent variable, FeNO level, was transformed logarithmically.See TableS11for corresponding numeric data.The IQRs for each pollutant and lag period are provided in TableS4.Abbreviations: BC, black carbon; UFPs, ultrafine particles; Acc, accumulated-mode particles; DLM, distributed lag linear; FeNO, fractional exhaled nitric oxide; IQR, interquartile range.

Table S7 . Estimated percent differences in FeNO (95% CI) per IQR increases in average particle concentrations 8 h and 24 h prior to the starting time of visits stratified by low or high average FBG and IR
FeNO, fractional exhaled nitric oxide; FBG, fasting blood glucose.All models were single-pollutant linear mixed-effects models, and adjusted for ambient temperature on the previous day, average relative humidity during the 7 days before the visit, day of the week, age (continuous), sex, and smoking history (nonsmoker versus former smoker).Low-and high-FBG groups referred to participants with average level of FBG < 6.1 and ≥ 6.1 mmol/L, respectively.FeNO level was transformed logarithmically.The IQRs for each pollutant and lag period are provided in TableS4.a interaction p-value for all pairs of estimates according to IR and FBG Notes: BC, black carbon; UFPs, ultrafine particles; Acc, accumulated-mode particles; IQR, interquartile range; FeNO, fractional exhaled nitric oxide; FBG, fasting blood glucose; HOMA-IR, homeostasis model assessment insulin resistance.All models were single-pollutant linear mixed-effects models, and adjusted for ambient temperature on the previous day, average relative humidity during the 7 days before the visit, day of the week, age (continuous), sex, and smoking history (nonsmoker versus former smoker).FBG and IR status were dichotomous variables decided by the average FBG and HOMA-IR levels, respectively.Low-FBG group, high-FBG group, low-IR group, high-IR group referred to participants with average level of FBG < 6.1 mmol/L, FBG ≥ 6.1 mmol/L, HOMA-IR < 1.6 and HOMA-IR ≥ 1.6, respectively.FeNO level was transformed logarithmically.The IQRs for each pollutant and lag period are provided in TableS5.a interaction p-value for all pairs of estimates according to IR and FBG