Abstract
In recent years, a growing number of studies have shown an association between air pollution and the development of vasculitis. Therefore, in this study, we collected data on the monthly number of visits of patients with IgA vasculitis to the pediatric outpatient and inpatient clinics of the Second Central Hospital of Baoding City and the monthly average values of PM10, PM2.5, SO2, NO2, CO, and O3 in Baoding from January 2014 to December 2022. We correlated the monthly mean values of each air pollutant with the number of patients with IgA vasculitis per month using Spearman correlation analysis. The effect of different air pollutants on the number of IgA vasculitis cases was also analyzed using multiple linear regression analysis. We found that airborne concentrations of PM2.5, PM10, NO2, and CO were positively associated with the number of cases of IgA vasculitis, and airborne concentrations of O3 were negatively associated with IgA vasculitis. Among all air pollutants, NO2 has the greatest impact on the incidence of IgA vasculitis. So we thought there was a positive correlation between airborne NO2 and the development of IgA vasculitis.
Keywords: atmospheric pollutants, IgA vasculitis
1. Introduction
The number of studies on the correlation between air pollutants and the development of vasculitic diseases has gradually increased in recent years. It has been shown that air pollution can cause or exacerbate autoimmune diseases, including vasculitis.[1] Among air pollutants, PM2.5 has the most pronounced effect on autoimmune diseases.[2] PM2.5 can cause vascular inflammation by inducing oxidative stress in the lungs and promoting dyslipidemia.[3] In addition, the correlation between CO and the development of vasculitis in adults has been well established.[4,5] However, there are few studies on the association between air pollutants and the development of vasculitis in children. IgA vasculitis is a common vasculitic disease in pediatric patients. To further clarify the correlation between common air pollutants and the development of vasculitic diseases in children, the present study collected the number of outpatient and inpatient visits of children aged 1 month to 14 years with IgA vasculitis in the Second Central Hospital of Baoding from January 2014 to December 2022 and the monthly mean values of common air pollutants in the Baoding area during the same period. Spearman correlation analysis was used to correlate the monthly average values of common air pollutants with the number of IgA vasculitis visits per month. This study provides a basis for rationally controlling air pollution-induced IgA vasculitis in children.
2. Methods
2.1. Data collection
We collected data on the monthly average pollution levels of the major atmospheric pollutants PM2.5, PM10, SO2, NO2, CO, and O3 in Baoding City, Hebei Province, China, from January 2014 to December 2022 through the China Air Quality Online Monitoring Platform. We collected the number of pediatric outpatients and inpatients with IgA vasculitis per month from January 2014 to December 2022 from the “Hospital Inpatient and Outpatient Information System” of the Second Central Hospital of Baoding City by month. The collection method was a logical search via the system backend. The search qualifiers were visiting time, age, and IgA vasculitis. The age range was 1 month to 14 years. Multiple visits by 1 person were recorded as 1 case.
2.2. Disease definition
The validated EULAR/PRINTO/PRES criteria for diagnosing IgA vasculitis were used. This study did not include those younger than 1 month or older than l4 years old or with incomplete medical records. All patients who met the inclusion criteria were included.
2.3. Statistical methods
We used spss27.0 software to analyze the data. In 2020 there was an outbreak of the COVID-19 pandemic, to clarify the impact of the COVID-19 pandemic outbreak on the study data, according to the normal distribution of the data, we used the independent samples Mann–Whitney U test to compare the total number of outpatient and inpatient patients per month and the number of patients with IgA vasculitis per month before (2014–2019) and after (2020–2022) the outbreak of the COVID-19 epidemic. Before the correlation analysis, the Kolmogorov–Smirnov test was used to test whether the data in each group conformed to normal distribution. Then, according to the normal distribution of the data, Spearman or Kendall correlation analysis was used to correlate the monthly mean value of each air pollutant concentration with the number of patients with IgA vasculitis per month, respectively. Then, we performed multivariate linear regression analyses of monthly mean air pollutant concentrations and the number of IgA vasculitis cases per month. The higher the correlation coefficient (0 → 1) is, the stronger the correlation. The level of significance was set to 5%.
3. Results
3.1. Overview of the data
From January 2014 to December 2022, the total number of pediatric outpatients in our hospital was 1,845,255 cases, and the total number of inpatients was 30,636 cases, of which 2239 cases were children with IgA vasculitis. Detailed results of the monthly average concentration levels of each air pollutant, the total number of pediatric outpatients and inpatients per month, and the number of patients with IgA vasculitis are shown in Table 1.
Table 1.
The total number of outpatients and inpatients per month in our hospital, the monthly average concentration levels of each air pollutant, and the number of cases of IgA vasculitis from January 2014 to December 2022.
| Average value | Minimum value | Median | Maximum values | |
|---|---|---|---|---|
| PM2.5 | 72.73 | 19 | 62 | 214 |
| PM10 | 124.38 | 42 | 111 | 321 |
| SO2 | 27.56 | 6 | 16 | 145 |
| NO2 | 45.26 | 17 | 41 | 100 |
| CO | 1.19 | 0.29 | 0.866 | 4.65 |
| O3 | 94.12 | 17 | 84.5 | 210 |
| Number of patients with IgA vasculitis per month | 20.73 | 4 | 18 | 63 |
| Total number of pediatric outpatients and inpatients per month | 17369.36 | 2568 | 17207.50 | 35359 |
The units of PM10, PM2.5, SO2, NO2, and O3 are μg/m3, and the unit of CO is mg/m3.
PM10 = inhalable particulate matter 10, PM2.5 = particulate matter 2.5.
Since vasculitis is strongly correlated with the immune status of the body, as children of different ages have different immune functions, we grouped the data according to age into the following groups: age ≤ 1 year, 1 year < age ≤ 4 years, 4 years < age ≤ 8 years, and 8 years < age ≤ 14 years. Among them, IgA vasculitis was distributed mainly in those aged 4 to 8 (50.11%) and 8 to 14 (41.89%). The details are shown in Table 2. Figure 1 shows a bar chart of the data distribution in each age group.
Table 2.
Range of the data distribution by age group.
| Monthly average value | Minimum value | Maximum values | Number of patients | Percentage of the total data | |
|---|---|---|---|---|---|
| Age ≤ 1 | 0.19 | 0 | 5 | 20 | 0.89% |
| 1 < Age ≤ 4 | 1.48 | 0 | 11 | 160 | 7.15% |
| 4 < Age ≤ 8 | 10.39 | 0 | 43 | 1122 | 50.11% |
| 8 < Age ≤ 14 | 8.69 | 1 | 21 | 938 | 41.89% |
Figure 1.
Histogram of IgA vasculitis distribution by age group.
Seasonal variation in the onset of IgA vasculitis: There was a significant difference in the onset of IgA vasculitis among the 4 seasons (independent samples Kruskal–Wallis test value of 22.167 P < .001), with the onset occurring mainly in winter. Table 3 compares the number of patients with IgA vasculitis in all seasons. Figure 2 shows the seasonality of the onset of IgA vasculitis.
Table 3.
Comparison of the number of patients with IgA vasculitis among the 4 seasons.
| Test statistic | Standard error | Standard test statistic | Significance | Adjusted significance* | |
|---|---|---|---|---|---|
| Spring–summer | ‐1.093 | 8.518 | ‐.128 | 0.898 | 1.000 |
| Spring–autumn | ‐12.611 | 8.518 | ‐1.481 | 0.139 | 0.832 |
| Spring–winter | ‐35.259 | 8.518 | ‐4.140 | 0.000 | 0.000 |
| Summer–autumn | ‐11.519 | 8.518 | ‐1.352 | 0.176 | 1.000 |
| Summer–winter | ‐34.167 | 8.518 | ‐4.011 | 0.000 | 0.000 |
| Autumn–winter | ‐22.648 | 8.518 | ‐2.659 | 0.008 | 0.047 |
Significance values adjusted for multiple tests by the Bonferroni correction.
Figure 2.
Compartmentalized plot of the number of seasonal incidences of IgA vasculitis.
3.2. Impact of COVID-19 pandemic prevention and control measures on the incidence of IgA vasculitis in children
Taking January 2020 as the time point, we divided the data into 2 groups: pre-outbreak (2014–2019) and post-outbreak (2020–2022), and compared the data. The results are as follows: there was no significant difference in the total number of outpatients and inpatients per month or the number of patients with IgA vasculitis per month before and after the COVID-19 outbreak. The preventive and control measures of the COVID-19 pandemic did not affect the incidence of IgA vasculitis. Details are provided in Table 4.
Table 4.
Comparison of the total number of outpatients and inpatients, the number of patients with IgA vasculitis before and after the outbreak of COVID-19.
| Average value before the outbreak | Average value after the outbreak | Z value | P value | |
|---|---|---|---|---|
| The number of patients with IgA vasculitis per month | 57.03 | 49.43 | ‐1.190 | .234 |
| Total number of outpatient and inpatient visits per month | 55.72 | 52.06 | ‐0.574 | .566 |
3.3. Results of the correlation of each air pollutant with each other and the air pollutants with IgA vasculitis
Determination of the normality of the monthly mean concentrations of each air pollutant and the number of patients with IgA vasculitis per month: the number of patients with IgA vasculitis per month and the monthly mean concentrations of PM2.5, PM10, SO2, CO, NO2, and O3 did not conform to the normal distribution as detected by the Kolmogorov–Smirnov test. The detailed results are shown in Table 5.
Table 5.
Kolmogorov–Smirnov test results for each data set.
| Average value | Standard deviation | P value | |
|---|---|---|---|
| PM2.5 | 72.23 | 44.717 | <.001 |
| PM10 | 124.38 | 63.50 | <.001 |
| SO2 | 27.56 | 28.93 | <.001 |
| CO | 1.19 | 0.93 | <.001 |
| NO2 | 45.26 | 19.12 | .13 |
| O3 | 94.12 | 53.24 | <.001 |
| IgA vasculitis | 20.73 | 11.76 | <.001 |
PM10 = inhalable particulate matter 10, PM2.5 = particulate matter 2.5.
According to the Spearman correlation test, for each group of data, PM10, PM2.5, SO2, CO, and NO2 are positively correlated with each other, of which PM2.5 is obviously positively correlated with PM10 and CO, with correlation coefficients of 0.959. O3 showed a negative correlation with PM10, PM2.5, SO2, NO2, and CO and the strongest negative correlation with NO2, with a correlation coefficient of −0.584. The number of monthly patients with IgA vasculitis disease showed a weak positive correlation with the monthly average concentration of PM10, PM2.5, CO, NO2, and a weak negative correlation with the monthly average concentration of O3. The detailed results are shown in Table 6. Figure 3 shows the time series plot of each air pollutant except CO. Figure 4 shows the time series plot of CO. Figures 3 and 4 show that the same trend exists for each air pollutant except for ozone.
Table 6.
Results of correlation of air pollutants with each other and correlation of each air pollutant with IgA vasculitis.
| PM2.5 | PM10 | SO2 | NO2 | CO | O3 | |||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| r | P | r | P | r | P | r | P | r | P | r | P | |
| PM10 | 0.959 | <.001 | – | – | ||||||||
| SO2 | 0.861 | <.001 | 0.896 | <.001 | – | – | ||||||
| NO2 | 0.837 | <.001 | 0.825 | <.001 | 0.684 | <.001 | – | – | ||||
| CO | 0.959 | <.001 | 0.926 | <.001 | 0.877 | <.001 | 0.826 | <.001 | – | – | ||
| O3 | ‐0.371 | <.001 | ‐0.337 | <.001 | ‐0.125 | .198 | ‐0.584 | <.001 | ‐0.387 | <.001 | – | – |
| IgAV | 0.191 | .048 | 0.199 | .039 | 0.130 | .179 | 0.390 | <.001 | 0.193 | .045 | ‐0.253 | .008 |
“r” represents the correlation coefficient, and “P” represents the p value.
IgAV = IgA vasculitis, PM10 = inhalable particulate matter 10, PM2.5 = particulate matter 2.5.
Figure 3.
Time series plot of monthly average concentrations of each air pollutant except ozone from January 2014 to December 2022.
Figure 4.
Time series plot of monthly average CO concentrations from January 2014 to December 2022.
We established a multiple linear regression equation with the monthly number of cases of IgA vasculitis as the dependent variable Y, and PM2.5 (X1), PM10 (X2), CO (X3), NO2 (X4), and O3 (X5) as the independent variables, and the results showed that the linear equation was Y = 0.609X4 (R2 = 0.302, F = 8.833, P < .001). NO2 (t = 5.137, P < .001, Variance Inflation Factor = 5.428) which enters the equation is the most important influencing factor in air pollutants. Detailed results are shown in Table 7. Figure 5 shows the scatter plot of monthly mean NO2 concentration versus monthly number of IgA vasculitis cases and the fit of the multiple linear regression equation.
Table 7.
Results of multiple linear regression analysis.
| Model | Coefficient | t | Significance | Collinearity statistics | |
|---|---|---|---|---|---|
| Tolerance | VIF | ||||
| Constant | 6.050 | 1.203 | 0.232 | ||
| PM2.5 | ‐0.033 | ‐0.315 | 0.753 | 0.042 | 23.561 |
| PM10 | ‐0.089 | ‐1.687 | 0.095 | 0.084 | 11.958 |
| CO | ‐0.168 | ‐0.053 | 0.957 | 0.110 | 9.126 |
| NO2 | 0.609 | 5.137 | <0.001 | 0.184 | 5.428 |
| O3 | 0.009 | 0.396 | 0.693 | 0.591 | 1.692 |
PM10 = inhalable particulate matter 10, PM2.5 = particulate matter 2.5, VIF = Variance Inflation Factor.
Figure 5.
Scatterplot of mean monthly NO2 concentration versus monthly number of IgA vasculitis cases and the fit of the multiple linear regression equation.
4. Discussion
Vasculitis is a group of diseases in which inflammatory cell infiltration, fibrinoid degeneration, and necrosis of the vessel wall and its periphery are the main pathological changes, and the causative factors are very complex.[6,7] Air pollution is one of the causative factors.[1] IgA vasculitis is a common vasculitic disease in pediatric patients. A large body of evidence supports the notion that genetics plays a crucial role in the pathogenesis of IgA vasculitis.[8] However, it has also been shown that various predisposing events, such as infections, drug intake, food intolerance, insect bites, and vaccinations, may modulate the incidence and severity of IgA vasculitis in these genetically susceptible individuals. Thus, most cases of IgA vasculitis result from a combination of genetic and predisposing factors.[9,10] Our study revealed a weak positive correlation between IgA vasculitis and NO2, a very weak positive correlation with PM2.5, PM10, and CO, and a weak negative correlation with O3. Multiple linear regression analysis indicated that among the air pollutants, NO2 was the most important influencing factor in inducing the development of IgA vasculitis.
For NO2, it has been shown to increase leukotriene production in humans.[11] Furthermore, the expression level of leukotriene is significantly correlated with the severity of IgA vasculitis and has predictive value for the prognosis of IgA vasculitis patients.[12] Therefore, we speculated that nitrogen dioxide could induce the attack of IgA vasculitis and that the triggering mechanism is to increase leukotriene production in the body. However, leukotriene receptor antagonists, such as montelukast sodium, are not alternatives for treating IgA vasculitis. It has been shown that montelukast can induce adverse skin reactions, including purpura, in patients with asthma.[13] Moreover, there is also an association between leukotriene receptor antagonists and anti-neutrophil cytoplasmic antibody positivity, with a significantly greater risk of anti-neutrophil cytoplasmic antibody positivity in patients previously treated with leukotriene receptor antagonists. This finding may be due to an unbalanced stimulation of leukotriene receptors, which leads to increased mast cell activation and extracellular traps released by neutrophils.[14]
For PM2.5, PM10, and CO, there was a very weak positive correlation between all of the 3 and IgA vasculitis. In addition, it has been demonstrated that exposure of adults to elevated concentrations of NO2, nitrogen oxides (NOx), PM2.5, and PM10 can result in elevated leukotriene levels in sputum.[15] However, by the fact that PM10, PM2.5, SO2, NO2, and CO have a highly positive correlation with each other, it is not possible to determine whether the increased leukotriene levels induced by exposure to PM2.5 and PM10 are associated with concomitant exposure to NO2. Nevertheless, we believe the correlation between PM10, PM2.5, SO2, and CO and the development of IgA vasculitis will still be a direction for future research.
As for ozone, this study revealed that the O3 concentration negatively correlated with PM10, PM2.5, SO2, CO, and NO2. We presumed that this is due to the O3 produced by human factors, which is mainly a secondary pollutant generated by complex photochemical reactions of volatile organic compounds, NOx, and other substances at low altitudes under UV irradiation. Its concentration is affected by the intensity of UV radiation and the concentration of NOx; if the concentration of NOx is high, the O3 concentration will increase, and if the concentration of particulate matter is relatively high, it can block UV radiation so that the O3 concentration will be low. However, although NO2 is a crucial component of NOx, the relationship between nitrogen dioxide and ozone is not a simple linear relationship; it is extraordinarily complex and affected by many other factors.[16] In our study, NO2 was the air pollutant with the strongest negative correlation with O3. Therefore, we speculated that O3 is not directly associated with IgA vasculitis. However, because it is moderately strongly negatively correlated with NO2, it is statistically presented as negatively correlated with IgA vasculitis.
Regarding the impact of the new coronavirus outbreak, it has now been shown that COVID-19 infection may be a predisposing factor for IgA vasculitis.[17] However, due to the strong dynamic zeroing policy adopted by China after the COVID-19 pandemic outbreak, there was no COVID-19 pandemic in our region before the end of this policy. This precautionary measure continued until December 2022, so we had not been affected by the COVID-19 pandemic during our data collection period. The results of the comparison of the total number of outpatient visits and hospitalizations per month and the number of patients with IgA vasculitis per month before and after the pandemic outbreak verified this.
Finally, this study has some limitations because air pollutants increase the probability of respiratory infections, which also predispose to IgA vasculitis.[18] Infections can also lead to drug application and vaccination, which are also predisposing factors for IgA vasculitis. In addition, because the data on pediatric outpatient and inpatient diseases in only 1 general hospital were selected for this study, the sample size was limited, and there were obvious geographical limitations, which may have resulted in selection bias. Therefore, it is important to explore in the context of multiple cities or countries to generate convincing and accurate conclusions.
5. Conclusion
There was a correlation between the long-term explosion of nitrogen dioxide and the development of IgA vasculitis.
Acknowledgments
We want to thank all the members of the information department of the Second Central Hospital of Baoding for their excellent contribution to this case collection process.
Author contributions
Conceptualization: Fang Pu, Ya-Qin Hao.
Data curation: Fang Pu, Ya-Qin Hao.
Formal analysis: Fang Pu, Ya-Qin Hao.
Methodology: Fang Pu.
Project administration: Fang Pu.
Software: Fang Pu, Ya-Qin Hao.
Supervision: Fang Pu, Ya-Qin Hao.
Validation: Fang Pu.
Visualization: Fang Pu.
Writing – review & editing: Fang Pu.
Writing – original draft: Ya-Qin Hao.
Abbreviations:
- PM10
- inhalable particulate matter 10
- PM2.5
- particulate matter 2.5
Our study conformed to the Declaration of Helsinki and relevant guidelines. The Ethics Committee of the Second Central Hospital of Baoding approved this study (N202355) and waived the need for individual written informed consent. Because our study only captured the number of patients with IgA vasculitis per month and did not collect personal information, the Second Central Hospital of Baoding Ethics Review Committee waived written informed notification to the parents or legal guardians of participants under 16.
The authors have no funding and conflicts of interest to disclose.
The datasets generated during and/or analyzed during the current study are not publicly available, but are available from the corresponding author on reasonable request.
How to cite this article: Pu F, Hao Y-Q. Study on the correlation between atmospheric pollutants and the development of IgA vasculitis. Medicine 2025;104:22(e42617).
FP and Y-QH contributed equally to this work.
References
- [1].Farhat SC, Silva CA, Orione MA, Campos LM, Sallum AM, Braga AL. Air pollution in autoimmune rheumatic diseases: a review. Autoimmun Rev. 2011;11:14–21. [DOI] [PubMed] [Google Scholar]
- [2].Zhao N, Smargiassi A, Chen H, Widdifield J, Bernatsky S. Systemic autoimmune rheumatic diseases and multiple industrial air pollutant emissions: a large general population Canadian cohort analysis. Environ Int. 2023;174:107920. [DOI] [PubMed] [Google Scholar]
- [3].Hill BG, Rood B, Ribble A, Haberzettl P. Fine particulate matter (PM(2.5)) inhalation-induced alterations in the plasma lipidome as promoters of vascular inflammation and insulin resistance. Am J Physiol Heart Circ Physiol. 2021;320:H1836–50. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [4].Li J, Cui Z, Long JY, et al. The frequency of ANCA-associated vasculitis in a national database of hospitalized patients in China. Arthritis Res Ther. 2018;20:226. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [5].Zhao WM, Wang ZJ, Shi R, et al. Environmental factors influencing the risk of ANCA-associated vasculitis. Front Immunol. 2022;13:991256. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [6].Belizna CC, Hamidou MA, Levesque H, Guillevin L, Shoenfeld Y. Infection and vasculitis. Rheumatology (Oxford). 2009;48:475–82. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [7].Eleftheriou D, Brogan PA. Therapeutic advances in the treatment of vasculitis. Pediatr Rheumatol Online J. 2016;14:26. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [8].He X, Yu C, Zhao P, et al. The genetics of Henoch–Schonlein purpura: a systematic review and meta-analysis. Rheumatol Int. 2013;33:1387–95. [DOI] [PubMed] [Google Scholar]
- [9].Lopez-Mejias R, Castaneda S, Genre F, et al. Genetics of immunoglobulin-A vasculitis (Henoch–Schonlein purpura): an updated review. Autoimmun Rev. 2018;17:301–15. [DOI] [PubMed] [Google Scholar]
- [10].Xu Y, Wang JJ, Liu FF, et al. Predisposing factors of childhood Henoch–Schonlein purpura in Anhui province, China. J Investig Med. 2019;67:771–8. [DOI] [PubMed] [Google Scholar]
- [11].Glencross DA, Ho TR, Camina N, Hawrylowicz CM, Pfeffer PE. Air pollution and its effects on the immune system. Free Radic Biol Med. 2020;151:56–68. [DOI] [PubMed] [Google Scholar]
- [12].Zhu L, Zhang C, Xiang R, Luo Y. Correlations of leukotriene B4 and 25-hydroxyvitamin D3 levels with disease severity in children with Henoch–Schonlein purpura. Clin Lab. 2022;68:1622–9. [DOI] [PubMed] [Google Scholar]
- [13].Di Salvo E, Patella V, Casciaro M, Gangemi S. The leukotriene receptor antagonist Montelukast can induce adverse skin reactions in asthmatic patients. Pulm Pharmacol Ther. 2020;60:101875. [DOI] [PubMed] [Google Scholar]
- [14].Schroeder JW, Folci M, Losappio LM, et al. Anti-neutrophil cytoplasmic antibodies positivity and anti-leukotrienes in eosinophilic granulomatosis with polyangiitis: a retrospective monocentric study on 134 Italian patients. Int Arch Allergy Immunol. 2019;180:64–71. [DOI] [PubMed] [Google Scholar]
- [15].Kress S, Wigmann C, Zhao Q, et al. Chronic air pollution-induced subclinical airway inflammation and polygenic susceptibility. Respir Res. 2022;23:265. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [16].Lu K, Zhou H, Lee J, Nelson B, Zhang Y. Ozone mitigations beyond the control of nitrogen oxides and volatile organic compounds. Sci Bull (Beijing). 2023;68:1989–92. [DOI] [PubMed] [Google Scholar]
- [17].Messova A, Pivina L, Muzdubayeva Z, Sanbayev D, Urazalina Z, Adams A. COVID-19 and new onset IgA vasculitis: a systematic review of case reports. J Emerg Nurs. 2022;48:348–65. [DOI] [PMC free article] [PubMed] [Google Scholar]
- [18].Wang JJ, Xu Y, Liu FF, et al. Association of the infectious triggers with childhood Henoch–Schonlein purpura in Anhui province, China. J Infect Public Health. 2020;13:110–7. [DOI] [PubMed] [Google Scholar]