Environmental Risk Factors and Appendicitis Incidence: A Pooled Up Analysis

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Methods This study investigated the association between environmental risk factors and the incidence of appendicitis through a meta-analysis. Through searching in four databases (PubMed, Cochrane, Web of Science and Embase) up to May 2025 for cohort studies assessing the association between environment risk factors and appendicitis incidence. After study selection, a total of eight studies from five countries were included in the meta-analysis. Random-effect model was employed in the study, I 2 statistic assessed heterogeneity, and the Egger's test detected publication bias. Results A total of eight studies including 346304 appendicitis patients were included in this study. Analysis of overall odds ratio (OR) of appendicitis incidence associated with environment risk factors was estimated to be statistic significant (OR = 1.06, 95% CI 1.03–1.09). Further subgroup analysis showed that elevated temperature, PM₁₀, ozone (O₃), and nitrogen dioxide (NO₂) were significantly associated with an increased risk of appendicitis. Specifically, each unit rise in temperature was linked to a 7% higher risk (OR = 1.07, 95% CI 1.02–1.12), while increases in PM₁₀, O₃, and NO₂ were associated with 4% (OR = 1.04, 95% CI 1.01–1.07), 8% (OR = 1.08, 95% CI 1.06–1.11), and 13% (OR = 1.13, 95% CI 1.06–1.20) elevated risks, respectively. Notably, NO₂ exhibited the strongest effect. These findings suggest that environmental factors, particularly air pollutants and high temperature, may contribute to a higher incidence of appendicitis. Conclusion We found that the high temperature, O 3 , NO 2 and PM 10 was associated with high incidence of appendicitis. Health sciences/Diseases Earth and environmental sciences/Environmental sciences Health sciences/Health care Health sciences/Medical research Health sciences/Risk factors environment factors appendicitis temperature air pollution Figures Figure 1 Figure 2 Figure 3 Figure 4 Figure 5 Figure 6 Introduction Appendicitis, one of the most common surgical emergencies worldwide [ 1 ] , imposes a significant burden on healthcare systems due to its high incidence and potential complications [ 2 ] . The condition most commonly occurs between the ages of 10 and 20 years with a lifetime risk of 6.7% and 8.6% for males and females, respectively [ 3 , 4 ] . We noted that appendicitis from newly industrialized countries was sparse [ 5 ] . While the etiology of appendicitis remains multifactorial [ 6 ] , traditional research has predominantly focused on individual-level risk factors such as age, genetics, and lifestyle. However, emerging evidence suggests that environmental determinants may play a critical yet understudied role in its pathogenesis [ 5 , 6 ] . In recent decades, rapid industrialization and urbanization have intensified exposure to diverse environmental hazards, including air pollution [ 7 ] , dietary shifts, and climate variability. Climate change can be associated with adverse outcomes [ 8 – 10 ] . Previous studies reported that ambient temperature is related to gastroenteritis hospitalizations [ 11 ] . Notably, there are some evidences of interactive effects between temperature and the levels of ozone and PM 10 on daily deaths [ 12 – 16 ] . So, we speculate temperature fluctuations may have been hypothesized to influence appendicitis risk. Despite sporadic epidemiological reports on these associations, a systematic synthesis of evidence is lacking, particularly regarding the magnitude and consistency of effects across populations. This study aims to address this gap by conducting a meta-analysis of the relationship between environmental risk factors (e.g., temperature, air quality) and appendicitis incidence. By integrating global data, we seek to clarify the role of environmental exposures, identify high-risk populations, and preventive strategies. Our findings may contribute to a paradigm shift in understanding appendicitis etiology, emphasizing the interplay between environmental and individual factors in disease development. Methods This meta-analysis was registered with the PROSPERO international prospective register of systematic reviews (reference number: CRD420251032090) and the link is https://www.crd.york.ac.uk/PROSPERO/myprospero . The study was carried out in accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidance [ 17 ] . Literature search strategy We searched four databases including the PubMed, Embase, Cochrane Library databases and Web of Science. The searching strategy included two key words: acute appendicitis and environment factors. As for acute appendicitis, the searching strategy was as follows: “Appendicitis” OR “Acute Appendicitis” OR “Ruptured Appendicitis”. In terms of environment factors, the searching strategy was as follows: Weather OR Climate OR Pollution OR Seasons OR Air Pollution OR Temperature OR Atmosphere. Then, we use “AND” to combine the two key words. The language was limited in English. Inclusion and exclusion criteria Our meta-analysis aimed to analyze the effect of environment factors on the incidence of appendicitis, therefore, the inclusion criteria were as follows: 1. Patients were diagnosed with appendicitis confirmed by clinic radiology or pathology; 2. Study should be observational studies (cohort, case-control, cross-sectional); 3. Studies reporting quantitative associations between environmental exposures and appendicitis incidence (e.g., odds ratio(OR), relative risk (RR), hazard ratio(HR) with 95% CIs(Confidence interval)); 4. Studies providing extractable data on exposure levels, sample size, and statistical results. The exclusion criteria were as follows: 1. The article type was case report, review, letter to editor, comments or conference; 2. Studies reporting only p-values or raw counts without effect sizes; 3. Studies lacking quantitative environmental exposure metrics. Disagreement was settled by group discussion. Study selection Two reviewers searched the four databases, respectively. The duplicated studies were discharged firstly; Then, the titles and abstracts were screened to find eligible studies; After that, full texts would be checked to determine whether they were suitable for final analysis. Two reviewers conducted the study selection, final judgment was made after group discussion. Data extraction The data included study information, baseline information, exposure and outcome information. The study information included the first author, publishing year, publishing country and Newcastle-Ottawa Scales (NOS) score; The exposure and outcome information included the exposure type and effect estimates. These data were extracted independently and cross-checked by two reviewers. Quality Assessment The NOS score was used to evaluate the quality of the included studies [ 18 ] . When the score was nine points, it represented high quality; When the score was seven to eight points, it represented medium quality; The low-quality studies had scores less than seven points. Statistical analysis This meta-analysis systematically evaluated the association between environmental factors and appendicitis incidence by synthesizing data from observational studies. We extracted ORs of different exposures with 95% confidence intervals. Statistical heterogeneity was assessed using I² statistics [ 19 , 20 ] , with I²>50% or p < 0.05 indicating substantial heterogeneity warranting random-effects models, while fixed-effects models were applied for homogeneous data (I²≤50%). All analysis was performed using stata (vision 16.0). Forest plots visualized effect estimates, and sensitivity analysis tested result robustness. Publication bias was assessed via funnel plots when feasible. The findings provided quantitative estimates of environmental risks for appendicitis, with OR > 1 indicating increased risk (e.g., for high PM 2.5 exposure) and OR < 1 suggesting protective factor, offering evidence for public health interventions targeting modifiable environmental determinants of appendicitis. Results Study selection A total of 721 studies were identified in the four databases (364 studies in PubMed, 555 studies in Embase, 0 study in the Cochrane Library and 35 studies in Web of Science). There were 134 studies after removing the duplicated studies. Finally, 8 studies were left for final analysis. (Fig. 1 ) Baseline characteristics of studies A total of eight studies were identified [ 21 – 28 ] . The publishing year was from 2009 to 2025. Three studies were published in China, one study was published in Korea, one study was published in America, 1 study was published in Serbia and 2 study was published in Canada. The scope of the study was from 1998 to 2018. The survival volume, sample size, cut-off value and NOS score of each included study were shown in Table 1 . Table 1 Principle characteristics of included studies Author Year Study period Country Study design Patients Sex(male/female) Exposure NOS Yongho Jee 2024 2001–2018 Korea restrospective study 6526 appendicitis 51.09%/48.91% PM 10 and season 7 Kaplan 2013 2004–2008 Canada restrospective study 35811 appendicitis 54%/31% O 3 8 Sherbakov 2018 1999–2009 America restrospective study 219426 appendicitis / temperature 8 Yu 2025 1998–2019 China restrospective study 59128 appendicitis / temperature 6 Karanikolić 2016 2011–2013 Serbia restrospective study 395 appendicitis 45.8%/54.2% seasons, changes in atmospheric temperature and pressure, 5 Kaplan 2016 1999–2006 Canada restrospective study 5191 appendicitis 53.2%/46.8% Ozone, Sulfur dioxide, Nitrogen dioxide, Carbon monoxide, PM 2.5 , PM 10 5 Chen 2018 2009–2013 China restrospective study 18400 appendicitis / PM 2.5 , NO 2 , CO, and O 3 5 Ji 2023 2016–2018 China restrospective study 1427 appendicitis 82.9%/17.1% PM 2.5 , NO 2 , SO 2 6 Abbreviation:NOS, Newcastle-Ottawa Scales. Baseline information The baseline information included different exposures OR and 95% CIs. The subgroup analyses by pollutant type revealed significant variations in health risk associations (between-group heterogeneity p = 0.005). High temperature exposure showed no significant effect (pooled OR = 0.99, 95% CI 0.92–1.06, I²=97.5%), while air pollutants demonstrated consistent risk elevations: PM 10 (OR = 1.04, 95% CI 1.01–1.07,I²=77.4%), O 3 (OR = 1.09, 95% CI 1.06–1.13, I²=0.0%), and NO 2 (OR = 1.13, 95% CI 1.06–1.20, I²=75.1%). High temperature Among the eight selected articles, five addressed the impact of temperature on the incidence of appendicitis, we find the I 2 value was 97.5% and we conducted a sensitivity test by using leave-one-out analysis method (Fig. 2 ). The result indicated that Yongjho jee (2024) has a significant impact on the overall result. After excluding the Yongjho jee (2024). We re-analyzed the data and the result shows that I 2 value was 95.2%, indicating significant statistical heterogeneity, and high temperature group was associated with high incidence of incidence of appendicitis (OR = 1.07, 95% CI 1.02–1.12, P < 0.01). (Fig. 3 ) For publication bias, we conduct Egger's test which indicate that P = 0.531. There is no significant publication bias. Air pollution There studies reported the data of O 3 on incidence of appendicitis, after pooling up all the data, we found that the high Ozone group was associated with high incidence of appendicitis (OR = 1.08, 95% CI 1.06–1.11, P < 0.01). (Fig. 4 ) Three studies reported the data of NO 2 on the incidence of appendicitis, after pooling up all the data, we found that the high NO2 was associated with high incidence of appendicitis (OR = 1.13, 95% CI 1.06–1.20, P < 0.01). (Fig. 5 ) Four studies reported the data of PM 10 on incidence of appendicitis, after pooling up all the data, we found that the PM 10 was associated with high incidence of appendicitis (OR = 1.04, 95% CI 1.01–1.07, P < 0.01). (Fig. 6 ) Discussion A total of eight studies were included in the current meta-analysis. As for the exposure, after pooling up all the data, we found that the high temperature, Ozone, NO 2 and PM 10 was associated with high incidence of appendicitis. Our findings demonstrate significant correlations between these exposures and appendicitis risk, supporting the hypothesis that environmental triggers may contribute to the pathogenesis of this common surgical condition. Previous studies indicated that mortality risk attributable to high and low ambient temperature [ 29 , 30 ] . We found higher ambient temperature was associated with increased appendicitis incidence. Possible mechanisms may include Dietary and Behavioral Changes. Warmer weather may alter food storage conditions, increasing the risk of bacterial contamination and gastrointestinal infections [ 31 ] , which could indirectly trigger appendicitis. Second is immune Modulation. Heat stress may influence systemic inflammation or local immune responses in the appendix. Our results align with ecological studies reporting higher appendicitis rates in summer months [ 32 – 34 ] . Previous studies corroborated that particulate matter exposure could induce healthy problems [ 35 ] . We found a positive association with appendicitis, possibly due to systemic inflammation [ 36 – 38 ] or oxidative stress disrupting gut barrier function. We also discovered that urban airborne particulate matter via contaminated food can alter the gut microbiome and immune function under normal and inflammatory conditions [ 39 ] . The effects of NO 2 and O 3 were somewhat weaker but still significant. These pollutants may act through Oxidative stress pathways damaging intestinal epithelium [ 40 ] and DNA methylation [ 41 ] which influences inflammation. These pollutants may promote mucosal irritation or ischemic changes in the appendix, though the exact pathways remain unclear. While our study establishes epidemiological associations, several potential biological pathways warrant discussion. First is microbiome interaction. Emerging research indicates that both temperature extremes and air pollutants can alter gut microbiota composition [ 42 ] . Such dysbiosis might predispose to appendiceal inflammation. Second is epithelial barrier disruption. Experimental studies show that PM 2.5 exposure leads to loss of barrier function in human nasal epithelium [ 43 ] , we speculate that PM 2.5 may effects intestinal epithelial cells which potentially facilitate bacterial translocation. To our knowledge, our study is the first study to pool up environmental exposures on appendicitis. In our study, our analysis benefits from comprehensive inclusion of multiple environmental factors. However, several limitations merit consideration. Most studies used local pollution estimates rather than personal exposure data, potentially introducing misclassification. Variability in diagnostic criteria for appendicitis across studies may affect outcome classification. Therefore, multicenter, multiregional and high-quality studies should be carried out in the future. This study provides robust epidemiological evidence that environmental factors-particularly temperature and air pollution-are associated with appendicitis incidence. While further research is needed to establish causality and mechanistic pathways, these findings highlight the potential for environmental interventions to mitigate appendicitis risk. Clinicians and policymakers should consider environmental health strategies as part of broader appendicitis prevention efforts. In conclusion, these findings have several important implications suggesting these exposures may represent modifiable risk factors for disease prevention. The findings advocate targeted public health measures, including heat-health warning systems that incorporate appendicitis risk alerts, stricter air quality regulations with consideration of gastrointestinal health impacts, and community education programs about protective behaviors during high-risk environmental conditions. Clinicians should maintain heightened awareness of potential increased appendicitis presentations following extreme weather events or pollution episodes. These collective efforts could transform appendicitis from being viewed solely as a surgical emergency to a preventable condition influenced by environmental determinants, ultimately reducing its global disease burden through both clinical and environmental health approaches. The results underscore the importance of integrating environmental risk reduction into broader appendicitis prevention strategies. Declarations Data availability: The datasets generated and/or analyzed during the current study are not publicly available due but are available from the corresponding author upon reasonable request. Competing interests: The authors declare no conflicts of interest. Authors' contributions: Data extraction, Chen-Yu Xiang and Xiao-Yu Liu; quality assessments, Wei Lu, Jun-Nan Zhao; data analysis, Chen-Yu Xiang and Wei Lu; writing the main manuscript text, Chen-Yu Xiang and Xiao-Yu Liu; writing-review and editing, Chen-Yu Xiang and Wei Lu. Chen-Yu Xiang prepared figures. All authors read and approved the final manuscript. Funding: Not applicable. Acknowledgments: We acknowledge all the authors whose publications are referred in our article. References Liu F, Lv Q, Wang C Y, et al. 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09:53:20","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-7168890/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-7168890/v1","draftVersion":[],"editorialEvents":[],"editorialNote":"","failedWorkflow":false,"files":[{"id":89388788,"identity":"0d3ec197-4e4f-4ec4-ae89-5a71877fd2b0","added_by":"auto","created_at":"2025-08-19 12:43:27","extension":"jpg","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":649258,"visible":true,"origin":"","legend":"\u003cp\u003eFlowchart of study selection.\u003c/p\u003e","description":"","filename":"Fig1.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7168890/v1/8754dc58db6a3a67ba3f3ce9.jpg"},{"id":89388789,"identity":"9e356322-b115-4e0c-8db0-b92685a2c2c5","added_by":"auto","created_at":"2025-08-19 12:43:27","extension":"jpg","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":1339591,"visible":true,"origin":"","legend":"\u003cp\u003eSensitivity Analysis of temperature\u003c/p\u003e","description":"","filename":"fig2.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7168890/v1/682838d3dc17794b1e10d8e1.jpg"},{"id":89386278,"identity":"feabc332-737b-4c0c-8988-cdd4061ed608","added_by":"auto","created_at":"2025-08-19 12:35:27","extension":"jpg","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":116391,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of high temperature\u003c/p\u003e","description":"","filename":"fig3.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7168890/v1/5d41122588ce0fcb36b565c8.jpg"},{"id":89384942,"identity":"3fdb56d1-edb3-4929-a8d4-c962afce3900","added_by":"auto","created_at":"2025-08-19 12:27:27","extension":"jpg","order_by":4,"title":"Figure 4","display":"","copyAsset":false,"role":"figure","size":93646,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of Ozone\u003c/p\u003e","description":"","filename":"fig4.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7168890/v1/73a4f1abde3c153f8d41cd5a.jpg"},{"id":89384948,"identity":"b70d9932-67de-47d7-b1cb-01b92bf9abd4","added_by":"auto","created_at":"2025-08-19 12:27:27","extension":"jpg","order_by":5,"title":"Figure 5","display":"","copyAsset":false,"role":"figure","size":97865,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of NO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e","description":"","filename":"fig5.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7168890/v1/c2ac6b730298033797d485f2.jpg"},{"id":89384953,"identity":"a7f7d72c-62b8-478e-ab8b-0421f3ec9bab","added_by":"auto","created_at":"2025-08-19 12:27:27","extension":"jpg","order_by":6,"title":"Figure 6","display":"","copyAsset":false,"role":"figure","size":111394,"visible":true,"origin":"","legend":"\u003cp\u003eForest plot of PM\u003csub\u003e10\u003c/sub\u003e\u003c/p\u003e","description":"","filename":"fig6.jpg","url":"https://assets-eu.researchsquare.com/files/rs-7168890/v1/b39712bafef8752dd8a38efb.jpg"},{"id":90152219,"identity":"7ec38913-5bbb-43dc-87cc-d39cfb225a6a","added_by":"auto","created_at":"2025-08-29 07:24:11","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":2987659,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-7168890/v1/5cc3cff9-3a6b-4833-9608-28daf61fce88.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Environmental Risk Factors and Appendicitis Incidence: A Pooled Up Analysis","fulltext":[{"header":"Introduction","content":"\u003cp\u003eAppendicitis, one of the most common surgical emergencies worldwide\u003csup\u003e[\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e]\u003c/sup\u003e, imposes a significant burden on healthcare systems due to its high incidence and potential complications\u003csup\u003e[\u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]\u003c/sup\u003e. The condition most commonly occurs between the ages of 10 and 20 years with a lifetime risk of 6.7% and 8.6% for males and females, respectively\u003csup\u003e[\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e, \u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]\u003c/sup\u003e. We noted that appendicitis from newly industrialized countries was sparse\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]\u003c/sup\u003e. While the etiology of appendicitis remains multifactorial\u003csup\u003e[\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e, traditional research has predominantly focused on individual-level risk factors such as age, genetics, and lifestyle. However, emerging evidence suggests that environmental determinants may play a critical yet understudied role in its pathogenesis\u003csup\u003e[\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e, \u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003eIn recent decades, rapid industrialization and urbanization have intensified exposure to diverse environmental hazards, including air pollution\u003csup\u003e[\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e]\u003c/sup\u003e, dietary shifts, and climate variability. Climate change can be associated with adverse outcomes\u003csup\u003e[\u003cspan additionalcitationids=\"CR9\" citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e–\u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e]\u003c/sup\u003e. Previous studies reported that ambient temperature is related to gastroenteritis hospitalizations\u003csup\u003e[\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]\u003c/sup\u003e. Notably, there are some evidences of interactive effects between temperature and the levels of ozone and PM\u003csub\u003e10\u003c/sub\u003e on daily deaths\u003csup\u003e[\u003cspan additionalcitationids=\"CR13 CR14 CR15\" citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e–\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e]\u003c/sup\u003e. So, we speculate temperature fluctuations may have been hypothesized to influence appendicitis risk. Despite sporadic epidemiological reports on these associations, a systematic synthesis of evidence is lacking, particularly regarding the magnitude and consistency of effects across populations.\u003c/p\u003e\u003cp\u003eThis study aims to address this gap by conducting a meta-analysis of the relationship between environmental risk factors (e.g., temperature, air quality) and appendicitis incidence. By integrating global data, we seek to clarify the role of environmental exposures, identify high-risk populations, and preventive strategies. Our findings may contribute to a paradigm shift in understanding appendicitis etiology, emphasizing the interplay between environmental and individual factors in disease development.\u003c/p\u003e"},{"header":"Methods","content":"\u003cp\u003eThis meta-analysis was registered with the PROSPERO international prospective register of systematic reviews (reference number: CRD420251032090) and the link is \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.crd.york.ac.uk/PROSPERO/myprospero\u003c/span\u003e\u003cspan address=\"https://www.crd.york.ac.uk/PROSPERO/myprospero\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. The study was carried out in accordance with the preferred reporting items for systematic reviews and meta-analysis (PRISMA) guidance\u003csup\u003e[\u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003e\u003cb\u003eLiterature search strategy\u003c/b\u003e\u003c/p\u003e\u003cp\u003eWe searched four databases including the PubMed, Embase, Cochrane Library databases and Web of Science. The searching strategy included two key words: acute appendicitis and environment factors. As for acute appendicitis, the searching strategy was as follows: “Appendicitis” OR “Acute Appendicitis” OR “Ruptured Appendicitis”. In terms of environment factors, the searching strategy was as follows: Weather OR Climate OR Pollution OR Seasons OR Air Pollution OR Temperature OR Atmosphere. Then, we use “AND” to combine the two key words. The language was limited in English.\u003c/p\u003e\u003cp\u003e\u003cb\u003eInclusion and exclusion criteria\u003c/b\u003e\u003c/p\u003e\u003cp\u003eOur meta-analysis aimed to analyze the effect of environment factors on the incidence of appendicitis, therefore, the inclusion criteria were as follows: 1. Patients were diagnosed with appendicitis confirmed by clinic radiology or pathology; 2. Study should be observational studies (cohort, case-control, cross-sectional); 3. Studies reporting quantitative associations between environmental exposures and appendicitis incidence (e.g., odds ratio(OR), relative risk (RR), hazard ratio(HR) with 95% CIs(Confidence interval)); 4. Studies providing extractable data on exposure levels, sample size, and statistical results. The exclusion criteria were as follows: 1. The article type was case report, review, letter to editor, comments or conference; 2. Studies reporting only p-values or raw counts without effect sizes; 3. Studies lacking quantitative environmental exposure metrics. Disagreement was settled by group discussion.\u003c/p\u003e\u003cp\u003e\u003cb\u003eStudy selection\u003c/b\u003e\u003c/p\u003e\u003cp\u003eTwo reviewers searched the four databases, respectively. The duplicated studies were discharged firstly; Then, the titles and abstracts were screened to find eligible studies; After that, full texts would be checked to determine whether they were suitable for final analysis. Two reviewers conducted the study selection, final judgment was made after group discussion.\u003c/p\u003e\u003cp\u003e\u003cb\u003eData extraction\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe data included study information, baseline information, exposure and outcome information. The study information included the first author, publishing year, publishing country and Newcastle-Ottawa Scales (NOS) score; The exposure and outcome information included the exposure type and effect estimates. These data were extracted independently and cross-checked by two reviewers.\u003c/p\u003e\u003cp\u003e\u003cb\u003eQuality Assessment\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe NOS score was used to evaluate the quality of the included studies\u003csup\u003e[\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]\u003c/sup\u003e. When the score was nine points, it represented high quality; When the score was seven to eight points, it represented medium quality; The low-quality studies had scores less than seven points.\u003c/p\u003e\u003ch2\u003eStatistical analysis\u003c/h2\u003e\u003cp\u003eThis meta-analysis systematically evaluated the association between environmental factors and appendicitis incidence by synthesizing data from observational studies. We extracted ORs of different exposures with 95% confidence intervals. Statistical heterogeneity was assessed using I² statistics \u003csup\u003e[\u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e, \u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]\u003c/sup\u003e, with I²\u0026gt;50% or p \u0026lt; 0.05 indicating substantial heterogeneity warranting random-effects models, while fixed-effects models were applied for homogeneous data (I²≤50%). All analysis was performed using stata (vision 16.0). Forest plots visualized effect estimates, and sensitivity analysis tested result robustness. Publication bias was assessed via funnel plots when feasible. The findings provided quantitative estimates of environmental risks for appendicitis, with OR \u0026gt; 1 indicating increased risk (e.g., for high PM\u003csub\u003e2.5\u003c/sub\u003e exposure) and OR \u0026lt; 1 suggesting protective factor, offering evidence for public health interventions targeting modifiable environmental determinants of appendicitis.\u003c/p\u003e"},{"header":"Results","content":"\u003cp\u003e\u003cb\u003eStudy selection\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA total of 721 studies were identified in the four databases (364 studies in PubMed, 555 studies in Embase, 0 study in the Cochrane Library and 35 studies in Web of Science). There were 134 studies after removing the duplicated studies. Finally, 8 studies were left for final analysis. (Fig.\u0026nbsp;\u003cspan refid=\"Fig1\" class=\"InternalRef\"\u003e1\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eBaseline characteristics of studies\u003c/b\u003e\u003c/p\u003e\u003cp\u003eA total of eight studies were identified\u003csup\u003e[\u003cspan additionalcitationids=\"CR22 CR23 CR24 CR25 CR26 CR27\" citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR28\" class=\"CitationRef\"\u003e28\u003c/span\u003e]\u003c/sup\u003e. The publishing year was from 2009 to 2025. Three studies were published in China, one study was published in Korea, one study was published in America, 1 study was published in Serbia and 2 study was published in Canada. The scope of the study was from 1998 to 2018. The survival volume, sample size, cut-off value and NOS score of each included study were shown in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e.\u003c/p\u003e\u003cp\u003e\u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e\u003ccaption language=\"En\"\u003e\u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e\u003cdiv class=\"CaptionContent\"\u003e\u003cp\u003ePrinciple characteristics of included studies\u003c/p\u003e\u003c/div\u003e\u003c/caption\u003e\u003ccolgroup cols=\"9\"\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c4\" colnum=\"4\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c5\" colnum=\"5\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c6\" colnum=\"6\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c7\" colnum=\"7\"\u003e\u003c/div\u003e\u003cdiv align=\"left\" class=\"colspec\" colname=\"c8\" colnum=\"8\"\u003e\u003c/div\u003e\u003cdiv align=\"char\" char=\".\" class=\"colspec\" colname=\"c9\" colnum=\"9\"\u003e\u003c/div\u003e\u003cthead\u003e\u003ctr\u003e\u003cth align=\"left\" colname=\"c1\"\u003e\u003cp\u003eAuthor\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c2\"\u003e\u003cp\u003eYear\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c3\"\u003e\u003cp\u003eStudy period\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCountry\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c5\"\u003e\u003cp\u003eStudy design\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c6\"\u003e\u003cp\u003ePatients\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c7\"\u003e\u003cp\u003eSex(male/female)\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c8\"\u003e\u003cp\u003eExposure\u003c/p\u003e\u003c/th\u003e\u003cth align=\"left\" colname=\"c9\"\u003e\u003cp\u003eNOS\u003c/p\u003e\u003c/th\u003e\u003c/tr\u003e\u003c/thead\u003e\u003ctbody\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYongho Jee\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2024\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2001\u0026ndash;2018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eKorea\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003erestrospective study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e6526 appendicitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e51.09%/48.91%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePM\u003csub\u003e10\u003c/sub\u003e and season\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e7\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKaplan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2013\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2004\u0026ndash;2008\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCanada\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003erestrospective study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e35811 appendicitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e54%/31%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eO\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eSherbakov\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1999\u0026ndash;2009\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eAmerica\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003erestrospective study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e219426 appendicitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003etemperature\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e8\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eYu\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2025\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1998\u0026ndash;2019\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003erestrospective study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e59128 appendicitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003etemperature\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKaranikolić\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2011\u0026ndash;2013\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eSerbia\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003erestrospective study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e395 appendicitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e45.8%/54.2%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eseasons, changes in atmospheric temperature and pressure,\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eKaplan\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2016\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e1999\u0026ndash;2006\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eCanada\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003erestrospective study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e5191 appendicitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e53.2%/46.8%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003eOzone, Sulfur dioxide, Nitrogen dioxide, Carbon monoxide, PM\u003csub\u003e2.5\u003c/sub\u003e, PM\u003csub\u003e10\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eChen\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2009\u0026ndash;2013\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003erestrospective study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e18400 appendicitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e/\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePM\u003csub\u003e2.5\u003c/sub\u003e, NO\u003csub\u003e2\u003c/sub\u003e, CO, and O\u003csub\u003e3\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e5\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003ctr\u003e\u003ctd align=\"left\" colname=\"c1\"\u003e\u003cp\u003eJi\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c2\"\u003e\u003cp\u003e2023\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c3\"\u003e\u003cp\u003e2016\u0026ndash;2018\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c4\"\u003e\u003cp\u003eChina\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c5\"\u003e\u003cp\u003erestrospective study\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c6\"\u003e\u003cp\u003e1427 appendicitis\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c7\"\u003e\u003cp\u003e82.9%/17.1%\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"left\" colname=\"c8\"\u003e\u003cp\u003ePM\u003csub\u003e2.5\u003c/sub\u003e, NO\u003csub\u003e2\u003c/sub\u003e, SO\u003csub\u003e2\u003c/sub\u003e\u003c/p\u003e\u003c/td\u003e\u003ctd align=\"char\" char=\".\" colname=\"c9\"\u003e\u003cp\u003e6\u003c/p\u003e\u003c/td\u003e\u003c/tr\u003e\u003c/tbody\u003e\u003c/colgroup\u003e\u003ctfoot\u003e\u003ctr\u003e\u003ctd colspan=\"9\"\u003eAbbreviation:NOS, Newcastle-Ottawa Scales.\u003c/td\u003e\u003c/tr\u003e\u003c/tfoot\u003e\u003c/table\u003e\u003c/div\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eBaseline information\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThe baseline information included different exposures OR and 95% CIs. The subgroup analyses by pollutant type revealed significant variations in health risk associations (between-group heterogeneity p\u0026thinsp;=\u0026thinsp;0.005). High temperature exposure showed no significant effect (pooled OR\u0026thinsp;=\u0026thinsp;0.99, 95% CI 0.92\u0026ndash;1.06, I\u0026sup2;=97.5%), while air pollutants demonstrated consistent risk elevations: PM\u003csub\u003e10\u003c/sub\u003e (OR\u0026thinsp;=\u0026thinsp;1.04, 95% CI 1.01\u0026ndash;1.07,I\u0026sup2;=77.4%), O\u003csub\u003e3\u003c/sub\u003e (OR\u0026thinsp;=\u0026thinsp;1.09, 95% CI 1.06\u0026ndash;1.13, I\u0026sup2;=0.0%), and NO\u003csub\u003e2\u003c/sub\u003e (OR\u0026thinsp;=\u0026thinsp;1.13, 95% CI 1.06\u0026ndash;1.20, I\u0026sup2;=75.1%).\u003c/p\u003e\u003cp\u003e\u003cb\u003eHigh temperature\u003c/b\u003e\u003c/p\u003e\u003cp\u003eAmong the eight selected articles, five addressed the impact of temperature on the incidence of appendicitis, we find the I\u003csup\u003e2\u003c/sup\u003e value was 97.5% and we conducted a sensitivity test by using leave-one-out analysis method (Fig.\u0026nbsp;\u003cspan refid=\"Fig2\" class=\"InternalRef\"\u003e2\u003c/span\u003e). The result indicated that Yongjho jee (2024) has a significant impact on the overall result. After excluding the Yongjho jee (2024). We re-analyzed the data and the result shows that I\u003csup\u003e2\u003c/sup\u003e value was 95.2%, indicating significant statistical heterogeneity, and high temperature group was associated with high incidence of incidence of appendicitis (OR\u0026thinsp;=\u0026thinsp;1.07, 95% CI 1.02\u0026ndash;1.12, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). (Fig.\u0026nbsp;\u003cspan refid=\"Fig3\" class=\"InternalRef\"\u003e3\u003c/span\u003e) For publication bias, we conduct Egger's test which indicate that P\u0026thinsp;=\u0026thinsp;0.531. There is no significant publication bias.\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003cb\u003eAir pollution\u003c/b\u003e\u003c/p\u003e\u003cp\u003eThere studies reported the data of O\u003csub\u003e3\u003c/sub\u003e on incidence of appendicitis, after pooling up all the data, we found that the high Ozone group was associated with high incidence of appendicitis (OR\u0026thinsp;=\u0026thinsp;1.08, 95% CI 1.06\u0026ndash;1.11, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). (Fig.\u0026nbsp;\u003cspan refid=\"Fig4\" class=\"InternalRef\"\u003e4\u003c/span\u003e) Three studies reported the data of NO\u003csub\u003e2\u003c/sub\u003e on the incidence of appendicitis, after pooling up all the data, we found that the high NO2 was associated with high incidence of appendicitis (OR\u0026thinsp;=\u0026thinsp;1.13, 95% CI 1.06\u0026ndash;1.20, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). (Fig.\u0026nbsp;\u003cspan refid=\"Fig5\" class=\"InternalRef\"\u003e5\u003c/span\u003e) Four studies reported the data of PM\u003csub\u003e10\u003c/sub\u003e on incidence of appendicitis, after pooling up all the data, we found that the PM\u003csub\u003e10\u003c/sub\u003e was associated with high incidence of appendicitis (OR\u0026thinsp;=\u0026thinsp;1.04, 95% CI 1.01\u0026ndash;1.07, P\u0026thinsp;\u0026lt;\u0026thinsp;0.01). (Fig.\u0026nbsp;\u003cspan refid=\"Fig6\" class=\"InternalRef\"\u003e6\u003c/span\u003e)\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e\u003cp\u003e\u003c/p\u003e"},{"header":"Discussion","content":"\u003cp\u003eA total of eight studies were included in the current meta-analysis. As for the exposure, after pooling up all the data, we found that the high temperature, Ozone, NO\u003csub\u003e2\u003c/sub\u003e and PM\u003csub\u003e10\u003c/sub\u003e was associated with high incidence of appendicitis. Our findings demonstrate significant correlations between these exposures and appendicitis risk, supporting the hypothesis that environmental triggers may contribute to the pathogenesis of this common surgical condition.\u003c/p\u003e\u003cp\u003ePrevious studies indicated that mortality risk attributable to high and low ambient temperature\u003csup\u003e[\u003cspan citationid=\"CR29\" class=\"CitationRef\"\u003e29\u003c/span\u003e, \u003cspan citationid=\"CR30\" class=\"CitationRef\"\u003e30\u003c/span\u003e]\u003c/sup\u003e. We found higher ambient temperature was associated with increased appendicitis incidence. Possible mechanisms may include Dietary and Behavioral Changes. Warmer weather may alter food storage conditions, increasing the risk of bacterial contamination and gastrointestinal infections\u003csup\u003e[\u003cspan citationid=\"CR31\" class=\"CitationRef\"\u003e31\u003c/span\u003e]\u003c/sup\u003e, which could indirectly trigger appendicitis. Second is immune Modulation. Heat stress may influence systemic inflammation or local immune responses in the appendix. Our results align with ecological studies reporting higher appendicitis rates in summer months\u003csup\u003e[\u003cspan additionalcitationids=\"CR33\" citationid=\"CR32\" class=\"CitationRef\"\u003e32\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR34\" class=\"CitationRef\"\u003e34\u003c/span\u003e]\u003c/sup\u003e.\u003c/p\u003e\u003cp\u003ePrevious studies corroborated that particulate matter exposure could induce healthy problems\u003csup\u003e[\u003cspan citationid=\"CR35\" class=\"CitationRef\"\u003e35\u003c/span\u003e]\u003c/sup\u003e. We found a positive association with appendicitis, possibly due to systemic inflammation\u003csup\u003e[\u003cspan additionalcitationids=\"CR37\" citationid=\"CR36\" class=\"CitationRef\"\u003e36\u003c/span\u003e\u0026ndash;\u003cspan citationid=\"CR38\" class=\"CitationRef\"\u003e38\u003c/span\u003e]\u003c/sup\u003e or oxidative stress disrupting gut barrier function. We also discovered that urban airborne particulate matter via contaminated food can alter the gut microbiome and immune function under normal and inflammatory conditions\u003csup\u003e[\u003cspan citationid=\"CR39\" class=\"CitationRef\"\u003e39\u003c/span\u003e]\u003c/sup\u003e. The effects of NO\u003csub\u003e2\u003c/sub\u003e and O\u003csub\u003e3\u003c/sub\u003e were somewhat weaker but still significant. These pollutants may act through Oxidative stress pathways damaging intestinal epithelium\u003csup\u003e[\u003cspan citationid=\"CR40\" class=\"CitationRef\"\u003e40\u003c/span\u003e]\u003c/sup\u003e and DNA methylation\u003csup\u003e[\u003cspan citationid=\"CR41\" class=\"CitationRef\"\u003e41\u003c/span\u003e]\u003c/sup\u003e which influences inflammation. These pollutants may promote mucosal irritation or ischemic changes in the appendix, though the exact pathways remain unclear.\u003c/p\u003e\u003cp\u003eWhile our study establishes epidemiological associations, several potential biological pathways warrant discussion. First is microbiome interaction. Emerging research indicates that both temperature extremes and air pollutants can alter gut microbiota composition\u003csup\u003e[\u003cspan citationid=\"CR42\" class=\"CitationRef\"\u003e42\u003c/span\u003e]\u003c/sup\u003e. Such dysbiosis might predispose to appendiceal inflammation. Second is epithelial barrier disruption. Experimental studies show that PM\u003csub\u003e2.5\u003c/sub\u003e exposure leads to loss of barrier function in human nasal epithelium\u003csup\u003e[\u003cspan citationid=\"CR43\" class=\"CitationRef\"\u003e43\u003c/span\u003e]\u003c/sup\u003e, we speculate that PM\u003csub\u003e2.5\u003c/sub\u003e may effects intestinal epithelial cells which potentially facilitate bacterial translocation.\u003c/p\u003e\u003cp\u003eTo our knowledge, our study is the first study to pool up environmental exposures on appendicitis. In our study, our analysis benefits from comprehensive inclusion of multiple environmental factors. However, several limitations merit consideration. Most studies used local pollution estimates rather than personal exposure data, potentially introducing misclassification. Variability in diagnostic criteria for appendicitis across studies may affect outcome classification. Therefore, multicenter, multiregional and high-quality studies should be carried out in the future.\u003c/p\u003e\u003cp\u003eThis study provides robust epidemiological evidence that environmental factors-particularly temperature and air pollution-are associated with appendicitis incidence. While further research is needed to establish causality and mechanistic pathways, these findings highlight the potential for environmental interventions to mitigate appendicitis risk. Clinicians and policymakers should consider environmental health strategies as part of broader appendicitis prevention efforts.\u003c/p\u003e\u003cp\u003eIn conclusion, these findings have several important implications suggesting these exposures may represent modifiable risk factors for disease prevention. The findings advocate targeted public health measures, including heat-health warning systems that incorporate appendicitis risk alerts, stricter air quality regulations with consideration of gastrointestinal health impacts, and community education programs about protective behaviors during high-risk environmental conditions. Clinicians should maintain heightened awareness of potential increased appendicitis presentations following extreme weather events or pollution episodes. These collective efforts could transform appendicitis from being viewed solely as a surgical emergency to a preventable condition influenced by environmental determinants, ultimately reducing its global disease burden through both clinical and environmental health approaches. The results underscore the importance of integrating environmental risk reduction into broader appendicitis prevention strategies.\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eData availability:\u003c/strong\u003e The datasets generated and/or analyzed during the current study are not publicly available due but are available from the corresponding author upon reasonable request.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u003c/strong\u003e The authors declare no conflicts of interest.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions:\u0026nbsp;\u003c/strong\u003eData extraction, Chen-Yu Xiang and Xiao-Yu Liu; quality assessments, Wei Lu, Jun-Nan Zhao; data analysis, Chen-Yu Xiang and Wei Lu; writing the main manuscript text, Chen-Yu Xiang and Xiao-Yu Liu; writing-review and editing, Chen-Yu Xiang and Wei Lu. Chen-Yu Xiang prepared figures. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgments:\u003c/strong\u003e We acknowledge all the authors whose publications are referred in our article.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\n\u003cli\u003eLiu F, Lv Q, Wang C Y, et al. Single-port laparoscopic appendectomy using new surgical procedure versus conventional three-port laparoscopic appendectomy [J]. Updates Surg, 2024, 76(4): 1347-55.\u003c/li\u003e\n\u003cli\u003eCeresoli M, Zucchi A, Allievi N, et al. Acute appendicitis: Epidemiology, treatment and outcomes- analysis of 16544 consecutive cases [J]. World J Gastrointest Surg, 2016, 8(10): 693-9.\u003c/li\u003e\n\u003cli\u003eKrzyzak M, Mulrooney S M. Acute Appendicitis Review: Background, Epidemiology, Diagnosis, and Treatment [J]. 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Allergy Asthma \u0026amp; Immunology Research, 2020, 12(1): 56-71.\u003c/li\u003e\n\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":true,"highlight":"","institution":"","isAcceptedByJournal":false,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true},"keywords":"environment factors, appendicitis, temperature, air pollution","lastPublishedDoi":"10.21203/rs.3.rs-7168890/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-7168890/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003ch2\u003ePurpose\u003c/h2\u003e\u003cp\u003eThe purpose of this study was to analyze whether environment risk factors had an impact on appendicitis incidence.\u003c/p\u003e\u003ch2\u003eMethods\u003c/h2\u003e\u003cp\u003eThis study investigated the association between environmental risk factors and the incidence of appendicitis through a meta-analysis. Through searching in four databases (PubMed, Cochrane, Web of Science and Embase) up to May 2025 for cohort studies assessing the association between environment risk factors and appendicitis incidence. After study selection, a total of eight studies from five countries were included in the meta-analysis. Random-effect model was employed in the study, I\u003csup\u003e2\u003c/sup\u003e statistic assessed heterogeneity, and the Egger's test detected publication bias.\u003c/p\u003e\u003ch2\u003eResults\u003c/h2\u003e\u003cp\u003eA total of eight studies including 346304 appendicitis patients were included in this study. Analysis of overall odds ratio (OR) of appendicitis incidence associated with environment risk factors was estimated to be statistic significant (OR\u0026thinsp;=\u0026thinsp;1.06, 95% CI 1.03\u0026ndash;1.09). Further subgroup analysis showed that elevated temperature, PM₁₀, ozone (O₃), and nitrogen dioxide (NO₂) were significantly associated with an increased risk of appendicitis. Specifically, each unit rise in temperature was linked to a 7% higher risk (OR\u0026thinsp;=\u0026thinsp;1.07, 95% CI 1.02\u0026ndash;1.12), while increases in PM₁₀, O₃, and NO₂ were associated with 4% (OR\u0026thinsp;=\u0026thinsp;1.04, 95% CI 1.01\u0026ndash;1.07), 8% (OR\u0026thinsp;=\u0026thinsp;1.08, 95% CI 1.06\u0026ndash;1.11), and 13% (OR\u0026thinsp;=\u0026thinsp;1.13, 95% CI 1.06\u0026ndash;1.20) elevated risks, respectively. Notably, NO₂ exhibited the strongest effect. These findings suggest that environmental factors, particularly air pollutants and high temperature, may contribute to a higher incidence of appendicitis.\u003c/p\u003e\u003ch2\u003eConclusion\u003c/h2\u003e\u003cp\u003eWe found that the high temperature, O\u003csub\u003e3\u003c/sub\u003e, NO\u003csub\u003e2\u003c/sub\u003e and PM\u003csub\u003e10\u003c/sub\u003e was associated with high incidence of appendicitis.\u003c/p\u003e","manuscriptTitle":"Environmental Risk Factors and Appendicitis Incidence: A Pooled Up Analysis","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-08-19 12:27:22","doi":"10.21203/rs.3.rs-7168890/v1","editorialEvents":[{"type":"communityComments","content":0}],"status":"published","journal":{"display":true,"email":"[email protected]","identity":"researchsquare","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":true,"externalIdentity":"","sideBox":"","snPcode":"","submissionUrl":"/submission","title":"Research Square","twitterHandle":"researchsquare","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"","reportingPortfolio":"","inReviewEnabled":false,"inReviewRevisionsEnabled":true}}],"origin":"","ownerIdentity":"77b41469-5052-40dd-89ef-aa5c5cc0d16b","owner":[],"postedDate":"August 19th, 2025","published":true,"recentEditorialEvents":[],"rejectedJournal":[],"revision":"","amendment":"","status":"posted","subjectAreas":[{"id":53289822,"name":"Health sciences/Diseases"},{"id":53289823,"name":"Earth and environmental sciences/Environmental sciences"},{"id":53289824,"name":"Health sciences/Health care"},{"id":53289825,"name":"Health sciences/Medical research"},{"id":53289826,"name":"Health sciences/Risk factors"}],"tags":[],"updatedAt":"2025-08-29T07:23:35+00:00","versionOfRecord":[],"versionCreatedAt":"2025-08-19 12:27:22","video":"","vorDoi":"","vorDoiUrl":"","workflowStages":[]},"version":"v1","identity":"rs-7168890","journalConfig":"researchsquare"},"__N_SSP":true},"page":"/article/[identity]/[[...version]]","query":{"redirect":"/article/rs-7168890","identity":"rs-7168890","version":["v1"]},"buildId":"8U1c8b4HqxoKbykW_rLl7","isFallback":false,"isExperimentalCompile":false,"dynamicIds":[84888],"gssp":true,"scriptLoader":[]}