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The indicative role of inflammatory index in the progression of periodontal attachment loss

European Journal of Medical Research volume 28, Article number: 287 (2023) Cite this article

Abstract

Objective

To explore the forewarning immunological indicators during periodontal attachment loss progression in American adults.

Methods

A total of 5744 participants with periodontal attachment loss were enrolled from the National Health and Nutrition Examination Surveys (NHANES) 2009–2014. In which, dependent variable was the counts of teeth with severe attachment loss (depth of periodontal probing was above 5 mm). Independent variables were circulatory immunological indexes, including counts of white blood cells (WBC), Lymphocytes, Monocytes, Neutrophils, Eosinophils, and Basophils. The association among variables was examined using multivariable linear regression models, fitting with smoothing curves, and generalizing additive models.

Results

Based on the indicators of 5744 subjects, we found that severe attachment loss tended to occur in the elderly or males and was accompanied by higher WBC, Monocytes, and Neutrophils, as well as lower poverty-income ratio and educational qualification. WBC (above the inflection point: 6200 cells/µL) and Neutrophils (above the inflection point: 3300 cells/µL) counts were positively associated with attachment loss progression in each multivariable linear regression model. On subgroup analyses, stratified by sex and race, the positive correlation of WBC or Neutrophils with severe attachment loss was stable in both men and women, as well as in all races except blacks (WBC β = − 0.0576, 95% CI − 0.1945 to 0.0793, Neutrophils β = − 0.0527, 95% CI − 0.2285 to 0.1231).

Conclusion

Increasing WBC (above 6200 cells/µL) and Neutrophils (above 3300 cells/µL) counts were risk indicators of severe periodontal attachment loss among all races, except in blacks.

Introduction

With a prevalence of 47% in the American population over 30 years old [1, 2], periodontitis impaired the aesthetic and oral function [3, 4], mainly manifested as attachment loss and alveolar bone resorption [5,6,7]. Current studies focused on the correlated inflammation or immunity factors of severe periodontitis [8], but the in-depth monitoring of immunological indicators during attachment loss progression remains unknown.

On accounts of the abundant systemic circulation of the maxillofacial region, periodontitis causes or exacerbates comorbidities and resulting changes in circulating immune indicators (including white blood cells, Neutrophils, etc.) [7, 9, 10]. Previous studies showed that severe periodontitis was accompanied by changes in the levels of inflammatory indicators [11, 12], for example, patients with periodontitis are often accompanied by an increase in mean platelet volume and a decrease in eosinophilic counts. Meanwhile, circulatory immune indexes were widely utilized as forewarning or diagnostic criteria of infectious diseases. For instance, white blood cell (WBC) counts were generally expected to be closely associated with a respiratory infection, which diagnoses pneumonia, determines its etiology, and predict disease progression [13, 14]. To forewarn the occurrence and progression of severe periodontitis, it is necessary to explore the potential relationship between circulatory immunological indexes and periodontal attachment loss progression.

In this study, we aimed to explore the association between severe attachment loss progression and circulatory immunological indicators by multivariable linear regression based on the NHANES database. Severe periodontal attachment loss tended to occur in males and was accompanied by higher WBC, Monocytes, and Neutrophils. Furthermore, WBC, Monocytes, and Neutrophils counts were closely associated with periodontal attachment loss. This study sought to shed light on the correlation between the progression of severe periodontitis and immune-related indicators.

Methods

Study population

Data of the current study were abstracted from the National Health and Nutrition Examination Survey (NHANES). In total, 14,071 participants were enrolled from NHANES between 2009 to 2014. After excluding participants (n = 2336) with incomplete records of periodontal examination, 11,735 participants were available. Further, excluding participants who had the attachment loss < 5 mm or > 2 mm (n = 5771), and with missing data of the immune cell examination (n = 222), 5744 participants were finally enrolled in the study. The study was approved by the review board of the National Center for Health Statistics.

Dependent variable

Periodontal attachment loss was identified by dental examiners, who were dentists (D.D.S./D.M.D.) licensed in at least one U.S. state. All oral health assessments occurred in a designated room at the mobile examination center (MEC). In this experiment, attachment loss ≥ 5 mm was defined as severe attachment loss [15]. In addition, dependent variable was counts of teeth with severe attachment loss.

Independent variables and covariates

Circulatory immunological indexes (including white blood cells, Lymphocytes, Monocytes, Neutrophils, Eosinophils, and Basophils) were obtained from laboratory data. For covariates, including age, gender, education level (< 9th grade, 9–11th grade, high school, college, etc.), race/ethnicity (Mexican American, Hispanic, non-Hispanic White, non-Hispanic Black, and other races), PIR (poverty income ratio), Body Mass Index (BMI). Circulatory immunological indexes and other covariates acquisition processes are available on the NHANES dataset (http://cdc.gov/nchs/nhanes).

Statistical analysis

All statistical analyses were performed by using R (http://www.R-project.org), with statistical significance set at P < 0.05. All estimates were calculated by using sample weights following the analytical guideline edited by NCHS. Three multivariable linear regression models were constructed by hierarchical multiple regression to test the significance of variables: model 1, no covariates were adjusted; model 2, age, gender, and race were adjusted; model 3, all covariates presented in Table 1 were adjusted. Furthermore, smooth curve fittings and generalized additive models were used to address the nonlinearity. The inflection points were calculated using a recursive algorithm, with a two-piecewise linear regression model conducted on both sides of the inflection point when nonlinearity was detected.

Table 1 Characteristics of the study population
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Results

The demographic and laboratory data of the 5744 participants (3217 men and 2527 women), with the weighted characteristics of the participants subclassified based on quartiles of attachment loss teeth counts (Q1: 0; Q2: 1; Q3: 2–5; and Q4: 6–27), as presented in Table 1. There were significant differences in baseline characteristics between the attachment loss teeth quartiles, except for the counts of Eosinophils, Basophils, and Lymphocytes. Participants with generalized periodontal attachment loss tend to occur in the elderly or males and are accompanied with higher BMI, WBC, Monocytes, Neutrophils, and Eosinophils, as well as lower PIR and educational qualification.

The results of the multivariate regression analyses are presented in Tables 2 and 3. In the unadjusted model, WBC (β = 0.1632, 95% CI 0.1051–0.2214, P < 0.000001) and Neutrophils (β = 0.2069, 95% CI 0.1344–0.2795, P < 0.000001) were positively correlated to attachment loss progression. After adjustment for confounders, those positive associations were stable in model 2 (P < 0.000001) and model 3 (P < 0.000001). After converting WBC and Neutrophils from continuous variables to categorical variables (quartiles), the trends remained significant among different WBC or Neutrophils quartile groups (P < 0.001). Furthermore, individuals in the highest WBC and Neutrophils quartile had 0.8392 (P < 0.00001) and 0.8663 (P < 0.00001) more attachment loss than those in the lowest quartile, respectively.

Table 2 Association between WBC and periodontal attachment loss progression
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Table 3 Association between Neutrophils and periodontal attachment loss
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Smooth curve fittings and generalized additive models used to characterize the nonlinear relationship between WBC/Neutrophils and attachment loss progression are shown in Figs. 1, 2. The points of inflection were identified using the two-piecewise linear regression models, at 6200 cells/µL (WBC counts) and 3300 cells/µL (Neutrophils counts), respectively (Tables 4 and 5). For WBC < 620 cells/µL or Neutrophils < 3300 cells/µL, every 1000 cells/µL increase of WBC or Neutrophils was correlated with 0.0784 (95% CI −0.2836 to 0.1269) or 0.1494 (95% CI − 0.4550 to 0.1562) less attachment loss; by comparison, for individuals with WBC > 6200 cells/µL or Neutrophils > 3300 cells/µL, every 1000 cells/µL increase of WBC or Neutrophils was significantly associated with 0.2273 (95% CI 0.1492–0.3054) or 0.2737 (95% CI 0.1823–0.3651) more attachment loss.

Fig. 1
figure 1

The association between WBC and periodontal attachment loss. a Each black point represents a sample. b Solid rad line represents the smooth curve fit between variables. Blue bands represent the 95% of confidence interval from the fit

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Fig. 2
figure 2

The association between Neutrophils and periodontal attachment loss. a Each black point represents a sample. b Solid rad line represents the smooth curve fit between variables. Blue bands represent the 95% of confidence interval from the fit

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Table 4 Threshold effect analysis of WBC on the progression of attachment loss using the two piecewise linear regression model
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Table 5 Threshold effect analysis of Neutrophils on the progression of attachment loss using the two piecewise linear regression model
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On subgroup analyses, stratified by sex and race/ethnicity, reported in Tables 2 and 3, the positive correlation among WBC, Neutrophils and attachment loss progression remained in both males (P < 0.0001) and females (P < 0.001), as well as in Mexican American (P < 0.05), Hispanics (P < 0.05), whites (P < 0.000001), and other races (P < 0.05), but not in blacks. Among blacks, WBC (β = -0.0576, 95%CI: -0.1945–0.0793) or Neutrophils (β =  − 0.0527, 95% CI − 0.2285 to 0.1231) were negatively associated with attachment loss progression (Fig. 3).

Fig. 3
figure 3

The association between WBC, Neutrophils and periodontal attachment loss, stratified by race

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Discussion

Accompanied with attachment loss, severe periodontitis caused serious aesthetic problems and reduced chewing efficiency [16, 17]. Previous studies suggested that the progression of attachment loss was accompanied with increasing circulatory immunological indexes in severe periodontitis [13, 14], but immune cell counts serve as forewarning or diagnostic criteria for severe attachment loss or periodontitis progression remains unclear. Our multivariate logistic regression analyses indicated that elevated WBC or Neutrophils was correlated with attachment loss progression. However, on subgroup analysis, we identified the negative relationship between WBC or Neutrophils and attachment loss among blacks.

Phagocytosis by WBC, Neutrophils, and Monocytes constitutes the main defense mechanism against bacterial challenges in periodontitis [18]. As the enriched immune cell killing bacteria and destroying inflamed tissues [19], immunity homeostasis was essential for periodontal attachment maintenance [20]. In consist with our results, a previous study showed that severe periodontitis accompanied with higher WBC or Neutrophils levels than the healthy population [6]. On the other hand, infectious viruses, including Human simplex virus-1, Epstein-Barr virus, and Human cytomegalo virus, were commonly involved in the occurrence and development of periodontitis or attachment loss [21]. Simple viral infections accompanied with the decrease of WBC and Neutrophils [22], while combination of bacterial infections promotes WBC elevation [23]. Recent research identified the inflection point of fluctuating confounder was utilized as forewarning of periodontitis risk, and periodontal status [24]. Our multivariable linear regression analyses suggested that participants with WBC above 6200 cells/µl or Neutrophils above 3300 cells/µl obtained higher risk of periodontal attachment loss, which can serve for severe periodontitis prevention and treatment.

Previous studies identified the racial differences of WBC or Neutrophils counts between blacks and other races [25, 26]. In which, WBC or Neutrophils counts were significantly lower in blacks during dental plaque accumulation, but hyperactivity of circulating neutrophils appeared in blacks [26]. Importantly, the reactivity of oxidative burst was significantly lower in neutrophils from blacks, especially from African American males [27]. Periodontal attachment loss-related racial differences can provide accurate guidance for subsequent community prevention.

This study demonstrated the association between circulatory immunological indicators and periodontal attachment loss. However, several limitations are noticeable. First, all self-reported information might cause recall bias or misclassification bias. Second, further studies with larger sample sizes using more relevant variables (such as gingival sulcus fluid data and bone destruction) may discover more accurate factors in periodontal attachment loss. Third, circulating immune cells counts were affected by the whole-body state, periodontal pocket related immunological indexes may have better reproducibility.

Conclusion

Our study suggested that increasing WBC (above 6200 cells/µL) and Neutrophils (above 3300 cells/µL) counts were potential risk indicators of periodontal attachment loss progression, which provides an early warning for severe periodontitis.

Availability of data and materials

Publicly available datasets were analyzed in this study. Data used for this study are available on the NHANES website: https://wwwn.cdc.gov/nchs/nhanes/.

References

  1. Eke PI, Dye BA, Wei L, Thornton-Evans GO, Genco RJ, Cdc Periodontal Disease Surveillance workgroup. Prevalence of periodontitis in adults in the United States: 2009 and 2010. J Dent Res. 2012;91(10):914–20.

    Article  PubMed  CAS  Google Scholar 

  2. Eke PI, Dye BA, Wei L, Slade GD, Thornton-Evans GO, Borgnakke WS, et al. Update on prevalence of periodontitis in adults in the United States: NHANES 2009 to 2012. J Periodontol. 2015;86(5):611–22.

    Article  PubMed  PubMed Central  Google Scholar 

  3. Chapple ILC, Mealey BL, Van Dyke TE, Bartold PM, Dommisch H, Eickholz P, et al. Periodontal health and gingival diseases and conditions on an intact and a reduced periodontium: Consensus report of workgroup 1 of the 2017 World Workshop on the Classification of Periodontal and Peri-Implant Diseases and Conditions. J Periodontol. 2018;89(Suppl 1):S74–84.

    PubMed  Google Scholar 

  4. Mehrotra N, Singh S. Periodontitis. Treasure Island: StatPearls; 2022.

    Google Scholar 

  5. Gumus P, Nizam N, Nalbantsoy A, Ozcaka O, Buduneli N. Saliva and serum levels of pentraxin-3 and interleukin-1beta in generalized aggressive or chronic periodontitis. J Periodontol. 2014;85(3):e40–6.

    PubMed  CAS  Google Scholar 

  6. Botelho J, Machado V, Hussain SB, Zehra SA, Proenca L, Orlandi M, et al. Periodontitis and circulating blood cell profiles: a systematic review and meta-analysis. Exp Hematol. 2021;93:1–13.

    Article  PubMed  Google Scholar 

  7. Irwandi RA, Kuswandani SO, Harden S, Marletta D, D’Aiuto F. Circulating inflammatory cell profiling and periodontitis: a systematic review and meta-analysis. J Leukoc Biol. 2022;111(5):1069–96.

    Article  PubMed  CAS  Google Scholar 

  8. Gaddale R, Mudda JA, Karthikeyan I, Desai SR, Shinde H, Deshpande P. Changes in cellular and molecular components of peripheral blood in patients with generalized aggressive periodontitis. J Investig Clin Dent. 2016;7(1):59–64.

    Article  PubMed  Google Scholar 

  9. Hajishengallis G, Chavakis T. Local and systemic mechanisms linking periodontal disease and inflammatory comorbidities. Nat Rev Immunol. 2021;21(7):426–40.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  10. Liccardo D, Cannavo A, Spagnuolo G, Ferrara N, Cittadini A, Rengo C, et al. Periodontal disease: a risk factor for diabetes and cardiovascular disease. Int J Mol Sci. 2019;20(6):1414.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  11. Anand PS, Sagar DK, Mishra S, Narang S, Kamath KP, Anil S. Total and differential leukocyte counts in the peripheral blood of patients with generalised aggressive periodontitis. Oral Health Prev Dent. 2016;14(5):443–50.

    PubMed  Google Scholar 

  12. Lopez R, Loos BG, Baelum V. Hematological features in adolescents with periodontitis. Clin Oral Investig. 2012;16(4):1209–16.

    Article  PubMed  Google Scholar 

  13. Ustaoglu G, Erdal E, Inanir M. Does periodontitis affect mean platelet volume(MPV) and plateletcrit (PCT) levels in healthy adults? Rev Assoc Med Bras. 2020;66(2):133–8.

    Article  PubMed  Google Scholar 

  14. Anand PS, Sagar DK, Ashok S, Kamath KP. Association of aggressive periodontitis with reduced erythrocyte counts and reduced hemoglobin levels. J Periodontal Res. 2014;49(6):719–28.

    Article  PubMed  CAS  Google Scholar 

  15. Tonetti MS, Greenwell H, Kornman KS. Staging and grading of periodontitis: framework and proposal of a new classification and case definition. J Periodontol. 2018;89(Suppl 1):S159–72.

    PubMed  Google Scholar 

  16. Liu X, Dai B, Chuai Y, Hu M, Zhang H. Associations between vitamin D levels and periodontal attachment loss. Clin Oral Investig. 2023. https://doi.org/10.1007/s00784-023-05100-4.

    Article  PubMed  PubMed Central  Google Scholar 

  17. Sun W, Dai B, Hong L, Zhang H. The risk of dental restoration-related lead exposure on renal function. Chemosphere. 2023;337: 139405.

    Article  PubMed  CAS  Google Scholar 

  18. Carneiro VM, Bezerra AC, Guimaraes Mdo C, Muniz-Junqueira MI. Decreased phagocytic function in neutrophils and monocytes from peripheral blood in periodontal disease. J Appl Oral Sci. 2012;20(5):503–9.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Hajishengallis G. New developments in neutrophil biology and periodontitis. Periodontol 2000. 2000;82(1):78–92.

    Article  Google Scholar 

  20. Hajishengallis G, Chavakis T, Hajishengallis E, Lambris JD. Neutrophil homeostasis and inflammation: novel paradigms from studying periodontitis. J Leukoc Biol. 2015;98(4):539–48.

    Article  PubMed  CAS  Google Scholar 

  21. Puletic M, Popovic B, Jankovic S, Brajovic G. Detection rates of periodontal bacteria and herpesviruses in different forms of periodontal disease. Microbiol Immunol. 2020;64(12):815–24.

    Article  PubMed  CAS  Google Scholar 

  22. Pujani M, Raychaudhuri S, Verma N, Kaur H, Agarwal S, Singh M, et al. Association of Hematologic biomarkers and their combinations with disease severity and mortality in COVID-19- an Indian perspective. Am J Blood Res. 2021;11(2):180–90.

    PubMed  CAS  PubMed Central  Google Scholar 

  23. Qin R, He L, Yang Z, Jia N, Chen R, Xie J, et al. Identification of parameters representative of immune dysfunction in patients with severe and fatal COVID-19 infection: a systematic review and meta-analysis. Clin Rev Allergy Immunol. 2023;64(1):33–65.

    Article  PubMed  CAS  Google Scholar 

  24. Li W, Shi D, Song W, Xu L, Zhang L, Feng X, et al. A novel U-shaped relationship between BMI and risk of generalized aggressive periodontitis in Chinese: a cross-sectional study. J Periodontol. 2019;90(1):82–9.

    Article  PubMed  Google Scholar 

  25. Chen W, Srinivasan SR, Xu J, Berenson GS. Black-white divergence in the relation of white blood cell count to metabolic syndrome in preadolescents, adolescents, and young adults: the Bogalusa Heart Study. Diabetes Care. 2010;33(11):2474–6.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Wahaidi VY, Dowsett SA, Eckert GJ, Kowolik MJ. Neutrophil response to dental plaque by gender and race. J Dent Res. 2009;88(8):709–14.

    Article  PubMed  CAS  PubMed Central  Google Scholar 

  27. Siddiqi M, Garcia ZC, Stein DS, Denny TN, Spolarics Z. Relationship between oxidative burst activity and CD11b expression in neutrophils and monocytes from healthy individuals: effects of race and gender. Cytometry. 2001;46(4):243–6.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

Not applicable.

Funding

This work was supported by the 2022 Disciplinary Construction Project in School of Dentistry, Anhui Medical University (2022xkfyhz09), and Anhui Medical University Student Innovation and Entrepreneurship Training Program (S202210366087 and AYDDCxj2022101).

Author information

Author notes

  1. Wenhao Zhang, Yulong Zhang and Cong Jin are contributed equally to this study.

Authors and Affiliations

  1. Key Laboratory of Oral Diseases Research of Anhui Province, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China

    Wenhao Zhang, Yulong Zhang, Cong Jin, Ruihan Fang, Ruixue Hua & Hengguo Zhang

  2. The First Affiliated Hospital of USTC, Division of Life Sciences and Medicine, University of Science and Technology of China, Hefei, 230032, China

    Xiaodong Zang

  3. Department of Dental Implantology, College & Hospital of Stomatology, Anhui Medical University, Hefei, 230032, China

    Hengguo Zhang

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  1. Wenhao Zhang
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Contributions

ZW collected the data and wrote the manuscript; ZY and JC assisted ZW with data analyses. ZY, FR, HR and ZX performed statistical analyses. ZH conceived of this study. ZH and ZX analyzed the data and revised the manuscript. All authors read and approved the final manuscript.

Corresponding authors

Correspondence to Xiaodong Zang or Hengguo Zhang.

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The studies involving human participants were reviewed and approved by the institutional review board of the National Center for Health Statistics, CDC. The patients/participants provided their written informed consent to participate in this study.

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All authors agree to publish.

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The authors declare no competing interests.

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Zhang, W., Zhang, Y., Jin, C. et al. The indicative role of inflammatory index in the progression of periodontal attachment loss. Eur J Med Res 28, 287 (2023). https://doi.org/10.1186/s40001-023-01247-8

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European Journal of Medical Research

ISSN: 2047-783X

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