Key Words: Anemia; Chronic Periodontitis; Chronic Disease; Hematocrit; Smokers; Smokeless Tobacco.

Transcription

1 International Journal of Oral & Maxillofacial Pathology. 2013;4(2):18-23 ISSN Available online at or Original Article Anemia of Chronic Disease, Periodontal Disease and Tobacco use: An Association Based on Hematological Parameters Nagaraj B Kalburgi, Arati C Koregol, Akshay Muley, Shivraj Warad, Sandeep Patil Abstract Aims: Anemia of chronic disease is a frequent complication of chronic inflammatory conditions. The aim of the study was to investigate the clinical parameters and signs of anemia of chronic disease in chronic periodontitis patients in non-tobacco users, smokers and smokeless tobacco users. Materials and Methods: Present study included a total of 90 chronic periodontitis patients of which 30 non-tobacco users, 30 smokers and 30 smokeless tobacco users in the a group of years. Clinical parameters including Plaque Index, Gingival Index, Probing Depth and Clinical Attachment Loss were recorded. Laboratory blood investigations included Hemoglobin, Number of erythrocytes, Hematocrit/Packed cell volume, Mean corpuscular volume, Mean corpuscular hemoglobin and Mean corpuscular hemoglobin concentration were considered. Results: The values of Hemoglobin, Number of erythrocytes and Hematocrit/Packed cell volume were significantly lower in smokeless tobacco users group followed by smokers group and then by non-tobacco users group. In smokers and smokeless tobacco users groups, Plaque Index showed statistically significant negative correlation with Hemoglobin, Number of erythrocytes and Hematocrit/Packed cell volume. Conclusion: The current study indicates periodontitis needs to be considered as a chronic disease and together with the effect of cigarette smoking and/or smokeless tobacco may affect the systemic markers related to anemia of chronic disease. Key Words: Anemia; Chronic Periodontitis; Chronic Disease; Hematocrit; Smokers; Smokeless Tobacco. Nagaraj B Kalburgi, Arati C Koregol, Akshay Muley, Shivraj Warad, Sandeep Patil. Anemia of Chronic Disease, Periodontal Disease and Tobacco use: An Association Based on Hematological Parameters. International Journal of Oral & Maxillofacial Pathology; 2013:4(2): International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All Rights Reserved. Received on: 23/02/2013 Accepted on: 04/08/2013 Introduction Periodontitis is a multifactorial disease. It is widely recognized that certain systemic diseases such as osteoporosis, diabetes and immune diseases may increase the risk of periodontal diseases. However recently, a great deal of interest has been generated to explore the role that chronic oral diseases have on systemic health. The hypothesis that periodontal infections may be risk factors and indicators for important medical outcomes represents a paradigm shift in thinking about causality and directionality of oral and systemic associations. 1-3 However, the manifestation and progression of periodontitis is influenced by a wide variety of determinants and factors like systemic, genetic and environmental risk factors. Smoking tobacco and smokeless tobacco in the form of loose leaf, pouch or snuff 4 are one of the major environmental risk factors for periodontal disease. Smoking and smokeless tobacco have shown to impair various aspects of innate and immune host responses. 5 Smoking impairs numerous functions of oral and peripheral neutrophils like phagocytosis, superoxide and hydrogen peroxide generation, integrin expression and protease inhibitor production. Smoking tobacco has also shown to increase the production of IL- 1, IL-6 and TNF-α in gingival crevicular fluid and peripheral blood. 6 Use of tobacco in smokeless form is capable of stimulating Prostaglandin E2 (PGE2) and Interleukin-1 release by human gingival keratinocytes and the levels were higher in ST users as compared to non-users. Such inflammatory cytokines can depress erythropoietin production leading to the development of anemia. 1,7 Anemia of chronic disease (ACD) is a cytokine mediated clinical entity commonly encountered in clinical practice and a frequent complication of chronic inflammatory conditions. 6 It is defined as the anemia that occurs in chronic infections, inflammatory conditions, or neoplastic disorders that is not due to marrow 2013 International Journal of Oral and Maxillofacial Pathology. Published by Publishing Division, Celesta Software Private Limited. All Rights Reserved

2 19 Nagaraj B.Kalburgi, et al. ISSN deficiencies or other diseases and occurs despite the presence of adequate iron stores and vitamins. 1 Hutter et al. 8 suggested that periodontitis may have systemic effects and may tend towards anemia. Various susceptibility factors may interact to influence the host response generally and the immune response specifically. 9 Recent evidence suggests that the control and prevention of oral diseases, especially periodontitis, is important for patients with various systemic conditions that can be impacted by oral infections. As per available literature and to our knowledge this is the first study on evaluation of effect of smokeless tobacco and ACD in chronic periodontitis subjects. So the purpose of this study was to investigate the clinical parameters and signs of anemia of chronic disease in chronic periodontitis patients in non-tobacco users, smokers and smokeless tobacco users which will be of great importance in the diagnostic and preventive strategy of periodontal diseases. Materials and Methods The present study was conducted in the outpatient Department of Periodontics. The study population included a total 90 chronic periodontitis patients in the age group of years of which 30 were non-tobacco users, 30 smokers and 30 smokeless tobacco users. All the subjects were systemically healthy males. Exclusion criteria applied were females, history of periodontal treatment or use of vitamin supplements, antibiotics or iron supplements within previous six months, self reported history of any acute or chronic medical conditions including diabetes, viral, fungal or bacterial infection, recent history of trauma or tooth extractions and tooth with periapical periodontitis. None of them were alcohol consumers. After explaining the nature of the study and the method of sample collection, the patients signed an informed consent form. Verbal consent was obtained from all the participants during examination period. The study protocol was approved by the Ethical Committee. A full mouth examination was conducted. Probing Depth (PD) and Clinical Attachment Loss (CAL) were recorded with a Williams graduated probe at six sites on each tooth for both groups. Supragingival plaque was scored using Plaque Index (PI). Gingival inflammation was scored using Gingival Index (GI). The patients were diagnosed as having chronic periodontitis by probing depth of 6mm in >30% sites and bone loss >50% sites as seen in radiographs. 10 Among all subjects, each tobacco user was exclusively either a smoker or chewer who had smoked cigarettes or chewed tobacco for >15years. 11 Under aseptic measures, venous blood samples were drawn from antecubital fossa. 4ml blood was collected in an EDTA containing vacuum tube and transported to a clinical laboratory for processing within 4 hours. Hemoglobin (Hb), Number of erythrocytes (RBC count), Haematocrit / Packed cell volume (HCT), Mean corpuscular volume (MCV), Mean corpuscular hemoglobin (MCH), Mean corpuscular hemoglobin concentration (MCHC) were measured on a fully automated hematologic analyzer. Data were expressed as means and standard deviations. The statistical difference between the groups was tested with Kruskal Wallis ANOVA test and Mann-Whitney U test. Simple pair wise correlations were calculated according to the rank correlation of Pearson. Results The various parameters of red blood cell analysis in NTU group, SM group and group were analyzed. The levels of hemoglobin, the red blood cell count and hematocrit values were least in group, followed by SM group and then by NTU group. The difference between the values of MCV, MCH, and MCHC was not statistically significant but the values were within the normal range (Table 1). The Table 2 depicted the comparison of clinical parameters of GI, PI, CAL and PD showed statistically significant difference among all the three groups. Table 3 and 4 showed no statistical correlations between mean levels of serum and clinical parameters in NTU group although all the clinical parameters were in negative correlation with Hb, RBC and HCT. In SM group, there was significant negative correlation between PI and Hb, RBC and HCT while insignificant negative correlation was seen between CAL, PD with Hb, RBC and HCT. However, GI showed statistically insignificant positive correlation with Hb, RBC and HCT. In group, (Table 5) all the clinical parameters showed negative correlations with Hb, RBC and HCT, while

3 ISSN Anemia of Chronic Disease, Periodontal Disease the correlation between PI and Hb, RBC, HCT and MCH was statistically significant. Discussion The available literature suggested that periodontitis is associated with an increased risk for systemic diseases like cardiovascular diseases, cerebrovascular ischemia and atherosclerosis. 8 Previous studies have also demonstrated that Hb% NTU Kruskal Wallis ANOVA Test Mean SD H value P value SM periodontitis is associated with elevated levels of white blood cells and elevated plasma C-reactive proteins. 12 These associations indicate that periodontitis has systemic effects and most likely may present signs of subtle systemic inflammation. However, the systemic effects may not be as striking due to milder periodontal inflammatory condition compared to other systemic infections and conditions. Mann Whitney U Test SM SM vs * * * * RBC NTU SM * * * * HCT NTU SM MCV NTU SM MCH NTU SM MCHC NTU SM Table 1: Means and SDs of various parameters of Red Blood Cell analysis in NTU, SM and Kruskal Wallis ANOVA Test Mean SD H value P value Mann Whitney U Test SM SM vs GI NTU SM * 0.02* 0.02* 0.007* PI NTU SM * * * * CAL NTU SM * * * * PD NTU SM * * * * Table 2: Means and SDs of various clinical parameters in NSM, SM and It is now well established that tobacco use in smoking and smokeless form is among the most important preventable risk factor in the incidence and progression of periodontal diseases and has shown to tip the balance towards periodontal destruction. 13 Cigarette smoking is associated with increased alveolar bone loss increased prevalence and severity of periodontitis and a poor response to periodontal therapy. 14 Smokeless tobacco products, have been strongly associated with oral leukoplakia, an increased risk for oral cancer and is also associated with gingival recession and attachment loss at

4 21 Nagaraj B.Kalburgi, et al. ISSN the site of smokeless tobacco placement. Studies have confirmed that use of smokeless tobacco is as harmful as smoked tobacco. 15,16 The habit of chewing tobacco is increasing because of its free availability, cheaper cost and also increasing education about well established hazards of smoking and ban on smoking at public places in India. Variables GI PI PD CAL HB% RBC HCT MCV MCH MCHC Table 3: Correlation between serum and clinical parameters (NTU group) *p<0.05 Variables GI PI PD CAL HB% * RBC * HCT * MCV MCH MCHC Table 4: Correlation between serum and clinical parameters (SM group) *p<0.05 Variables GI PI PD CAL HB% * RBC * HCT * MCV MCH * MCHC Table 5: Correlation between serum and clinical parameters ( group) *p<0.05 In India, anemia is more prevalent in females because of poor nutrition, increased menstrual losses, high incidence of tropical and intestinal infections. Iron deficiency anemia is the most common type of anemia seen in India. Females are more prone to hormonal imbalance, alterations in host immune response and microbial flora leading to exaggerated response of the periodontal tissues to local factors. Therefore, to eliminate the bias, only male patients were included in the study. 10 In the current study, group has lower values of Hb, RBC count and HCT as compared to SM group, while these values were highest in NTU group. These findings were in parallel to the findings of ACD. A depressed level of MCV (microcytosis) relates to iron deficiency anemia and elevated levels of MCV (macrocytosis) relates anemia of vitamin deficiency. In our study MCV levels, in all the groups were within the reference values, indicating normocytic anemia, as commonly seen in ACD. 17,18 Therefore, lower value of hematocrit can be significantly attributed to significantly lower number of erythrocytes. Similarly, the mean Hb values were significantly lower in group followed by SM group and NTU group, although the MCH and MCHC values were within the normal range. In a study, Hutter et al. has suggested that periodontitis may cause lower numbers of erythrocytes and consequently lower haemoglobin levels. This pathogenesis was reported to be similar as for rheumatoid arthritis i.e. depressed erythropoesis by

5 ISSN Anemia of Chronic Disease, Periodontal Disease systemically circulating pro-inflammatory cytokines resulting from local chronic inflammatory process. 8 Cytokines such as interleukin-1 (IL-1), interleukin- 6 (IL-6), tumor necrosis factor- α (TNF-α), and interferons are hypothesized to be involved in the maintenance of red blood cell production or stability. Many studies have shown a correlation between inflammation, elevated circulating cytokines and anemia in patients and in mice, but whether these inflammatory cytokines act alone or regulate other pathways that are important for red blood cell production is unclear. 19 Tobacco components have been shown to modify the production of cytokines or inflammatory mediators. Nicotine, one of the deleterious products of cigarette has shown to increase release of IL-6 by cultured murine osteoblasts. Smoking has shown to have a greater effect on the release of cytokines from neutrophils than periodontitis. Overall data analysis of the present study showed that subjects in SM group had lesser Hb, RBC, HCT than in NTU group. This result was in accordance with the results shown by Erdemir etal. 1 Smoking also affects erythrocytes and other blood parameters. 10 Values of GI showed a positive correlation with HB, HCT, RBC count in SM group which can be explained by the fact that smokers have less bleeding on probing than never smokers. 20 In the present study there was statistically significant negative correlation of PI with HB, HCT, RBC count in both SM group and group. Other clinical parameters showed statistically insignificant negative correlation which can be attributed to the increased predisposition for accumulation of dental plaque and poor oral hygiene in smokers and smokeless tobacco users. Singh etal also demonstrated the similar impact of smokeless tobacco use was higher on all periodontal health indicators viz. PI, GI, clinical attachment loss, gingival recession, mobility, furcation and probing pocket depth. 5,21 The use of tobacco in smokeless form was seen to play a significant role in the elevation of IL-6 PGE2, IL-α, IL-β which may tend towards depressed erythropoesis leading to anemia. 7,22 As the multiple risk factors for periodontal disease become more clearly elucidated, the practitioner will be able to more accurately determine an individual s risk for present and future periodontal disease, based on a systematic assessment of their individual risk characteristics. 23 Based on this evidence, dental health professionals should advise patients of tobacco s negative health effects as well as the benefits of quitting tobacco use and tobacco cessation counselling should be part of the armamentarium of the dental office. 14 Collectively, this data provides a strong basis for tobacco cessation counselling in the dental office. 23 A greater integration of medicine and dentistry will likely require that dentists take more responsibility for the management of their patients systemic health and conversely that physicians assume a more active role in their patients oral health. 3 Conclusion The current study indicates periodontitis also needs to be considered as a chronic disease and together with the effect of cigarette smoking and/or smokeless tobacco may affect the systemic markers related to anemia of chronic disease. These facts are of important consideration for treatment planning and tobacco cessation counselling thus providing powerful motivating factors for dental health professionals for definitive preventive strategies for periodontal diseases. Acknowledgement We would like to acknowledge all the staff members of periodontics department for their support and guidance. Author Affiliations 1.Dr.Nagaraj B.Kalburgi, Professor, 2.Dr.Arati C Koregol, Reader, 3.Dr.Akshay Muley, 4.Dr.Shivraj Warad, Head of the Department, 5.Dr.Sandeep Patil, Department of Periodontics, P.M.N.M. Dental College, Bagalkot , Karnataka State, India. Reference 1. Erdemir EO, Nalcaci R, Caglayan O. Evaluation of systemic markers related to anaemia of chronic disease in the peripheral blood of smokers and nonsmokers with chronic periodontitis. Eur J Dent 2008;2: Yamamoto T, Tsuneishi M, Furuta M, Ekuni D, Morita M, Hirata Y. Relationship between decrease of erythrocyte count and progression of periodontal disease in rural Japanese population. J Periodontol 2011;82: Garcia RI, Henshaw MM, Krall EA. Relationship between periodontal

6 23 Nagaraj B.Kalburgi, et al. ISSN disease and systemic health. Periodontal ;25: Chu YH, Tatakis DN, Wee AG. Smokeless tobacco use and periodontal health in a rural male population. J Periodontol 2010;81: Fisher MA, Taylor GW, Tilashalski KR. Smokeless tobacco and severe active periodontal disease, NHANES III. J Dent Res 2005;84(8): Pradeep AR, Anuj S, Raju AP. Anemia of chronic disease and chronic periodontitis: Does periodontal status have an effect on anemia status? J Periodontol 2011; 82: Johnson G, Poore T, Payne J, Organ C. The effects of smokeless tobacco extract on human gingival keratinocyte levels of Prostaglandin E 2, Interleukin-1. J Periodontol 1996;67: Hutter JW, Van der Velden U, Varoufaki A, Huffels RAM, Hoek FJ, Loos BG. Lower numbers of erythrocytes and lower levels of hemoglobin in periodontitis patients compared to controls. J Clin Periodontol 2001;28: Kinane DF. Causation and pathogenesis of periodontal disease. Periodontal ;25: Gokhale S, Sumanth S, Padhye A. Evaluation of blood parameters in patients with chronic periodontitis for signs of anemia. J Periodontol 2010;81: Giraud DW, Martin HD, Driskell JA. Erythrocyte and plasma B-6 vitamer concentrations of long-term tobacco smokers, chewers, and nonusers. Am J Clin Nutr 1995;62: Loos BG, Craandijk J, Hoek FJ, van Dillen W, van der Velden U. Elevation of systemic markers related to cardiovascular diseases in the peripheral blood of periodontitis patients. J Periodontol 2000;71: Ryder MI. The influence of smoking on host responses in periodontal infections. Periodontol ;43: American Academy of Periodontology (AAP). Position paper: tobacco use and the periodontal patient. Research, science and therapy committee of the American Academy of Periodontology. J Periodontol 1999;70: Weintraub JA, Burt BA. Periodontal effects and dental caries associated with smokeless tobacco use. Public Health Rep 1987;102: Gajalakshimi V, Petro R, Kanaka TS, Jha P. Smoking and mortality from tuberculosis and other diseases in India: retrospective study of adult male death and controls. Lancet 2003;362: Ward PC. Investigation of macrocytic anemia. Postgrad med J 1979;65: Samson D. The anemia of chronic disorders. Postgrad Med J 1983;59: Weinstein DA, Roy CN, Fleming MD, Loda MF, Wolfsdorf JI, Andrews NC. Inappropriate expression of hepcidin is associated with iron refractory anemia: implications for the anemia of chronic disease. Blood 2002;100: Dietrich T, Bernimoulin JP, Glynn RJ. The effect of cigarette smoking on gingival bleeding. J Periodontol 2004;75: Singh GP, Rizvi I, Gupta V, Bains VK. Influence of smokeless tobacco on periodontal health status in local population of north India: A crosssectional study. Dent Res J 2011;8(4): Sharma M, Bairy I, Pai K, Satyamoorthy K, Prasad S, Berkovitz B, Radhakrishnan R. Salivary IL-6 levels in oral leukoplakia with dysplasia and its clinical relevance to tobacco habits and periodontitis. Clin Oral Invest 2011;15: Johnson GK, Slach NA. Impact of tobacco use on periodontal patient. J Dent Edu 2001;65(4): Corresponding Author Dr.Arati C. Koregol. Reader, Department of Periodontics, P.M.N.M. Dental College, Bagalkot , India. Ph: aratikperio@yahoo.co.in Source of Support: Nil, Conflict of Interest: None Declared.