REVIEW ARTICLE. Effect of Cigarette Smoking on the Clinical Outcomes of Periodontal Surgical Procedures

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1 REVIEW ARTICLE Effect of Cigarette Smoking on the Clinical Outcomes of Periodontal Surgical Procedures Fawad Javed, PhD, Abdulaziz Al-Rasheed, MSC, Khalid Almas, MSC, George E. Romanos, PhD and Khalid Al-Hezaimi, MSC Abstract: Introduction: Experimental studies have revealed that nicotine upregulates the expression of receptors of advanced glycation end products and retards fibroblastic cell migration in the gingiva of smokers, thereby inducing a proinflammatory effect. The aim of this study was to review the effect of cigarette smoking on the clinical outcomes of periodontal surgical procedures. Methods: To address the focused question, What is the effect of clinical outcomes after periodontal surgical interventions?, databases were searched from 1968 to May 2010 using various combinations of the following key words: inflammation, mucoperiosteal flap, periodontal surgery, smoking and tobacco. The inclusion criteria included all levels of available evidence. Articles published only in the English language were evaluated, and unpublished data were not sought. Results: Twenty-four clinical studies were included. The duration of smoking habit ranged from at least 5 to Sixteen studies showed that reductions in probing depth and gains in clinical attachment levels were compromised in smokers in comparison with. Three studies showed residual recession after periodontal surgical interventions to be significantly higher in smokers. Three case reports showed periodontal healing to be uneventful in smokers. Conclusion: Cigarette smoking has a negative effect on periodontal wound healing after surgical interventions. Key Indexing Terms: Inflammation; Mucoperiosteal flap; Periodontal surgery; Smoking; Tobacco. [Am J Med Sci 2012;343(1):78 84.] The primary goals of periodontal therapy are to eliminate or reduce bacterial plaque and contributing factors to arrest disease progression. Subgingival scaling and root planning may result in resolution of inflammation to some extent 1 ; however, with deep probing depths (PD), a mucoperiosteal flap surgery may be necessary to achieve a greater reduction in PD and gain in clinical attachment level (CAL). 2,3 Risk factors for periodontal inflammatory conditions include smoking, stress and immunodeficiency. 4 7 It has been hypothesized that smoking is associated with an increased expression of receptor of advanced glycation end products (RAGE) in gingival tissues. 8,9 In their experimental study, Katz et al 8 showed an increased expression of RAGE in gingival epithelial cells of smokers. Furthermore, it has been reported that nornicotine (a metabolite of nicotine) upregulates RAGE expression in the gingiva of From the Eng A.B. Growth Factors and Bone Regeneration (FJ, AA-R, KA-H), Department of Periodontics and Community Dentistry (AA-R, KA-H), College of Dentistry, King Saud University, Riyadh, Saudi Arabia; Division of Periodontology (KA), University of Connecticut, Farmington, Connecticut; and Eastman Institute for Oral Health (GER), Division of Periodontology, University of Rochester, Rochester, New York. Submitted October 25, 2010; accepted in revised form March 2, Correspondence: Fawad Javed, PhD, Eng. A. B. Growth Factors and Bone Regeneration, College of Dentistry, King Saud University, Riyadh, Saudi Arabia ( fawjav@gmail.com). elicits a proinflammatory effect by stimulating the secretion of cytokines and reactive oxygen species that directly cause destruction of the periodontal apparatus. 9 The vasoconstrictive effects of nicotine increase platelet adhesiveness, increase the risk of microvascular occlusion and cause tissue ischemia. 10 Smoking is also associated with catecholamines release resulting in vasoconstriction and decreased tissue perfusion. 10 These phenomena can negatively influence periodontal wound healing and the repair and regenerative capacities of periodontal tissues in smoking patients. Other proposed mechanisms regarding the negative effect of smoking on periodontal tissues include (1) decreased vascular flow; (2) decreased immunoglobulin G production and lymphocyte proliferation; (3) altered neutrophilic function; (4) amplified prevalence of periodontal pathogens; (5) impaired fibroblast attachment and function; and (6) negative local effects on growth factor and cytokine production. 11,12 Because various mechanisms may contribute in impairing the periodontal healing process in smokers, the aim of this study was to review the literature with regard to the effect of clinical outcomes after open flap curettage (OFC) procedures. MATERIALS AND METHODS Focused Question The addressed focused question was What is the effect of clinical outcomes after periodontal surgical interventions? Eligibility Criteria The eligibility criteria encompassed the following: (1) original articles; (2) clinical and experimental studies; (3) case reports; (4) studies designed specifically to investigate the effect of smoking on clinical outcomes of periodontal surgical procedures; (5) reference list of pertinent original and review studies; and (6) articles published only in English language. Letters to the editor, historic reviews and unpublished articles were excluded. Search Strategy The authors searched the MEDLINE/PubMed (National Library of Medicine, Bethesda, Maryland) and the Google scholar databases for appropriate articles addressing the focused question. Databases were explored from 1968 up to and including May 2010 using the following keywords in various combinations: inflammation, mucoperiosteal flap, periodontal surgery, smoking and tobacco. Titles and abstracts of articles that satisfied the eligibility criteria were screened by the authors and checked for agreement. The full text of the articles judged by title and abstract to be relevant were read and independently assessed against the eligibility criteria. Any disagreements between the authors were resolved via discussion. Hand searching of the reference lists of original and review studies that were found to be relevant in the previous 78 The American Journal of the Medical Sciences Volume 343, Number 1, January 2012

2 Cigarette Smoking and Periodontal Surgery FIGURE 1. Summary of the search strategy (also see Appendix). step was performed, and once again, any disagreement between the authors was resolved via discussion. The initial search yielded 51 articles. Twenty-seven studies that did not abide by the eligibility criteria were excluded (see Appendix). The search strategy is summarized in Figure 1. In total, 24 studies were retrieved, which were processed for data extraction (Table 1). RESULTS Characteristics of Included Studies All studies that fulfilled the eligibility criteria were clinical and were either performed at universities or oral healthcare centers. The numbers of participants ranged between 1 subject and 172 individuals, and all were regular cigarette smokers. All individuals were adults and their ages ranged between 22 and 77. The number of cigarettes smoked daily ranged between 1 and 20. Most of the studies that fulfilled our eligibility criteria were controlled clinical trials. 14,16 18,20,22 28,30,33 36 Three studies were case reports, 13,15,19 and 4 case-control studies were also included. 21,29,31,32 Eight studies 13,15,18,20,25,29,31,35 reported the duration of smoking, which ranged from at least 5 to In 17 studies, OFC procedures were performed; whereas in 7 studies, the patients had undergone guided tissue regeneration (GTR) for the correction of periodontal defects. In studies on patients who underwent periodontal flap surgeries, 3 studies 19,27,28 were performed with osteotomy, whereas in 4 studies, 22,24,25,29 periodontal flap surgery (PFS) was performed without osteotomy. In the studies, 13 18,20,21,23,26 it was unclear whether or not osteotomy was performed after PFS. The maintenance/follow-up period ranged between 2 months and 5. Sixteen studies 14,16,17,19,22 24,27 30,32 36 reported reductions in PD and gains in CAL to be compromised in smokers in comparison with. Three studies 18,20,26 reported residual recession to be significantly higher in smokers after PFS. In 3 case reports, 13,15,19 periodontal inflammatory parameters were not compromised after PFS. Six 30 33,35,36 of the 7 studies, where GTR was performed, reported treatment outcomes to be poorer in smokers. Scabbia and Trombelli 34 reported no significant changes from baseline recession depth and CAL recordings in treated with GTR. DISCUSSION Even though smoking is an inevitable risk factor for a less favorable periodontal healing response after surgical interventions; the role of confounding parameters (such as poorly controlled diabetes mellitus, stress, immunodeficiency, increasing age and female gender) that may also impair periodontal healing after surgical interventions cannot be disregarded. 4,37 40 Hence, it may be argued that such confounding parameters may also play a role in impairing healing after periodontal surgery; however, further studies are needed in this regard. From the literature reviewed, it was observed that only a limited number of studies 13,15,17,31,32 expressed the exposure to cigarettes in pack-. In this regard, we expressed the habit in terms of the numbers of cigarettes smoked daily, which, however, may be regarded as a limitation of the current study. We found no consistent patterns between the numbers of cigarettes smoked daily and their effect on periodontal surgical interventions. For example, the results from Kaldahl et al 27 and Preber and Bergström 29 showed that individuals who smoked at least 20 cigarettes daily exhibited significantly less reduction in plaque index and PD. In the study by Kim et al, 17 the periodontal status of patients was reevaluated 6 months after periodontal surgery. The results showed that PD reductions and gains in vertical attachment level were compromised in patients who smoked at least 1 cigarette per day. 17 It may therefore be postulated that individuals who smoke once a day may not be pardoned from the detrimental effects of smoking on wound healing subjects smoking more than 20 times daily. Because of lack of relevant information, the authors found it arduous to assess the effect of duration of smoking on periodontal healing in smokers. From the studies included, we observed that smokers with a less favorable periodontal healing response after surgical interventions had been smoking since at least 5 ; however, the authors emphasize that a history of smoking of less than 5 should not be considered safe in terms of periodontal healing. Further studies are warranted in this regard. Interestingly, the 3 case reports 13,15,19 that were included in the current review reported that regular smokers were not susceptible to impairments in periodontal healing after surgical interventions. Nevertheless, several essential parameters that could have influenced the long-term success of the surgical treatment in these patients were not addressed. For example, in the study by Blanchard et al, 13 the postoperative healing was uneventful; however, the periodontally involved tooth was extracted. In the study by Walter et al, 15 smoking cessation was advised to the patient before periodontal surgery. It was 2012 Lippincott Williams & Wilkins 79

3 Javed et al TABLE 1. Authors, aim, subject(s), mean age and age range, duration of smoking, numbers of cigarettes smoked daily, statistical methods and main results of selected studies Authors Open flap curettage Blanchard et al 13 Yilmaz et al 14 Walter et al 15 Dastoor et al 16 Kim et al 17 Silva et al 18 von Arx et al 19 Silva et al 20 Aim smoking on the treatment of a furcation defect in a male patient smoking on healing response of intrabony defects after surgical periodontal therapy the healing of periodontal lesions in a smoker To assess the adjunctive effects of systemic antibiotics in combination with periodontal surgery in smokers with chronic periodontitis To investigate the effect of cigarette smoking on surgical periodontal therapy the outcome CPF in the treatment of gingival recession defects To assess the changes in periodontal parameters in a patient having undergone apical surgery smoking on the outcome CPF in the treatment of gingival recession defects Subject/s (n) Mean age and range (yr) Duration of smoking habit (yr) Numbers of cigarettes smoked daily Main results One male At least 20/day Healing after the periodontal open flap debridement surgery was uneventful 24 NA (32 50) NA At least 10/day Reduction in PD and CAL gains was poorer in smokers One male At least 20/d Healing after the periodontal open flap debridement surgery was uneventful, and the periodontal status was uneventful after 32 months of follow-up (35 65) NA At least 20/d At 6 months of follow-up, adjunctive antibiotic therapy in combination with periodontal surgery failed to enhance PD reduction and clinical attachment gain ( ) NA At least 1/d At 6 months of maintenance, PD reduction and RAL-V gain were significantly less in smokers 20 NA (22 53) At least 5 At least 10/d At 24 months of maintenance, residual recession was significantly greater in smokers. The stability of the CPF was less stable in smokers One male NA NA NA At 2 months of follow-up, smoking habit did not have any significant effects on PD, CAL and plaque and bleeding on probing indices after apical surgery (22 53) At least 5 At least 10/d At 6 months of follow-up, smokers presented greater residual recession depth and lower percentage of root coverage (Continued) 80 Volume 343, Number 1, January 2012

4 Cigarette Smoking and Periodontal Surgery TABLE 1. Authors Erley et al 21 (Continued) Trombelli et al 22 Tonetti et al 23 Scabbia et al 24 Boström et al 25 Trombelli and Scabbia 26 Kaldahl et al 27 Ah et al 28 Preber and Bergström 29 Aim the healing of subepithelial connective tissue grafts To evaluate the treatment outcome of flap debridement surgery in cigarette To evaluate the clinical effect of flap surgery with or without the application of enamel matrix proteins To compare the treatment outcome after flap surgery among cigarette To assess the influence of smoking on the outcome of periodontal surgery To assess the gingival healing response in cigarette consumption on periodontal therapy To investigate the effect of smoking on the clinical response to surgical and nonsurgical periodontal therapy To investigate the effect the reduction of pocket probing depth after surgical therapy Subject/s (n) Mean age and range (yr) Duration of smoking habit (yr) Numbers of cigarettes smoked daily Main results 17 NA (27 45) NA At least 10/d At 3- and 6-month maintenance, root coverage was significantly less in smokers (30 50) NA At least 10/d At 6 months of maintenance, smokers presented a lesser horizontal CAL gain (39 57) NA Less than 20/d PD reduction and CAL gains were significantly less in smokers (27 56) NA At least 10/d At 6 months of maintenance, PD reductions and CAL gains were poorer in smokers (33 77) /d In terms of alveolar bone height, the results were less favorable among smokers. GCF levels of TNF- were significantly increased in smokers compared with (23 40) NA At least 10/d Smokers showed significantly less reduction in recession depth and root coverage ( ) NA At least 20/d Smokers demonstrated less PD reduction and less CAL gain compared with past (NA) NA At least 10/d During each of the 6 of maintenance, smokers exhibited significantly less reduction of PD and less gain of CAL (33 49) 5 At least 20/d At the 1 year of maintenance, smokers exhibited significantly less reduction in plaque index and PD compared with (Continued) 2012 Lippincott Williams & Wilkins 81

5 Javed et al TABLE 1. (Continued) Authors Guided tissue regeneration Stavropoulos et al 30 Machtei et al 31 Klein et al 32 Bokan and Bill 33 Scabbia and Trombelli 34 Rosen et al 35 Tonetti et al 36 Aim To assess the affect of smoking outcome of GTR procedures in cigarette To investigate the outcome of GTR procedures in cigarette To assess periodontal healing in infrabony pockets treated by GTR in To evaluate clinical outcome 24 months after GTR in smokers and To assess the stability of soft tissue conditions in gingival recession defects in treated with GTR To compare the shortterm and long-term clinical results of regenerative therapy in the healing response after GTR in deep infrabony pockets Subject/s (n) Mean age and range (yr) Duration of smoking habit (yr) Numbers of cigarettes smoked daily Main results (NA) NA NA PD reduction was less pronounced in smokers than in. Smoking impaired the healing outcome of GTR treatment of intrabony defects (35 61) At least 8 At least 10/d Smoking prevented the periodontal tissue maturation and mineralization (21 64) NA At least 10/d At 24 months of followup, smokers showed a reduced CAL compared with ( ) NA NA At 24 months of maintenance, PD reductions was poorer in smokers compared with (23 57) NA At least 10/d At 4 of follow-up, no significant changes from baseline recession depth and CAL recordings were observed (28 69) At least 10 Less than or equal to 20/d At 1 year and 2 5 of follow-up, smokers exhibit poorer treatment results in terms of CAL gain (18 59) NA At least 10/d At 1 year of follow-up, smokers gained significantly less CAL than PD, probing depth; CAL, clinical attachment level; NA, not available; RAL-V, vertical relative attachment level; CPF, coronally positioned flaps; GTR, guided tissue regeneration; GCF, gingival crevicular fluid; TNF-, tumor necrosis factor-alpha. unclear that whether the patient quitted smoking or not; however, in case he did, then this could be an explanation for the success of OFC in this individual. Similarly, in the study by von Arx et al, 19 factors such as duration and daily frequency of smoking that may influence periodontal healing after surgery were not documented. In addition, in this study, 19 the follow-up was performed after 2 months. We hypothesize that the longterm success of the offered OFC could be challenged in case the patient continued with the smoking habit. Thus, results from these case reports remain debatable. Smoking cessation has been suggested to be effective in reducing wound complications of various types of invasive surgeries. 41 However, the optimal duration of smoking cessation that may reduce the risk of impaired periodontal healing remains unclear. Results from Boström et al 25 and Kim et al 17 showed an improved periodontal healing in former smokers in comparison with current smokers; however, in these studies, former smokers were defined as individuals who ceased the smoking habit since at least 5 and 1 year. Further long-term longitudinal clinical trials are warranted to assess the benefits of smoking cessation on periodontal wound healing. CONCLUSION Although periodontal surgical interventions exhibit less favorable healing outcomes in smokers, the role of other confounding parameters (such as poorly controlled diabetes mellitus, stress, immunodeficiency, 82 Volume 343, Number 1, January 2012

6 Cigarette Smoking and Periodontal Surgery increasing age and female gender) that may also impair periodontal healing after surgical interventions cannot be disregarded. Hence, further studies are warranted in this regard. Smoking cessation should be an important component in the overall treatment of periodontal inflammatory conditions. APPENDIX: LIST OF EXCLUDED STUDIES (REASON/S FOR EXCLUSION IS/ARE SHOWN IN PARENTHESIS) Y Balaji SM. Tobacco smoking and surgical healing of oral tissues: a review. Indian J Dent Res 2008;19: (Review) Y Blomlöf L, Jonsson B, Blomlöf J, et al. A clinical study of root surface conditioning with an EDTA gel. II. Surgical periodontal treatment. Int J Periodontics Restorative Dent 2000;20: (Focused Y Cortellini P, Bowers GM. Periodontal regeneration of intrabony defects: an evidence-based treatment approach. Int J Periodontics Restorative Dent 1995;15: (Focused Y Danesh-Meyer MJ, Wikesjö UM. 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Ann Periodontol 2000;5: (Focused Y Lazarovici TS, Yahalom R, Taicher S, et al Bisphosphonate-related osteonecrosis of the jaws: a single-center study of 101 patients. J Oral Maxillofac Surg 2009;67: (Focused Y Machtei EE, Frankenthal S, Blumenfeld I, et al. Dental implants for immediate fixed restoration of partially edentulous patients: a 1-year prospective pilot clinical trial in periodontally susceptible patients. J Periodontol 2007;78: (Focused Y Mehlbauer MJ, Greenwell H, Nouneh I, et al. Improved closure rate of Class III furcations using a layered GTR technique. Int J Periodontics Restorative Dent 2000;20: (Focused Y Molly L, Vandromme H, Quirynen M, et al. Bone formation following implantation of bone biomaterials into extraction sites. J Periodontol 2008;79: (Focused Y Paolantonio M, Dolci M, Esposito P, et al. Subpedicle acellular dermal matrix graft and autogenous connective tissue graft in the treatment of gingival recessions: a comparative 1-year clinical study. J Periodontol 2002;73: (Focused Y Parodi R, Liuzzo G, Patrucco P, et al. Use of Emdogain in the treatment of deep intrabony defects: 12-month clinical results. Histologic and radiographic evaluation. Int J Periodontics Restorative Dent 2000;20: (Focused Y Roos-Jansåker AM. Long time follow up of implant therapy and treatment of peri-implantitis. Swed Dent J Suppl 2007;188:7 66. (Focused Y Roos-Jansåker AM, Renvert H, Lindahl C, et al. Submerged healing following surgical treatment of peri-implantitis: a case series. J Clin Periodontol 2007;34: (Focused Y Rossmann JA, Rees TD. A comparative evaluation of hemostatic agents in the management of soft tissue graft donor site bleeding. J Periodontol 1999;70: (Focused Y Said S, Mohd H, Sander L, et al. GCF levels of MMP-3 and MMP-8 following placement of bioresorbable membranes. J Clin Periodontol 1999;26: (Focused Y Sculean A, Blaes A, Arweiler N, et al. The effect of postsurgical antibiotics on the healing of intrabony defects following treatment with enamel matrix proteins. J Periodontol 2001;72: (Focused Y Söder B, Nedlich U, Jin LJ. Longitudinal effect of nonsurgical treatment and systemic metronidazole for 1 week in with refractory periodontitis: a 5-year study. J Periodontol 1999;70: (Focused Y Soileau KM. Oral postsurgical complications following the administration of bisphosphonates given for osteopenia related to malignancy. J Periodontol 2006;77: (Focused Y Stavropoulos A, Sculean A, Karring T. GTR treatment of intrabony defects with PLA/PGA copolymer or collagen bioresorbable membranes in combination with deproteinized bovine bone (Bio-Oss). Clin Oral Investig 2004; 8: (Focused Y Wituła A, Drugacz J, Malara P. Influence of smoking tobacco on the condition of dentition and occurrence of periodontal diseases in patients of the Clinic of Maxillo- Facial Surgery at the Silesian Medical Academy in Katowice. Przegl Lek 2005;62: (Article in Polish) Y Zahedi S, Blase D, Bercy P. Is periodontal guided tissue regeneration a reproducible technic? A review of the literature. Rev Belge Med Dent 1998;53: (Article in French, Review) Y Zahedi CS, Miremadi SA, Brunel G, et al. Guided tissue regeneration in human class II furcation defects using a diphenylphosphorylazide-cross-linked collagen membrane: a consecutive case series. J Periodontol 2003;74: (Focused Y Zitzmann NU, Schärer P, Marinello CP. Factors influencing the success of GBR. Smoking, timing of implant placement, implant location, bone quality and provisional restoration. J Clin Periodontol 1999;26: (Focused REFERENCES 1. Buchmann R, Conrads G, Sculean A. Short-term effects of systemic antibiotics during periodontal healing. Quintessence Int 2010;41: Santana RB, de Mattos CM, Van Dyke T. Efficacy of combined regenerative treatments in human mandibular class II furcation defects. J Periodontol 2009;80: Lippincott Williams & Wilkins 83

7 Javed et al 3. Stein JM, Fickl S, Yekta SS, et al. Clinical evaluation of a biphasic calcium composite grafting material in the treatment of human periodontal intrabony defects: a 12-month randomized controlled clinical trial. J Periodontol 2009;80: Falasca K, Vecchiet F, Ucciferri C, et al. Periodontitis and cytokine patterns in HIV positive patients. Eur J Med Res 2008;13: Johannsen A, Rydmark I, Söder B, et al. Gingival inflammation, increased periodontal pocket depth and elevated interleukin-6 in gingival crevicular fluid of depressed women on long-term sick leave. J Periodontal Res 2007;42: Pradeep AR, Hadge P, Arjun Raju P, et al. Periodontitis as a risk factor for cerebrovascular accident: a case-control study in the Indian population. J Periodontal Res 2010;45: Javed F, Romanos GE. Impact of diabetes mellitus and glycemic control on the osseointegration of dental implants: a systematic literature review. J Periodontol 2009;80: Katz J, Yoon TY, Mao S, et al. 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J Periodontol 2007;78: Blanco-Carrion J, Liñares-Gonzalez A, Batalla-Vazquez P, et al. Morbidity and economic complications following mucogingival surgery in a hemophiliac HIV-infected patient: a case report. J Periodontol 2004;75: Javed F, Klingspor L, Sundin U, et al. Periodontal conditions, oral Candida albicans and salivary proteins in type 2 diabetic subjects with emphasis on gender. BMC Oral Health 2009;9: Javed F, Näsström K, Benchimol D, et al. Comparison of periodontal and socioeconomic status between subjects with type 2 diabetes mellitus and non-diabetic controls. J Periodontol 2007;78: Padubidri AN, Yetman R, Browne E, et al. Complications of postmastectomy breast reconstructions in smokers, ex-smokers, and. Plast Reconstr Surg 2001;107: Volume 343, Number 1, January 2012