< First part

Under the scanning electron microscope, cells showed microvilli and philopodia formation at the plasma surface, with incresing nicotine concentrations. These cellulars expansions, which are generally associated to cellular motility, were more frequently found in the proximity of culture substrate; the authors hypothesized that they might represent adaptation mechanisms, by which cells try to adhere to substrate areas less contaminated by nicotine.

In the authors’ opinion, these results might be related to the reduced probing depth that is found in non-smokers after non-surgical therapy. As a matter of fact, a reduced adhesive capacity might render fibroblasts more susceptible to periodontal diseases and less susceptible to start the formation of new attachment. Concurrently with the described cellular alterations, the presence of an increased number of intracellular vacuoles was noted. This may reflect the presence of nicotine at the intracellular level, before its excretion or metabolization. On the contrary, Peacok et al. showed a positive cellular effect of nicotine with respect to the adhesion of human gum fibroblasts to the culture substrate and a modest stimulating effect on fibroblast proliferation at nicotine concentrations similar to those found in occasional smokers. However, increasing nicotine concentrations, similar to those found in heavy smokers, reduced the number of cultured cells, suggesting a direct effect on cell metabolism.

Fang et al. showed that low nicotine concentrations suppress osteoblastic proliferation.

Monaco et al. evaluated the effect of high nicotine concentrations, close to those that may be found in heavy smokers, on human cultured fibroblasts. These concentrations caused a 30 % inhibition of cell proliferation, compared to controls.

Noble and Penny evaluated the chemiotaxis of peripheral venous blood leucocytes in 14 smokers and 13 non-smokers. In smokers, the sample was taken at morning time, in order to evaluate the effect of a night-long abstinence; a second sample was taken immediately after smoking 2 cigarettes containing 1.6 mg of nicotine. Chemiotaxis and leucocyte number were significantly lower in smokers compared to non-smokers and to smokers following a night of abstinence. The authors hypothesized the presence in the blood of a labile leucotoxic factor linked to cigarette consumption; on the other hand, nicotine is a powerful stimulator of cathecolamines release, and induces a temporary increase of 3’, 5’ cyclic adenosine monophosphate (cAMP), that in turn may negatively influence the chemiotaxis of polymorphonucleates.

Kenney et al. analyzed the phagocytosis of polymorphonucleates taken from the oral cavity of 9 smokers (consuming > 20 cigarettes) with a mean age of 26 years. Compared to non-smokers, phagocytosis was significantly reduced in smokers. Moreover, the sample of leucocytes after smoking a cigarette resulted in a further depression of phagocytosis, that was more evident in non-smokers compared to smokers.

The authors hypothesized that an abnormality of polymorphonucleates is responsible for the greater susceptibility of gums to the bacterial attack.

Kraal et al. showed that a concentrate of cigarette smoke, dissolved in water to obtain a concentration of 5 mg of non-volatile residue/ml, had an inhibitory effect on the migration of polymorphonucleates taken from the ginigval sulcus of Beagle dogs.

Eichel et al. reported that exposure of the oral cavity to tobacco smoke, even of a single cigarette, provides toxic material in a sufficient amount to completely inhibit the function of local leucocytes exposed to this compound.

Bridges et al. analyzed both volatile and non-volatile components of cigarette smoke and showed in both cases an inhibitory effect on chemiotaxis of polymorphonucleates isolated from peripheral venous blood of male non-smoking volunteers aged 21-35 years.

Holt et al. studied the effect of smoke on immunosystem cells (lymphocytes and macrophages), fibroblasts and epithelial cells; the former were shown to be most sensitive to the toxic effects of the various tobacco components.

According to Bostrom et al., a fundamental role in the pathogenesis of periodontal disease in smokers is played by TNF-alpha, a pro-inflammatory cytokine produced by leucocytes (monocytes/macrophages) in response to bacterial attack, that is responsible for collagen tissue destruction and osteolysis.

In this study, levels of TNF-alpha in the crevicular fluid were far more elevated in smokers compared to non-smokers, whereas levels of albumin, IgA and IgG remained similar in both groups.

Another evaluation parameter studied by Dinsdale et al. is the difference in the sub-gingival temperature between smokers and non-smokers. Accordingly, sub-lingual temperature is more elevated in smokers.

At the periodontal level, on the contrary, the temperature is more elevated in smokers if the testing sites are affected by periodontal disease; however, if the testing sites are healthy, temperature will be lower in non-smokers.

Smoke effect on periodontal therapy
Preber et al. showed that the response to therapy appears to be different in smokers, since the reduction in probing depth after root planing is minimal, whilst new pocketing is higher one year after periodontal surgery interventions.

Cortellini et al. found reduced formation of new attachment in smokers following surgery with guided periodontal tissue regeneration based on Gore-tex membranes apposition.

Sweet and Butler analysed the effect of smoke in a series of 200 patients who underwent bilateral removal of unerupted inferior third molars.

Alveolar osteitis was found in 12 % of smokers and 2.6 % of non-smokers. A 26.3 % incidence of osteitis was found in patients who declared to have smoken in the immediate post-operative time, in spite of the surgeon’s recommendation to refrain from smoke. The authors concluded that smoke consumption should be avoided for at least five days following periodontal surgery interventions.

Crawford et al. investigated the influence of smoke in patients who underwent implant therapy; they showed that implant failures were greater in smokers compared to non-smokers.

In a dermatologic study, Goldminz et al. showed that smokers and former smokers have a greater susceptibility to tissue necrosis following flap surgery or cutaneous graft interventions. The authors attributed to nicotine and carbon monoxide the negative effects on microcirculation and the induction of flap or graft necrosis.

Smoke abstinence for two days before surgery and for one week afterwards was recommended for heavy smokers. Although these results were obtained from experiments performed in various body districts, they are nevertheless indicative and important in the study of post-surgical complications affecting the oral cavity of smokers.

Baumert et al. evaluated the effects of smoke in response to periodontal therapy. The action of smoke was found to induce a reduced healing response on tissues. In particular, the authors found that smokers have less reduction in probing depth and less recovery of attachment level following periodontal therapy, compared to non-smokers.

According to Trombelli and Scabbia, the tissue response during GTR in individuals affected by Miller class I and II recessions does not show relevant variations in the pre-surgical phase. Following surgery, on the other hand, the tissue response shows marked differences in the root covering, amounting to 56 % in smokers and 78 % in non-smokers.

In conlcusion, the results indicate that root covering procedures using GTR in case of gum recession are not compatible with cigarette smoke.

Conclusions
The smoke-related problems herein evaluated allow reserchers to suggest that smoke has armful effects on the periodontium, by altering health and defense mechanisms.

Smoke contains potentially toxic substances for periodontal tissues, among them nicotine has been the most studied, whereas other components (nitrosoamines) have been analyzed only recently.

Exposure of periodontal tissues to smoke for a variable period of time is likely to be a fundamental element in quantifying the possible biological damage.

Most authors generally agree in believing that the number of cigarettes which is necessary to produce a significant clinical effect should be grater than 10/day for at least 2 years.

Any modification of the bacterial plaque, together with a compromised function of polymorphonucleates, alters the efficacy of the cellular phase of inflammation, particularly its phagocitic capacity; such modifications favor a worsening, or at least a more difficult response to periodontal therapies. Therefore, it can be concluded that exposure to smoke induces a complete modification of the inflammatory response to the bacteria insult and of the repair pocess. This situation may clearly induce serious damages to periodontal structures such as chronic inflammation, increased probing depth, lesions to periodontal ligaments, loss of alveolar bone, which may lead to loss of teeth or failures in implantology procedures in most serious cases.

In conclusion, these data suggest that smokers are more susceptible to periodontal diseases and less responsive to conventional periodontal therapies; therefore, these data should be carefully evaluated before any kind of treatment is begun. Moreover, any special care should be taken in order to inform the patients on the higher risk of therapy failure.

Summary
The authors have examined the general scientific literature on the association of smoke and periodontal disease. The features of periodontium in smokers are described, and the epidemiological, etiological and pathogenetic problems are analyzed. Finally, the results of surgery in smokers are considered.

Key words
Smoke
Periodontal disease
Nicotine

Bibliografy

1. ARMITAGE T.K., DOLLERY C.T., GEORGE C.F., HOUSEMAN T.H., LEWIS P.J.,TURNER D.M.: "Absorpion and metabolism of nicotine from cigarettes." British Med. J., 4: 313-316, 1975
2. ARNO A., WAERHAUG J., LOVDAL A., SHEI O.: "Incidence of gingivitis as related to sex, occupation, tobacco compsumption, toothbrushing and age." Oral Surg., 11: 287-595, 1958
3. BAAB D.A., OBERG P.A.: "The effect of cigarette smoking on gingival blood flow in humans." J. Clin. Periodontol., 14: 418-424, 1987
4. BAUMERT M., JOHNSON G., KALDAHL W., PATIL K., KALKWARF K.L.: "The effect of smoking and the response to periodontal therapy." J. Clin. Periodontol., 2: 91- 97, 1994
5. BENOWITZ N.L., PEYTON J. III: "Nicotine and carbon monoxide intake from high and low-yield cigarettes." Clin. Pharmacol. Ther., 8: 265-270, 1984
6. BERGSTROM J.: "Oral hygiene compliance and gingivitis expression in cigarette smokers." Scand. J. Dent. Res., 98: 497-503, 1990
7. BERGSTROM J., ELIASSON S., PREBER H.: "Cigarette smoking and periodontal bone loss." J. Periodontol., 62: 242-246, 1991
8. BERGSTROM J., BLOMLOFF L.: "Tobacco smoking major risk factor associated with refractory periodontal disease." J. Dent. Res. Abst., 71: 297, 1992
9. BERGSTROM J., FLODERUSMYRHED B.: "Co-twuin control study of the relationship betweensmoking and some periodontal disease factors." Comunity Dent. Oral. Epidemiol., 11: 113-116, 1983
10. BERGSTROM J., ELIASSON S.: "Noxius effect of cigarette smoking on periodontal healt." J. Periodont. Res., 22: 513-517, 1987
11. BERGSTROM J., PREBER H.: "Tobacco use as a risk factor." J. Periodontol., 65: 545-550, 1994
12. BOLIN A., LAVSTEDT S., FRITHIOF L., HENRIKSON C.O.: "Proximal alveolar bone loss in a longitudinal radiographic investigation: IV. Smoking and other factors influencing the progress in a material of individuals with at least 20 remaining teeth." Acta Odontol. Scand., 44: 263-269, 1986
13. BOSTROM L.,LINDER LE.,BERGSTROM J.: "Clinical expression of TNF-a in smoking associated periodontal disease." J. Clin. Periodontol., 10: 767-773, 1998
14. BRIDGES R.B., HSIEH L.: "Effects of cigarette smoke fractions on the chemotaxis of polymorphonuclear leukocytes." J. Leukocyte Biol., 40: 73-85, 1986
15. CHAMSON A., FREY J., HIVERT M.: "Effects of tobacco smoke extracts on collagen byosinthesis by fibroblasts cell cultures." Toxicol. Environ. Healt, 19: 921-925, 1982
16. CORTELLINI P., PINI PRATO G., TONETTI M.: "Effect of smoking on periodontal regeneration (GTR)." J. Dent. Res. Abst. 1472, 1994
17. CRAWFORD P.R.: "All implants succed—all implants fail. Part two." J. Can. Dent. Assoc. 55(6):461-463, 1989
18. DINSDALE C., RAWLINSON A., WALSH T.: "Subgingival temperature in smokers and non smokers with periodontal disease." J. Clin. Periodontol., 10: 761- 766, 1997
19. EICHEL B., ARTO SHAHRIK H.: "Tobacco smoke toxicity: loss of human oral leukocyte function and fluid-cell metabolism." Science, 166: 1424-1428, 1969
20. FANG M.A., FROST P.J., IIDAKLEIN A., HAHN T.J.: "Effects of nicotine on cellular function in UMR 106-01 osteobast-like cells." Bone, 12: 283-286, 1991
21. FUNG C.K.Y., CORBET E.F.: "Gingival bleeding response in smokers and non-smokers." J. Dent. Res., abst. 541, 1995
22. GIANNOPOULOU C., GEINOZ A., CIMASONI G.: "Effects of ncotine on periodontal ligament fibroblasts in vitro." J. Clin. Periodontol., 1: 49-55, 1999
23. GOLDMINZ D., BENNET R.G.: "Cigarette smoking and flap and full-thickness graft necrosis." Arch. Dermatol., 127: 1012-1015, 1991
24. HABER J., KENT R.L.: "Cigarette smoking in a periodontal practice." J. Periodontol., 63: 100-106, 1992
25. HABER J., WATTLES J., CROWLEY M., MANDELL R., JOSHIPURA K., KENT R.L.: "Evidence for cigarette smoking as a major risk factor for periodontitis." J. Periodontol., 64: 16-23, 1993
26. HABER J.: "Smoking is a major risk factor for periodontitis." Curr. Opin.in Periodontol., 12-18, 1994
27. HANES P.J., SCHUSTER G.S., LUBAS S.: "Binding uptake and release of nicotine by human gingival fibroblasts." J. Periodontol., 62: 147-152, 1991
28. HILL P., MARQUARDT H.: "Plasma and urine changes after smoking different brands of cigarettes." Clin. Pharmacol. Ther., 5: 652-658, 1980
29. HOLT P.G., BARTHOLOMAEUS W.N., KEAST D.: "Differential toxicity of tobacco smoke to various cell types including those of the immune system." Ajebac, 52 (Pt.1): 211-214, 1974
30. ISMAIL II., BURT B.A., EKLUND S.A.: "Epidemiologic patterns of smoking and periodontal disease in the United States." J. Am. Dent. Assoc., 106: 617-623, 1983
31. JOHNSON W.T., JOHNSON G.K., TODD G.L., FUNG Y.K.: "Effects of systemic and topical nicotine on pulpal blood flow in dogs." Endod. Dent. Traumatol., 9: 71-74,
32. 1993 KENNEY E.B., KRAAL J.H., SAXE S.R., JONES J.: "The effect of cigarette smoke on human oral polymorphonuclear leucocytes." J. Periodontal Res., 12: 227-234, 1977
33. KRAAL J.H., CHANCELLOR M.B., BRIDGES R.B., BEMIS K.G., HAWKE J.E.: "Variations in the gingival polymorphonuclear leukocyte migration rete in dogs induced by chemotactic autologous serum and migration inibitor from tobacco smoke." J. Periodontal Res., 12: 242.249, 1977
34. LEONE C., BURKLEY T., MONACO G., LAI Y.L., LIMB L.: "Nicotine effect of fibroblasts." J. Dent. Res., abst. 1540, 1995
35. LIE M.A., VAN DER WEIJDEN G.A.,TIMMERMAN M.F.,LOOS B.G.,VAN STEEMBERGEN T.J.M., VAN DER VELDEN U.: "Oral microbiota in smokers and non smochers in natural and experimentally-induced gingivitis." J. Clin. Periodontol., 25: 677-686, 1998
36. LIE M.A., TIMMERMAN M.F., VAN DER VELDEN U., VAN DER WEIJDEN G.A.: "Evaluaton of 2 methods to assess gingival bleeding in smokers and non smokers in natural and experimental gingivitis." J. Clin. Periodontol., 25: 695-700, 1998
37. LINDEN G.J., MULLARY B.H.: "Cigarette smoking and periodontal destruction in young adults." J. Periodontol., 65: 718-723, 1994
38. LOCKER D., LEAKE J.L.: "Risk indicators and risk markers for periodontal disease experience in older adults living indipendently in Ontario, Canada." J. Dent. Res., 72: 9-17, 1993
39. MAcGREGOR I.D.M.: "Toothbrushing efficiency in smokers and non smokers." J. Clin. Periodontol., 11: 313-320, 1984
40. MAcFARLANE G., HERZBERG M., WOLFF L., HARDE N.: "Refractory periodontitis associated with abnormal polymorphonuclear leukocyte phagocytosis and cigarette smoking." J. Periodontol., 63: 908-913, 1992
41. MARTINEZ-CANUT P., LORCA A., MAGAN R.: "Smoking and periodontal disease severity." J. Clin. Periodontol., 22: 743-749, 1995
42. MONACO G., CHECCHI L.: "Fumo e malattia parodontale. Rassegna della letteratura." Prev. & Assist. Dent., 4: 11-16, 1996
43. NOBLE R.C., PENNY B.B.: "Comparison of leukocyte count and function in smoking and non-smoking young men." Infection and Immunity, 9: 550-555, 1975
44. PEACOCK M.E., SUTHERLAND D.E., SCHUSTER G.S., BRENNAN W.A., O’NEAL R.B., STRONG S.L., E COLL.: "The effect of nicotine on reproduction and attachment of human gingival fibroblasts in vitro." J. Periodontol., 64: 658-665, 1993
45. PERSSON L., BERGSTROM J., GUSTAFSSON A., ASMAN B.: "Tobacco smoking and gingival neutrophil activity in young adults." J. Clinic. Periodontol., 1: 9-13, 1999
46. PINDBORG J.J.: "Tobacco and gingivitis. II. Correlation between consumption of tobacco, ulcero-membranous gingivitis and calculus." J. Dent. Res., 28: 460-463, 1949
47. PREBER H., BERGSTROM J., LINDER L.E.: "Occurence of periodontophatogens in smoker and non-smoker patients." J. Clin. Periodontol., 19: 667-671, 1992
48. PREBER H., BERGSTROM J.: "The effect of non-surgical treatment on periodontal pockets in smokers and non-smokers." J. Clin. Periodontol., 13: 319-323, 1985
49. PREBER H., BERGSTROM J.: "Effect of cigarette smoking on periodontal healing following surgical therapy." J. Clin. Periodontol., 17: 324-328, 1990
50. PREBER H., LINDER L., BERGSTROM J.: "Periodontal healing and periodontogenic microflora in smokers and non-smokers." J. Clin. Periodontol., 12: 946-952, 1995
51. RAULIN L.A., McPHERSON III J.C., McQUADE M.J., HANSON B.S.: "The effect of nicotine on theattachment of human fibroblasts to glass and human root surfaces in vitro." J. Periodontol., 5: 318-325, 1988
52. RENVERT S., DAHLEN G., WIKSTROM M.: "The clinical and microbiological aspects of non-surgical periodontal therapy in smokers and non-smokers." J. Clin. Periodontol., 2: 153-157, 1998
53. SHEIHAM A.: "Periodontal disease and oral cleanliness in tobacco smokers." J. Periodontol., 42: 259-263, 1971
54. STOLTEMBERG J.L., OSBORN J.B., PIHLSTROM B.L., HERZBERG M.C., AEPPLI D.M., WOLFF L.F., E COLL.: "Association between cigarette smoking, bacterial pathogens, and periodontal status." J. Periodontal., 64: 1225-1230, 1993
55. SWEET J.B., BUTLER D.P.: "The relationship of smoking to localized osteitis." J. Oral. Surg., 7: 732-735, 1979
56. TRIKILIS N., RAWILSON A., WALSH T.F.: " Periodontal probing depht and subgengival temperature in smokers and non-smokers." J. Clin. Periodontol. 1: 38-43, 1999
57. TROMBELLI L., SCABBIA A.: "Healing response of gingival recession defects following guided tissue regeneration procedures in smokers and non smokers." J. Clin. Periodontol., 8: 529-533, 1997