The Effect of Conventional Versus Electronic Cigarette Use on Treatment Outcomes of Peri-Implant Disease

doi:10.21203/rs.3.rs-268135/v1

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Research article

The Effect of Conventional Versus Electronic Cigarette Use on Treatment Outcomes of Peri-Implant Disease

https://doi.org/10.21203/rs.3.rs-268135/v1

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Background: Treatment outcomes associated with the peri-implant diseases are significantly influenced by individual habits. Several studies identified smoking as one of the important risk factors associated with ineffective treatment outcomes. The present study aims to compare changes in periodontal clinical parameters between conventional and electronic cigarette smokers with non-smokers. It further evaluates changes of salivary inflammatory biomarkers (IL-1 β, IL-6, MMP-8 and TIMP1) after treating peri-implantitis. Participants were divided into three groups: conventional cigarette smokers, E-smokers and non-smokers; each consisting of 20 participants.

Results: Findings of the study indicated that the change in gingival color from red to pink is significantly higher in cigarette smokers and non-smokers when compared with electronic smokers (p=0.043). The gingival consistent changed to be firm in cigarettes smokers and non-smokers. The prevalence of PI, BOP and PD it has reduced across the groups of cigarette and smokers over the four intervals of observation. Besides, no statistically significant difference with the means values of KTW. The level of MMP-8 at baseline of three groups had reduced but increased marginally at sixth month and at the completion of one year among cigarette and e-smokers. The mean IL-6 values had significantly reduced, except for electronic smoking. The IL-1 β values had significantly increased in all groups. The increase of TIMP-1 values in non-smokers is higher at all the three-time points.

Conclusion: All clinical parameters show enhancement post treatment. However, salivary biological biomarkers (MMP-8, IL-1 β and IL-6) have shown a decline in all groups treated.

Dentistry

Smoking

Peri-Implant Disease

Risk factor

Peri-implantitis therapy

Dental implant fixtures, being the commonly used treatment for peri-implant diseases develop significant challenges for dental surgeons due to the inflammatory conditions taking place post treatment [1, 2]. The presentation of peri-implant disease appears as an inflammation of the tissue surrounding the implant providing support to the peri implant tissues during chronic conditions [3]. Peri-implant mucositis and peri-implantitis are the two types of peri-implant disease which are characterized and portrayed at the Primary European Workshop on Periodontology in Ittingen in 1993 [4]. Peri‐implant mucositis is defined as the inflammation of mucosa that surrounds the implant fixture without extending to the supportive alveolar bone [5]. Some common symptoms of peri-implant mucositis include; redness, swelling and bleeding on gentle probing [6]. Peri‐implantitis on the other hand refers to a condition that affect the tissues around the dental implant by the inflammatory reaction on mucosa and permanent loss of supporting alveolar bone [7]. According to the consensus report of World Workshop (2017), peri-implant diseases, based on their clinical presentation are divided into four categories: 1. Peri-implant health 2. Peri-implant mcositis 3. Peri-implantitis 4. Soft and hard tissue deficiencies [8].

Atieh et al. [9] in the systematic review and meta-analysis outlined three important risk factors associated to the development of peri-implantitis, which include: smoking, diabetes and periodontal disease. A conventional tobacco cigarette has been identified as one of the most causative factors of peri-implantitis and periodontitis [10]. Studies indicated that the overall frequency of participants presenting the peri-implant diseases has been significantly higher among smokers [1, 9, 11, 12]. Besides, a robust overall correlation has been reported between smoking, tooth loss and implant failure [12–14]. Furthermore, a prospective study showed a high degree of implant failure in patients that are heavy smokers [15].

In 2004, Electronic cigarette (E-cigarette) was introduced as a new version of nicotine delivery system [16]. A study suggested that E-cigarette is less cytotoxic than the tobacco cigarette [17], while another study indicated that menthol in E-cigarettes causes similar harm to periodontal ligament fibroblast in comparison with a conventional cigarette [18]. This is due to the fact that nicotine serves as the main ingredient in both conventional and E-cigarettes and is present in similar concentration causing very similar vasoconstrictive activity on gingival blood vessels, along with its damaging effect on gingival fibroblast [19].

Since peri-implantitis is an inflammatory process, detection of biological inflammatory markers’ levels was found to be valid additive diagnostic tools to detect the peri-implant disease activity. These markers can be found in peri-implant soft tissue, peri-implant sulcular fluid (PISF) or saliva [20–21]. Certain biomarkers when extracted from active sites of peri-implantitis showed statistical difference when compared to healthy stable peri-implant sites [22]. These include matrix metalloproteinase MMP-8 (Collagenase-2) which is the main enzyme in extracellular collagen matrix degradation [21, 23]. Furthermore, several investigations reported that MMP-8/TIMP-1 ratio can be a predicable sign of active hard tissue destruction around implant that can be faster than the area around periodontitis lesion [24]. The previous was also reported in sites with peri-implant disease progression when measured in oral saliva [25]. Another important marker of active inflammatory process is Interleukin 1beta (IL-1β). A strong correlation was found between high level of IL-1β and abrupt inflammatory progressive stages when measured from different sites [26]. Similarly, high concentration of interleukin 6 (IL-6) appears in peri-implantitis cases which was correlated with active phase of bone resorption [27]. On the other hand, the inhibitor of matrix metalloproteinase 1 (TIMP-1) can be used as a detection tool to disease regression since it was proven to be in higher concentrations in sites exhibiting sign of periodontal and peri-implant tissue health [28]. The success of the implant treatment depends on all the above stated considerable factors which in combination contribute towards the wellbeing of patient’s periodontal health.

To emphasize it further, the success of dental implant is important in terms of both patients’ and clinical perspective as it is one of the expensive periodontal treatment, and its failure may represent a poor financial investment for patient Another considerable point is the treatment procedure itself which entails significant surgical risks and complications as a result of implant failure. Since according to the recent statistics, 15.60% population has been identified as smokers in Saudi Arabia [29], and is more prone to develop peri-implantitis, thus it is crucial to understand the effect of peri-implant treatment on both e-smokers and conventional smokers prospectively in comparison with non-smokers. Furthermore, the manifestation of electronic smoking when compared to conventional cigarette smoking on peri-implantitis treatment is still lacking in the present literature; therefore, this prospective study intends to achieve the following aims:

To compare clinical marker changes between conventional and E- cigarette smokers with non-smokers.

To evaluate changes of salivary inflammatory biomarkers (IL-1 β, IL-6, MMP-8 and TIMP-after treating peri-implantitis.

Study Design and Participant

The study follows a cross sectional design and was conducted in King Saud University’s Dental College, Riyadh, Saudi Arabia, and included patients of both genders, who received conventional-length (> 6 mm), non-turned, 2- and 3-piece titanium implants* (Straumann) and those suffering from peri-implantitis on the same implant placed. 60 patients with dental implants were enrolled in the study consisted of partially edentulous patients with one or more missing tooth being replaced by single crown implant-supported restoration with a minimum period of 6 months of functional occlusal loading during the appointment for an evaluation. However, in accordance with Konstantinidis et al., [30] and Schwarz et al., [31], the following exclusion criteria were elucidated: (1) any uncontrolled systemic disorders that could influence the implant therapy outcome (e.g., diabetes [HbA1c > 7], osteoporosis); (2) pregnancy or breastfeeding in women; (3) Intake of medicaments that could have an effect on turnover of the bone and mucosal healing (i.e., steroids, antiresorptive therapy); (4) Antibiotic use for a medical or dental reason within the 2 months prior to the examination; (5) Any restorations that did not allow for the calculation of periodontal pocket depths(PPD); (6) lack of ability or refusal to sign the informed consent form and (7) Absence of baseline radiographs taken at the time of placement of the implant or final crown.

Participants were arranged according to their smoking status as follows; Group 1: conventional cigarette smokers; Group 2: E-smoker and Group 3; non-smokers. The enrolled patients were consecutively included, and the data were collected from June 2018 to September 2019 during regular implant maintenance visits. Implant surgical operations and prosthetic restorations were all performed in the same institute. Furthermore, all clinical measurements were taken by a single-blinded investigator to exclude possible operator-dependent bias at baseline, and the time intervals of one month, six months and one year of post peri-implantitis treatment.

Anamnestic Data and Implant Site Characteristics

The following study variables were assessed: 1. Patients’ age 2. Gender and 3. Smoking frequency. The following implant site characteristics were considered: 1. Implant type 2. Implant size 3. Implant location.

Treatment Protocol

Before the intervention, all patients were subjected to initial treatment comprising diagnosis of peri-implant mucosal health and marginal bone level according to make uniform proceedings as well as stimulus and briefing of the patients. The choice of therapeutic approach was based on the severity of clinical and radiologic parameters, time interval between first signs of peri-implant pathology and referral to the specialist clinic, and effect of peri-implantitis on the patient’s well-being and oral health-related quality of life. All peri-implantitis cases’ bone morphology and severity were classified according to Monje et al. [32] as Cl II, which is defined as mostly being Supracrestal/horizontal defects. These defects that were accordingly treated with a combination of osseous recontouring and implantoplasty surgery using an open-flap approach and granulation tissue removal using a set of diamond drills (PerioSet; Intensiv Swiss Dental Products, Montagnola, Switzerland) [3, 33].

Clinical Parameter

The following clinical parameters were assessed using a plastic probe (11 Colorvue Probe, Hu-Friedy) at each implant site:

Periodontal probing depth (PD) was measured by inserting the probe within sulcus area with gentle pressure (less than 0.25Ncm) exerted at three points of buccal and lingual around the neck of an implant along with a probe placed parallel to the crown of the implanted tooth titled 10 degrees inward at the proximal points [34].

Bleeding on probing (BOP) was assessed either by the presence (+) or absence (-) of bleeding at the site of probing immediately after periodontal pocket depth measurement [35].

Plaque index (PI) was assessed either by the presence (+) or absence (-) of Plaque on four surfaces (mesial, distal, palatal and buccal) of a crown after placing disclosing agent. The measurements of PD, BOP, and PI were performed at six aspects per implant: mesio-buccal, mid-buccal, disto-buccal, and respective lingual/palatal sites.

Gingival color and consistency were evaluated via direct visual assessment, i.e., visibility of the periodontal probe.

The presence or absence of Keratinized Tissue Width (KTW) (≥ 2 mm) was also assessed. The former was measured from the peri-implant marginal mucosa to the muco-gingival junction (MGJ) at the buccal and lingual marginal portion of the implant’s mucosa. Finally, standardized periapical radiographs were taken at the time of the clinical examination with the long cone paralleling method and film holders (Rinn XCP, Dentsply Corporate, York, PA, USA) and for bone level confirmation compared with a baseline radiograph taken at the time of prosthesis placement [2]. Remarkably, the radiographs were scanned to obtain standardized digital images with a resolution of 1,200 dpi. These digital images were imported and analyzed using specialized computer software (ImageJ v 1.49, Research Services Branch, National Institute of Health, Bethesda, MD, USA). The calibration of the pixel/mm ratio was performed using the length of the implant as a fixed reference point to compensate for the potential radiographic distortion. For the bone loss evaluation, the radiographic distance between the implant shoulder level and the most coronal bone-to-implant contact level was calculated medially and distally, parallel with the long axis of the implant. The same-blinded examiner performed all radiographic measurements.

Biological Parameters and Enzyme-Linked Immuno-Sorbent Assays

Unstimulated saliva samples were collected from all subjects to evaluate the relative amount of MMP-8, IL-6, IL-1 β and TIMP-1. Enzyme-linked immunosorbent assay (ELISA) was used to study the levels biomarkers (Elabsciences ®, Houston, Texas, USA). ELISA results were read at 450 nm by using a microplate reader (Bio-Rad Laboratories Inc., Hercules, CA). ELISAs was performed in accordance with the manufacturer's instructions [30–31]. ELISA kit uses Sandwich-ELISA as the method. The micro ELISA plate provided in the used kit (Elabscience) has been pre-coated with an antibody specific to Human MMP-8, IL-6, IL-1 β and TIMP-1. Standards or samples were added to appropriate micro ELISA plate wells and combined with the specific antibody. Then biotinylated detection antibodies specific for Human testes proteases and Avidin- Horseradish Peroxidase (HRP) conjugate were added to each micro plate successively and incubated. After incubation, free components were washed away.

The substrate reagent was added to each well, only those wells that contain Human MMP-8, IL-6, IL-1 β and TIMP-1, biotinylated detection antibody and Avidin-HRP conjugate appeared blue in color. The enzyme-substrate reaction was terminated by adding Stop Solution and appeared yellow in color. The optical density (OD) was measured by using Biotek Synergy HT microplate reader (Synergy HT, Biotek, Vermont, USA) at a wavelength of 450 nm ± 2 nm. The OD value is proportional to the concentration of biomarkers. The concentrations in samples were calculated by comparing the OD of the samples with the standard curve [36].

Maintenance Visits

Patients were contacted and asked to undergo through clinical and radiologic examination at the time intervals of one month, six months and one-year post treatment. The primary endpoints were the resolution rate of peri-implantitis disease and peri‐implant marginal bone stability after surgical therapy. Disease resolution was assessed according to the absence of the established peri‐implantitis case definition determined as: changes in the crestal bone level in incorporation with bleeding on probing with or without associated deepening of peri‐implant pockets. Peri‐implant marginal bone stability was established if no further or progressive peri‐implant bone loss occurred after surgical combined resective‐implantoplasty therapy over the follow‐up examination [5].

Data Analysis

Descriptive statistics (mean, standard deviation, frequencies and percentages) were used to describe the categorical and quantitative outcome variables. Pearson’s chi-square test was used to compare the distribution of the categorical variables among the three study groups at each point of follow-up. Two-way repeated analysis of variance was used to compare the mean values of quantitative outcome variables among the three study groups across the 4 time points (baseline, one month, six months and one year) of follow up. A p-value of ≤ 0.05 was used to report the statistically significant of results. Statistical analysis was carried out using SPSS 24.0 version (IBM Inc., Chicago USA) statistical software.

Ethical Considerations

The present study was carried out in accordance with the Helsinki Declaration of 1975, as revised in 2013. The protocol used in this study was approved by the Institutional Committee of Research Ethics at King Saud University, Riyadh, Saudi Arabia (87563). Each patient was given a detailed description of the procedure, and an informed consent was obtained prior to participation in the study.

All the selected participants were classified into three groups as per their smoking methods, such that 20 participants were placed in the group of Cigarette smokers, 20 were E-smokers and remaining 20 were non-smokers. The gender distribution across the three groups were approximately evenly distributed. The mean age was higher in cigarette smoking subjects. The implant site was evenly distributed across the groups, with maximum implant site was tooth number 26 in all the three groups. Bone level implant type was higher in subjects who smoke electronic method (95%) and non-smokers (90%). The implant size of 4.1x 10mm was frequently used across the three groups. (Table 1)

Table 1

Characteristics of study subjects with their method of smoking
Characteristics	Cigarettes (n = 20)	Electronic (n = 20)	None (n = 20)
	Mean (SD)	Mean (SD)	Mean (SD)
Age (years)	54.1 (11.5) years	40.8 (11.4) years	46.9 (12.8) years
Gender
Male	12 (60)	9 (45)	10 (50)
Female	8 (40)	11 (55)	10 (50)
	Frequency (%)	Frequency (%)	Frequency (%)
Implant Site
14	2 (10)	2 (10)	2 (10)
15	2 (10)	3 (15)	2 (10)
16	2 (10)	2(10)	3(15)
25	1(5)	0	0
26	4 (20)	5 (25)	4 (20)
34	2 (10)	1 (5)	1 (5)
35	2 (10)	2 (10)	2 (10)
36	2 (10)	2 (10)	2 (10)
45	1 (5)	1 (5)	2 (10)
46	2 (10)	2 (10)	2 (10)
Implant Type
Bone level	13 (65)	19 (95)	18 (90)
Tissue level	7 (35)	7 (35)	29 (10)
Implant Size
4.1x10mm	12 (60)	13 (65)	12 (60)
4.1x12mm 4.8x 10mm	2 (10) 4 (20)	3 (15) 0	2 (10) 3 (15)
3.3x8mm	0	2 (10)	2 (10)
3.3x8mm	2 (10)	2 (10)	1 (5)

Furthermore, findings related to the comparison of outcome variables among the three groups at each of the four observations conducted after specific time intervals are presented in Table 2. The gingival color was red in all the 20 subjects of three groups at baseline, whereas it has changed to pink in 90% of cigarettes smokers, 55% of E- smokers and 100% in non-smokers at one month and similar pattern was observed at six months and at one year of post treatment. The change of gingival color was statistically significant at one year of post treatment, where the change from red to pink is statistically significantly higher in cigarette smokers and non-smokers in comparison with E-smokers (p = 0.043).

Table 2

Comparison of categorical outcome variables in relation to the smoking type over 4 time points of study follow-up period
Outcome Variables	Time period & Smoking type^#
Outcome Variables	Baseline			1 month			6 months			1 Year
Gingival color Red Pink	Cig. F (%)	E F (%)	None F (%)	Cig. F (%)	E F (%)	None F (%)	Cig. F (%)	E F (%)	None F (%)	Cig. F (%)	E F (%)	None F (%)
Gingival color Red Pink	20(100)	20(100)	20(100)	2(10) 18(90)	9(45) 11(55)	0 20(100)	4(21) 15(79)	7(37) 12(63)	2(10) 18(90)	5(25) 15(75)	9(45) 11(55)	2(10) 18(90)
^ꭕ2-value; p-value	----			---			-----			6.307; 0.043*
Gingival consistency Endematous Firm	14(70) 6(30)	10(50) 10(50)	17(85) 3(15)	2(10) 18(90)	9(45) 11(55)	0 20(100)	4(21.1) 15(78.9)	9(47.4) 10(52.6)	2(10) 18(90)	5(25) 15(75)	10(50) 10(50)	2(10) 18(90)
^ꭕ2-value; p-value	5.70; 0.058			14.92; 0.001			7.06 ; 0.029			8.04 ; 0.018*
Plaque index 0 1	9(45) 11(55)	7(35) 13(65)	0 20(100)	16(80) 4(20)	13(65) 7(35)	20(100) 0	15(79) 4(21)	13(68.4) 6(31.6)	18(95) 1(5)	16(80) 4(20)	13(65) 7(35)	19(95) 1(5)
^ꭕ2-value; p-value	11.42; 0.003			8.24; 0.016			--			--
BOP Yes No	13(72) 5(28)	13(76.5) 4(23.5)	16(88.9) 2(11.1)	3(15) 17(85)	2(10) 18(90)	0 20(100)	5(26.3) 14(73.7)	9(47.4) 10(52.6)	2(10.5) 17(89.5)	6(30) 14(70)	10(50) 10(50)	2(10) 18(90)
^ꭕ2-value; p-value	1.64; 0.441			----			----			7.62; 0.022*
^# Cig.= Cigarettes; E = Electronic; None = No smoking *Statistical Significant: P < 0.05

The gingival consistency (Edematous & firm) distribution across the three groups is not statistically significant at baseline, but it is statistically significant at one-month (p = 0.001), six months (p = 0.029) and at the completion of one-year (p = 0.018*) post treatment. A statistically significant change was observed in cigarette smokers and non-smokers, where 70% of Edematous at baseline in cigarettes smokers had changed to 'firm' in 90% at one-month duration, 78.9% after six months and 75% at the completion of one year. Whereas 85% of Endematous at baseline in non-smokers had changed to 'firm' in 100% at one month, 90% after six months and 90% at the completion of one-year. The difference is statistically significant at one month, (p = 0.001), after six months (p = 0.029) and at the completion of one year (p = 0.018). The plaque index distribution (0 vs 1) across the three groups has shown statistically significant difference at baseline, where 100% of non-smokers had plaque index 1, when compared with other two groups (55% & 65%) who had plaque index of 1 (p = 0.003). But significant change was observed at one month, where the plaque index of 100% of non-smokers had changed to ‘0’ and 35% change in cigarettes and 30% change in E-smokers which is statistically significant (p = 0.016). Similar pattern of change was observed after six months and one year of post treatment. The prevalence of BOP was observed in the three groups as 72%, 76.5% and 88.9% at baseline; however, at one month it had reduced to 15%, 10% and 0%. A significant increase was observed among the three groups after one year of the treatment, with a p-value of 0.022.

The comparison of clinical parameters among the three groups across four-time intervals is showed in Table 3. However, no statistically significant difference in relation to the mean values of KTW was observed. The mean values of PD have shown statistically significant change across the three groups over the four-time intervals of observation. The mean values of PD had significantly reduced from baseline to one month and the reduction has maintained the same pattern at six months and one-year post treatment, except for E- smoking group where the mean PD values has increased after six months and one year. Both the time period and its interaction with smoking type are statistically significant. (p < 0.0001; p = 0.024).

Table 3

Comparison of quantitative clinical outcome variables in relation to the smoking type over 4 time points of study follow-up period
Outcome Variables	Time period & Smoking type^#-- Mean (Sd.,)
Outcome Variables	Baseline			1 month			6 months			1 Year
KTW	Cig.	E	None	Cig.	E	None	Cig.	E	None	Cig.	E	None
KTW	1.7 (0.9)	1.9 (1.4)	1.9 (1.1)	1.7 (.9)	1.9 (1.4)	1.9 (1.1)	1.8 (1.1)	1.7 (1.3)	1.9 (1.1)	1.7 (0.9)	1.9 (1.4)	1.9 (1.1)
F-value ; p-value	Time period: 0.006; 0.941 Time period ^# smoking type: 0.207; 0.814
PD	6.9 (0.9)	6.3 (1.4)	6.5 (1.3)	4.4 (.5)	4.7 (.5)	4.2 (0.6)	4.7 (0.6)	5.5 (1.1)	4.5 (0.8)	4.8 (0.9)	5.6 (1.1)	4.4 (0.8)
F-value; p-value	Time period: 39.98; p < 0.0001 Time period ^# smoking type : 2.53; 0.024
MMP8	20.1 (6.3)	27.1 (5.3)	9.4 (4.3)	10.1 (1.6)	11.4 (1.8)	3.3 (0.8)	14.9 (16.3)	22.9 (35.2)	5.2 (4.6)	12.2 (5.6)	16.9 (7.9)	4.1 (2.2)
F-value ; p-value	Time period: 8.52 ; p < 0.0001 Time period ^# smoking type : 0.78; p = 0.583
IL6	153.7 (20.6)	183 (8.4)	47.2 (3.7)	63.2 (11.3)	85.6 (6.4)	15.6 (2.3)	65.4 (15.6)	96.3 (34.5)	18.6 (10.6)	80.6 (43.3)	120.6 (50)	19.4 (11.1)
F-value ; p-value	Time period: 127.82; p < 0.0001 Time period ^# smoking type: 10.86; p < 0.0001
IL1 β **	3.55 (0.06)	3.62 (0.08)	2.84 (0.04)	1.96 (0.10)	2.14 (0.11)	1.28 0.17)	2.01 (0.09)	2.44 (0.44)	1.32 (0.19)	2.30 (0.62)	2.84 (0.75)	1.47 (0.49)
F-value ; p-value	Time period: 168.95; p < 0.0001 Time period ^# smoking type : 26.38; p < 0.0001
TIMP1	4.61 (3.4)	1.8 (2.4)	6.9 (2.0)	25.6 (16.8)	14.2 (4.8)	49.8 (19.6)	10.6 (5.4)	5.9 (4.1)	42.3 (25.6)	10.1 (5.8)	5.7 (4.1)	43.6 (24.4)
F-value ; p-value	Time period: 42.44; p < 0.0001 Time period ^# smoking type : 10.12, p < 0.0001
^#Cig.= Cigarettes; E = Electronic; None = No smoking; ^##Log₁₀ values due skewness

The mean values of MMP-8 at baseline of three groups had significantly reduced when compared with the time interval of one month in all the three groups, but increased marginally at sixth month and at the completion of one year. However, the change is statistically significant in the mean values of MMP-8 of all the three groups when compared with baseline to other three time points. Also, for E-smoking group, significant difference in the mean values of MMP-8 at the three different time intervals (one month, six months and at the completion of one year) was observed in comparison with the cigarette smokers and non-smokers.

The mean values of IL-6 have shown statistically significant change across the three groups when observed at the given time intervals. The mean values of IL-6 had significantly reduced from baseline to one month, following a similar pattern after six months and one year. Findings indicated statistically significant association between the time period and its interaction with smoking type (p < 0.0001; p < 0.0001).

The comparison of mean values of IL-1 β has shown statistically significant change across the three groups over the four intervals of observation. The mean values of IL-1 β had significantly reduced from baseline to one month and the reduction of values were consistent after six months. However, the mean values of IL-1 β has increased after the completion of one year but was still significantly lower than the baseline values. Both the time period and its interaction with smoking type are statistically significant (p < 0.0001; p < 0.0001).

The comparison of mean values of TIMP-1 has shown statistically significant change across the three groups during the four time intervals. Across all the three groups, the increase in the mean values TIMP-1 from baseline is substantial but the increase of TIMP-1 values in non-smokers is significantly higher at all the three intervals when compared to its base line values. A statistically significant association was found between the time period and smoking type (p < 0.0001; p < 0.0001). (Table 3).

The present study compared clinical marker changes between conventional and E- cigarette smokers with non-smokers, along with the evaluation of salivary inflammatory biomarker changes among patients treated with peri-implantitis. Prior studies outlined the role of cigarette consumption as a risk factor for peri-implantitis and reported conflicting results [37–38]. Recent evidence found that smoking, among various other cofactors, had a negative impact on clinical outcomes and peri-implant lesion resolution [37]. It further stated smoking as an essential risk indicator for surgical peri-implantitis treatment success [39–40].

However, findings in the current study showed that short term outcomes were comparable at one-month post-therapy. However, at one-year follow-up, non-smokers had favorable results when compared to both groups of smokers. Interestingly, E-smokers showed persistent inflammatory outcomes compared to cigarette smokers in gingival color and consistency. This unexpected finding may suggest that specific components in smoking are responsible for reduced blood flow and inflammatory responses in comparison with vaping as supported by previous observations provided by de Waal et al., [39].

As for plaque accumulation, the plaque index was higher in the group of non-smokers in comparison with the other two groups at baseline. Nevertheless, the significant clinical improvement observed in the three groups noted through one month, decreased slightly after six months and one year follow up but maintained in a lesser amount compared to baseline. The prevalence of BOP showed improvement as well after the treatment. However, it can be noticed that changes were more among non-smokers compared with other smoking groups due to the vasoconstrictive effect of nicotine and other smoke by-products as well as heat on blood vessels and capillaries [37]. Finally, mean PD reduced among non-smokers and cigarette smokers in all the four intervals, while in E-smokers, this reduction had relapsed after six months.

In regards to salivary biological biomarkers which can give a depth vision to the systemic biologic response to different levels and fluctuations of inflammation, MMP-8, IL1 β and IL-6 have shown statistically significant decrease after one month of the treatment from the baseline. However, their values raised marginally at sixth month and one year after the treatment having more raise among E-smokers followed by cigarette smokers and non-smokers. This observation is in line with several previous studies, as for instance, Al-Sowygh et al. [41] in a case-control study reported higher levels of MMP-8 in smoking groups when compared with non-smoker. Furthermore, in another case-control study by Abduljabbar et al., [42] a significantly increased level of IL-1 β and IL-6 in the peri-implant sulcus fluid was observed among smokers’ group in comparison to the non-smokers [42]. On the other hand, all study groups revealed increase values of TIMP-1 throughout the treatment period and demonstrating the highest values among non-smokers and least among E-smokers. In contrast, these values again showed some relapse through long term follow up, especially in the E-smoking group.

These changes in biological markers confirm the clinical presentations among the three groups along the period of the study, proving that non-smokers group has the best response to peri-implantitis treatment compared to other groups. Results proposed in this study confirm that the major source of inflammation and infection is controlled, and preferable biological and clinical response is usually predicted [40]. Moreover, when major risk factors are present such as smoking, the expected treatment outcomes can be more challenging to attain optimal success. Several previous studies had elaborated that even among smokers, successful immediate results can be shown post-treatment of periimplantitis [38].

Upon authors knowledge, this study is considered the first study to compare peri-implantitis treatment outcomes among cigarette smokers and E-smokers. Since E-smoking is a new and widely spread method among people, the investigations related to the effect of this type of smoking on the periodontium and implant supporting structure are important. Therefore, it is worthwhile to provide investigational efforts to understand how this new type of smoking can act among inflammatory cascades. Moreover, the response in regards to peri-implant and periodontal tissue is to achieve proper treatment protocol and prevention for electrical smokers receiving dental implants.

Limitations of the present study include relatively sample size in each group as well as a lack of information from certain participants regarding the frequency of smoking, number of cigarettes (e.g. Heavy smokers vs light smokers) as well as types of E-cigarettes. Therefore, future researchers are recommended to conduct the study over a large sample size, along with the inclusion of diverse demographic and racial groups to understand different responses and to compare different types of electronic smoking methods. The above recommendations are further important to understand the variations among different products and to have more understanding of their by-products. Finally, it is suggested to compare different approaches to peri-implant treatment based on different peri-implantitis stages and related defects’ properties to achieve a cornerstone of favorable treatment approaches that can achieve long term success.

Among patients suffering from peri-implantitis, E-smokers have shown least favorable long term clinical and biological outcomes related to treatment in compared to cigarette smokers and non-smokers which the last showed the best long-term outcomes after 1 year follow up. Overall, all clinical parameters show enhancement after starting the therapy in comparison to baseline. Salivary biological biomarkers (MMP-8, IL1 β and IL-6) have shown a decline in all groups treated. However, their values increased marginally at six months and one year having more raise among E-smokers followed by cigarette smokers followed by non-smokers. On the other hand, the TIMP1 growing in all groups throughout the treatment.

Bleeding on Probing (BOP)

Bleeding on probing is used as the diagnostic tool for the presence of periodontal diseases, and serve as a reliable indicator for gingival inflammation and is also helpful for future clinical procedures.

Electronic Cigarette (E-Cigarette)

It refers to a device that is pen, cigar or cigarette shaped and consists of flavorings, nicotine, and other chemicals instead of nicotine (National Cancer Institute, n.d.).

Interleukin 1 beta (IL-1 β)

refers to a proinflammatory cytokine, which is critical for host defense responses to injury and infection (Lopez-Castejon and Brough, 2011).

Keratinized Tissue Width (KTW)

Keratinized tissue refers to the band of tissue presented around the teeth, specifically where gums meet. However, the width of Keratinized is important to assess when planning for dental implant placement.

Matrix Metalloproteinase (MMP-8)

MMP-8 belongs to the extracellular proteinases that consists of two conserved motifs. One of the major functions of MMM is to prevent from catalytic activity.

Probing Depth (PD)

PD refers to the depth of periodontal pocket or sulcus, that is measured by assessing the distance between gingival margin to the base of sulcus (Farlex, n.d.).

Tissue Inhibitor of Metalloproteinase (TIMP-1)

TIMP are the regulators of protein in MMPs family, and plays a critical role in evaluating the influence proposed by the extracellular matrix (Murphy, 2011).

Ethical approval and consent to participate

The study has been declared by the committee of King Saud University.

Consent for publication

Not applicable

Availability of data and materials

The datasets used and analyzed during the current study are available from the corresponding author on reasonable request.

Competing interest

The authors declare no competing interest.

Funding

This research is not funded by any resource.

Author contributions

RAJ: conception design, correspondence, literature, analysis and editing.

MZ: analysis and drafting.

MAS: analysis and drafting.

Acknowledgement

The authors are very thankful to all the associated personnel in any reference that contributed in/for the purpose of this research.

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You are reading this latest preprint version

The Effect of Conventional Versus Electronic Cigarette Use on Treatment Outcomes of Peri-Implant Disease

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Version 1

Abstract

Background

Methods

Study Design and Participant

Anamnestic Data and Implant Site Characteristics

Treatment Protocol

Clinical Parameter

Biological Parameters and Enzyme-Linked Immuno-Sorbent Assays

Maintenance Visits

Data Analysis

Ethical Considerations

Results

Discussion

Conclusion

Abbreviations

Declarations

References

Status:

Version 1