Received: 13 January 2018 | Revised: 25 January 2018 | Accepted: 27 January 2018

DOI: 10.1111/cid.12597

ORIGINAL ARTICLE

Peri-implant parameters, tumor necrosis factor-alpha, and

interleukin-1 beta levels in vaping individuals

Khulud A. Al-Aali CAGS, DScD1 | Mohammed Alrabiah MDS, FRCDC2 |

Aws S. ArRejaie CAGS, DScD, FRCDC2 | Tariq Abduljabbar BDS, MSc, DMSc2 |

Fahim Vohra BDS, MClinDent, MProsRCS2 | Zohaib Akram BDS, MDSc3

1
Department of Prosthodontics, College of
Dentistry, Princess Nourah Bint
Abstract
Abdulrahman University, Riyadh, Saudi
Background: To the author’s knowledge, there has been no study that has assessed clinical, radio-
Arabia
2
graphic, and immunological peri-implant parameters among individuals vaping e-cigarette (e-cig).
Department of Prosthetic Dental Science,
College of Dentistry, King Saud University, Purpose: This pilot study aimed to compare clinical and radiographic peri-implant parameters and
Riyadh, Saudi Arabia
levels of tumor necrosis factor alpha (TNF-a) and interleukin (IL)-1b levels among individuals vap-
3
Department of Periodontology, Faculty of
ing e-cigs and never smoker (NS).
Dentistry, Ziauddin University, Karachi,
Pakistan Materials and Methods: Forty-seven individuals vaping e-cigs (group-1) and 45 NS (group-2)
were included. Demographic and implant-related data were collected using a structured baseline
Correspondence
Tariq Abduljabbar, Department of questionnaire. Peri-implant plaque index (PI), bleeding on probing (BOP), and probing depth (PD)
Prosthetic Dental Science, College of were recorded and peri-implant bone loss (PIBL) were assessed using standardized digital radio-
Dentistry, King Saud University, Riyadh graphs. Enzyme-linked immunosorbent assay was used to assess the levels of TNF-a and IL-1b in
11545, Saudi Arabia.
peri-implant sulcular fluid.
Email: tajabbar@ksu.edu.sa
Results: Bleeding on probing showed statistically significantly higher values in group-2 patients as
Funding information
compared to group-1 patients (P < .01). Probing depth  4 mm and PIBL was statistically signifi-
Grant Sponsors: College of Dentistry
Research Center, King Saud University, cantly higher in group-1 patients as compared to group-2 patients (P < .05). Mean concentrations
Saudi Arabia; Deanship of Scientific of TNF-a (P < .001) and IL-1b (P < .01) were statistically significantly increased in individuals in
Research, King Saud University, Saudi
group 1 as compared with group 2. A significant positive correlations were found between TNF-a
Arabia
levels and BOP (P 5 .024) and PIBL (P 5 .016); and significant positive correlation was found
between IL-1b and PIBL (P 5 .018) in group 1, respectively.

Conclusions: Clinical and radiographic peri-implant parameters are compromised among vaping
individuals. Increased levels of proinflammatory cytokines in peri-implant sulcular fluid may suggest
greater local inflammatory response in vaping individuals for peri-implant inflammation.

KEYWORDS
electronic cigarettes, interleukin, peri-implant bone loss, tumor necrosis factor alpha

1 | INTRODUCTION and an atomizer connected by a battery. The heating element trans-

Electronic cigarette (also known as e-cig) is a new form of tobacco
smoking habit which is more common among young adults (age, 18–25
1
years) and poses a serious health concern. Electronic cigarettes are
available in pen-shaped devices that are battery operated and consist
of a metal-heating element in a stainless steel case, a cartridge within,
forms the solution containing a mixture of chemicals including nicotine
and other base-carrying additives such as propylene glycol, glycerine/
glycerol, and flavoring agents that give fruity flavors.2 Individuals may
misapprehend e-cig vaping as less harmful than regular cigarette smok-
ing.3 Recent data by several researchers have suggested that vaping e-
cigs aerosol causes increased oxidative/carbonyl stress, inflammatory

Clin Implant Dent Relat Res. 2018;1–6. wileyonlinelibrary.com/journal/cid V

C 2018 Wiley Periodicals, Inc. | 1
2 |
responses, alteration of lung cellular function, and promotes DNA
4,5
damage.
From dental health perspective, vaping has been associated with
several oral disorders including submucous fibrosis and periodontal dis-
eases.6,7 In a laboratory investigation by Sundar and colleagues8
reported that e-cig aerosols with flavoring agents may have a negative
impact on oral epithelial cells and gingival fibroblasts through DNA
damage and elevated expression of proinflammatory cytokines such as
cyclooxygenase (COX)-2 and prostaglandin E2 (PGE2). Furthermore, in
a recent cross-sectional pilot study by Javed and colleagues9 demon-
strated statistically higher periodontal inflammation among individuals
vaping e-cigs as compared to never smokers (NSs). It is postulated that
the same mechanisms may be associated with soft tissue inflammation
around dental implants in individuals vaping e-cigs. To the authors’
knowledge from indexed literature, there are no clinical studies that
have investigated clinical (plaque index [PI], bleeding on probing [BOP],
and probing depth [PD]) and radiographic (peri-implant bone loss
[PIBL]) status among individuals vaping e-cigs. We hypothesize that (1)
clinical and radiographic peri-implant parameters are poor in vaping
individuals compared with NS; and (2) the levels of tumor necrosis fac-
tor alpha (TNF-a) and interleukin (IL)-1b in peri-implant sulcular fluid
(PISF) are higher among vaping individuals compared with NS.
This pilot study aimed to compare the clinical and radiographic
peri-implant inflammatory parameters and the levels of TNF-a and IL-
1b among individuals vaping e-cigs and NS.
2 | MATERIALS AND METHODS
2.1 | Ethical guidelines
This study was performed by following guidelines recognized by the
Declaration of Helsinki as revised in 2013 for experimentation involv-
ing human patients. The study protocol was reviewed and approved by
the research review committee of Ziauddin University. All participants
were requested to read and sign a consent form that explained the
objectives and methods of this study. All individuals had the rights to
retire from the study at any stage without penalty.
2.2 | Study groups
All study individuals were recruited between January 2016 and March
2017. A total of 92 individuals were enrolled and recruited from special-
ist prosthodontic private practice (T. Abduljabbar). All study participants
had noncontributory medical condition and were either habitual vaping
e-cigs (group 1), or had never used tobacco in any form (group 2).
2.3 | Inclusion and exclusion criteria
The following inclusion criteria were entailed: (a) group 1: current
vapers who reported vaping e-cigs for at least the past year; (b) group
2: participants who never consumed tobacco in any form during their
life time10; and (c) at least 1 dental implant in both groups which has
been in service for 36 months. Exclusion criteria were as follows: (i)
current cigarette smokers, (ii) waterpipe smokers, (iii) smokeless
AL-AALI ET AL.
tobacco users, (iv) patients suffering from debilitating systemic disease
such as diabetes mellitus, acquired immune deficiency syndrome/HIV,
cardiovascular disorders, and renal diseases, (v) edentulous patients (vi)
participants who had used antibiotics, steroidal, or nonsteroid anti-
inflammatory drugs within the past 6 months, and (vii) patients who
had undergone periodontal therapy within the last 6 months.
2.4 | Study questionnaire
All participants in both groups were handed a baseline structured ques-
tionnaire that included the following details: (a) demographics (gender,
age); (b) mean duration of implants in service; (c) duration and daily fre-
quency of vaping e-cigs; (d) duration of vaping session (in minutes) of
e-cigs; and (e) oral hygiene care that included details regarding daily
brushing frequency.
2.5 | Clinical peri-implant assessment
All clinical examinations were carried out by a single masked evaluator
(FV). The kappa statistics for intra-examiner reliability assessing peri-
implant PD was .89 and considered a good agreement. Peri-implant
parameters were recorded using peri-implant PI, BOP, and PD of
4 mm with references to the Consensus report of the Seventh Euro-
pean Workshop on Periodontology-2011.11 All recordings were
recorded at 6 sites of each implant (mesiobuccal, mid-buccal, distobuc-
cal, distolingual/palatal, mid-lingual/palatal, and mesiolingual/palatal)
and reported as mean percentages per individual. Probing depth was
measured to the closest millimeter by the help of a manual periodontal
probe (UNC-15 Hu-Friedy, Chicago, Illinois).
2.6 | Radiographic evaluation of peri-implant
bone loss
All radiographic examinations were carried out by a trained assessor
(ZA) who was masked to the study groups. The kappa statistics for radi-
ographic evaluation was .80. Digital periapical radiographs were taken
and assessed on a standardized computer display (Samsung SyncMas-
ter digital TV monitor, Korea) using an image analyzer (Scion Image
Analyzer, Scion, Frederick, Maryland).12 These radiographs were further
scanned at 800 dots per inch using a scanner (HP Scanjet 3c/1, Hew-
lett Packard, Singapore). Peri-implant bone loss was measured on the
radiograph as the vertical distance from the crest of the alveolar bone
to the platform of dental implant.13
2.7 | Collection of PISF
Supragingival plaque was carefully removed from the crown surface
and peri-implant sites were isolated with sterile cotton rolls and dried
with an air syringe. Two PISF samples were collected from each sample
by inserting paper strips (Periopaper, Interstate Drug Exchange,
Amityville, New York) in 1–2 mm of peri-implant sulcus or pocket for
30 seconds. Contaminated PISF samples with blood stains or saliva
were discarded and new PISF samples were collected from the same
site after 15 minutes, if required. The collected PISF volume was
AL-AALI ET AL. | 3

measured using a calibrated electronic gingival fluid measuring device T AB LE 1 Demographic and implant related characteristics of the
(Periotron 8000, Oraflow, Inc., Amityville, New York). The 2 PISF sam- study groups
ples from the same site were pooled and eluted in 1 mL phosphate- Vaping Never
buffered saline for 1 hour before freezing at 2808C. individuals smokers
Parameters (group 1) (group 2)

Total participants (n) 47 45

2.8 | Measurement of TNF-a and IL-1b in PISF
Gender (males) 47 45
Analyses of biomarkers were carried out as explained in the previous
study.14 Centrifugation of all PISF samples was carried out at 5000g Mean age 6 SD (in years) 35.8 6 6.2 42.6 6 2.7

for 15 minutes at 48C. The levels of TNF-a and IL-1b were quantified Total number of implants 68 57
using enzymatic immunosorbent assay (ELISA) according to the manu- Implant position (maxilla/mandible) 46/22 34/23
facturer’s recommendations (Quantikine, R&D Systems, Minneapolis,
Duration of implants 51.8 6 13.7 47.2 6 20.5
Minnesota). In summary, 100 lL of detection antibody was distributed in months (mean 6 SD)
in to the wells, except blank, mixed gently, and incubated overnight at
Mean duration of habit (in years) 4.4 6 1.8 –
room temperature. Plates were washed thrice with standard solution
Daily frequency of habit 6.5 6 0.9 –
and PISF was dispensed in duplicate in to the wells. After incubation,
the plates were washed again with wash buffer and incubated with Mean duration of session 37.7 6 11.3 –
(in minutes)
100 mL of conjugate for 1 hour at room temperature. Plates were
washed again thrice and 100 mL of substrate was dispensed and incu- Brushing frequency (%)

bated in the dark for 15 minutes at room temperature. The reaction Once 56 60
was terminated by adding 50 mL of stop solution, and absorbance was Twice 44 40
determined in an automated microplate spectrophotometer Bio-Rad,
Hercules, California, USA. The levels of TNF-a and IL-1b were deter-
mined as picograms per milliliters (pg/mL). The results were calculated frequency of vaping e-cigs was 6.5 times. Duration of vaping session
using the standard curves created in each assay. was 37.7 minutes. Among patients in groups 1 and 2, twice brushing
daily was reported by 44% and 40% of individuals in group 1 and group
2.9 | Statistical analyses 2, respectively (Table 1).

Statistical analyses were carried out using a statistical software (SPSS v.

23, IBM, Chicago, Illinois). Data were reported as percentages of means 3.2 | Clinical and radiographic peri-implant parameters
with standard deviations. Normality of distribution of the variables was
tested with Shapiro–Wilk and Kolmogorov–Smirnov tests and further Clinical and radiographic findings for vaping individuals and NS are listed

confirmed by Q–Q plots. Between-group comparison of means for clini- in Table 2. The mean findings of peri-implant BOP (P < .01) showed

cal parameters was verified with Kruskal–Wallis test. The comparison of statistically significantly higher values in group-2 patients as compared

cytokine levels between groups was performed using Mann-Whitney U to group-1 patients. Probing depth of 4 mm was statistically signifi-

test. Bonferroni post hoc adjustment test was applied for multiple com-
parisons. Power and sample sizes were calculated using nQuery Advisor
software. 15
With inclusion of at least 45 patients per group (assuming a
standard deviation of 1.0%), the study power was estimated to be 80%
to detect an association between TNF-a and IL-1b levels and clinical
peri-implant parameters among both groups (with a 2-sided significance
level of .05). P value of <.05 was considered statistically significant.
cantly higher in group-1 patients as compared to group-2 patients
(P < .05). Peri-implant PI showed no significant difference between the
groups. Peri-implant bone loss was significantly higher in group-1 indi-
viduals as compared to group-2 individuals (P < .05) (Table 2).
T AB LE 2Mean clinical and radiographic peri-implant parameters
among vaping individuals and NS

Vaping individuals Never smokers

3 | RESULTS Peri-implant parameters (group 1) n 5 47 (group 2) n 5 45

Plaque index (%) 52.6 6 11.9 47.6 6 9.6

3.1 | Demographic and implant-related characteristics
Bleeding on probing (%) 24.7 6 5.3a 39.8 6 18.1
of the study groups
Probing depth 4 mm (%) 5.9 6 1.4b 4.5 6 0.7
Ninety-two male individuals were included in this study (47 vaping indi-
Peri-implant bone loss (mm)
viduals and 45 NS). The mean age was comparable among individuals Mesial 1.6 6 0.7b 0.8 6 0.2
in both groups. A total of 68 implants in group 1 and 57 implants in Distal 2.1 6 1.0b 1.1 6 0.5
Total 1.8 6 0.9b 0.9 6 0.3
group 2 were assessed. The mean duration of dental implants in groups
1 and 2 was 51.8 months and 47.2 months, respectively. The mean a
Compared with group 2 (P < .01).
duration of vaping e-cigs among group 1 was 4.4 years. The daily
b
Compared with group 2 (P < .05).
4 | AL-AALI ET AL.

TA BL E 3 Concentrations of proinflammatory cytokines (TNF-a and T AB LE 4 Pearson’s correlation analysis among proinflammatory
IL-1b) in PISF among vaping individuals and NS cytokines and peri-implant parameters

Vaping Never Vaping Never

individuals smokers individuals smokers
(group 1) (group 2) Parameters (group 1) (group 2)
Parameters n 5 47 n 5 45
TNF-a
Volume of PISF collected (in lL) 3.1 6 0.6a 1.5 6 0.5 PI
Correlation coefficient 0.8111 20.5167
Level of TNF-a (in pg/mL) 24.3 6 32.4b 6.7 6 8.1
P value 0.9137 0.3801
Level of IL1b (in pg/mL) 205.2 6 230.7a 19.7 6 22.3 BOP
Correlation coefficient 0.1341 20.1145
a
Compared with group 2 (P < .01). P value 0.0245a 0.7816
b
Compared with group 2 (P < .001). PD
Correlation coefficient 0.5127 20.9672
P value 0.1728 0.4123
3.3 | Cytokine levels in PISF among study groups PIBL
Correlation coefficient 0.3200 20.4455
The PISF volume (P < .05) collected for vaping individuals was statistically P value 0.0167a 0.8914
significantly higher than NS (Table 3). Mean concentration of TNF-a in
IL-1b
group-1 individuals was 24.3 6 32.4 pg/mL, whereas mean concentration PI
of IL-1b was 205.2 6 230.7 pg/mL (Figure 1A,B). Mean concentrations Correlation coefficient 0.5067 20.4276
P value 0.7436 0.1983
of TNF-a (P < .001) and IL-1b (P < .01) were statistically significantly
BOP
increased in individuals in group 1 as compared with group 2. Correlation coefficient 0.8116 20.3145
P value 0.2867 0.4810
PD
3.4 | Pearson’s correlation analysis among Correlation coefficient 0.3345 20.7669
P value 0.9723 0.0912
proinflammatory cytokines and peri-implant PIBL
parameters Correlation coefficient 0.4201 20.3772
P value 0.0181a 0.8168
Pearson’s correlation coefficient was calculated to analyze any correla- a
Significant at P < .05.
tions among TNF-a and IL-1b levels and the clinical and radiographic
parameters were assessed in both groups (Table 4). When the individ-
higher PDs, poor attachment loss, and increased marginal bone loss as
ual groups were analyzed, a significant positive correlations were found
compared to NSs9; however, to the authors’ knowledge, this is the first
between TNF-a levels and BOP (P 5 .024) and PIBL (P 5 .016); and sig-
study to compare the clinical and radiographic status around dental
nificant positive correlation was found between IL-1b and PIBL
implants and local proinflammatory cytokine levels among vaping indi-
(P 5 .018) in group 1, respectively.
viduals and nonsmokers. This study supports the hypothesis that peri-
implant clinical and radiographic parameters are worse and the levels of
4 | DISCUSSION proinflammatory cytokine are higher among vaping e-cigs when com-
pared with individuals who have never consumed tobacco in any form.
Recent findings on vaping e-cigs and clinical/radiographic periodontal The explanation for our findings can be corroborated by recent
outcomes indicate that individuals vaping e-cigs showed significantly results that indicate the potential hazardous effects of vaping e-cigs on

FIGURE 1 Dot plots representing mean concentration of (A) TNF-a and (B) IL-1b among vaping e-cigs and NS
AL-AALI ET AL. | 5

oral epithelial cells and periodontal fibroblasts to e-cig vapor/aerosol with IL-1b in the PISF of vaping individuals compared with NS. The raised
flavoring agents that enhance DNA damage and increase the expression level of TNF-a and IL-1b in the PISF is a clear representation of the
of proinflammatory cytokines such as COX-2 and PGE2 in these site-specific deterioration around implants among vaping e-cig individu-
cells.16,17 In addition, it has also been suggested that vaping e-cigs has als. Further investigations are needed to test the mechanisms involved
the potential to induce oxidative stress and increases the expression of in increased peri-implant breakdown in individuals vaping e-cigs.
advanced glycation end products (AGEs) and their receptors in cells, This study is associated with certain limitations. The cross-
including gingival/periodontal tissues.8 In this context, these mechanisms sectional research study, retrospective data, and self-reported out-
may also explain the detrimental effects of vaping on peri-implant tissues. comes which rely on the patients’ own recall abilities may have
Nicotine in tobacco smoke has been reported to reduce the cellular affected the outcomes of our results. Past history of cigarette smoking
healing response and to reduce the tendency of bleeding.18,19 It is note- from vaping individuals was not reported as this may have been an
worthy that the percentage of peri-implant sites that bled was signifi- important confounder and may possibly have altered the outcomes of
cantly lower in vaping individuals compared with NS. It is known that our investigation. The accuracy of measurements was not calibrated in
clinical assessment of BOP is a classical indicator for periodontal and this study which might have contributed to geometric errors in the
peri-implant inflammation.20,21 However, just as cigarette smokers remain assessment of PIBL on the digital radiographs. In addition, bite-wing
unaware of the continuous oral tissue inflammatory changes, individuals radiographs would have been better for the nature of this study for
vaping e-cigs may also remain unaware as they present less bleeding better standardized measurements in terms of accuracy. Furthermore,
signs in gingival tissues compared with nonsmoker and also with the mis-
the main strength of this study is the investigation of local proinflam-
apprehension that they consider vaping as less hazardous than cigarette
matory cytokines. Future studies should also evaluate and compare the
smoking.22 It is suggested that nicotine exerts vasoconstriction on gingi-
severity of peri-implant inflammation in vaping individuals with ciga-
val blood vessels, which in turn reduces gingival bleeding in smokers com-
rette smokers. Future longitudinal studies may help to assess the evolu-
pared with individuals who do not smoke.23,24 Our results clearly indicate
tion of destruction of peri-implant structures among vaping individuals.
the reason why vaping individuals showed fewer percentage sites with
Within these limits, individuals vaping e-cigs may be at risk of poor
BOP as compared to NS. In addition, the severity of peri-implant inflam-
peri-implant tissue inflammation. Clinicians should instruct and educate
mation was low in individuals vaping e-cigs; however, the differences
young adults regarding the association of peri-implant inflammation
were statistically significantly higher than NS. The sites with PD of
and detrimental effects of vaping e-cigs and provide frequent counsel-
4 mm were higher and PIBL was worse in vaping individuals. It is well
ing to such patients to abstain from vaping. In addition, community
established that IL-1b is implicated in increased amount of alveolar bone
health awareness programs should be performed and antitobacco com-
loss.25,26 This could be attributed with the levels of increased IL-1b in
panies should routinely educate the general public about the harmful
PISF of vaping individuals as shown in the data of our findings.
effects of tobacco use on overall oral and general health.32
Tumor necrosis factor alpha and IL-1b are proinflammatory cyto-
kines that appear to have a central role in peri-implant tissue destruc-
tion.27 The biological effects of IL-1b depend on its tissue 5 | CONCLUSIONS
concentration. The properties of these cytokines that relate to tissue
destruction involve stimulation of bone resorption and induction of Clinical and radiographic peri-implant parameters are compromised
tissue-degrading proteinases.28 Tumor necrosis factor alpha is a proin- among vaping individuals. The increased levels of proinflammatory
flammatory cytokine with similar properties to IL-1b. It is the main cytokines in PISF may suggest greater local inflammatory response in
mediator in response to Gram-negative bacteria and the concentration vaping individuals for peri-implant inflammation.
of TNF-a reflects the amount of bacteria and the stage of inflammation.
The findings of this study showed that the levels of harmful proinflam-
ACK NOWLE DGME NT S
matory cytokines (TNF-a and IL-1b) were statistically significantly
The authors would like to thank the College of Dentistry Research
higher among individuals in group 1 compared with group 2. One expla-
Center and Deanship of Scientific Research at King Saud University,
nation in this regard is that vaping e-cigs increases the levels of AGEs in
8 Saudi Arabia for funding this research project.
oral tissues including gingival and periodontal tissues. Augmented
interfaces between AGEs and their receptors have been associated with
the formation of ROS that induce a state of oxidative burst within gingi- CON FLICT OF INT E RE ST
val tissues, functional alterations of chemotaxis, and phagocytosis of
The authors declare that they have no conflicts of interest with the
polymorphonuclear cells, decrease production of antibodies, increase
content of this article.
adherence of bacterial adhesion, and increase systemic and local inflam-
matory burden by increasing the expression of cytokines in the serum
and crevicular fluid.29–31 These mechanisms have been related with oral ORC ID

connective tissue inflammation and alveolar bone deterioration around Tariq Abduljabbar BDS, MSc, DMSc http://orcid.org/0000-0001-
natural teeth in individuals with vaping e-cigs. It is postulated that the 7266-5886
same mechanisms may be associated with raised levels of TNF-a and Zohaib Akram BDS, MDSc http://orcid.org/0000-0001-9618-8818
6 |
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How to cite this article: Al-Aali KA, Alrabiah M, ArRejaie AS,
Abduljabbar T, Vohra F, Akram Z. Peri-implant parameters,
tumor necrosis factor-alpha, and interleukin-1 beta levels in
vaping individuals. Clin Implant Dent Relat Res. 2018;00:1–6.
https://doi.org/10.1111/cid.12597