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ORIGINAL RESEARCH

Systemic Inflammatory Markers Among Waterpipe


Smokers, Cigarette Smokers, and Nonsmokers
Bhavita Kumari, MPH, MBBS, Syeda Kanwal Aslam, MSc, MBBS, Sidra Zaheer, MSc,
Syed Omair Adil, MS, and Kashif Shafique, PhD, MPH, MBBS
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Key Words: inflammatory markers, tobacco, waterpipe smoking


Objective: To determine the levels of neutrophil to lymphocyte ratio
(NLR) and platelet to lymphocyte ratio (PLR) among exclusive (J Addict Med 2018;xx: xxx–xxx)
groups of waterpipe (WP) smokers, cigarette smokers, and non-
smokers.
Methods: This cross-sectional study was conducted among adults, W aterpipe smoking is on the rise in many countries and is
replacing cigarettes. Numerous efforts have been
directed toward examining the adverse health effects of
apparently healthy individuals, aged between 18 and 40 years of
either gender. NLR and PLR as measures of systemic inflammation waterpipe (WP) smoking. The smoke inhaled during a single
were studied in association with individuals’ sociodemographic,
session of WP smoking is said to have several folds higher
dose of tobacco-related toxicants in comparison to cigarette
health, and tobacco use related characteristics. The results of linear
smoke. It is justly speculated that WP-related health effects
and logistic regression models were reported as crude and adjusted
can be similar to those of cigarette smoking and even worse
beta coefficients and odds ratios with 95% confidence intervals (CIs).
(Eissenberg and Shihadeh, 2009; Shihadeh et al., 2015).
Results: Out of 190 participants, 34.2% (n ¼ 65) exclusively smoked However, there is a dearth of evidence related to long-term
WP, 32.6% (n ¼ 62) smoked cigarettes, and 33.2% (n ¼ 63) were effects of WP smoking (Maziak et al., 2014).
nonsmokers. The mean NLR and PLR were significantly higher One of the several explanations given for the biological
among WP smokers when compared with nonsmokers; however, the plausibility of the etiological link between cigarette smoking
comparison between WP smokers and cigarette smokers for both and chronic diseases is tobacco smoke-mediated systemic
NLR and PLR was not statistically significant. The odds of raised inflammation (Krüger et al., 2015; Shiels et al., 2014). Several
NLR was 4.40 times higher (AOR ¼ 4.40, 95% CI ¼ 1.97, 9.85), and studies have reported that systemic inflammation may be one
the odds of raised PLR was 3.48 times higher (AOR ¼ 3.48, 95% of the precursors for several chronic diseases, including
CI ¼ 1.60, 7.57) for WP smokers compared to nonsmokers. diabetes mellitus, cardiovascular disorders, and cancers (Fol-
Conclusions: WP smoking has a significant association with sys- som et al., 1999, 2002; Nakanishi et al., 2002; Pitsavos et al.,
temic inflammation as measured by NLR and PLR. The study and 2007). Thus, it can be speculated that WP smoking may also
existing evidence implicate an urging need to regulate WP industry be associated with these chronic diseases plausibly mediated
and its policies. through its systemic inflammatory effects.
Varieties of biochemical and haematological markers
are available to measure the systemic inflammation.
From the School of Public Health, Dow University of Health Sciences (BK, Although, novel disease-specific biomarkers have been iden-
SKA, SZ, KS); Department of Research, Dow University of Health tified, most of which are time consuming and expensive.
Sciences, Karachi Pakistan (SOA); Institute of Health and Wellbeing,
Public Health, University of Glasgow, Glasgow, UK (KS). Neutrophil to lymphocyte ratio (NLR) and platelet to lym-
Received for publication November 10, 2017; accepted June 10, 2018. phocyte ratio (PLR) could be an important measure of sys-
All procedures performed in studies involving human participants were in temic inflammation as it is cost-effective, readily available
accordance with the ethical standards of the institutional and/or national and easily calculated. Recent studies have reported that higher
research committee and with the 1964 Helsinki declaration and its later
amendments or comparable ethical standards.
NLR and PLR are not only associated with different malig-
Informed consent: Informed consent was obtained from all individual par- nancies and cardiovascular diseases but also influenced by
ticipants included in the study. demographic, lifestyle and environmental factors as well
The authors declare that they have no conflict of interest. (Durmus et al., 2015; Lin et al., 2016; Yodying et al.,
Supplemental digital content is available for this article. Direct URL citation 2016). It has been reported that WP smoking affects leukocyte
appears in the printed text and is provided in the HTML and PDF versions
of this article on the journal’s Web site (www.journaladdictionmedici- and platelet count, coagulation, and lipid profile (Al-Dahr,
ne.com). 2010). However, studies on the prognostic significance of the
Send correspondence to Kashif Shafique, PhD, MPH, MBBS, Institute of relationship between elevated NLR and PLR with WP smok-
Health and Wellbeing, Public Health, University of Glasgow, 1-Lilybank ing are scarce; we thus aim to examine the association of WP
Gardens, Glasgow, UK. E-mail: kashif.shafique@glasgow.ac.uk
Copyright ß 2018 American Society of Addiction Medicine
smoking with systemic inflammation. Further the specific
ISSN: 1932-0620/16/0000-0001 objective of the study was to measure and compare levels of
DOI: 10.1097/ADM.0000000000000446 neutrophil to lymphocyte ratio and platelet to lymphocyte

J Addict Med  Volume 00, Number 00, Month/Month 2018 1

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Kumari et al. J Addict Med  Volume 00, Number 00, Month/Month 2018

ratio among exclusive groups of WP smokers, cigarette Operational Definitions


smokers, and nonsmokers.
Exposure
METHODS Waterpipe smoker was defined as a person who had at
least one WP session per month in the last 6 months. Non-
Study Setting and Participants smoker was defined as a person who has not smoked WP or
This cross-sectional study was conducted among adults cigarette in the last 6 months. Whereas, a cigarette smoker
in Karachi, the largest metropolitan city of Pakistan, with a was defined as a person who has smoked >100 cigarettes, and
population of more than 20 million people. Waterpipe smok- is currently smoking every day or >3 days per week.
ing is gaining popularity as a trendy social substance abuse To avoid duplication, only those participants were
among the metropolis dwellers and is being readily accepted considered who reported the exclusive use of WP or cigarette
as a norm, as roots of WP origin lie in the Indian subcontinent smoking, and those participants using both types of tobacco
(Maziak et al., 2004). A recent study reported almost quarter were excluded from the study.
of university students regularly smoke WP (Jawaid et al.,
2008). Outcome
NLR and PLR have been calculated as follows:
Ethical Considerations Total number of neutrophil
The study was approved by the institutional review NLR ¼
board (IRB No: IRB-536/DUHS/-14). The participants were Total number of lymphocyte
detailed about the study objectives, data collection, sample
collection procedures, and possible side effects. The partic- Total number of platelet
ipants were assured of their autonomy, confidentiality, and PLR ¼
right to withdraw from the study at any time. They were Total number of lymphocyte
recruited after signing an informed consent form.
The values were read on a continuous scale, dividing it
Sampling Technique in 2 groups using median cutoff.
The current WP smoking university students were used
as starting point for the snowball sampling to reach potential Study Variables
participants. A comparison group was also recruited as a The 2 diagnostic ratios, NLR and PLR, were taken as
control group, which was apparently similar to those in outcome variables. The outcome variables were studied in
WP smoking group but did not smoke any form of tobacco. association with individuals’ sociodemographic, health, and
Furthermore, a comparison group of cigarette smokers was tobacco use related characteristics (independent variables).
also included who were currently exclusive cigarette smokers.
Statistical Analysis
Inclusion/Exclusion Criteria Descriptive characteristics were reported as frequencies
Apparently healthy individuals, aged between 18 and and percentages (categorical variables); and means and stan-
40 years, who were eligible to be in one of the 3 groups, that is, dard deviations (continuous variables). Nonparametric anal-
WP smokers, cigarette smokers, or nontobacco smokers group yses including Kruskal-Wallis and Chi-square test were used
criteria (operational definitions provided below), were to assess the associations between 3 groups and all other study
included in this study. Pregnant or lactating women and variables. Kruskal-Wallis test (P < 0.001) suggested very
individuals with any self-reported noncommunicable disease, strong evidence of a difference between mean ranks of at least
namely, diabetes, hypertension, cardiac disease, blood disor- one pair of groups. As multiple tests are being carried out,
ders, liver or kidney disease, recent infection, fever, or Dunn’s Bonferroni corrections used to correct for inflated
ingestion of medications (within past 14 days); were type 1 error rates associated with multiple comparisons
excluded. applying for continuous outcomes NLR and PLR both
(Kao and Green, 2008).
Data Collection Associations of tobacco smoking status and systemic
A structured questionnaire using standardized Global inflammatory markers were further assessed using univariate
Tobacco Surveillance System (GTSS) was used to collect and multivariate linear regression models; the NLR and PLR
sociodemographic, and tobacco use related information were taken as the outcome. In multivariate linear regression
(CDC). Furthermore, a trained qualified nurse from public analyses, results were adjusted for age, sex, marital status,
sector university hospital carried out a physical examination education level, income level, physical activity, blood pres-
and collected blood samples. A blood sample was collected sure, heart rate, and waist circumference, and were reported as
from the ante-cubital vein with a 3-mL syringe without using a beta coefficients, standard errors with 95% confidence inter-
tourniquet. Blood was collected in an ethylene diamine tetra vals (CIs) and P values.
acetic acid tube and shaken properly, inverting the tube 3 to Furthermore, the diagnostic ratios were also divided
4 times, as to avoid coagulation. Samples were stored at room into 2 categories, using the median as the cutoff. NLR of
temperature and tested for complete cell blood count in an 1.47 was coded as low, and >1.47 as high; PLR of >107.35
automated Abbott—Cell Dyne Ruby analyzer. as low, and >107.35 as high. Univariate and multivariate

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J Addict Med  Volume 00, Number 00, Month/Month 2018 Waterpipe Smoking and Its Association With Systemic Inflammation

binary logistic regression analyses were then conducted, Social Characteristics of Waterpipe Smokers
and results were reported as crude and adjusted odds Mean age of starting WP among WP smokers was
ratio, with 95% CI and their corresponding P values. In 18.74 years, and mean frequency of WP use was 6.89 times
multivariate logistic regression analyses, results were also per month, with mean puff frequency in one session being
adjusted for age, sex, marital status, education level, income 23.88. The mean duration of a single session was 2.2 hours. A
level, physical activity, blood pressure, heart rate, and majority (72.3%) of participants smoked it in the company of
waist circumference. friends, while 15.4% took it mostly with family, and 12.3%
smokers reported smoking WP alone. Most of the participants
RESULTS (70.8%) smoked WP at cafes or restaurants and considered the
A total of 250 individuals were invited for participation in availability of WP smoking facility while choosing a restau-
the study, 200 consented to participate (response rate ¼ 80%). rant (data not shown).
Ten individuals were excluded due to ineligibility, and final
analysis was based on 190 participants. Among participants, NLR and Tobacco Smoking Status
34.2% (n ¼ 65) exclusively smoked WP, 32.6% (n ¼ 62%) The mean NLR varied significantly according to
smoked cigarettes, and 33.2% (n ¼ 63) were nonsmokers. tobacco smoking status among participants (P < 0.01). The
mean NLR was highest among WP smokers as compared to
Basic Health Characteristics cigarette smokers (P ¼ 0.124, adjusted using the Bonferroni
Furthermore, regarding basic health characteristics of correction), and nonsmokers (P < 0.001, adjusted using the
participants, 77.4% (n ¼ 147) of them were not involved in Bonferroni correction) (Table 1, Table S1, http://links.
any physical activity; participants had a mean heart rate of lww.com/JAM/A91). Results of univariate linear regression
91.03 beats/min; 119.39 mm Hg mean systolic blood pressure, analysis (Model 0) indicate that WP smoking status was
and 77.84 mm Hg mean diastolic blood pressure; and mean positively associated with increased NLR (Beta ¼ 0.58,
waist circumference of 30.65 in. No statistically significant 95% CI 0.23, 0.93, P < 0.01) as compared to nonsmoking,
differences in baseline characteristics were observed between and this association remained the same after the adjustment of
the 3 groups of WP smokers, cigarette smokers, and non- all other factors in Model 1 (Beta ¼ 0.61, 95% CI 0.25, 0.96,
smokers (Table 1). P < 0.01). It is also noted that the positive unit change of NLR

TABLE 1. Descriptive Characteristic of Respondents According to Smoking Status (n ¼ 190)


Waterpipe Smokers (n ¼ 65) Cigarette Smokers (n ¼ 62) Nonsmokers (n ¼ 63)
Characteristics Mean  SD Mean  SD Mean  SD P
Inflammatory markers
NLR 1.73  0.79 1.48  0.61 1.15  0.58 <0.01
PLR 117.38  42.62 108.66  31.89 98.27  43.81 <0.01
Blood pressure
Systolic 120.46  16.83 121.69  17.10 116.03  15.50 0.13
Diastolic 78.62  10.84 78.63  11.02 76.27  8.56 0.47
Heart rate 90.69  15.38 91.58  16.95 90.84  16.01 0.98
Waist circumference 31.02  3.46 31.18  3.10 29.76  3.15 0.08
Moderate physical activity, min/wk
138.57  70.88 157.50  45.10 185.59  60.97 0.10

n (%) n (%) n (%) P


Age
<25 years 41 (31.8) 42 (32.6) 46 (35.7) 0.48
25 years 24 (39.3) 20 (32.3) 17 (27.9)
Gender
Male 54 (34.8) 54 (34.8) 47 (30.3) 0.18
Female 11 (31.4) 08 (22.9) 16 (45.7)
Marital status
Single 55 (33.7) 53 (32.5) 55 (33.7) 0.90
Married 10 (37.0) 09 (33.3) 08 (29.6)
Education level
School (12 years) 17 (39.5) 12 (27.9) 14 (32.6) 0.85
Graduate (13–16 years) 44 (33.6) 44 (33.6) 43 (32.8)
Postgraduate (>16 years) 04 (25.0) 06 (37.5) 06 (37.5)
Monthly income (in PKR)
10,000–50,000 25 (35.2) 26 (36.6) 20 (28.2) 0.63
50,001–80,000 23 (35.4) 17 (26.2) 25 (38.5)
80,001 R 17 (31.5) 19 (35.2) 18 (33.3)
NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio.

P value calculate by using Kruskal-Wallis test.

P value calculate by using Chi-square test.

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TABLE 2. Association of Tobacco Smoking Status and Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio
Model 0 Model 1
Beta SE 95% CI P Beta SE 95% CI P
Neutrophil to lymphocyte ratio
Smoking status
Nonsmokers Reference Reference
Cigarette smokers 0.33 0.178 0.01, 0.68 0.06 0.38 0.185 0.02, 0.74 0.03
Waterpipe smokers 0.58 0.176 0.23, 0.93 <0.01 0.61 0.182 0.25, 0.96 <0.01
Platelet to lymphocyte ratio
Smoking status
Nonsmokers Reference Reference
Cigarette smokers 10.39 0.178 10.03, 10.74 <0.01 12.43 0.185 12.07, 12.79 <0.01
Waterpipe smokers 19.11 0.178 18.76, 19.45 <0.01 20.86 0.182 20.51, 21.21 <0.01
Model 0 ¼ univariate analysis.
Model 1 ¼ Model 0 þ age, gender, marital status, education level, income, physical activity, systolic blood pressure, diastolic blood pressure, heart rate, waist circumference.
CI, confidence interval; NLR, neutrophil to lymphocyte ratio; PLR, platelet to lymphocyte ratio; SE, standard error.

was higher among WP smokers as compared to cigarette Furthermore, linear associations between systemic
smokers in Models 0 and 1 (Table 2). Furthermore, logistic inflammatory markers among WP and cigarette smokers
regression analysis also indicated that the odds of raised NLR indicated that WP smoking remained positively associated
was significantly higher for WP smokers compared to non- with NLR (Beta ¼ 0.27, 95% CI 0.08, 0.62, P ¼ 0.13) and
smokers (Model 0, OR ¼ 3.40, 95% CI 1.64, 7.03, P < 0.01; PLR (Beta ¼ 9.23, 95% CI 8.87, 9.58, P < 0.01) as compared
Model 1, OR ¼ 4.40, 95% CI 1.97, 9.85, P < 0.01), even after to cigarette smoking (Table 4).
adjustment with all study variables (Table 3).
DISCUSSION
PLR and Tobacco Smoking Status The findings of this study indicate that WP smoking is
The mean PLR was significantly higher among WP significantly associated with raised systemic inflammatory
smokers (mean 117.39, S.D  42.62) as compared to non- markers, particularly NLR and PLR. Although, the NLR and
smokers (P-value 0.003, adjusted using the Bonferroni cor- PLR values were in normal range among WP smokers,
rection) (see Table 1, Table S1, http://links.lww.com/JAM/ cigarette smokers, and nonsmokers, the average NLR and
A91). Furthermore, Model 0 indicates that WP smoking status PLR values were significantly higher among WP smokers
was positively associated with PLR as compared to nonsmok- compared with nonsmokers. Comparing the inflammatory
ing. Even after adjusting for all important physical health, and effects of the different forms of smoked tobacco, WP smokers
socio-demographic covariates (Model 1), WP smoking had higher odds of raised NLR and PLR as compared to
remained positively associated with PLR as compared to cigarette smokers. Furthermore, study also adds evidence
nonsmoking (Beta ¼ 20.86, 95% CI 20.51, 21.21, P < 0.01) related to the social and behavioral characteristics of the
(Table 2). Furthermore, adjusted logistic regression analysis WP smoking, indicating that majority of them initiated
also indicates that the odds of raised PLR were 3.48 times use in late teens; were having at least 7 to 8, 1-hourly
higher for WP smokers compared to nonsmokers (OR ¼ 3.48, smoking sessions in a month; and were using it as a social
95% CI 1.60, 7.57, P < 0.01) (see Table 3). drug in company of friends, preferring the cafes and

TABLE 3. Logistic Regression Odds Ratio of Higher Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio
Model 0 Model 1
Characteristics OR (95% CI) P OR (95% CI) P
NLR (compared to NLR < 1.47)
Smoking status
Nonsmokers 1 1
Cigarette smokers 1.86 (0.90–3.82) 0.08 2.40 (1.09–5.30) 0.03
Waterpipe smokers 3.40 (1.64–7.03) <0.01 4.40 (1.97–9.85) < 0.01
PLR (compared to PLR < 107.36)
Smoking status
Nonsmokers 1 1
Cigarette smokers 1.73 (0.85–3.55) 0.12 2.06 (0.95–4.45) 0.06
Waterpipe smokers 2.97 (1.44–6.09) <0.01 3.48 (1.60–7.57) < 0.01
Model 0 ¼ univariate analysis.
Model 1 ¼ Model 0 þ age, gender, marital status, education level, income, physical activity, systolic blood pressure, diastolic blood pressure, heart rate, waist circumference.
CI, confidence interval; NLR, neutrophil to lymphocyte ratio; OR, odds ratio; PLR, platelet to lymphocyte ratio.

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TABLE 4. Association of Tobacco Smoking Status and Neutrophil to Lymphocyte Ratio and Platelet to Lymphocyte Ratio
Model 0 Model 1
Beta SE 95% CI P Beta SE 95% CI P

Neutrophil to lymphocyte ratio


Smoking status
Cigarette smokers Reference Reference
Waterpipe smokers 0.25 0.177 0.09, 0.59 0.16 0.27 0.18 0.08, 0.62 0.13

Platelet to lymphocyte ratio


Smoking status
Cigarette smokers Reference Reference
Waterpipe smokers 8.72 0.177 8.37, 9.06 <0.01 9.23 0.18 8.87, 9.58 <0.01
Model 0 ¼ univariate analysis
Model 1 ¼ Model 0 þ age, gender, marital status, education level, income, physical activity, systolic blood pressure, diastolic blood pressure, heart rate, waist circumference.
CI, confidence intervals; SE, standard error.

restaurants which offered WP smoking facility at the venue (Flouris et al., 2012). Although the biological plausibility
(data not shown). of the association has not been studied much, it may be
In light of existing literature, various mediators have explained by the cellular response of blood components to
been linked with onset of systemic inflammation, including inflammation which is mediated by endothelial dysfunction
obesity, lack of physical activity, stress, and even cigarette (Marsland et al., 2010). Similarly, a relation between chronic,
smoking (Bell and O’Keefe, 2007; Brooks et al., 2010; low-grade, subclinical inflammation, and insulin resistance
Copeland et al., 2014; Nakanishi et al., 2002; Pirkola et al., leading to clinically over diabetes mellitus has also been
2010; Pitsavos et al., 2007; Yasue et al., 2006). Comparing reported (Pitsavos et al., 2007). In case of establishing the
study results with existing evidence available in this regard, association between WP use and systemic inflammation, it
raised total leukocyte count among WP smokers had been may then also be well justified to state that, WP smoking, in
reported in several studies (Bentur et al., 2014; Khabour the long run, maybe a potential risk factor for developing
et al., 2012), and the results are also comparable with studies chronic diseases like metabolic syndrome, diabetes, and
that have reported raised total leukocyte count among cigarette cardiovascular disease. However, present evidence in this
smokers (Shenwai and Aundhakar, 2012; Tell et al., 1985; regard is limited and calls for further investigations.
Whitehead et al., 1995). Our study adds to the limited evidence The findings of the study may also be used for effective
available. Even after adjusting for several important health- advocacy against the use of WP smoking, which at the
related parameters including blood pressure, body mass index, moment is emerging as a popular, relatively less harmful
physical activity, NLR, and PLR remained significantly asso- form of smoked tobacco, among users (Maziak et al., 2004).
ciated with WP smoking as evident from study results where As discussed earlier, though, NLR and PLR were at a higher
WP smokers were found to have higher odds of raised inflam- level among WP smokers as compared to cigarette smokers
matory markers as compared to cigarette smokers. and nonsmokers in our study, these values were in normal
As far as use of NLR and PLR as inflammatory markers ranges among all 3 groups. It may take several years before we
in the present study is concerned, they have been used in have large-scale, multiyear epidemiological studies to vali-
several studies to assess the presence of low-grade systemic date the chronic health effects of WP smoking. In such
inflammation, in association with cardiovascular diseases, circumstances, evidence from studies like this may hold
cancer survival, and chronic diseases (Bovill et al., 1996; importance with regard to the advocacy to prevent the use
Freedman et al., 1996; Imtiaz et al., 2012; Yasue et al., 2006). of WP usage at the population level. Previous findings related
However, to the best of our knowledge, this is the first study to to the characteristics of WP smokers are also important, as
report the association of the NLR and PLR with WP smoking, they clearly indicate that majority of the users unaware of the
and thus the results warrant further investigations to confirm harmful effects of WP smoking, consider it relatively safe as
the finding. In case the findings related to use of NLR and compared to cigarette smoking (Maziak et al., 2004).
PLR as a valid measure of low-grade systemic inflammation is Although cigarette use may have declined in several devel-
confirmed, these can be used as a simple, cost-effective oped countries, it is currently a big dilemma for the antito-
measure of low-grade systemic inflammation in resource- bacco efforts, that the newer products like e-cigarettes and re-
limited scenarios. emerging popular forms like WP have gained ground as
Regarding the implications of raised inflammatory relatively safe social drugs (Maziak et al., 2004, 2014).
markers among WP smokers, a chronic systemic inflamma- Our study had various limitations; first, as an observa-
tory effect may lead to several diseases like cardiovascular tional study, it cannot outline a causal association between
diseases, diabetes mellitus, hypertension. For instance, leu- WP smoking and inflammatory effect. However, supporting
kocytosis caused by cigarette smoking has been found to be evidence points in the same direction, and it may be well
associated with low-grade inflammation in atherosclerosis justified to speculate causative role of WP smoking in

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systemic inflammation. Nevertheless, the results call for a Folsom AR, Rosamond WD, Shahar E, et al. Prospective study of markers of
further understanding of the phenomenon through longitudi- hemostatic function with risk of ischemic stroke. Circulation
1999;100:736–742.
nal studies. Secondly, we used nonprobability sampling tech- Folsom AR, Aleksic N, Catellier D, et al. C-reactive protein and incident
nique, because of a hindrance to reaching the target coronary heart disease in the Atherosclerosis Risk In Communities (ARIC)
population. It is also important to note here, that the partic- study. Am Heart J 2002;144:233–238.
ipants were selected on basis of their exclusive smoking Freedman DS, Joesoef MR, Barboriak JJ, et al. Correlates of leukocyte counts
in men. Ann Epidemiol 1996;6:74–82.
habits. However, in reality, users may use WP along with Imtiaz F, Shafique K, Mirza SS, et al. Neutrophil lymphocyte ratio as a
cigarettes. Therefore, there are fair chances that participants measure of systemic inflammation in prevalent chronic diseases in Asian
who might have been exposed to higher doses of toxicants due population. Int Arch Med 2012;5:2.
to synergistic effects of combined WP and cigarette use may Jawaid A, Zafar A, Rehman T, et al. Knowledge, attitudes and practice of
have been completely missed. Nevertheless, a study of exclu- university students regarding waterpipe smoking in Pakistan. Int J Tuberc
Lung Dis 2008;12:1077–1084.
sive WP and cigarette smoking groups enabled us to compare Kao LS, Green CE. Analysis of variance: is there a difference in means and
the inflammatory effects caused by the 2 different forms of what does it mean? J Surg Res 2008;144:158–170.
smoked tobacco. Furthermore, any results can also be masked Khabour OF, Alzoubi KH, Bani-Ahmad M, et al. Acute exposure to waterpipe
by environmental air pollution, as well as any underlying tobacco smoke induces changes in the oxidative and inflammatory markers
in mouse lung. Inhal Toxicol 2012;24:667–675.
health conditions, which were not studied in the present study. Krüger K, Dischereit G, Seimetz M, et al. Time course of cigarette smoke-
induced changes of systemic inflammation and muscle structure. Am J
CONCLUSIONS Physiol Lung Cell Mol Physiol 2015;309:L119–L128.
Waterpipe smoking has a significant association with Lin BD, Hottenga JJ, Abdellaoui A, et al. Causes of variation in the
neutrophil–lymphocyte and platelet–lymphocyte ratios: a twin-family
systemic inflammation as measured by NLR and PLR. The
study. Biomark Med 2016;10:1061–1072.
study and existing evidence implicate the need to regulate the Marsland AL, McCaffery JM, Muldoon MF, et al. Systemic inflammation and
WP industry and its policies. Public awareness policies are the metabolic syndrome among middle-aged community volunteers.
required to correct the perception regarding the safety of WP. Metabolism 2010;59:1801–1808.
Maziak W, Ward K, Soweid RA, et al. Tobacco smoking using a waterpipe:
a re-emerging strain in a global epidemic. Tob Control 2004;13:
ACKNOWLEDGMENTS 327–333.
We would like to thank all personnel who provided Maziak W, Taleb ZB, Bahelah R, et al. The global epidemiology of waterpipe
support for logistic support. We would also like to thank smoking. Tob Control 2014;24(suppl 1):i3–i12.
all study participants and organizations involved in this study. Nakanishi N, Sato M, Shirai K, et al. White blood cell count as a risk factor for
hypertension; a study of Japanese male office workers. J Hypertens
2002;20:851–857.
REFERENCES Pitsavos C, Tampourlou M, Panagiotakos DB, et al. Association between low-
Al-Dahr MHS. Impact of smoking on platelet, coagulation and lipid profile in grade systemic inflammation and type 2 diabetes mellitus among men and
young male subjects. WASJ 2010;11:118–123. women from the ATTICA Study. Rev Diabet Stud 2007;4:98–104.
Bell DS, O’Keefe JH. White cell count, mortality, and metabolic syndrome in Pirkola J, Vääräsmäki M, Ala-Korpela M, et al. Low-grade, systemic inflam-
the Baltimore longitudinal study of aging. J Am Coll Cardiol 2007;50: mation in adolescents: association with early-life factors, gender, and
1810. lifestyle. Am J Epidemiol 2010;171:72–82.
Bentur L, Hellou E, Goldbart A, et al. Laboratory and clinical acute effects of Shenwai M, Aundhakar N. Effect of cigarette smoking on various haemato-
active and passive indoor group water-pipe (narghile) smoking. Chest logical parameters in young male smokers. Indian J Basic Appl Med Res
2014;145:803–809. 2012;2:386–392.
Bovill EG, Bild DE, Heiss G, et al. White blood cell counts in persons aged Shiels MS, Katki HA, Freedman ND, et al. Cigarette smoking and variations
65 years or more from the Cardiovascular Health Study. Correlations with in systemic immune and inflammation markers. J Natl Cancer Inst
baseline clinical and demographic characteristics. Am J Epidemiol 1996;143: 2014;106:dju294.
1107–1115. Shihadeh A, Schubert J, Klaiany J, et al. Toxicant content, physical properties
Brooks GC, Blaha MJ, Blumenthal RS. Relation of C-reactive protein to and biological activity of waterpipe tobacco smoke and its tobacco-free
abdominal adiposity. Am J Cardiol 2010;106:56–61. alternatives. Tob Control 2015;24(suppl 1):i22–i30.
CDC. Smoking and tobacco use. Available at: http://www.cdc.gov/tobacco/ Tell G, Grimm R, Vellar O, et al. The relationship of white cell count, platelet
global/gtss/. Accessed August 1, 2014. count, and hematocrit to cigarette smoking in adolescents: the Oslo Youth
Copeland WE, Wolke D, Lereya ST, et al. Childhood bullying involvement Study. Circulation 1985;72:971–974.
predicts low-grade systemic inflammation into adulthood. Proc Natl Acad Whitehead T, Robinson D, Allaway S, et al. The effects of cigarette smoking
Sci U S A 2014;111:7570–7575. and alcohol consumption on blood haemoglobin, erythrocytes and leuco-
Durmus E, Kivrak T, Gerin F, et al. Neutrophil-to-lymphocyte ratio and cytes: a dose related study on male subjects. Clin Lab Haematol
platelet-to-lymphocyte ratio are predictors of heart failure. Arq Bras 1995;17:131–138.
Cardiol 2015;105:606–613. Yasue H, Hirai N, Mizuno Y, et al. Low-grade inflammation, thrombogenicity,
Eissenberg T, Shihadeh A. Waterpipe tobacco and cigarette smoking: direct and atherogenic lipid profile in cigarette smokers. Circ J 2006;70:8–13.
comparison of toxicant exposure. Am J Prev Med 2009;37:518–523. Yodying H, Matsuda A, Miyashita M, et al. Prognostic significance of
Flouris AD, Poulianiti KP, Chorti MS, et al. Acute effects of electronic and neutrophil-to-lymphocyte ratio and platelet-to-lymphocyte ratio in oncol-
tobacco cigarette smoking on complete blood count. Food Chem Toxicol ogic outcomes of esophageal cancer: a systematic review and meta-
2012;50:3600–3603. analysis. Ann Surg Oncol 2016;23:646–654.

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