Cardiopulmonary Risk of Waterpipe Smoke : A Meta-Analysis

Page 31 of 40 Cardiopulmonary Risk of Waterpipe Smoke: A Meta-Analysis Matthew Randolph Marshall1*, Marya Ghazipura2, Tanzib Hossain3, Terry Gordon1, Lung-Chi Chen1 1New York University School of Medicine, Department of Environmental Health Sciences, New York University Langone Medical Center, New York, NY 2New York University School of Medicine, Department of Population Health, New York, NY 3New York University School of Medicine Division of Pulmonary, Critical Care, and Sleep Medicine, Department of Medicine, New York, NY


Introduction
According to the 2010 Global Burden of Disease Study, cardiopulmonary diseases are responsible for the top 5 causes of death worldwide 1 .Within the United States (U.S), mortality data from 2015 shows cardiovascular disease (CVD) ranked as the leading cause of death in the U.S., 2 with about 80% of CVD being preventable, 3 and chronic lower respiratory diseases ranked third 2 .Additionally, within the second leading cause of death in the U.S., cancer, lung and bronchus cancer is the leading cause of mortality in both men and women 4 .One of the greatest risk factors for developing cardiopulmonary disease is cigarette smoking, 5 but with major public health efforts since 1965, the prevalence of cigarette smoking has been declining 6 .
In contrast to cigarette use, in the last decade, waterpipe (WP) use, commonly referred to as hookah, nargile, shisha, or hubblebubble, has risen in popularity in Western countries, especially among adolescent populations [7][8][9] .In the United States, 8% of adolescents 13 -17 years old and 20% of high-school seniors reported using a WP, according to the 2011 National Youth Tobacco Survey 9 .The increase in popularity is partially attributable to the misconception that waterpipe smoke (WPS) is less deleterious than cigarette smoke 8,10 .Nonetheless, similar to cigarettes, an association between WPS and cardiopulmonary disease has been documented 11 .
Studies have shown that during a typical WPS session, which varies in length from 30 minutes to 90 minutes with the average duration around 45 minutes, there can be acute increases in hemodynamic parameters of cardiopulmonary function such as systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and heart rate (HR), as well as an increase in expired carbon monoxide (CO) and carboxyl hemoglobin (COHb) 7,12,13 .
Although these common parameters of cardiopulmonary function appear to correlate with WPS in some studies, the short-term and long-term health effects of WPS on the cardiopulmonary system are still not well understood.Thus, this meta-analysis aims to summarize the effects of WPS on several common hemodynamic parameters of cardiopulmonary function and respiratory markers of tobacco exposure.

Methods
A comprehensive literature review was conducted in March 2017 for all relevant publications up to that date in English using Ovid MEDLINE, Ovid MEDLINE In-Process and Other Non-Indexed Citations, Ovid Embase, the Centre for Reviews and Dissemination database Cumulative Index to Nursing & Allied Health Literature (CINAHL Plus), Google Scholar, and the Wiley Cochrane Library.PubMed Reminer was used to help refine the search strategy and ensure all appropriate and relevant terms were included.Medical Subject Heading (MeSH) terms and keywords that were included are detailed in Table 1.A grey literature search was also conducted by hand searching OAIster, Open Grey, Grey Literature Report, and Proceedings of the National Academy of Sciences.All studies comparing the before and after hemodynamic effects of WPS were included, including several that analyzed smokers who used both waterpipes and cigarettes.Studies that did not distinguish between tobacco use or indicate a proper cessation from cigarette smoke were excluded.The references for selected studies were hand searched to identify any additional literature.The process of selecting studies for the final inclusion in this systematic review, as well as the reasons for exclusion, is outlined in Figure 1.Relevant data were extracted on study design and setting, population, the type of WP being used, and outcomes of HR, SBP, DBP, expired CO, and COHb.Two authors independently assessed the relevance and quality of all included studies.The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria was used to ensure thorough and transparent evaluation of all included literature 14 .
The quality of the body of evidence for each hemodynamic parameter and respiratory marker of tobacco exposure was assessed in accordance to the Grading of Recommendations Assessment, Development and Evaluation (GRADE) Working Group 15 .Using this tool, outcomes from each study were graded as high, moderate, low, or very low quality, based on the methodology reported in the individual studies.Risk of bias, inconsistency, indirectness, imprecision, and publication bias were taken into account, and any limitations in these fields resulted in downgrading the quality of evidence.
Using the "meta" and "forestplot" packages in R, metaanalyses were conducted to derive effect estimates of all relevant cardiopulmonary health markers 16,17 .Mean differences with corresponding 95% confidence intervals were calculated using a random effects model to account for the high heterogeneity (I 2 statistic) and corresponding forest plots were created to graphically depict the results.

Results
As noted in Figure 1, the literature search yielded a total of 73 studies from the databases searched, and another 10 studies were identified through other sources.After the removal of duplicates, 81 studies were screened for titles, and 48 studies remained for abstract screening and application of the inclusion criteria.Of these abstracts, 29 studies were eligible for full-text review, and 15 studies were ultimately included in the meta-analysis altogether.The inter-rater reliability was computed using the Cohen's kappa coefficient and was calculated to be 0.91.The results of the synthesis are summarized in Table 2   Fifteen studies were used in the meta-analyses to determine the effects of WPS on CVD and respiratory markers of tobacco exposure by assessing changes in intermediate hemodynamic parameters affecting cardiopulmonary function, including MAP, SBP, DBP, and HR, as well as expired CO and COHb concentration to assess WPS exposure 18 .A pooled analysis of the results revealed an association between a WPS session and an increase in mean SBP and DBP of 6.45 mmHg (95% CI 3.87 to 9.04; p < 0.0001) and 3.71 mmHg (95% CI 2.34 to 5.08; p < 0.0001), respectively (Figure 2).Additionally, MAP increased by 5.54 mmHg (95% CI 3.33 to 7.76; p < 0.0001), following a WPS session (Figure 3).There was also an increase in COHb levels by 4.11% (95% CI 3.38 to 4.84; p < 0.0001) and expired CO by 22.53 ppm (95% CI 15.99 to 29.08; p < 0.0001) (Figures 4  and 5, respectively).Figure 6 illustrates that a WPS session is also associated with elevated HR by 7.03 bpm (95% CI 4.60 to 9.46; p < 0.0001).All the meta-analyses had substantial heterogeneity (>90%), which we accounted for by pooling the results with a random effects model.
Using GRADE, the quality of evidence for each study was assessed.Three studies received a high GRADE, 8  were moderate GRADE, and 4 were low GRADE.To further analyze our data, we conducted a sensitivity analyses by stratifying by the GRADE of the studies and by type of WPS.Upon performing a subgroup analysis of only high/ moderate GRADE studies, heterogeneity (I 2 statistic) decreased from >90% to 0.0% in the meta-analysis for the outcome of SBP and 62.3% for DBP.Unfortunately, there was limited overlap in the type and size of the WPS between each study and many studies did not report this level of detail, thereby limiting our ability to conduct sensitivity analyses on these factors.

Discussion
WPS is a common practice with increasing prevalence globally, especially amongst younger generations [19][20][21] .The perception that WPS carries fewer health risks than cigarette smoking has propelled its growth and contributed to limited regulations, [19][20][21] despite the fact that several studies have shown that WPS may have similar health consequences as cigarette smoking [20][21][22][23][24] .The findings from our pooled analyses, showing statistically significant increases in all measured hemodynamic parameters of cardiopulmonary function, parallel the effects seen with smoking cigarettes 25 .
The nicotine in cigarettes has been found to increase systolic blood pressure 5-10 mmHg and HR by 10-15 bpm; 25 similarly, our analysis found an increase in SBP by 6.45 mmHg and HR by 7.03 bpm.More recently, a Mendelian Randomization Meta-Analysis looking at the effect of smoking on blood pressure and resting heart rate measurements revealed that smoking one additional cigarette per day was associated with a 0.08 mmHg increase in SBP, 0.05 mmHg increase in DBP, and 0.21 bpm increase in HR 26 .Additionally, not only does the literature suggest comparable changes in hemodynamic parameters with acute use of cigarettes or WPS, but also that WPS may actually be associated with higher levels of exposure to some toxicants such as tobacco-specific nitrosamines, polycyclic aromatic hydrocarbons, volatile aldehydes, benzene, nitric oxide, heavy metals, and CO due to the burning of charcoal to heat tobacco-or nontobacco-based shisha in the hookah WP 20,21,27,28 .In a direct comparison of toxicant exposure between WPS and cigarette smoking, Eissenberg and Shihadeh in 2009 found that WPS was associated with an average increase in expired CO by 23.9 ppm whereas the average expired CO for cigarette smoking was 2.7 ppm 28 .However, the peak nicotine levels for WPS and tobacco cigarettes were similar in the study, 28 which Abbreviations: CI, confidence interval; CO, carbon monoxide; ppm, parts per million can explain why WPS has similar effects on hemodynamic parameters as does smoking cigarettes.In fact, the level of nicotine in the blood can increase up to 250% after one session of hookah smoking and remain elevated for 40-45 minutes 20,21 .Of course, the dose of nicotine and other harmful and potentially harmful constituents varies with the duration and intensity of both hookah and smoking cigarettes.
As with smoking cigarettes, the changes seen in hemodynamic parameters of cardiopulmonary function in this meta-analysis can be attributed to the nicotine and CO exposures obtained with WPS 20,21,25,30 .Nicotine is an agonist at nicotinic receptors in the brain, at neuromuscular junctions, the adrenal medulla, and autonomic ganglia.It acutely increases norepinephrine and epinephrine release, which in turn increases heart rate, myocardial contractility, and cardiac output 20,25,30,31 .High levels of CO can lead to decreased oxygen supply to tissues, including myocardial muscles, due to the production of COHb, which prevents the binding and distribution of oxygen to the body 20,25,32 .Lastly, exposure to additional toxicants in WPS can lead to oxidative stress, which in turn can induce inflammation and endothelial dysfunction 25,33 .Together, these factors combine to increase myocardial oxygen demand and decrease in oxygen supply, putting strain on the heart, and can also lead to vascular damage 20,25,30,31 .Although acutely these changes lead to increases in blood pressure and HR, cumulative exposures are beginning to show a trend toward development of cardiopulmonary disease 20,24 .
This meta-analysis indicates that the acute effect of WPS on the cardiopulmonary system parallels smoking cigarettes and long term studies are also starting to show a trend toward negative health effects 34 .Similarly, Haddad, et al. 29 performed a systematic review and found that WPS may be as harmful as cigarettes in several hemodynamic parameters of cardiopulmonary function, but regulations of WPS remain limited 21 .In the United States, hookah establishments are often exempted from smoke free air laws in several states, 21 but some hookah establishments must use tobacco-free shisha instead of the traditional tobacco shisha 35 .Importantly, even tobacco-free shisha can affect hemodynamic parameters.Despite the absence of nicotine, tobacco-free shisha can acutely increase expired CO and COHb levels and has been shown to compromise cardiopulmonary regulation 7,36 .As the evidence on the negative cardiopulmonary, and overall, health effects of WPS grows, policy changes will be necessary to protect the public 37 .
In this meta-analysis, we found statistically significant increases in hemodynamic parameters of cardiopulmonary function and expired CO content after WPS exposure, but a limitation was the high heterogeneity of the data.This can be attributed to the geographic diversity of the studies analyzed, the multiple study protocols, and the various different forms of waterpipes, shisha, and charcoal that exist, as noted by Chaouachi et al [38][39][40] as a serious limitation of the existing WPS literature.For future studies, standardized approaches to evaluating WPS exposures and outcomes across a varied global population will be necessary to more definitively associate WPS with long term cardiopulmonary disease.

Conclusion
WPS exposure is associated with statistically significant and potentially clinically relevant short term increases in hemodynamic parameters of cardiopulmonary function, including SBP, DBP, MAP, HR, and the amount of expired CO.Importantly, these findings parallel the acute effects seen with smoking cigarettes.Studies looking at the long-term effects of repeated WPS exposures on cardiopulmonary disease are in their infancy, but initial results point towards development of cardiopulmonary disease with cumulative WPS exposure.If the trend toward cardiopulmonary disease persists, health policy changes will need to take place in response to the negative cardiopulmonary health effects of WPS.However, standardized approaches to evaluating WPS exposures and outcomes are necessary for more definitive associations with health outcomes.

Figure 1 :
Figure 1: Process of Inclusion of Studies.

Figure 2 .Figure 3 .Figure 4 .
Figure 2. Forest plot of the mean difference of a WPS session and an acute elevation in SBP/DBP.

Figure 6 .
Figure 6.Forest plot of the mean difference of a WPS session and an acute elevation in HR measured in bpm Abbreviations: bpm, beats per minute; HR, heart rate; WPS, water pipe smoke; CI, confidence interval

Figure 5 .
Figure 5. Forest plot of the mean difference of acute elevation in expired CO measured in ppm.

Table 1 .
. MeSH Headings Used to Identify Relevant Studies.

Table 2 . Markers of Cardiopulmonary Function in Waterpipe Smoking Author, Year Study Design and Location Sample Size and Characteristics Waterpipe & Equipment Properties Comments and Limitations
Cross-sectional designVolunteers smoked for 45-minutes in a well ventilated room Tobacco cessation prior to beginning of study: 84 hours School of Medicine in Amman, Jordan Age range: 20 -45 years old Average age in years (Mean ± SD): 27 ± 8 Average WP use in years (Mean ± SD): 3.8 ± 2.3 (smoked at least 3 times per week) n = 18 (100% male) Convenience sampling WP: Large-size Arghileh 20 grams of HB Mu'asel BP measured by mercury sphygmomanometer CO measured by a trained person using a portable Bedfont EC50-MICRO CO monitor smokerlyser.HR measurement technique not reportedAbbreviations: BP, blood pressure; bpm, beats per minute; CO, carbon monoxide; COHb, carboxyl hemoglobin; DBP, diastolic blood pressure; HR, heart rate; MAP, mean arterial pressure; mmHG, millimeter of mercury; n, sample size; NR, not reported; s, seconds; SBP, systolic blood pressure; WP, waterpipe; WPS, waterpipe smoke; PAH, polyaromatic hydrocarbons; UAE, United Arab Emirates