Chronic tobacco smoke exposure revealed a significant increase in LDH release compared to air-exposed cells for all groups Fig. Cigarette smoke induces IL-8 secretion from pulmonary epithelia, which is notable because IL-8 is a chemoattractant that is responsible for neutrophil infiltration Chronic LC exposure led to significantly increased IL-8 secretion in media that was significantly greater than air or Kentucky exposures Fig.
During the smoking regimen used in Fig. Therefore, we further evaluated the effects of 10 equal puffs- from Kentucky cigarettes, Swisher Sweets and two commercial cigarette brands Marlboro and Camel; Fig.
Despite generating equal numbers of puffs, the chosen biomarkers of exposure, i. Five days of chronic Kentucky cigarette smoke exposure caused a significant decrease in ASL height Fig. Bands corresponding to the relevant protein sizes kD are shown in the figure. A comparative analysis of the gene expression patterns indicated that exposure to Swisher Sweets LCs altered significantly more genes than Kentucky cigarettes Fig. A total of genes were differentially expressed in the LC-exposed group compared to air.
However, 74 genes were altered in both smoke exposure groups and LCs altered 62 unique genes Fig. In contrast, Kentucky cigarette exposure altered genes, of which 30 were unique Fig. The full list of significantly altered genes is shown in Supplementary Tables 1—3. Furthermore, while the clustering coefficient remained same for both exposure groups 0.
Pathway analysis further revealed that LC exposure changed pathways involved in cellular functions, biological regulation, responses to stimuli, localization and immune responses Fig. LC exposure also caused significant alterations in protein groups involved in membrane trafficking, immunity, signalling molecules, cell adhesion molecules, nucleic acid binding, hydrolase and transferase activity Fig.
HBECs derived from 3 individual donors were exposed to chronic smoke from Kentucky cigarettes vs. Swisher Sweets LCs for 5 days vs. Since ASL is important for innate defense of the lung 6 , we next used a proteomics approach to comprehensively measure biomarkers of LC exposure.
A complete list of all proteins used in the quantification can be found in Supplementary Table 4. Consistent with the increased biological effects seen with LC exposure Fig.
As shown in Fig. However, proteins involved in the immune response and apoptosis were also altered. We next performed pathway analysis on these proteins. Tobacco smoke is a complex and dynamic mixture of thousands of compounds including several carcinogens and oxidants To see if the increased toxicity of LCs correlated with an increased chemical output, we evaluated the tar particle phase of LCs and Kentucky cigarettes. LC deposited significantly more tar particles per puff on Cambridge filter pads than Kentucky cigarette Supplementary Fig.
We then collected the tar particles from whole tobacco smoke and solubilized them in methanol to comprehensively evaluate all detectable chemical entities as a measure of relative chemical deposition using GC-MS. This analysis revealed that extracts from LC tar particles displayed a markedly different chemical profile to Kentucky cigarettes. Gas chromatography mass spectra indicated that compounds present in all tobacco products were found in higher quantities in LCs relative to Kentucky cigarettes Fig.
Additionally, unique 49 compounds were identified in LCs that were absent from Kentucky cigarettes Fig. Whole tobacco smoke tar particles were analyzed by GC-MS and 30 chemicals were found to be common to all the tobacco products. In contrast, 6 unique chemicals were identified in Kentucky cigarettes. Cigarettes are known to be highly toxic and can exert multiple effects on the pulmonary system, including, but not limited to, increases in apoptosis, inflammation, protease activation, DNA breaks as well as deranging the mucus clearance system 6.
However, whilst the biological effects of cigarettes have been well studied, next to nothing is known about the effects of LC exposure to the lung. Thus, whilst secondhand smoke from LCs impairs arterial flow-mediated dilation in rats 19 , the potential for LCs to induce harm in humans remains undetermined.
Using surface airway epithelia obtained directly from human lungs, we found that LCs exerted greater cytotoxicity and pro-inflammatory cytokine secretion and wrought greater changes at both the gene and protein levels. Thus, based on our data, we propose that cigarette exposure cannot be used as a proxy for LC exposure and that LCs need to be evaluated independently.
Furthermore, HBECs have previously been shown to be predictive of outcomes in both cystic fibrosis patients and smokers 21 , suggesting that their use is valid. For example, ion transport rapidly declines after 10 puffs of tobacco smoke in vitro and in vivo 9 and hypertonic saline elicits a more durable effect on mucus clearance rates in cystic fibrosis patients than normal subjects that is mirrored in HBECs Schamberger et al.
Of note, Knowles et al. As with the transepithelial electrical resistance data Fig. Given that a reduction in mature CFTR protein levels has extensively been linked to airway disease 6 that LCs cause a greater decrease in CFTR levels should be taken very seriously and indeed suggests that chronic LC use may have a greater propensity for causing lung pathology.
We also observed a significant decrease in cilia abundance Fig. Like the reduction in ASL height, decreased cilia function is indicative of impaired mucus clearance and impending lung disease, and may be a precursor to airways remodeling 6. The degree of deciliation was significantly greater after LC exposure than for cigarette smoke exposure, likely indicating a greater toxic burden induced by LCs. For example, propidium iodide binds to DNA, and can only get access to cells when they are damaged, and LDH is only released from damaged cells.
For both measures of cytotoxicity, the effects were significantly greater for LCs Fig. Chronic neutrophilia is a hallmark of chronic bronchitis, and the subsequent release of neutrophil elastase contributes to lung damage Tobacco smoke exposure has previously been shown to alter several genes in both HBECs and in vivo in health smokers Here, we found that 74 genes were commonly altered after both LC or cigarette smoke exposure Fig.
However, an additional 62 unique genes were altered by chronic LC exposure Fig. Of these genes, it is interesting that FOXJ1, which stimulates ciliogenesis 29 was significantly downregulated after LC exposure, which is consistent with the deciliation seen in Fig.
Similarly, consistent with the increase in cytokine secretion observed in Fig. Taken together, these unique gene changes are strongly suggestive of an increased inflammatory burden after LC exposure that may be associated with greater airways remodeling. Consistent with the effects seen on cellular toxicity, ASL proteome changes were significantly greater with LCs than Kentucky cigarettes Fig.
It is interesting that many of the altered proteins were involved in key pathways that would be used to ameliorate the increased toxic burden, including proteins involved in the detoxification of xenobiotics, e. Reactive oxygen species are thought to contribute to the toxicity of tobacco exposure 34 and upregulation of these proteins is likely a contributory response to this process.
Given that the ASL is involved in innate defense and that we observed dysregulation of innate defense proteins, our data suggest that pulmonary defenses may be altered by tobacco exposure. Indeed, tobacco smokers are thought to be immunocompromised and less able to deal with both viral and bacterial infections and our data suggest that LC users may be more compromised than cigarette users However, further epidemiological data will be needed to confirm or refute these observations.
It is important to note that the ASL proteome in vitro is derived from a relatively pure population of bronchial epithelial cells whilst in vivo , alveolar epithelia, macrophages, and glandular secretions all contribute to the ASL proteome.
Thus, an advantage of our preparation is that we can definitively say that LC exposure significantly altered the airway epithelial proteome. However, the effect of LCs on other pulmonary cell types will need to be determined and likely, greater differences will be observed in samples derived directly from patients. Previous reports indicated that LC smoke contains greater amounts of toxic chemicals compared to lung compared to cigarette smoke However, these studies were limited to the elemental composition.
Whilst LCs generate more tar per unit than Kentucky, equal puffs of LCs still resulted in significantly increased toxicity Fig. Furthermore, using a highly sensitive GC-MS technique, we identified a large number of previously undescribed compounds that were present in tar extract from LCs but not Kentucky cigarettes Figs 6 and 7. For example, 4-methylcatechol induces carcinogenecity in rats 37 and has been linked to cytotoxicity Furthermore, benzoic acid derivatives induce differentiation of cancer cell lines 39 and catechol estrogens have been shown to act as initiators of cancer Thus, we speculate that the increased tar produced Supplementary Fig.
LC sales have been increasing, especially amongst youth and young adults, and they are seen as a cheap alternative to cigarettes since they are taxed at a lower rate Because of the perception of reduced risk from LCs use and the availability of different flavors, LCs have thus gained popularity amongst younger smokers Flavors are thought to help with the initiation of smoking by masking the harsh taste of tobacco, thus facilitating addiction Although the use of these products amongst younger smokers has been well documented 44 , these products have historically not been regulated as strictly as cigarettes, in part due to a lack of information regarding their effects on health.
Thus, our data may i provide further data to help regulate these products and ii raise awareness that LCs are not safer than cigarettes and in fact, may be more toxic.
Collectively our data indicate that LCs exert significantly more toxic effects than regular cigarettes and elicit a greater biological response from the epithelia as they adapt to the noxious environment caused by chronic tobacco exposure. The distinctly different chemical makeup of LCs and their more severe effects suggest that strict regulation on sale, use and advertisement of these products for the sake of general public health safety effected.
All methods were performed following relevant guidelines and regulations. Informed consent was obtained from all donors or authorized representatives of the donors. Cultures were used after 3—6 weeks of seeding. Unless otherwise noted, tobacco smoke was generated according to ISO standards using a Borgwaldt LC1 smoke engine and applied to cells that were located in a specially designed smoke chamber 9.
Tobacco smoke was generated using identical parameters by either an LM1 or LX1 smoke engine Borgwaldt. We tested 3 commercial tobacco products: The brand names were Swisher Sweets, weight 1. For air exposure, cells were exposed to 18 air puffs that was equivalent to the mean number of puffs obtained from LCs. Cells were exposed to smoke from 1 cigarette or LC every day vs. Mean fluorescence was recorded on a multi-plate reader Infinite Pro, Tecan and representative images were captured on a Leica SP8 confocal microscope with a 40X dry objective.
While this group identified that cigarillo smoking was likely to have health effects, these were seen to be less than would occur with cigarettes. They saw smoking cigarillos as a safer alternative to smoking cigarettes. Interestingly, while some did not inhale the smoke, other did so and were even surprised at hearing that it was not normal practice to do so. These cigarillo smokers tended to have established brand relationships, only smoking specific brands although this was often a matter of convenience, that is, being able to commonly buy these brands.
That said, there was some sense that some brands were of higher quality than others, although this was often related to familiarity, with cigarillo smokers generally not having a large amount of previous knowledge of other brands than their preferred.
This group of cigarillo smokers customarily purchased their preferred brands from local tobacconists, with some brands available in other places that stocked cigarettes such as newsagents, bottleshops and supermarkets. Overall Appeal There appeared to be a divide between the packs tested with four brands Mayfair plain package , Wee Willem, Cafe Creme and Henri Wintermans being less appealing. Meanwhile, the other two brands Davidoff and Captain Black were seen to be more appealing.
As shown in the table below, the Mayfair plain package pack was seen to be the least appealing pack average rank 4.
Wee Willem, Cafe Creme and Henri Wintermans were also seen to be relatively less appealing average ranking 3. The Davidoff pack was the most appealing pack average ranking of 2. The table below shows the average ranking of each pack ordered from least appealing to most appealing. Table 6. Looking at these six cigarillo packs, please rank each of these packs in terms of 'appeal', 'quality of cigarillos', 'harm to health', 'how hard it would be to quit', 'noticeability of health warning'.
Please write the number '1' next to the pack you think is 'most From the qualitative discussions it was clear that respondents found the plain packaged cigarillo to be highly unattractive. This site complies with the HONcode standard for trustworthy health information: verify here. This content does not have an English version. This content does not have an Arabic version. See more conditions. Request Appointment. Healthy Lifestyle Quit smoking.
Products and services. Is cigar smoking safer than cigarette smoking? Answer From J. Taylor Hays, M. Thank you for Subscribing Our Housecall e-newsletter will keep you up-to-date on the latest health information. Please try again. However, a 3-gram bowl of tobacco with mg of nicotine can deliver a small amount of nicotine into the bloodstream. All tobacco products contain a number of toxins that come from a variety of sources: pesticides in the field, additives, and chemical changes that occur when tobacco with additives are burned.
Tar , arsenic , carbon monoxide , and polonium are just a few of the chemicals that are harmful to human health in tobacco smoke. To date, upwards of 7, chemicals and 70 carcinogenic compounds have been identified in tobacco and tobacco smoke.
The manufacture, packaging, and labeling of all tobacco products must meet FDA guidelines, as well as how products are advertised, promoted, sold and even imported. As of Dec. The FDA also has authority over components used with tobacco products. In this case, that would mean the pipes used to smoke the tobacco. All newly regulated tobacco products in the U. Nicotine is an addictive chemical. If the manufacturer submits a self-certification form to the FDA, along with proof that their newly regulated product is nicotine-free, then the required label will read: "This product is made from tobacco.
Ultimately, federal regulation over tobacco products helps to protect consumers. While all tobacco products are hazardous to health, FDA guidelines are meant to ensure that manufacturers are not able to secretly manipulate tobacco recipes in ways that could cause more harm than they already do.
It has been well documented that there is no safe level of exposure to tobacco smoke. This is true regardless of the form tobacco comes in. Smokers and non-smokers all face risks to their health when breathing in tobacco smoke. If you are a smoker who is trying to find a "healthier" alternative to cigarettes, know that the only good choice is to wean yourself off of tobacco entirely.
There are a number of ways to quit successfully. Nicotine addiction is enslaving, and quitting is difficult , but it's possible to do the work now to quit and shed the limits addiction puts on your life. Others have done it and you can, too. So you're ready to finally quit smoking? Our free guide can help you get on the right track. Sign up and get yours today. Am J Public Health. Pipe tobacco. Updated October 6, Nicotine content of domestic cigarettes, imported cigarettes and pipe tobacco in Iran.
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