Thirdhand smoke can damage epithelial cells in the respiratory system by stressing cells and causing them to fight for survival, a research team led by scientists at the University of California, Riverside, has found.
The finding could assist physicians treating patients exposed to thirdhand smoke.
“Our data show that cells in humans are affected by thirdhand smoke,” said Prue Talbot, a professor in the Department of Molecular, Cell and Systems Biology, who led the research.
“The health effects of THS, have been studied in cultured cells and animal models, but this is the first study to show a direct effect of thirdhand smoke on gene expression in humans.”
Study results appear in JAMA Network Open.
Thirdhand smoke, or THS, results when exhaled smoke and smoke emanating from the tip of burning cigarettes settles on surfaces such as clothing, hair, furniture, and cars.
Not strictly smoke, THS refers to the residues left behind by smoking.
“THS can resurface into the atmosphere and can be inhaled unwillingly by nonsmokers,” said Giovanna Pozuelos, the first author of the research paper and a graduate student in Talbot’s lab.
“It has not been widely studied, which may explain why no regulations are in place to protect nonsmokers from it.”
The researchers obtained nasal scrapes from four healthy nonsmokers who had been exposed to THS for three hours in a laboratory setting at UC San Francisco.
The UCR researchers then worked to get good quality RNA from the scrapes – necessary to examine gene expression changes.
RNA sequencing identified genes that were over- or under-expressed.
They found 382 genes were significantly over-expressed; seven other genes were under-expressed. They then identified pathways affected by these genes.
“THS inhalation for only three hours significantly altered gene expression in the nasal epithelium of healthy nonsmokers,” Pozuelos said.
“The inhalation altered pathways associated with oxidative stress, which can damage DNA, with cancer being a potential long-term outcome.
It’s extremely unlikely a three-hour exposure to THS would cause cancer, but if someone lived in an apartment or home with THS or drove a car regularly where THS was present, there could be health consequences.”
Because gene expression in the nasal epithelium is similar to the bronchial epithelium, the researchers note that their data is relevant to cells deeper in the respiratory system.
In the samples they studied, the researchers also found that brief THS exposure affected mitochondrial activity. Mitochondria are organelles that serve as the cell’s powerhouses. If left unchecked, the observed effects would lead to cell death.
Pozuelos explained that the team focused on the nasal epithelium because the nasal passage is one way THS can enter people’s lungs.
The other common exposure route is through the skin, which the researchers did not study, but plan to in the future.
Already, the researchers are working with groups in San Diego, California, and Cincinnati to study long-term exposure to THS, made possible with access to homes where people are being exposed to THS.
“Many people do not know what THS is,” said Talbot, the director of the UCR Stem Cell Center.
“We hope our study raises awareness of this potential health hazard. Many smoking adults think, ‘I smoke outside, so my family inside the house will not get exposed.’ But smokers carry chemicals like nicotine indoors with their clothes. It’s important that people understand that THS is real and potentially harmful.”
THS refers to tobacco residue and stale or aged secondhand smoke.
THS is not strictly smoke but rather the residues left behind by smoking
It refers to the contamination of surfaces in contact with compounds emitted in SHS, the products generated by chemical transformations of these components, and the off-gassing of volatile components into the air.1,2
The phrase “the four Rs” provides a working definition of THS:
tobacco chemicals (some toxic) that remain, react, re-emit, and/or are resuspended long after active smoking ends.
THS constituents may remain adsorbed to surfaces and dust particles, often penetrating deep into materials such as wallboard or upholstery; as they persist they may react with atmospheric oxidants to yield potentially harmful byproducts.
Both precursors and byproducts may be re-emitted back to the gas phase, and airborne particles that initially deposited onto indoor surfaces may be resuspended.
Differences between THS and SHS
THS is conceptually distinct from SHS, which is the aerosol (particle-bound and gas phase constituents) present while smoking is taking place.
Nonsmokers’ exposures to SHS are associated with freshly emitted smoke.
Hence, the primary pathway is inhalation, and the time scales for exposure are relatively short (minutes to a few hours).
By contrast, exposure pathways for THS include not only inhalation but also dermal uptake from contact with contaminated surfaces (potentially including the clothing of smokers) and ingestion of THS that is on the hands or perhaps food.
For toddlers, mouthing of objects in their environment is another route of potential oral exposure to THS.
The time scale for the presence of THS indoors will generally be much longer than that for SHS and could stretch to months.
Why Study THS?
Inhalation of tobacco smoke, both by those smoking actively and by nonsmokers involuntarily inhaling tobacco smoke, has been causally linked to a wide range of diseases and other adverse consequences.3
Interest in THS accelerated after the results of internal research at Phillip Morris in the 1980s were made public through litigation settlements.4
A researcher and coauthor of this paper (Schick) at the University of California San Francisco found records in Philip Morris papers showing that SHS can become more toxic as it ages.
An analysis of unpublished results revealed that concentrations of carcinogenic tobacco-specific nitrosamines (TSNAs) increased over time in aging SHS.
Soon after Schick’s article appeared,4 a laboratory study5 showed that nicotine on surfaces can react with a common indoor pollutant to produce TSNAs under conditions that are commonly found in indoor environments.
These high-impact discoveries directed attention to the concept that THS as a distinct entity poses health risks for children and adults.
By 2011, both laboratory5,6 and field studies7,8 had produced sufficient evidence to warrant pursuing a programmatic research agenda to close gaps in our current understanding of the chemistry, exposure, toxicology, and health effects of THS, as well as its behavioral, economic, and sociocultural considerations and consequences.2
The California Consortium on Thirdhand Smoke was launched in 2011 and renewed in 2014 to carry out the research agenda.
Objectives for This Perspective
This Perspective describes progress made by the Consortium and other investigators during the past five years, updating the review published in 2011.2
This multidisciplinary Perspective covers THS chemistry, the occurrence of tobacco-derived substances in real world environments, including carcinogens, the toxicity of THS using in vitro and animal models, studies of human exposure using biomarkers, possible approaches to remediation of THS-contaminated environments, and how the results of research can influence public policy to reduce THS exposure.
It is hoped that illuminating the toxic substance exposure potential of THS will encourage smoking cessation and tobacco control efforts.
Approach
The long-term goals of the California Consortium on Thirdhand Smoke are to identify the health effects of exposure to THS, develop environmental indicators and biomarkers of exposure to THS, and devise and disseminate evidence-based policies to prevent and remediate such exposures.
The first three years (Phase I of the Consortium’s collaborative multidisciplinary research) have led to sufficient understanding of exposure to and the mechanisms by which THS causes injury in order to lay the groundwork for more extensive investigation of its health effects and their policy implications.
During the two years of Phase II, the Consortium has continued to use its highly successful collaborative structure to move the research toward addressing the question of how much harm THS causes to human health.
The outcomes of the Consortium’s research will be used to develop risk assessments as a basis for motivating and guiding policy development and implementation, particularly to those groups most likely to have the highest exposures.
Evidence of Human Exposure
The presence and amount of THS can be assessed through environmental sampling in air, in dust, and on surfaces.
The study mentioned above14 found elevated levels of nicotine in dust collected in the homes of Danish smokers, and the researchers observed a strong positive association of nicotine with smoking level.
They concluded that nonsmokers inhale nicotine and other tobacco smoke constituents from respirable dust, even if smoking does not occur while the nonsmokers are present. Matt et al.7 used a standardized dust sampling protocol in homes of smoking mothers of infants with and without indoor smoking bans.7
In addition to dust, they also observed elevated levels of nicotine on household surfaces (e.g., coffee table in living room, bedframe where the infant slept), and on the hands of the smoking mother.
Compared to infants in homes where no smoking was allowed, concentrations of cotinine (a biomarker for exposure to nicotine) in the urine were much higher in infants whose parents smoked indoors.
If the parents only smoked outdoors, the infants had lower cotinine levels, but still many times higher than infants of nonsmoking parents.
By the time the California Consortium began functioning in 2011, Matt’s group had also documented THS levels in nonsmokers’ homes that had been recently occupied by smokers15 and in used cars.16,17
Since then, nicotine and other THS constituents have been found in virtually any indoor environment in which tobacco has been smoked regularly, as well as in nonsmoking indoor environments that are near areas frequented by smokers, which will be discussed in subsequent sections of this Perspective.
Dynamic Behavior of Tobacco Smoke Pollutants in Indoor Environments
Mechanical or natural ventilation is the main process by which harmful pollutant concentrations can be kept at acceptable levels.8
Typical ventilation (air exchange) rates in US residential and commercial buildings remove most airborne indoor pollutants over just a few hours by introducing cleaner outdoor air.
However, ventilation alone cannot achieve acceptable indoor air quality if there is smoking.18
The residence time of many airborne SHS constituents in indoor air is usually short.
By contrast, surface-bound THS constituents can remain in contact with indoor air for days, weeks, and months, thus providing ample time for chemical transformations to take place as THS on surfaces interact with reactive pollutants in indoor air.
The reactive atmospheric species of outdoor origin that can drive these reactions are significantly depleted during the outdoor-to-indoor transit; e.g., indoor ozone levels are often 20–70% of the outdoor concentration measured simultaneously, and OH radicals can be reduced by more than an order of magnitude compared with outdoor air.
However, these compounds are not completely removed from indoor air and often drive indoor chemistry.19–21
Indoor combustion sources, such as gas stoves, may generate other reactive species, including nitrous acid (HONO), hydrogen peroxide (H2O2), and free radicals.
Even though direct sunlight is absent from many indoor settings, recent evidence indicates that the role of direct photolysis in the generation of indoor OH and NO3 radicals is more significant than originally thought.22,23
Thus, oxygen- and nitrogen-containing radicals, oxidants, and nitrosating species can be present at levels that can support reactions of THS compounds with indoor pollutants.
With the long residence times observed for surface-bound THS constituents, there is potential for these constituents to be slowly transformed into various byproducts as they age.
Nicotine is one of the most prevalent constituents in tobacco smoke, and it is a critically important constituent in THS chemistry because of its high emission rate and its high concentrations and persistence on indoor surfaces.24,25
In contact with ozone, nicotine oxidizes, yielding numerous volatile and semivolatile species, as well as new ultrafine particles.26Laboratory studies have revealed that several of the identified oxidation byproducts are multifunctional carbonyls, amides, N-oxides, and carboxylic acids that have an asthma hazard index higher than that of nicotine, indicating that oxidative aging may lead to more harmful residues in THS.
In addition, reactive oxygen species were detected in secondary organic aerosol (SOA) formed by ozonation of nicotine.27,28
While ozone- and OH radical-driven oxidation is a major pathway for indoor chemistry, other reactions also lead to the formation of harmful byproducts.
The nitrosation of nicotine by HONO emitted from combustion sources (including smoking) produced tobacco-specific nitrosamines (TSNAs) on indoor surfaces.5
These TSNAs included N′-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), and 4-(methylnitrosamino)-4-(3-pyridyl)butanal (NNA), a TSNA that is specific to THS as it is not commonly found in fresh smoke (Scheme 1) and must be formed by reaction with HONO from the combustion sources.
The mechanisms of nitrosamine formation are similar to those described for gas phase formation of volatile nitrosamines and formation of TSNAs in aqueous media.29,30
These studies replicated and extended unpublished research performed by Philip Morris in the 1980s, which revealed that TSNA concentrations increase over time and that secondhand smoke becomes more toxic as it ages.4
Interest in THS accelerated after these findings were uncovered because some TSNAs, in particular NNK and NNN, are highly carcinogenic.
Formation of TSNAs from the Reaction of Nicotine and Nitrous Acid
More information:JAMA Network Open (2019). DOI: 10.1001/jamanetworkopen.2019.6362
Journal information: JAMA Network Open
Provided by University of California – Riverside
