March 8, 2016

Stanton A. Glantz, PhD

Korean kids who use e-cigarettes have a lot more asthma and days lost from school

Jun Ho Cho and Samuel Y Pak just published an excellent paper, “Association between electronic cigarette use and asthma among high school students in South Korea,” which convincingly demonstrates that high school students (around 16 years old) who use e-cigarettes are much more likely to develop asthma (diagnosed by a doctor) and miss more days of school.
 
They did a very careful analysis that controlled for a wide variety of risk factors for asthma accounted for whether or not the youth were or had used cigarettes in the past.  Youth who already had asthma were excluded.
 
While they consider all the different patterns of cigarette and e-cigarette use, the most compelling results are from youth who that never smoked a cigarette.  Among this group, youth who used e-cigarettes were
 

  • 2.7 times more likely to develop asthma
  • 15.4 times more likely to miss 4 or more days from school due to asthma
  • 5.0 times more likely to miss 1-3 days from school due to asthma

 
The Discussion section of the paper has an excellent discussion about why e-cigarettes are likely to be having this big effect, which highlights the fact that e-cigarettes are toxicologically different from conventional cigarettes:
 

Asthma is known to be associated with inflammation. The results from this study are consistent with recent data reporting the effects of ECs on the lung, with increased airway epithelial inflammation in young people [26].The results are also supported by the recent animal experimental finding that the inhalation of nicotine solution in ECs worsened asthmatic symptoms by increasing inflammatory cells, including eosinophils, into the airways, which resulted in airway inflammation and hyper-responsiveness, possibly driven by the growth in the production of interleukin (IL)-4, IL-5, IL-13 and ovalbumin -specific IgE [27].
 
The EC cartomizer includes a nicotine cartridge, glass-fiber wick and reservoir, and heating filaments, which are comprised of chromium and nickel. Some or all of these materials may play a role in the pathogenesis of asthma. It is possible that fragments of glass fibers may be inhaled together with nicotine aerosols when inhaling EC aerosols. As a result, the respiratory system may be exposed to glass fiber fragments. A recent study showed that silicon, calcium, aluminum, and magnesium were among the most abundant elements in EC aerosol, and these were found in the silicate beads and fragments of the glass-fiber wick by scanning electron microscopy (SEM) and electron dispersion spectroscopy (EDS) [1]. Dorger et al. [14, 15] reported that the persistence of the glass fibers in the bronchial tree was correlated to the process of macrophagic phagocytosis and production of toxic oxygen radicals and superoxide dismutase (SOD), which contribute to the inflammatory process. The metals that are present in EC aerosols may also promote the pathogenesis of asthma. The concentrations of nine of eleven elements in EC aerosol were higher than or equal to the corresponding concentrations in CC [1]. The concentrations of four elements (sodium, iron, aluminum, nickel) were higher in EC aerosol, and the concentrations of five elements (copper, magnesium, lead, chromium, and manganese) were roughly equal to their levels in CC smoke. All of the metals in EC aerosols can adversely affect the respiratory system [1]. For example, inhalation of sodium may cause lung irritation, shortness of breath, and bronchitis. Iron may cause respiratory irritation, metal fume fever, siderosis, and fibrosis. Aluminum may cause asthma and pulmonary fibrosis. And nickel may cause chronic bronchitis, reduced lung function, lung inflammation, lung/nasal sinus cancer, and pulmonary fibrosis. Nicotine, a primary constituent of ECs, may also contribute to the pathogenesis of asthma. Among children diagnosed with asthma, concentrations of nicotine in the settled dusts from the bedrooms were significantly higher than in the controls [16]. Also, soluble components of EC, including nicotine caused dose-dependent loss of lung endothelial barrier function, were associated with oxidative stress and brisk inflammation [17]. Finally, a recent study has shown that particle analysis of EC aerosol revealed the presence of nanoparticles (

 
This paper is consistent with an earlier paper from Hong Kong that shows that never-smoking youth who use e-cigarettes are about twice as likely to suffer respiratory symptoms as those who did not use e-cigarettes.

Comments

Comment: 

 
Further evidence of metals in electronic cigarette aerosol can be found here, Williams et al, 2015: http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138933...
As they conclude:
“In summary, quality control in the manufacturing and labeling of EC has been a concern since their introduction [http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0138933.... In this study, the levels of tin in EC aerosols were variable between and within brands, demonstrating a lack of quality control in the manufacture of these products. Poor quality solder joints correlated with higher levels of tin in EC aerosols. These data support the idea that tin in EC could be reduced to negligible levels by: (1) improving the quality of tin solder joints in EC, (2) replacing tin solder with brass clamps, and/or (3) moving high quality tin solder joints outside the atomizing unit, as was done in brand D. Lowering levels of metals in EC aerosols would decrease the possibility of adverse health effects developing with prolonged use.”
 Can the Industry respond? Mmmmmmmmm:
 http://www.nytimes.com/2014/12/14/business/international/chinas-e-cigare...
 1) “In a grimy workshop, among boiling vats of chemicals, factory workers are busy turning stainless steel rods into slender tube casings, a crucial component of electronic cigarettes. Not long ago, Skorite Electronics was a tiny firm struggling to produce pen parts. Today, it is part of an enormous — and virtually unregulated — supply chain centered here that produces about 90 percent of the world’s e-cigarettes.”
2) “I worry about overseas consumers,” says Danny Zhu, who runs KangerTech, a large Shenzhen e-cigarette maker. “There are lots of small workshops here, with 10 or 20 people, and they have no quality control or safety certifications for the material they use. Some of their products are covered with a layer of paint. It’s unhealthy.”
David Bareham.

Comment: 

Perhaps study shows if asthma prevents youth from smoking, they'll vape. Moreover, perhaps ECs are used by asthmatics to quit, avoid or reduce smoking. A (rertospective) longitudinal study contradicts the implausible findings that dual use worsens asthma (http://www.mdpi.com/1660-4601/11/5/4965" title="http://www.mdpi.com/1660-4601/11/5/4965";http://www.mdpi.com/1660-4601/1...), which would raise questions about the directionality of the associations of this cross-sectional study.
This paper, like others, avoids mentioning that metals in EC vapor are below levels permitted for chronic use in inhalation medicines -- much below permissable levels for occupational exposures. This sleight-of-hand raises serious questions on bias and the validity of their other findings.

Comment: 

The comparison with medicines (which have demonstrated therapuetic value) and occupational exposures (which are much higher than allowed in ambient enviroments the general public is expose to) is not appropriate.
 
More important, this comment misses the point.&nbsp; The Korean study showed increased asthma in e-cigarette-smoking youth <em;who had never smoked a cigarette. </em;(There is a separate analysis of former smokers; see the paper for details.)
&nbsp;
The Polusa study that the commenter cites shows that e-cigarette only and dual users had fewer measures of asthma over time, which is a different question.

Comment: 

Not so in France: http://www.jahonline.org/article/S1054-139X(15)00732-6/abstract";http://www.jahonline.org/article/S1054-139X(15)00732-6/abstract
A B S T R A C T
Purpose: Electronic cigarettes are marketed as a tool to give up or reduce cigarette smoking, and
their use has risen sharply in recent years. There is concern that use is increasing particularly
among adolescents and that they are not being used as a cessation tool but as a novel experience in
their own right.
&nbsp;
Methods: The present research assessed prevalence and sociodemographic correlates of e-cigarette
use and standard cigarette use and also explored the extent to which e-cigarettes appear to be used
as a cessation tool. This was assessed using a questionnaire administered to 1,486 French adolescents aged 16 years.
&nbsp;
Results: Prevalence of e-cigarette experimentation was high (54%) and comparable to that for
standard cigarettes (55%). Furthermore, 20% of those who had experimented with e-cigarettes had
never tried standard cigarettes, and among regular smokers of standard cigarettes, intentions to
quit were not associated with e-cigarette usage frequency. Experimentation with both e-cigarettes
and standard cigarettes was significantly predicted by higher age, higher socioeconomic status,
and parental smoking of standard cigarettes (in particular the father). Being male marginally
predicted e-cigarette use, whereas being female significantly predicted standard cigarette use.
&nbsp;
Conclusions: These findings give cause for concern: <STRONG;e-cigarette usage experimentation is</strong;
<STRONG;extremely high, and is not associated with attempts to quit smoking standard cigarettes.</strong; Rather, it
is exposing adolescents to a highly addictive drug (nicotine) and may pave the way for a future
cigarette habit.
&nbsp;
David Bareham

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