Electronic Cigarettes, Vaping, and Lung Disease: A Short
Primer
Max Deschner
1
, Marcel Tunks
2
, Cory Yamashita
3
1
Department of Medicine, Western University, London, ON, Canada
2
Department of Medicine, Division of Respirology, McMaster University
3
Department of Medicine, Division of Respirology, Western University
Received: 15 November 2019; Accepted: 25 May 2020; Published: 18 November 2020
DOI: http://dx.doi.org/10.22374/cjgim.v15i4.408
ABSTRACT
In recent years there has been a proliferation in the practice of vaping to consume nicotine-
and cannabis-based products. While evidence on the benefits and risks of electronic cigarettes
(e-cigarettes) is evolving, this brief primer highlights important new information about vaping
for clinicians, researchers and the public. In 2018, the Canadian government passed legislation
to regulate tobacco and vaping products. We discuss evidence comparing e-cigarettes versus
nicotine replacement therapy for smoking cessation and highlight limitations of this body of
research. While e-cigarettes are felt to contain fewer toxins than cigarettes, the long-term effects
of vaping remain unknown. Emerging data demonstrates associations between vaping and acute
and chronic lung disease. We discuss the emergence of an outbreak of severe lung injury associated
with e-cigarette use in the United States and similar cases in Canada. Finally, we review evidence
demonstrating the growing prevalence of vaping and smoking amongst Canadian youth.
RESUME
Ces dernières années, on a assisté à une prolifération de la pratique de la vaporisation pour
consommer des produits à base de nicotine et de cannabis. Alors que les preuves sur les avantages
et les risques des cigarettes électroniques (e-cigarettes) évoluent, ce bref aperçu met en lumière de
nouvelles informations importantes sur le vaping pour les cliniciens, les chercheurs et le public.
En 2018, le gouvernement canadien a adopté une loi pour réglementer les produits du tabac
et les produits à base de vapeur. Nous examinons les données comparant les e-cigarettes et les
thérapies de remplacement de la nicotine pour le sevrage tabagique et soulignons les limites de
ce corpus de recherche. Bien que lon estime que les e-cigarettes contiennent moins de toxines
que les cigarettes, les effets à long terme des vapeurs restent inconnus. Les données émergentes
démontrent des associations entre l’inhalation de vapeurs et les maladies pulmonaires aiguës
et chroniques. Nous discutons de l’émergence dune épidémie de lésions pulmonaires graves
associées à l’utilisation des e-cigarettes aux États-Unis et de cas similaires au Canada. Enfin, nous
passons en revue les preuves démontrant la prévalence croissante des vapeurs et du tabagisme
chez les jeunes Canadiens.
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There are growing concerns regarding the proliferation of vaping
products in Canada. With increased use of, mainly, nicotine
and cannabis-based products, the legal, social, and medical
landscapes of electronic cigarettes (e-cigarettes) continue to
evolve. While governments and the public grapple with issues
around the regulation and safe use of e-cigarettes, physicians
also face questions about the role of e-cigarettes in smoking
cessation, associations between e-cigarettes and lung disease,
and the rising popularity of vaping products among youth. In
view of emerging evidence on the potential public health risks
and benefits of e-cigarette use, this article offers a brief primer
for physicians on important new information about e-cigarettes
and vaping.
Vaping involves inhaling and exhaling aerosols produced
when an electronic cigarette or similar device heats a substance
such as nicotine, tetrahydrocannabinol (THC), or cannabidiol
(CBD). Combusted aerosols are generally in liquid form;
however, some vaping products may enable combustion of
solid or dried substances like cannabis. E-cigarettes have gone
through several generational designs since their introduction
in the early 2000s but traditionally have included a battery, a
mouthpiece, a heating device, and a chamber containing liquid
solution. Depending on the maker and generation, e-cigarettes
may be called cigalikes, vape pens, mods, e-hookahs, tank
systems, pod vapes, or electronic nicotine delivery systems
(ENDS). Older generation devices like cigalikes are disposable
and cannot be recharged or refilled. Newer generation devices
tend to be rechargeable, feature refillable cartridges, and may
deliver relatively higher concentrations of nicotine compared
with older devices. Vaping devices may include additives such
as chemical flavorings, propylene glycol, glycerol, benzoic acid,
or vitamin E acetate, a synthetic form of vitamin E.
1
E-cigarettes are approved for sale in Canada and regulated
under federal law. The Tobacco and Vaping Products Act
(TVPA)—passed in May 2018—regulates manufacturing, sales,
labeling, and advertising of tobacco and vaping products in
Canada.
2
This law authorizes the federal government to ban
certain ingredients in vaping devices and prohibits minors from
using tobacco and vaping products. The Cannabis Act governs
the production, distribution, sale, and possession of cannabis
across Canada.
3
Other federal regulations governing vaping
include the Canada Consumer Product Safety Act, the Food
and Drugs Act, and the Non-smokers’ Health Act.
4
In recent years, nicotine-based e-cigarettes have grown in
popularity, in part, because they may be perceived by the public,
some physicians, and healthcare organizations as a less harmful
alternative to traditional tobacco cigarettes. This has led to their
use as a smoking cessation tool in some jurisdictions. While
e-cigarettes are not approved by Health Canada for smoking
cessation, Public Health England recommends tobacco smokers
try regulated nicotine vaping products in addition to smoking
cessation medications and behavioral support interventions.
5
European Union regulations limit the nicotine concentration in
vaping liquids to a maximum of 20 mg/mL while Canada limits
concentrations to 66 mg/mL.
6,7
Unlike other approved tools for
smoking cessation, e-cigarettes did not undergo robust pre-clinical
safety or efficacy studies before being introduced for sale.
8
A
recent randomized, controlled trial comparing e-cigarettes to
nicotine replacement therapy (NRT) over 3 months found that
at 1 year, 18% of e-cigarette users versus 9.9% of NRT users
abstained from tobacco (P < 0.001).
9
However, it is worthwhile
noting that 80% of e-cigarette subjects compared with 9% of
NRT subjects were still using their assigned method at the end of
study follow-up.
9
It remains unclear whether e-cigarettes extend
nicotine dependency or prompt relapse to tobacco cigarette
smoking among former smokers.
10
More studies are needed
comparing e-cigarettes with other Health Canada-approved
smoking cessation tools such as varenicline and bupropion.
Emerging data have highlighted the development of acute,
sub-acute, and chronic lung injury among individuals who vape.
Vaping has been associated with chronic bronchitic symptoms
and development of asthma and chronic obstructive pulmonary
disease.
11–13
Studies in humans have suggested associations
between vaping and ciliary dysfunction, immune suppression,
and delayed recovery from pulmonary infection.
14,15
Although
studies suggest some biological plausibility that e-cigarettes may
be linked to lung injury, the population health effects of vaping
may not be evident for years—just as the long-term health effects
of tobacco smoking (including causal links to lung cancer)
took decades to become apparent. No long-term toxicology or
safety studies on e-cigarettes and vaping have been completed
in humans.
8
As such, statements about the relative safety of
e-cigarettes over tobacco cigarettes cannot be made conclusively.
Various forms of acute and sub-acute lung injury have been
linked to vaping. In August 2019, the US Centers for Disease
Control (CDC) reported an outbreak of severe lung injury
associated with e-cigarette use across the United States (US).
The number of cases peaked in September 2019 and declined
through early 2020.
1,16
Various patterns of lung injury have been
described including acute eosinophilic pneumonia, organizing
pneumonia, diffuse alveolar hemorrhage, diffuse alveolar
damage, and acute respiratory distress syndrome.
17
The CDC
termed this group of conditions “e-cigarette or vaping product
use-associated lung injury” or EVALI. As of February 18, 2020, a
total of 2807 cases of EVALI were reported in the US, including
68 deaths.
1
In Canada, as of April 7, 2020, a total of 19 cases of
vaping-associated lung illness were reported to the Public Health
Agency of Canada.
18
It is noteworthy that THC use either alone
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or in combination with nicotine was identified in nearly 80% of
early cases in the US.
16
Only seven of 19 cases in Canada were
associated with THC-containing products.
18
Although no deaths
had been reported in Canada, severe cases had emerged including
one patient with vaping-associated acute bronchiolitis who
required intubation and extracorporeal membrane oxygenation,
and developed chronic airway obstruction after resolution of
the critical illness.
18,19
In November 2019, the CDC reported
that laboratory testing of bronchoalveolar lavage samples from
29 patients with evidence of EVALI from across the US found
vitamin E acetate in all samples.
1
The results showed 82% of
samples contained THC and 62% contained nicotine.
1
Many
products linked to cases of EVALI in the US were obtained from
the black market, leading to concern that vitamin E acetate was
used to thicken or dilute illicit THC-based vaping liquids.
20,21
While vitamin E acetate has been highly associated with EVALI, it
still appears that no single product accounts for all case findings
in Canada and the US. In view of the outbreak, the CDC has
recommended that individuals completely abstain from THC-
containing e-cigarettes.
1
Health Canada has issued a warning
about potential risks of pulmonary illness associated with vaping
and recommended avoiding vaping products obtained from
illegal or unregulated sources.
18
While the long-term health effects of inhaling aerosolized
compounds remain unknown, evidence is clear that vaping
among youth is on the rise. An analysis of cross-sectional
surveys showed that the prevalence of smoking tobacco and
vaping among Canadian youth aged 16–19 years increased
between 2017 and 2018 (P < 0.001).
11
It has been speculated
that targeted advertising of vaping products to youth may play
a key role in this observation. For example, one study found
that young people who recalled seeing e-cigarette marketing in
retail stores were more likely to initiate vaping up to 2.5 years
later (adjusted odds ratio [aOR] 1.99, P < 0.05) (aOR 1.30, P <
0.05).
22
Furthermore, e-cigarette use is linked to increased use
of tobacco cigarettes among youth.
23
Although a direct causal
pathway has not been proven, a prospective cohort study found
an association between 30-day use of e-cigarettes and smoking
a whole cigarette (aOR 2.12) and daily smoking (aOR 1.79).
23
In summary, e-cigarette use has increased in recent years,
particularly among young people and smokers who are attempting
to quit. While evidence evolves about the risks and benefits
of vaping, studies suggest e-cigarettes are associated with the
development of acute, sub-acute, and chronic lung disease
and increased tobacco use among youth. More robust research
is needed to determine the short-term and long-term health
consequences of vaping in view of the growing array of substances
and products available in regulated and illicit markets. This
will give physicians the information to better counsel patients
and contribute to future public health discussions and policies.
References
1. Centers for Disease Control and Prevention. Outbreak of lung injury
associated with the use of e-cigarette, or vaping, products [Internet]. 2020.
Available from: https://www.cdc.gov/tobacco/basic_information/e-cigarettes/
severe-lung-disease.html
2. Government of Canada. Tobacco and Vaping Products Act S.C. 1997, c. 13,
s. 1; 2018, c. 9, s. 2 [Internet]. 2019. Available from: https://laws-lois.justice.
gc.ca/eng/acts/t-11.5/page-1.html
3. Government of Canada. Cannabis act S.C. 2018, c. 16 [Internet]. 2019.
Available from: https://laws-lois.justice.gc.ca/eng/acts/c-24.5/
4. Health Canada. Vaping product regulations [Internet]. 2020. Available from:
https://www.canada.ca/en/health-canada/services/smoking-tobacco/vaping/
product-safety-regulation.html
5. McNeill A, Brose L, Caulder R, Bauld L, Robson D. Vaping in
England: An evidence update including mental health and pregnancy,
March 2020: A report commissioned by Public Health England
[Internet]. Available from: https://www.gov.uk/government/
publications/vaping-in-england-evidence-update-march-2020/
vaping-in-england-2020-evidence-update-summary-authors-and-citation
6. European Union. Tobacco products directive (Directive 2014/40/EU)
[Internet]. 2014. Available from: https://ec.europa.eu/health/sites/health/
files/tobacco/docs/dir_201440_en.pdf
7. Government of Canada. Vaping products labelling and packaging regulations,
SOR/2019-353 [Internet]. 2019. Available from: https://laws-lois.justice.gc.ca/
eng/regulations/SOR-2019-353/FullText.html
8. Gotts JE, Jordt SE, McConnell R, Tarran R. What are the respiratory effects of
e-cigarettes? BMJ. 2019;366:l5275. http://dx.doi.org/10.1136/bmj.l5275
9. Hajek P, Phillips-Waller A, Przulj D, Pesola F, Smith KM, Bisal N, et al. A
randomized trial of e-cigarettes versus nicotine-replacement therapy. N Engl
J Med. 2019;380(7):629–37. http://dx.doi.org/10.1056/NEJMoa1808779
10. Caponnetto P, DiPiazza J, Cappello GC, Demma S, Maglia M, Polosa R,
et al. Multimodal smoking cessation in a real-life setting: Combining
motivational interviewing with official therapy and reduced risk
products. Tob Use Insights. 2019;12:1179173X19878435. http://dx.doi.
org/10.1177/1179173X19878435
11. Hammond D, Reid JL, Rynard VL, Fong G, Michael CK, McNeill A, et al.
Prevalence of vaping and smoking among adolescents in Canada, England,
and the United States: Repeat national cross sectional surveys. BMJ.
2019;365:l2219. http://dx.doi.org/10.1136/bmj.l2219
12. Wills TA, Pagano I, Williams RJ, Tam EK. E-cigarette use and respiratory
disorder in an adult sample. Drug Alcohol Depend. 2019;194:363–70. http://
dx.doi.org/10.1016/j.drugalcdep.2018.10.004
13. McConnell R, Barrington-Trimis JL, Wang K, Urman R, Hong H, Unger
J, et al. Electronic cigarette use and respiratory symptoms in adolescents.
Am J Respir Crit Care Med. 2017;195(8):1043–9. http://dx.doi.org/10.1164/
rccm.201604-0804OC
14. Carson JL, Zhou L, Brighton L, Mills KH, Zhou H, Jaspers I, et al. Temporal
structure/function variation in cultured differentiated human nasal
epithelium associated with acute single exposure to tobacco smoke or
E-cigarette vapor. Inhal Toxicol. 2017;29(3):137–44. http://dx.doi.org/10.1080
/08958378.2017.1318985
15. Martin EM, Clapp PW, Rebuli ME, Pawlak EA, Glista-Baker E, Benowitz NL,
et al. E-cigarette use results in suppression of immune and inflammatory-
response genes in nasal epithelial cells similar to cigarette smoke. Am
J Physiol Lung Cell Mol Physiol. 2016;311(1):L135–44. http://dx.doi.
org/10.1152/ajplung.00170.2016
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16. Perrine CG, Pickens CM, Boehmer TK, King BA, Jones CM, DeSisto CL,
et al. Characteristics of a multistate outbreak of lung injury associated with
e-cigarette use, or vaping—United States, 2019. MMWR Morb Mortal Wkly
Rep. 2019;68(39):860–4. http://dx.doi.org/10.15585/mmwr.mm6839e1
17. Christiani DC. Vaping-induced lung injury. N Engl J Med. 2020;382:960–2.
http://dx.doi.org/10.1056/NEJMe1912032
18. Government of Canada. Vaping-associated lung illness [Internet]. 2020
Apr 16. Available from: https://www.canada.ca/en/public-health/services/
diseases/vaping-pulmonary-illness.html#a1
19. Landman ST, Dhaliwal I, Mackenzie CA, Martinu T, Steele A, Bosma KJ,
et al. Life-threatening bronchiolitis related to electronic cigarette use in a
Canadian youth. CMAJ. 2019;191(48):E1321–31. http://dx.doi.org/10.1503/
cmaj.191402
20. Layden JE, Ghinai I, Pray I, Kimball A, Layer M, Tenforde M,
et al. Pulmonary illness related to e-cigarette use in Illinois and
Wisconsin—Preliminary report. N Engl J Med. 2020;382:903–16. http://
dx.doi.org/10.1056/NEJMoa1911614
21. Kirkham C, Dastin J. Explainer: One possible culprit in vaping lung
illnesses—“Dank Vapes. Reuters [Internet]. September 13, 2019. Available
from: https://www.reuters.com/article/us-health-vaping-industry-explainer/
explainer-one-possible-culprit-in-vaping-lung-illnesses-dank-vapes-
idUSKCN1VY2ET
22. Loukas A, Paddock EM, Li X, Harrell MB, Pasch KE, Perry CL. Electronic
nicotine delivery systems marketing and initiation among youth and young
adults. Pediatrics. 2019;144(3):e20183601. http://dx.doi.org/10.1542/
peds.2018-3601
23. Hammond D, Reid JL, Cole AG, Leatherdale ST. Electronic cigarette use
and smoking initiation among youth: A longitudinal cohort study. CMAJ.
2017;189(43):E1328–36. http://dx.doi.org/10.1503/cmaj.161002
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Second-Line Therapy for Immune Thrombocytopenia:
Real-World Experience in Canada
Hasmik Nazaryan
1
, Yang Liu
1
, Emily Sirotich
1
, Joanne Duncan
1
, Ishac Nazy
1
, Emily Sokolov
1
, John Kelton
1
, Donald M. Arnold
1,2
1
McMaster Centre for Transfusion Research, Department of Medicine, McMaster University, Hamilton, ON, Canada;
2
Canadian Blood
Services, Hamilton, ON, Canada
Corresponding Author: Donald M. Arnold: arnold@mcmaster.ca
Received: 08 April 2020; Accepted: 19 August 2020; Published: 18 November 2020
DOI: https://doi.org/10.22374/cjgim.v15i4.450
ABSTRACT
Background
The sequence of second-line therapy used for the treatment of immune thrombocytopenia (ITP)
is variable. This study aimed to describe the types and sequences of second-line therapies for a
large cohort of ITP patients in Canada.
Methods
We completed a retrospective cohort study of the McMaster ITP Registry. We included patients
with primary or secondary ITP who had received one or more second-line therapies including
any of the splenectomy, rituximab, danazol, dapsone, or thrombopoietin receptor agonists
(TPO-RAs), or immunosuppressant medications. Immunosuppressant medications included
azathioprine, cyclophosphamide, cyclosporine, or mycophenolate given alone or in combination.
Results
We identified 204 ITP patients who had received one or more second-line therapies. The
most common second-line therapies were immunosuppressant medications (n = 106; 52.0%),
splenectomy (n = 106; 52.0%), TPO-RAs (n = 75; 36.8%), danazol (n = 73; 35.8%), and rituximab
(n = 67; 32.8%). For patients who received only one second-line therapy (n = 88), the most
common treatment was splenectomy (n = 28; 31.8%). For patients who received more than one
second-line therapy (n = 116), the most common treatment sequence was splenectomy, followed
by immunosuppressant medications (n = 7; 6.0%). Of the 154 evaluable patients at the end of
follow-up, 69 (44.8%) achieved a complete platelet count response and 101 (65.5%) achieved a
partial response.
Conclusion
Immunosuppressant medications and splenectomy are commonly used as second-line therapies
for ITP in Canada. Treatment choices and the sequence of treatments were variable.
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RESUME
Contexte
La séquence de la thérapie de deuxième ligne utilisée pour le traitement de la thrombocytopénie
immunitaire (PTI) est variable. Cette étude visait à décrire les types et les séquences des thérapies
de deuxième ligne pour une large cohorte de patients atteints de PTI au Canada.
Méthodes
Nous avons réalisé une étude de cohorte rétrospective du registre ITP de McMaster. Nous avons
inclus des patients atteints de PTI primaire ou secondaire qui avaient reçu une ou plusieurs
thérapies de deuxième ligne, y compris une splénectomie, du rituximab, du danazol, de la
dapsone ou des agonistes des récepteurs de la thrombopoïétine (AR-TPO), ou des médicaments
immunosuppresseurs. Les médicaments immunosuppresseurs comprennent lazathioprine, le
cyclophosphamide, la cyclosporine ou le mycophénolate, administrés seuls ou en combinaison.
Résultats
Nous avons identifié 204 patients atteints de PTI qui avaient reçu une ou plusieurs thérapies de
seconde ligne. Les thérapies de deuxième ligne les plus courantes étaient les immunosuppresseurs
(n = 106; 52.0%), la splénectomie (n = 106; 52.0%), les AR-TPO (n = 75; 36.8%), le danazol
(n = 73; 35.8%) et le rituximab (n = 67; 32.8%). Pour les patients qui nont reçu quun seul
traitement de deuxième intention (n = 88), le traitement le plus courant était la splénectomie
(n = 28; 31.8%). Pour les patients qui ont reçu plus d’un traitement de deuxième ligne (n = 116),
la séquence de traitement la plus courante était la splénectomie, suivie par les médicaments
immunosuppresseurs (n = 7; 6.0%). Sur les 154 patients évaluables à la fin du suivi, 69 (44.8%) ont
obtenu une réponse complète de la numération plaquettaire et 101 (65.5%) une réponse partielle.
Conclusion
Les médicaments immunosuppresseurs et la splénectomie sont couramment utilisés comme
traitements de deuxième intention pour le PTI au Canada. Les choix de traitement et la séquence
des traitements sont variables.
Keywords: immunosuppressants; ITP; platelets; registry; thrombocytopenia; thrombopoietin
Introduction
Immune thrombocytopenia (ITP) is an autoimmune platelet
disorder, characterized by peripheral blood platelet counts
below 100 × 10
9
/L with no underlying cause. ITP is considered
primary when there is no associated illness, and secondary when
it occurs in the context of infection, malignancy, or autoimmune
disease.
1
The estimated incidence of ITP is 1.6 to 3.9 per 100,000
persons per year; however, the prevalence is significantly higher,
especially in adults, as the disease is often chronic and patients
require multiple lines of therapy. Morbidity among patients with
ITP results from bleeding,
2
reduced quality of life,
3
fatigue,
4
and
toxicities from treatments.
5,6
Establishing the diagnosis of ITP can be challenging in the
outpatient setting as there is no diagnostic test with adequate
performance characteristics. Thus, providers must exclude other
causes of thrombocytopenia based on information they obtain
from history, physical examination, and laboratory investigations.
Our approach in the case of a patient with thrombocytopenia
in the outpatient setting is presented in Figure 1. Once the
diagnosis is established, the treatment decisions will depend
on the severity of the thrombocytopenia (treatment is generally
not required for platelet counts of >30 × 10
9
/L),
7,8
other risk
factors for bleeding (e.g., use of anticoagulant or anti-platelet
medications), lifestyle activities that can be associated with
trauma (e.g., high impact sports), and the presence or absence
of bleeding manifestations such as petechiae and oral purpura
(Figure 2).
9,10
First-line therapy for ITP consists of corticosteroids, with
or without intravenous immune globulins or rhesus immune
globulins, which are effective in raising the platelet count in
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