1

Title:

Organizing Pneumonia related to Electronic Cigarette Use: A Case

Report and Review of Literature
Authors and Email addresses:

Mohammad Saud Khana : mohammad.khan2@utoledo.edu

Faisal Khateebb: faisal.khateeb@utoledo.edu
Jamal Akhtarc: jamal.akhtar@stvincenthospital.com
Zubair Khana: zubair.khan@utoledo.edu
Amos Lalc: amos.lal@stvincenthospital.com
Veronika Kholodovychd: veronika.kholodovych@utoledo.edu
Jeffrey Hammersleyb: jeffrey.hammersley@utoledo.edu

Authors’ Affiliations:
a
Department of Internal Medicine, University of Toledo Medical Center, Toledo,
Ohio, U.S.A.
b
Division of Pulmonary, Critical care and Sleep medicine, University of Toledo
Medical Center, Toledo, Ohio, U.S.A.
c
Department of Internal Medicine, Saint Vincent Hospital, Worcester, Massachusetts,
U.S.A.
d
Department of Pathology, University of Toledo Medical Center, Toledo, Ohio,
U.S.A.

Corresponding Author:
Mohammad Saud Khan
Department of Internal Medicine,
University of Toledo Medical Center,
3000 Arlington Avenue,
Mail Stop 1150,
Toledo, Ohio, 43614.

Authors’ Contributions: Mohammad Saud Khan and Faisal Khateeb designed the
study and drafted the manuscript. Zubair Khan collected data about the case. Jamal
Akhtar and Amos Lal analyzed the data and performed literature search. Veronika
Kholodovych provided histopathological details. Jeffrey Hammersley designed and
supervised the study. All authors performed critical revision of the manuscript for
important intellectual content.

Conflict of Interest: The authors declare that no conflicts of interest exist regarding
the publication of this paper.

Ethics approval: Not applicable.

This article has been accepted for publication and undergone full peer review but has not been
through the copyediting, typesetting, pagination and proofreading process which may lead to
differences between this version and the Version of Record. Please cite this article as an
‘Accepted Article’, doi: 10.1111/crj.12775
This article is protected by copyright. All rights reserved.
 2

Abstract:

Background and Objectives: Electronic cigarettes (e cigarettes) are battery operated

devices that produce aerosol by heating a solution typically made up of nicotine,
propylene glycol, glycerin and flavoring agents. The use of e cigarettes has risen
dramatically in recent years especially among adolescents and young adults. These
devices have been marketed as safer alternatives to tobacco smoking by their
manufactures despite lack of adequate safety data.
Methods: We present a case of 40-year-old female patient who developed significant
pulmonary toxicity secondary to e cigarette use and searched existing literature
relevant to the case.
Results: To our knowledge this is the second reported case of organizing pneumonia
and tenth reported case of pulmonary toxicity related to e cigarette use. Our patient
presented with symptoms of worsening dyspnea and intermittent chest pain for past 1
month. She reported increased use of e cigarettes during this time period to help her
quit smoking. Patient developed acute hypoxemic respiratory failure requiring
intubation and mechanical ventilation. She was diagnosed with organizing pneumonia
on open lung biopsy and was successfully treated with steroids along with abstinence
from e cigarette use.
Conclusion: As the current data on health effects of e cigarettes is limited, case
reports can serve important piece of information in this regard. The use of e cigarettes
has increased exponentially in recent years and continue to rise; therefore, physicians
should be aware of adverse effects and toxicity related to its use.

Introduction: Electronic cigarettes (e cigarettes) belong to growing class of

electronic nicotine delivery systems (ENDS). E cigarettes are electrical devices which
produce aerosols (or vapors) by heating a liquid mixture. The liquid mixture (also
called as e liquid) consists of varying concentration of nicotine, distilled water,
propylene glycol, glycerin and flavoring agents [1]. E cigarettes are composed of a
battery part (usually a lithium battery), a reservoir that contains the liquid, and an
atomizer with a heating element. Electric current from battery heats the metallic coil,
aerosolizing the liquid conducted from the reservoir to the coil by a wick generally
made up of cotton or silica. These devices have been marketed as safer alternatives to
tobacco smoking by their manufactures despite lack of adequate safety data. We
present a case of 40-year-old female patient who presented with acute hypoxemic
respiratory failure and was diagnosed with organizing pneumonia secondary to E
cigarettes use.

Case Report: 40year old African American female presented to the hospital with for
dyspnea and intermittent chest pain for past 1 month. She described the pain as sharp,
intermittent and on both sides of the chest. Dyspnea had worsened recently and was
present both at rest and on exertion. She smoked half a pack a day for more than 10
years, until recently, about 1 month prior, when she switched to e cigarettes to help
her quit. Vital signs at the time of presentation reveled tachycardia (110 beats/min),
tachypnea (21/min) with normal blood pressure (118/74 mm Hg) and no fever (98.7
F). On physical examination crackles and wheezes were auscultated in bilateral (B/L)
lung fields, S1 and S2 were normal with no jugular venous distention.
Electrocardiogram at the time of presentation showed sinus tachycardia without any
ST or T wave abnormality. Initial laboratory studies showed normal white cell count,

This article is protected by copyright. All rights reserved.

 3

hematocrit, kidney and liver functions. Chest radiograph showed scattered bilateral
pulmonary infiltrates (Figure 1). Arterial blood gas analysis was consistent with
hypoxemia (PO2 of 52 on 3L of oxygen by nasal cannula). Computed Tomography
(CT) of the chest showed multifocal discrete and confluent ground glass opacities
diffusely involving bilateral lung lobes (Figure 2A). Patient was initially managed as
a case of multifocal pneumonia and was started on empiric antibiotics. Next day,
patient became more hypoxic with respiratory distress requiring intubation and
mechanical ventilation. A diagnostic bronchoscopy was performed which revealed
normal tracheobronchial anatomy. Bronchoalveolar lavage and transbronchial biopsy
was done and tissue samples were drawn. Extensive workup including gram stain,
fungal and bacterial cultures, viral studies, acid-fast stain, and immunoassays were
negative. An open lung biopsy was performed and histopathological examination
showed organizing pneumonia. Antibiotics were discontinued and patient was started
on high dose methylprednisolone. Over the course of few days her respiratory status
improved and she was extubated successfully. Patient was transitioned to oral
prednisone and was discharged to home on a prednisone taper. She was seen as follow
up in outpatient clinic and reported significant improvement in her symptoms. A
follow up CT was done which showed resolution of ground glass opacities (Figure
2B).

Discussion: E cigarettes were first introduced in China, in year 2004. In United

States, e cigarettes became commercially available in year 2007. Since than the
popularity of e cigarettes had risen dramatically, especially in recent years. In 2016,
3.2% adults aged more than 18 years reported regular use of e cigarettes, while 15.3%
adults aged more than 18 years have used an e cigarette sometime in their lifetime [2,
3]. Of this, the highest rate of use of e cigarettes is seen among the young adult
population between 18-24 years of age, with 4.7% of individuals in this age group
reporting regular use of e cigarettes [2, 3]. The rate of e cigarettes use in youth and
young adults has risen rapidly and e cigarettes now are the most commonly used
tobacco product in this population [4]. This increased popularity of e cigarettes may
be due to its ability to deal with behavioral component of smoking in addition to
providing nicotine. Use of e cigarettes simulates smoking behavior and is able to
provide sensation of traditional cigarette smoking. These features are absent in other
nicotine replacement therapies such as oral gums or patches.

Effect of e cigarette use on pulmonary function has been in a number of studies,

which have yielded variable results. While some of the studies found that e cigarette
users experience increased airway resistance along with compromise in pulmonary
function upon exposure to e cigarette vapor [5, 6], others reported that short term use
of e cigarettes have no significant changes in lung function [7, 8]. Further, two studies
reported immediate reduction in exhaled nitric oxide similar to what is seen in
tobacco smoking [5, 6]. Another study found increase in inflammatory signaling
molecules upon inhalation, in resemblance to what is seen in tobacco smoking [9].

Clinical studies evaluating the safety and risk profile of e cigarette use in humans are
limited and most the current data is obtained from in vitro studies on cultured cells
and in vivo experiments in animal models. The short-term in-vitro studies using
cultured cells have shown that exposure to e liquid or aerosols reduces cell viability,
induces cytokine production and causes oxidative stress [10]. Additional information
on health effects of e cigarettes use can be gained from case reports. Our search of

This article is protected by copyright. All rights reserved.

 4

literature revealed 9 cases reports of adverse effects of e cigarettes on pulmonary

system (Table 1) [11-19]. Of these, 2 cases were diagnosed with lipoid pneumonia
and 1 case each of bronchiolitis, acute eosinophilic pneumonia (AEP), pneumonia
with bilateral pleural effusion, suspected acute hypersensitivity pneumonitis (AHP),
respiratory bronchiolitis interstitial lung disease (RB ILD), bronchiolitis obliterans
organizing pneumonia (BOOP) and diffuse alveolar hemorrhage (DAH). All the
patients presented with respiratory symptoms of dyspnea and cough. In 6 cases
(including 2 cases of lipoid pneumonia, 1 case each of subacute bronchial toxicity,
RB ILD, BOOP and DAH) the onset of symptoms was gradual, occurring after more
than 1 week of starting e cigarettes use and in 3 cases (1 case each of pneumonia with
bilateral pleural effusions, AEP and AHP) the symptoms onset occurred within 3 -7
days of e cigarettes use. The patient who developed bronchiolitis had previous history
of pulmonary adenocarcinoma with brain metastasis while the patient who developed
DAH had history of lung carcinoma with left upper lobectomy and chronic
obstructive pulmonary disease. The patient who developed RB ILD had history of
germ cell tumor with multiple pulmonary metastasis. 6 out of these 9 patients had
previous smoking history and in 3 cases the smoking history had not been specified.
All of them except one had favorable outcome with resolution of symptoms with
abstinence from e cigarette use. Mantilla et al [18] reported first case of organizing
pneumonia related to e cigarette use in a 27-year-old male patient with history of
tobacco smoking. Imaging with CT of chest in this patient showed multiple small
pulmonary nodules in bilateral lung fields unlike in our patient who had bilateral
discrete and confluent ground glass opacities and patches of consolidation, which is
characteristic of organizing pneumonia. This patient like our patient had favorable
outcome after being treated with steroids with resolution of symptoms. Although no
definitive association has yet been established between toxins in e cigarettes and
organizing pneumonia, this is the most likely etiology in our case. However, further
studies would be needed to establish a definitive causal relationship.

Conclusion: As the clinical data on the health effects of e cigarettes is limited, case
reports serve as important piece of information. To our knowledge, this is the second
reported case of organizing pneumonia related secondary to e cigarette use.

References:

1. Grana, R., N. Benowitz, and S.A. Glantz, E-cigarettes: a scientific review.

Circulation, 2014. 129(19): p. 1972-86.
2. QuickStats: Percentage of Adults Who Ever Used an E-cigarette and
Percentage Who Currently Use E-cigarettes, by Age Group — National
Health Interview Survey, United States, 2016. MMWR Morb Mortal Wkly
Rep 2017;66:892. DOI: http://dx.doi.org/10.15585/mmwr.mm6633a6.
3. Erratum: Vol. 66, No. 33. MMWR Morb Mortal Wkly Rep 2017;66:1238. DOI:
http://dx.doi.org/10.15585/mmwr.mm6644a11.
4. U.S. Department of Health and Human Services. E-Cigarette Use Among
Youth and Young Adults. A Report of the Surgeon General. Atlanta, GA: U.S.
Department of Health and Human Services, Centers for Disease Control and
Prevention, National Center for Chronic Disease Prevention and Health
Promotion, Office on Smoking and Health, 2016.

This article is protected by copyright. All rights reserved.

 5

5. Vardavas, C.I., et al., Short-term pulmonary effects of using an electronic

cigarette: impact on respiratory flow resistance, impedance, and exhaled
nitric oxide. Chest, 2012. 141(6): p. 1400-1406.
6. Marini, S., et al., Short-term effects of electronic and tobacco cigarettes on
exhaled nitric oxide. Toxicol Appl Pharmacol, 2014. 278(1): p. 9-15.
7. Flouris, A.D., et al., Acute impact of active and passive electronic cigarette
smoking on serum cotinine and lung function. Inhal Toxicol, 2013. 25(2): p.
91-101.
8. Ferrari, M., et al., Short-term effects of a nicotine-free e-cigarette compared
to a traditional cigarette in smokers and non-smokers. BMC Pulm Med,
2015. 15: p. 120.
9. Shields, P.G., et al., A Review of Pulmonary Toxicity of Electronic Cigarettes
in the Context of Smoking: A Focus on Inflammation. Cancer Epidemiol
Biomarkers Prev, 2017. 26(8): p. 1175-1191.
10. Chun, L.F., et al., Pulmonary toxicity of e-cigarettes. Am J Physiol Lung Cell
Mol Physiol, 2017. 313(2): p. L193-L206.
11. McCauley, L., C. Markin, and D. Hosmer, An unexpected consequence of
electronic cigarette use. Chest, 2012. 141(4): p. 1110-1113.
12. Modi, S., R. Sangani, and A. Alhajhusain, Acute Lipoid Pneumonia
Secondary to E-Cigarettes Use: An Unlikely Replacement for Cigarettes.
Chest, 2015. 148(4, Supplement): p. 382A.
13. Hureaux, J., M. Drouet, and T. Urban, A case report of subacute bronchial
toxicity induced by an electronic cigarette. Thorax, 2014. 69(6): p. 596-7.
14. Thota, D. and E. Latham, Case report of electronic cigarettes possibly
associated with eosinophilic pneumonitis in a previously healthy active-duty
sailor. J Emerg Med, 2014. 47(1): p. 15-7.
15. Moore, K., H.Y. II, and M.F. Ryan, Bilateral Pneumonia and Pleural Effusions
Subsequent to Electronic Cigarette Use. Open Journal of Emergency
Medicine, 2015. Vol.03No.03: p. 5.
16. Atkins, G. and F. Drescher, Acute Inhalational Lung Injury Related to the
Use of Electronic Nicotine Delivery System (ENDS). Chest, 2015. 148(4,
Supplement): p. 83A.
17. Flower, M., et al., Respiratory bronchiolitis-associated interstitial lung
disease secondary to electronic nicotine delivery system use confirmed with
open lung biopsy. Respirol Case Rep, 2017. 5(3): p. e00230.
18. Mantilla, R.D., R.T. Darnell, and U. Sofi, Vapor Lung: Bronchiolitis
Obliterans Organizing Pneumonia (BOOP) in Patient with E-Cigarette Use,
in D22. REDUCING HARMS OF TOBACCO USE. 2016, American Thoracic
Society. p. A6513-A6513.
19. Long, J.L., et al., Diffuse Alveolar Hemorrhage Due to Electronic Cigarette
Use, in A54. CRITICAL CARE CASE REPORTS: ACUTE HYPOXEMIC
RESPIRATORY FAILURE/ARDS. 2016, American Thoracic Society. p.
A1862-A1862.

This article is protected by copyright. All rights reserved.

Table 1: Case Reports of pulmonary toxicity caused by e cigarettes.

Age/Sex Preexisting Smoking Duration Presentation/Sign Diagnosis Treatment/Outcome

Medical History of E and Symptoms
Conditions Cigarette
use
before
diagnosis
42/F Asthma, Not 7 months Dyspnea, cough, Exogenous Recovery with
[11] Rheumatoid specified fever lipoid abstinence from e
arthritis, pneumonia cigarette
Fibromyalgia,
Schizoaffective
disorder,
Hypertension
20/M None Not 3 days Dyspnea and cough Acute Recovery with
[14] specified eosinophilic abstinence from e
pneumonia cigarette and systemic
steroids
43/M Lung Smoker, 45 4 weeks Dyspnea and cough Subacute Recovery with
[13] adenocarcinoma pack year bronchial abstinence from e
with isolated toxicity cigarette
brain metastasis
31/F Not specified Smoker, 3 months Dyspnea and cough Exogenous Recovery with
[12] unspecified lipoid abstinence from e
pneumonia cigarette and systemic
steroids
43/M Hypertension Smoker, 3 days Dyspnea and Pneumonia and Recovery with
[15] unspecified pleuritic chest pain bilateral pleural abstinence from e
effusions cigarette
60/M Not specified Smoker, Not Weakness and Suspected acute Recovery with
[16] unspecified specified cough hypersensitivity abstinence from e
pneumonitis cigarette
33/M Mixed Germ cell Smoker, 10 3 months Dyspnea Respiratory Recovery with
[17] tumor with pack years bronchiolitis abstinence from e
multiple interstitial lung cigarette
pulmonary disease
metastasis
27/M None Smoker, 7 months Dyspnea, cough, Bronchiolitis Recovery with
[18] unspecified fever and obliterans abstinence from e
hemoptysis organizing cigarette and systemic
pneumonia steroids
70/M Lung cancer Not 4 weeks Dyspnea and cough Diffuse alveolar Death
[19] with left upper specified damage
lobectomy and
COPD

This article is protected by copyright. All rights reserved.

Figure 1: Chest Radiograph showing scattered pulmonary infiltrates in bilateral lung fields.

This article is protected by copyright. All rights reserved.

Figure 2: (A) CT of the chest showed multifocal discrete and confluent ground glass opacities diffusely
involving bilateral lung lobes. (B) Follow up CT of chest 2 months later showing complete resolution of
ground glass opacities.

This article is protected by copyright. All rights reserved.

Figure 3: (A) Low power view of organizing pneumonia showing several rounded and elongated nodules of
fibrous tissue compressing adjacent lung. (B) High power view shows nodules of fibroblasts and
myofibroblasts arranged in whorls with pale gray matrix (Masson bodies) within the airspace.

This article is protected by copyright. All rights reserved.