The n e w e ng l a n d j o u r na l of m e dic i n e
C or r e sp ondence
Pulmonary Lipid-Laden Macrophages and Vaping
To the Editor: Recent case clusters of a respira-
tory syndrome associated with e-cigarette use
(vaping) have been identified, as now reported in
the Journal by Layden et al.1 We describe clinical
features of six cases in Utah that help character-
ize this nascent syndrome. We present the most
severe case in our series here; the remaining five
are summarized in Table 1 and in the Supple-
mentary Appendix, available with the full text of
this letter at NEJM.org.
A previously healthy 21-year-old man who had
been vaping nicotine and tetrahydrocannabinol
(THC) daily presented with 1 week of dyspnea,
cough, abdominal pain, nausea, and vomiting.
He had bilateral interstitial opacities on chest
radiography and was empirically treated for bac-
terial pneumonia. His condition deteriorated, and
he was intubated for acute respiratory distress
syndrome. Chest computed tomography (CT)
showed diffuse consolidative opacities (Fig. S1 in
the Supplementary Appendix). Laboratory studies
were notable for negative HIV testing and a
markedly elevated level of C-reactive protein
(30.7 mg per deciliter) (Table 1). Bronchoalveolar
lavage (BAL) fluid showed neutrophilic predom-
inance (49%) and more than 50% lipid-laden
macrophages by oil red O staining. Testing of
this fluid by culture and polymerase-chain-reac-
tion assay for bacterial, fungal, and viral patho-
gens did not reveal any evidence of infection.
Methylprednisolone (1 mg per kilogram of body
weight) was administered, but refractory hypox-
emia developed, and the patient was treated with
venovenous extracorporeal membrane oxygen-
ation (ECMO). During the next 7 days, his con-
dition improved, with resolution of radiographic
opacities, and he was extubated and weaned
from ECMO. He was discharged home without
supplemental oxygen 2 weeks after initial pre-
sentation.
These cases are similar to those reported by
Layden et al.,1 with diffuse pulmonary opacities,
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systemic symptoms, and elevated levels of in-
flammatory markers (Table 1; also see the Sup-
plementary Appendix). A notable and consistent
feature of the cases we report is the presence
of lipid-laden macrophages seen with oil red O
staining in BAL samples that are not attributable
to aspiration of exogenous lipoid material. In
addition, the diffuse parenchymal opacities seen
on CT scans did not have low attenuation (in
Hounsfield units) consistent with classic lipoid
pneumonia.2 Although the pathophysiological
significance of these lipid-laden macrophages
and their relation to the cause of this syndrome
are not yet known, we posit that they may be a
useful marker of this disease.3-5 Further work is
needed to characterize the sensitivity and specific-
ity of lipid-laden macrophages for vaping-related
lung injury, and at this stage they cannot be
used to confirm or exclude this syndrome. How-
ever, when vaping-related lung injury is suspected
and infectious causes have been excluded, the
presence of lipid-laden macrophages in BAL fluid
may suggest vaping-related lung injury as a pro-
visional diagnosis.
Sean D. Maddock, M.D.
Meghan M. Cirulis, M.D.
Sean J. Callahan, M.D.
Lynn M. Keenan, M.D.
Cheryl S. Pirozzi, M.D.
Sanjeev M. Raman, M.B., B.S., M.D.
Scott K. Aberegg, M.D., M.P.H.
University of Utah Health
Salt Lake City, UT
sean​.­callahan@​­hsc​.­utah​.­edu
Drs. Maddock and Cirulis contributed equally to this letter.
Disclosure forms provided by the authors are available with
the full text of this letter at NEJM.org.
This letter was published on September 6, 2019, at NEJM.org.
1. Layden JE, Ghinai I, Pray I, et al. Pulmonary illness related
to e-cigarette use in Illinois and Wisconsin — preliminary report.
N Engl J Med. DOI:​10.1056/NEJMoa1911614.
2. Betancourt SL, Martinez-Jimenez S, Rossi SE, Truong MT,
1
 2
Table 1. Presentation, Characteristics, and Outcome of Six Patients in Utah with Pulmonary Illness Related to E-Cigarette Use.*

Variable Patient 1 Patient 2 Patient 3 Patient 4 Patient 5 Patient 6

Age (yr) 20 25 29 23 23 47
Approximate time from symptom onset
to presentation† 9 days 9 days 2 wk 2 mo 5 days 6 wk
Initial laboratory studies†
Blood white-cell count (per mm3) 16,300 18,200 10,600 4800 12,300 13,800
Differential count (%)
Granulocytes 92.0 93.7 92.2 84.5 90.2 89.2
Lymphocytes 1.5 3.8 6.0 8.9 5.7 7.0
Eosinophils 0.9 0.0 0.3 2.9 0.8 0.0
ESR (mm/hr)‡ NA 122 105 90 128 60
C-reactive protein (mg/dl)§ 30.7 20.4¶ 22.6 28.0 25.8 21.7
The

Bronchoalveolar lavage
Lipid-laden macrophages (%)‖ >50 Approx. 50 30 25 >75 Approx. 60
Differential count (%)
Macrophages 32 79 71 61 43 46
Bronchial lining cells 12 2 7 1 5 0
Lymphocytes 5 0 3 9 14 25
Neutrophils 49 18 19 26 38 27
Eosinophils 12 1 0 3 0 2
Management and outcomes
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Medical therapy Antibiotics; high-dose Antibiotics; high-dose Glucocorticoids; Glucocorticoids; Antibiotics None
glucocorticoids glucocorticoids ­antibiotics** a­ntibiotics**
Other interventions Mechanical ventila- High-flow nasal None Supplemental oxygen Supplemental oxygen Supplemental oxygen
tion; venovenous ­cannula by nasal cannula by nasal cannula by nasal cannula
ECMO

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m e dic i n e

Outcome Alive; hypoxemia Alive; oxygen at Alive; fevers resolved Alive; hypoxemia Alive; hypoxemia Alive; hypoxemia
­resolved ­discharge ­resolved ­resolved ­resolved

* ECMO denotes extracorporeal membrane oxygenation, ESR erythrocyte sedimentation rate, and NA not available.
† Shown are data at admission to our facility.
‡ The reference range is 0 to 10 mm per hour.

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§ The reference range is 0.0 to 0.8 mg per deciliter.
¶ Shown are data for high-sensitivity C-reactive protein; the reference range is less than 0.3 mg per deciliter.
‖ Lipid-laden macrophages were measured by means of oil red O staining.
** With respect to glucocorticoids, a short course of prednisone was prescribed by an outpatient provider before hospitalization.
 Correspondence

Carrillo J, Erasmus JJ. Lipoid pneumonia: spectrum of clinical
and radiologic manifestations. AJR Am J Roentgenol 2010;​194:​
103-9.
3. Modi S, Sangani R, Alhajhusain A. Acute lipoid pneumonia
secondary to e-cigarettes use: an unlikely replacement for ciga-
rettes. Chest 2015;​148(4):​Suppl:​382A.
4. Viswam D, Trotter S, Burge PS, Walters GI. Respiratory fail-
ure caused by lipoid pneumonia from vaping e-cigarettes. BMJ
Case Rep 2018;​2018:​224350.
5. McCauley L, Markin C, Hosmer D. An unexpected conse-
quence of electronic cigarette use. Chest 2012;​141:​1110-3.
DOI: 10.1056/NEJMc1912038
Correspondence Copyright © 2019 Massachusetts Medical Society.

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