Correspondence

Long-term outcomes of
EVALI: a 1-year
retrospective study
E-cigarette, or vaping, product use-
associated lung injury (EVALI) was
first described in 2019,1 and according
to the US Centers for Disease Control
and Prevention (CDC) at the end of
2020, 2807 patients were admitted
to hospitals with EVALI and 68 died.2
The long-term respiratory sequelae
and outcomes in patients with EVALI
remain unknown. We previously
reported acute findings from patients
with EVALI at the University of
Pittsburgh Medical Center3 and here,
we report the long-term clinical
characteristics and outcomes of
patients with EVALI 1 year after initial
hospital admission.
We retrospectively reviewed
electronic medical records of 41 patients
diagnosed with confirmed or probable
EVALI (on the basis of CDC diagnostic
criteria)1 and admitted to any of the
University of Pittsburgh Medical Center
hospitals between July, 2019, and Sept,
2020. Predefined outcomes of interest
were type and duration of symptoms,
all-cause mortality, readmissions or
emergency department encounters,
and chest radiographical and pulmonary
function abnormalities. Data are
presented as the number of patients
with percentages or as medians with
IQR. This research was reviewed by the
of 41 patients), and most (28 [68%]) 4·9%. The cause of death for these two
had at least one comorbidity. Eight patients was not directly attributed
(29%) of 28 patients had underlying to EVALI. Notably, the baseline death Published Online
lung disease, specifically asthma, rate of individuals aged 25–34 years October 25, 2021
https://doi.org/10.1016/
chronic obstructive pulmonary in Pennsylvania (USA) in 2019, was S2213-2600(21)00415-X
disease, or cystic fibrosis. None of the 153·8 per 100 000.4
patients died during initial hospital 18 (44%) of 41 patients had
admission. 33 (80%) of 41 patients had follow-up radiographical imaging.
a subsequent health-care encounter 12 (67%) of these 18 patients
(outpatient, emer­gency department had complete resolution and
visit, or inpatient). 29 (71%) patients four (22%) had improvement in
were seen in the clinic. Ten (24%) initial radiographical abnormalities
patients had at least one emergency (appendix p 3). Two (11%) patients See Online for appendix
department visit and ten (24%)
required at least one hospital admis­
Patients
sion in the 1 year following initial
Symptoms during outpatient follow-up (n=29)
hospital admission, with median
Any symptom 13 (45%)
time to readmission of 23·5 days
Fatigue 6 (21%)
(IQR 3·7–199∙0). Of 33 patients with a
Dyspnoea 6 (21%)
documented subsequent health-care
Decreased exercise capacity 4 (14%)
encounter, 16 (48%) reported to have
Cough 3 (10%)
stopped vaping, four (12%) continued
Anorexia 2 (7%)
use of e-cigarettes, and for 13 (39%)
Abdominal pain 1 (3%)
patients the vaping assessment was not
Pulmonary function testing at initial outpatient follow-up*
recorded by the health-care providers.
Spirometry (n=12)
Follow-up patient data are
FVC% 72·0 (63·5–98·2)
shown in the table. At the out­
FEV1% 76·0 (58·5–99·2)
patient follow-up visit, 13 (45%)
FEV1/FVC 82·5 (73∙0–88∙0)
of 29 patients reported persistent
FEF25–75% 90·5 (63·7–96·7)
symptoms (fatigue, dyspnoea, Diffusing capacity for carbon monoxide corrected 68·0 (51∙0–87·2)
decreased exercise capacity, cough, for haemoglobin percentage (n=10)
anorexia, and abdominal pain). Total lung capacity percentage 86·0 (69∙0–109·2)
Symptoms later resolved in nine Pulmonary function testing at second outpatient follow-up (n=9)*
(69%) of 13 patients. The median Time after first set of pulmonary function testing 35·0 (23·7–40·5)
time to documented symptom (days)
resolution in these patients was Spirometry (n=6)
48∙0 days (IQR 15∙0–185∙0). FVC% 101·5 (95·5–123·7)
Eight (28%) of 29 patients were FEV1% 99·0 (89·7–112·7)

University of Pittsburgh Institutional prescribed systemic steroids, and one FEV1/FVC 82·0 (74∙0–89∙0)

Review Board and determined to be received corticosteroid inhalers as FEF25–75% 87·5 (73·5–115∙0)

exempt from informed consent. The
funders (National Institutes of Health,
Breathe Pennsylvania, and Parker B
Francis Foundation) of this research
Correspondence had no role in the
design, data collection, data analysis,
data interpretation, and writing of the
report, or the decision to submit for
publication.
Patient characteristics at the time of
initial hospital admission are shown
in the appendix (p 2). Median patient
age was 21∙0 years (IQR 18·5–31∙0),
patients were mostly men (32 [78%]
an outpatient. None of the patients
required oxygen supplementation
after hospital discharge.
Of the ten inpatient hospital
readmissions, six (60%) were due
to respiratory diagnoses including
persistent or recurrent EVALI, asthma,
or bacterial pneumonia. Eight (80%)
of the patients who were read­
mitted had at least one comor­
bidity. Two patients with substantial
underlying medical comorbidities
died after hospitalisation, with a
1-year all-cause mortality rate of
Diffusing capacity for carbon monoxide corrected 90·0 (range 81∙0–91∙0)
for haemoglobin percentage (n=3)
Percentage change compared with initial pulmonary function testing
FVC 41·4 (11·5–50·8)
FEV1 32·1 (0∙0–70·7)
Diffusing capacity for carbon monoxide 51·7 (range 51∙0–54∙0)
Follow-up radiographical imaging (n=18)
Resolved 12 (67%)
Improved 4 (22%)
Focal scarring 2 (11%)
Data are n (%), median (IQR), or % (range). FVC=forced vital capacity. FEF=forced
expiratory flow. *One additional patient with very severe underlying obstructive
respiratory disease before EVALI was not included in the median or IQR calculations.
Table: Patient follow-up data

www.thelancet.com/respiratory Vol 9 December 2021 e112

 Correspondence
showed focal pulmonary scarring
(appendix pp 4–5). In patients who
had radiological tests, the median
time to resolution of radiographical
abnormalities was 76 days
(IQR 41·5–166·5).
12 (29%) of 41 patients had
pulmonary function testing performed
after initial hospital admission;
nine (75%) of these 12 patients had
abnormal results (table). Five patients
had a restrictive ventilatory defect
and one had a mixed obstructive
and restrictive ventilatory defect;
none had an obstructive ventilatory
defect. Diffusion capacity for carbon
monoxide was abnormal in six
(60%) of ten patients for whom
measurements were available. Three
patients had restriction with reduced
diffusion capacity and three had an
isolated reduction in diffusion capacity
for carbon monoxide. Six patients had
repeat pulmonary function testing
within 1 year after initial hospital
admission (table). In all six patients,
the pulmonary function testing
abnormalities had resolved.
To summarise, we assessed 1-year
outcomes of patients with EVALI.
We found that nearly half of patients
remained symptomatic at the time
of the first outpatient visit, but most
became asymptomatic within the
first year. Several patients continued
to vape despite admission to hospital
and counselling regarding cessation.
The importance of vaping cessation is
paramount, because the nidus for EVALI
is vaping. Beyond EVALI, e-cigarette use
has been associated with self-reported
chronic cough, phlegm production,
and wheezing.5 The 1-year all-cause
hospital readmission rate was 24·4%.
Most patients who were readmitted
to hospital had underlying medical
comorbidities and most readmissions
were due to respiratory illness. Animal
and in vitro studies suggest that
vaping could increase airway hyper-
reactivity5 or susceptibility to respiratory
pathogens.5
Radiographical abnormalities
improved within 6 months in most
e113 www.thelancet.com/respiratory Vol 9 December 2021
patients who had follow-up imaging.
Two patients had focal pulmonary
scarring after EVALI. The persistence
of radiographic abnormalities has
also been shown in patients with
acute respiratory distress syndrome
(ARDS) after the acute phase.6 We
showed that most patients with
available pulmonary function testing
had abnormal results at short-term
follow-up, which is similar to other
small studies of patients with EVALI.7,8
In all patients with repeat pulmonary
function testing, abnormalities
resolved within 1 year of hospital
discharge. Studies of the acute effects
of e-cigarettes on pulmonary function
testing remain inconclusive and
long-term data are needed.5
Limitations of our retrospective
research presented in our study
include a small sample size, absence of
a control group, and an absence of a
standardised algorithm for outpatient
follow-up, and radiographical and
pulmonary function testing. The
small sample size and low incidence
of specific abnormalities does not
allow for reliable statistical inference;
therefore, our findings should be
seen as descriptive and hypothesis
generating.
There was a high rate of patients
presenting to the emergency depart­
ment or readmission to hospital within
1 year of initial hospital admission,
particularly when considering the
young age of patients with EVALI. The
prevalence of persistent physiological
and radiographical abnormalities
following EVALI still remains unclear.
Given the high readmission rates,
rate of death, and risk of persistent
pulmonary deficits, close outpatient
follow-up is recommended. Assess­
ment of patients who continue
vaping and cessation counselling is
paramount because redevelopment
of EVALI occurred in one patient who
continued vaping. Future studies on
long-term effects of EVALI would
allow for a prospective study design
and standardised follow-up proto­
cols to better characterise long-term
consequences and potentially improve
outcomes of EVALI.
JJR is supported by the Breathe Pennsylvania and the
Parker B Francis Foundation. JJR, AM, and BJM are
supported by grants from the National Institutes of
Health: K08 HL136857 (JJR), R01 HL140963–S1
(AM, BJM), R01 HL136143–03S1 (BJM), and
2 P01 HL114453–06 (BJM). JJR is a cofounder of
Omnibus Medical Devices and a shareholder, officer,
and director of Globin Solutions, outside of the
submitted work. JJR is a coinventor on patents and
applications related to using carbon monoxide
scavenging molecules as therapies for carbon
monoxide poisoning, licensed to Globin Solutions.
Globin Solutions have a license for technologies
using nitrite as a therapy against cardiovascular
disease from the National Institutes of Health and
the University of Pittsburgh. JJR is a coinventor on a
patent of using nitrite as a treatment for chemical
and smoke inhalational injuries. All other authors
declare no competing interests.
Georgios A Triantafyllou, Perry J Tiberio,
Richard H Zou, Michael J Lynch,
John W Kreit, Bryan J McVerry,
Alison Morris, *Jason J Rose
rosejj@upmc.edu
Division of Pulmonary, Allergy, and Critical Care
Medicine (GAT, PJT, RHZ, JWK, BJM, AM, JJR, MJL)
and Department of Emergency Medicine (MJL),
University of Pittsburgh School of Medicine,
Pittsburgh, PA 15261, USA
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