CLINICAL COMMUNICATION TO THE EDITOR
Severe Pulmonary Alveolar
Proteinosis in a Young Adult
To the Editor:
Pulmonary alveolar proteinosis is a rare lung disorder char-
acterized by abnormal accumulation of surfactant within
alveoli. Clinical presentation is nonspecific, but associated with
characteristic radiologic findings and unique management
options. We highlight a case of severe pulmonary alveolar
proteinosis requiring total lung lavage in a young healthy
man.
CASE REPORT
A 37-year-old man with a history of nicotine abuse pre-
sented with a 5-month history of progressive dyspnea on
exertion and 1 month of nonproductive cough. He denied
associated fever, chest pain, and hemoptysis. He endorsed
a history of industrial dust exposure from prior employment.
Physical examination and initial laboratory study results
were unremarkable. An extensive infectious and rheumatologic
workup returned negative. Chest x-ray showed bilateral
lung disease, and chest computed tomography demon-
strated extensive bilateral ground-glass opacification, most
pronounced peripherally, and anterior lobular septal thick-
ening (Figure A). Bronchoalveolar lavage returned positive
for periodic acid–Schiff staining, consistent with pulmo-
nary alveolar proteinosis.
The patient was scheduled for total lung lavage with supple-
mental vest percussion. A double-lumen endotracheal tube was
used to lavage 1 lung with warmed saline while indepen-
dently ventilating the other lung. Initial effluent was noted
to be milky, but cleared with subsequent saline infusions
(Figure B). The patient was counseled on smoking cessa-
tion and discharged after an uncomplicated postprocedural
course. Postdischarge laboratory testing revealed antibodies
to granulocyte-macrophage colony-stimulating factor,
Funding: None.
Conflict of Interest: None.
Authorship: All authors had access to the data and played a role in writing
this manuscript.
Request for reprints should be addressed to Vijay Duggirala, MD, The
Ohio State University Wexner Medical Center, M112 Starling Loving Hall,
320 W. 10th Ave, Columbus, OH 43210.
E-mail address: vijay.duggirala@osumc.edu
0002-9343/$ - see front matter © 2018 Elsevier Inc. All rights reserved.
solidifying a diagnosis of autoimmune pulmonary alveolar
proteinosis.
DISCUSSION
Pulmonary alveolar proteinosis is a rare lung disease char-
acterized by accumulation of surfactant and apoproteins in
distal air spaces. Three main forms of this disorder are
recognized: congenital, secondary, and autoimmune, which
is the most common subtype.1 In a large cohort study of
patients with autoimmune pulmonary alveolar proteinosis,
patients presented at a median age of 51 years with exertional
dyspnea as the most common presenting symptom. Alterna-
tive presenting symptoms included cough, increased
sputum production, and fatigue. One third of patients were
asymptomatic on presentation, whereas 56% reported a
history of smoking and 23% endorsed a history of dust
exposure.2
Although physical examination and laboratory studies com-
monly reveal nonspecific abnormalities, chest radiographs
often exhibit alveolar opacities in a “bat wing” distribution. High-
resolution computed tomography demonstrates ground-glass
opacities and concurrent thickening of intralobular structures,
nicknamed “crazy paving.”3 Bronchoscopy with bronchoalveolar
lavage frequently exhibits periodic acid–Schiff positive
proteinaceous material in alveolar spaces. Lung biopsy and
measurement of antibodies to granulocyte-macrophage
colony-stimulating factor may help solidify the definitive
diagnosis of pulmonary alveolar proteinosis.4 Treatment choice
is determined by symptoms and gas exchange status: For
asymptomatic patients, pulmonary function tests and chest
imaging are recommended; for mild symptoms (eg, dyspnea
with exertion, cough, and malaise), supportive care and supple-
mental oxygen are indicated; for severe symptoms (eg, dyspnea
with minimal exertion or at rest), total lung lavage, granulocyte-
macrophage colony-stimulating factor, and rituximab may be
used.5 Total lung lavage should be pursued when patients
with pulmonary alveolar proteinosis meet 1 of the follow-
ing criteria: resting partial pressure of oxygen <65 mm Hg,
resting alveolar-arterial oxygen gradient ≥40 mm Hg, or severe
dyspnea.3
CONCLUSIONS
PAP is a rare pulmonary disease in which excessive pulmo-
nary surfactant accumulates within the alveoli. Symptoms
are nonspecific and almost one third of patients are asymp-
tomatic. If PAP is considered in the differential, a CT
e200 The American Journal of Medicine, Vol 131, No 5, May 2018

Figure (A) Coronal computed tomography demonstrating extensive bilateral ground-glass opaci-
fication, most pronounced at the periphery, and anterior lobular septal thickening. (B) Effluent, initially
noted to be milky, cleared with progressive saline infusions during lung lavage.

scan of the chest should be pursued with subsequent References

bronchoscopy with BAL, PAS staining, and anti-GM-CSF
1. Kitamura T, Tanaka N, Watanabe J, et al. Idiopathic pulmonary alveo-
antibody evaluation. Once diagnosis is established, thera- lar proteinosis as an autoimmune disease with neutralizing antibody against
peutic decisions can be determined based on the underlying granulocyte/macrophage colony-stimulating factor. J Exp Med.
etiology. 1999;190(6):875-880.
2. Inoue Y, Trapnell BC, Tazawa R, et al. Characteristics of a large
Alisha Kamboj, BSa cohort of patients with autoimmune pulmonary alveolar proteinosis in
Michael Lause, BSa Japan. Am J Respir Crit Care Med. 2008;177(7):752-762.
Vijay Duggirala, MDb 3. Michaud G, Reddy C, Ernst A. Whole-lung lavage for pulmonary al-
a
The Ohio State University College of Medicine veolar proteinosis. Chest. 2009;136(6):1678-1681.
4. Maygarden SJ, Iacocca MV, Funkhouser WK, et al. Pulmonary alveo-
Columbus, Ohio lar proteinosis: a spectrum of cytologic, histochemical, and ultrastructural
b
Department of Internal Medicine findings in bronchoalveolar lavage fluid. Diagn Cytopathol. 2001;24(6):389-
The Ohio State University Wexner Medical Center 395.
Columbus, Ohio 5. Borie R, Debray M-P, Laine C, et al. Rituximab therapy in autoim-
mune pulmonary alveolar proteinosis. Eur Respir J. 2009;33(6):1503-
https://doi.org/10.1016/j.amjmed.2017.12.019 1506.