This document describes the case of a 47-year-old female smoker who presented with shortness of breath. Imaging showed abnormalities consistent with pulmonary alveolar proteinosis (PAP). PAP is a rare lung disease characterized by accumulation of lipoproteinaceous material in the distal airways. Biopsy confirmed the diagnosis of PAP. Treatment involves whole lung lavage to remove the accumulated material from the lungs.

1. PULMONARY GRAND
ROUNDS
Salman Alim
Pulmonary Critical Care Fellow
Cleveland Clinic Florida

2. HISTORY
CC: Shortness of breath
HPI:
47 yo female who was presented to Northwest
Medical Center on 08/18/14 for shortness of breath at
rest
No history of fever and chills
Cough which is seldom productive,
No orthopnea, No PND or leg swelling
No history of wheezing, atopy

3.  10 days prior to presentation, she was
treated by urgent care with PO antibiotics
with a presumed diagnosis of pneumonia
 3 months ago, she was told by her PCP
about abnormal CXR and was
recommended to have a CT Chest done
 She did not have any respiratory symptoms
hence she did not get the CT Chest

4. PMH & PSH
 Irritable bowel syndrome
 Dyslipidemia
 GERD
 Anxiety
 Dyslipidemia
 PSH: History of gastric bypass, History
of breast augmentation
Denied history of COPD, Asthma, history
of lupus, arthritis, congestive heart failure

5. MEDICATIONS
Xanax 0.5 mg QHS PRN
Nexium 40 mg PO Daily
Percocet 5/325 1 tab PO Q4 PRN
Potassium Chloride 20 meq PO Daily

6. SOCIAL HISTORY
 Smoker: ½ PPD x 20 yrs
 Alcohol: Glass of wine with meals
nearly every night
 Occupation: Works as a RN.
 Exposures: Denies any exposure to
asbestos, does not have any birds or
cats in the house
 Travel: Jamaica 2 yrs ago for vacation

7. FAMILY HISTORY
No family history of connective tissue disease
No family history of lung cancer
Review of Systems
No weight loss, no changes in appetite
No problems with bowel or bladder reported
Denies morning stiffness of the joints
Denies any numbness, tingling or weakness in either
extremity

8. PHYSICAL EXAM
 General: AO x3, in no distress
 HEENT: Moist mucus membranes
 Skin: No ulcers, no rashes
 Neck: Supple, No palpable thyroid
 Chest: CTA B/L with basilar crackles
 Abdomen: Soft Obese NT, + BS
 Extremities: No edema B/L
 Musculoskeletal: No joint deformities, no
synovitis

9.  ABG: 7.4/38/66 O2 Sat 93% on Room
Air
CBC
Hb/Hct 13/38.6
WBC 8.22 (N-68%, Eos-0.1%,
Lymph- 22.7)
Plt 200
BMP
Na 140, K 3.1, Cl 102, CO2 29,
BUN/Cr 12/0.96

10. IMAGING STUDIES
 CXR
 CT CHEST

11.  ANA 1:80
 RF negative
 Anti CCP negative
 Other rheumatological work up not
available

12. Pulmonary Function Tests
(10/22/2014)
Spirometry
FVC (2.28 L) 74%
FEV1 (2.06 L) 78%
FEV/FVC 90
Lung Volumes
• FRC 90%
• RV 103.6%
• TLC 83.5%
Lung Diffusion Capacity
• DLCO 56%

13. PATHOLOGY
 Underwent VATS wedge biopsy of the
left lung
 Patchy air space filling process
 Airspace exudate comprising granular
eosinophilic debris containing
occasional macrophages and “cell
ghosts”
 Findings are diagnostic of PAP

14. PULMONARY ALEVOLAR
PROTEINOSIS

15. PAP OR PA
Phospholipoproteinosis
 Diffuse lung disease characterized by accumulation
of amorphous PAS positive lipoproteinaceous
material in the distal airways
 Incidence: 3 per million, more common in males
 Symptoms: Cough, Dyspnea, low grade fever.
 1/3 of patients can be asymptomatic

16. CAUSES OF PAP
CONGENITAL
Mutations in surfactant
Mutations in GM-CSF receptor
Secondary
Allogeneic bone marrow transplantation for myeloid malignancy
Hematologic malignancy
Infections (Nocarida, PCP, viral)
Pneumoconioses (Acute silica, aluminum dust, titanium)
Acquired or autoimmune
Anti GM CSF antibodies

17. PATHOGENESIS

19. Anti GM-CSF
 Elevated anti GM-CSF titer is 100%
sensitive and 91-98% specific for acquired
PAP
 BAL levels correlate better than serum
 Useful in monitoring of disease activity
 Concentration > 19 micrograms/ml is
specific for autoimmune PAP while <10 has
a good negative predictive value

21.  Diagnostic accuracy of PAS staining of fluid obtained
by BAL and tissue obtained by transbronchial biopsy
has reduced the need for open or throacoscopic lung
biosy
 In a case series of 248 patients –
diagnosis was made by
HRCT and BAL 59%
HRCT, BAL and TBBX 34%
VATs biopsy 7%

23. RADIOLOGY – “Crazy
Paving”
 Reticular pattern superimposed on
ground glass opacity
 Appearance of paths made with
broken pieces of glass or concrete
 Ground Glass – presence of airspace
abnormalities
 Reticular pattern – thickening of the
intralobular interstitium

24. Crazy Paving

25. Differential Diagnosis of Crazy
Paving
 Crazy paving is not pathognomic for PAP
 Several other conditions can cause Crazy Paving
such as:
 Infection: PCP
 Neoplasm: Mucinous Bronchoalveolar
 Idiopathic: Sarcoidosis
 Inhalation: Lipoid Pneumonia
 ARDS, Pulmonary Hemorrhage Syndrome

26. TREATMENT
 Whole Lung Lavage

28.  Clinical course is variable
 30-40% of patients require only one
lavage
 Rest require repeat lavages every 6-
12 months

29. GM-CSF
(Sargramostim; Bayer) can be inhaled
or delivered subcutaneously
All data is derived from small trials
In a trial of 25 patients who received
subcutaneous GM-CSF, 48% improved
in terms of A-a gradient and 6 min walk

30. Inahled GM-CSF
 In a Japanese trial of 12 patients, 68%
of the patients showed improvement
 Currently, a clinical trial using inhaled
GM CSF is underway being conducted
at Childrens Hospital of Cincinnati

32. Rituximab
 Monoclonal Ab directed against CD20 antigen on B
lymphocytes
 Deplete antigen presenting B cells – affecting T cell
activation – decreasing cytokine production and
amount of plasma cells producing GM-CSF auto
antibodies
 Current data about use of Rituximab is limited to
case reports only

33. Plasmapheresis
 Anti Gm-CSF titres are reduced
 In some cases, CXR and A-a gradient
improvement has been described.

34. Clinical Course of PAP
 Rule of 1/3
 1/3 remain stable
 1/3 improve
 1/3 are likely to develop progressive
disease

35. Treatment Approach