pulmonary alveolar proteinosis

PULMONARY GRAND

ROUNDS

Salman Alim

Pulmonary Critical Care Fellow

Cleveland Clinic Florida

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

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

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

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

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

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

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

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

IMAGING STUDIES

CXR

CT CHEST

ANA 1:80

RF negative

Anti CCP negative

Other rheumatological work up not

available

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%

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

PULMONARY ALEVOLAR

PROTEINOSIS

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

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

PATHOGENESIS

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

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%

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

Crazy Paving

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

TREATMENT

Whole Lung Lavage

Clinical course is variable

30-40% of patients require only one

lavage

Rest require repeat lavages every 6-

12 months

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

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

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

Plasmapheresis

Anti Gm-CSF titres are reduced

In some cases, CXR and A-a gradient

improvement has been described.

Clinical Course of PAP

Rule of 1/3

1/3 remain stable

1/3 improve

1/3 are likely to develop progressive

disease

Treatment Approach