2. INTRODUCTION
is a diffuse lung disease characterized by the
accumulation of amorphous, periodic acid-Schiff
(PAS)-positive lipoproteinaceous material in the
distal air spaces
3.
4. pathogenesis
1- Role of GM-CSF: effects of GM-CSF on surfactant clearance by alveolar
macrophages are mediated, at least in part, by transcription factor peroxisome
proliferator-activated receptor-gamma (PPAR-gamma) dependent pathways.
Compared to normal controls, alveolar macrophages from patients with PAP
demonstrate decreased levels of PPAR-gamma and the macrophage scavenger
receptor CD36, which PPAR-gamma regulates; PPAR-gamma and CD36 levels can
be restored to normal following treatment with GM-CSF administered
subcutaneously . The interrelationship between GM-CSF and PPAR-gamma may
explain how GM-CSF deficiency could cause alveolar and macrophage accumulation
of surfactant lipoprotein.
5. Cont.
2-Macrophage dysfunction :
Alveolar MQ obtained from patients with PAP after therapeutic
whole lung lavage have greater migratory response compared with
macrophages from the same patients prior to the lavage.
Other causes of acquired macrophage dysfunction, such as
immunosuppressive drug therapy or hematologic malignancies,
may explain the occasional finding of PAP associated with these
disorders .
6. CP
Symptoms: progressive dyspnea on exertion,
cough, fatigue, weight loss, and low-grade fever.
expectoration of "chunky" gelatinous material may
occasionally occur.
Physical examination :often normal; clubbing
and cyanosis are present in about 25%. Crackles are
present in approximately 50 %.
7. INVESTIGATIONS
1-Lab.:
polycythemia, hypergammaglobulinemia, and increased LDH
levels
Elevated levels of lung surfactant proteins A and D (SP-A and SP-D)
Sputum examination may suggest PAP in the correct clinical setting,
based on the identification of PAS-positive material in macrophages
Anti-GM-CSF titer: In the absence of any known 2ry cause of
PAP, an elevated serum anti-GM-CSF titer is 100 % sensitive and 91
to 98% specific for the diagnosis of acquired PAP. BAL fluid levels of
anti-GM-CSF antibodies correlate better with the severity of PAP
compared to serum titers.
2-PFTs: restrictive ventilatory defect or sometimes an isolated
decrease in DLCO.
3- Radiological:
8.
9.
10. Cont.
4-BAL:
milky appearance due to the abundant lipoproteinaceous
material
MQs are engorged with the PAS-positive material
Large acellular eosinophilic bodies in a background of
eosinophilic granules
PAS staining of proteinaceous material
5- Lung Biobsy:
11.
12.
13.
14.
15.
16. TREATMENT
1- Conservative : for asymptpmatic or mild
symptoms(with regular FUP)
2- Whole lung lavage : For patients who have
moderate to severe symptoms and hypoxemia. After
whole lung lavage, patients often feel dramatically
better, with improvement in exertional dyspnea. The
clinical course is variable. 30-40%of patients require
only one lavage, while others require repeat lung
lavages at intervals of 6 to 12 ms.
17. Cont.
3- GM-CSF:Experimental therapy with GM-CSF has been
used in patients with PAP. Preliminary data suggests that
the proportion of responders to GM-CSF is less than with
whole lung lavage. Given the experimental nature of GM-
CSF therapy, we use lung lavage as primary therapy.
4-Other therapies — Lung transplantation has been
performed in patients who deteriorate despite whole lung
lavage, but recurrence in the allograft has been reported .
Treatment with plasmapheresis and rituximab have
yielded mixed results .
Editor's Notes
Bat wing
After whole lung lavage, patients often feel dramatically better, with improvement in exertional dyspnea. The clinical course is variable. Thirty to 40 percent of patients require only one lavage, while others require repeat lung lavages at intervals of 6 to 12 months.