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Pulmonary Alveolar Proteinosis


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Measurement of GM-CSF autoantibody

Pulmonary Alveolar Proteinosis

Clinical Features

Epidemiology

Autoimmune PAP (ref.2)
  • 90% of adult onset acquired PAP
  • The median onset is in the 6th decade of life.
  • Male to female ratio is 2.1:1
  • 25% of patients have a history of occupational dust inhalation
  • Serum is positive for GM-CSF autoantibodies
  • Prognosis is generally good. Rarely, respiratory failure may develop.
  • 30% of patients are asymptomatic. Dyspnea on exertion, cough, and sputum are frequent, while fever is uncommon.
Secondary PAP (ref.8)
  • 6% of adult onset PAP
  • The median onset is in the 5th and 6th decades of life.
  • Male to female ratio is 1.5:1
  • Underlying diseases such as hematological disorders, especially myelodysplastic syndrome, are most frequently followed by pulmonary infection and autoimmune disease
  • GM-CSF autoantibody negative
  • Prognosi is poor (2 year survival is 49%; 5 years survival is 35%)s
  • Most patients are symptomatic. Symptoms are variable. Fever is seen in 22% of cases
  • Reference Eur Respir J. 2011;37(2):465

HRCT Findings

HRCT findings in autoimmune PAP (ref.9)
patchy geographic pattern
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Ground glass opacification generally has sharply defined straight and angulated margins, giving a “geographic” appearance.
sub pleural sparing
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sub pleural sparing
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Subpleural sparing GGO in the peripheral lung means that GGO is not seen in the subpleural regions.
GGOに伴う小葉間隔壁の肥厚や小葉内網状影
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Crazy Paving Appearance. A pattern of fine overlapping lines forming 3-10 mm polygonal shapes occurs in the majority of cases. Superimposition with GGO gives an appearance known as “crazy paving”, which is characteristic but not diagnostic of PAP.
autoimmune PAP

To evaluate craniocaudal distribution, the proportion of the involved area of GGO was compared by a visual scoring system among the upper, middle, and lower lung fields. The mean score for autoimmune PAP was smaller in the upper lung field (2.8 and 2.9, respectively, for the right and left lung fields) compared to the lower lung field (3.8 and 3.7, respectively, for the right and left lung fields; p < 0.05). The visual scores were not different between the right and left lung.

HRCT findings in secondary PAP (ref.9)
びまん性パターン(Diffuse pattern)
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A diffuse pattern with predominant GGO in patients with secondary PAP (62%).
Major 3 patterns seen in patients with secondary PAP
地図状パターン
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A: Geographic GGO
diffuse GGO pattern
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B: Diffuse GGO
胞壁肥厚パターン
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C: Diffuse GGO with interlobular septal thickening.

To evaluate craniocaudal distribution, the proportion of the involved area of GGO was compared by a visual scoring system among the upper, middle, and lower lung fields. The visual scores were even among lung fields, with a mean value of 3.4 for both the right and left lung fields.

Comparison of HRCT findings between autoimmune and secondary PAP

HRCT findings for both autoimmune and secondary PAP demonstrated GGO, consolidation, interlobular septal thickening, and a low-attenuation area. Honeycombing was not seen in any case. GGO was recognized bilaterally in all patients with autoimmune and secondary PAP and consolidation was also frequently seen. The consolidation consisted of small nodular features (mostly 5 mm), typical of both autoimmune and secondary PAP, although some large consolidations with an air bronchogram also were also observed.

Laboratory Findings

Autoimmune PAP
  • In 50% of patients, arterial oxygen (PaO2) is under 70 mmHg. Arterial carbon dioxide is typically within normal limits.
  • %VC is within the normal range except in advanced disease.
  • %DLCO is reduced in the early stage.
  • Normal FEV1
  • CRP and ESR are normal.
  • RBC often increases.
  • Elevated KL-6, CEA, SP-A, SP-D and LDH. These are higher than in IPF, sarcoidosis, collagen vascular disease.
  • KL-6 and CEA are correlated with A-aDO2.
  • Serum GM-CSF autoantibody is positive.
Secondary PAP
  • %VC is within the normal range except in advanced disease.
  • %DLCO is reduced in the early stage.
  • Normal FEV1
  • Elevated KL-6, CEA, SP-A, SP-D and LDH. KL6 and CEA are higher than in other diffuse lung diseases.
  • KL-6 and CEA are correlated with A-aDO2.
  • Serum GM-CSF autoantibody is negative.

Findings of Bronchoalveolar Lavage Fluid Sediment

In autoimmune PAP, BALF has a characteristic “milky” appearance. Cytologic examination of BALF reveals numerous granular, acellular, eosinophilic, and amorphous material in the background. Alveolar macrophages comprise large foamy- and small monocyte like- macrophages. The former have an enlarged and engorged cytoplasm with a foamy, vacuolated appearance. The nucleus is usually small and deviated. In the early stages, lymphocyte and neutrophil levels are increased, probably as a consequence of elevated MCP-1, although whole cell levels are decreased in advanced disease.

In secondary PAP, BALF also has a characteristic “milky” appearance. Large foamy macrophages are usually seen which sometimes have atypical nuclei. Lymphocytes and neutrophils levels are frequently increased.

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