Rare Lung Diseases II: Pulmonary Alveolar Proteinosis

Juvet, S.; Hwang, David; Waddell, Thomas K.; Downey, Gregory P.

doi:10.1155/2008/528948

Cited by 22 publications

(55 citation statements)

References 83 publications

(79 reference statements)

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“…7,14,21,26 Recently, investigators have proposed to classify the idiopathic form as autoimmune due to the finding of increased serum values of autoantibodies against granulocyte macrophage-colony stimulating factor (GM-CSF). 3,13,21,25 GM-CSF, is a potent stimulator of myeloid hematopoiesis, 13 and is necessary for the terminal differentiation and function of alveolar macrophages, 3,23 which are responsible for clearance of surfactant from alveoli. 13,21,25 …”

Section: Discussionmentioning

confidence: 99%

“…3,13,21,25 GM-CSF, is a potent stimulator of myeloid hematopoiesis, 13 and is necessary for the terminal differentiation and function of alveolar macrophages, 3,23 which are responsible for clearance of surfactant from alveoli. 13,21,25 …”

Section: Discussionmentioning

confidence: 99%

“…7 It is caused by rare gene mutations that include SP-B deficiency/mutation; SP-C mutations, granulocyte-macrophage colony-stimulating factor (GM-CSF) receptor β or α chain abnormalities, and ATP-binding cassette transporter A3 (ABCA3) gene mutations. 3,10,13,22 …”

Section: Discussionmentioning

confidence: 99%

“…13 The congenital form has a poor prognosis and is treated with supportive care or lung transplantation. 13 Further reviews of current therapies and the molecular basis of PAP and surfactant homeostasis are available. 3,10,12,13,18,25 Herein we report seven cases resembling PAP in "Moustached Tamarins" ( Saguinus mystax ).…”

Section: Introductionmentioning

confidence: 99%

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Spontaneous Pulmonary Alveolar Proteinosis in Captive “Moustached Tamarins” (Saguinus mystax)

et al. 2011

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Pulmonary alveolar proteinosis (PAP) is a rare human disease characterized by accumulation of surfactant in alveoli without generating an inflammatory response. Lung lesions resembling PAP were observed in seven adult tamarins (five males and two females). Gross lesions were characterized by areas of discoloration, slight bulging over the lung parenchyma, and occasional consolidation. Histological examination of tamarin lung samples revealed intra-alveolar accumulation of an amorphous, amphophilic, PAS-positive, finely granular to dense material. In some cases type II pneumocyte hypertrophy and hyperplasia with pleural and septal thickening and fibrosis were observed. Large numbers of intra-alveolar foamy macrophages were noted surrounding and/or in the vicinity of the lesions. Immunohistochemical analysis of the lung lesions using polyclonal (surfactant proteins A, B, and C) and monoclonal (surfactant protein D) antibodies revealed the granular material to be composed largely of surfactant protein B, followed by surfactant protein A. Surfactant proteins C and D (SP-D) were present in lesser quantities; with SP-D observed surrounding the lipoproteinaceous deposits. Transmission electron microscopy of the affected lungs showed numerous, irregularly-shaped, osmiophilic lamellar bodies in type II pneumocytes. The cytoplasm in alveolar macrophages was expanded, containing ingested surfactant with swollen mitochondria and rough endoplasmic reticulum. Thoracic radiographs, available in one animal, depicted the lesions as small multifocal opacities randomly distributed in cranial and diaphragmatic lung lobes. This is, to our knowledge, the first report of spontaneous PAP in nonhuman primates.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Spontaneous Pulmonary Alveolar Proteinosis in Captive “Moustached Tamarins” (Saguinus mystax)

et al. 2011

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“…It can be divided into 3 categories: idiopathic PAP (90% of total cases), congenital PAP (2% of total cases) and secondary PAP (<10% of total cases) [1]. When PAP accompanies other nonrespiratory diseases, it is generally regarded as secondary PAP.…”

Section: Introductionmentioning

confidence: 99%

Pulmonary Alveolar Proteinosis as a Terminal Complication in a Case of Myelodysplastic Syndrome with idic(20q–)

Xue

Han²,

Li³

et al. 2009

Acta Haematol

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Secondary pulmonary alveolar proteinosis (PAP) is a rare lung disease that has been reported in 13 cases of myelodysplastic syndromes (MDS). A dicentric isochromosome of deleted chromosome 20q, idic(20q–), is a newly recognized rare, but recurrent, cytogenetic anomaly that has been described in 28 cases of MDS. Recently, we encountered an interesting MDS patient with idic(20q–) and secondary PAP. At presentation, she was a 40-year-old woman with pancytopenia and dysplasia involving 2 cell lineages that were compatible with refractory cytopenia with multilineage dysplasia. A chromosome analysis of bone marrow cells using the R-banding technique revealed a karyotype of 46,XX,–20 and +a small metacentric marker chromosome. Fluorescence in situ hybridization demonstrated this marker chromosome to be idic(20q–). Three years after presentation, her disease was complicated by secondary PAP that was confirmed by chest computed tomographic scans and a thoracoscopic lung biopsy, revealing the characteristic periodic acid Schiff stain-positive materials filling the alveoli. The patient subsequently died of respiratory failure 45 months after diagnosis. To our knowledge, this is the first MDS patient with idic(20q–) and secondary PAP to be reported in the literature. Moreover, this patient is also the 29th MDS case with idic(20q–).

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A Randomized Phase IIb Study of Mavrilimumab and Golimumab in Rheumatoid Arthritis

Weinblatt

McInnes²,

Kremer

et al. 2017

Arthritis & Rheumatology

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ObjectiveThis 24‐week, phase IIb, double‐blind study was undertaken to evaluate the efficacy and safety of mavrilimumab (a monoclonal antibody to granulocyte–macrophage colony‐stimulating factor receptor α) and golimumab (a monoclonal antibody to tumor necrosis factor [anti‐TNF]) in patients with rheumatoid arthritis (RA) who have had an inadequate response to disease‐modifying antirheumatic drugs (DMARDs) (referred to as DMARD‐IR) and/or inadequate response to other anti‐TNF agents (referred to as anti‐TNF–IR).MethodsPatients with active RA and a history of DMARD‐IR (≥1 failed regimen) or DMARD‐IR (≥1 failed regimen) and anti‐TNF–IR (1–2 failed regimens) were randomized 1:1 to receive either mavrilimumab 100 mg subcutaneously every other week or golimumab 50 mg subcutaneously every 4 weeks alternating with placebo every 4 weeks, administered concomitantly with methotrexate. The primary end points were the American College of Rheumatology 20% improvement (ACR20), 50% improvement, and 70% improvement response rates at week 24, percentage of patients achieving a Disease Activity Score in 28 joints using C‐reactive protein level (DAS28‐CRP) of <2.6 at week 24, percentage of patients with a score improvement of >0.22 on the Health Assessment Questionnaire (HAQ) disability index (DI) at week 24, and safety/tolerability measures. This study was not powered to formally compare the 2 treatments.ResultsAt week 24, differences in the ACR20, ACR50, and ACR70 response rates between the mavrilimumab treatment group (n = 70) and golimumab treatment group (n = 68) were as follows: in all patients, −3.5% (90% confidence interval [90% CI] −16.8, 9.8), −8.6% (90% CI −22.0, 4.8), and −9.8% (90% CI −21.1, 1.4), respectively; in the anti‐TNF–IR group, 11.1% (90% CI −7.8, 29.9), −8.7% (90% CI −28.1, 10.7), and −0.7% (90% CI −18.0, 16.7), respectively. Differences in the percentage of patients achieving a DAS28‐CRP of <2.6 at week 24 between the mavrilimumab and golimumab groups were −11.6% (90% CI −23.2, 0.0) in all patients, and −4.0% (90% CI −20.9, 12.9) in the anti‐TNF–IR group. The percentage of patients achieving a >0.22 improvement in the HAQ DI score at week 24 was similar between the treatment groups. Treatment‐emergent adverse events were reported in 51.4% of mavrilimumab‐treated patients and 42.6% of golimumab‐treated patients. No deaths were reported, and no specific safety signals were identified.ConclusionThe findings of this study demonstrate the clinical efficacy of both treatments, mavrilimumab at a dosage of 100 mg every other week and golimumab at a dosage of 50 mg every 4 weeks, in patients with RA. Both regimens were well‐tolerated in patients who had shown an inadequate response to DMARDs and/or other anti‐TNF agents.

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Rare Lung Diseases II: Pulmonary Alveolar Proteinosis

Cited by 22 publications

References 83 publications

Spontaneous Pulmonary Alveolar Proteinosis in Captive “Moustached Tamarins” (Saguinus mystax)

Spontaneous Pulmonary Alveolar Proteinosis in Captive “Moustached Tamarins” (Saguinus mystax)

Pulmonary Alveolar Proteinosis as a Terminal Complication in a Case of Myelodysplastic Syndrome with idic(20q–)

A Randomized Phase IIb Study of Mavrilimumab and Golimumab in Rheumatoid Arthritis

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