Oil red O stain of alveolar macrophages is an effective screening test for gastroesophageal reflux disease in lung transplant recipients

Hopkins, Peter; Kermeen, F.; Duhig, Edwina; Fletcher, Linda M.; Gradwell, Judith; Whitfield, Lenore; Godinez, Coral; Musk, M.; Chambers, Daniel C.; Gotley, D. C.; McNeil, Keith

doi:10.1016/j.healun.2010.03.015

Cited by 24 publications

(20 citation statements)

References 19 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Masson’s trichrome staining was used to identify collagen deposition (Newcomer Supply). Intracellular lipid deposits were identified by Oil Red O staining after fixation with 10% buffered formalin, incubation in propylene glycol (Newcomer Supply), and counterstaining with hematoxylin (44). …”

Section: Methodsmentioning

confidence: 99%

Modeling pulmonary alveolar microlithiasis by epithelial deletion of the Npt2b sodium phosphate cotransporter reveals putative biomarkers and strategies for treatment

et al. 2015

View full text Add to dashboard Cite

Pulmonary alveolar microlithiasis (PAM) is a rare, autosomal recessive lung disorder associated with progressive accumulation of calcium phosphate microliths. Inactivating mutations in SLC34A2, which encodes the NPT2b sodium-dependent phosphate cotransporter, has been proposed as a cause of PAM. We show that epithelial deletion of Npt2b in mice results in a progressive pulmonary process characterized by diffuse alveolar microlith accumulation, radio-graphic opacification, restrictive physiology, inflammation, fibrosis, and an unexpected alveolar phospholipidosis. Cytokine and surfactant protein elevations in the alveolar lavage and serum of PAM mice and confirmed in serum from PAM patients identify serum MCP-1 (monocyte chemotactic protein 1) and SP-D (surfactant protein D) as potential biomarkers. Microliths introduced by adoptive transfer into the lungs of wild-type mice produce marked macrophagerich inflammation and elevation of serum MCP-1 that peaks at 1 week and resolves at 1 month, concomitant with clearance of stones. Microliths isolated by bronchoalveolar lavage readily dissolve in EDTA, and therapeutic whole-lung EDTA lavage reduces the burden of stones in the lungs. A low-phosphate diet prevents microlith formation in young animals and reduces lung injury on the basis of reduction in serum SP-D. The burden of pulmonary calcium deposits in established PAM is also diminished within 4 weeks by a low-phosphate diet challenge. These data support a causative role for Npt2b in the pathogenesis of PAM and the use of the PAM mouse model as a preclinical platform for the development of biomarkers and therapeutic strategies.

show abstract

Section: Methodsmentioning

confidence: 99%

Modeling pulmonary alveolar microlithiasis by epithelial deletion of the Npt2b sodium phosphate cotransporter reveals putative biomarkers and strategies for treatment

et al. 2015

View full text Add to dashboard Cite

show abstract

“…In addition, examination of BAL for markers of aspiration (e.g. oil red O staining and determination of a lipid index, BAL fluid pepsin and BAL fluid bile acids) has been reported as useful for the detection of microaspiration of refluxed gastro-oesophageal material [66,130,131]. However, additional studies correlating BAL markers of aspiration with GOR and BOS are needed to facilitate selection of recipients with BOS who may benefit from interventions such as laparoscopic fundoplication.…”

Section: Remarksmentioning

confidence: 99%

An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome

et al. 2014

View full text Add to dashboard Cite

Bronchiolitis obliterans syndrome (BOS) is a major complication of lung transplantation that is associated with poor survival. The International Society for Heart and Lung Transplantation, American Thoracic Society, and European Respiratory Society convened a committee of international experts to describe and/or provide recommendations for 1) the definition of BOS, 2) the risk factors for developing BOS, 3) the diagnosis of BOS, and 4) the management and prevention of BOS.A pragmatic evidence synthesis was performed to identify all unique citations related to BOS published from 1980 through to March, 2013. The expert committee discussed the available research evidence upon which the updated definition of BOS, identified risk factors and recommendations are based. The committee followed the GRADE (Grading of Recommendation, Assessment, Development and Evaluation) approach to develop specific clinical recommendations.The term BOS should be used to describe a delayed allograft dysfunction with persistent decline in forced expiratory volume in 1 s that is not caused by other known and potentially reversible causes of posttransplant loss of lung function. The committee formulated specific recommendations about the use of systemic corticosteroids, cyclosporine, tacrolimus, azithromycin and about re-transplantation in patients with suspected and confirmed BOS.The diagnosis of BOS requires the careful exclusion of other post-transplant complications that can cause delayed lung allograft dysfunction, and several risk factors have been identified that have a significant association with the onset of BOS. Currently available therapies have not been proven to result in significant benefit in the prevention or treatment of BOS. Adequately designed and executed randomised controlled trials that properly measure and report all patient-important outcomes are needed to identify optimal therapies for established BOS and effective strategies for its prevention. Executive summaryMany lung transplant recipients develop delayed allograft dysfunction that has been traditionally referred to as bronchiolitis obliterans syndrome (BOS), which is thought to be caused by inflammation, destruction and fibrosis of small airways in the lung allograft that leads to obliterative bronchiolitis (OB). Because a definitive diagnosis of OB is difficult to make without a surgical lung biopsy, a decrease in the forced expiratory volume in 1 s (FEV1) has been used as a surrogate marker to identify patients who develop a syndrome of significant and persistent loss of lung allograft function with onset three or more months following transplantation. However, it is now recognised that numerous factors apart from OB can lead to a delayed onset, significant decline in lung function, and these causes of delayed onset graft dysfunction must be carefully excluded when a diagnosis of BOS is made. In general, BOS responds poorly to therapeutic interventions but may stabilise, and some patients may have a significant improvement in FEV1 with certain ther...

show abstract

“…that accumulate in lipid-rich organelles (Brown et al, 1992;Hopkins et al, 2010). Vital dyes for lysosome function, namely acridine orange, Lyso-ID V R , and Lysotracker V R are also suitable to identify PLD-inducing drugs like chloroquine (Fr€ ohlich et al, 2012;Meindl et al, 2015a).…”

Section: Cellular Screeningmentioning

confidence: 99%

Toxicity of orally inhaled drug formulations at the alveolar barrier: parameters for initial biological screening

Frőhlich

2017

Drug Delivery

View full text Add to dashboard Cite

To cite this article: Eleonore Fröhlich (2017) Toxicity of orally inhaled drug formulations at the alveolar barrier: parameters for initial biological screening, Drug Delivery Oral delivery is the most common mode of systemic drug application. Inhalation is mainly used for local therapy of lung diseases but may also be a promising route for systemic delivery of drugs that have poor oral bioavailability. The thin alveolar barrier enables fast and efficient uptake of many molecules and could deliver small molecules and proteins, which are susceptible to degradation and show poor absorption by oral application. The low rate of biotransformation and proteolytic degradation increases bioavailability of drugs but accumulation of not absorbed material may impair normal lung function. This limitation is more relevant for compounds that should be systematically active because higher doses have to be applied to the lung. The review describes processes that determine absorption of orally inhaled formulations, namely dissolution in the lung lining fluid and uptake and degradation by alveolar epithelial cells and macrophages. Dissolution testing in simulated lung fluid, screening for cytotoxicity and pro-inflammatory action in respiratory cells and study of macrophage morphology, and phagocytosis can help to identify adverse effects of pulmonary formulations. ARTICLE HISTORY

show abstract

Oil red O stain of alveolar macrophages is an effective screening test for gastroesophageal reflux disease in lung transplant recipients

Cited by 24 publications

References 19 publications

Modeling pulmonary alveolar microlithiasis by epithelial deletion of the Npt2b sodium phosphate cotransporter reveals putative biomarkers and strategies for treatment

Modeling pulmonary alveolar microlithiasis by epithelial deletion of the Npt2b sodium phosphate cotransporter reveals putative biomarkers and strategies for treatment

An international ISHLT/ATS/ERS clinical practice guideline: diagnosis and management of bronchiolitis obliterans syndrome

Toxicity of orally inhaled drug formulations at the alveolar barrier: parameters for initial biological screening

Contact Info

Product

Resources

About