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Stachybotrys Induced Hemorrhage in the Developing Lung
Date study started January, 1999; Date Study Completed January, 2004
Recruitment status verified February, 2001 This study is currently recruiting
patients. Sponsored by National Institute of Environmental Health Sciences (NIEHS)
Purpose: The majority of the workscope of this project is focused on an infant
animal model of toxigenic mold induced pulmonary hemorrhage. Clinically related
studies are directed only to the description of human infants diagnosed with
idiopathic pulmonary hemorrhage regarding their clinical parameters, and
collecting samples of secretion, blood, and urine for analysis for fungal spores
and mycotoxins. These latter analyses are being developed using the infant rat
model.
Condition: Idiopathic Pulmonary Hemorrhage
Further Study Details:
Over the past seven years in the Cleveland, Ohio area there have been 47 cases
of unexplained pulmonary hemorrhage in young infants. Sixteen of the infants
have died. A CDC case-control study found an association with water-damaged
homes and the toxigenic fungus, Stachybotrys chartarum, which requires water
soaked cellulose to grow. The spores of this fungus are not infectious in the
lung but do contain very potent mycotoxins which appear to be particularly toxic
to the rapidly developing lungs of young infants. Secondary stresses, e.g.
environmental tobacco smoke, appear to be important triggers of overt
hemorrhage. Concern that there may be a larger number of undetected young
infants with this disorder led to the examination of all infant coroner cases,
which revealed six sudden infant death syndrome cases with major amounts of
pulmonary hemosiderin-laden macrophages, indicating extensive hemosiderosis
existing prior to death. All of these infants had lived in the eight zip code
area where all but fifteen of the patients have lived. This disorder may extend
beyond Cleveland since toxigenic fungi are widespread. We are aware of a total
of 138 infants with idiopathic pulmonary hemorrhage across the country over the
past four years. The purpose of this proposal is to establish an infant animal
model for this stachybotryomycotoxicosis which can be used to understand the
developmental pathophysiology by which the fungal spores induce hemorrhage and
to address practical problems faced in the clinical care of these infants and in
public health prevention. The model uses tracheal instillation of toxic
Stachybotrys spores in neonatal to weanling rats to initiate the pathological
process, followed by stresses to trigger acute hemorrhage. Capillary fragility
to transmural pressures will be assessed by morphometric analysis of electron
micrographs. Markers of Stachybotrys exposure which can be applied to clinical
cases are being developed and tested in the rats.
Dorr G Dearborn, MD,PhD,
dxd9@po.cwru.edu