Stachybotrys Induced Hemorrhage in the Developing Lung
Stachybotrys Induced Hemorrhage in the Developing Lung
The majority of the workscope of this project is focussed 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.
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.
Inclusion: infant (<12 mo old) with unexplained pulmonary hemorrhage, discharged home from
 newborn nursery Exclusion: hemorrhage occurred in hospital prior to going home prior to
 discharge from newborn nursery