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