Over the past 4 years in Cleveland, Ohio there have been 34 cases of pulmonary hemorrhage and hemosiderosis in young infants. To date, ten infants have died. A CDC case-controlled study found an association with water damaged homes and the toxigenic fungus called Stachybotrys atra which requires water-saturated cellulose to grow. The spores of this fungus do not germinate in the lung, but do not 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 for overt hemorrhage. Concern that there may be a large number of undetected infants with the disorder ted to 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 lived in the same contiguous area as the majority of the hemosiderosis patients. This disorder may extend beyond Cleveland, since toxigenic fungi are widespread. We are aware of 122 infants with idiopathic pulmonary hemorrhage in this country in the past 4 years. The purpose of this proposal is to establish an original rat pup model for Stachybotrymycotoxicosis which can be used to understand the developmental pathophysiology by which fungal spores induces hemorrhage, address practical problems in clinical care, and foster public health prevention. This model uses tracheal instillation of toxic Stachybotrys spores in neonatal to weanling rats to initiate the pathologic process.
Specific aim 1 will evaluate dose response to Stachybotrys spore inhalation, critical age of vulnerability, histopathology, inflammatory mediator response, and change in lung function during injury and recovery.
Specific aim 2 will explore the vulnerability of pulmonary capillaries to leakage in the Stachybotrys exposed pups in vivo and in vitro, specific stress triggers of hemorrhage, and efficacy of anti- inflammatory therapy.
Specific aim 3 will develop and test biochemical markers for Stachybotrys exposure including toxins and antibody production. The experiments in this proposal will provide fundamental new information on Stachybotrys exposure applicable to detection and treatment of this new disorder.
