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Blood, 15 September 2008, Vol. 112, No. 6, pp. 2529-2538. Prepublished online as a Blood First Edition Paper on June 25, 2008; DOI 10.1182/blood-2008-01-132506.
RED CELLS Histopathology of experimentally induced asthma in a murine model of sickle cell disease1 Department of Surgery, Division of Pediatric Surgery, 2 Department of Pediatrics, Division of Pulmonary/Critical Care, and 3 Department of Anesthesiology, Medical College of Wisconsin, Blood Research Institute, Children's Research Institute, Cardiovascular Center, Milwaukee, WI; 4 Department of Pediatrics, Division of Allergy and Pulmonary Medicine and Division of Genetics, Washington University School of Medicine, St Louis, MO; and 5 Department of Pediatrics, Division of Hematology/Oncology, Children's Research Institute, Cardiovascular Center, Milwaukee, WI
Asthma is a comorbid condition associated with increased rates of pain, acute chest syndrome, and premature death in human sickle cell disease (SCD). We developed an experimental asthma model in SCD and control mice expressing either normal human or murine hemoglobin to determine its effect on mortality and lung pathology. To induce lung inflammation, experimental mice were sensitized to ovalbumin (OVA) by subcutaneous OVA implantation (Sen), allowed 2 weeks to recover, and then divided into 2 groups, each receiving over a subsequent 10-day period the same dosage of aerosolized OVA but 2 different levels of exposure: 15 minutes (LoSen) and 30 minutes (HiSen). During recovery, 10% of SCD mice died compared with no deaths in control mice. An additional 30% of HiSen SCD mice died during aerosolization compared with 10% in LoSen SCD. Histologic indices of lung inflammation (eg, eosinophil recruitment, airway and vessel wall thickening, and immunoreactive TGFβ and fsp-1) and bronchial alveolar lavage fluid eosinophil peroxidase activity differentially increased in sensitized mice compared with unsensitized mice. Our findings indicate SCD mice with experimentally induced asthma are more susceptible to death and pulmonary inflammation compared with control mice, suggesting that asthma contributes significantly to morbidity and mortality in SCD.
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