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Development of Obliterative Bronchiolitis in a Murine Model of Orthotopic Lung Transplantation
Published on: July 10, 2012
Obstructive lung disease after allogeneic marrow transplantation. Clinical presentation and course
J G Clark1, S W Crawford, D K Madtes
1Fred Hutchinson Cancer Research Center, Seattle, Washington.
Abstract:
To describe the clinical presentation and progression of obstructive lung disease after marrow transplantation, we examined a sequential sample of 35 patients who had allogeneic marrow transplantation between January 1980 and January 1987, were 16 years or older, had normal pulmonary function tests before transplantation, and developed airflow obstruction defined as FEV1/FVC less than 70% and FEV1 less than 80% predicted 50 days or more after transplantation. Cases were selected from 1029 adult (older than 16 years) patients who underwent allogeneic marrow transplantation during the same period. Patients with airflow obstruction presented with symptoms of cough, dyspnea, or wheezing, or a combination. In 80% the chest radiograph was normal. Airflow obstruction was diagnosed within 1.5 years after transplantation in 33 of 35 patients. Clinical, extensive, chronic graft-versus-host disease was present in 24 patients. Only 4 patients had a complete response to primary therapy of chronic graft-versus-host disease. Serum IgG and IgA levels were decreased in 15 and 25 patients, respectively. The FEV1 declined rapidly (decrease in FEV1 greater than 30% between tests) in 21 patients, but 14 patients with slowly progressive or reversible disease were identified. Mortality was 65% at 3 years after transplant, a significantly higher value (P = 0.016) than the 3-year mortality rate of 44% in a comparison group of 412 concurrent patients with chronic graft-versus-host disease who were 16 years or older, survived more than 80 days after transplantation, and had normal pulmonary function. We concluded that obstructive lung disease after marrow transplantation may be variable with respect to time of onset and rate of progression. Obstructive lung disease was frequently associated with serum immunoglobulin deficiency and clinical, extensive, chronic graft-versus-host disease that was not readily responsive to treatment. Mortality was high but long-term survivors were identified.
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