No abstract

Despite advances in the management of myeloablative allogeneic hematopoietic stem cell transplants, airflow obstruction (AFO) remains a significant complication. We conducted a 12-year study to examine the recent epidemiology of AFO and its associated mortality. Using the rate of percent predicted FEV1 decline after transplant, we defined AFO as a more than 5% per year decline in percent predicted FEV1 with the lowest post-transplant FEV1/FVC ratio less than 0.8. New obstruction was more frequent than previous estimates (26% overall, 32% among patients with chronic graft-versus-host disease [GVHD]) and was significantly associated with older age at transplant, lower pretransplant FEV1/FVC ratio, history of both acute and chronic GVHD, and respiratory viral infection within the first 100 days after transplant. AFO was associated with significant attributable mortality rates of 9% at 3 years, 12% at 5 years, and 18% at 10 years after transplant, which were much higher for the subpopulation of patients with chronic GVHD (22% at 3 years, 27% at 5 years, and 40% at 10 years). These results suggest that the incidence of AFO may have been underestimated previously, and its presence significantly increases the mortality of long-term survivors of myeloablative allogeneic hematopoietic stem cell transplant patients.

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.

The fibroproliferative reaction to acute lung injury may limit restoration of normal lung function and increase mortality in patients with acute lung injury. A biologic marker of collagen synthesis in the lung may be useful for studying the pathogenesis of acute lung injury and for identifying patients with acute lung injury who are at high risk for death and might benefit from new therapeutic modalities. Using an immunoassay, type III procollagen NH2 terminal peptide was measured in the pulmonary edema fluid of 44 patients with either acute lung injury or hydrostatic pulmonary edema (control group) within the first 24 h after endotracheal intubation for acute respiratory failure. Patients with acute lung injury (n = 33) or hydrostatic edema (n = 11) had the same degree of lung dysfunction as measured by the severity of oxygenation defect, the level of positive end-expiratory pressure, the decrease in static lung compliance, and the extent of infiltrates on the chest radiograph. However, the median procollagen III level was 5-fold higher in the pulmonary edema fluid of patients with acute lung injury than in the patients with hydrostatic pulmonary edema (p = 0.0001). Of the 33 patients with acute lung injury, 21 patients died and 12 lived. Nonsurvivors had significantly higher procollagen III levels than did survivors (p = 0.05). The positive and negative predictive values for nonsurvival for a procollagen III level > or = 1.75 U/ml were 74 and 83%, respectively. The relative risk of dying in the presence of a procollagen III value > or = 1.75 U/ml was 4.5 (95% CI, 0.7 to 27). Collagen synthesis in the lung, as reflected by elevated levels of procollagen III in pulmonary edema fluid, begins within the first 24 h of acute lung injury concurrent with the acute phase of increased endothelial and epithelial permeability to protein. This evidence suggests that fibrosing alveolitis begins much earlier in the course of clinical acute lung injury than has previously been appreciated. In addition, the presence of an elevated level of procollagen III is an early predictor of poor outcome. Thus, elevation of procollagen III in pulmonary edema fluid may have both pathogenetic and prognostic significance in patients with acute lung injury.