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Increased Exhaled Nitric Oxide Following Autologous Peripheral Hematopoietic Stem-Cell Transplantation^*

A Potential Marker of Idiopathic Pneumonia Syndrome

^* From the Division of Pulmonary, Critical Care and Sleep Medicine (Drs. Qureshi, Girgis, Dandapantula, and Soubani), and Department of Biostatistics (Dr. Abrams), Wayne State University School of Medicine, Detroit, MI.

Correspondence to: Ayman O. Soubani, MBBS, FCCP, Harper University Hospital, Division of Pulmonary, Critical Care and Sleep Medicine, 3990 John R-3 Hudson, Detroit, MI 48201; e-mail: asoubani{at}med.wayne.edu

Abstract

Background: Increased production of nitric oxide (NO) and oxidative stress following bone marrow transplantation may play a role in the pathogenesis of idiopathic pneumonia syndrome (IPS). We hypothesize that patients who received high-dose chemotherapy followed by autologous peripheral hematopoietic stem-cell transplantation (APHSCT) have increased exhaled NO.

Method: We measured exhaled lower respiratory tract NO concentration with a chemiluminescent NO analyzer during a slow vital capacity maneuver against a positive pressure of 16 cm H₂O at an expiratory flow rate of 50 mL/s in 20 female patients who received high-dose chemotherapy (cyclophosphamide, carmustine, and cisplatin) followed by APHSCT for the treatment of stage III or IV breast carcinoma. Pulmonary function tests were performed, and exhaled NO measurements and clinical and laboratory data were obtained before transplantation and at every 6-week visit after transplantation for 24 weeks.

Results: All study patients had evidence of IPS with dyspnea and reduction in diffusion capacity of the lung for carbon monoxide (DLCO). Lower respiratory tract exhaled NO was significantly higher after APHSCT and during the 6 months of follow-up. Mean (± SD) exhaled NO increased from (mean ± SD) 12.54 ± 1.32 parts per billion (ppb) before APHSCT to 21.26 ± 1.94 ppb at 6 weeks (p = 0.099), 21.26 ± 1.94 ppb (p = 0.006) at 12 weeks, 24.62 ± 2.55 ppb (p = 0.012) at 18 weeks, and 25.28 ± 3.31 ppb (p = 0.013) at 24 weeks (all p values were compared to baseline). There was a strong negative correlation between DLCO and exhaled NO (regression coefficient - 0.60, p = 0.01).

Conclusion: Lower respiratory tract concentration of exhaled NO is significantly increased following APHSCT and correlates with reduction in DLCO. Increase in lower respiratory tract concentration of NO is a potential marker of IPS.

Key Words: bone marrow transplantation • exhaled nitric oxide • idiopathic pneumonia syndrome • nitric oxide • peripheral hematopoietic stem-cell transplantation • pulmonary complications • pulmonary drug toxicity