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2265323 
Journal Article 
Abstract 
Nasal nitric oxide is reduced in children treated with tacrolimus after lung transplantation 
Kritzinger, F; Solomon, M; Grasemann, H 
2010 
Yes 
American Journal of Respiratory and Critical Care Medicine
ISSN: 1073-449X
EISSN: 1535-4970 
181 
A3308 
English 
WOS:000208771002419 
is part of a larger document 3452678 Proceedings of the American Thoracic Society 2010 International Conference, May 14-19, 2010, New Orleans
Rationale
Decreased airway nitric oxide (NO) production may impair host-defense against certain respiratory pathogens. Recent evidence suggests that the immunosuppressive drug tacrolimus (FK506) may reduce vascular NO production. The aim of this study was to investigate a possible effect of tacrolimus on airway NO production in children treated with tacrolimus to prevent graft rejection after solid organ transplantation.

Methods
Nasal and exhaled NO was measured in 8 pediatric lung transplant patients, 11 recipients of other solid organ transplants (SOT) and 18 healthy non-atopic, non-asthmatic children following published ERS/ATS recommendations for the measurements of NO in children (Eur Respir J. 2002;20:223-37). Lower airway NO was measured at a constant exhalation flow of 50 ml/sec. Mean (range) age was 14 (12-18) years in lung recipients, 12 (8-16) years in SOT patients and 11.7 (6-17) years in controls. Forced vital capacity (FVC) was 73.5 (50-92) %, 80.2 (30-118) %and 95 (71-111) % of predicted, and forced expiratory volume in one second (FEV1) was 67.1 (37-100) %, 78.2 (22-102) % and 98 (80-113) % of percent predicted in the three groups, respectively. All transplant patients were treated with tacrolimus (FK506); drug serum levels between the transplant groups were not significantly different. One way ANOVA with Dunn’s multiple comparison test was performed for group comparisons.

Results
Mean (±SEM) nasal NO was significantly reduced in all transplant recipients compared to controls (469.3 ± 99.8 vs. 963.4 ± 77.1 ppb, p < 0.05). Nasal NO in lung transplant recipients was significantly lower than in controls (209.8 ± 109.1 ppb, p <0.001), while nasal NO in SOT patients was not significantly different from either lung transplant patients or healthy controls. When looking at all transplanted patients, tacrolimus serum levels and nasal NO concentrations showed a linear correlation (r = -0.60, p = 0.006) and nasal NO was significantly lower in patients with tacrolimus level > 10 (n=7) compared to < 10 µg/L (n=12) (104.4 ± 53.4 vs. 659.4 ± 111.2 ppb, p < 0.001). No differences between groups were found for exhaled NO.

Conclusions
Tacrolimus treatment after solid organ transplantation results in a dose dependent reduction of nasal NO production. Further studies are needed to determine the biological consequences of the tacrolimus-related reduction in upper airway NO production in pediatric transplant recipients. 
American Thoracic Society 2010 International Conference 
New Orleans, LA 
May 14-19, 2010