CORRESPONDENCE observations suggest that NETs by themselves affect host cell cytotoxicity, such as NET-mediated vascular injury, microcirculation obstruction by NET-mediated platelet thrombus, platelet aggregation, or leukocyte-platelet aggregation. In lungs of lipopolysaccharide-treated mice, both anchored and cell-free NETs were observed in the alveolar space, pulmonary capillaries, and the pulmonary interstitial space. Our observations strongly support the findings of Sayah and colleagues, which may indicate that both platelet inhibition and intrabronchial DNaseI administration reduced NETs in the alveolar space, resulting in the reduction of lung injury and improvement of oxygenation. If NETs were detected in the alveolar space, pulmonary capillaries, and the pulmonary interstitial space of their murine PGD models, not only intrabronchial but also intravenous administration of DNaseI would work for PGD. n Author disclosures are available with the text of this letter at www.atsjournals.org. Koji Tanaka, M.D., Ph.D. Yuji Toiyama, M.D., Ph.D. Yasuhiro Inoue, M.D., Ph.D. Toshimitsu Araki, M.D., Ph.D. Yasuhiko Mohri, M.D., Ph.D. Akira Mizoguchi, M.D., Ph.D. Masato Kusunoki, M.D., Ph.D. Mie University Graduate School of Medicine Mie, Japan

that NETs were formed in the vascular spaces and that intravenous DNaseI was effective in reducing lung injury (2). We have not used intravenous DNaseI in the mouse lung transplant model. n Author disclosures are available with the text of this letter at www.atsjournals.org. David M. Sayah, M.D., Ph.D. University of California, Los Angeles Los Angeles, California Beñat Mallavia, Ph.D. Mark R. Looney, M.D. University of California, San Francisco San Francisco, California

References 1. Sayah DM, Mallavia B, Liu F, Ortiz-Muñoz G, Caudrillier A, DerHovanessian A, Ross DJ, Lynch JP III, Saggar R, Ardehali A, et al.; Lung Transplant Outcomes Group Investigators. Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med 2015;191: 455–463. 2. Caudrillier A, Kessenbrock K, Gilliss BM, Nguyen JX, Marques MB, Monestier M, Toy P, Werb Z, Looney MR. Platelets induce neutrophil extracellular traps in transfusion-related acute lung injury. J Clin Invest 2012;122:2661–2671.

Copyright © 2015 by the American Thoracic Society

References

Mistaken Step-Up Units 1. Sayah DM, Mallavia B, Liu F, Ortiz-Muñoz G, Caudrillier A, DerHovanessian A, Ross DJ, Lynch JP III, Saggar R, Ardehali A, et al.; Lung Transplant Outcomes Group Investigators. Neutrophil extracellular traps are pathogenic in primary graft dysfunction after lung transplantation. Am J Respir Crit Care Med 2015;191:455–463. 2. Tanaka K, Koike Y, Shimura T, Okigami M, Ide S, Toiyama Y, Okugawa Y, Inoue Y, Araki T, Uchida K, et al. In vivo characterization of neutrophil extracellular traps in various organs of a murine sepsis model. PLoS ONE 2014;9:e111888.

Copyright © 2015 by the American Thoracic Society

Reply: Neutrophil Extracellular Traps in Primary Graft Dysfunction after Lung Transplantation From the Authors: We appreciate the insightful commentary of Tanaka and colleagues. As detailed in our article (1), both in experimental lung transplantation in mice and in human lung transplant recipients, we found that neutrophil extracellular trap (NET) abundance during primary graft dysfunction (PGD) was increased in bronchoalveolar lavage fluid but not in plasma. In our animal experiments, therefore, we directed DNaseI treatment to the alveolar spaces via intrabronchial instillation and found that this substantially reduced PGD. Although our results support a pathogenic role for NETs in the airspaces, we agree this does not exclude a role for intravascular or interstitial NETs in PGD. Indeed, in a model of transfusion-related acute lung injury, we found Correspondence

To the Editor: I read with interest the article by Prin and Wunsch (1). The authors include a group of “step-up” patients in the classification of those admitted to the stepdown units (SDUs), a new nomenclature that contradicts their own definition of these units. I worry that they give recognition to a practice that is not supported by the literature and risk causing confusion about its possible interest. Scaling to an SDU rather than to the intensive care unit (ICU) is an unproven practice that may be unsafe, and even dangerous, if the triage is incorrect. The hospital mortality of undertriaged patients is significantly higher than for those patients correctly triaged (2). An SDU that operates independently and is not coordinated with the ICU may be a dangerous barrier to ICU admission, preventing adequate patient care, and may also increase costs (3). The use of ICU severity scores for assessing patients admitted to the SDU is misleading. They should not be used in non–critically ill patients because they are not validated in this population, and if the patients are critically ill, their admission to the SDU is not justified. The statement that “stepdown patient outcomes are better than expected due to improvements in care” is not plausible because it means that lesser care produces better results, and therefore the medical or nursing care would be harmful. Prognostic models should be reliable and valid before they are applied to assess quality of care (4). Furthermore, it would be advisable to use the standardized mortality ratio based on 30-day, instead of hospital, mortality to assess SDU performance, avoiding different hospital discharge practices. 1089

Reply: neutrophil extracellular traps in primary graft dysfunction after lung transplantation.

Reply: neutrophil extracellular traps in primary graft dysfunction after lung transplantation. - PDF Download Free
414KB Sizes 3 Downloads 10 Views