Published online April 2, 2007
PEDIATRICS Vol. 119 No. 4 April 2007, pp. 670-678 (doi:10.1542/peds.2006-2683)

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ARTICLE

Inflammatory Markers and Mediators in Tracheal Fluid of Premature Infants Treated With Inhaled Nitric Oxide

William E. Truog, MD^a, Philip L. Ballard, MD, PhD^b, Michael Norberg, BS, MDiv^a, Sergio Golombek, MD, MPH^c, Rashmin C. Savani, MBChB^b,d, Jeffrey D. Merrill, MD^b, Lance A. Parton, MD^c, Avital Cnaan, PhD^b, Xianqun Luan, MS^b, Roberta A. Ballard, MD^b and the Nitric Oxide (to Prevent) Chronic Lung Disease Study Investigators

^a Section of Neonatology, Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, Kansas City, Missouri
^b Children's Hospital of Philadelphia, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania
^c Maria Fareri Children's Hospital at Westchester Medical Center, New York Medical College, Valhalla, New York
^d Department of Pediatrics, University of Texas Southwestern, Dallas, Texas

OBJECTIVE. We compared serial measurements of inflammatory mediators and markers in infants treated with inhaled nitric oxide or placebo to assess the effects of inhaled nitric oxide therapy on lung inflammation during bronchopulmonary dysplasia. We investigated relationships between respiratory severity scores and airway concentrations of inflammatory markers/mediators.

METHODS. As part of the Nitric Oxide (to Prevent) Chronic Lung Disease trial, a subset of 99 infants (52 placebo-treated infants and 47 inhaled nitric oxide-treated infants; well matched at baseline) had tracheal aspirate fluid collected at baseline, at 2 to 4 days, and then weekly while still intubated during study gas treatment (minimum of 24 days). Fluid was assessed for interleukin-1ß, interleukin-8, transforming growth factor-ß, N-acetylglucosaminidase, 8-epi-prostaglandin F₂, and hyaluronan. Results were normalized to total protein and secretory component of immunoglobulin A.

RESULTS. At baseline, there was substantial variability of each measured substance and no correlation between tracheal aspirate fluid levels of any substance and respiratory severity scores. Inhaled nitric oxide administration did not result in any time-matched significant change for any of the analytes, compared with the placebo-treated group. There was no correlation between any of the measured markers/mediators and respiratory severity scores throughout the 24 days of study gas administration. In the posthoc analysis of data for inhaled nitric oxide-treated infants, there was a difference at baseline in 8-epi-prostaglandin F₂ levels for infants who did (n = 21) and did not (n = 26) develop bronchopulmonary dysplasia at postmenstrual age of 36 weeks.

CONCLUSIONS. Inhaled nitric oxide, as administered in this study, seemed to be safe. Its use was not associated with any increase in airway inflammatory substances.

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Key Words: bronchopulmonary dysplasia • nitric oxide • inflammation

Abbreviations: BPD—bronchopulmonary dysplasia • iNO—inhaled nitric oxide • MLEC—mink lung epithelial cell • NAG—N-acetylglucosaminidase • IgA—immunoglobulin A • NO—nitric oxide • TAF—tracheal aspirate fluid • TGF—transforming growth factor • NO-CLD—nitric oxide (to prevent) chronic lung disease • 8-epi-PGF₂—8-epi-prostaglandin F₂ • FIO₂—fraction of inspired oxygen • IL-1ß—interleukin-1ß • IL-8—interleukin-8 • ELISA—enzyme-linked immunosorbent assay • bHABP—biotinylated hyaluronic acid-binding peptide

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Accepted Dec 13, 2006.

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