title: Inflammatory markers and mediators in tracheal fluid of premature infants treated with inhaled nitric oxide.
abstract: 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-1beta, interleukin-8, transforming growth factor-beta, N-acetylglucosaminidase, 8-epi-prostaglandin F2alpha, 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 F2alpha 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.
authors.affiliation: Department of Pediatrics, Section of Neonatology, Children's Mercy Hospitals and Clinics, University of Missouri-Kansas City School of Medicine, 2401 Gillham Rd, Kansas City, MO 64108, USA. wtruog@cmh.edu
authors.forename: William E
authors.initials: WE
authors.lastname: Truog
authors.forename: Philip L
authors.initials: PL
authors.lastname: Ballard
authors.forename: Michael
authors.initials: M
authors.lastname: Norberg
authors.forename: Sergio
authors.initials: S
authors.lastname: Golombek
authors.forename: Rashmin C
authors.initials: RC
authors.lastname: Savani
authors.forename: Jeffrey D
authors.initials: JD
authors.lastname: Merrill
authors.forename: Lance A
authors.initials: LA
authors.lastname: Parton
authors.forename: Avital
authors.initials: A
authors.lastname: Cnaan
authors.forename: Xianqun
authors.initials: X
authors.lastname: Luan
authors.forename: Roberta A
authors.initials: RA
authors.lastname: Ballard
mesh_terms: D000280:Administration, Inhalation; D015415:Biomarkers / Q000032:analysis; D001997:Bronchopulmonary Dysplasia / Q000175:diagnosis / Q000401:mortality / Q000628:therapy*; D016207:Cytokines / Q000032:analysis*; D015237:Dinoprost / Q000032:analysis; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D018836:Inflammation Mediators / Q000032:analysis*; D053583:Interleukin-1beta / Q000032:analysis; D016209:Interleukin-8 / Q000032:analysis; D008297:Male; D009569:Nitric Oxide / Q000627:therapeutic use*; D011379:Prognosis; D012016:Reference Values; D015203:Reproducibility of Results; D012121:Respiration, Artificial / Q000379:methods; D012680:Sensitivity and Specificity; D014132:Trachea / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000032:analysis; D016896:Treatment Outcome
chemical_list: D015415:Biomarkers; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D016209:Interleukin-8; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; D015237:Dinoprost