title: Association between inhaled nitric oxide treatment and long-term pulmonary function in survivors of acute respiratory distress syndrome.
abstract: BACKGROUND
  Assessment of treatments for acute respiratory distress syndrome (ARDS) has focused on short-term outcomes (for example, mortality); little information exists regarding long-term effects of ARDS treatment. Survivors of ARDS episodes may have long-term obstructive/restrictive pulmonary abnormalities and pulmonary gas exchange impairment. A 2004 prospective randomized placebo-controlled trial assessed the efficacy and safety of inhaled nitric oxide (iNO) in patients with non-septic ARDS; the primary endpoint was days alive and off assisted breathing. This analysis examined potential effects of iNO or placebo on pulmonary function six months post-treatment in ARDS survivors from that original study.
  
  
  METHODS
  ARDS survivors (N = 92) from a large-scale randomized, placebo-controlled study evaluating mortality after either 5 ppm iNO or placebo for up to 28 days were assessed six months post-treatment. Pulmonary function testing across seven parameters was conducted.
  
  
  RESULTS
  At 6 months post-treatment, results indicated significantly better absolute values for iNO versus placebo for mean ± SD total lung capacity (TLC, 5.54 ± 1.42 vs. 4.81 ± 1.00; P = 0.026). There were also significantly better values for mean ± SD percent predicted values for a) forced expiratory volume in 1 second (FEV1, 80.23 ± 21.21 vs. 69.51 ± 28.97; P = 0.042), b) forced vital capacity (FVC, 83.78 ± 19.37 vs. 69.84 ± 27.40; P = 0.019), c) FEV1/FVC (96.14 ± 13.79 vs. 87.92 ± 19.77; P = 0.033), and d) TLC (93.33 ± 18.21 vs. 76.10 ± 21.84; P < 0.001). Nonsignificant differences were found in absolute FEV1, FEV1/FVC, FVC, forced expiratory flow from 25% to 75% of FVC, functional residual capacity, and CO diffusion.
  
  
  CONCLUSIONS
  ARDS patients surviving after treatment with low-dose iNO had significantly better values for select pulmonary function tests at six months post-treatment than placebo-treated patients. Further trials are warranted to determine the effects of iNO on chronic lung function in ARDS survivors, a factor in long-term morbidity and quality of life in this population.
  
  
  BACKGROUND
  A Double-blind, Randomized, Placebo-controlled, Dose-response Study of Inhaled Nitric Oxide in the Treatment of Acute Respiratory Distress Syndrome. NCT number: ISRCTN53268296.
authors.affiliation: Division of Critical Care Medicine, Department of Medicine, Cooper University Hospital, 1 Cooper Plaza, Camden, NJ 08103, USA. dellinger-phil@cooperhealth.edu.
authors.forename: R Phillip
authors.initials: RP
authors.lastname: Dellinger
authors.forename: Stephen W
authors.initials: SW
authors.lastname: Trzeciak
authors.forename: Gerard J
authors.initials: GJ
authors.lastname: Criner
authors.forename: Janice L
authors.initials: JL
authors.lastname: Zimmerman
authors.forename: Robert W
authors.initials: RW
authors.lastname: Taylor
authors.forename: Helen
authors.initials: H
authors.lastname: Usansky
authors.forename: Joseph
authors.initials: J
authors.lastname: Young
authors.forename: Brahm
authors.initials: B
authors.lastname: Goldstein
mesh_terms: D000280:Administration, Inhalation; D000328:Adult; D019540:Area Under Curve; D016009:Chi-Square Distribution; D004311:Double-Blind Method; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009569:Nitric Oxide / Q000008:administration & dosage*; D010919:Placebos; D011446:Prospective Studies; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000401:mortality / Q000503:physiopathology; D012129:Respiratory Function Tests; D018709:Statistics, Nonparametric; D016896:Treatment Outcome
chemical_list: D010919:Placebos; D009569:Nitric Oxide