title: Tracheobronchial aspirate fluid neutrophil lipocalin, elastase- and neutrophil protease-4-alpha1-antitrypsin complexes, protease inhibitors and free proteolytic activity in respiratory distress syndrome.
abstract: This study aimed to determine whether the protease/protease inhibitor balance and neutrophil activity is of pathophysiological importance in the severity and resolution of respiratory distress syndrome (RDS) and the eventual development of neonatal chronic lung disease (CLD). Ventilated preterm infants with RDS (n = 43) were studied during their first week of life. Tracheobronchial aspirate fluid (TAF) concentrations of neutrophil lipocalin, the elastase- and neutrophil protease-4 (NP4) complex concentrations, and alpha1-antitrypsin (alpha1AT), antichymotrypsin (ACT) and secretory leucocyte protease inhibitor (SLPI) levels were analysed. Free proteolytic and elastolytic activities were also determined. CLD correlated with low alpha1AT (p = 0.02) and ACT (p = 0.02) levels at 3-4 d of age and low SLPI (p = 0.03) at 7-8 d of age. No correlations were found between CLD or severity of RDS (as judged from radiological examination) and neutrophil lipocalin, elastase- and NP4-alpha1AT complexes during the first week of life, with one exception: RDS X-ray severity and the elastase-alpha1AT complex concentration were correlated at 3-4d of age (p = 0.02). Free proteolytic activity occurred in the TAF of 7/30 infants tested on day 3-4 and free elastolytic activity in 1 patient. During the rest of the first week of life no free elastolytic or proteolytic activities were observed. Caesarean section was correlated with low levels of SLPI on day 3-4 (p = 0.01), NP4 (p = 0.03) and ACT (p = 0.05) on day 5-6. Gestational age was positively correlated with protease inhibitors and their complexes at 3-4 d of age.
  
  
  CONCLUSIONS
  Free proteolytic or elastolytic activity in the TAF of RDS infants in the first week of life occurred by way of exception. Elastase-/NP4-alpha1AT complex or neutrophil lipocalin levels were not correlated with the development of CLD. The correlation between CLD and low alpha1AT or ACT at 3-4 d and SLPI at 7-8 d of age may be due to either immaturity or complex formation. The severity of RDS as judged from radiological examination was correlated with elastase-alpha1AT complex on day 3-4. The main hypothesis, that TAF protease/protease inhibitor levels or imbalance and leucocyte activity are important factors indicating a high risk of severe RDS and subsequent CLD development, was principally not confirmed.
authors.affiliation: Department of Paediatrics, University of Lund, University Hospital, Malmö, Sweden.
authors.forename: T
authors.initials: T
authors.lastname: Sveger
authors.forename: K
authors.initials: K
authors.lastname: Ohlsson
authors.forename: S
authors.initials: S
authors.lastname: Polberger
authors.forename: G
authors.initials: G
authors.lastname: Noack
authors.forename: H
authors.initials: H
authors.lastname: Mörse
authors.forename: S
authors.initials: S
authors.lastname: Laurin
mesh_terms: D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology*; D001997:Bronchopulmonary Dysplasia / Q000175:diagnosis* / Q000209:etiology; D010450:Endopeptidases / Q000032:analysis; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D007234:Infant, Premature; D018836:Inflammation Mediators / Q000032:analysis*; D007363:Intensive Care Units, Neonatal; D019272:Leukocyte Elastase / Q000032:analysis; D008297:Male; D009504:Neutrophils / Q000378:metabolism; D010196:Pancreatic Elastase / Q000032:analysis; D011336:Probability; D011379:Prognosis; D011480:Protease Inhibitors / Q000032:analysis; D012127:Respiratory Distress Syndrome, Newborn / Q000150:complications / Q000175:diagnosis*; D012680:Sensitivity and Specificity; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric; D000515:alpha 1-Antitrypsin / Q000032:analysis
chemical_list: D018836:Inflammation Mediators; D011480:Protease Inhibitors; D000515:alpha 1-Antitrypsin; D010450:Endopeptidases; D010196:Pancreatic Elastase; D019272:Leukocyte Elastase