High Concentrations of Keratinocyte Growth Factor in Airways of Premature Infants Predicted Absence of Bronchopulmonary Dysplasia

Abstract

Premature lungs are highly susceptible to lung injuries, leading to bronchopulmonary dysplasia (BPD). Keratinocyte growth factor (KGF) is produced by the developing lung and may reduce the risk of BPD by preventing injury to the lung epithelium and enhancing its repair. To determine whether KGF concentrations in the airways during the initial phase of hyaline membrane disease are correlated with subsequent development of BPD defined as the need for supplemental oxygen at a postconceptional age of 36 weeks, we obtained tracheal aspirates within 3 hours of birth (Day 0) from 91 intubated neonates with a gestational age of 30 weeks or less. Repeat samples were obtained from 42 neonates within 5 days after birth. KGF in aspirate supernatants was measured by enzyme-linked immunosorbent assay. On Day 0, KGF was detected in all but six neonates. A significant increase in KGF concentration was found from the first to the second samples. The highest KGF concentration within 5 days after birth (KGF(max)) was significantly higher in survivors without BPD than in those with BPD. A KGF(max) value higher than 110 pg/ml had a positive predictive value of 95% for absence of BPD. KGF may hold promise for the treatment of very premature neonates.

Gelatinase activities in the airways of premature infants and development of bronchopulmonary dysplasia

“…Once secreted, MMP-9 can be activated by many products present in inflammatory airways, especially oxidants (29) and neutrophil elastase (34). In our study, the presence and amount of (8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21)(22) Values are medians with 25th-75th percentiles in parentheses; n, no. of neonates.…”

“…The intersubject coefficient of variation of sIgA in 60 samples was 18.2%, demonstrating a much lower variability in the dilution factor than that observed with higher aliquot volumes (9). Furthermore, our laboratory previously demonstrated with this method a high correlation between expression of results per milliliter of supernatant and per nanogram of sIgA (r ϭ 0.823; P Ͻ 0.0001) (8). Thus the dilution factor induced by our method is low and does not introduce significant bias in results expressed per milliliter of supernatant.…”

Angiopoietin 2 concentrations in infants developing bronchopulmonary dysplasia: attenuation by dexamethasone

“…24 Others have been unable to confirm IL-1b, IL-6, macrophage inflammatory protein-1-a, -b and endothelin-1 31 in the TA as markers for BPD. 29,32 Infants with subsequent development of BPD had lower hepatocyte growth factor, 33 keratinocyte growth factor 34 and parathyroid hormone-related protein concentrations in TAs. 35 Babies developing BPD had lower 36 or no association 31 with VEGF in TAs compared with those surviving without BPD.…”

Bronchopulmonary dysplasia and emphysema: in search of common therapeutic targets

“…FGF18 and FGF2 were found to inversely control the expression of elastic fiber components in myofibroblasts [95]. Although FGF7 (or keratinocyte growth factor) binds another FGFR, high FGF7 concentrations in tracheal effluents from premature infants predicted the absence of BPD [96], which might relate to the protective properties of this factor for alveolar epithelium. Last, fibroblasts isolated from human emphysematous lung have been found to present markedly reduced basal production of HGF and lowered production of FGF7 in response to stimuli [97].…”