Advertisement

Intensive Care Medicine

, 34:1858 | Cite as

Secretory phospholipase A2 and neonatal respiratory distress: pilot study on broncho-alveolar lavage

  • Daniele De LucaEmail author
  • Silvia Baroni
  • Giovanni Vento
  • Marco Piastra
  • Domenico Pietrini
  • Federica Romitelli
  • Ettore Capoluongo
  • Costantino Romagnoli
  • Giorgio Conti
  • Enrico Zecca
Pediatric Original

Abstract

Purposes

Secretory phospholipase A2 hydrolyzes phosphoglycerides and it has been shown to be involved in alveolar inflammation and surfactant degradation. It plays an important role in acute lung injury but it has never been studied in newborn infants. We were aimed to investigate the phospholipase A2 activity in neonatal lung injury and its relationship with ventilatory findings.

Setting

Third level university hospital NICU.

Methods

We measured phospholipase activity in broncho-alveolar lavage fluid of 21 neonates with hyaline membrane disease, 10 with pneumonia or sepsis and 10 controls, ventilated for extrapulmonary reasons. Fluid was obtained before surfactant administration on the first day of life and phospholipase activity was measured using an ultrasensitive enzymatic method. Before lavage, lung mechanics in pressure controlled synchronized intermittent mandatory ventilation was analyzed.

Results

Phospholipase A2 was higher in babies ventilated for sepsis/pneumonia compared to hyaline membrane disease and to control babies. Phospholipase correlated negatively with dynamic compliance, positively with inspired oxygen fraction, mean airway pressure and oxygenation index. These correlations still remained significant after multivariate analysis, adjusting for possible confounding factors. Phospholipase was not correlated with blood and alveolar pH, gestational age, birth weight, blood gases, Apgar score, tidal volume, surfactant need and ventilation time.

Conclusions

These are the first data about phospholipase A2 in neonates. The enzyme plays a role in neonatal lung injury, especially in infection related respiratory failure. It is associated with lung stiffness, higher mean airway pressure and need for oxygen.

Keywords

Phospholipase A2 Lung injury Newborn infants Neonatal respiratory distress syndrome 

Notes

Acknowledgments

We thank Mr. Maurizio Ginepro, MEng (bioengineer) for his invaluable technical help about lung mechanics measurements. We have no funding or competing interests to declare.

References

  1. 1.
    Touqui L, Wu YZ (2003) Interaction of secreted phospholipase A2 and pulmonary surfactant and its pathophysiological relevance in acute respiratory distress syndrome. Acta Pharmacol Sin 24:1292–1296PubMedGoogle Scholar
  2. 2.
    Dennis EA (1997) The growing phospholipase A2 superfamily of signal transduction enzymes. Trends Biochem Sci 22:1–2PubMedCrossRefGoogle Scholar
  3. 3.
    Waite M (1996) Phospholipases. In: Vance DE, Vance JE (eds) Biochemistry of lipids, lipoproteins and membranes, 3rd edn edn. Elsevier , AmsterdamGoogle Scholar
  4. 4.
    Touqui L, Arbibe L (1999) A role for phospholipase A2 in ARDS pathogenesis. Mol Med Tod 5:244–249CrossRefGoogle Scholar
  5. 5.
    Nakos G, Kitsiouli E, Hatzidaki E, Koulouras V, Touqui L, Lekka ME (2005) Phospholipases A2 and platelet-activating-factor acetylhydrolase in patients with acute respiratory distress syndrome. Crit Care Med 33:772–779PubMedCrossRefGoogle Scholar
  6. 6.
    Wheeler DS (2005) Phospholipases A2 and acute lung injury: it’s just not that simple. Crit Care Med 33:904–905PubMedCrossRefGoogle Scholar
  7. 7.
    Avery G (2005) Avery’s diseases of the newborn. In: Taeusch HW, Ballard R, Gleason CA (eds) 8th edn. Elsevier/Saunders, Amsterdam/Philadelphia Google Scholar
  8. 8.
    Khammash H, Perlman M, Wojtulewicz J, Dunn M (1993) Surfactant therapy in full-term neonates with severe respiratory failure. Pediatrics 92:135–139PubMedGoogle Scholar
  9. 9.
    Herting E, Gefeller O, Land M, van Sonderen L, Harms K, Robertson B, Members of the Collaborative European Multicenter Study Group (2000) Surfactant treatment of neonates with respiratory failure and group B streptococcal infection. Pediatrics 106:957–964PubMedCrossRefGoogle Scholar
  10. 10.
    De Luca D, Baroni S, Piastra M, Pietrini D, Romagnoli C, Zecca E (2007) Secretory phospholipase A2 and lung mechanics in neonatal acute lung injury: preliminary results. Acta Paediatr 96(suppl 456):83 (abstract)Google Scholar
  11. 11.
    Walti H, Couchard M, Relier JP (1989) Neonatal diagnosis of respiratory distress syndrome. Eur Respir J 2(suppl 2):22s–27sGoogle Scholar
  12. 12.
    American Heart Association, American Academy of Pediatrics (2006) 2005 Amercian Heart Association guidelines for cardiopulmonary resuscitation and emergency cardiovascular care of pediatric and neonatal patients: neonatal resuscitation guidelines. Pediatrics 117:1029–1038CrossRefGoogle Scholar
  13. 13.
    Zecca E, De Luca D, Baroni S, Vento G, Tiberi E, Romagnoli C (2008) Bile acid induced lung injury in newborn infants: a broncho-alveolar lavage fluid study. Pediatrics 121:e146–e149PubMedCrossRefGoogle Scholar
  14. 14.
    Reynolds LJ, Hughes LL, Yu L, Dennis EA (1994) 1-Hexadecyl-2-arachidonoylthio-2-deoxy-sn-glycero-3-phosphorylcholine as a substrate for the microtiterplate assay of human cytosolic phospholipase A2. Anal Biochem 217:25–32PubMedCrossRefGoogle Scholar
  15. 15.
    Capoluongo E, Ameglio F, Lulli P, Minucci A, Santonocito C, Concolino P, Di Stasio E, Boccacci S, Vendettuoli V, Giuratrabocchetta G, De Cunto A, Tana M, Romagnoli C, Zuppi C, Vento G (2007) Epithelial lining fluid free IGF-I-to-PAPP-A ratio is associated with bronchopulmonary dysplasia in preterm infants. Am J Physiol Endocrinol Metab 292:E308–E313PubMedCrossRefGoogle Scholar
  16. 16.
    Rennard SI, Basset G, Lecossier D, O’Donnell KM, Pinkston P, Martin PG, Crystal RG (1986) Estimation of volume of epithelial lining fluid recovered by lavage using urea as marker of dilution. Appl Physiol 60:532–538Google Scholar
  17. 17.
    Eberhard A, Carry PY, Perdrix JP, Fargnoli JM, Biot L, Baconnier PF (2003) A program based on a ‘selective’ least-squares method for respiratory mechanics monitoring in ventilated patients. Comput Methods Programs Biomed 71:39–61PubMedCrossRefGoogle Scholar
  18. 18.
    Cappa P, Sciuto SA, Silvestri S (2006) Experimental evaluation of errors in the measurement of respiratory parameters of the newborn performed by a continuous flow neonatal ventilator. J Med Eng Technol 30:31–40PubMedCrossRefGoogle Scholar
  19. 19.
    Norusis M (2004) SPSS 13.0 advanced statistical procedures companion. Prentice Hall Inc., Upper Saddle-RiverGoogle Scholar
  20. 20.
    Attalah HL, Wu Y, Alaoui-El-Azher M, Thouron F, Koumanov K, Wolf C, Brochard L, Harf A, Delclaux C, Touqui L (2003) Induction of type IIA secretory phospholipase A2 in animal models of acute lung injury. Eur Respir J 21:1040–1045PubMedCrossRefGoogle Scholar
  21. 21.
    Murakami M, Nakatani Y, Atsumi G, Inoue K, Kudo I (1997) Regulatory functions of phospholipase A2. Crit Rev Immunol 17:225–283PubMedGoogle Scholar
  22. 22.
    Yoshikawa S, Miyahara T, Reynolds SD, Stripp BR, Anghelescu M, Eyal FG, Parker JC (2005) Clara cell secretory protein and phospholipase A2 activity modulate acute ventilator-induced lung injury in mice. J Appl Physiol 98:1264–1271PubMedCrossRefGoogle Scholar
  23. 23.
    De Castro CM, Bureau MF, Nahori MA, Dumarey CH, Vargaftig BB, Bachelet M (1995) Modulation by dexamethasone of phospholipase A2 activities in endotoxemic guinea pigs. J Appl Physiol 79:1271–1277PubMedGoogle Scholar
  24. 24.
    Andreani M, Olivier JL, Berenbaum F, Raymondjean M, Bereziat G (2000) Transcriptional regulation of inflammatory secreted phospholipases A2. Biochim Biophys Acta 1488:149–158PubMedGoogle Scholar
  25. 25.
    Sweet D, Bevilacqua G, Carnielli V, Greisen G, Plavka R, Didrik Saugstad O, Simeoni U, Speer CP, Valls-I-Soler A, Halliday H, Working Group on Prematurity of the World Association of Perinatal Medicine, European Association of Perinatal Medicine (2007) European consensus guidelines on the management of neonatal respiratory distress syndrome. J Perinat Med 35:175–186Google Scholar
  26. 26.
    Arbibe L, Koumanov K, Vial D, Rougeot C, Faure G, Havet N, Longacre S, Vargaftig BB, Bereziat G, Voelker DR, Wolf C, Touqui L (1998) Generation of lyso-phospholipids from surfactant in acute lung injury is mediated by type-II phospholipase A2 and inhibited by a direct surfactant protein A-phospholipase A2 protein interaction. J Clin Invest 102:1152–1160PubMedCrossRefGoogle Scholar
  27. 27.
    Gregory TJ, Longmore WJ, Moxley MA, Whitsett JA, Reed CR, Fowler AAIII, Hudson LD, Maunder RJ, Crim C, Hyers TM (1991) Surfactant chemical composition and biophysical activity in acute respiratory distress syndrome. J Clin Invest 88:1976–1981PubMedCrossRefGoogle Scholar
  28. 28.
    Sun B, Curstedt T, Lindgren G, Franzén B, Alaiya AA, Calkovská A, Robertson B (1997) Biophysical and physiological properties of a modified porcine surfactant enriched with surfactant protein A. Eur Respir J 10:1967–1974PubMedCrossRefGoogle Scholar
  29. 29.
    Anzueto A, Baughman RP, Guntupalli KK, Weg JG, Wiedmann HP, Raventos AA, Lemaire F, Long W, Zaccardelli DS, Pattishall EN (1996) Aerosolized surfactant in adults with sepsis-induced acute respiratory distress syndrome. Exosurf Acute Respiratory Distress Syndrome Sepsis Study Group. N Engl J Med 344:1417–1421CrossRefGoogle Scholar
  30. 30.
    Wang Z, Chang Y, Schwan AL, Notter RH (2007) Activity and inhibition resistance of a phospholipase-resistant synthetic surfactant in rat lungs. Am J Respir Cell Mol Biol 37:387–394PubMedCrossRefGoogle Scholar
  31. 31.
    Duncan Hite R, Seeds MC, Safta AM, Jacinto RB, Gyves JA, Bass DA, Waite BM (2005) Lysophospholipid generation and phosphatidylglicerol depletion in phospholipase A2-mediated surfactant dysfunction. Am J Physiol Lung Cell Mol Physiol 288:L618–L624PubMedCrossRefGoogle Scholar
  32. 32.
    Kim DK, Fukuda T, Thompson BT, Cockrill B, Hales C, Bonventre JV (1995) Bronchoalveolar lavage fluid phospholipase A2 activities are increased in human adult respiratory distress syndrome. Am J Physiol 269:109–118Google Scholar
  33. 33.
    Abraham E, Naum C, Bandi V, Gervich D, Lowry SF, Wunderink R, Schein RM, Macias W, Skerjanec S, Dmitrienko A, Farid N, Forgue ST, Jiang F (2003) Efficacy and safety of LY315920Na/S-5920, a selective inhibitor of 14-kDa group IIA secretory phospholipase A2, in patients with suspected sepsis and organ failure. Crit Care Med 31:718–728PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  • Daniele De Luca
    • 1
    Email author
  • Silvia Baroni
    • 2
  • Giovanni Vento
    • 1
  • Marco Piastra
    • 3
  • Domenico Pietrini
    • 3
  • Federica Romitelli
    • 2
  • Ettore Capoluongo
    • 2
  • Costantino Romagnoli
    • 1
  • Giorgio Conti
    • 3
  • Enrico Zecca
    • 1
  1. 1.Neonatal Intensive Care Unit, Department of PediatricsUniversity Hospital “A. Gemelli”, Catholic University of the Sacred HeartRomeItaly
  2. 2.Institute of Clinical BiochemistryUniversity Hospital “A. Gemelli”, Catholic University of the Sacred HeartRomeItaly
  3. 3.Pediatric Intensive Care Unit, Department of Anaesthesiology and Intensive CareUniversity Hospital “A. Gemelli”, Catholic University of the Sacred HeartRomeItaly

Personalised recommendations