The Physiological Significance of a Dysfunctional Lung Surfactant

Abstract

I. Introduction 359II. Physiological Function of Pulmonary Surfactant 360III. Surfactant Composition 362IV. Surfactant Metabolism 363V. Acute Lung Injury 363VI. Alterations of Surfactant During ALI 365VII. Mechanisms by Which Alterations of Surfactant Occur 366VIII. Mechanisms by Which Alterations of SurfactantLead to a Loss in Function 368IX. Exogenous Surfactant Administration in ALI 368X. Conclusions and Future Directions 371Acknowledgments 372References 372I. IntroductionPulmonary surfactant is essential for normal lung function (1). This physiologicalimportance is obvious from the observed lung dysfunction in premature babiesdeficient in lung surfactant and the subsequent improvement in lung function fol-lowing exogenous surfactant supplementation (2,3). In fact, the clinical term forlung impairment in premature neonates due to surfactant deficiency is neonatalrespiratory distress syndrome (NRDS). The association of surfactant deficiencywith this clinical syndrome has been the main rationale for the extensivestudies on various aspects of the pulmonary surfactant system over the last 40years (4,5). However, surfactant deficiency is not the only clinical situation inwhich the pulmonary surfactant contributes to physiological abnormalities.Several clinical conditions have been associated with alterations of the pulmon-ary surfactant system including acute lung injury (ALI) (6,7). In this chapter, wewill focus on the role of surfactant in the development and treatment of ALI.First, we will briefly review the pulmonary surfactant system and ALI. Thiswill be followed by a description of the alterations of surfactant in ALI. Therest of the chapters will then focus on the consequences of surfactant impairmentin ALI, the mechanisms by which surfactant impairment occurs, and the potentialof surfactant therapy for ALI. These discussions will be presented from a broadphysiological-biochemical perspective. For further details on specific aspects,the reader will be referred to a number of recent review articles as well asother chapters in the current volume.