Pulmonary Surfactant

Biochemical, Functional, Regulatory, and Clinical Concepts

Jacques R. Bourbon

• Publisher: CRC Press
• Year: 2019
• ISBN:
  9781000722475
• Edition: 1
• Topic: Medicine
• Subtopic: Medical Theory, Practice & Reference

This book represents a comprehensive update on pulmonary surfactant by merging classical knowledge with new information. Topics include surfactant secretion and alveolar processing and recycling; physical bases and different theoretical models of the physiological mechanism for pulmonary surfactant action; recent findings on surfactant-like material in other organs; developmental processes and multifactorial regulation; etiology and physiopathology of neonatal respiratory distress; and modern methods for functional explorations of the lung in neonates and experimental models in animals. The book also contains a discussion on the management of hyaline membrane disease, from both the experimental and clinical points of view.

Chapter 1

PULMONARY SURFACTANT — AN OVERVIEW

Jacques R. Bourbon

TABLE OF CONTENTS

I.	Introduction: The Need for a Synthesis
II.	Historical Perspective
III.	Physiological Roles of Pulmonary Surfactant A. Surfactant and Pulmonary Mechanics B. Role in Alveolar Fluid Homeostasis C. Role in Lung Permeability D. Role in Defense Mechanisms 1. Physical-Chemical Protective Effects 2. Relationships with Immunomechanisms a. Proper Antibacterial Activity b. Interaction with Alveolar Macrophages c. Interaction with Lymphocytes
IV.	Current Trends

References

I. INTRODUCTION: THE NEED FOR A SYNTHESIS

Pulmonary surfactant is a complex of lipids — principally phospholipids — proteins, and carbohydrates which line the surface of lung alveoli and respiratory bronchioles. Its functions appear to be multiple (see Section III below), but its principal role, the one which has led to its discovery, is related to lung mechanics and alveolar stability. The importance of its functional significance is illustrated by the fact that surfactant deficiency, the major cause of which is lung immaturity in the prematurely delivered newborn, leads to neonatal respiratory distress syndrome (RDS), otherwise designated hyaline membrane disease (HMD). The latter represents in developed countries the first cause of neonatal mortality and morbidity.¹ Although not presenting as an initial cause, but rather as a secondary aggravating factor, surfactant deficiency is also involved in the pathogenesis of adult respiratory distress syndrome.²

As stated in the following section, pulmonary surfactant has been a fast-evolving topic recently. The recently gained data, the new questions which have arisen, and the new perspectives offered by modern methods of investigations and novel therapeutical approaches certainly call for a synthesis. Such an attempt at a comprehensive view of the present state of the topic is the objective of this book. Without doubt, growing knowledge about surfactant will require other updates in the future.

This book does not pretend to be exhaustive. It tries nevertheless to take into account most of the various aspects of the topic. Some aspects are considered, at least briefly, in several chapters, due to the fact that each chapter has been conceived so that it can be read independently from the others. A major part is devoted to basic research, but the last chapters establish the link with the clinical aspects that the practitioner has to face. In a first step, the characteristic features and properties of the surfactant-producing cell, alveolar type II epithelial cell or type II pneumocyte, are analyzed in detail. The next chapters describe the composition of surfactant, the role of its lipid and protein components, their biosynthetic pathways, processing, and regulation. The examination of the comparative aspects of pulmonary surfactant allows one to point out its early appearance and strong conservation in evolution. Dynamic aspects, i.e., secretion, alveolar processing and recycling of surfactant material, and their regulation, are then considered. A critical appraisal of the physiological bases for the surfactant mechanism of action is presented next, along with an examination of the presence of surfactants in other organs, which brings insights as to the general significance of surfactants as lining layers of interfacial structures in the organism. Since surfactant, as stated above, is particularly important in the perinatal period, maturational aspects of the surfactant system are given particular emphasis in the next chapters, including hormonal regulation, an aspect which has received considerable attention during the last 20 years. Three chapters are especially devoted to the clinical aspects of surfactant with analysis of etiology of RDS, its functional exploration in the neonate and in animal models, the assessment of lung maturity through biochemical and biophysical methods, and the promising prospect of surfactant-replacement therapy for the care of neonates with RDS.

II. HISTORICAL PERSPECTIVE

It is customary to begin a scientific monograph by the recall of its historical aspects. In the particular instance of pulmonary surfactant, this presents a special interest for at least two reasons. Firstly, the discovery by von Neergaard³ of the role played by surface forces in the alveoli is a typical example of “premature discovery”.⁴ Secondly, the knowledge relative to surfactant has increased considerably in recent years; recent observations and questioning about classical concepts have led to renewed appraisal of the topic. Since excellent, extensive surveys of the history of surfactant research are available,^4,5,6,7 the present analysis is limited to the major steps which stand out as landmarks in this history.

Neergaard’s pioneer work appeared in 1929. A congress held in 1989 could accordingly be named “60 Years of Surfactant Research.” The first half of this period has, however, been quite different from the last 30 years since the work by von Neergaard was ignored by the scientific community for 25 years. The model he had conceived should have led to the search for a biological substance with surface properties, present in the pulmonary alveolus. Neither Neergaard nor other investigators pursued this matter. It was only during the 1950s that the concept of alveolar surface-active material was rediscovered and that the material itself was evidenced with the works by Radford, ⁸ Pattle, ⁹ and Clements.¹⁰

Until 1959, the research was essentially basic in nature and directed toward the biophysical aspects of surfactant. The discovery (and rediscovery) of surfactant dealt mostly with the problem of surface tension at the alveolar surface assimilated to a spherical air-water interface and with the role of surfactant in alveolar stability. Pulmonary surface-active material was accordingly referred to by Clements et al. as an antiatelectasis factor.^10,11,12 By contrast, Pattle stressed the antipulmonary edema properties of surface-active material.⁹

The year 1959, just 30 years after the initial publication, opened a new era in surfactant research with the demonstration by Avery and Mead¹³ of pulmonary-surfactant deficiency in infants succumbing to HMD. The convergence between this practical clinical problem and the previous biophysical studies led to considerable interest in surfactant and initiated the tremendous growth of research carried out in the field which has been seen subsequently and has characterized the second half of the 60 years. The chemical composition of surfactant, the role of the different lipid components (see Chapter 3), and the biochemical maturation of the lung in the course of fetal development (see Chapter 10) have received particular attention.

The identification of phosphatidylcholine as the major surfactant component^14,15 was made in 1961. Formerly, the prevailing view held that the surface layer was a mucoprotein.⁷ The following 20 years were mostly devoted to the study of the lipid moiety of surfactant. Between 1962 and 1967, the timing of appearance of surfactant phospholipids during late gestation was described in various mammalian species.^16,17,18,19 The years 1969 to 1971 were marked by important discoveries with considerable clinical implications. On the one hand, it was found in 1969 that prenatal administration of glucocorticoids to the fetal lamb accelerated lung functional maturity.²⁰ It was soon demonstrated that this acceleration was related to precocious appearance of surfactant in fetal lung.²¹ On the other hand, the discovery of the predictability of amniotic fluid lecithin/sphingomyelin ratios²² allowed a prenatal assessment of lung maturity (see Chapter 12). This permitted the prevention of RDS in at-risk pregnancies, principally through prevention of premature delivery. Another important practical step was the discovery that phosphatidylglycerol could also be used as a biochemical marker of surfactant maturity.²³ The period was still characterized by considerable improvement in the care of neonates with RDS through aggressive mechanical ventilation^24,25 with continuous positive airway pressure.²⁶ In parallel, the intimate mechanisms of surfactant phospholipid biosynthesis were elucidated with special attention paid to the peculiarities of the alveolar type II pneumocyte, as compared with other tissues (see Chapter 3). Two important steps in this regard were represented by the definitive demonstration by electron microscopic autoradiography of the role of type II pneumocytes as the unique source of pulmonary surfactant with issues as to the role of various subcellular organelles,²⁷ and the recognition that lung phosphatidylcholine biosynthesis proceeded primarily de novo through the cytidine diphosphocholine pathway.²⁸ Simultaneously, the first indication of recycling and reutilization of alveolar surfactant material was reported through the observatio...