Synthesis, storage, and release of alveolar surfactant lipids and proteins occur within the type II pneumocytes (Figure 3). Synthesis and processing starts within the endoplasmic reticulum and Golgi where the phospholipids and some of the surfactant proteins are combined (2). The components are packaged into vesicles, which progress from immature forms to mature tightly packed lamellar bodies. The lamellar bodies are a characteristic microscopic finding of type II cells, and serve as the site of surfactant storage. Release of surfactant results from fusion and exocytosis of the lamellar bodies with the alveolar surface membrane. Surfactant release is triggered by numerous physiologic and pharmacologic stimuli including deep inspiratory effort, which may serve to explain, in part, the importance of sighs in normal respiration (3). After secretion, surfactant components mix with the subphase of the alveolar lining fluid forming highly organized arrays called tubular myelin, and ultimately adsorb with the existing monolayer at the air-liquid interface. Although it was once believed that the surfactant film existed only as a monolayer, newer fixation techniques have clarified that alveolar surfactant forms bi- and multilayers that are presumed to change dynamically during each respiratory cycle (4). After repetitive use or injury, surfactant lipids and proteins undergo reuptake and recycling via multivesicular bodies for eventual rerelease into the alveolus. This process is principally performed within the type II pneumocyte, although the alveolar macrophages and type I pneumocytes may also contribute.
PC is the most abundant individual phospholipid, making up approximately 80% of the total phospholipid pool. This feature of surfactant is unique, and serves to differentiate surfactant phospholipid pools from the typical phospholipid composition of cell membranes. PC plays a critical role in the structure of the air-liquid monolayer predominantly through its highly saturated di-palmitoyl (16:0,16:0) PC fraction (DPPC). The rigidity of DPPC is key to the ability of surfactant to pack tightly during maximum compression (exhalation), and allow surface tension to approach extremely low levels (approximately 0 mN/m). DPPC also performs a structural role through binding to surfactant protein A (SP-A). However, DPPC does not provide a complete surfactant. DPPC does not readily adsorb to the air liquid interface after exocytosis from the type II pneumocyte nor does it rapidly reexpand (inhalation) after maximum compression of the film. The other lipids and proteins provide those functions.
Phosphatidylglycerol (PG) is the second most abundant phospholipid (10%), and plays an important role in the adsorption and reexpansion of the film. This effect of PG, an anionic phospholipid, is the result of its close interaction with surfactant protein B (SP-B), a hydrophobic surfactant apoprotein, which is critical in adsorption and reexpansion (5). Phosphatidylinositol (PI) is also anionic, and may mimic the action of PG. Although PI typically makes up a small percentage of surfactant phospholipid (2%–5%), PI levels may increase and maintain surfactant function in states of PG deficiency. PI also serves as the principal phospholipid to which surfactant protein D (SP-D) binds.
The predominant neutral lipid in surfactant is cholesterol (Figure 1). The typical role of cholesterol in membranes is to maintain fluidity at body temperature by lowering the phase transition temperature. In surfactant, the phase transition temperature of DPPC is 41°C, which means that at temperatures less than 41°C, DPPC alone would tend to form a gel. The unsaturated fatty acids present on some phospholipid subtypes also contribute to phase transition temperature of the film. In surfactant, neutral lipids also play an important role in adsorption and remixing of the phospholipid monolayer on reexpansion (inhalation) along with PG and the proteins.
The most characterized components of surfactant are the proteins (Figure 1). These are generally classified into two subgroups, hydrophobic and hydrophilic, based on their characteristics during lipid extraction. The hydrophilic proteins (SP-A, SP-D) are water soluble, partition into the aqueous phase during extraction, and are removed. In contrast, the hydrophobic proteins (SP-B, SP-C) are tightly bound to the phospholipid, and are retained with the phospholipids in the organic fraction during extraction.
The hydrophobic proteins, are small (SP-B ∼8 kDa, SP-C ∼4 kDa), and serve primarily to enhance surface tension lowering activity, and maintain the structure of the monolayer (6). SP-B is more essential than SP-C, despite the fact that SP-C is more abundant in molar concentration and that the combined presence of SP-B and SP-C results in significantly better function. SP-B knockout mice do not survive ex utero and SP-B deficiency in newborns is a lethal mutation, whereas states of SP-C deficiency are not as functionally significant(7).
The role of the hydrophilic proteins in surface tension lowering activity is less than the hydrophobic proteins, but optimal activity only occurs in the presence of SP-A. SP-A is the most abundant surfactant protein and has marked structural similarities to collagen. Its effects on surface function are through a direct interaction with SP-B, and its specific role in promoting the formation of tubular myelin in the subphase. The principal roles of SP-A and SP-D are in host defense. Each of the hydrophilic proteins has multiple carbohydrate recognition domains that can bind pathogens (bacteria, fungi, and mycobacteria) and airway particulate (2). SP-A and SP-D are recognized by host immune cells, such as alveolar macrophages, and promote the inflammatory response. The combination of collagen-like domains and globular carbohydrate recognition domains regions makes both SP-A and SP-D members of a family of proteins known as collectins.
A surfactant is defined as a substance that is “surface active” or that lowers interfacial tension. Tension exists at an air liquid interface as a result of unopposed attractive forces in the liquid molecules at the surface. All liquid molecules contain attractive forces, and when surrounded by other liquid molecules, the forces are equalized. However, gas molecules present at the liquid’s surface have little attraction for the liquid molecules. As a result, the imbalance of forces in those liquid molecules at the surface leads to the surface drawing inward. This principal is best exemplified by Neergard’s landmark experiment, performed more than 70 years ago, which examined the differences in pressure-volume relationships of excised lungs filled separately with air and liquid (8). Lungs filled with air require a significant level of pressure before a critical “opening pressure” is achieved and inflation begins. During deflation, gas-filled lungs exhibit a very different pressure-volume relationship than on inflation, with volume being maintained at much lower pressures than during inflation, a phenomenon known as hysteresis. In contrast, lungs filled with liquid require no opening pressure, and the inflation and deflation pressure-volume curves are superimposable. These differences are explained by the absence of an air-liquid interface in the liquid-filled lungs.
A second key principal is that surface tension within all alveoli cannot be equal. Using the LaPlace equation for a sphere (P = 2γ/r), the pressure (P) at which alveoli are patent can be measured. If the surface tension in all alveoli (γ) were equal, smaller alveoli (smaller radius, r) would have higher pressures, and would collapse into larger alveoli. To maintain the patency of the greatest proportion of alveoli, surfactant adjusts γ to maintain a constant P across different alveoli, and as a result prevent atelectasis and collapse. At equilibrium, pulmonary surfactant maintains a γ of approximately 25 mN/m (1,5). In vitro studies demonstrate that between a 10% to 25% reduction in surface area is required to lower γ to ∼2 mN/m. Similarly, in situ studies using intact lungs estimate γ = 30 mN/m at total lung capacity (TLC) and 1 mN/m at functional residual capacity.
The complex composition and structural arrangements of pulmonary surfactant described earlier are required to achieve these biophysical goals. The surface forces of the alveolar subphase are balanced by the insertion of the polar phospholipid head groups whereas the hydrophobic fatty acid side chains orient toward the alveolar lumen (see Figure 3). At maximum surface compression, the DPPC molecules provide sufficient rigidity to allow γ to approach zero without collapse of the film. To attain a DPPC-rich monolayer at maximum compression, other lipids such as PG are “squeezed” out into surface-active reservoirs or multilayers (6). The hydrophobic proteins (SP-B, SP-C), cholesterol, and calcium, play important roles in the process of squeezing out, and subsequent respreading during inspiration. Several methods to measure the surface tension of pulmonary surfactants have been developed (Langmuir-Wilhelmy balance, bubble surfactometers), but none are currently used for clinical purposes.
Lowering γ has more effects on the alveolus than maintaining its patency. Low γ also decreases the hydrostatic driving force for fluid movement from the alveolar interstitium to the alveolus (9). Loss of surfactant leads to pulmonary edema, drying of the interstitium and decreased pulmonary lymphatic and venous flow.
The role of surfactant is not limited to the alveolus. Thirty years ago, Macklem and colleagues first suggested that surfactant prevents collapse of terminal bronchioles (10). More recently, novel models by Enhorning (capillary surfactometer and murine conducting airways) have supported the importance of airway surfactant in maintaining patency in the conducting airways (11). In the presence of an air-liquid interface, the absence of surfactant requires a greater degree of pressure to achieve airflow and more rapid reaccumulation of a liquid column. The findings from these models have been supported by observations of surfactant abnormalities in a variety of diseases characterized by airflow obstruction. These clinical observations will be discussed in more detail below.
Surfactant also contributes to the mucociliary clearance mechanisms of the airways (12). Using electron microscopy, a surfactant layer has been demonstrated within the largest airways including trachea and main stem bronchi. This function is important for clearance of airway mucous and clearance of airway particulates. Although the origins and synthesis of airway surfactant are not fully understood, it appears that at least in part, it arises from alveolar surfactant pools which are extruded from the alveolus during exhalation and then proximally migrate through the airways via the mucociliary ladder.
Beyond its biophysical roles, pulmonary surfactant also plays a critical role in host defense. Extensive basic and clinical investigation including mice knockout models have demonstrated that abnormalities in SP-A and SP-D result in a significantly greater risk of developing lower respiratory tract infections from a variety of pathogens (13). The development of recombinant forms of SP-A and SP-D as future therapeutic interventions in numerous respiratory infectious diseases is an exciting area of ongoing research.
SURFACTANT DEFICIENCY STATES
Only pulmonary alveolar proteinosis (PAP), an uncommon disorder, is characterized by an excess of pulmonary surfactant. Very interesting recent studies have significantly enhanced our understanding of PAP, including the role of granulocyte-macrophage colony-stimulating factor in regulation of surfactant secretion, and as a potential therapeutic intervention in adult PAP (14). However, the additional details regarding PAP will not be examined herein to allow focus on the more common and numerous disease states characterized by surfactant deficiency.
Respiratory Distress Syndrome
The link between surfactant deficiency and the death of premature newborns from hyaline membrane disease or neonatal respiratory distress syndrome (RDS) was established more than 40 years ago by Avery and Mead (15). The principal mechanism of RDS in newborns of 30 weeks gestation or less is developmental immaturity of the lung, which results in inadequate production of both phospholipids and proteins. A low ratio of lecithin (another term used for PC) to sphingomyelin (L/S ratio) serves as a crude indicator of lung maturity, and is used on analysis of amniotic fluid by clinicians to guide decisions regarding labor in preterm mothers. More complete analysis of lavage fluid from premature newborns reveals increased γ, decreased levels of protein (SP-A, SP-B, SP-C) and decreased phospholipids (particularly PG) (16). Consequently, surfactant replacement in neonatal RDS serves as a primary therapeutic intervention by replacing a true deficiency, which will correct once the premature newborn has sufficient time for growth and development.
The RDS of term newborns, children, and adults is both similar to and quite different from neonatal RDS. The abnormalities of surfactant in RDS and acute respiratory distress syndrome (ARDS) are quite similar, and are again notable for increased γ, reduced levels of phospholipid (PC and PG), and reduced surfactant-associated protein (17). However, a critical difference in the nonpremature patient is the presence of an extensive inflammatory exudate within the lungs, which results from damage to and leak across the alveolar-capillary barrier. This damage is typically driven by an inflammatory response, which is triggered by processes such as septic shock, severe trauma or pancreatitis. This inflammatory process serves as the mechanism for surfactant deficiency by: 1) directly damaging the available alveolar surfactant, 2) directly damaging the type II pneumocytes required for new surfactant synthesis, recycling, and release, and 3) leak of inhibitors of surfactant function into the alveolus. The list of surfactant inhibitors is extensive including proteins (e.g., albumin, fibrinogen, collagen, hemoglobin), which interfere with the air-liquid interface, lipid mediators (e.g., lysophospholipids, cell membranes), and enzymes That can directly damage the surfactant phospholipids (e.g., phospholipases) and proteins (e.g., oxidants, proteases). In these settings, surfactant deficiency is a secondary abnormality, and consequently, the effect of surfactant replacement therapy is less sustained because the exogenous surfactant will be damaged and inhibited should the inflammatory process persist.
Obstructive Lung Diseases
Since Enhorning’s observations in experimental airway models, attention toward and recognition of the potential role of surfactant injury in the conducting airways of patients with obstructive lung diseases has increased dramatically. These diseases include asthma, chronic bronchitis, cystic fibrosis, and bronchiolitis.
Several groups of investigators, including our group, have reported the presence of significant surfactant dysfunction in stable asthmatics who undergo endobronchial antigen challenge and in exercise-induced asthma (18). Analysis of bronchoalveolar lavage (BAL) fluid after challenge reveals increased γ and an inability to maintain patency of an air-fluid level in the capillary surfactometer. Similarly, the surface activity of sputum from asthmatics suffering from an acute exacerbation is reduced. Significant increases in airway protein and eosinophils are seen in BAL after endobronchial challenge, and investigators have attributed the surfactant functional changes to elevated protein levels. In contrast, our studies have identified reduced levels of PG and increased hydrolysis of PG by secretory phospholipases in asthmatics who develop dysfunctional surfactant after endobronchial antigen challenge (19). Furthermore, the functional abnormalities most closely correlate with the decrease in than the increase in either protein or eosinophils.
Airway dysfunction in chronic bronchitis may also be influenced by abnormalities in surfactant. Although little direct evidence is available regarding defined surfactant abnormalities in patients with chronic bronchitis, substantial evidence exists on the impact of cigarette smoking, the most common risk factor for patients with chronic bronchitis. Studies of surfactant function using ex vivo exposure of surfactant to cigarette smoke or comparisons of BAL from nonsmokers, asymptomatic smokers, and smokers with chronic obstructive pulmonary disease consistently reveal reduced surface activity. Recent studies demonstrated that the ’tar’ component of cigarette smoke inhibits surface activity (20). Speculation concerning surfactant’s importance in chronic bronchitis is furthered by the abnormalities in mucociliary clearance in these patients.
Evidence of surfactant dysfunction in the obstructive physiology of cystic fibrosis (CF) is difficult to separate from the effects of the superimposed infectious processes of that disease, and will be discussed below. Implications of a role for surfactant in the pathophysiology of bronchiolitis stem from findings in infants with respiratory syncytial virus and patients post lung transplantation with varying degrees of infection and rejection. These studies remain preliminary, and are inconclusive.
Interpretation of surfactant changes in respiratory infections is extremely complex. Changes identified with BAL studies or in animal models cannot clearly distinguish the direct effects of infection on surfactant versus responses of surfactant to infection as a part of host defense. Abnormalities in surface activity have been reported in several human diseases ranging from ventilator-associated pneumonia to interstitial pneumonia. Changes in phospholipid composition and protein content also occur, including reduced PG and SP-A. Characterization of surfactant changes from infection is most complete for Pneumocystis carinii pneumonia (PCP) in patients with human immunodeficiency virus (HIV). Phospholipid levels are severely reduced, with predominantly a loss in PC while maintaining PG levels. SP-A protein levels are more variable, and are often increased, which may reflect the role of SP-A in pathogen recognition or altered protein synthesis as a consequence of HIV infection.
In children with CF, functional abnormalities in surfactant appear to more closely correspond to the presence or absence of ongoing infection (21). In an animal model of pneumonia from Pseudomonas aeruginosa, a frequent pathogen in CF patients, total surfactant pool sizes and SP-A levels were decreased. In contrast, as CF patients become older and exhibit more chronic airway changes, surfactant dysfunction and reduced levels of phospholipid and proteins can be demonstrated.
Studies of BAL from patients with idiopathic pulmonary fibrosis (IPF) are significant for reduced levels of total phospholipid (particularly PG) and reduced levels of the hydrophilic proteins (SP-A, SP-D) (22). Interestingly, SP-A levels and SP-D levels in the serum of IPF patients are markedly increased, and may ultimately prove to be useful clinical biomarkers of disease activity. The mechanisms to explain these contrasting results in SP-A levels between BAL and serum are not fully understood, although leak of alveolar SP-A into the serum has been suggested. Likewise, the functional implication of reduced surfactant components in BAL from IPF patients is also poorly understood. In animals with bleomycin-induced pulmonary fibrosis, neutral lipid content is altered, which may play an important role in altered lung compliance. In other conditions that are clinically similar to IPF, such as sarcoidosis or asbestosis, similar derangements in surfactant have been evaluated, but do not appear to be present.
SURFACTANT REPLACEMENT THERAPY
Exogenous surfactants have been available for more than two decades. The extensive basic research outlined has fueled rapidly progressing clinical applications in a variety of diseases. Appropriate interpretation of this information requires an understanding of the available preparations, delivery methods utilized, delivered dose, and the disease setting in which therapy was attempted.
The compositions of several surfactant preparations are summarized in Table 1. Although not an extensive list, these preparations are commonly utilized in the United States or are currently undergoing large clinical trials. Important differences distinguish each preparation, and these differences must be considered during interpretation of the results from any trial utilizing one or more of the compounds.
The most important difference in exogenous surfactants is to distinguish natural from synthetic surfactants. Natural surfactants are derived from lung lavage or lung extracts from large animals, typically bovine or porcine. These samples undergo extensive extraction and purification steps, and addition of supplemental compounds frequently is required to achieve optimum surface tension lowering activity. In all instances, extraction of natural surfactants leads to complete loss of the hydrophilic proteins (SP-A and SP-D). Synthetic surfactants are not derived from animals and are completely generated from the mixing of phospholipid, protein (not all) and supplemental compounds to provide surface activity.
Survanta (Beractant; Abbott-Ross Laboratories, Columbus, OH), also known as Surfactant TA in some countries outside the United States, was the first available natural surfactant for large-scale clinical trials in the United States. It is an extract of bovine lung, and undergoes a more extensive extraction process as compared to other natural surfactants, which results in important differences. Survanta is relatively deficient in PG and cholesterol, and very low levels of SP-B despite an approximately normal amount of SP-C. Curosurf (Poractant; Dey; Darmstadt, Germany) is a porcine-derived natural surfactant, and is the most extensively studied and utilized natural surfactant in Europe. It was only recently approved for use in the United States. Curosurf retains a more complete surfactant composition including PG, cholesterol, and hydrophobic proteins, and requires the addition of fewer supplements than Survanta. Infasurf [Calf lung surfactant extract (CLSE); Ony-Forest, Amherst, NY] is a bovine-derived natural surfactant, which has a more complete composition similar to Curosurf. The levels of hydrophobic proteins in Infasurf are the highest of any natural surfactant and closely approximate the levels of SP-B and SP-C seen in endogenous surfactant.
Exosurf (Glaxo Wellcome, Research Triangle Park, NC) was the first available synthetic surfactant. Its composition consists of DPPC, hexadecanol (an alcohol which promotes spreading), and tyloxapol (a nonionic surfactant that promotes dispersion), which makes Exosurf the most unnatural of exogenous surfactant mixtures. The absence of protein and PG in Exosurf are major disadvantages of this compound. Although utilized extensively in neonatal intensive care units earlier this decade, use of Exosurf has been reduced due to the superiority of the natural surfactants.
Recently, two new synthetic surfactants have been reported in clinical testing. The phospholipid fractions are similar in both preparations with fixed ratios of DPPC, PG, and free palmitic acid. Each has attempted to correct the protein deficiency of Exosurf, but use very different and novel approaches. Venticute (rSP-C surfactant; Byk Gulden, Konstanz, Germany) includes human recombinant SP-C with two amino acid substitutions. Surfaxin (KL4-Surfactant; Discovery Laboratories, Doylestown, PA) includes a synthetic peptide analog of SP-B, which consists of repeating sequences of leucine (L) and lysine (K) in a 4:1 ratio. Each demonstrates good surface activity using in vitro methods and animal models of neonatal RDS and ARDS.
On first glance, the need for synthetic surfactants given the presence of effective natural compounds might not be evident. However, the cost of natural surfactants is high, ranging from $350 to $700 per kilogram of body weight (23). This cost is easily afforded and justified in the setting of neonatal RDS, where proven benefit is high and body weights are low, typically ranging between 0.75 and 2.0 kg. However, cost becomes substantial as body size increases and can exceed $20,000 to 30,000 per dose in normal-sized adults (approximately 70 kg). This figure is further amplified when consideration of greater requirements for multiple dosing in adults is included in the calculations. In addition, some question the ability of industry to produce sufficient quantities of natural surfactants for the adult clinical markets from animal sources, and the potential risk for transmission of slow viruses from infected livestock.
Dosing is typically based on the quantity of phospholipid per body weight. The only disease, which has been studied sufficiently to make reasonable estimates of dosing requirement, is neonatal RDS. The typical quantity of phospholipid delivered per dose is 100 mg/kg (24), and typical dosing patterns lead to 50% to 75% of patients receiving three or more doses. A recently successful trial in pediatric ARDS using Infasurf utilized a dosing regimen of 2800 mg/m2 (25).
Route of Delivery
The optimal route of delivery remains controversial. Different methods include bolus intratracheal administration via an endotracheal tube, aerosolization, and bronchoscopic administration with or without dilute surfactant lavage to remove inflammatory mediators and inhibitors. At this time, dosing is typically bolus administration due to its relative ease, improved drug delivery into poorly ventilated dependent lung zones for ARDS, and the lack of proven superiority of other methods.
Almost 30 years after Avery and Mead’s report, the first successful large-scale, multicenter, randomized, double-blind trial of surfactant replacement in therapy with neonatal RDS was reported by Fujiwara and colleagues (24). Using a single dose of Surfactant TA, outcome benefits included acute reduction in the severity of RDS over the initial 48 hours post treatment, and reduced risk of barotrauma, bronchopulmonary dysplasia, and intracranial hemorrhage. Although the Fujiwara trial was not sufficiently sized to demonstrate a benefit in mortality, subsequent trials have confirmed it. Consequently, surfactant replacement therapy for the prevention and treatment of RDS in premature newborns is a firmly established standard of care in the field of neonatology, and represents one of the landmark therapeutic interventions in modern medicine.
More recent trials in neonatal RDS have directly compared surfactant preparations. Similar to experiments performed in premature newborn lambs earlier this decade, surfactants with the most protein demonstrate therapeutic superiority to Exosurf, the initial synthetic surfactant, and Survanta, the bovine surfactant relatively deficient in SP-B (26).
Although initial surfactant trials in adult ARDS earlier this decade were often discouraging, more recent trials have been more successful. A key reason for the slower progress in adults has been the lack of a large affordable supply of surfactant with which to perform sufficient trials. One large scale, multicenter, randomized trial was conducted using aerosolized Exosurf, but showed no difference in mortality, oxygenation, or requirements for mechanical ventilation in the treated group (27). The failure of the Exosurf trial cast significant doubt toward the future of surfactant therapy in ARDS for many investigators, but its failure may have been more dependent on its design than a failure in the concept of surfactant therapy in ARDS. The compositional deficiencies of Exosurf, including the complete lack of protein and PG, and the choice of aerosolization was suboptimal. Models Using the nebulizers utilized in the Exosurf trial reveal that less than 10% of phospholipid is delivered to the distal lungs. Furthermore, in ARDS, aerosolization leads to preferential delivery of drug to well ventilated lung units while direct instillation promotes better delivery and spreading to the most dependent and injured lung units through gravitational forces.
Fortunately, a subsequent smaller ARDS trial using direct installation of Survanta demonstrated significant improvements in oxygenation and a trend toward improved mortality (28). More recently, a pediatric ARDS trial using installation of Infasurf demonstrated improvements in oxygenation and reductions in days requiring mechanical ventilation and ICU days (25). The success of the Survanta and Infasurf trials suggest that surfactant therapy in ARDS will be ultimately effective, although its use will be limited by the high cost of natural surfactants and the cost of the large trials needed to achieve FDA approval. However, preliminary reports of the new synthetic surfactants, Venticute (Phase II) and Surfaxin (Phase I), have confirmed their safety and demonstrated improvements in mortality and requirements for mechanical ventilation (29,30). Larger Phase II and Phase III studies are currently ongoing.
For obstructive lung diseases, less data regarding the effectiveness of replacement therapy are available than for RDS. In asthma, small trials in patients with acute exacerbations have demonstrated modest acute improvements in spirometry after nebulization of Survanta (31). These intriguing data are insufficient to change current management of asthmatics, except possibly those with life-threatening status asthmaticus. Larger trials with closer attention to dosing and route of delivery are warranted. They should focus on the potential benefits of surfactant therapy in reducing rates of hospitalization in acute exacerbations, and simpler methods of drug delivery, including adaptation to inhalers. In stable patients with chronic bronchitis, Anzueto and colleagues reported improvements in spirometry and mucociliary clearance over a 3-week period after three doses of nebulized Exosurf (32). In severe bronchiolitis, intratracheal administration of Curosurf reduced time on mechanical ventilation and ICU stay.
In lung transplantation, trials of surfactant therapy have focused on potential benefits with prolonged graft survival post harvest, and reduced complications post transplantation including rejection.
Although far more information can be provided on the importance of surfactant in adult respiratory diseases than can be discussed within this brief review, it has hopefully served to provide a brief insight into this rapidly advancing field. Recent investigations have broadened our view of the many roles pulmonary surfactant plays in maintaining lung function, and in so doing has broadened our view of its potential therapeutic implications (Figure 4). This broader view is also brighter with the success of recent surfactant replacement trials in ARDS and neonatal RDS.
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Keywords:© 2002 Lippincott Williams & Wilkins, Inc.
Surfactant; Inflammation; ARDS; Obstructive lung disease; Replacement therapy