Surfactant alteration and replacement in acute respiratory distress syndrome

Abstract

The acute respiratory distress syndrome (ARDS) is a frequent, life-threatening disease in which a marked increase in alveolar surface tension has been repeatedly observed. It is caused by factors including a lack of surface-active compounds, changes in the phospholipid, fatty acid, neutral lipid, and surfactant apoprotein composition, imbalance of the extracellular surfactant subtype distribution, inhibition of surfactant function by plasma protein leakage, incorporation of surfactant phospholipids and apoproteins into polymerizing fibrin, and damage/inhibition of surfactant compounds by inflammatory mediators. There is now good evidence that these surfactant abnormalities promote alveolar instability and collapse and, consequently, loss of compliance and the profound gas exchange abnormalities seen in ARDS. An acute improvement of gas exchange properties together with a far-reaching restoration of surfactant properties was encountered in recently performed pilot studies. Here we summarize what is known about the kind and severity of surfactant changes occurring in ARDS, the contribution of these changes to lung failure, and the role of surfactant administration for therapy of ARDS.

Supplementary Figure 1

Schematic illustration of trigger mechanisms leading to acute respiratory distress syndrome (ARDS). Four key pathophysiological and clinical findings are encountered in ARDS: firstly, noxious agents may attack the alveolar compartment directly or hit the lung via the intravascular compartment (indirect, classical ARDS). Secondly, during the early exudative phase, a self-perpetuating inflammatory process involves the entire gas exchange unit leading to type II cell injury, loss of epithelial (and endothelial) integrity, alveolar edema formation, and severe impairment of surfactant function. Thirdly, as a result a ventilation-perfusion mismatch with extensive shunt flow is observed. Fourthly, aggravating complications including new inflammatory events, such as recurrent or persistent sepsis, or acquisition of secondary (nosocomial) pneumonia may repetitively worsen the state of lung function and then progressively favour proliferative processes characterized by mesenchymal cell activation and ongoing lung fibrosis. infl., inflammatory, interst., interstitial.

Figure 2

Biophysical surfactant properties of isolated large surfactant aggregates from healthy volunteers (Control) and patients with cardiogenic lung edema (CLE), ARDS (with extrapulmonary trigger), severe pneumonia necessitating mechanical ventilation (PNEU), or ARDS and lung infection (ARDS + PNEU). Surface tension [mN/m] at minimum bubble size after 5 min of film oscillation (γ min) is given (pulsating bubble surfactometer, at 2 mg/ml phospholipid). Single events (circles), means (triangles), and medians (squares) are indicated. ^***(P < 0.001). From [26], with permission.

Supplementary Figure 3

Diagram of changes in the surfactant subtype distribution in acute respiratory distress syndrome (ARDS). Under physiological conditions, some 80–90% of the extracellular surfactant material is in the large surfactant aggregate fraction, which has a high surfactant apoprotein B (SP-B) content and excellent surface activity (γmin; = minimum surface tension after 5 min of film oscillation). In inflammatory lung disease (as in severe pneumonia or ARDS), the small surfactant aggregates increase as SP-B and surface activity within the large-aggregate fraction decrease.

Figure 4

Diagram representing inhibition of pulmonary surfactant by fibrin formation and concept of collapse induration. Under physiological conditions the phospholipid lining layer at the air–water interface reduces the surface tension and thereby promotes lung expansion upon inspiration and prevents lung collapse during expiration. In inflammatory diseases (such as ARDS, severe pneumonia) fibrinogen, leaking into the alveolus, is converted into fibrin due to a pronounced procoagulatory actvity in the alveolar compartment. Surfactant function is greatly inhibited by incorporation of hydrophobic surfactant components (PL, SP-B/C) into polymerizing fibrin. Persistence of this 'specialized' fibrin matrix promotes fibroprolifertive processes ('collapse induration'), whereas a complete lysis results in the liberation of intact surfactant material with re-opening of formerly collapsed alveoli.

Figure 5

Time course of the PaO₂/FiO₂ ratio in 10 patients with ARDS upon transbronchial application of 300 and 200 mg/kg body weight of a surfactant extract from calf lung. ^***P < 0.001, as compared with baseline value. From [68], with permission.

Figure 6

Example of the course of PaO₂ in response to transbronchial surfactant application in an 18-year-old female with severe sepsis-induced ARDS. The original on-line recording of the PaO₂ at a constant FiO₂ of 1.0 after administration of a surfactant extract from calf lung (Alveofact^®, 300 mg/kg body weight) is shown. The PaO₂ increased from about 60 mmHg (baseline) to about 220 mmHg after surfactant application. From [68], with permission.