ARDS includes a complex series of events leading to alveolar damage, high permeability pulmonary edema, and respiratory failure. The endogenous pulmonary surfactant system is crucial to maintaining normal lung function, and only recently has it been appreciated that alterations in the surfactant system significantly contributed to the pathophysiology of the lung injury of patients with ARDS. Through a combination of analyzing BAL samples from patients with ARDS and extensive animal studies, there have been significant insights into the variety of surfactant abnormalities that can occur in injured lungs. These include altered surfactant composition and pool sizes, abnormal surfactant metabolism, and inactivation of alveolar surfactant by serum proteins present within the airspace. Positive effects of exogenous surfactant administration on acute lung injury have been reported. There is now a prospective, randomized clinical trial evaluating the efficacy of aerosolized exogenous surfactant in patients with ARDS. This trial has demonstrated improvements in gas exchange and a trend toward decreased mortality in response to the surfactant. Despite these encouraging results, there are multiple factors requiring further investigation in the development of optimal surfactant treatment strategies for patients with ARDS. Such factors include the development of optimal surfactant delivery techniques, determining the ideal time for surfactant administration during the course of injury, and the development of optimal exogenous surfactant preparations that will be used to treat these patients. With further clinical trials and continued research efforts, exogenous surfactant administration should play a useful role in the future therapeutic approach to patients with ARDS.

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The hyporesponsive state of lung-derived mononuclear leukocytes has been, in part, attributed to the effects of the lipid rather than the protein components of pulmonary surfactant. In the present study, however, the results suggest that purified preparations of pulmonary surfactant-associated protein A (SP-A) suppress both phytohemagglutinin (PHA, 1 microgram/ml)- and anti-CD-3 (1 to 10 ng/ml) activated proliferation of human peripheral blood and tonsillar mononuclear cells in a dose-dependent manner at concentrations as low as 50 pM (6.25 micrograms/ml) when added at the initiation of cultures. Addition of SP-A to PHA-stimulated peripheral blood mononuclear cells (PBMC) as late as 24 to 36 h after PHA was also capable of suppressing [3H]thymidine incorporation measured at 72 h. In contrast, concanavalin A (Con A; 2 micrograms/ml)-stimulated PBMC proliferation was slightly augmented by the addition of SP-A. Analysis of the supernatants of PHA-stimulated cultures treated with SP-A revealed that accompanying the inhibition of proliferation was a corresponding decline in measurable interleukin-2 (IL-2) concentrations, from 154 pg/ml for the PHA-treated cells to 57.8, 28.4, 5.2, and less than 2 pg/ml of IL-2 when SP-A was added at 6.25, 12.5, 25, and 50 micrograms/ml, respectively. We suggest that the action of SP-A on PHA-stimulated human PBMC may involve the blocking of a costimulatory signal crucial for in vitro T-cell activation.

A number of conditions, such as pneumonia, trauma, or systemic sepsis arising from the gut, may result in the acute respiratory distress syndrome (ARDS). Because of its significant morbidity and mortality, ARDS has been the focus of extensive research. One specific area of interest has been the investigation of the role of the surfactant system in the pathophysiology of this disease. Several studies have demonstrated that alterations of surfactant contribute to the lung dysfunction associated with ARDS, which has led to investigations into the use of exogenous surfactant as a therapy for this syndrome. Clinical experience with surfactant therapy has been variable owing to a number of factors including the nature of the injury at the time of treatment, the specific surfactant preparation utilized, the dose and delivery method chosen, the timing of surfactant administration over the course of the disease, and the mode of ventilation used during and after surfactant administration.