The best magazine
Objective: The primary objective of this study was to test the hypothesis that in patients intubated for acute lung injury, lower concentrations of surfactant proteins A and D in the pulmonary edema fluid and higher concentrations in the plasma are associated with more severe lung injury and worse clinical outcomes.
Design: Observational study.
Setting: Intensive care unit patients in a tertiary university hospital and a university-affiliated city hospital.
Patients: Thirty-eight intubated, mechanically ventilated intensive care unit patients with acute lung injury or acute respiratory distress syndrome as defined by the North American European Consensus Conference.
Interventions: Undiluted pulmonary edema fluid and plasma samples were collected within 24 hrs of endotracheal intubation in all patients.
Measurements and Main Results: The concentrations of surfactant proteins A and D were measured in pulmonary edema fluid and in plasma. Plasma surfactant protein A, but not surfactant protein D, was higher in patients with fewer days of unassisted ventilation (p = .03) and in patients with an absence of intact alveolar fluid clearance (p = .03). In contrast, pulmonary edema fluid surfactant protein D, but not surfactant protein A, was lower in patients with worse oxygenation, as measured by the alveolar-arterial oxygen difference (p = .01) and was lower in the patients who died (2646 ng/mL) compared with those who survived (5503 ng/mL; p = .02).
Conclusions: These results demonstrate that reduced pulmonary edema fluid surfactant protein D and elevated plasma surfactant protein A concentrations at the onset of acute lung injury may be associated with more severe disease and worse clinical outcome and may serve as valuable biochemical markers of prognosis.
These findings indicate that surfactant protein-A and surfactant protein-D have different responses to acute lung injury and may be differentially regulated or degraded in the distal airspaces.
Acute lung injury is an important cause of acute respiratory failure that occurs in association with several clinical disorders, including sepsis, aspiration, pneumonia, and trauma. Injury to the alveolar epithelial barrier is a major determinant of the extent and severity of clinical acute lung injury. The alveolar type II cell plays a critical role in both ion and fluid transport and surfactant secretion. In the setting of acute lung injury, decreased synthesis, secretion, or uptake of surfactant as well as an increase in alveolar epithelial permeability could all contribute to inadequate surface-active material in the distal air spaces of the lung. Furthermore, surfactant composition and function may be impaired by inhibitory factors in protein-rich pulmonary edema fluid or by degradation in the alveolar space.
One recent clinical study of acute lung injury found that patients who died had significantly lower bronchoalveolar lavage (BAL) concentrations of surfactant protein (SP)-D. Serum concentrations of SP-A also tended to be higher in the patients who died. In that study, the primary objective was to investigate the changes in surfactant proteins that occurred in patients at risk for acute respiratory distress syndrome (ARDS) and throughout the course of established ARDS. Approximately 40% of the patients in that study had trauma as a cause of acute lung injury, which may represent a distinct pathophysiologic mechanism for development of the disease. Although major trauma is an important cause of ARDS, most large studies of ARDS include <20% of patients with trauma as the primary associated clinical disorder. Furthermore, the overall mortality rate in the study by Greene et al. was 23%, significantly lower than the overall rate of approximately 40% reported in the literature, most likely reflecting the lower mortality rate in ARDS associated with trauma. Finally, the measurements in that study were made in diluted BAL fluid, which can make interpretation of the surfactant protein concentrations less certain.
Therefore, the rationale for this study was to determine whether the concentrations of SP-A and SP-D in the undiluted pulmonary edema fluid and plasma of patients early after the onset of acute lung injury would correlate with important clinical, physiologic, and outcome variables. The primary hypothesis was that lower concentrations of SP-A and SP-D in the pulmonary edema fluid and higher concentrations in the plasma would be associated with more severe lung injury and worse clinical outcomes. Also, since alveolar type II cell injury may affect the capacity for alveolar epithelial fluid transport, we tested the hypothesis that altered concentrations of surfactant proteins in the plasma or distal airspaces might correlate with impaired alveolar fluid clearance, an important determinant of outcome in experimental and clinical lung injury.
Source: ...