Serial Changes in Surfactant-associated Proteins in Lung and Serum before and after Onset of ARDS

Abstract

The goal of this study was to determine the changes that occur in surfactant-associated proteins in bronchoalveolar lavage fluid (BAL) and serum of patients at risk for ARDS and during the course of ARDS. We found that the concentrations of SP-A and SP-B were low in the BAL of patients at risk for ARDS before the onset of clinically defined lung injury, whereas the concentration of SP-D was normal. In patients with established ARDS, BAL SP-A and SP-B concentrations were low during the entire 14-d observation period, but the median SP-D concentrations remained in the normal range. Immunoreactive SP-A and SP-D were not increased in the serum of patients at risk for ARDS, but both increased after the onset of ARDS to a maximum on Day 3 and remained elevated for as long as 14 d. The BAL SP-A concentrations were significantly lower in at-risk patients who developed ARDS, and no patient with a BAL SP-A concentration greater than 1.2 microg/ml developed ARDS. On Days 1 and 3 of ARDS, the BAL SP-D concentration was significantly lower in patients who died, and the BAL SP-D concentration was significantly related to the PI(O(2))/FI(O(2)) ratio. Thus, surfactant protein abnormalities occur before and after the onset of ARDS, and the responses of SP-A, SP-B, and SP-D differ in important ways. The BAL SP-A and SP-D measurements can be used to classify patients as high or low risk for progression to ARDS and/or death after the onset of ARDS. Strategies to increase these surfactant proteins in the lungs of patients with ARDS could be useful to modify the onset or the course of ARDS.

Proteomic and Computational Analysis of Bronchoalveolar Proteins during the Course of the Acute Respiratory Distress Syndrome

“…Using TNF-a as an example, the network analysis showed that in addition to proinflammatory proteins, TNF-a interacted with bacterial opsonins (complement proteins, SFTPA), mediators of apoptosis (annexin A5, annexin A1), and proteins involved in lung repair (EGFR) (30)(31)(32). This suggests that TNF-a modulates pathways involved in innate immunity and repair in the lungs, in addition to inflammation.…”

Elevation of KL-6, a lung epithelial cell marker, in plasma and epithelial lining fluid in acute respiratory distress syndrome

“…When alveolar type II cells are injured, normal alveolar epithelial fluid transport and removal of alveolar edema fluid are impaired (23). Furthermore, injury to type II cells reduces the production and turnover of surfactant (12) and may also cause intrapulmonary bacterial translocation, leading to sepsis (21).…”

“…For example, the appearance of type III procollagen peptide in edema fluid or bronchoalveolar lavage (BAL) fluid identifies patients with fatal outcomes, perhaps because it indicates that fibrosing alveolitis has begun early in the course of ALI (7,8). Abnormalities of surfactant-associated proteins in BAL fluid and plasma have also been associated with poor clinical outcomes (3,12). However, very few clinical studies have measured biochemical markers in ALI to assess pulmonary epithelial damage per se.…”

Lung Surfactant and Its Use in Lung Diseases

“…Обнаружено также уменьшение содержания САБ: SP А, SP В и SP С, но не SP D [8, 91 93]. Уменьшение содержания SP А и SP В сохранялось на 14 й день после начала ОРДС [93]. При ОРДС нарушена и структурная организация ЛС: содержание больших агрегатов существенно уменьшено, а малых увеличе но [8,94,95].…”

“…[94]. Несмотря на то, что вклад от дельных компонентов ЛС в защитные механизмы легочного по вреждения до конца не ясен, полагают, что существенное сниже ние содержания SP А [8,90,92,93], деградация SP А в легочной ткани [107] и уменьшение его опсонизирующей способности по отношению к различным патогенам вносят существенный вклад в снижение резистентности больных к гнойно септическим ос ложнениям ОРДС и ИВЛ [92,108].…”