Abstract
BackgroundAlterations to pulmonary surfactant composition have been encountered in the Acute Respiratory Distress Syndrome (ARDS). However, only few data are available regarding the time-course and duration of surfactant changes in ARDS patients, although this information may largely influence the optimum design of clinical trials addressing surfactant replacement therapy. We therefore examined the time-course of surfactant changes in 15 patients with direct ARDS (pneumonia, aspiration) over the first 8 days after onset of mechanical ventilation.MethodsThree consecutive bronchoalveolar lavages (BAL) were performed shortly after intubation (T0), and four days (T1) and eight days (T2) after intubation. Fifteen healthy volunteers served as controls. Phospholipid-to-protein ratio in BAL fluids, phospholipid class profiles, phosphatidylcholine (PC) molecular species, surfactant proteins (SP)-A, -B, -C, -D, and relative content and surface tension properties of large surfactant aggregates (LA) were assessed.ResultsAt T0, a severe and highly significant reduction in SP-A, SP-B and SP-C, the LA fraction, PC and phosphatidylglycerol (PG) percentages, and dipalmitoylation of PC (DPPC) was encountered. Surface activity of the LA fraction was greatly impaired. Over time, significant improvements were encountered especially in view of LA content, DPPC, PG and SP-A, but minimum surface tension of LA was not fully restored (15 mN/m at T2). A highly significant correlation was observed between PaO2/FiO2 and minimum surface tension (r = -0.83; p < 0.001), SP-C (r = 0.64; p < 0.001), and DPPC (r = 0.59; p = 0.003). Outcome analysis revealed that non-survivors had even more unfavourable surfactant properties as compared to survivors.ConclusionWe concluded that a profound impairment of pulmonary surfactant composition and function occurs in the very early stage of the disease and only gradually resolves over time. These observations may explain why former surfactant replacement studies with a short treatment duration failed to improve outcome and may help to establish optimal composition and duration of surfactant administration in future surfactant replacement studies in acute lung injury.
Highlights
Alterations to pulmonary surfactant composition have been encountered in the Acute Respiratory Distress Syndrome (ARDS)
Six of the 15 patients died within 28 days and the average ventilator-free days accounted for 1.6 ± 1.4 days
A considerable improvement in surfactant composition and function was noted over time, with some parameters reaching the normal range, while others still remained different from controls at T2
Summary
Alterations to pulmonary surfactant composition have been encountered in the Acute Respiratory Distress Syndrome (ARDS). Pulmonary surfactant, which covers the large alveolar surface in all mammalian species investigated, is composed primarily of phospholipids (80–85%), with dipalmitoylated phosphatidylcholine (DPPC) predominating (~50% of all PC species). It contains neutral lipids (10%) and surfactant-specific proteins (SP-A, SP-B, SP-C, SP-D; together 5–10%) [1,2]. Alterations to the pulmonary surfactant system have long been implicated in the course of inflammatory lung diseases such as the Acute Respiratory Distress Syndrome (ARDS). The inhibitory action of fibrin(ogen) [9] and other plasma proteins [10] entering the alveolar space, proteases [11], phospholipases [12] and reactive oxygen species [13] on surfactant function has been described
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