Abstract
ObjectiveAdiponectin (APN) is an anti-inflammatory hormone derived from adipose tissue that attenuates acute lung injury in rodents. In this study, we investigated the association between circulating APN and outcomes among patients with acute respiratory distress syndrome (ARDS).MethodsWe performed a retrospective cohort study using data and plasma samples from participants in the multicenter ARDS Network Fluid and Catheter Treatment Trial.ResultsPlasma APN concentrations were measured in 816 (81.6%) trial participants at baseline and in 568 (56.8%) subjects at both baseline and day 7 after enrollment. Clinical factors associated with baseline APN levels in multivariable-adjusted models included sex, body mass index, past medical history of cirrhosis, and central venous pressure (model R2 = 9.7%). We did not observe an association between baseline APN and either severity of illness (APACHE III) or extent of lung injury (Lung Injury Score). Among patients who received right heart catheterization (n = 384), baseline APN was inversely related to mean pulmonary artery pressure (β = −0.015, R2 1.5%, p = 0.02); however, this association did not persist in multivariable models (β = −0.009, R2 0.5%, p = 0.20). Neither baseline APN levels [HR per quartile1.04 (95% CI 0.91–1.18), p = 0.61], nor change in APN level from baseline to day 7 [HR 1.04 (95% CI 0.89–1.23), p = 0.62)] were associated with 60 day mortality in Cox proportional hazards regression models. However, subgroup analysis identified an association between APN and mortality among patients who developed ARDS from extra-pulmonary etiologies [HR per quartile 1.31 (95% CI 1.08–1.57)]. APN levels did not correlate with mortality among patients developing ARDS in association with direct pulmonary injury [HR 0.96 (95% CI 0.83–1.13)], pinteraction = 0.016.ConclusionsPlasma APN levels did not correlate with disease severity or mortality in a large cohort of patients with ARDS. However, higher APN levels were associated with increased mortality among patients developing ARDS from extra-pulmonary etiologies.
Highlights
Adiponectin (APN) is a highly abundant circulating hormone with pleotrophic effects upon diverse pulmonary cell types [1,2,3,4] including alveolar macrophages, epithelium, and vascular endothelium [3,5,6]
Adiponectin and Clinical Factors Analysis of plasma APN levels showed that median APN levels increased over the course of hospitalization: baseline [7245 pg/ml (IQR 3610–13288)], day 7 [9451 pg/ml (IQR 5038–15576)] and change from baseline to day 7 [1346 pg/ml (IQR 22194–5879), p,0.001]
Factors associated with baseline APN levels after inclusion in multivariable-adjusted models included sex, body mass index, past medical history of cirrhosis, and central venous pressure (Table 1, N = 666, model R2 = 9.7%)
Summary
Adiponectin (APN) is a highly abundant circulating hormone with pleotrophic effects upon diverse pulmonary cell types [1,2,3,4] including alveolar macrophages, epithelium, and vascular endothelium [3,5,6]. APN has been shown to have important anti-inflammatory and vascular protective actions, prompting preclinical studies examining the role of APN in the pathogenesis of pulmonary disorders including acute respiratory distress syndrome (ARDS) [2,3,4,8]. Mice deficient in APN are prone to developing pulmonary vascular abnormalities including elevated pulmonary artery pressures [5], a hemodynamic alteration associated with increased mortality among patients with ARDS [10]. Together, these pre-clinical findings prompted our current investigation into the relationship of circulating APN to outcomes in ARDS
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