The association between BMI and plasma cytokine levels in patients with acute lung injury

Abstract

Background: Obesity is associated with poor outcomes in many diseases, although recent data suggest that acute lung injury (ALI) is an exception. This is particularly interesting because obesity is marked by increased levels of proinflammatory mediators associated with increased morbidity and mortality in ALI. We hypothesized that cytokine response might be attenuated in patients who are obese and critically ill or that obesity might modify the relationship between plasma cytokines and clinical outcomes in ALI.

Methods: We analyzed plasma biomarker levels (interleukin [IL]-6, IL-8, tumor necrosis factor-alpha receptor 1, surfactant protein D [SP-D], soluble intracellular adhesion molecule, von Willebrand factor (vWF), protein C, and plasminogen activator inhibitor-1) collected at baseline and day 3 in 1,409 participants in prior National Heart, Lung, and Blood Institute Acute Respiratory Distress Syndrome Network (ARDSNet) trials. BMI was calculated for each patient, and associations with cytokine levels and ventilator-free days (VFDs), organ failure-free days (OFDs), and mortality were investigated in regression models adjusting for confounders.

Results: In adjusted analyses, plasma IL-6 (P = .052), IL-8 (P = .001), and SP-D (P < .001) were inversely related to BMI, whereas vWF (P = .001) and WBC count (P = .042) increased proportionally with BMI. BMI was not associated with increased morbidity or mortality and did not modify the association between baseline biomarker levels and mortality, VFDs, or OFDs.

Conclusions: Patients who are obese and have ALI have lower levels of several proinflammatory cytokines, suggesting that the inflammatory response may be altered in patients with ALI and a high BMI. Lower SP-D but higher vWF suggests decreased epithelial and increased endothelial injury in the lung of patients who are obese. Mechanisms by which obesity may modulate innate immunity in critical illness are unclear, and future studies should elucidate such mechanisms.

Figure 1.

Box plots of IL-6 and IL-8 plasma levels at baseline in each BMI category. Plotted data are unadjusted. P values (*) result from multivariable linear regression including log-transformed cytokine levels and BMI as a continuous variable with adjustment for gender, Acute Physiologic and Chronic Health Evaluation (APACHE) III score, comorbid diabetes, and acute lung injury (ALI) risk factor. IL = interleukin.

Figure 2.

Odds ratio of death in each BMI category relative to patients who were of normal weight, after adjusting for gender, APACHE III score, ALI risk factor, comorbid diabetes, and tidal volume group assignment. There was no statistically significant difference in mortality between any BMI category and patients of normal weight. Error bars show 95% CI. See Figure 1 legend for expansion of abbreviations.