Mortality, expressed as Hazard Ratios with bias-corrected 95% confidence intervals for baseline data.

<p>Mortality, expressed as Hazard Ratios with bias-corrected 95% confidence intervals for baseline data.</p

BALF levels and BALF/blood ratios of monocytic TREM-1.

<p>Box (interquartile) and whisker (range) plots showing expression of TREM-1 by CD14+ monocytes in BALF (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109686#pone-0109686-g001" target="_blank">Figure 1a</a>) and the BALF/blood ratio of TREM-1 expression by monocytes in blood and BALF (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0109686#pone-0109686-g001" target="_blank">Figure 1b</a>) from patients with VAP, non-VAP (ventilated non-pulmonary infected control) and NVC (non-ventilated control). BALF levels were corrected for dilution occurring with bronchoscopy using urea measurement. Statistically significant differences between groups were determined using the Mann-Whitney U and post hoc Dunn correction as follows: monocyte TREM-1 levels for VAP versus non-VAP and NVC (p<0.001)* and BALF/blood monocytic TREM-1 ratio VAP versus non-VAP and NVC (p<0.001)*. MFI = mean fluorescence intensity.</p

Characteristics of patients recruited to study.

<p>The median and range (lowest-highest) is shown for each group. APACHE II and CPIS are only applicable to the ventilated patients. Some variables are presented as percentages. Statistically significant differences between the groups were determined using the Mann-Whitney U test with post-hoc Dunn correction and are indicated as follows: VAP versus NVC (p<0.001)* and non-VAP versus NVC (p<0.001)^†. CPIS = Clinical Pulmonary Infection Score. APACHE II = Acute Physiology and Chronic Health Evaluation II score. VAP = ventilator-associated pneumonia. NVC = non-ventilated control. Non-VAP = ventilated non-pulmonary infected control. CXR = Chest X-ray. WCC = White cell count. CRP = C-reactive protein.</p><p>Characteristics of patients recruited to study.</p

Expression of cell-surface and soluble proteins in study participants with VAP, non-VAP and NVC.

<p>The median and interquartile range for each patient group is reported. Statistically significant differences between groups were determined using the Mann-Whitney U and post hoc Dunn correction as follows: VAP and non-VAP versus NVC (p<0.001)^*, VAP versus NVC (p<0.001)^† and non-VAP versus NVC (p<0.05)^‡, VAP versus non-VAP and NVC (p<0.001)^§, VAP versus non-VAP (p<0.01)^**, VAP versus non-VAP (p<0.001)^††, VAP versus NVC (p<0.01)^‡‡, VAP versus non-VAP (p<0.001)^§§ and NVC>non-VAP (p<0.01)^ll. The lower limits of detection for the sTREM-1, IL-1β, IL-6, IL-8 and PCT assays were 0.01 µg/ml, 0.001 µg/ml, 0.0007 µg/ml, 0.004 µg/ml and 0.05 ng/ml respectively. N/A indicates below assay detection limit. BALF levels were corrected for dilution occurring with bronchoscopy using urea analysis. BALF/blood ratios were only calculable if BALF and blood measurements were obtained. VAP = ventilator-associated pneumonia. Non-VAP = ventilated patients with no evidence of pulmonary infection. NVC = non-ventilated non-infected patients.</p><p>Expression of cell-surface and soluble proteins in study participants with VAP, non-VAP and NVC.</p

COPD prognostic staging in high and low risk, according to the ES-FRC composite index.

<p>COPD prognostic staging in high and low risk, according to the ES-FRC composite index.</p

Characteristics of the study population.

<p>Characteristics of the study population.</p

Kaplan Meier curves for the COPD population, categorized according to A) ES optimal threshold of 55%, B) ES subthresholds of 30 and 65%, C) FRC % predicted optimal threshold of 210% and D) ES-FRC composite index.

<p>Kaplan Meier curves for the COPD population, categorized according to A) ES optimal threshold of 55%, B) ES subthresholds of 30 and 65%, C) FRC % predicted optimal threshold of 210% and D) ES-FRC composite index.</p

Characteristics of patients and controls.

<p>Data are presented as mean±standard deviation.</p>*<p>Comparison between all patients and controls.</p>**<p>Time from diagnosis to blood sample collection.</p><p>BMI, body mass index; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; DL_CO, diffusing capacity for carbon monoxide; PaCO₂, arterial partial pressure of carbon dioxide; PaO₂, arterial partial pressure of oxygen; A-aDO₂, alveolar-arterial oxygen pressure difference; SP-D, surfactant protein-D; PGF_2α, prostaglandin F_2α; NA, not available.</p

Clinical Relevance of Plasma Prostaglandin F_2α Metabolite Concentrations in Patients with Idiopathic Pulmonary Fibrosis

<div><p>Background</p><p>Idiopathic pulmonary fibrosis (IPF) is a devastating lung disease of unknown etiology with few current treatment options. Recently, we determined an important role of prostaglandin F_2α (PGF_2α) in pulmonary fibrosis by using a bleomycin-induced pulmonary fibrosis model and found an abundance of PGF_2α in bronchoalveolar lavage fluid of IPF patients. We investigated the role of PGF_2α in human IPF by assessing plasma concentrations of 15-keto-dihydro PGF_2α, a stable metabolite of PGF_2α.</p><p>Methods</p><p>We measured plasma concentrations of 15-keto-dihydro PGF_2α in 91 IPF patients and compared these values with those of controls (n = 25). We further investigated the relationships of plasma 15-keto-dihydro PGF_2α concentrations with disease severity and mortality.</p><p>Results</p><p>Plasma concentrations of 15-keto-dihydro PGF_2α were significantly higher in IPF patients than controls (<i>p</i><0.001). Plasma concentrations of this metabolite were significantly correlated with forced expiratory volume in 1 second (<i>Rs</i> [correlation coefficient] = −0.34, <i>p</i> = 0.004), forced vital capacity (<i>Rs</i> = −0.33, <i>p</i> = 0.005), diffusing capacity for carbon monoxide (<i>Rs</i> = −0.36, <i>p</i> = 0.003), the composite physiologic index (<i>Rs</i> = 0.40, <i>p</i> = 0.001), 6-minute walk distance (<i>Rs</i> = −0.24, <i>p</i> = 0.04) and end-exercise oxygen saturation (<i>Rs</i> = −0.25, <i>p</i> = 0.04) when patients with emphysema were excluded. Multivariate analysis using stepwise Cox proportional hazards model showed that a higher composite physiologic index (relative risk = 1.049, <i>p</i> = 0.002) and plasma 15-keto-dihydro PGF_2α concentrations (relative risk = 1.005, <i>p</i> = 0.002) were independently associated with an increased risk of mortality.</p><p>Conclusions</p><p>We demonstrated significant associations of plasma concentrations of PGF_2α metabolites with disease severity and prognosis, which support a potential pathogenic role for PGF_2α in human IPF.</p></div

Cox proportional hazard model results for evaluating the risk of mortality.

<p>CI, confidence interval; FEV₁, forced expiratory volume in 1 second; FVC, forced vital capacity; DL_CO, diffusing capacity for carbon monoxide; SP-D, surfactant protein-D; PGF_2α, prostaglandin F_2α.</p