RT Journal Article
SR Electronic
T1 Linoleic acid-derived lipid mediators increase in a female-dominated subphenotype of COPD
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 1645
OP 1656
DO 10.1183/13993003.01080-2015
VO 47
IS 6
A1 David Balgoma
A1 Mingxing Yang
A1 Marcus Sjödin
A1 Stuart Snowden
A1 Reza Karimi
A1 Bettina Levänen
A1 Heta Merikallio
A1 Riitta Kaarteenaho
A1 Lena Palmberg
A1 Kjell Larsson
A1 David J. Erle
A1 Sven-Erik Dahlén
A1 Barbro Dahlén
A1 C. Magnus Sköld
A1 Åsa M. Wheelock
A1 Craig E. Wheelock
YR 2016
UL http://erj.ersjournals.com/content/47/6/1645.abstract
AB Chronic obstructive pulmonary disease (COPD) is a leading cause of mortality; however, the role of inflammatory mediators in its pathobiology remains unclear. The aim of this study was to investigate the influence of gender in COPD on lipid mediator levels.Bronchoalveolar lavage fluid (BALF) and serum were obtained from healthy never-smokers, smokers and COPD patients (Global Initiative for Chronic Obstructive Lung Disease stage I–II/A–B) (n=114). 94 lipid mediators derived from the cytochrome-P450, lipoxygenase, and cyclooxygenase pathways were analysed by liquid chromatography-mass spectrometry.Multivariate modelling identified a 9-lipid panel in BALF that classified female smokers with COPD from healthy female smokers (p=6×10−6). No differences were observed for the corresponding male population (p=1.0). These findings were replicated in an independent cohort with 92% accuracy (p=0.005). The strongest drivers were the cytochrome P450-derived epoxide products of linoleic acid (leukotoxins) and their corresponding soluble epoxide hydrolase (sEH)-derived products (leukotoxin-diols). These species correlated with lung function (r=0.87; p=0.0009) and mRNA levels of enzymes putatively involved in their biosynthesis (r=0.96; p=0.003). Leukotoxin levels correlated with goblet cell abundance (r=0.72; p=0.028).These findings suggest a mechanism by which goblet cell-associated cytochrome-P450 and sEH activity produce elevated leukotoxin-diol levels, which play a putative role in the clinical manifestations of COPD in a female-dominated disease sub-phenotype.Linoleic acid-derived lipids in BALF may indicate the transition from healthy smoker to COPD in a female subphenotype http://ow.ly/XowqN