Lipoxygenase, cyclo-oxygenase and cytochrome P450 (CYP) products of arachidonic acid (AA) are implicated in pulmonary vasoregulation. The CYP-mediated epoxyeicosatrienoates (EETs) have been described previously as the predominant eicosanoids in human lungs upon stimulation with the Ca 2+ ionophore A23187. In this study, we challenged perfused human lungs with two microbial agents: Escherichia coli haemolysin (ECH) and formylmethionyl-leucyl-phenylalanine (fMLP). Both stimuli elicited pronounced generation of leukotrienes (LTs), hydroxyeicosatetraenoic acids (HETEs), prostanoids (PTs) and EETs/dihydroxyeicosatrienoic acids (DHETs), as assessed by liquid chromatography-mass spectrometry, paralleled by pulmonary artery pressor response and lung oedema formation. The maximum buffer concentrations of EETs/DHETs surpassed those of LTs plus HETEs and PTs by a factor of four (ECH) or three (AA/fMLP). Dual 5-lipoxygenase/ cyclo-oxygenase inhibition caused pronounced reduction of AA/fMLP-induced LT/PT synthesis and oedema formation but only limited attenuation of pulmonary vasoconstriction, while inhibition of CYP epoxygenase clearly attenuated AA/fMLP-induced EET/DHET synthesis and vasoconstriction but not oedema formation, suggesting a major contribution of LTs/PTs to vascular leakage and of EETs/DHETs to pressor response.Consequently, generation of EETs/DHETs is greater than that of LTs plus HETEs and PTs in ex vivo perfused human lungs upon microbial challenge suggesting a substantial contribution of these mediators to inflammatory-infectious pulmonary injury.

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Lung hyperinflation is a main determinant of dyspnoea in patients with chronic obstructive pulmonary disease (COPD). Surgical or bronchoscopic lung volume reduction are the most efficient therapeutic approaches for reducing hyperinflation in selected patients with emphysema. We here report the case of a 69-year old woman with COPD (GOLD stage 3-D) referred for lung volume reduction. She complained of persistent disabling dyspnoea despite appropriate therapy. Chest imaging showed marked emphysema heterogeneity as well as severe hyperinflation of the right lower lobe. She was deemed to be a good candidate for bronchoscopic treatment with one-way endobronchial valves. In the absence of interlobar collateral ventilation, 2 endobronchial valves were placed in the right lower lobe under general anaesthesia. The improvement observed 1 and 3 months after the procedure was such that the patient no longer met the pulmonary function criteria for COPD. The benefit persisted after 3 years.