Summary of Study ST000843

This data is available at the NIH Common Fund's National Metabolomics Data Repository (NMDR) website, the Metabolomics Workbench, https://www.metabolomicsworkbench.org, where it has been assigned Project ID PR000600. The data can be accessed directly via it's Project DOI: 10.21228/M83X2W This work is supported by NIH grant, U2C- DK119886.

See: https://www.metabolomicsworkbench.org/about/howtocite.php

Study ID	ST000843
Study Title	Statin Immuno-Metabolomics in Asthma (part I)
Study Type	Placebo-controled trial
Study Summary	Innovative and novel therapies are urgently needed for the treatment of patients with severe asthma, especially those who are refractory to standard-of-care bronchodilators and inhaled corticosteroids. The Zeki lab is investigating the role of the mevalonate (MA) pathway, in the pathogenesis of airway inflammation and remodeling. Although statins all inhibit HMGCR in the same manner in terms of enzyme binding site, the statins’ varied physiochemical properties with respect to their polarity (i.e. lipophilicity) result in very different immune and lipid effects. The major significance of this work is to advance a new class of inhaler therapies for asthma; the statins which work by an entirely different mechanism than current ICS/LABA mainstays. Evidence suggests that statins may have an additive benefit to corticosteroids in asthma, thereby confirming a unique mechanism, namely via MVA pathway inhibition. This becomes particularly important in the severe asthma population which is highly corticosteroid-resistant, is poorly controlled with high exacerbation rates and hospitalizations, and has the highest healthcare costs of all asthma phenotypes. In essence, the potential public health impact of even an incremental improvement in asthma symptom control cannot be underestimated. Even the prevention of 1 asthma attack preserves lung function and reduces the adverse personal and financial impact. This study aimed to determine if statin polarity affects airway drug concentration and systemic drug absorption and to determine the effect of inhaled statins on naïve airway immune cell populations and alveolar-capillary membrane and epithelial barrier integrity in healthy rhesus monkeys. In this particular component of the study, we investigated the metabolic effects resulting from the use of statins in these healthy rhesus monkeys. Specifically, the Newman lab analyzed for lipid mediator (oxylipin, endocannabinoid, fatty acid, and nitro lipid) in lung and trachea tissue, plasma, and BAL and bile acid changes in the lung and trachea tissue and plasma.
Institute	University of California, Davis
Department	USDA Western Human Nutrition Research Center
Laboratory	Newman's Lab
Last Name	Newman
First Name	John
Address	430 West Health Sciences Dr. Davis, Ca, 95616
Email	John.Newman@ars.usda.gov
Phone	(530) 752-1009
Submit Date	2017-08-09
Raw Data Available	Yes
Raw Data File Type(s)	wiff
Analysis Type Detail	LC-MS
Release Date	2017-10-11
Release Version	1

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Sample Preparation:

Sampleprep ID:	SP000877
Sampleprep Summary:	Oxylipins, endocannabinoids, and fatty acids were isolated by solid phase extraction on 60 mg Waters Oasis-HLB cartridges (Milford, MA), as previously described by Luria et al (1). Prior to extraction, cartridges were washed with 1 column volume ethyl acetate followed by 2 column volumes methanol and conditioned with 2 mL of 95:5 v/v water/methanol (MeOH) with 0.1% acetic acid. The column reservoir was spiked with 5 µL anti-oxidant solution, (0.2 mg/ml solution BHT/EDTA in 1:1 MeOH:water), and 10 μL 1000nM analytical surrogates (See Table 2 below for specific compounds). Sample aliquots (500 µL media) were then introduced to the column reservoir and diluted with 1 column volume wash solution (5% MeOH, 0.1% acetic acid) and allowed to gravity extract into tubes containing 10% bleach solution to decontaminate sample waste. SPE cartridges were dried by vacuum @ -7.5in Hg for 20 min. Analytes were then eluted by gravity with 0.5 mL MeOH, followed by 1.25 mL Ethyl Acetate, into 2 mL autosampler vials containing 10 µL 20% glycerol solution in MeOH. Eluent was dried by vacuum evaporation for 35 min, and residues were re-constituted with 100uL of 100 nM internal standard solution containing 1-cyclohexyl ureido,3-dodecanoic acid (CUDA) and 1-Phenyl 3-Hexadecanoic Acid Urea (PHAU), in 50:50 MeOH:ACN and let sit for 10 min at ambient temperature. Vials were then chilled 15 min on wet ice, and extracts were transferred to a centrifugal filter (0.1 µm Durapore, Millipore, Billerica, MA), centrifuged for 3 min at 6ºC at <4500g (rcf) and transferred to 150 uL glass inserts within 2 mL amber vials, and capped. Extracts were stored at -20ºC until analysis by UPLC-MS/MS. The internal standard was used to quantify the recovery of the deuterated extraction surrogates by ratio response.

Sampleprep ID:

SP000877

Sampleprep Summary:

Oxylipins, endocannabinoids, and fatty acids were isolated by solid phase extraction on 60 mg Waters Oasis-HLB cartridges (Milford, MA), as previously described by Luria et al (1). Prior to extraction, cartridges were washed with 1 column volume ethyl acetate followed by 2 column volumes methanol and conditioned with 2 mL of 95:5 v/v water/methanol (MeOH) with 0.1% acetic acid. The column reservoir was spiked with 5 µL anti-oxidant solution, (0.2 mg/ml solution BHT/EDTA in 1:1 MeOH:water), and 10 μL 1000nM analytical surrogates (See Table 2 below for specific compounds). Sample aliquots (500 µL media) were then introduced to the column reservoir and diluted with 1 column volume wash solution (5% MeOH, 0.1% acetic acid) and allowed to gravity extract into tubes containing 10% bleach solution to decontaminate sample waste. SPE cartridges were dried by vacuum @ -7.5in Hg for 20 min. Analytes were then eluted by gravity with 0.5 mL MeOH, followed by 1.25 mL Ethyl Acetate, into 2 mL autosampler vials containing 10 µL 20% glycerol solution in MeOH. Eluent was dried by vacuum evaporation for 35 min, and residues were re-constituted with 100uL of 100 nM internal standard solution containing 1-cyclohexyl ureido,3-dodecanoic acid (CUDA) and 1-Phenyl 3-Hexadecanoic Acid Urea (PHAU), in 50:50 MeOH:ACN and let sit for 10 min at ambient temperature. Vials were then chilled 15 min on wet ice, and extracts were transferred to a centrifugal filter (0.1 µm Durapore, Millipore, Billerica, MA), centrifuged for 3 min at 6ºC at <4500g (rcf) and transferred to 150 uL glass inserts within 2 mL amber vials, and capped. Extracts were stored at -20ºC until analysis by UPLC-MS/MS. The internal standard was used to quantify the recovery of the deuterated extraction surrogates by ratio response.