Effects of cyclo-oxygenase inhibition on exhaled eicosanoids in patients with COPD

Background: Leukotriene (LT) B4 concentrations are increased and prostaglandin (PG) E2 concentrations are decreased in exhaled breath condensate (EBC) in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to investigate the short term effects of cyclo-oxygenase (COX)...

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Published in:Thorax 2005-10, Vol.60 (10), p.827-833
Main Authors: Montuschi, P, Macagno, F, Parente, P, Valente, S, Lauriola, L, Ciappi, G, Kharitonov, S A, Barnes, P J, Ciabattoni, G
Format: Article
Language:English
Subjects:
Biological and medical sciences
Blood Gas Analysis - methods
Chronic Obstructive Pulmonary Disease
COPD
COX
Cross-Over Studies
cyclo-oxygenase
Cyclooxygenase Inhibitors - therapeutic use
Dinoprostone - metabolism
Double-Blind Method
EBC
Eicosanoids - metabolism
exhaled breath condensate
Female
FEV1
Forced Expiratory Volume - physiology
forced expiratory volume in 1 second
forced vital capacity
FVC
Humans
Ibuprofen - therapeutic use
Lactones - therapeutic use
leukotriene B4
Leukotriene B4 - metabolism
LTB4
Male
Medical sciences
Middle Aged
non-steroidal anti-inflammatory drug
Nonsteroidal anti-inflammatory drugs
NSAID
Outpatient care facilities
Patients
PGE2
Pneumology
prostaglandin E2
Pulmonary Disease, Chronic Obstructive - drug therapy
Pulmonary Disease, Chronic Obstructive - metabolism
Sputum - chemistry
Sulfones - therapeutic use
thromboxane B2
Thromboxane B2 - metabolism
TxB2
Vital Capacity - physiology
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container_end_page 833
container_issue 10
container_start_page 827
container_title Thorax
container_volume 60
creator Montuschi, P
Macagno, F
Parente, P
Valente, S
Lauriola, L
Ciappi, G
Kharitonov, S A
Barnes, P J
Ciabattoni, G
description Background: Leukotriene (LT) B4 concentrations are increased and prostaglandin (PG) E2 concentrations are decreased in exhaled breath condensate (EBC) in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to investigate the short term effects of cyclo-oxygenase (COX) inhibition on exhaled LTB4 and PGE2 concentrations in patients with COPD and to identify the COX isoform responsible for exhaled PGE2 production. Methods: Two studies were performed. A double blind, crossover, randomised, placebo controlled study with ibuprofen (400 mg qid for 2 days), a non-selective COX inhibitor, was undertaken in 14 patients with stable COPD, and an open label study with oral rofecoxib (25 mg once a day for 5 days), a selective COX-2 inhibitor, was undertaken in a different group of 16 COPD patients. EBC was collected before and after drug treatment. Exhaled LTB4 and PGE2 concentrations were measured with specific immunoassays. Results: All patients complied with treatment as indicated by a reduction in ex vivo serum thromboxane B2 concentrations (ibuprofen) and a reduction in lipopolysaccharide induced increase in ex vivo plasma PGE2 values (rofecoxib) of more than 80%. Exhaled LTB4 was increased after ibuprofen (median 175.5 (interquartile range 128.8–231.5) pg/ml v 84.0 (70.0–98.5) pg/ml, p
doi_str_mv 10.1136/thx.2004.035592
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A study was undertaken to investigate the short term effects of cyclo-oxygenase (COX) inhibition on exhaled LTB4 and PGE2 concentrations in patients with COPD and to identify the COX isoform responsible for exhaled PGE2 production. Methods: Two studies were performed. A double blind, crossover, randomised, placebo controlled study with ibuprofen (400 mg qid for 2 days), a non-selective COX inhibitor, was undertaken in 14 patients with stable COPD, and an open label study with oral rofecoxib (25 mg once a day for 5 days), a selective COX-2 inhibitor, was undertaken in a different group of 16 COPD patients. EBC was collected before and after drug treatment. Exhaled LTB4 and PGE2 concentrations were measured with specific immunoassays. Results: All patients complied with treatment as indicated by a reduction in ex vivo serum thromboxane B2 concentrations (ibuprofen) and a reduction in lipopolysaccharide induced increase in ex vivo plasma PGE2 values (rofecoxib) of more than 80%. Exhaled LTB4 was increased after ibuprofen (median 175.5 (interquartile range 128.8–231.5) pg/ml v 84.0 (70.0–98.5) pg/ml, p&lt;0.001) and exhaled PGE2 was reduced (93.5 (84.0–105–5) pg/ml v 22.0 (15.0–25.5) pg/ml, p&lt;0.0001). Rofecoxib had no effect on exhaled LTB4 (p = 0.53) or PGE2 (p = 0.23). Conclusions: Non-selective COX inhibition decreases PGE2 and increases LTB4 in EBC, whereas selective COX-2 inhibition has no effect on these eicosanoids. PGE2 in EBC is primarily derived from COX-1 activity, and COX inhibition may redirect arachidonic acid metabolism towards the 5-lipoxygenase pathway.</description><identifier>ISSN: 0040-6376</identifier><identifier>EISSN: 1468-3296</identifier><identifier>DOI: 10.1136/thx.2004.035592</identifier><identifier>PMID: 16192367</identifier><identifier>CODEN: THORA7</identifier><language>eng</language><publisher>London: BMJ Publishing Group Ltd and British Thoracic Society</publisher><subject>Biological and medical sciences ; Blood Gas Analysis - methods ; Chronic Obstructive Pulmonary Disease ; COPD ; COX ; Cross-Over Studies ; cyclo-oxygenase ; Cyclooxygenase Inhibitors - therapeutic use ; Dinoprostone - metabolism ; Double-Blind Method ; EBC ; Eicosanoids - metabolism ; exhaled breath condensate ; Female ; FEV1 ; Forced Expiratory Volume - physiology ; forced expiratory volume in 1 second ; forced vital capacity ; FVC ; Humans ; Ibuprofen - therapeutic use ; Lactones - therapeutic use ; leukotriene B4 ; Leukotriene B4 - metabolism ; LTB4 ; Male ; Medical sciences ; Middle Aged ; non-steroidal anti-inflammatory drug ; Nonsteroidal anti-inflammatory drugs ; NSAID ; Outpatient care facilities ; Patients ; PGE2 ; Pneumology ; prostaglandin E2 ; Pulmonary Disease, Chronic Obstructive - drug therapy ; Pulmonary Disease, Chronic Obstructive - metabolism ; Sputum - chemistry ; Sulfones - therapeutic use ; thromboxane B2 ; Thromboxane B2 - metabolism ; TxB2 ; Vital Capacity - physiology</subject><ispartof>Thorax, 2005-10, Vol.60 (10), p.827-833</ispartof><rights>Copyright 2005 Thorax</rights><rights>2005 INIST-CNRS</rights><rights>Copyright: 2005 Copyright 2005 Thorax</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-b553t-faa55134655a51088cfd2ab21532a83c77c53b0bec62c97fa9c5dca5f9b53d3e3</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1747215/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC1747215/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&amp;idt=17193358$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/16192367$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Montuschi, P</creatorcontrib><creatorcontrib>Macagno, F</creatorcontrib><creatorcontrib>Parente, P</creatorcontrib><creatorcontrib>Valente, S</creatorcontrib><creatorcontrib>Lauriola, L</creatorcontrib><creatorcontrib>Ciappi, G</creatorcontrib><creatorcontrib>Kharitonov, S A</creatorcontrib><creatorcontrib>Barnes, P J</creatorcontrib><creatorcontrib>Ciabattoni, G</creatorcontrib><title>Effects of cyclo-oxygenase inhibition on exhaled eicosanoids in patients with COPD</title><title>Thorax</title><addtitle>Thorax</addtitle><description>Background: Leukotriene (LT) B4 concentrations are increased and prostaglandin (PG) E2 concentrations are decreased in exhaled breath condensate (EBC) in patients with chronic obstructive pulmonary disease (COPD). A study was undertaken to investigate the short term effects of cyclo-oxygenase (COX) inhibition on exhaled LTB4 and PGE2 concentrations in patients with COPD and to identify the COX isoform responsible for exhaled PGE2 production. Methods: Two studies were performed. A double blind, crossover, randomised, placebo controlled study with ibuprofen (400 mg qid for 2 days), a non-selective COX inhibitor, was undertaken in 14 patients with stable COPD, and an open label study with oral rofecoxib (25 mg once a day for 5 days), a selective COX-2 inhibitor, was undertaken in a different group of 16 COPD patients. EBC was collected before and after drug treatment. Exhaled LTB4 and PGE2 concentrations were measured with specific immunoassays. Results: All patients complied with treatment as indicated by a reduction in ex vivo serum thromboxane B2 concentrations (ibuprofen) and a reduction in lipopolysaccharide induced increase in ex vivo plasma PGE2 values (rofecoxib) of more than 80%. Exhaled LTB4 was increased after ibuprofen (median 175.5 (interquartile range 128.8–231.5) pg/ml v 84.0 (70.0–98.5) pg/ml, p&lt;0.001) and exhaled PGE2 was reduced (93.5 (84.0–105–5) pg/ml v 22.0 (15.0–25.5) pg/ml, p&lt;0.0001). Rofecoxib had no effect on exhaled LTB4 (p = 0.53) or PGE2 (p = 0.23). Conclusions: Non-selective COX inhibition decreases PGE2 and increases LTB4 in EBC, whereas selective COX-2 inhibition has no effect on these eicosanoids. PGE2 in EBC is primarily derived from COX-1 activity, and COX inhibition may redirect arachidonic acid metabolism towards the 5-lipoxygenase pathway.</description><subject>Biological and medical sciences</subject><subject>Blood Gas Analysis - methods</subject><subject>Chronic Obstructive Pulmonary Disease</subject><subject>COPD</subject><subject>COX</subject><subject>Cross-Over Studies</subject><subject>cyclo-oxygenase</subject><subject>Cyclooxygenase Inhibitors - therapeutic use</subject><subject>Dinoprostone - metabolism</subject><subject>Double-Blind Method</subject><subject>EBC</subject><subject>Eicosanoids - metabolism</subject><subject>exhaled breath condensate</subject><subject>Female</subject><subject>FEV1</subject><subject>Forced Expiratory Volume - physiology</subject><subject>forced expiratory volume in 1 second</subject><subject>forced vital capacity</subject><subject>FVC</subject><subject>Humans</subject><subject>Ibuprofen - therapeutic use</subject><subject>Lactones - therapeutic use</subject><subject>leukotriene B4</subject><subject>Leukotriene B4 - metabolism</subject><subject>LTB4</subject><subject>Male</subject><subject>Medical sciences</subject><subject>Middle Aged</subject><subject>non-steroidal anti-inflammatory drug</subject><subject>Nonsteroidal anti-inflammatory drugs</subject><subject>NSAID</subject><subject>Outpatient care facilities</subject><subject>Patients</subject><subject>PGE2</subject><subject>Pneumology</subject><subject>prostaglandin E2</subject><subject>Pulmonary Disease, Chronic Obstructive - drug therapy</subject><subject>Pulmonary Disease, Chronic Obstructive - metabolism</subject><subject>Sputum - chemistry</subject><subject>Sulfones - therapeutic use</subject><subject>thromboxane B2</subject><subject>Thromboxane B2 - metabolism</subject><subject>TxB2</subject><subject>Vital Capacity - physiology</subject><issn>0040-6376</issn><issn>1468-3296</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2005</creationdate><recordtype>article</recordtype><recordid>eNqFkd1v0zAUxS3ExLrCM28oEoIHpHT-qD_yMgl1YxuaGIKxV-vGsReXNC5xOtr_HkepNuBlkiU_nJ-Pz70HodcEzwhh4rivtzOK8XyGGecFfYYmZC5UzmghnqNJEnAumBSH6CjGJcZYESJfoEMiSEGZkBP07cw5a_qYBZeZnWlCHra7O9tCtJlva1_63oc2S8dua2hslVlvQoQ2-ComIltD722bDH77vs4W119PX6IDB020r_b3FP34dHazuMivrs8vFx-v8pJz1ucOgHPC5oJz4AQrZVxFoaSEMwqKGSkNZyUurRHUFNJBYXhlgLui5Kxilk3Ryei73pQrW5mUooNGrzu_gm6nA3j9r9L6Wt-Fe03kXA7fTNH7vUEXfm1s7PXKR2ObBlobNlELJZgqMH0SJJIVUsoBfPsfuAybrk1bSIwiUmCVRp6i45EyXYixs-4hM8F6qFWnWvVQqx5rTS_e_D3qI7_vMQHv9gBEA43roDU-PnKSFIxxlbh85Hzs7fZBh-6nTi6S6y-3C_2d3px-VrdYD74fRr5cLZ9M-QcIyMfl</recordid><startdate>20051001</startdate><enddate>20051001</enddate><creator>Montuschi, P</creator><creator>Macagno, F</creator><creator>Parente, P</creator><creator>Valente, S</creator><creator>Lauriola, L</creator><creator>Ciappi, G</creator><creator>Kharitonov, S A</creator><creator>Barnes, P J</creator><creator>Ciabattoni, G</creator><general>BMJ Publishing Group Ltd and British Thoracic Society</general><general>BMJ</general><general>BMJ Publishing Group LTD</general><general>BMJ Group</general><scope>BSCLL</scope><scope>IQODW</scope><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>BENPR</scope><scope>BTHHO</scope><scope>CCPQU</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7T5</scope><scope>H94</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20051001</creationdate><title>Effects of cyclo-oxygenase inhibition on exhaled eicosanoids in patients with COPD</title><author>Montuschi, P ; Macagno, F ; Parente, P ; Valente, S ; Lauriola, L ; Ciappi, G ; Kharitonov, S A ; Barnes, P J ; Ciabattoni, G</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-b553t-faa55134655a51088cfd2ab21532a83c77c53b0bec62c97fa9c5dca5f9b53d3e3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2005</creationdate><topic>Biological and medical sciences</topic><topic>Blood Gas Analysis - methods</topic><topic>Chronic Obstructive Pulmonary Disease</topic><topic>COPD</topic><topic>COX</topic><topic>Cross-Over Studies</topic><topic>cyclo-oxygenase</topic><topic>Cyclooxygenase Inhibitors - therapeutic use</topic><topic>Dinoprostone - metabolism</topic><topic>Double-Blind Method</topic><topic>EBC</topic><topic>Eicosanoids - metabolism</topic><topic>exhaled breath condensate</topic><topic>Female</topic><topic>FEV1</topic><topic>Forced Expiratory Volume - physiology</topic><topic>forced expiratory volume in 1 second</topic><topic>forced vital capacity</topic><topic>FVC</topic><topic>Humans</topic><topic>Ibuprofen - therapeutic use</topic><topic>Lactones - therapeutic use</topic><topic>leukotriene B4</topic><topic>Leukotriene B4 - metabolism</topic><topic>LTB4</topic><topic>Male</topic><topic>Medical sciences</topic><topic>Middle Aged</topic><topic>non-steroidal anti-inflammatory drug</topic><topic>Nonsteroidal anti-inflammatory drugs</topic><topic>NSAID</topic><topic>Outpatient care facilities</topic><topic>Patients</topic><topic>PGE2</topic><topic>Pneumology</topic><topic>prostaglandin E2</topic><topic>Pulmonary Disease, Chronic Obstructive - drug therapy</topic><topic>Pulmonary Disease, Chronic Obstructive - metabolism</topic><topic>Sputum - chemistry</topic><topic>Sulfones - therapeutic use</topic><topic>thromboxane B2</topic><topic>Thromboxane B2 - metabolism</topic><topic>TxB2</topic><topic>Vital Capacity - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Montuschi, P</creatorcontrib><creatorcontrib>Macagno, F</creatorcontrib><creatorcontrib>Parente, P</creatorcontrib><creatorcontrib>Valente, S</creatorcontrib><creatorcontrib>Lauriola, L</creatorcontrib><creatorcontrib>Ciappi, G</creatorcontrib><creatorcontrib>Kharitonov, S A</creatorcontrib><creatorcontrib>Barnes, P J</creatorcontrib><creatorcontrib>Ciabattoni, G</creatorcontrib><collection>Istex</collection><collection>Pascal-Francis</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health &amp; 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A study was undertaken to investigate the short term effects of cyclo-oxygenase (COX) inhibition on exhaled LTB4 and PGE2 concentrations in patients with COPD and to identify the COX isoform responsible for exhaled PGE2 production. Methods: Two studies were performed. A double blind, crossover, randomised, placebo controlled study with ibuprofen (400 mg qid for 2 days), a non-selective COX inhibitor, was undertaken in 14 patients with stable COPD, and an open label study with oral rofecoxib (25 mg once a day for 5 days), a selective COX-2 inhibitor, was undertaken in a different group of 16 COPD patients. EBC was collected before and after drug treatment. Exhaled LTB4 and PGE2 concentrations were measured with specific immunoassays. Results: All patients complied with treatment as indicated by a reduction in ex vivo serum thromboxane B2 concentrations (ibuprofen) and a reduction in lipopolysaccharide induced increase in ex vivo plasma PGE2 values (rofecoxib) of more than 80%. Exhaled LTB4 was increased after ibuprofen (median 175.5 (interquartile range 128.8–231.5) pg/ml v 84.0 (70.0–98.5) pg/ml, p&lt;0.001) and exhaled PGE2 was reduced (93.5 (84.0–105–5) pg/ml v 22.0 (15.0–25.5) pg/ml, p&lt;0.0001). Rofecoxib had no effect on exhaled LTB4 (p = 0.53) or PGE2 (p = 0.23). Conclusions: Non-selective COX inhibition decreases PGE2 and increases LTB4 in EBC, whereas selective COX-2 inhibition has no effect on these eicosanoids. PGE2 in EBC is primarily derived from COX-1 activity, and COX inhibition may redirect arachidonic acid metabolism towards the 5-lipoxygenase pathway.</abstract><cop>London</cop><pub>BMJ Publishing Group Ltd and British Thoracic Society</pub><pmid>16192367</pmid><doi>10.1136/thx.2004.035592</doi><tpages>7</tpages><oa>free_for_read</oa></addata></record>
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source Open Access: PubMed Central
subjects Biological and medical sciences
Blood Gas Analysis - methods
Chronic Obstructive Pulmonary Disease
COPD
COX
Cross-Over Studies
cyclo-oxygenase
Cyclooxygenase Inhibitors - therapeutic use
Dinoprostone - metabolism
Double-Blind Method
EBC
Eicosanoids - metabolism
exhaled breath condensate
Female
FEV1
Forced Expiratory Volume - physiology
forced expiratory volume in 1 second
forced vital capacity
FVC
Humans
Ibuprofen - therapeutic use
Lactones - therapeutic use
leukotriene B4
Leukotriene B4 - metabolism
LTB4
Male
Medical sciences
Middle Aged
non-steroidal anti-inflammatory drug
Nonsteroidal anti-inflammatory drugs
NSAID
Outpatient care facilities
Patients
PGE2
Pneumology
prostaglandin E2
Pulmonary Disease, Chronic Obstructive - drug therapy
Pulmonary Disease, Chronic Obstructive - metabolism
Sputum - chemistry
Sulfones - therapeutic use
thromboxane B2
Thromboxane B2 - metabolism
TxB2
Vital Capacity - physiology
title Effects of cyclo-oxygenase inhibition on exhaled eicosanoids in patients with COPD
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