Acute effect of inhaled iloprost on exercise dynamic hyperinflation in COPD patients: A randomized crossover study
We tested whether the prostacyclin analog inhaled iloprost modulates dead space, dynamic hyperinflation (DH), and systemic inflammation/oxidative stress during maximal exercise in subjects with chronic obstructive pulmonary disease (COPD) who were not selected based on pulmonary hypertension (PH). T...
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creator | Lammi, Matthew R. Ghonim, Mohamed A. Johnson, Jessica D'Aquin, Johnny Zamjahn, John B. Pellett, Andy Okpechi, Samuel C. Romaine, Connie Pyakurel, Kusma Luu, Hahn H. Shellito, Judd E. Boulares, A. Hamid deBoisblanc, Bennett P. |
description | We tested whether the prostacyclin analog inhaled iloprost modulates dead space, dynamic hyperinflation (DH), and systemic inflammation/oxidative stress during maximal exercise in subjects with chronic obstructive pulmonary disease (COPD) who were not selected based on pulmonary hypertension (PH).
Twenty-four COPD patients with moderate-severe obstruction (age 59 ± 7 years, FEV1 53 ± 13% predicted) participated in a randomized, double-blind, placebo-controlled crossover trial. Each subject received a single nebulized dose of 5.0 μg iloprost or placebo on non-consecutive days followed by maximal cardiopulmonary exercise tests. The primary outcome was DH quantified by end-expiratory lung volume/total lung capacity ratio (EELV/TLC) at metabolic isotime.
Inhaled iloprost was well-tolerated and reduced submaximal alveolar dead-space fraction but did not significantly reduce DH (0.70 ± 0.09 vs 0.69 ± 0.07 following placebo and iloprost, respectively, p = 0.38). Maximal exercise time (9.1 ± 2.3 vs 9.3 ± 2.2 min, p = 0.31) and peak oxygen uptake (17.4 ± 6.3 vs 17.9 ± 6.9 mL/kg/min, p = 0.30) were not significantly different following placebo versus iloprost.
A single dose of inhaled iloprost was safe and reduced alveolar dead space fraction; however, it was not efficacious in modulating DH or improving exercise capacity in COPD patients who were not selected for the presence of PH.
•Iloprost is an inhaled prostacyclin analog that may improve ventilation-perfusion matching.•This randomized crossover trial studied the acute effects of iloprost on COPD patients.•Iloprost was safe but did not improve dynamic hyperinflation or exercise capacity in COPD patients. |
doi_str_mv | 10.1016/j.rmed.2021.106354 |
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Twenty-four COPD patients with moderate-severe obstruction (age 59 ± 7 years, FEV1 53 ± 13% predicted) participated in a randomized, double-blind, placebo-controlled crossover trial. Each subject received a single nebulized dose of 5.0 μg iloprost or placebo on non-consecutive days followed by maximal cardiopulmonary exercise tests. The primary outcome was DH quantified by end-expiratory lung volume/total lung capacity ratio (EELV/TLC) at metabolic isotime.
Inhaled iloprost was well-tolerated and reduced submaximal alveolar dead-space fraction but did not significantly reduce DH (0.70 ± 0.09 vs 0.69 ± 0.07 following placebo and iloprost, respectively, p = 0.38). Maximal exercise time (9.1 ± 2.3 vs 9.3 ± 2.2 min, p = 0.31) and peak oxygen uptake (17.4 ± 6.3 vs 17.9 ± 6.9 mL/kg/min, p = 0.30) were not significantly different following placebo versus iloprost.
A single dose of inhaled iloprost was safe and reduced alveolar dead space fraction; however, it was not efficacious in modulating DH or improving exercise capacity in COPD patients who were not selected for the presence of PH.
•Iloprost is an inhaled prostacyclin analog that may improve ventilation-perfusion matching.•This randomized crossover trial studied the acute effects of iloprost on COPD patients.•Iloprost was safe but did not improve dynamic hyperinflation or exercise capacity in COPD patients.</description><identifier>ISSN: 0954-6111</identifier><identifier>EISSN: 1532-3064</identifier><identifier>DOI: 10.1016/j.rmed.2021.106354</identifier><identifier>PMID: 33721696</identifier><language>eng</language><publisher>England: Elsevier Ltd</publisher><subject>Administration, Inhalation ; Aged ; Alveoli ; Chronic obstructive pulmonary disease ; Cross-Over Studies ; Double-Blind Method ; Dyspnea ; Exercise ; Exercise - physiology ; Exercise test ; Exercise Test - methods ; Female ; Humans ; Hypertension ; Iloprost ; Iloprost - administration & dosage ; Inflammation ; Lung diseases ; Lung Volume Measurements ; Lungs ; Male ; Metabolism ; Middle Aged ; Obstructive lung disease ; Oxidative stress ; Oxidative Stress - drug effects ; Oxygen Consumption ; Oxygen uptake ; Patients ; Placebos ; Prostacyclin ; Pulmonary arteries ; Pulmonary Disease, Chronic Obstructive - drug therapy ; Pulmonary Disease, Chronic Obstructive - metabolism ; Pulmonary Disease, Chronic Obstructive - physiopathology ; Total Lung Capacity</subject><ispartof>Respiratory medicine, 2021-04, Vol.180, p.106354-106354, Article 106354</ispartof><rights>2021 Elsevier Ltd</rights><rights>Copyright © 2021 Elsevier Ltd. All rights reserved.</rights><rights>2021. Elsevier Ltd</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c483t-328647060804b5ce5fd6009235baa0b7cd5874dfd1ffc3755df20a800275db903</citedby><cites>FETCH-LOGICAL-c483t-328647060804b5ce5fd6009235baa0b7cd5874dfd1ffc3755df20a800275db903</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.rmed.2021.106354$$EHTML$$P50$$Gelsevier$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33721696$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Lammi, Matthew R.</creatorcontrib><creatorcontrib>Ghonim, Mohamed A.</creatorcontrib><creatorcontrib>Johnson, Jessica</creatorcontrib><creatorcontrib>D'Aquin, Johnny</creatorcontrib><creatorcontrib>Zamjahn, John B.</creatorcontrib><creatorcontrib>Pellett, Andy</creatorcontrib><creatorcontrib>Okpechi, Samuel C.</creatorcontrib><creatorcontrib>Romaine, Connie</creatorcontrib><creatorcontrib>Pyakurel, Kusma</creatorcontrib><creatorcontrib>Luu, Hahn H.</creatorcontrib><creatorcontrib>Shellito, Judd E.</creatorcontrib><creatorcontrib>Boulares, A. Hamid</creatorcontrib><creatorcontrib>deBoisblanc, Bennett P.</creatorcontrib><title>Acute effect of inhaled iloprost on exercise dynamic hyperinflation in COPD patients: A randomized crossover study</title><title>Respiratory medicine</title><addtitle>Respir Med</addtitle><description>We tested whether the prostacyclin analog inhaled iloprost modulates dead space, dynamic hyperinflation (DH), and systemic inflammation/oxidative stress during maximal exercise in subjects with chronic obstructive pulmonary disease (COPD) who were not selected based on pulmonary hypertension (PH).
Twenty-four COPD patients with moderate-severe obstruction (age 59 ± 7 years, FEV1 53 ± 13% predicted) participated in a randomized, double-blind, placebo-controlled crossover trial. Each subject received a single nebulized dose of 5.0 μg iloprost or placebo on non-consecutive days followed by maximal cardiopulmonary exercise tests. The primary outcome was DH quantified by end-expiratory lung volume/total lung capacity ratio (EELV/TLC) at metabolic isotime.
Inhaled iloprost was well-tolerated and reduced submaximal alveolar dead-space fraction but did not significantly reduce DH (0.70 ± 0.09 vs 0.69 ± 0.07 following placebo and iloprost, respectively, p = 0.38). Maximal exercise time (9.1 ± 2.3 vs 9.3 ± 2.2 min, p = 0.31) and peak oxygen uptake (17.4 ± 6.3 vs 17.9 ± 6.9 mL/kg/min, p = 0.30) were not significantly different following placebo versus iloprost.
A single dose of inhaled iloprost was safe and reduced alveolar dead space fraction; however, it was not efficacious in modulating DH or improving exercise capacity in COPD patients who were not selected for the presence of PH.
•Iloprost is an inhaled prostacyclin analog that may improve ventilation-perfusion matching.•This randomized crossover trial studied the acute effects of iloprost on COPD patients.•Iloprost was safe but did not improve dynamic hyperinflation or exercise capacity in COPD patients.</description><subject>Administration, Inhalation</subject><subject>Aged</subject><subject>Alveoli</subject><subject>Chronic obstructive pulmonary disease</subject><subject>Cross-Over Studies</subject><subject>Double-Blind Method</subject><subject>Dyspnea</subject><subject>Exercise</subject><subject>Exercise - physiology</subject><subject>Exercise test</subject><subject>Exercise Test - methods</subject><subject>Female</subject><subject>Humans</subject><subject>Hypertension</subject><subject>Iloprost</subject><subject>Iloprost - administration & dosage</subject><subject>Inflammation</subject><subject>Lung diseases</subject><subject>Lung Volume Measurements</subject><subject>Lungs</subject><subject>Male</subject><subject>Metabolism</subject><subject>Middle Aged</subject><subject>Obstructive lung disease</subject><subject>Oxidative stress</subject><subject>Oxidative Stress - drug effects</subject><subject>Oxygen Consumption</subject><subject>Oxygen uptake</subject><subject>Patients</subject><subject>Placebos</subject><subject>Prostacyclin</subject><subject>Pulmonary arteries</subject><subject>Pulmonary Disease, Chronic Obstructive - drug therapy</subject><subject>Pulmonary Disease, Chronic Obstructive - metabolism</subject><subject>Pulmonary Disease, Chronic Obstructive - physiopathology</subject><subject>Total Lung Capacity</subject><issn>0954-6111</issn><issn>1532-3064</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2021</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kU2P0zAQhiMEYsvCH-CALHHhkuLvJAitVJVPaaXlAGfLscfUVWIHO6kovx6XLivgwMnyzDOv5p23qp4SvCaYyJf7dRrBrimmpBQkE_xetSKC0Zphye9XK9wJXktCyEX1KOc9xrjjHD-sLhhrKJGdXFVpY5YZEDgHZkbRIR92egCL_BCnFHOpBQTfIRmfAdlj0KM3aHecIPngBj370vcBbW8-vUFT-UKY8yu0QUkHG0f_o0iZopPjARLK82KPj6sHTg8Znty-l9WXd28_bz_U1zfvP24317XhLZtrRlvJGyxxi3kvDAhnZTFAmei1xn1jrGgbbp0lzhnWCGEdxbrFmDbC9h1ml9XVWXda-nInUzZLelBT8qNORxW1V393gt-pr_GgWk4Flm0ReHErkOK3BfKsRp8NDIMOEJesCkVa3jWdKOjzf9B9XFIo9gpFhWS4IaxQ9Ez9ukgCd7cMweoUqdqrU6TqFKk6R1qGnv1p427kd4YFeH0GoBzz4CGpbEoMBqxPJVRlo_-f_k9DK7Oo</recordid><startdate>20210401</startdate><enddate>20210401</enddate><creator>Lammi, Matthew R.</creator><creator>Ghonim, Mohamed A.</creator><creator>Johnson, Jessica</creator><creator>D'Aquin, Johnny</creator><creator>Zamjahn, John B.</creator><creator>Pellett, Andy</creator><creator>Okpechi, Samuel C.</creator><creator>Romaine, Connie</creator><creator>Pyakurel, Kusma</creator><creator>Luu, Hahn H.</creator><creator>Shellito, Judd E.</creator><creator>Boulares, A. Hamid</creator><creator>deBoisblanc, Bennett P.</creator><general>Elsevier Ltd</general><general>Elsevier Limited</general><scope>6I.</scope><scope>AAFTH</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>7U9</scope><scope>ASE</scope><scope>FPQ</scope><scope>H94</scope><scope>K6X</scope><scope>K9.</scope><scope>M7N</scope><scope>NAPCQ</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20210401</creationdate><title>Acute effect of inhaled iloprost on exercise dynamic hyperinflation in COPD patients: A randomized crossover study</title><author>Lammi, Matthew R. ; Ghonim, Mohamed A. ; Johnson, Jessica ; D'Aquin, Johnny ; Zamjahn, John B. ; Pellett, Andy ; Okpechi, Samuel C. ; Romaine, Connie ; Pyakurel, Kusma ; Luu, Hahn H. ; Shellito, Judd E. ; Boulares, A. Hamid ; deBoisblanc, Bennett P.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c483t-328647060804b5ce5fd6009235baa0b7cd5874dfd1ffc3755df20a800275db903</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2021</creationdate><topic>Administration, Inhalation</topic><topic>Aged</topic><topic>Alveoli</topic><topic>Chronic obstructive pulmonary disease</topic><topic>Cross-Over Studies</topic><topic>Double-Blind Method</topic><topic>Dyspnea</topic><topic>Exercise</topic><topic>Exercise - physiology</topic><topic>Exercise test</topic><topic>Exercise Test - methods</topic><topic>Female</topic><topic>Humans</topic><topic>Hypertension</topic><topic>Iloprost</topic><topic>Iloprost - administration & dosage</topic><topic>Inflammation</topic><topic>Lung diseases</topic><topic>Lung Volume Measurements</topic><topic>Lungs</topic><topic>Male</topic><topic>Metabolism</topic><topic>Middle Aged</topic><topic>Obstructive lung disease</topic><topic>Oxidative stress</topic><topic>Oxidative Stress - drug effects</topic><topic>Oxygen Consumption</topic><topic>Oxygen uptake</topic><topic>Patients</topic><topic>Placebos</topic><topic>Prostacyclin</topic><topic>Pulmonary arteries</topic><topic>Pulmonary Disease, Chronic Obstructive - drug therapy</topic><topic>Pulmonary Disease, Chronic Obstructive - metabolism</topic><topic>Pulmonary Disease, Chronic Obstructive - physiopathology</topic><topic>Total Lung Capacity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Lammi, Matthew R.</creatorcontrib><creatorcontrib>Ghonim, Mohamed A.</creatorcontrib><creatorcontrib>Johnson, Jessica</creatorcontrib><creatorcontrib>D'Aquin, Johnny</creatorcontrib><creatorcontrib>Zamjahn, John B.</creatorcontrib><creatorcontrib>Pellett, Andy</creatorcontrib><creatorcontrib>Okpechi, Samuel C.</creatorcontrib><creatorcontrib>Romaine, Connie</creatorcontrib><creatorcontrib>Pyakurel, Kusma</creatorcontrib><creatorcontrib>Luu, Hahn H.</creatorcontrib><creatorcontrib>Shellito, Judd E.</creatorcontrib><creatorcontrib>Boulares, A. Hamid</creatorcontrib><creatorcontrib>deBoisblanc, Bennett P.</creatorcontrib><collection>ScienceDirect Open Access Titles</collection><collection>Elsevier:ScienceDirect:Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Virology and AIDS Abstracts</collection><collection>British Nursing Index</collection><collection>British Nursing Index (BNI) (1985 to Present)</collection><collection>AIDS and Cancer Research Abstracts</collection><collection>British Nursing Index</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><collection>Nursing & Allied Health Premium</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Respiratory medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Lammi, Matthew R.</au><au>Ghonim, Mohamed A.</au><au>Johnson, Jessica</au><au>D'Aquin, Johnny</au><au>Zamjahn, John B.</au><au>Pellett, Andy</au><au>Okpechi, Samuel C.</au><au>Romaine, Connie</au><au>Pyakurel, Kusma</au><au>Luu, Hahn H.</au><au>Shellito, Judd E.</au><au>Boulares, A. Hamid</au><au>deBoisblanc, Bennett P.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Acute effect of inhaled iloprost on exercise dynamic hyperinflation in COPD patients: A randomized crossover study</atitle><jtitle>Respiratory medicine</jtitle><addtitle>Respir Med</addtitle><date>2021-04-01</date><risdate>2021</risdate><volume>180</volume><spage>106354</spage><epage>106354</epage><pages>106354-106354</pages><artnum>106354</artnum><issn>0954-6111</issn><eissn>1532-3064</eissn><abstract>We tested whether the prostacyclin analog inhaled iloprost modulates dead space, dynamic hyperinflation (DH), and systemic inflammation/oxidative stress during maximal exercise in subjects with chronic obstructive pulmonary disease (COPD) who were not selected based on pulmonary hypertension (PH).
Twenty-four COPD patients with moderate-severe obstruction (age 59 ± 7 years, FEV1 53 ± 13% predicted) participated in a randomized, double-blind, placebo-controlled crossover trial. Each subject received a single nebulized dose of 5.0 μg iloprost or placebo on non-consecutive days followed by maximal cardiopulmonary exercise tests. The primary outcome was DH quantified by end-expiratory lung volume/total lung capacity ratio (EELV/TLC) at metabolic isotime.
Inhaled iloprost was well-tolerated and reduced submaximal alveolar dead-space fraction but did not significantly reduce DH (0.70 ± 0.09 vs 0.69 ± 0.07 following placebo and iloprost, respectively, p = 0.38). Maximal exercise time (9.1 ± 2.3 vs 9.3 ± 2.2 min, p = 0.31) and peak oxygen uptake (17.4 ± 6.3 vs 17.9 ± 6.9 mL/kg/min, p = 0.30) were not significantly different following placebo versus iloprost.
A single dose of inhaled iloprost was safe and reduced alveolar dead space fraction; however, it was not efficacious in modulating DH or improving exercise capacity in COPD patients who were not selected for the presence of PH.
•Iloprost is an inhaled prostacyclin analog that may improve ventilation-perfusion matching.•This randomized crossover trial studied the acute effects of iloprost on COPD patients.•Iloprost was safe but did not improve dynamic hyperinflation or exercise capacity in COPD patients.</abstract><cop>England</cop><pub>Elsevier Ltd</pub><pmid>33721696</pmid><doi>10.1016/j.rmed.2021.106354</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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source | MEDLINE; ScienceDirect Journals (5 years ago - present); EZB-FREE-00999 freely available EZB journals |
subjects | Administration, Inhalation Aged Alveoli Chronic obstructive pulmonary disease Cross-Over Studies Double-Blind Method Dyspnea Exercise Exercise - physiology Exercise test Exercise Test - methods Female Humans Hypertension Iloprost Iloprost - administration & dosage Inflammation Lung diseases Lung Volume Measurements Lungs Male Metabolism Middle Aged Obstructive lung disease Oxidative stress Oxidative Stress - drug effects Oxygen Consumption Oxygen uptake Patients Placebos Prostacyclin Pulmonary arteries Pulmonary Disease, Chronic Obstructive - drug therapy Pulmonary Disease, Chronic Obstructive - metabolism Pulmonary Disease, Chronic Obstructive - physiopathology Total Lung Capacity |
title | Acute effect of inhaled iloprost on exercise dynamic hyperinflation in COPD patients: A randomized crossover study |
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