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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Veröffentlicht in:Respiratory medicine 2021-04, Vol.180, p.106354-106354, Article 106354
Hauptverfasser: 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.
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container_end_page 106354
container_issue
container_start_page 106354
container_title Respiratory medicine
container_volume 180
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.
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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. 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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 &amp; 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. 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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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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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