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Randomized Controlled Trial
. 2021 Apr-May:180:106354.
doi: 10.1016/j.rmed.2021.106354. Epub 2021 Mar 8.

Acute effect of inhaled iloprost on exercise dynamic hyperinflation in COPD patients: A randomized crossover study

Matthew R Lammi  1 , Mohamed A Ghonim  2 , Jessica Johnson  3 , Johnny D'Aquin  4 , John B Zamjahn  5 , Andy Pellett  5 , Samuel C Okpechi  6 , Connie Romaine  7 , Kusma Pyakurel  8 , Hahn H Luu  8 , Judd E Shellito  7 , A Hamid Boulares  8 , Bennett P deBoisblanc  9
Affiliations
Randomized Controlled Trial

Acute effect of inhaled iloprost on exercise dynamic hyperinflation in COPD patients: A randomized crossover study

Matthew R Lammi et al. Respir Med. 2021 Apr-May.

Abstract

Background and objective: 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).

Methods: 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.

Results: 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.

Conclusions: 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.

Keywords: Chronic obstructive pulmonary disease; Cross-over studies; Exercise test; Iloprost; Inflammation.

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Conflict of interest statement

Conflicts of interest: MRL, MAG, JJ, JD, JBZ, AP, SCO, CR, KP, HHL, JES, AHB, and BPD do not report any relevant conflicts of interest.

Figures

Figure 1:
Figure 1:
(A) Study flow. On Visit 1, all patients underwent baseline measurements. On Visits 2 and 3, patients received either placebo or iloprost and underwent cardiopulmonary exercise testing (CPET). The order was randomized and there was a median of 3 days between the 1st and 2nd CPETs. (B) Patient enrollment. Sequence “AB” was placebo on CPET 1 and iloprost on CPET 2, and sequence “BA” was iloprost on CPET 1 and placebo on CPET 2. FEV1=forced expiratory volume in 1 second. PFT=pulmonary function test, CPET=cardiopulmonary exercise test.
Figure 2:
Figure 2:
Dynamic hyperinflation (EELV/TLC) after placebo (A) and iloprost (B). Measurements were made at rest (prior to exercise) and at 3 matched metabolic isotimes. Significant DH occurred after placebo (A, p=0.02 for linear trend) but iloprost did not reduce DH (B). EELV=end-expiratory lung volume; TLC=total lung capacity.
Figure 3:
Figure 3:
Maximal exercise time (A) and peak VO2 (B) after placebo and iloprost. Data points represent individual patient values in this crossover trial.
See this image and copyright information in PMC

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