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Original Research: COPD |

Relapse in FEV1 Decline After Steroid Withdrawal in COPDLong-term Steroid Withdrawal in COPD

Lisette I. Z. Kunz, MD; Dirkje S. Postma, MD, PhD; Karin Klooster, BSc; Thérese S. Lapperre, MD, PhD; Judith M. Vonk, PhD; Jacob K. Sont, PhD; Huib A. M. Kerstjens, MD, PhD; Jiska B. Snoeck-Stroband, MD, PhD; Pieter S. Hiemstra, PhD; Peter J. Sterk, MD, PhD; the GLUCOLD Study Group
Author and Funding Information

From the Department of Pulmonology (Drs Kunz, Lapperre, and Hiemstra and the GLUCOLD Study Group) and Department of Medical Decision Making (Drs Sont and Snoeck-Stroband), LUMC, Leiden, The Netherlands; Department of Pulmonary Medicine (Drs Postma and Kerstjens and Ms Klooster) and Department of Epidemiology (Dr Vonk), UMCG, University of Groningen, Groningen, The Netherlands; Department of Respiratory and Critical Care Medicine (Dr Lapperre), Singapore General Hospital, Singapore; and Department of Respiratory Medicine (Dr Sterk), Academic Medical Center, Amsterdam, The Netherlands.

CORRESPONDENCE TO: Lisette I. Z. Kunz, MD, Department of Pulmonology, LUMC, Albinusdreef 2, NL2333-ZA Leiden, The Netherlands; e-mail: L.I.Z.Kunz@lumc.nl


Part of this article has been presented in poster form at the American Thoracic Society International Conference, May 16-21 2014, San Diego, CA, and published in abstract form (Kunz LIZ, Lapperre T, Snoeck-Stroband J, et al.; the GLUCOLD study group. American Thoracic Society International Conference Abstract. 2014;271:A6674.

FUNDING/SUPPORT: The study was funded by the Netherlands Organisation for Scientific Research (NWO) [Grant 940-35-033], Lung Foundation Netherlands [Grant 93.96.3], GlaxoSmithKline plc of The Netherlands [Grant SCO107656], UMCG, and LUMC.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians. See online for more details.


Chest. 2015;148(2):389-396. doi:10.1378/chest.14-3091
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BACKGROUND:  We previously observed that 30 months of inhaled corticosteroid (ICS) treatment can attenuate FEV1 decline in COPD, but it is unclear whether withdrawal induces a relapse. We hypothesized that FEV1 decline, airway hyperresponsiveness (AHR), and quality of life (QOL) deteriorate after ICS cessation even after prolonged use.

METHODS:  One hundred fourteen patients with moderate to severe COPD finished randomized 6-month or 30-month treatment with fluticasone (500 μg bid), 30-month treatment with fluticasone and salmeterol (500/50 μg bid), or placebo (first part of the Groningen and Leiden Universities Corticosteroids in Obstructive Lung Disease [GLUCOLD] study [GL1]). The subsequent 5 years, patients were prospectively followed annually, treated by their physician (GLUCOLD follow-up study [GL2]). Postbronchodilator FEV1, AHR, and QOL were initially recorded at baseline, at 30 months (GL1), and annually during GL2. Analysis was performed by linear mixed-effects models.

RESULTS:  Among 101 adherent patients during GL1, 79 patients started and 58 completed GL2. Patients using ICSs during GL1, but only using ICSs 0% to 50% of the time during GL2 (n = 56 of 79), had significantly accelerated annual FEV1 decline compared with GL1 (difference GL2-GL1 [95% CI]: 30-month treatment with fluticasone and salmeterol, −68 mL/y [−112 to −25], P = .002; 30-month treatment with fluticasone, −73 mL/y [−119 to −26], P = .002), accompanied by deterioration in AHR and QOL.

CONCLUSIONS:  ICS discontinuation after 30 months in COPD can worsen lung function decline, AHR, and QOL during 5-year follow-up. This suggests that ICS treatment lacks sustained disease-modifying effect after treatment cessation.

TRIAL REGISTRY:  ClinicalTrials.gov; No.: NCT00158847; URL: www.clinicaltrials.gov

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