Effects of doxycycline on local and systemic inflammation in stable COPD patients, a randomized clinical trial. (January 2016)

• Record Type: Journal Article
• Authors: Prins, Hendrik J.; Daniels, Johannes M.A.; Lindeman, Jan H.; Lutter, René; Boersma, Wim G.
• Is Part Of: Respiratory medicine. Volume 110(2016)
• Page Start: 46
• Page End: 52
• Publication Date: 2016-01
• Subjects: COPD -- Inflammation -- Doxycycline -- Anti-inflammatory effect; COPD Chronic Obstructive Pulmonary Disease -- MPO Myeloperoxidase -- MMP's matrix metalloproteinases -- TNF Tumour necrosis factor -- IL1 Interleukin 1 -- IL6 Interleukin 6 -- CRP C-reactive protein -- ECM Extracellular matrix -- DTT Dithiothreitol -- FVC Forced vital capacity -- FEV1 Forced expiratory volume in 1 s -- IQR Inter quartile range -- AA Abdominal aneurysm -- PPM's Potential pathogenic microorganisms; Chest -- Diseases -- Periodicals; Chest -- Diseases -- Great Britain -- Periodicals; Respiratory organs -- Diseases -- Periodicals; Respiratory Tract Diseases -- Periodicals; Appareil respiratoire -- Maladies -- Périodiques; Thorax -- Maladies -- Périodiques; Appareil respiratoire -- Maladies -- Traitement -- Périodiques; Electronic journals; 616.2
• DOI: 10.1016/j.rmed.2015.10.009
• Languages: English
• ISSNs: 0954-6111

Abstract

Abstract: Neutrophilic inflammation plays a causal role in Chronic Obstructive Pulmonary Disease (COPD). Neutrophil derived myeloperoxidase(MPO) matrix metalloproteinases(MMP's), and elastases are thought to contribute to the perpetuation of the disease. The tetracycline analogue doxycycline has been shown to inhibit neutrophil-mediated inflammation. It was thus reasoned that doxycycline may attenuate neutrophil-mediated inflammation in COPD. Methods: In this double blind randomized controlled trial the effect of a 3-week course of doxycycline on sputum and systemic inflammatory parameters was evaluated in stable COPD patients. In order to exclude inflammation by bacterial colonisation patients must have 2 negative sputum cultures in the previous year. The effect of doxycycline treatment on inflammatory markers (TNF-α, IL-1β and IL-6) and neutrophil specific markers in sputum (MPO, MMP's, and IL-8) and serum C-reactive protein was evaluated. Sputum was obtained by sputum induction with hypertonic saline. Results: A total of 41 patients were included. Ten patients were excluded as they were not able to produce sputum at the first or second visit. Baseline characteristics were similar in the two groups. In the remaining patients doxycycline did not influence sputum MPO concentrations. Also MMP-8 and 9, IL-6 and IL-8 concentrations as well as lung function parameters were not affected by doxycycline. Systemic inflammation by means of CRP was also not influenced by doxycycline. Conclusion: A three week course of doxycycline did not influence MPO sputum levels nor any of the other inflammatory sputum and systemic markers. Trial registry: ClinicalTrials.gov; No.:NCT00857038 URL:clinicaltrials.gov . Highlights: We conducted a RCT with doxycycline in stable non colonized patients with COPD. Our endpoints were decrease in local and systemic inflammation. Doxycycline does not act as an anti-inflammatory agent in our trial.