Effect of Low-Dose, Long-Term Roxithromycin on Airway Inflammation and Remodeling of Stable Noncystic Fibrosis Bronchiectasis

Abstract

Background. Noncystic fibrosis bronchiectasis (NCFB) is characterized by airway expansion and recurrent acute exacerbations. Macrolide has been shown to exhibit anti-inflammatory effects in some chronic airway diseases. Objective. To assess the efficacy of roxithromycin on airway inflammation and remodeling in patients with NCFB under steady state. Methods. The study involved an open-label design in 52 eligible Chinese patients with NCFB, who were assigned to control (receiving no treatment) and roxithromycin (receiving 150 mg/day for 6 months) groups. At baseline and 6 months, the inflammatory markers such as interleukin- (IL-)8, neutrophil elastase (NE), matrix metalloproteinase- (MMP)9, hyaluronidase (HA), and type IV collagen in sputum were measured, along with the detection of dilated bronchus by throat computed tomography scan, and assessed the exacerbation. Results. Forty-three patients completed the study. The neutrophil in the sputum was decreased in roxithromycin group compared with control (P < 0.05). IL-8, NE, MMP-9, HA, and type IV collagen in sputum were also decreased in roxithromycin group compared with the control group (all P < 0.01). Airway thickness of dilated bronchus and exacerbation were reduced in roxithromycin group compared with the control (all P < 0.05). Conclusions. Roxithromycin can reduce airway inflammation and airway thickness of dilated bronchus in patients with NCFB.

A systematic review of pharmacotherapeutic clinical trial end-points for bronchiectasis in adults

“…Macrolides are typically referred to as both antibiotic and anti-inflammatory. We classified them as antibiotics for the purposes of analysis, except in one case where the investigators specifically referred to the trial as testing the anti-inflammatory effect [15]. Table 2 shows an overview of the selected trials used in this review and the end-points which each trial used grouped into seven main categories.…”

“…Of the 23 RCTs identified by our search, we counted 31 primary end-points (five studies used co-primary end-points: HERNANDO et al [17], BILTON et al [20] and LIU et al [15] each used two, WONG et al [18] Initial search: PubMed Clinical trials in humans published in English between 2008-2018 "bronchiectasis"…”

“…We found, however, that exacerbation end-points were also used in short studies where the chance of a patient exacerbating within such a brief time frame is low [17,20,21,23,24]. From the trials reviewed, Mannitol BILTON [20] Ciprofloxacin DPI WILSON [21] BAT ALTENBURG [12] BLESS SERISIER [22] ORBIT-2 SERISIER [23] Azithromycin DE DIEGO [24] Azithromycin LOURDESAMY [28] Inhaled mannitol BILTON [29] Roxithromycin LIU [15] Tobramycin ORRIOLS [13] STRATUS DE SOYZA [30] Inhaled colistin HAWORTH [25] Atorvastatin MANDAL [26] AIR-BX1 and AIR-BX2 BARKER [27] RESPIRE I and II DE SOYZA [8] and AKSAMIT [9] Hyaluronic acid plus 7% hypertonic saline, HERRERO-CORTINA [10] Nebulised amikacin AILIYAER [31] Green: end-point(s) passed; pink: end-point(s) failed; orange: not clear or mixed results. HRQoL: healthrelated quality of life.…”

Adult patients with bronchiectasis: clinical guideline of European Respiratory Society

“…Экспертами выявлено 8 систематических обзоров [65-72] и 17 исследований, относящихся к данной проблеме [36,52,[73][74][75][76][77][78][79][80][81][82][83][84][85][86]. В резюме собранных доказательств показано, что у взрослых пациентов с БЭ при длительной АБТ -как ингаляционной, так и пероральной -уменьшается число обострений, увеличивается время до очередного обострения, снижаются гнойность мокроты и одышка, однако АБТ также сопровождается нарастанием побочных эффектов и антибактериальной резистентности.…”

Bronchiectasis in the Last Five Years: New Developments

“…They demonstrated a pooled reduction in exacerbation frequency of nearly 60% with macrolide therapy (risk ratio: 0.42 (0.29, 0.61) [44] and increased time to first exacerbation, cementing their role in this disorder [45] (Table 2). A small ( n = 52) open label parallel trial comparing 150 mg/day roxithromycin to a placebo over six months found that roxithromycin significantly increased time to first exacerbation (median 264 vs. 113 days, p = 0.022), reduced sputum biomarkers of airway inflammation, and improved CT-based measures of airway thickness [46]. Type of macrolide used, dose, and duration of therapy varies amongst studies, making direct comparisons difficult.…”