Chronic rhinosinusitis (CRS) is a condition characterised by chronic inflammation of the paranasal sinuses, which shows a high prevalence worldwide and significantly affects patients’ quality of life (1). The treatment of CRS according to the European Position Paper on Rhinosinusitis and Nasal Polyps (EPOS) 2012 consists of intranasal or oral corticosteroids, nasal saline irrigation, antibiotics and surgery. The efficacy of antibiotics, however, remains controversial in the treatment of CRS (1).
Of the available antibiotics, the macrolides have been shown to have good bioavailability and tissue penetration, following oral administration (2,3). Since the first demonstration by Kikuchi and colleagues (4) of the effectiveness of long-term treatment with low-dose erythromycin in a cohort of 26 patients with CRS, this macrolide has been recommended in the treatment of CRS in Japan (5), as well as in the treatment of CRS without nasal polyps (CRSsNP) by the EPOS (1). Although the macrolides were widely applied for treating bacterial pathogens in CRS, increasing evidence has demonstrated that the macrolides possessed both anti-inflammatory and immunomodulatory effect (6-10), and lead to the concept of macrolides being immune-modulatory rather than anti-bacterial. However, several studies have shown some macrolides to have no significant benefits compared to placebo in the treatment of CRS (11-13), and therefore a matter of much debate presently. Pynnonen and colleagues (14) have conducted a meta-analysis of studies investigating the outcomes of long-term macrolide therapy for CRS and shown limited evidences to support long-term macrolide therapy. In particular, while studies in patients from Asian countries such as China and Japan have demonstrated macrolide and nasal steroids to provide a similar clinical effect for CRSsNP and both improving symptoms of CRS (13,15,16); some studies in patients from western countries have demonstrated different outcomes (11,17). Indeed, it is as been demonstrated that there was a difference of macrolide efficacy between Asian and western patients due to CRS endotypes (18), possibly as a result of differences in the inflammatory mechanisms in the ethnicity of the patients.
Since the publication of the meta-analysis by Pynnonen and colleagues (14), several studies investigating the curative effects of long-term macrolide therapy for CRS have been published. Thus, we have performed another meta-analysis of all available studies to date to re-evaluate the efficacy of macrolide therapy for CRS with additional objective measurements (endoscopic examination and CT examination) as well as distinguish the possible different curative effect between Asian and Caucasian.
PubMed, Embase and Cochrane databases were systematically searched by two independent reviewers for appropriate studies published up to December 2017. The search terms were “Macrolide” or “Clarithromycin” or “Erythromycin” or “Roxithromycin” or “Azithromycin” and “Chronic rhinosinusitis”. All published studies were included in the meta-analysis if they met the following criteria: (I) the criteria for diagnosis of CRS employed in all studies were clear and as recommended outline by the Rhinosinusitis Task Force (19) or European position paper on rhinosinusitis and nasal polyps (1); (II) the patients were aged over 14 years old; (III) all patients had received oral macrolide therapy; (IV) outcomes such as Sino-Nasal Outcome Test-20 (SNOT-20), SNOT-22, endoscopic scores, and computed tomography (CT) scan scores were reported; (V) all patients had signed informed consent before participation in the study; and (VI) published in English or Chinese language. Articles published as reviews, and abstracts or reports presented at scientific/medical meetings were excluded.