Aleksandar Perić, Danilo Vojvodić, Nenad Baletić, Aneta Perić and Olivera Miljanović
Immunomodulatory and Clinical Effects of Long-Term Low-Dose Macrolide Treatment of Chronic Rhinosinusitis with Nasal Polyposis
Immunomodulatory treatment of chronic rhinosinusitis with nasal polyposis (CRSwNP) by macrolide antibiotics represents a challenging alternative to conventional therapy and surgery, still being at the very beginning. Immune and inflammatory processes in nasal and paranasal sinus mucosa, crucial in the etiopathogenesis of nasal polyps (NPs) are reflected in levels of various local mediators, found both in mucosa and nasal fluid. In this prospective study, we assessed the immunomodulatory and clinical effects of longterm low-dose oral macrolide treatment in the management of CRSwNP. Twenty-two (n = 22) nonasthmatic, nonallergic patients with CRSwNP were administered clarithromycin (CAM) 500 mg/day single oral dose for eight weeks. We measured the levels of proinflammatory cytokines TNF-α, TNF-β, and IL-1β, Th1 cytokines IL-2, IL-12, and IFN-γ, Th2 cytokines IL-4, IL-5, IL-6, and IL-10, and chemokine IL-8 in the nasal fluid samples, before and after treatment, using a flow cytometric method. We also scored each of the 22 patients before and after therapy according to Tsicopoulos' global nasal symptom score and Malm's endoscopic score. Following treatment, we found significantly reduced levels of IL-8 (p<0.01) and TNF-α (p<0.01) in nasal secretions. Macrolide therapy decreased the size of polyps in 45.45% of the patients. We concluded that long-term low-dose treatment with CAM was effective in the management of CRSwNP. We suggest that macrolides can be an alternative to topical and systemic corticosteroids in the management of CRSwNP.
Aleksandar Perić, Danilo Vojvodić, Biserka Vukomanović-Đurđević and Nenad Baletić
Eosinophilic Inflammation in Allergic Rhinitis and Nasal Polyposis
On histopathological examination, nasal polyps and nasal mucosa in allergic rhinitis show different forms of pseudostratified respiratory epithelium, whereas the dominant characteristic of lamina propria is an eosinophilic infiltration. The aim of this study was to compare interleukin (IL)-5 and eosinophilic cationic protein (ECP) levels in the nasal fluid of 42 patients: 12 with allergic rhinitis and nasal septal deviation, 17 non-atopic patients with nasal polyposis, and 13 atopic nasal polyp patients were enrolled in this cross-sectional study. Nasal secretion samples were collected a few days before surgery. The levels of IL-5 were measured using flow cytometry and the ECP using a commercial ELISA kit. In addition, we counted eosinophils in hematoxylin-and-eosin-stained sections of all nasal polyp and all nasal mucosa samples taken from the inferior nasal turbinates during septoplasty. A significantly higher concentration of IL-5 was found in the nasal fluid of atopic patients with nasal polyposis than in non-atopic nasal polyp patients (p=0.025) and patients with allergic rhinitis (p=0.05). ECP was higher in atopic nasal polyp patients than in patients with allergic rhinitis (p<0.0001) and than in non-atopic nasal polyp patients (p<0.0001). Polyp eosinophils were higher in atopic' than in non-atopic patients (p<0.0001) and higher than in the mucosa of patients with allergic rhinitis (p<0.0001). These however had significantly more mucosal eosinophils than was found in the polyps of non-atopic patients' (p=0.025). ECP levels in nasal fluid and eosinophil counts in tissue specimens correlated well in all three groups of patients. Our study has shown that atopic nasal polyp patients have a higher level of eosinophilic inflammation than non-atopic patients with nasal polyps and patients with allergic rhinitis.