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Perić Aleksandar
12/2013Dissertation
The concentrations of inflammatory mediators in nasal secretions could reflect the inflammatory status of the nasal mucosa and evolution of sinus disease. The results of previous investigations suggest that macrolide antibiotics could be effective in the treatment of chronic rhinosinusitis and nasal polyposis. The mean goal of this study was to compare the efects of preoperative clarithromycin administration and surgical treatment with sole surgical treatment in patients with nasal polyposis. Therefore, we assessed the immunomodulatory and clinical efects of long-term low-dose clarithomycin treatment in allergic and non-allergic patients with nasal polyps. Method. Eighty (n = 80) patients with nasal polyposis were included in this investigation. Twenty-two non-allergic and 18 allergic patients were administered clarithromycin 500 mg/day single oral dose for eigth weeks. We measured the levels of Th1 cytokines IL-2, IL-12 and IFN-γ, Th2 cytokines IL-4, IL-5 and IL-6, proinflammatory cytokines TNF-α, TNF-β and IL-1β, an antiinflammatory cytokine IL-10, and a chemokine IL-8 in the nasal secretions, before and after antibiotic administration. We also scored each of the patients, before and after treatment, according to nasal symptom score and endoscopic score. After macrolide treatment, endoscopic sinus surgery was performed in all patients in whom we endoscopically found nasal polyps of different sizes. The eosinophils were counted in hematoxylin-eosin stained sections of nasal poyp samples, in the epithelium and the lamina propria separately. The second investigatied group consisted of 40 patients with nasal polyposis, 20 non-atopic and 20 atopic, treated only surgically, and also scored clinically before and after surgery. All remowed nasal polyps were also analysed pathohistologically. The nasal symptom scores and endoscopic scores after macrolide treatment/surgical treatment, and 6 and 12 months postoperatively were evaluated. Results. Long-term low-dose clarithromycin treatment showed similar clinical effects in non-allergic and allergic patients with nasal polyposis. After antibiotic administration, we found significantly lower levels of chemokine IL-8 in the nasal secretions in both non-atopic and atopic patients. Therefore, in non-atopic nasal polyp patients we found reduced levels of TNF-α, whereas in atopic ones, we found lower concentration of IL-1β, IL-6 and IL- 12. The decreases in IL-8 levels in nasal secretions were assiciated with reduction of polyp size both in atopics and non-atopics. Nasal polyps with more intense epithelial eosinophil infiltration respond worse to long-term low-dose clarithromycin therapy. Finally, at the time point of 12 months afret surgical treatment, in the group of preoperitevely treated, the number of nasal polyp patients was 27.5% less than in the group of only surgically treated patients. Conclusion. Long-term low-dose clarithromycin administration have similar clinical effects in non-allergic and allergic aptients with nasal polyposis, due to immunomodulatory and antiinflammatory action. On the other hand, clarithomycin use shows different immunomodulatory effects in non-atopic and atopic effects. Evaluation of the inflammatory mediator levels in nasal secretions can be valuable path for assessment the effects of antibiotic treatment in patients with nasal polyposis. These results suggest that preoperative clarithromycin administration postpones nasal polyp relapse after endoscopic sinus surgery. Koncentracije medijatora zapaljenske reakcije u nosnom sekretu odražavaju status zapaljenja sluzokože nosa, kao i razvoj zapaljenske bolesti u paranazalnim sinusima. Rezultati prethodnih istraživanja sugerišu da primena makrolidnih antibiotika može biti efikasna u lečenju hroničnog rinosinuzitisa i nosno-sinusne polipoze. Osnovni cilj istraživanja bio je da se uporede efekti preoperativne primene makrolidnog antibiotika klaritromicina i naknadnog hirurškog lečenja sa efektima isključive primene hirurškog lečenja u bolesnika sa nosno-sinusnom polipozom. Osim toga, bilo je potrebno proceniti imunomodulacijske i kliničke efekte dugotrajne, niskodozirane terapije klaritromicinom u alergičnih i nealergičnih pacijenata sa nosnom polipozom. Metod. U studiju je bilo uključeno ukupno osamdesetoro (80) bolesnika sa nosno-sinusnom polipozom. Ukupno četrdeset bolesnika, 22-oje nealergičnih i 18-oro alergičnih je dobijalo klaritromicin u jednoj dnevnoj dozi od 500 miligrama (500 mg) tokom osam nedelja. Određivane su koncentracije Th1 citokina IL-2, IL-12 i IFN-γ, Th2 citokina IL-4, IL-5 i IL-6, proinflamatornih citokina TNF-α, TNF-β, IL-1β, antiinflamatornog citokina IL-10 i jednog hemokina (IL- 8) u uzorcima nosnog sekreta, pre i nakon lečenja. Svaki od pacijenata je bio klinički klasifikovan pre i nakon lečenja, u skladu sa nosnim simptom skorom i endoskopskim skorom. Nakon antibiotskog lečenja, svakom od ispitanika kod koga su endoskopski pregledom verifikovani nosni polipi, isti su bili hirurški odstranjeni. U uzorcima tkiva nosnih polipa bojenih hematoksilin-eozin tehnikom, brojani su eozinofili, posebno u epitelu i lamini propriji. U drugu grupu je bilo uključeno ukupno 40-oro bolesnika sa nosnom polipozom (20-oro nealergičnih i 20-oro alergičnih), koji su bili isključivo hirurški lečeni i koji su takođe bili klinički klasifikovani pre i nakon lečenja. I u ovoj grupi bolesnika su odstranjeni polipi bili patohistološki analizirani. Nakon završene terapije, svih 80-oro bolesnika je biti kontrolisano rinoskopskim i endoskopskim pregledom, a preseci u praćenju su bili pravljeni nakon 6 i nakon 12 meseci. Rezultati. Dugotrajna, niskodozirana primena klaritromicina pokazala je približno iste kliničke efekte u nealergičnih i alergičnih bolesnika sa nosnim polipima. Koncentracije hemokina IL-8 bila je nakon terapije klaritromicinom snižena u uzorcima nosnog sekreta i u nealergičnih i u alergičnih bolesnika. Koncentracije proinflamatornog Th1 citokina TNF-α bila je značajno snižena u nealergičnih, dok su koncentracije citokina IL- 1β, IL-6 i IL-12 bile značajno manje u alergičnih bolesnika. Uočena je povezanost između sniženja koncentracija IL-8 u nosnom sekretu i smanjivanja veličine nosnih polipa u obe grupe ispitanika. Primena klaritromicina je imala slabije efekte u pacijenata sa većim brojem eozinofila u uzorcima tkiva nosnih polipa, konkretno u onih sa gušćom eozinofilnom infiltracijom epitelnog sloja nosne sluzokože. Na kraju, u grupi preoperativno lečenih klaritromicinom, 12 meseci nakon hirurškog lečenja, bilo je za 27,5% manje ispitanika kojima je endoskopskim pregledom verifikovano ponovno prisustvo polipa u nosu, u odnosu na ispitanike koji su bili lečeni samo hirurški. Zaključak. Dugotrajna, niskodozirana primena klaritromicina ima slične kliničke efekte u nealergičnih i alergičnih pacijenata sa nosnom polipozom, zahvaljujući svom imunomodulacijskom i antiinflamatornom dejstvu. Sa druge strane, primena ovog leka pokazuje različite imunomodulacijske efekte kod nealergičnih i alergičnih pacijenata. Merenje koncentracija medijatora zapaljenske reakcije u nosnom sekretu može biti koristan izvor informacija za procenu efekata antibiotskog lečenja nosne polipoze. Rezultati sugerišu da preoperativna primena klaritromicina odlaže ponovni rast nosnih polipa.
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