| Objective:To systematically evaluate the efficacy and safety of long-term low-dose macrolides in the treatment of adult chronic rhinosinusitis(chronic rhinosinusitis,CRS),and to provide reference for the clinical application and research of this drug.Methods:According to the relevant requirements of the systematic review,Pubmed,The Cochrane Library,Chinese national knowledge infrastructure(CNKI),Wanfang Medical Network and VIP Database(VIP)were searched by computer to collect all the published research of long-term low-dose macrolides for treatment of adult patients,the search time limit was from the establishment of the library to September 2018.All studies of chronic rhinosinusitis(CRS)were based on pre-established inclusion and exclusion criteria for literature screening and quality evaluation.Data were extracted from the literature and Revman software was used for Meta-analysis.Finally,the results were fully interpretated and discussed.Results:Finally,34 articles including 3 369 subjects with chronic rhinosinusitis met the inclusion criteria,including 1588 subjects in the experimental group and 1781 subjects in the control group.Meta analysis showed:1.Compared with glucocorticoids nasal spray,clarithromycin significantly reduced facial pain scores,the difference was statistically significant [MD = 0.39,95% CI(0.07,0.72),Z = 2.36,P = 0.02].The improvement of the VAS score of overall symptoms,nasal congestion score,headache score,nasal discharge score,and olfactory disorder score was not superior to that of glucocorticoids nasal spray.The difference was not statistically significant[MD=0.10,95% CI(-0.36),0.56),Z = 0.42,P = 0.68;MD = 0.11,95% CI(-0.41,0.62),Z =0.41,P = 0.68;MD =-0.38,95% CI(-1.26,0.51),Z = 0.83,P = 0.40;MD = 0.12,95% CI(-0.62,0.87),Z = 0.33,P = 0.74;MD = 0.13,95% CI(-0.41,0.69),Z = 0.48,P = 0.63 ].2.The total effect of clarithromycin 250 mg was better than that of amoxicillin clavulanate potassium.The difference was statistically significant [OR=3.13,95% CI(2.23,4.41),Z=6.54,P<0.00001].The incidence of adverse reactions of clarithromycin 250 mg was lower than that of amoxicillin clavulanate potassium,the difference was statistically significant [OR=0.27,95% CI(0.14,0.55),Z=3.63,P=0.0003].Compared with amoxicillin clavulanate potassium,clarithromycin 250 mg significantly reduced nasal congestion score[MD=-1.84,95% CI(-2.26,-1.43),Z=8.70,P<0.00001],headache score [MD=-1.77,95% CI(-2.82,-0.72),Z = 3.30,P = 0.0010],nasal discharge score [MD =-1.79,95% CI(-2.25,-1.33),Z = 7.59,P < 0.00001],The difference was statistically significant.There was no significant improvement in the VAS score of overal symptoms and olfactory disorder score.The difference was not statistically significant [MD=-3.92,95% CI(-7.86,0.02),Z=1.95,P =0.05;MD = 0.24,95% CI(-1.60,2.07),Z = 0.25,P = 0.80].3.Compared with Biyuanshu combined placebo,clarithromycin 250 mg combined placebo significantly reduced nasal congestion score [MD=-1.08,95%ci(-2.10,-0.06),Z=2.07,P=0.04],nasal discharge score [MD=-1.12,95%ci(-2.14,-0.10),Z=2.15,P=0.03],and the difference was statistically significant.However,there was no significant improvement in the overall symptom of VAS score of overall symptoms and headache score.The difference was not statistically significant [MD=-0.92,95% CI(-1.88,0.04),Z=1.88,P=0.06;MD=-0.76,95% CI(-1.89,0.37),Z = 1.32,P = 0.19].4.The total efficacy of clarithromycin 250 mg combined basic treatment was better than that of single-use basic treatment.The difference was statistically significant [OR=4.80,95%CI(3.10,7.42),Z=7.04,P<0.00001].The incidence of adverse reactions was comparable between the two groups,and the difference was not statistically significant [OR=0.97,95% CI(0.53,1.80),Z=0.08,P=0.93].Compared with using basic treatment alone,clarithromycin250 mg combined basic treatment significantly reduced the overall VAS score of the overall symptoms [MD=-1.24,95% CI(-1.14,-1.08),Z=15.02,P<0.00001],nasal congestion score[MD=-0.86,95% CI(-1.57,-0.15),Z=2.38,P=0.02],headache score [MD=-0.82,95% CI(-1.09,-0.55),Z=5.99,P <0.00001],nasal discharge score [MD=-1.22,95% CI(-1.56,-0.87),Z=6.91,P<0.00001],olfactory disorder score [MD=-0.49,95% CI(-0.95,-0.03),Z=2.09,P=0.04],Lund-Mackay sinus CT score [MD=-1.51,95% CI(-2.19,-0.83),Z=4.33,P<0.00001],Lund-Kennedy endoscopic Score [MD=-1.51,95% CI(-1.93,-1.10),Z=7.12,P<0.00001],sino-nasal outcome test scale(SNOT)[MD=-0.46,95% CI(-0.61,-0.31),Z =6.11,P < 0.00001],the difference was statistically significant.However,the improvement in facial pain score was not statistically significant compared with using basic treatment alone[MD=-0.88,95% CI(-2.26,0.50),Z=1.25,P=0.21].5.The total efficacy of roxithromycin 150 mg combined basic treatment was better than that of using basic treatment alone,and the difference was statistically significant [OR=10.63,95% CI(5.17,21.87),Z=6.42,P<0.00001].Compared with using basic treatment alone,roxithromycin 150 mg combined basal treatment significantly reduced Lund-Mackay sinus CT scores [MD=-1.81,95% CI(-1.52,-0.84),Z=6.77,P<0.00001] and Lund-Kennedy nasal endoscopy score [MD=-1.85,95% CI(-1.95,-1.75),Z=35.08,P<0.00001],the difference was statistically significant,but compared with using basic treatment alone,the improvement of the overall symptoms of the VAS score of overall symptoms,the difference was not statistically significant compared with the baseline treatment [MD=-2.75,95% CI(-5.59,0.09),Z=1.90,P=0.06].6.Compared with placebo,macrolides significantly reduced the sino-nasal outcome scale(SNOT)scores,and the difference was statistically significant [MD=-0.45,95% CI(-0.89,-0.01),Z=2.01,P =0.04].There was no significant increase in the incidence of adverse reactions between macrolides and placebo,and the difference was not statistically significant(OR=0.88,95% CI(0.22,3.48),Z=0.18,P=0.86].However,compared with placebo,macrolides did not improve nasal congestion score,headache score,nasal discharge score,olfactory disorder score,facial pain score,Lund-Kennedy endoscopic score,and peak nasal inspiratory flow(PNIF).Significantly,the difference was not statistically significant[MD=0.30,95% CI(-1.36,1.96),Z=0.35,P=0.72;MD=0.40,95% CI(-1.09,1.89),Z=0.52,P= 0.60;MD=0,95% CI(-1.37,1.37),Z=0.00,P=1.00;MD=0.63,95% CI(-0.95,2.22),Z=0.79,P=0.43;MD=1.30,95% CI(-0.19,2.79),Z = 1.71,P = 0.09;MD =-0.50,95% CI(-1.05,0.05),Z = 1.77,P = 0.08;MD = 3.02,95% CI(-11.25,17.29),Z = 0.42,P = 0.68].Conclusion:1.The combined efficacy of clarithromycin 250 mg is comparable to that of nasal glucocorticoids,but it is superior to nasal glucocorticoids in improving facial pain.2.The comprehensive effect of clarithromycin 250 mg is better than that of amoxicillin and clavulanate potassium.The incidence of adverse reactions is also relatively lower.Clarithromycin 250 mg is superior to amoxicillin and clavulanate in improving nasal congestion,headache and salivation.3.Clarithromycin 250 mg + placebo compared with Biyuanshu + placebo showed no difference in improvement of overall symptoms,especially headache,but improved nasal congestion and salivation better than Biyuanshu + placebo.4.Clarithromycin 250 mg + basic treatment is better than the basic treatment alone,and the incidence of adverse reactions is better.The results of subjective and objective assessment also show that the improvement of facial pain is better than the basic treatment alone..5.The total efficacy of roxithromycin 150mg+ basic therapy is better than that of single-use basic therapy.In the objective assessment,roxithromycin 150mg+ basic therapy is better than single-use basic therapy,but the subjective disease assessment results show that it is compared with single-use basic therapy.There is not much difference.6.Comparison of the efficacy of the two macrolides with placebo showed that macrolides were superior to placebo in addition to placebo in the nasal sinus outcome scale(SNOT),in the remaining subjective assessments.There was no significant improvement in VAS score,nasal endoscopy score,and PNIF.The incidence of adverse reactions of macrolides is comparable to placebo.7.Long-term low-dose macrolides showed high safety in multiple groups of tests,and all of them showed good therapeutic effects in the comparison of the efficacy of different groups,and the incidence of adverse reactions was low.(The macrolides have no significant advantage compared with placebo,Biyuanshu,and nasal glucocorticoids,but can beeffectively treated with amoxicillin or clavulanate potassium or as an additional treatment for basic treatment.No increased adverse reactions. |
PDF Full Text Request