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BACKGROUND - Omalizumab is indicated for treatment of patients with moderate to severe allergic asthma. Previous studies have shown 70% of these patients also have chronic rhinosinusitis (CRS). The present series examines the impact of omalizumab on medication use for CRS in a cohort of asthmatic CRS patients who received this therapy.
METHODS - The sample included 25 patients with adequate prescription data preinitiation and postinitiation of therapy. Data was available for a full 12 months both preinitiation and postinitiation of therapy in 20 of 25 patients and for 4 to 8 months in the remaining 5 of 25. Average antibiotic use (# of unique prescriptions per month) and systemic steroid dose (mg/month) were tabulated for each patient and compared before and after initiation of therapy.
RESULTS - Mean antibiotic prescriptions/month decreased by 37%, and this was statistically significant (p = 0.013). Antibiotic use decreased in 15 of 25 (60%), was the same in 7 of 25 (28%), and increased in 3 of 25 (12%) patients. Chronic steroid administration was required in 19 of 25 patients, and dosing was highly variable. Mean monthly steroid dose decreased substantially in 8 of 19 (42%) patients, with reduction ranging from 40% to 100% from pretreatment levels. A modest decrease of 17% to 30% was observed in 4 of 19 (21%) patients. Steroid use was essentially unchanged in 4 of 19 (21%), but dramatically increased (71% to 366% above pretreatment dose) in 3 of 19 (15%) patients.
CONCLUSION - Omalizumab therapy is associated with a decrease in overall antibiotic use for CRS. A subset of patients also experience significant reduction in steroid dependence. Further study is necessary to determine factors predictive of response.
© 2015 ARS-AAOA, LLC.
Tuberculosis affects nine million individuals and kills almost two million people every year. The only vaccine available, Bacillus Calmette-Guerin (BCG), has been used since its inception in 1921. Although BCG induces host-protective T helper 1 (Th1) cell immune responses, which play a central role in host protection, its efficacy is unsatisfactory, suggesting that additional methods to enhance protective immune responses are needed. Recently we have shown that simultaneous inhibition of Th2 cells and Tregs by using the pharmacological inhibitors suplatast tosylate and D4476, respectively, dramatically enhances Mycobacterium tuberculosis clearance and induces superior Th1 responses. Here we show that treatment with these two drugs during BCG vaccination dramatically improves vaccine efficacy. Furthermore, we demonstrate that these drugs induce a shift in the development of T cell memory, favoring central memory T (Tcm) cell responses over effector memory T (Tem) cell responses. Collectively, our findings provide evidence that simultaneous inhibition of Th2 cells and Tregs during BCG vaccination promotes vaccine efficacy.
© 2014 by The American Society for Biochemistry and Molecular Biology, Inc.
MDR1 (P-glycoprotein) is an important factor in the disposition of many drugs, and the involved processes often exhibit considerable interindividual variability that may be genetically determined. Single-strand conformational polymorphism analysis and direct sequencing of exonic MDR1 deoxyribonucleic acid from 37 healthy European American and 23 healthy African American subjects identified 10 single nucleotide polymorphisms (SNPs), including 6 nonsynonymous variants, occurring in various allelic combinations. Population frequencies of the 15 identified alleles varied according to racial background. Two synonymous SNPs (C1236T in exon 12 and C3435T in exon 26) and a nonsynonymous SNP (G2677T, Ala893Ser) in exon 21 were found to be linked (MDR1*2 ) and occurred in 62% of European Americans and 13% of African Americans. In vitro expression of MDR1 encoding Ala893 (MDR1*1 ) or a site-directed Ser893 mutation (MDR1*2 ) indicated enhanced efflux of digoxin by cells expressing the MDR1-Ser893 variant. In vivo functional relevance of this SNP was assessed with the known P-glycoprotein drug substrate fexofenadine as a probe of the transporter's activity. In humans, MDR1*1 and MDR1*2 variants were associated with differences in fexofenadine levels, consistent with the in vitro data, with the area under the plasma level-time curve being almost 40% greater in the *1/*1 genotype compared with the *2/*2 and the *1/*2 heterozygotes having an intermediate value, suggesting enhanced in vivo P-glycoprotein activity among subjects with the MDR1*2 allele. Thus allelic variation in MDR1 is more common than previously recognized and involves multiple SNPs whose allelic frequencies vary between populations, and some of these SNPs are associated with altered P-glycoprotein function.