Association between TLR2/TLR4 gene polymorphisms and COPD phenotype in a Greek cohort.

BACKGROUND: Considering that the innate immune system plays a pivotal role in the pathogenesis of chronic obstructive pulmonary disease (COPD), we hypothesized that functional single-nucleotide polymorphisms (SNPs) of innate immune genes affect the disease phenotype and prognosis. AIM: To elucidate the contribution of common functional TLR2 and TLR4 SNPs and genotypic deficiency of the mannose-binding lectin (MBL) protein, both as single parameters and in combination, in Greek COPD patients. RESULTS: In a cohort of 114 Greek COPD patients, we confirmed that the presence of TLR4-D299G or TLR4-T399I SNPs was significantly associated with an earlier COPD stage (p = 0.003 and p = 0.009, respectively). In comparison, the absence of any analyzed polymorphism, including those of TLR2-R753Q and genotypic MBL deficiency, was significantly associated with a more severe disease phenotype, characterized by more frequent exacerbations (p = 0.045). CONCLUSION: Our findings support the notion that the presence of innate immune SNPs, such as functional polymorphisms of TLRs along with MBL deficiency, might exert a protective effect on the COPD phenotype, similar with other immune-mediated disorders.

Efficacy and tolerability of vildagliptin as first line treatment in patients with diabetes type 2 in an outpatient setting.

BACKGROUND: Inhibitors of dipeptidyl-peptidase IV are recommended as second-line therapy in type 2 diabetes (DT2), but data, as a first-line treatment in everyday clinical practice are scarce. To address this issue we conducted a 12-month, clinical study in an outpatient setting, using vildagliptin as the first-line treatment. METHODS: Ninety-one drug naïve patients with DT2 started with vildagliptin monotherapy (100 mg daily) for 4 months and were scheduled to regular 4-monthly visits for 1 year. Patients received add-on treatment with metformin or metformin and glimepiride according to their glycosylated hemoglobin (HbA1c) at each study-visit. RESULTS: HbA1c was significantly decreased with vildagliptin monotherapy from 8.16 % ± 1.60 to 7.52 % ± 1.60, p < 0.001. Only 39 % of the patients achieved the target of HbA1c ≤ 7.0 % at the end of the 4th month. Mean change in HbA1c was significantly correlated with baseline HbA1c values (r = -0.51, p < 0.001). At the end of the study only 35 % of the patients remained on vildagliptin monotherapy while the rest required add-on treatment with metformin or metformin and sulfonylurea. CONCLUSIONS: Vildagliptin is well tolerated either as monotherapy or in combination but the majority of patients require add-on therapy shortly after the beginning of treatment.