We showed that patients with CYP2B6*4 (rs2279343) variant had lower success rate with bupropion. Likely, the CYP2B6*4 variant, which leads to a rapid predicted metabolic phenotype for the isoenzyme, influences the pharmacological activity of bupropion. Our finding suggests that CYP2B6*4 may be an important genetic marker for individualized bupropion pharmacotherapy.

Background: The large individual variability in response to drugs for smoking cessation suggests that specific treatments can be more effective in particular subgroups of smokers. In the context of personalized medicine, the main aim of the present study was to evaluate whether the CHRNA4 and CHRNB2 polymorphisms are associated with response to smoking cessation therapies in patients from a smoker assistance program.Methods: This cohort study enrolled 483 smoking patients who received behavioral counseling and drug treatment (varenicline, bupropion, and/or nicotine replacement therapy). Smoking cessation success was considered for patients who completed 6 months of continuous abstinence. Fagerström test for nicotine dependence (FTND) and Issa situational smoking scores were analyzed for nicotine dependence. The CHRNA4 (rs1044396 and rs2236196) and CHRNB2 (rs2072660 and rs2072661) polymorphisms were genotyped by high resolution melting analysis.Results: Patients with rs1044396 CC genotype had lower success rate in treatment with varenicline (29.5%) compared with carriers of CT or TT genotypes (50.9%; p = 0.007, n = 167). The CT or TT genotypes were associated with higher odds ratio for success (OR = 1.67, 95% CI = 1.10–2.53, p = 0.02), in a multivariate model. We did not observe significant differences in the FTND and Issa scores according to the studied polymorphisms.Conclusion: The CHRNA4 rs1044396 is associated with smoking cessation in individuals on varenicline therapy. We suggest that this polymorphism influences the varenicline response, but replications of this finding are needed.

BackgroundThe identification of variants in the nicotinic acetylcholine receptor (nAChR) subunit genes associated with smoking phenotypes are increasingly important for prevention and treatment of nicotine dependence. In the context of personalized medicine, the aims of this study were to evaluate whether cholinergic receptor nicotinic alpha 2 (CHRNA2), cholinergic receptor nicotinic alpha 3 (CHRNA3), cholinergic receptor nicotinic alpha 5 (CHRNA5) and cholinergic receptor nicotinic beta 3 (CHRNB3) polymorphisms were associated with nicotine dependence severity, and to investigate possible pharmacogenetics markers of smoking cessation treatment.MethodsThis study cohort enrolled 1049 smoking patients who received pharmacological treatment (varenicline, varenicline plus bupropion, bupropion plus/or nicotine replacement therapy). Smoking cessation success was considered for patients who completed 6 months of continuous abstinence. Fagerström test for nicotine dependence (FTND) and Issa situational smoking scores (Issa score) were analyzed for nicotine dependence. CHRNA2 (rs2472553), CHRNA3 (rs1051730), CHRNA5 (rs16969968 and rs2036527) and CHRNB3 (rs6474413) polymorphisms were genotyped by high resolution melting analysis.ResultsFemales with GA and AA genotypes for CHRNA5 rs16969968 and rs2036527 polymorphisms had higher success rate in smoking cessation treatment: 44.0% and 56.3% (rs16969968), 41.5% and 56.5% (rs2036527), respectively, compared with carriers of the GG genotypes: 35.7% (rs16969968), 34.8% (rs2036527), (P = 0.03, n = 389; P = 0.01, n = 391). The GA or AA genotypes for the rs16969968 and rs2036527 were associated with higher odds ratio for success in women (OR = 1.63; 95% CI = 1.04 to 2.54; P = 0.03 and OR = 1.59, 95% CI = 1.02 to 2.48; P = 0.04; respectively). We did not find association of these polymorphisms with nicotine dependence related scores. Polymorphisms in the CHRNA2, CHRNA3 and CHRNB3 genes were not associated with the phenotypes studied.ConclusionCHRNA5 rs16969968 and rs2036527 were associated with higher success rate in the smoking cessation treatment in women. These findings might contribute to advances in personalized medicine.Electronic supplementary materialThe online version of this article (10.1186/s12881-018-0571-3) contains supplementary material, which is available to authorized users.

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INTRODUCTION Varenicline effectively helps smokers quit by reducing withdrawal symptoms and blocking the reward of smoking. However, most quitters return to smoking within one year. 'Cue Restricted Smoking' is a behavioral technique designed to increase quit rates by asking smokers attempting to quit to restrict smoking to the standing position, while alone, in an isolated area facing a wall, with the cigarette as the only stimulus. METHODS Using retrospective clinic records we compared quit rates in 281 smokers (50% males) instructed in the cue restricted smoking cessation method during 2016-2018 to quit rates in 324 smokers (46% males) advised to completely stop smoking on the target quit date which we previously used during 2011-2014. All were prescribed varenicline for 12 weeks alone, with the addition of bupropion if needed after 4 weeks. Follow-up consisted of behavioral support at 4-6 visits during active drug treatment and telephone counselling at 24 and 52 weeks. The smoking cessation rate was confirmed with exhaled carbon monoxide at the clinic visit at 12 weeks and only by telephone at 52 weeks. RESULTS The mean age of smokers was 49 years in both groups and the number of cigarettes smoked daily was similar (18/day in the cue restricted vs 19/day in the target quit day group). The smoking cessation rate at 12 weeks was 75% in the cue restricted versus 45% in the target quit day group (relative risk, RR=1.8; 95% CI: 1.4-2.2, p<0.001). At 52 weeks the quit rate was 65% vs 34%, respectively (RR=1.9; 95% CI: 1.5-2.4, p<0.001). CONCLUSIONS Cue restricted smoking was associated with a substantially increased chance of quitting compared with standard advice during treatment with varenicline. These results should be further studied in a randomized controlled trial.

Introduction: Smoking is considered the leading cause of preventable morbidity and mortality worldwide. Studies have sought to identify predictors of response to smoking cessation treatments. The aim of this study was to analyze a possible association of target gene expression for smoking cessation with varenicline. Methods: We included 74 smokers starting treatment with varenicline. Gene expression analysis was performed through the custom RT² Profiler qPCR array assay, including 17 genes. Times for sample collection were before the start of therapy (T0) and two weeks (T2) and four weeks (T4) after the start of treatment. Results: For gene expression analysis, we selected 14 patients who had success and 13 patients resistant to varenicline treatment. Success was considered to be when a patient achieved tobacco abstinence until the fourth week of treatment and resistant was when a patient had not stopped smoking as of the fourth week of treatment. We observed a significant difference for CHRNA7 gene expression: in the resistant group, samples from T2 and T4 had lower expression compared with T0 (fold change: 0.38, P = 0.007; fold change: 0.67, P = 0.004; respectively). Conclusion: This exploratory clinical study, searching for a possible predictor of effectiveness for varenicline, reaffirmed the association of the α7 nAChR subunit for nicotine dependence and smoking therapy effectiveness with varenicline.

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Objetivo: Descrever e discutir os parâmetros do suporte ventilatório de pacientes com COVID-19, assim como os critérios e métodos utilizados para o desmame da Ventilação Mecânica Invasiva (VMI). Revisão bibliográfica: De acordo com a análise literária, o modo ventilação com pressão controlada com volume corrente baixo está dentro dos parâmetros iniciais recomendados para a VMI. O desmame, por sua vez, engloba fatores individuais, como a carga e a capacidade do sistema respiratório, e os aspectos psicológicos, físicos e nutricionais. Em pacientes com COVID-19, os critérios tradicionais de extubação permanecem os mesmos, sendo o processo feito de forma gradual, englobando a redução gradativa do nível de Pressão Expiratória Final Positiva (PEEP) ao mesmo tempo em que é feita a checagem das metas de oxigenação. Além disso, a fisioterapia respiratória se faz necessária antes e após a realização da extubação. Considerações finais: Apesar da escassez de estudos e a falta de consenso em relação às condutas no manejo da COVID-19, estabeleceu-se um ponto de partida efetivo no tratamento de tais pacientes no que diz respeito aos parâmetros da VMI e ao desmame de tal terapia, culminando no sucesso de tais intervenções.