Smoking cessation and COPD.

Background: Many studies have shown that smoking cessation is cost-effective; however, there have been no pharmacoeconomic trials directly comparing nicotine replacement therapy (NRT) with bupropion SR, the current mainstays of pharmacologic therapy for nicotine dependence. Objective: To evaluate and compare clinical efficacy and cost-effectiveness of either NRT or once-daily bupropion SR using patient-reported continuous six-month quit rates and pharmacoeconomic evaluation. Methods: Retrospective data on six-month abstinence rates were obtained on 287 Veterans Affairs people who enrolled in our smoking cessation programs from August 1997 to May 1998. These subjects received either NRT patches or once-daily bupropion SR along with counseling on behavioral modification. Quit rates were calculated to compare the efficacy of NRT versus once-daily bupropion SR. Pharmacoeconomic cost analysis data were calculated to determine actual and guideline cost of each medication group. The costs of success and failure of both NRT patches and bupropion SR were also determined. Results: Six-month quit rates were not significantly different in NRT patches versus bupropion SR groups (27.7% vs. 31%; p > 0.702). Pharmacoeconomic analysis revealed that overall cost of therapy was $158 for medication/patient receiving NRT versus $67/patient taking bupropion SR. Actual cost of success for NRT was $140/patient compared with $199/patient if doses matched guideline recommendations. Actual cost of failure for NRT was $166/patient compared with $138/patient if guideline doses were used. Patients who successfully quit smoking with NRT used pharmacologic treatment for approximately three weeks less than the guideline time period; patients who failed with NRT used therapy about 10 days longer than the guideline time. Actual cost of success for bupropion SR was $74/patient compared with $42/patient if guideline doses were used. Cost of failure with bupropion SR was $63/patient compared with $32/patient if guidelines were followed. Patients successful with bupropion SR used the treatment six weeks longer than our guideline, while patients who failed on bupropion SR used the therapy eight weeks beyond the guideline. Conclusions: NRT and bupropion SR were equally efficacious; however, bupropion SR was more cost-effective than NRT. Increasing the duration of therapy with NRT beyond our guideline period increased the cost of failure.

Cigarette smoking (CS) can impact the immune system and induce pulmonary disorders such as chronic obstructive pulmonary disease (COPD), which is currently the fourth leading cause of chronic morbidity and mortality worldwide. Accordingly, the most significant risk factor associated with COPD is exposure to cigarette smoke. The purpose of the present study is to provide an updated overview of the literature regarding the effect of CS on the immune system and lungs, the mechanism of CS-induced COPD and oxidative stress, as well as the available and potential treatment options for CS-induced COPD. An extensive literature search was conducted on the PubMed/Medline databases to review current COPD treatment research, available in the English language, dating from 1976 to 2014. Studies have investigated the mechanism by which CS elicits detrimental effects on the immune system and pulmonary function through the use of human and animal subjects. A strong relationship among continued tobacco use, oxidative stress, and exacerbation of COPD symptoms is frequently observed in COPD subjects. In addition, therapeutic approaches emphasizing smoking cessation have been developed, incorporating counseling and nicotine replacement therapy. However, the inability to reverse COPD progression establishes the need for improved preventative and therapeutic strategies, such as a combination of intensive smoking cessation treatment and pharmaceutical therapy, focusing on immune homeostasis and redox balance. CS initiates a complex interplay between oxidative stress and the immune response in COPD. Therefore, multiple approaches such as smoking cessation, counseling, and pharmaceutical therapies targeting inflammation and oxidative stress are recommended for COPD treatment.

Nicotine addiction is a chronic relapsing condition that can be difficult to treat. Until recently, pharmacological options for the treatment of tobacco dependence were primarily limited to nicotine replacement therapy (NRT). Sustained-release bupropion (bupropion SR) is the first non-nicotine pharmacological treatment approved for smoking cessation. Bupropion SR is recommended for first-line pharmacotherapy alongside NRT in the updated US Clinical Practice Guidelines and the UK Health Education Authority Guidelines. The UK National Institute of Clinical Excellence recommends NRT and bupropion SR for smokers who have expressed a desire to quit smoking. This review presents evidence that bupropion SR is an effective first-line therapy for smoking cessation in a wide range of patient populations. It is associated with significantly higher smoking cessation rates compared with placebo in patients with or without a history of prior bupropion SR or NRT use, and its effect is independent of gender. Bupropion SR treatment is effective in the prevention of relapse to smoking in those patients who have successfully quit, and re-treatment is effective in smokers who recommence smoking after a previous course of bupropion SR. Bupropion SR treatment relieves the symptoms of craving and nicotine withdrawal, and attenuates the weight gain that often occurs after smoking cessation. Data collected from motivational support programmes and employer-based studies provide strong evidence of the effectiveness of bupropion SR as an aid to smoking cessation in 'real life' situations, and confirm the efficacy seen in clinical trials.

IntroductionCigarette Smoking is the leading cause of COPD; smoking cessation in COPD reduces mortality and is the only intervention proven to reduce the rate of FEV1 decline. Stop Smoking Services...

UK COPD treatment: failing to progress

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RationaleSmoking is the primary cause of chronic obstructive pulmonary disease (COPD); however, only 10–20% of smokers develop the disease suggesting possible genomic association in the causation of the disease. In the present study, we aimed to explore the whole genome transcriptomics of blood monocytes from COPD smokers (COPD-S), COPD Ex-smokers (COPD-ExS), Control smokers (CS), and Control Never-smokers (CNS) to understand the differential effects of smoking, COPD and that of smoking cessation.MethodsExploratory analyses in form of principal component analysis (PCA) and hierarchical component analysis (uHCA) were performed to evaluate the similarity in gene expression patterns, while differential expression analyses of different supervised groups of smokers and never smokers were performed to study the differential effect of smoking, COPD and smoking cessation. Differentially expressed genes among groups were subjected to post-hoc enrichment analysis. Candidate genes were subjected to external validation by quantitative RT-PCR experiments.ResultsCNS made a cluster completely segregated from the other three subgroups (CS, COPDS and COPD-ExS). About 550, 8 and 5 genes showed differential expression, respectively, between CNS and CS, between CS and COPD-S, and between COPD-S and COPD-ExS. Apoptosis, immune response, cell adhesion, and inflammation were the top process networks identified in enrichment analysis. Two candidate genes (CASP9 and TNFRSF1A) found to be integral to several pathways in enrichment analysis were validated in an external validation experiment.ConclusionControl never smokers had formed a cluster distinctively separated from all smokers (COPDS, COPD-ExS, and CS), while amongst all smokers, control smokers had aggregated in a separate cluster. Smoking cessation appeared beneficial if started at an early stage as many genes altered due to smoking started reverting towards the baseline, whereas only a few COPD-related genes showed reversal after smoking cessation.

Background: Despite its high and increasing prevalence and mortality, the pathogenesis of COPD remains unclear and there is no effective treatment available that halts the irreversible and progressive tissue destruction and small airway wall fibrosis which are characteristic of the disease. Aim of the work: investigation of ANA and CRP in COPD patients and their relation to;smoking behavior & lung function. Patients and methods: the study included 80 subjects, 20 stable COPD (group 1 ), 20 with COPD exacerbation (group2); 20 smokers non COPD (group3) and finally 20 non COPD non- smokers (healthy controls). ANA and CRP were estimated according to methods described by (Jaskowski et al., 1996), and (Koenig et al., 1999) respectively. Results: There was significant difference between groups regarding positive CRP (90% of COPD exacerbation group had positive CRP, 25.0% of stable COPD, 10% of non COPD smokers and 5.0% of non -smoker non COPD groups had positive CRP).ANA was positive in 24 cases out of 80 cases (30.0%) and there was significant difference between studied groups (it was positive in 65.0%, 45.0%, 5.0% and 5.0% in COPD exacerbation, stable COPD, non COPD smokers and non-smokers non COPD groups respectively). There was significant association between CRP and ANA with ECG changes, but no association was found with BMI. Conclusion: CRP and ANAs increased levels are correlated to the severity of COPD. These results confirmed that inflammation and autoimmunity play a role in COPD pathogenesis. In addition, the results of the present study might suggest a role for immunomodulating anti-inflammatory drugs in treatment of COPD.

<div>Abstract<p>Nicotine replacement therapy (NRT) for up to 12 weeks is well established, safe and efficacious for fostering smoking cessation. Some smokers at a high risk of relapse may benefit from long-term use, and so long-term NRT safety and efficacy have become a paramount question for the FDA and others. Laboratory studies have indicated a carcinogenic potential of nicotine. Animal model studies reported in this issue of the journal by Maier and colleagues (beginning on page 1743) and Murphy and colleagues (beginning on page 1752), however, provide additional reassurance that NRT does not promote lung cancer. Very long-term studies of NRT effects do not yet exist and would be needed to definitively answer the question about NRT efficacy and cancer risk and some decision making will need to be made based on limited human data and experimental studies. The overall NRT safety question is complex and requires consideration of three contexts and comparator groups (long-term NRT/abstinence vs. smoking, long-term intermittent NRT/reduced smoking vs. smoking, and long-term NRT/abstinence vs. abstinence without long-term NRT). Although the data on these issues are insufficient, the first comparison seems intuitive and may be compelling enough to allow the FDA to approve a long-term indication for NRT. An important public health goal is to help smokers and their health care providers understand the implications of potential long-term NRT risks in the context of its potential benefits and the far greater risks of continued smoking. <i>Cancer Prev Res; 4(11); 1719–23. ©2011 AACR</i>.</p></div>

The aim of nicotine replacement therapy (NRT) is to replace nicotine from cigarettes. This reduces withdrawal symptoms associated with smoking cessation thus helping resist the urge to smoke cigarettes. The aims of this review were to determine the effectiveness of the different forms of nicotine replacement therapy (chewing gum, transdermal patches, nasal spray, inhalers and tablets) in achieving abstinence from cigarettes, or a sustained reduction in amount smoked; to determine whether the effect is influenced by the clinical setting in which the smoker is recruited and treated, the dosage and form of the NRT used, or the intensity of additional advice and support offered to the smoker; to determine whether combinations of NRT are more effective than one type alone; and to determine its effectiveness compared to other pharmacotherapies. We searched the Cochrane Tobacco Addiction Group trials register in April 2001. Randomized trials in which NRT was compared to placebo or no treatment, or where different doses of NRT were compared. We excluded trials which did not report cessation rates, and those with follow-up of less than six months. We extracted data in duplicate on the type of subjects, the dose and duration and form of nicotine therapy, the outcome measures, method of randomization, and completeness of follow-up. The main outcome measures was abstinence from smoking after at least six months of follow-up. We used the most rigorous definition of abstinence for each trial, and biochemically validated rates if available. Where appropriate, we performed meta-analysis using a fixed effects model (Peto). We identified 108 trials; 94 with a non NRT control group. The odds ratio for abstinence with NRT compared to control was 1.73 (95% confidence interval 1.62-1.85), The odds ratios for the different forms of NRT were 1.66 for gum, 1.76 for patches, 2.27 for nasal spray, 2.08 for inhaled nicotine and 1.73 for nicotine sublingual tablet. These odds were largely independent of the duration of therapy, the intensity of additional support provided or the setting in which the NRT was offered. In highly dependent smokers there was a significant benefit of 4 mg gum compared with 2mg gum (odds ratio 2.67, 95% confidence interval 1.69 to 4.22). There was weak evidence that combinations of forms of NRT are more effective. Higher doses of nicotine patch may produce small increases in quit rates. Only one study directly compared NRT to another pharmacotherapy, in which bupropion was significantly more effective than nicotine patch or placebo. All of the commercially available forms of NRT (nicotine gum, transdermal patch, the nicotine nasal spray, nicotine inhaler and nicotine sublingual tablets) are effective as part of a strategy to promote smoking cessation. They increase quit rates approximately 1.5 to 2 fold regardless of setting. The effectiveness of NRT appears to be largely independent of the intensity of additional support provided to the smoker. Provision of more intense levels of support, although beneficial in facilitating the likelihood of quitting, is not essential to the success of NRT. There is promising evidence that bupropion may be more effective than NRT (either alone or in combination). However, its most appropriate place in the therapeutic armamentarium requires further study and consideration.

NRT, bupropion, varenicline and cytisine have been shown to improve the chances of quitting. Combination NRT and varenicline are equally effective as quitting aids. Nortriptyline also improves the chances of quitting. On current evidence, none of the treatments appear to have an incidence of adverse events that would mitigate their use. Further research is warranted into the safety of varenicline and into cytisine's potential as an effective and affordable treatment, but not into the efficacy and safety of NRT.

Objective To evaluate effectiveness of prevention and treatment for patients with chronic obstructive pulmonary disease (COPD) for one year at community health-care service (CHS)centers. Methods A quasi-experiment design was used to evaluate effectiveness of community management for patients with COPD who visited and registered at Xiaokunshan and Xinbang CHS centers in Songjiang district of Shanghai in 2008, with COPD patients from Xiaokunshan community CHS center as management group and those from Xinbang as control. Measures for community management included training for local general practitioners in essential knowledge of COPD prevention and treatment, allocation of necessary drugs for COPD treatment, and health education for COPD patients and their family members. No special measures were taken for control group except routine treatment. Results A total of 132 patients were diagnosed as COPD according to their pulmonary function on 2008, 61 at Xiaokunshan and 71 at Xinbang CHS canters.One hundred and two patients, 47 at Xiaokunshan and 55 at Xinbang, finished one-year follow-up. Five patients from Xiaokunshan who were smokers at their first visits and three of them quitted smoking after oneyear management. Meanwhile, none of nine smoked patients from Xinbang quitted smoking in the same period. There was no statistically significant difference in symptom scores, pulmonary function, and forced expiratory volume at the first second (FEV1) between patients in the two groups during one-year follow-up.Average score of quality of life in patients at Xiaokunshan dropped to 39. 12 after one-year management from 46. 96 at their first visits, and that in patients at Xinbang increased to 62. 11 from 56. 55 (P＜0.01).Average six-minute walking distance (6-MWD) in patients at Xiaokunshan reduced to 354. 26 meters after one-year management from 361.66 meters at their first visits, meanwhile that in patients at Xinbang reduced to 351.18 meters from 398.07 meters (P =0. 008). Scores of functional dyspnea in patients at Xiaokunshan fell to 0.34 from 0.40 at their first visit, meanwhile that in patients at Xinbang increased to 1.00 from 0.95(P =0.038). During the one-year follow-up, 13 patients at Xiaokunshan and 53 at Xinbang visited emergency departments for treatment, and four at Xiaokunshan were hospitalized and none died, and five at Xinbang were hospitalized due to acute exacerbation of COPD and four of them died. Conclusions The study suggests that strengthening prevention and treatment for COPD patients at community level by general practitioners, patients themselves and their family members can improve their quality of life, reduce emergency visits and hospitalization, alleviate dyspnea symptoms and delay the decline of 6MWD. Key words: Pulmonary disease, chronic obstructive; Community health centers; Disease management

Aims: This study aimed to identify overlapping or diverging dysregulated genes, lncRNAs, miRNAs and signaling pathways in smoking and non-smoking chronic obstructive pulmonary disease (COPD). Methods: Compared to normal controls, we identified the shared and divergent differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs) in smoking and non-smoking COPD by RNA-sequencing and bioinformatics analysis. Functional annotation of DEmRNAs were performed. Both cis and trans-target DEmRNAs of DElncRNAs were identified. The target DEmRNAs of DEmiRNAs were identified as well. The DEmiRNA-DEmRNA-DElncRNA interaction network was constructed. The validation was performed by QRT-PCR. Results: Compared to normal control, 1234 DEmRNAs, 96 DElncRNAs and 151 DEmiRNAs were identified in non-smoking patients with COPD; 670 DEmRNAs, 44 DElncRNAs and 63 DEmiRNAs were identified in smoking patients with COPD. Leukocyte transendothelial migration and pathways in cancer were significantly enriched pathways in non-smoking and smoking COPD, respectively. MiR-122-5p-A2M-LINC00987/A2M-AS1/linc0061 interactions might play key roles in COPD irrespective with the smoking status. Let-7-ADRB1-HLA-DQB1-AS1 might play a key role in the pathogenesis of smoking COPD while miR-218-5p/miR15a-RORA-LOC101928100/LINC00861 and miR-218-5p/miR15a-TGFs3-RORA-AS1 interactions might involve with non-smoking COPD. Conclusions: We identified the shared and diverging genes, lncRNAs, miRNAs and their interactions and pathways in smoking and non-smoking COPD which provided clues for understanding the mechanism and developing novel diagnostic and therapeutic strategies for COPD.

Smoking cessation in patients with respiratory disease: existing treatments and future directions

Varenicline, a partial agonist of α4β2 nicotinic acetylcholine receptors, is the most recently approved drug for smoking cessation. This paper reviews the outcomes of Phase 2 and Phase 3 clinical trials that assess the efficacy of varenicline in comparison to placebo and other smoking cessation pharmacotherapies, ie, sustained-release bupropion (bupropion SR) and nicotine transdermal patch. Varenicline has higher abstinence rates than placebo and the alternative active treatments at the end of standard regimen treatment periods. Significantly higher abstinence rates were also found with varenicline in comparison to both placebo and bupropion SR at the end of a 40-week non-treatment follow-up period. Varenicline typically tripled the abstinence rates compared with placebo. In addition, varenicline reduced craving and withdrawal symptoms as well as some of the positive experiences associated with smoking to a greater extent than placebo, bupropion SR, and nicotine replacement therapy (NRT). These findings are consistent with the proposed agonist/antagonist effects of varenicline. Preliminary studies assessing individual variables such as smoking dependency level and smoking reinforcement types provide justification to examine further the effects of varenicline according to these individual factors. Outcomes from such research could improve our understanding of varenicline’s mechanism of action and could ultimately help clinicians to develop individualized smoking cessation programs. Also, given varenicline’s ability to reduce the reward from smoking, it might be helpful to use it before cessation to motivate or prepare smokers for a quit attempt.