Hurt, R. Douglas

The purpose of this commentary is to better inform physicians about the often-unrecognized consequences of cigarette smoking. It highlights knowledge gained from involvement in over 70 legal cases between smokers and cigarette companies in the Florida Engle Trials. As a physician with many years of experience in treating nicotine addiction, the author participated as a paid expert witness in these cases, 45 of which went to trial. Depositions included family members and close associates of the smoker, which allowed the gathering of voluminous information not usually available to a physician. This provided a level of insight into the suffering experienced that was illuminating. Based on this experience as an expert witness, 3 cases are presented that are clear examples of the tragedy experienced by smokers and their families. While not randomly selected, they are representative of the cases in which I participated. The impact of cigarettes on both smokers and those around them is difficult to quantify and is often not observable by healthcare professionals. The documented attitudes of cigarette lawyers, as seen in depositions and at trials, demonstrate an incredible lack of empathy and compassion. On the other hand, the cigarette companies are completely aware that almost 500 000 Americans die each year from use of their products, but death is only 1 outcome. What a sad commentary on the companies that knowingly perpetuated this epidemic and the lawyers who continue to defend them. Sadly, to both parties, it isn’t about the pain, suffering, morbidity, and death that these products cause. Rather, it is simply about money and staying in business on the one hand and money and winning on the other. However, the paramount lesson learned for all of us who take care of smoking patients is first to help them stop smoking and second to appreciate the wide-reaching ramifications of their tobacco dependence. Taking this empathic approach to their care will go a long way to demonstrating the compassion that is needed to provide a healing environment for the patient, their family, and loved ones.

Objective: To determine if the implementation of smoke-free workplace laws reduced the incidence of the acute coronary events including myocardial infarction (MI) and sudden cardiac death (SCD). Background: Nonsmokers chronically exposed to second-hand smoke (SHS) are at increased risk of death from heart disease. However, a nonlinear dose relationship exists between SHS exposure and coronary heart disease (CHD) such that the relative risk of CHD is 1.31 for nonsmokers and 1.78 for smokers. Reductions in admissions for MI in locales where smoke-free workplace laws have been implemented have been observed, but none have assessed SCD. On January 1, 2002, a smoke-free restaurant law (Ordinance #1) was implemented in Olmsted County, Minnesota, and on October 1, 2007, all workplaces became smoke-free (Ordinance #2). Methods: Under the auspices of the Rochester Epidemiology Project, we measured the incidence of MI and SCD during the 18-month calendar period before and after implementation of each smoke-free ordinance. All MI were validated using biomarkers, cardiac pain, and Minnesota coding of the ECG. SCD was defined as out-of-hospital deaths assigned to CHD (ICD-9 codes 410 through 414). Results: For the overall study period of the 18 months before the implementation of the smoke-free restaurant ordinance and 18 months after the implementation of the smoke-free workplace ordinance, we observed a 45% decline in the incidence for MI (p <0.01) and a 50% decline in the incidence for SCD (p <0.01). See Table. During this same period, the prevalence of hypertension, diabetes, hypercholesterolemia, and obesity either remained constant or increased while the prevalence of smoking among adults declined by 23% (22% to 17%). Conclusion: In the Olmsted County population, substantial declines in the incidence of MI and SCD were observed after smoke-free laws were implemented. Smoke-free workplace laws may not only be associated with a decrease in MI but SCD as well.

Abstract Background: Assessment of nicotine metabolism and disposition has become an integral part of nicotine dependency treatment programs. Serum nicotine concentrations or urine cotinine concentrations can be used to guide nicotine patch dose to achieve biological concentrations adequate to provide the patient with immediate relief from nicotine withdrawal symptoms, an important factor in nicotine withdrawal success. Absence of nicotine metabolites and anabasine can be used to document abstinence from tobacco products, an indicator of treatment success. Methods: The procedure was designed to quantify nicotine, cotinine, trans-3′-hydroxycotinine, anabasine, and nornicotine in human serum or urine. The technique required simple extraction of the sample with quantification by HPLC–tandem mass spectrometry. Results: The procedure for simultaneous analysis of nicotine, its metabolites, and tobacco alkaloids simultaneously quantified five different analytes. Test limit of quantification, linearity, imprecision, and accuracy were adequate for clinical evaluation of patients undergoing treatment for tobacco dependency. The test readily distinguished individuals who had no exposure to tobacco products from individuals who were either passively exposed or were abstinent past-tobacco users from those who were actively using a tobacco or nicotine product. Conclusions: Nicotine, cotinine, trans-3′-hydroxycotinine, nornicotine, and anabasine can be simultaneously and accurately quantified in either serum or urine by HPLC–tandem mass spectrometry with imprecision &lt;10% at physiologic concentrations and limits of quantification ranging from 0.5 to 5 μg/L. Knowledge of serum or urine concentrations of these analytes can be used to guide nicotine replacement therapy or to assess tobacco abstinence in nicotine dependency treatment. These measurements are now an integral part of the clinical treatment and management of patients who wish to overcome tobacco dependence.

Abstracttrans-3′-Hydroxycotinine (THOC) has been recognized as the most abundant metabolite of nicotine. In an attempt to assess THOC and cotinine (COT) concentrations during nicotine transdermal therapy, we developed a new quantitative gas chromatography–mass spectrometry (GC–MS) method for simultaneous determination of total and free THOC and COT in human urine. The method utilizes the following: (a) hydrolysis of conjugated THOC and COT by β-glucuronidase; (b) basic extraction of THOC and COT with mixed dichloromethane and n-butyl acetate; (c) derivatization of THOC with bis(trimethylflurosilyl)acetamide; and (d) separation and identification by GC–MS with selective ion monitoring. Lower limits of quantification for the assay were 50 and 20 μg/L for THOC and COT, respectively. The intra- and interassay CVs were 4.4% and 11% for THOC, and 3.9% and 10% for COT at 1000 μg/L. The results from six consecutive 24-h urine collections in 71 subjects administered daily transdermal nicotine doses of 11, 22, and 44 mg showed that, on average, free THOC was 76% of total THOC and free COT was 48% of total COT in all subjects. THOC is the major metabolite of nicotine and constitutes 20% of total nicotine intake at steady state, whereas urinary nicotine and COT excretion were 8% and 17%, respectively. The method is useful for simultaneous determination of free and total THOCand COT and can be used to assess the urinary excretion of these metabolites during transdermal nicotine therapy.

The number of global tobacco-related deaths is projected to increase from about 6 million to 8 million annually by 2030, with more than 80% of these occurring in low- and middle-income countries (LMICs). The World Health Organization Framework Convention on Tobacco Control (FCTC) came into force in 2005 and Article 14 relates specifically to the treatment of tobacco dependence. However, LMICs, in particular, face several barriers to implementing tobacco dependence treatment. This paper is a descriptive evaluation of a novel grant funding mechanism that was initiated in 2014 to address these barriers. Global Bridges. Healthcare Alliance for Tobacco Dependence Treatment aims to create and mobilize a global network of healthcare professionals and organizations dedicated to advancing evidence-based tobacco dependence treatment and advocating for effective tobacco control policy. A 2014 request for proposals (RFP) focused on these goals, particularly in LMICs, where funding for this work had been previously unavailable. 19 grants were awarded by Global Bridges to organizations in low- and middle-income countries across all six WHO regions. Virtually all focused on developing a tobacco dependence treatment curriculum for healthcare providers, while also influencing the political environment for Article 14 implementation. As a direct result of these projects, close to 9,000 healthcare providers have been trained in tobacco dependence treatment and an estimated 150,000 patients have been offered treatment. Because most of these projects are designed with a “train-the-trainer” component, two years of grant funding has been a tremendous catalyst for accelerating change in tobacco dependence treatment practices throughout the world. In order to foster such exponential growth and continue to maintain the impact of these projects, ongoing financial, educational, and professional commitments are required.

Smoking is a major risk factor for failure of coronary artery bypass grafts (CABG). Experiments were designed to determine effects of transdermal nicotine, independent of smoking, on structure and function of CABG. Saphenous veins were placed as CABG in untreated dogs (control) or in dogs treated with transdermal nicotine (one 11-mg or two 22-mg patches/day) for 5 wk. Serum nicotine and plasma nitric oxide were measured. Grafts were removed and prepared for organ chamber studies and histology. Serum nicotine averaged 12.1 and 118.7 ng/ml in the 11 mg/day and 44 mg/day groups, respectively. Plasma nitric oxide was higher in dogs treated with 11 mg/day doses compared with controls. In organ chamber studies, endothelium-dependent relaxations to thrombin and A-23187 and endothelium-independent relaxations to nitric oxide were greatest in grafts from dogs treated with 11 mg/day doses. Intimal thickness of the grafts were similar among groups. However, staining for bone sialoprotein was increased in the media of grafts from the 11 mg/day treatment group. These data suggest that transdermal nicotine in doses comparable and double to those used for conventional smoking cessation treatment in humans does not adversely affect early patency of canine CABG up to 4 wk postoperatively. Transdermal nicotine, however, may increase production of and response to nitric oxide in bypass grafts.

Nicotine patches are available as an over-the-counter medication for aid in smoking cessation. This study was designed to determine how nicotine patch therapy over time and dose ranges used in smoking cessation programs in humans affects endothelium-dependent relaxations. Dogs were treated with nicotine patches (11, 22, or 44 mg/day) for 2 and 5 wk. Circulating nicotine and oxidized products of nitric oxide (NOx) were measured. Coronary arteries were prepared for measurement of isometric force and aortic endothelial cells were prepared for measurement of mRNA or NO synthase (NOS) activity. Circulating nicotine increased with increasing concentrations of nicotine patches. After 5 wk of treatment with 22 mg/day patches, circulating NOx was reduced but NOS activity was increased. NOS mRNA was similar among groups. Only after 5 wk of treatment with 22 mg/day patches were endothelium-dependent relaxations reduced to α2-adrenergic agonists, ADP, and the calcium ionophore A-23187. These results suggest a time and biphasic dose effect of nicotine treatment on endothelium-dependent responses that may be related to bioavailability of NO. This complex relationship of duration and dose of nicotine treatment may explain, in part, discrepancies in effects of nicotine on endothelium-dependent responses.