Will nicotine genetics and a nicotine vaccine prevent cigarette smoking and smoking-related diseases?

This paper briefly explains why it would be unwise to use genetic and neurobiological knowledge to prevent cigarette smoking and tobacco-related disease. However implausible these uses may seem to those who are well informed about the genetics of tobacco use or tobacco-control policy, it is the preventive uses of genetic information and nicotine vaccines that most excite the interest of the media and the public. The major challenges that these approaches face need to be widely understood if we are to prevent these superfi cially attractive but controversial uses from undermining effective control policies and the development of better methods of helping smokers to quit.

The burden of smoking related ill health in the UK

Background: Smoking is one of the biggest avoidable causes of morbidity and mortality in the United Kingdom. This paper quantifies the current health and economic burden of smoking in the UK. It provides comparisons with previous studies of the burden of smoking in the UK and with the costs for other chronic disease risk factors.

Methods: A systematic literature review to identify previous estimates of National Health Service costs attributable to smoking was undertaken. Information from the World Health Organization’s Global Burden of Disease Project and routinely collected mortality data were used to calculate mortality due to smoking in the UK. Population-attributable fractions for smoking-related diseases from the Global Burden of Disease Project were applied to NHS cost data to estimate direct financial costs.

Results: Previous studies estimated that smoking costs the NHS about £1.4 billion to £1.7 billion in 1991 and has been responsible for about 100 000 deaths per annum over the past 10 years. This paper estimates that the number of deaths attributable to smoking in 2005 was 109 164 (19% of all deaths, 27% deaths in men and 11% of deaths in women). Smoking was directly responsible for 12% of disability adjusted life years lost in 2002 (15.4% in men; 8.5% in women) and the direct cost to the NHS was £5.2 billion in 2005–6.

Conclusion: Smoking is still a considerable public health burden in the UK. Accurately establishing the burden in terms of death, disability and financial costs is important for informing national public health policy.

Cost of tobacco-related diseases, including passive smoking, in Hong Kong

Background: Costs of tobacco-related disease can be useful evidence to support tobacco control. In Hong Kong we now have locally derived data on the risks of smoking, including passive smoking. Aim: To estimate the health-related costs of tobacco from both active and passive smoking. Methods: Using local data, we estimated active and passive smoking-attributable mortality, hospital admissions, outpatient, emergency and general practitioner visits for adults and children, use of nursing homes and domestic help, time lost from work due to illness and premature mortality in the productive years. Morbidity risk data were used where possible but otherwise estimates based on mortality risks were used. Utilisation was valued at unit costs or from survey data. Work time lost was valued at the median wage and an additional costing included a value of US$1.3 million for a life lost. Results: In the Hong Kong population of 6.5 million in 1998, the annual value of direct medical costs, long term care and productivity loss was US$532 million for active smoking and US$156 million for passive smoking; passive smoking accounted for 23% of the total costs. Adding the value of attributable lives lost brought the annual cost to US$9.4 billion. Conclusion: The health costs of tobacco use are high and represent a net loss to society. Passive smoking increases these costs by at least a quarter. This quantification of the costs of tobacco provides strong motivation for legislative action on smoke-free areas in the Asia Pacific Region and elsewhere.

Evaluation of hospitalized patients in terms of their knowledge related to smoking

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Usual interstitial pneumonia and smoking-related interstitial fibrosis display epithelial to mesenchymal transition in fibroblastic foci

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

Noninvasive biomarkers for early smoking related lung disease

Chronic obstructive pulmonary disease (COPD) is a slowly progressive disease characterized by airway inflammation and largely irreversible airflow limitation. One major risk factor for COPD is cigarette smoking. Since the inflammatory process starts many years prior to the onset of clinical symptoms and still continues after smoking cessation, there is an urgent need to find simple non-invasive biomarkers that can be used in the early diagnosis of COPD and which could help in predicting the disease progression. The first aim of the present study was to evaluate the involvement of different oxidative/nitrosative stress markers, matrix metalloproteinases (MMPs) and their tissue inhibitor-1 (TIMP-1) in smokers and in COPD. Elevated numbers of inducible nitric oxide synthase (iNOS), nitrotyrosine, myeloperoxidase (MPO) and 4-hydroxy-2-nonenal (4-HNE) positive cells and increased levels of 8-isoprostane and lactoferrin were found in sputum of non-symptomatic smokers compared to non-smokers, and especially in subjects with stable mild to moderate COPD, and they correlated with the severity of airway obstruction. This suggests that an increased oxidant burden exists already in the airways of smokers with normal lung function values. However, none of these markers could differentiate healthy smokers from symptomatic smokers with normal lung function values i.e. those individuals who are at risk of developing COPD. In contrast what is known about asthma exhaled nitric oxide (FENO) was lower in smokers than in non-smokers, the reduced FENO value was significantly associated with neutrophilic inflammation and the elevated oxidant burden (positive cells for iNOS, nitrotyrosine and MPO). The levels of sputum MMP-8 and plasma MMP-12 appeared to differentiate subjects who have a risk for COPD development but these finding require further investigations. The levels of all studied MMPs correlated with the numbers of neutrophils, and MMP-8 and MMP-9 with markers of neutrophil activation (MPO, lactoferrin) suggesting that especially neutrophil derived oxidants may stimulate the tissue destructive MMPs already in lungs of smokers who are not yet experiencing any airflow limitation. When investigating the role of neutrophil proteases (neutrophil elastase, MMP-8, MMP-9) during COPD exacerbation and its recovery period, we found that levels of all these proteases were increased in sputum of patients with COPD exacerbation as compared to stable COPD and controls, and decreased during the one-month recovery period, giving evidence for a role of these enzymes in COPD exacerbations. In the last study, the effects of subject`s age and smoking habits were evaluated on the plasma levels of surfactant protein A (SP-A), SP-D, MMP-9 and TIMP-1. Long-term smoking increased the levels of all of these proteins. SP-A most clearly correlated with age, pack years and lung function decline (FEV1/FVC), and based on the receiver operating characteristic curve analysis, SP-A was the best marker for discriminating subjects with COPD from controls. In conclusion, these findings support the hypothesis that especially neutrophil derived oxidants may activate MMPs and induce an active remodeling process already in the lungs of smokers with normal lung function values. The marked increase of sputum levels of neutrophil proteases in smokers, stable COPD and/or during its exacerbations suggest that these enzymes play a role in the development and progression of COPD. Based on the comparison of various biomarkers, SP-A can be proposed to serve as sensitive biomarker in COPD development.

Accessibility and availability of smoking-related associations in smokers

A free association test was used in the present study to examine the availability and accessibility of positive vs negative smoking-related information in the long-term memories of smokers. Participants were asked to generate smoking-related associations across a 4-minute interval. Although smokers generated more positive smoking-associations than non-smokers, both groups produced a greater number of negative than positive associations per se. Of particular interest was the finding that whilst the ratio of positive/negative associations generated was constant across time in non-smokers, this ratio varied in smokers. Specifically, smokers generated proportionately more of their available positive associations and proportionately less of their negative associations in the early time interval. It is suggested that these results not only indicate a greater availability of positive smoking-associations in smokers compared to non-smokers, but also a greater accessibility too. It is proposed that positive smoking associations are more automatically activated than negative associations in smokers, even though they have generally more negative associations available.

Face and content validity of smoking-related and matched control pictures

Smoking-related pictures and matched controls are useful tools in experimental tasks of attentional bias. Noteworthy the procedures used to produce and validate these pairs of pictures are poorly reported. This study aimed to describe the production and evidence of validity of a set of smoking-related pictures and their matched controls. Two studies were conducted to assess validity. An online internet-based survey was used to assess face validity of 12 pictures related to smoking behavior and 12 matched controls. All pictures were colored and were 95mm length x 130mm width. Participants were asked if the pictures were related or not to the smoking behavior and also rated how much each picture was related to smoking behavior. The second study investigated attentional bias in smokers (n = 47) and non-smokers (n = 50), and examined how they assessed all pictures in terms of pleasantness and the 12 smoking-related pictures in terms of relevance to their own smoking behavior. Craving was assessed before and after the experiment. Results indicate that this set of pictures are valid since smoking-related pictures were considered more related to smoking behavior compared to their matched controls. Moreover, smokers showed greater attentional bias for smoking-related pictures than non-smokers. Craving and relevance of the smoking-related pictures were higher in smokers than in non-smokers. Smokers considered smoking-related pictures them less unpleasant than non-smokers. These findings provide evidence of face and content validity of this set of pictures, which will be available to researchers, contributing to maximize the standardization of future investigations.

The potential for tobacco control to reduce PBS costs for smoking-related cardiovaccular disease

Objective: To estimate Pharmaceutical Benefits Scheme (PBS) subsidies for drugs to treat smoking-related cardiovascular disease (CVD) in 2001-02, and over the period of the government's Intergenerational Report (IGR), assuming current smoking prevalence rates and a 5% absolute reduction.

Design and setting: An Australian epidemiological study, using prescribing data, aetiological fraction methodology, and IGR trends.

Main outcome measures: Estimated smoking-related PBS subsidy costs in 2001-02 and predicted cumulative subsidies until 2041-42, under current and reduced smoking prevalence assumptions.

Results: The PBS costs of smoking-related CVD in 2001-02 were $126 million, 9.77% of the cost of drugs for CVD and 2.96% of total PBS subsidies. The cumulative difference in these costs over the 40-year period with a 5% drop in smoking prevalence was predicted to be $4.5 billion, a 17% reduction. The saving would be $1.14 billion discounting future costs at 5% per year.

Conclusions: Further investment in tobacco control interventions could curb the increasing cost of the PBS and contribute to government efforts to ensure the viability of Australia's healthcare-financing programs. The net present value of a campaign to reduce smoking prevalence was estimated at $1 billion, with an internal rate of return of 33%.

Aptamer-based therapeutics of the past, present and future: from the perspective of eye-related diseases

 Aptamers have emerged as a novel and powerful class of biomolecules with an immense untapped potential. The ability to synthesise highly specific aptamers against any molecular target make them a vital cog in the design of effective therapeutics for the future. However, only a minutia of the enormous potential of this dynamic class of molecule has been exploited. Several aptamers have been studied for the treatment of eye-related disorders, and one such strategy has been successful in therapy. This review gives an account of several eye diseases and their regulatory biomolecules where other nucleic acid therapeutics have been attempted with limited success and how aptamers, with their exceptional flexibility to chemical modifications, can overcome those inherent shortcomings.

Dietary components may prevent mutation-related diseases in humans

Since it is not always possible to reduce human exposure to mutagens, attempts have been directed to identify potential antimutagens and anticarcinogens for use in protecting the population against environmental disease. The purpose of this paper is to provide the reader with information about the antimutagenic and anticarcinogenic potentials of some dietary constituents and foods widely consumed in Brazil, and to reinforce diet as a key factor in determining genomic stability and preventing human diseases. In this report, we have summarized data that show interactive effects between some dietary components and specific chemical mutagens or carcinogens using in vitro and in vivo short- or medium-term assays. The summary indicates that certain dietary compounds may be useful agents for disease prevention. (C) 2003 Elsevier B.V. All rights reserved.

Leptin as a link between the immune system and kidney-related diseases: leading actor or just a coadjuvant?

Food intake and nutritional status modify the physiological responses of the immune system to illness and infection and regulate the development of chronic inflammatory processes, such as kidney disease. Adipose tissue secretes immune-related proteins called adipokines that have pleiotropic effects on both the immune and neuroendocrine systems, linking metabolism and immune physiology. Leptin, an adipose tissue-derived adipokine, displays a variety of immune and physiological functions, and participates in several immune responses. Here, we review the current literature on the role of leptin in kidney diseases, linking adipose tissue and the immune system with kidney-related disorders. The modulation of this adipose hormone may have a major impact on the treatment of several immune- and metabolic-related kidney diseases.

Important research questions in allergy and related diseases: nonallergic rhinitis: a GA2LEN paper

Nonallergic rhinitis (NAR) can be defined as a chronic nasal inflammation which is not caused by systemic IgE-dependent mechanisms. It is common and probably affects far more than 200 million people worldwide. Both children and adults are affected. However, its exact prevalence is unknown and its phenotypes need to be evaluated using appropriate methods to better understand its pathophysiology, diagnosis and management. It is important to differentiate between infectious rhinitis, allergic/NAR and chronic rhinosinusitis, as management differs for each of these cases. Characterization of the phenotype, mechanisms and management of NAR represents one of the major unmet needs in allergic and nonallergic diseases. Studies on children and adults are required in order to appreciate the prevalence, phenotype, severity and co-morbidities of NAR. These studies should compare allergic and NAR and consider different age group populations including elderly subjects. Mechanistic studies should be carried out to better understand the disease(s) and risk factors and to guide towards an improved diagnosis and therapy. These studies need to take the heterogeneity of NAR into account. It is likely that neuronal mechanisms, T cells, innate immunity and possibly auto-immune responses all play a role in NAR and may also contribute to the symptoms of allergic rhinitis.