Resistant Smokers Research Articles

Clustering-based COPD subtypes have distinct longitudinal outcomes and multi-omics biomarkers

IntroductionChronic obstructive pulmonary disease (COPD) can progress across several domains, complicating the identification of the determinants of disease progression. In our previous work, we applied k-means clustering to spirometric and...

Expression of aquaporins in bronchial tissue and lung parenchyma of patients with chronic obstructive pulmonary disease


 
 
 
 Background: Aquaporins AQP1 and AQP5 are highly expressed in the lung. Recent studies have shown that the expression of these proteins may be mechanistically involved in the airway inflammation and in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the expression of AQP1 and AQP5 in the bronchial tissue and the lung parenchyma of patients with COPD and COPD-resistant smokers.
 Methods: Using a case–control design, we selected a group of 15 subjects with COPD and 15 resistant smokers (smokers without COPD) as a control, all of whom were undergoing lung resection surgery due to a lung neoplasm. We studied the expression of AQP1 and AQP5 in the bronchial tissue and the lung parenchyma by means of immunohistochemistry and reverse-transcription real-time polymerase chain reaction. Tissue expression of AQP1 and AQP5 was semi-quantitatively assessed in terms of intensity and expression by immunohistochemistry using a 4-point scale ranging from 0 (none) to 3 (maximum).
 Results: There were no significant differences in gene expression between COPD patients and resistant smokers both in the bronchial tissue and in the lung parenchyma. However, AQP1 gene expression was 2.41-fold higher in the parenchyma of smokers with COPD compared to controls, whereas the AQP5 gene showed the opposite pattern, with a 7.75-fold higher expression in the bronchus of smokers with COPD compared with controls. AQP1 and AQP5 proteins were preferentially expressed in endothelial cells, showing a higher intensity for AQP1 (66.7% of cases with an intensity of 3, and 93.3% of subjects with an extension of 3 among patients with COPD). Subtle interstitial disease was associated with type II pneumocyte hyperplasia and an increased expression of AQP1.
 Conclusions: This study provides pilot observations on the differences in AQP1 and AQP5 expression between COPD patients and COPD-resistant smokers. Our findings suggest a potential role for AQP1 in the pathogenesis of COPD.
 
 
 

Abstract 5229: Candidate gene analysis of exome sequencing data in smokers susceptible and resistant to chronic obstructive pulmonary disease

Abstract Background: Chronic obstructive pulmonary disease (COPD) is a major comorbidity for Lung cancer (LC), the presence of COPD conferring a three- to 10-fold increased risk of LC. Therefore, we employed an extreme-phenotype approach, focused on exome sequencing of 109 susceptibility loci identified in recent genome-wide association studies (GWAS) of LC, COPD, lung function and smoking behavior, to search for COPD disease-causing rare germline mutations. Methods: We selected two extreme categories of smokers from COPDGene: 1) Resistant long-term smokers with normal lung function defined as post-bronchodilator FEV1 ≥ 80% predicted, FEV1/FVC ≥ 0.7, with smoking histories of 15+ pack-years, considered as resistant to the effects of smoking, n = 318; 2) Susceptible smokers with severe COPD defined as GOLD spirometry grades III-IV (post-bronchodilator FEV1 < 50% predicted and FEV1/FVC < 0.7), with smoking histories of 10+ pack-years, n = 309. We performed whole exome sequencing and analyzed rare (minor allele frequency [MAF] < 0.01 in reference exome databases) variants predicted to be functional in the 109 susceptibility loci previously identified by GWAS. We tested our results using two independent series including the Boston Early-Onset pedigrees sequencing study (n = 350) and the Exome Sequencing Project (ESP)-COPDGene study (n = 400). Results: Our analysis revealed two genes with multiple rare non-synonymous substitution variants significantly associated with COPD risk. We identified six rare variants in 10q23.33 Myoferlin (MYOF: p.Arg572Gln, p.Phe1400Leu, p.Tyr1163His, p.Glu1339Lys, p.Leu1582Pro, and p.Arg1630Gln) occurring in 12 susceptible smokers with severe COPD, and three rare variants in 15q15.2 Transglutaminase 5 (TGM5: p.Thr42Asn, Pro136Leu, and p.Val202Ile) occurring in nine susceptible smokers with severe COPD, compared with none of these variants identified in resistant smokers. MAF of these mutations were very rare (range from 0 to 0.003) in the 1000 Genomes and ESP databases. All of these mutations were predicted to be protein damaging and deleterious by bioinformatics algorithms (SIFT, PolyPhen2, Mutation Taster, etc.). We also observed three suggestive rare mutations, 6p21.32 ZBTB9 p.Leu43Val, 9q34.2 DBH p.Gly482Arg, and 10q23.33 IFIT3 p.Leu390Arg, each of which were present in three susceptible smokers and none in resistant smokers. However, we were not able to validate these abovementioned candidate variants in the two replication datasets. This could due to potential false positive results or difference of exome sequencing depth and coverage of the target regions from different platforms. Conclusion: Our results demonstrated potentially disruptive COPD risk-conferring MYOF and TGM5 rare germline mutations that are associated with susceptibility to COPD in one population of smokers, but additional replication of these results in larger populations will be required. Citation Format: Yanhong Liu, Michael H Cho, Dandi Qiao, Farrah Kheradmand, Spiridon Tsavachidis, Georgina Armstrong, Michael Scheurer, David Wheeler, Christopher Amos, Edwin Silverman, Margaret Spitz. Candidate gene analysis of exome sequencing data in smokers susceptible and resistant to chronic obstructive pulmonary disease. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 5229.

Exome Sequencing Analysis in Severe, Early-Onset Chronic Obstructive Pulmonary Disease.

Genomic regions identified by genome-wide association studies explain only a small fraction of heritability for chronic obstructive pulmonary disease (COPD). Alpha-1 antitrypsin deficiency shows that rare coding variants of large effect also influence COPD susceptibility. We hypothesized that exome sequencing in families identified through a proband with severe, early-onset COPD would identify additional rare genetic determinants of large effect. To identify rare genetic determinants of severe COPD. We applied filtering approaches to identify potential causal variants for COPD in whole exomes from 347 subjects in 49 extended pedigrees from the Boston Early-Onset COPD Study. We assessed the power of this approach under different levels of genetic heterogeneity using simulations. We tested genes identified in these families using gene-based association tests in exomes of 204 cases with severe COPD and 195 resistant smokers from the COPDGene study. In addition, we examined previously described loci associated with COPD using these datasets. We identified 69 genes with predicted deleterious nonsynonymous, stop, or splice variants that segregated with severe COPD in at least two pedigrees. Four genes (DNAH8, ALCAM, RARS, and GBF1) also demonstrated an increase in rare nonsynonymous, stop, and/or splice mutations in cases compared with resistant smokers from the COPDGene study; however, these results were not statistically significant. We demonstrate the limitations of the power of this approach under genetic heterogeneity through simulation. Rare deleterious coding variants may increase risk for COPD, but multiple genes likely contribute to COPD susceptibility.

Whole exome sequencing identifies novel candidate genes that modify chronic obstructive pulmonary disease susceptibility.

BackgroundChronic obstructive pulmonary disease (COPD) is characterized by an irreversible airflow limitation in response to inhalation of noxious stimuli, such as cigarette smoke. However, only 15–20 % smokers manifest COPD, suggesting a role for genetic predisposition. Although genome-wide association studies have identified common genetic variants that are associated with susceptibility to COPD, effect sizes of the identified variants are modest, as is the total heritability accounted for by these variants. In this study, an extreme phenotype exome sequencing study was combined with in vitro modeling to identify COPD candidate genes.ResultsWe performed whole exome sequencing of 62 highly susceptible smokers and 30 exceptionally resistant smokers to identify rare variants that may contribute to disease risk or resistance to COPD. This was a cross-sectional case-control study without therapeutic intervention or longitudinal follow-up information. We identified candidate genes based on rare variant analyses and evaluated exonic variants to pinpoint individual genes whose function was computationally established to be significantly different between susceptible and resistant smokers. Top scoring candidate genes from these analyses were further filtered by requiring that each gene be expressed in human bronchial epithelial cells (HBECs). A total of 81 candidate genes were thus selected for in vitro functional testing in cigarette smoke extract (CSE)-exposed HBECs. Using small interfering RNA (siRNA)-mediated gene silencing experiments, we showed that silencing of several candidate genes augmented CSE-induced cytotoxicity in vitro.ConclusionsOur integrative analysis through both genetic and functional approaches identified two candidate genes (TACC2 and MYO1E) that augment cigarette smoke (CS)-induced cytotoxicity and, potentially, COPD susceptibility.Electronic supplementary materialThe online version of this article (doi:10.1186/s40246-015-0058-7) contains supplementary material, which is available to authorized users.

Expression of aquaporins in bronchial tissue and lung parenchyma of patients with chronic obstructive pulmonary disease.

BackgroundAquaporins AQP1 and AQP5 are highly expressed in the lung. Recent studies have shown that the expression of these proteins may be mechanistically involved in the airway inflammation and in the pathogenesis of chronic obstructive pulmonary disease (COPD). The aim of this study was to investigate the expression of AQP1 and AQP5 in the bronchial tissue and the lung parenchyma of patients with COPD and COPD-resistant smokers.MethodsUsing a case–control design, we selected a group of 15 subjects with COPD and 15 resistant smokers (smokers without COPD) as a control, all of whom were undergoing lung resection surgery due to a lung neoplasm. We studied the expression of AQP1 and AQP5 in the bronchial tissue and the lung parenchyma by means of immunohistochemistry and reverse-transcription real-time polymerase chain reaction. Tissue expression of AQP1 and AQP5 was semi-quantitatively assessed in terms of intensity and expression by immunohistochemistry using a 4-point scale ranging from 0 (none) to 3 (maximum).ResultsThere were no significant differences in gene expression between COPD patients and resistant smokers both in the bronchial tissue and in the lung parenchyma. However, AQP1 gene expression was 2.41-fold higher in the parenchyma of smokers with COPD compared to controls, whereas the AQP5 gene showed the opposite pattern, with a 7.75-fold higher expression in the bronchus of smokers with COPD compared with controls. AQP1 and AQP5 proteins were preferentially expressed in endothelial cells, showing a higher intensity for AQP1 (66.7% of cases with an intensity of 3, and 93.3% of subjects with an extension of 3 among patients with COPD). Subtle interstitial disease was associated with type II pneumocyte hyperplasia and an increased expression of AQP1.ConclusionsThis study provides pilot observations on the differences in AQP1 and AQP5 expression between COPD patients and COPD-resistant smokers. Our findings suggest a potential role for AQP1 in the pathogenesis of COPD.

Whole exome re-sequencing implicates CCDC38 and cilia structure and function in resistance to smoking related airflow obstruction.

Chronic obstructive pulmonary disease (COPD) is a leading cause of global morbidity and mortality and, whilst smoking remains the single most important risk factor, COPD risk is heritable. Of 26 independent genomic regions showing association with lung function in genome-wide association studies, eleven have been reported to show association with airflow obstruction. Although the main risk factor for COPD is smoking, some individuals are observed to have a high forced expired volume in 1 second (FEV1) despite many years of heavy smoking. We hypothesised that these “resistant smokers” may harbour variants which protect against lung function decline caused by smoking and provide insight into the genetic determinants of lung health. We undertook whole exome re-sequencing of 100 heavy smokers who had healthy lung function given their age, sex, height and smoking history and applied three complementary approaches to explore the genetic architecture of smoking resistance. Firstly, we identified novel functional variants in the “resistant smokers” and looked for enrichment of these novel variants within biological pathways. Secondly, we undertook association testing of all exonic variants individually with two independent control sets. Thirdly, we undertook gene-based association testing of all exonic variants. Our strongest signal of association with smoking resistance for a non-synonymous SNP was for rs10859974 (P = 2.34×10−4) in CCDC38, a gene which has previously been reported to show association with FEV1/FVC, and we demonstrate moderate expression of CCDC38 in bronchial epithelial cells. We identified an enrichment of novel putatively functional variants in genes related to cilia structure and function in resistant smokers. Ciliary function abnormalities are known to be associated with both smoking and reduced mucociliary clearance in patients with COPD. We suggest that genetic influences on the development or function of cilia in the bronchial epithelium may affect growth of cilia or the extent of damage caused by tobacco smoke.

Cluster analysis in the COPDGene study identifies subtypes of smokers with distinct patterns of airway disease and emphysema

BackgroundThere is notable heterogeneity in the clinical presentation of patients with COPD. To characterise this heterogeneity, we sought to identify subgroups of smokers by applying cluster analysis to data from...

C-Reactive Protein and Serum Amyloid A Overexpression in Lung Tissues of Chronic Obstructive Pulmonary Disease Patients: A Case-Control Study

Background. Although researchers have consistently demonstrated systemic inflammation in chronic obstructive pulmonary disease (COPD), its origin is yet unknown. We aimed to compare the lung bronchial and parenchymal tissues as potential sources of major acute-phase reactants in COPD patients and resistant smokers.Methods. Consecutive patients undergoing elective surgery for suspected primary lung cancer were considered for the study. Patients were categorized as COPD or resistant smokers according to their spirometric results. Lung parenchyma and bronchus sections distant from the primary lesion were obtained. C-reactive protein (CRP) and serum amyloid A (SAA1, SAA2 and SAA4) gene expressions were evaluated by RT-PCR. Protein levels were evaluated in paraffin embedded lung tissues by immunohistochemistry and in serum samples by nephelometry.Results. Our study included 85 patients with COPD and 87 resistant smokers. In bronchial and parenchymal tissues, both CRP and SAA were overexpressed in COPD patients. In the bronchus, CRP, SAA1, SAA2, and SA4 gene expressions in COPD patients were 1.89-fold, 4.36-fold, 3.65-fold, and 3.9-fold the control values, respectively. In the parenchyma, CRP, SAA1, and SAA2 gene expressions were 2.41-, 1.97-, and 1.76-fold the control values, respectively. Immunohistochemistry showed an over-stained pattern of these markers on endovascular cells of COPD patients. There was no correlation with serum protein concentration.Conclusions. These results indicate an overexpression of CRP and SAA in both bronchial and parenchymal tissue in COPD, which differs between both locations, indicating tissue/cell type specificity. The endothelial cells might play a role in the production of theses markers.

Increased Levels of Soluble ICAM-1 in Chronic Obstructive Pulmonary Disease and Resistant Smokers are Related to Active Smoking

Serum ICAM-1 (sICAM-1) is known to be a smoking-associated inflammatory marker, but data in chronic obstructive pulmonary disease (COPD) are lacking. A total of 142 COPD cases (48 active smokers) and 55 controls (41 active smokers) were consecutively enrolled in this cross-sectional study. The peripheral blood concentrations of sICAM-1, IL-8 (CXCL8), CRP and serum amyloid A (SAA) were determined by ELISA. CRP and SAA (log-scale) were elevated in the patients with COPD compared with the control subjects (p = 0.005 for CRP and p = 0.024 for SAA). sICAM-1 was associated with active smoking when corrected for age, gender, the presence of COPD, inhaled corticosteroid use, BMI and forced expiratory volume in 1 s as covariates. The present study confirms an association between sICAM-1 levels and active smoking in a group of COPD and non-COPD active smokers.

Ongoing Self‐Engagement in Quit Attempts and Cessation Outcomes Among Rural Smokers Who Were Unable to Quit After 2 Years of Repeated Interventions

As many smokers experience repeated failures with cessation attempts, it has been postulated that we may create a cadre of highly resistant smokers who are unlikely to engage in treatment or succeed in quitting. Our purpose was to follow a group of recalcitrant rural smokers and examine their ongoing engagement in smoking cessation activities. At the end of a 24-month disease management program for rural smokers, we identified participants who reported ongoing daily smoking despite exposure to 4 previous cycles of smoking cessation interventions. At month 36 (1 year after conclusion of the study), we contacted these participants and assessed changes in smoking status and ongoing engagement in cessation activities over the preceding 6 months. We assessed quit attempts and use of pharmacotherapy during the prior 6 months, as well as smoking abstinence at 36 months. Among 333 recalcitrant smokers, 49% reported at least one 24-hour quit attempt during the preceding 6 months, 29% tried smoking cessation pharmacotherapy, and 5% quit smoking. Significant predictors of having at least one 24-hour quit attempt were lower numbers of cigarettes smoked per day, being in preparation stage of change, and more pharmacotherapy-assisted quit attempts during the original 24-month trial. Higher motivation to quit and more previous pharmacotherapy-assisted quit attempts significantly predicted cessation medication use. Use of varenicline was strongly associated with cessation. Many recalcitrant rural smokers continue to engage in treatment and make quit attempts even in the absence of active interventions.

Association of TNF-α–308G/A, SP-B 1580 C/T, IL-13 –1055 C/T gene polymorphisms and latent adenoviral infection with chronic obstructive pulmonary disease in an Egyptian population

IntroductionChronic obstructive pulmonary disease (COPD) is a leading cause of disability and death. The most common cause of COPD is smoking. There is evidence suggesting that genetic factors influence COPD susceptibility and variants in several candidate genes have been significantly associated with COPD. In this study, we aimed to investigate the possible association of the TNF-α –308, SPB+1580, IL-13 –1055 gene polymorphisms and latent adenovirus C infection with COPD in an Egyptian population.Material and methodsOur study included 115 subjects (75 smokers with COPD, 25 resistant smokers and 15 non-smokers) who were subjected to spirometric measurements, identification of adenovirus C and genotyping of TNF-α –308G/A, SP-B+1580 C/T and IL-13 –1055 C/T polymorphisms by real-time PCR.ResultsThe adenovirus C gene was identified in all subjects. The distribution of TNF-α genotypes showed no significant differences between different groups. However, homozygous A genotype was associated with a significant decrease in FEV1, FEV1/FVC and FEF25/75% of predicted in COPD (p < 0.05). As regards SP-B genotypes, resistant smokers had a significantly higher homozygous T genotype frequency compared to COPD and non smokers (p = 0.005). Interleukin 13 genotypes showed no significant difference between different groups. There was a significant decrease in FEF25/75% of predicted in T allele carriers in COPD patients (p = 0.001).ConclusionsThe COPD is a disease caused by the interaction of combined genes and environmental influences, in the presence of smoking and latent adenovirus C infection, TNF-α –308A, SPB +1580 T and IL-13 –1055 T polymorphisms predispose to the development of COPD.

Cyclooxygenase-2 −765G&gt;C polymorphism is associated with C-reactive protein levels in resistant smokers but not in chronic obstructive pulmonary disease patients

We sought to investigate whether the serum concentrations of several inflammatory biomarkers are related to the cyclooxygenase-2 (COX2) -765G>C polymorphism in chronic obstructive pulmonary disease (COPD) and a control group of non-COPD smokers. Serum inflammatory markers (CRP, SAA, CXCL8, and sICAM-1) were measured by ELISA in 144 patients with COPD and in 55 control subjects. Genomic DNA was extracted from peripheral blood leukocytes, and the COX2 -765G>C (rs20417) polymorphism was genotyped. After adjustment for age and active smoking, CRP and SAA concentrations were associated with the COX2 polymorphism in controls (p=0.041 and 0.014, respectively) but not in COPD patients. The CXCL8 and sICAM-1 concentrations were not associated with the COX2 polymorphism for either cases or controls. The results of the present study indicate that there is a relationship between the COX2 -765G>C polymorphism and the concentrations of CRP and SAA in non-COPD smokers and that this relationship does not exist in COPD patients.

The cyclooxygenase-2-765C promoter polymorphism protects against the development of chronic obstructive pulmonary disease

Susceptibility to Chronic Obstructive Pulmonary Disease (COPD) has a genetic component. We undertook a study to determine if a genetic variant of the gene encoding the cyclooxygenase-2 gene influences the likelihood of developing COPD. In a case control study the frequency of a single nucleotide polymorphism in the promoter region of the cyclooxygenase-2 gene (-765 G → C) was determined in 205 subjects with COPD, 171 chronic smokers with normal lung function (resistant smokers) and 95 healthy blood donors using the polymerase chain reaction and restriction enzyme fragment length polymorphism. The frequency of the C allele of the -765 cyclooxygenase-2 polymorphism was higher in resistant smokers (24.6%) compared with subjects with COPD (14.4%, OR = 1.98, 95% CI = 1.28-3.06, p = 0.003) and blood donors (14.7%, OR = 1.97, 95% CI = 1.14-3.41, p = 0.03). The -765C allele, which has been shown to be associated with decreased promoter activity of the cyclooxygenase-2 gene, is more common in resistant smokers. This raises the possibility that decreased activity of cyclooxygenase-2 may protect smokers against the development of COPD.

Association of Tumor Necrosis Factor-α-863C/A Gene Polymorphism with Chronic Obstructive Pulmonary Disease

The aim of this study was to investigate genetic effects on the pathogenesis of chronic obstructive pulmonary disease (COPD). The study was conducted as a prospective case-control study in a medical center in southern Taiwan. The patient group consisted of 145 male patients with smoking-related COPD and a control group of 139 resistant smokers from July 2004 to September 2009. We compared allele and genotype frequencies of three tag single nucleotide polymorphisms (SNP) of the TNF-alpha gene promoter region at -308, -863, and -1031 in all subjects. We also analyzed the influence of each genetic variant on pulmonary function parameters, body mass index (BMI), serum TNF-alpha levels, and outcomes among heavy smokers with or without COPD. COPD patients had a significantly lower A allele frequency (9.7 vs. 15.1%, OR = 0.6, p = 0.048, false discovery rate q = 0.144) and a significantly lower A carrier genotype frequency (19.3 vs. 30.2%, OR = 0.52, p = 0.042, q = 0.135) than resistant smokers. The -863 CA genotype was associated with a better FEV(1)/FVC ratio (79 vs. 71.5%, p = 0.034), and higher BMI (24.9 vs. 23.6 kg/m(2), p = 0.048). In addition, COPD patients with the -1031 C carrier genotype had higher serum TNF-alpha levels (20.9 vs. 16.2 pg/ml, p = 0.01). BMI (hazard ratio = 0.84, 95% CI = 0.74-0.96, p = 0.008) was the only independent predictor for mortality. The TNF-alpha -863 A allele may confer a degree of resistance to the susceptibility to and muscle wasting of COPD among heavy smokers.

Estimation of TGF-β1 genotypes in Egyptian smokers; association with FEV(1) in COPD patients.

IntroductionTGF-β1 is a cytokine with many different effects on cell proliferation, differentiation and inflammation and can protect against the development of COPD. This work aims to study the association between COPD and the TGF-β1 gene genotypes.Material and methodsThe study included 70 males: 25 smokers with COPD, 25 resistant smokers, and 20 normal non-smokers as the control. They were subjected to spirometry pre- and post-bronchodilator (FEV1, FEV1/FVC), estimation of serum level of TGF-β1 gene by PCR and RFLP.ResultsThe percent of Pro-Leu was 28% in the COPD group, 84% in the resistant smokers group and 85% in the control group. There was a highly significant statistical difference in FEV1% of predicted associated with the distribution of TGF-β1 gene genotypes: 56.9 ±8.4% with Pro-Leu genotype and 35.5 ±8.8% with Leu-Leu genotype in COPD patients, 93.2 ±6.2% with Pro-Leu genotype and 86.7 ±0.9% with Leu-Leu genotype in the resistant smokers group.ConclusionsThe Pro-allele genotype is associated with increased production of TGF-β1, which has a protective role against the development of COPD and is important in preserving the decline of FEV1 in COPD patients.

Characteristics and prevalence of hardcore smokers attending UK general practitioners

BackgroundSmoking remains a public health problem and although unsolicited GPs' advice against smoking causes between one and three percent of smokers to stop, a significant proportion of smokers are particularly resistant to the notion of stopping smoking. These resistant smokers have been called "hardcore smokers" and although 16% of smokers in the community are hardcore, little is known about hardcore smokers presenting to primary care physicians. Consequently, this study reports the characteristics and prevalence of hardcore smokers attending UK GPs.MethodsA cross-sectional survey using data from two different research projects was conducted. Data for this analysis had been collected from surgery consultation sessions with 73 GPs in Leicestershire, England, (42 GPs from one project). Research assistants distributed pre-consultation questionnaires to 4147 adults attending GPs' surgery sessions. Questionnaires identified regular smokers, the proportion of hardcore smokers and their characteristics. Non-hardcore and hardcore smokers' ages, gender and nicotine addiction levels were compared.Results1170 regular smokers attended surgery sessions and, 16.1% (95% CI, 14.1 to 18.4) were hardcore smokers. Hardcore smokers had higher levels of nicotine addiction than others (p = 0.000), measured by the Heaviness of Smoking Index and were more likely to be male [50.5% hardcore versus 35.3% non-hardcore, (OR = 1.88, 95% CI = 1.4 to 2.6)] but no age differences were observed between groups.ConclusionA significant minority of the smokers who present in general practice are resistant to the notion of smoking cessation and these smokers are more heavily nicotine addicted than others. Although clinical guidelines suggest that GPs should regularly advise all smokers against smoking, it is probable that hardcore smokers do not respond positively to this and help to make up the 97%–99% of smokers who do not quit after being advised to stop smoking by GPs. General practitioners need to find approaches for raising the issue of smoking during consultations in ways that do not reinforce the negative opinions of hardcore smokers concerning smoking cessation.

The Austrian Multicentre Study on Smoking: Subgroups of Nicotine Dependence and Their Craving

Background: The misconception of tobacco smoking as a ‘bad habit’ has been replaced by a diagnosis of addiction. Although help to quit is offered by nicotine replacement, antidepressants and psychotherapeutic support, there is no cure yet. One cause of impediment might be psychiatric comorbidity. Therefore, we searched for smoker subgroups, needing different treatments. Aim of the Study: The study aimed at subtyping smokers in an attempt to better understand the phenomenon of resistant smokers and provide more information that could potentially become useful to treatment centres assuming the subtypes correlate directly with outcomes of different smoking cessation treatments, tailor-made according to subtypes. Methods: 330 out of 430 recruited smokers were classified as nicotine dependent (ICD-10) and tobacco dependent (DSM-IV) and remained in the study. They were investigated with different diagnostic assessments: Fagerström Test (FT), Lübeck Craving Risk Relapse Questionnaire and Lesch Typology Questionnaire (the last two being modified for smoking). Results: Dependence severity degree is reflected by the FT. FT scores ≧5 indicated higher conspicuousness. Four clusters for nicotine craving were found: (1) ‘depressed’, (2) ‘stimulated’, (3) ‘relaxed mood state’ and (4) ‘socially triggered tensed mood’. In contrast to alcoholism, ‘stimulation’ was one of the major craving conditions in smokers. The decision tree, consisting of the FT and the Lesch Typology Questionnaire, distinguishes four subgroups of nicotine-dependent persons. Conclusion: The subgroups reflect different reinforcement and psychosocial disturbances. They match treatment and can be applied as outcome predictors in controlled treatment and relapse prevention studies.

A novel approach for assessment of cancer predisposing roles of GSTM1 and GSTT1 genes: use of putatively cancer resistant elderly tumor-free smokers as the referents

We applied an alternative approach to assess the controversial evidence for the role of GSTM1 and GSTT1 deficiencies (null genotypes) in cancer susceptibility. In this study setting, the prevalence of GSTM1 and GSTT1 null genotypes in the lung cancer patients (LCs, n=167) were compared with those in the group of putatively cancer resistant individuals, i.e. elderly tumor-free donors (EDs, n=324). Healthy middle-aged donors (HDs, n=339) were used as another comparison group. Our results support the previous conclusions of a modest protective effect associated with presence of at least one functional copy of GSTM1 gene; the prevalence of GSTM1 deficiency in LCs (54%) did not differ from that observed in HDs (54%), but showed a significant increase when compared with EDs (45%) (OR=1.46, 95% CI=1.00–2.12). Furthermore, in agreement with mechanistic considerations, the GSTM1 null genotypes were more prevalent in squamous cell carcinoma patients (58%) and in lung cancer patients with seemingly low cumulative carcinogen exposure dose (non-smokers: 63%; patients aged below 50 years: 76%). Contrary to GSTM1, no significant effect in the lung cancer proneness was observed for the GSTT1 genotypes. The results of this study are thus in good agreement with the body of literature data, including several published meta-analyses. Consequently, the suggested study design involving additional “cancer resistant” group of non-affected subjects appears to provide highly demonstrative data and to be well suited for pilot investigations and for resolving controversial issues.

Clusters of precontemplating smokers defined by the perception of the pros, cons, and self-efficacy

Western smoker populations contain high percentages of smokers who are not motivated to quit. In order to develop self-help smoking cessation interventions for these smokers, it is of importance to know whether there are subtypes among this group. In the present study, cluster analysis was used to search for clusters of precontemplating smokers. The clusters were described by three cognitive clustering variables: the pros of quitting, the cons of quitting, and self-efficacy expectations. On the basis of earlier studies, three cluster solutions were tested: the 3-, 4-, and 5-cluster solutions. To cross-validate the findings, data from two independently recruited samples of precontemplating smokers were used. Three clusters, which were found in earlier studies in the United States, were replicated. In the present study these were called Unmotivated Pessimists, Motivated Pessimists, and Disengaged. Two additional clusters were identified, which might be typical for the tolerant Dutch smoking culture: Unmotivated Optimists and Motivated Optimists. It is argued that the replicated types are more nicotine-dependent and resistant to change, and represent the hard core smoker population, and that both optimistic types are less dependent, less resistant smokers who will quit with increasing societal anti-smoking pressure. Longitudinal analyses showed that cluster membership was predictive of increases in intention to quit and quitting activity.