Sputum Vitamin D Binding Protein (VDBP) GC1S/1S Genotype Predicts Airway Obstruction: A Prospective Study in Smokers with COPD.

Introduction: The vitamin D binding protein (VDBP, also known as GC-globulin) and vitamin D deficiency have been associated with chronic obstructive pulmonary disease (COPD). rs7041 and rs4588 are two single nucleotide polymorphisms of the VDBP gene, including three common allelic variants (GC1S, GC1F and GC2). Previous studies primarily assessed the serum levels of vitamin D and VDBP in COPD. However, less is known regarding the impact of the local release of VDBP on COPD lung function. Thus, we examined the association of sputum and plasma VDBP with lung function at baseline and at four years, and examined potential genetic polymorphism interactions. Methods: The baseline levels of sputum VDBP, plasma VDBP and plasma 25-OH vitamin D, as well as the GC rs4588 and rs7041 genotypes, were assessed in a 4-year Finnish follow-up cohort (n = 233) of non-smokers, and smokers with and without COPD. The associations between the VDBP levels and the longitudinal decline of lung function were further analysed. Results: High frequencies of the haplotypes in rs7041/rs4588 were homozygous GC1S/1S (42.5%). Higher sputum VDBP levels in stage I and stage II COPD were observed only in carriers with GC1S/1S genotype when compared with non-smokers (p = 0.034 and p = 0.002, respectively). Genotype multivariate regression analysis indicated that the baseline sputum VDBP and FEV1/FVC ratio at baseline independently predicted FEV1% at follow-up. Discussion and Conclusion: The baseline sputum VDBP expression was elevated in smokers with COPD among individuals with the GC1S/1S genotype, and predicted follow-up airway obstruction. Our results suggest that the GC polymorphism should be considered when exploring the potential of VDBP as a biomarker for COPD.

Reactive oxygen species-regulating proteins peroxiredoxin 2 and thioredoxin, and glyceraldehyde-3-phosphate dehydrogenase are differentially abundant in induced sputum from smokers with lung cancer or asbestos exposure.

Lung cancer is a deadly disease, typically caused by known risk factors, such as tobacco smoke and asbestos exposure. By triggering cellular oxidative stress and altering the antioxidant pathways eliminating reactive oxygen species (ROS), tobacco smoke and asbestos predispose to cancer. Despite easily recognizable high-risk individuals, lung cancer screening and its early detection are hampered by poor diagnostic tools including the absence of proper biomarkers. This study aimed to recognize potential lung cancer biomarkers using induced sputum noninvasively collected from the lungs of individuals in risk of contracting lung cancer. Study groups composed of current and former smokers, who either were significantly asbestos exposed, had lung cancer, or were unexposed and asymptomatic. Screening of potential biomarkers was performed with 52, and five differentially abundant proteins, peroxiredoxin 2 (PRDX2), thioredoxin (TXN), glyceraldehyde-3-phosphate dehydrogenase (GAPDH), extracellular matrix protein 1 (ECM1), and protein S100 A8 (S100A8), were chosen to undergo validation, for their previously known connection with oxidative stress or cancer. Results from the validation in 123 sputa showed that PRDX2, TXN, and GAPDH were differentially abundant in sputa from individuals with lung cancer. TXN had a negative correlation with asbestos exposure, yet a positive correlation with smoking and lung cancer. Thus, tobacco smoking, asbestos exposure, and lung carcinogenesis may disturb the cellular redox state in different ways. A strong correlation was found among PRDX2, TXN, GAPDH, and S100A8, suggesting that these proteins may present a diagnostic biomarker panel to aid recognizing individuals at high risk of contracting lung cancer.

Lung tissue proteomics identifies elevated transglutaminase 2 levels in stable chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous disease characterized by irreversible airflow limitation. Cigarette smoking represents the main risk factor, but the specific mechanisms of COPD are not completely understood. Our aim was to identify COPD-specific proteomic changes involved in disease onset and severity. A comparative proteomic analysis of 51 lung tissues from nonsmokers, smokers, smokers with mild to moderate (stage I-II) COPD, severe to very severe COPD (stage III-IV), and patients with α-1-antitrypsin deficiency (AATD) and idiopathic pulmonary fibrosis (IPF) was performed by cysteine-specific two-dimensional difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry. Selected COPD-specific changes were validated by immunoblotting and further by ELISA in 120 induced sputum and plasma samples from nonsmokers, smokers, and patients with COPD (stage I-III). Altogether 82 altered proteins were identified comprising COPD-, AATD-, and IPF-specific, overlapping, and unspecific changes. Cathepsin D (CTSD), dihydropyrimidinase-related protein 2 (DPYSL2), transglutaminase 2 (TGM2), and tripeptidyl-peptidase 1 (TPP1) were validated as COPD-specific. TGM2 was not associated with smoking and correlated with COPD severity in lung tissue. TGM2 levels in sputum and plasma were elevated in patients with COPD (stage II-III) and correlated with lung function. In conclusion, new proteins related to COPD onset and severity could be identified with TGM2 being a novel potential diagnostic and therapeutic target for COPD. Further studies in carefully characterized cohorts are required to validate the identified changes.

Varenicline and Nicotine Patch Therapies in Young Adults Motivated to Quit Smoking: A Randomized, Placebo-controlled, Prospective Study.

This study compares the nicotine patch to placebo in young adult light smokers, and the nicotine patch to varenicline in heavy smokers. Volunteer daily smokers were recruited into a randomized, placebo-controlled study via community media, colleges and the army (aged 18-26 years). Those subjects with light tobacco dependence were randomized to (i) placebo patch (n = 86) and (ii) nicotine patch 10 mg/16 hr for 8 weeks (n = 94), and those with stronger dependence to (iii) nicotine patch 15 mg/16 hr for 8 weeks (n = 51) and (iv) varenicline for 12 weeks (n = 60). The primary outcome variable was self-reported smoking abstinence at week 12. Secondary outcome variables were self-reported smoking abstinence at weeks 4 and 26, and self-reported abstinence verified by saliva cotinine level at week 12. The prevalence of self-reported smoking abstinence did not differ statistically significantly in light smokers during the follow-up (week 4: 19.8% for placebo patch and 26.6% for nicotine patch 10 mg/16 hr; week 12: 17.4% versus 23.4%; week 26: 15.1% versus 20.2%), but the groups of heavy smokers differed significantly for 12 weeks (week 4: 19.6% for nicotine patch 15 mg/16 hr and 73.3% for varenicline, p < 0.001; week 12: 15.7% versus 36.7%, p = 0.018). This statistically significant difference did not endure for the entire follow-up (week 26: 9.8% versus 18.3%, p = 0.280). However, saliva cotinine verified abstinence at week 12 did not support self-reported abstinence. Varenicline may be more effective than the nicotine patch as a smoking cessation pharmacotherapy among young adult heavy smokers in the short-term.

Clinical characteristics of COPD syndrome: A 6-year follow-up study of adult smokers.

BACKGROUND: There is little quantitative information about the development of chronic obstructive pulmonary disease (COPD) among adult smokers and of what happens to patients who have already developed COPD. OBJECTIVES: To examine the development and performance of COPD status over time, and the clinical characteristics of new COPD cases according to the Global Initiative for Chronic Obstructive Lung Disease (GOLD) 2007 and 2011 classifications. METHODS: Healthy asymptomatic smokers were recruited through newspaper announcements. They filled in questionnaires and had an individualized assessment of their health history during all three visits (visit 1, visit 2 after three years, visit 3 after six years). RESULTS: Of the eligible 621 heavy smokers, 572 attended visit 2. A total of 513 subjects completed the 6-year follow-up examination. According to GOLD 2007, COPD was present in 22.8% (n = 117) of these smokers. The severity of COPD changed during the years of follow-up. Furthermore, health status and prevalence of chronic respiratory symptoms both in the smokers with normal lung function and in the COPD groups varied over the time period. CONCLUSIONS: GOLD 2011 recognized the complex patient subgroups better than GOLD 2007. Variability in chronic symptoms or in health status correlated poorly with the severity of airway limitation.

Soluble receptor for advanced glycation end-products and progression of airway disease.

BACKGROUND: The receptor for advanced glycation end-products (RAGE) is highly expressed in the lung, where it is believed to have a homeostatic role. Reduced plasma levels of soluble RAGE (sRAGE) have been reported in patients with chronic obstructive pulmonary disease (COPD). The aim of the present study was to evaluate the association of plasma sRAGE levels with a longitudinal decline of lung function. We have also measured plasma levels of high mobility group box 1 (HMGB1), a RAGE ligand which has been associated with chronic inflammatory diseases including COPD. METHODS: Baseline plasma concentrations of sRAGE and HMGB1 were measured in non-smokers (n = 32), smokers without COPD (n = 212), and smokers with COPD (n = 51), and the associations of the plasma sRAGE and HMGB1 levels with longitudinal declines of lung function during a 4-year follow-up period were analysed. RESULTS: The plasma levels of sRAGE were significantly lower in smokers without COPD and in smokers with COPD, as compared to those of non-smokers. Plasma sRAGE levels positively correlated with FVC and FEV1 and inversely correlated with BMI and pack-years. Lower sRAGE levels were associated with greater declines of FEV1/FVC over 4 years in all participants. Moreover, multivariate regression analysis indicated that the baseline plasma sRAGE concentration was an independent predictor of FEV1/FVC decline in all groups. A subgroup analysis showed that decreased sRAGE levels are significantly associated with a more rapid decline of FEV1/FVC in smokers with COPD. There was no significant correlation between plasma HMGB1 levels and longitudinal decline of lung function. CONCLUSIONS: Lower plasma concentrations of sRAGE were associated with greater progression of airflow limitations over time, especially in smokers with COPD, suggesting that RAGE might have a protective role in the lung.

Environmental exposure as an independent risk factor of chronic bronchitis in northwest Russia.

BACKGROUND: In some parts of the northwest Russia, Murmansk region, high exposures to heavy mining and refining industrial air pollution, especially sulphur dioxide, have been documented. OBJECTIVE: Our aim was to evaluate whether living in the mining area would be an independent risk factor of the respiratory symptoms. DESIGN: A cross-sectional survey of 200 Murmansk region adult citizens was performed. The main outcome variable was prolonged cough with sputum production that fulfilled the criteria of chronic bronchitis. RESULTS: Of the 200 participants, 53 (26.5%) stated that they had experienced chronic cough with phlegm during the last 2 years. The prevalence was higher among those subjects living in the mining area with its high pollution compared to those living outside this region (35% vs. 18%). Multivariable regression model confirmed that the risk for the chronic cough with sputum production was elevated in a statistical significant manner in the mining and refining area (adjusted OR 2.16, 95% CI 1.07-4.35) after adjustment for smoking status, age and sex. CONCLUSIONS: The increased level of sulphur dioxide emitted during nickel mining and refining may explain these adverse health effects. This information is important for medical authorities when they make recommendations and issue guidelines regarding the relationship between environmental pollution and health outcomes.

Dual use of cigarettes and Swedish snuff (snus) among young adults in Northern Finland.

BACKGROUND: The sale of smokeless tobacco has been totally banned in Finland since the country joined the European Union in 1995. Adolescents have continued to use smokeless tobacco even after the sales ban. The objective was to describe dual use of Swedish snuff (snus) and cigarettes in young adults living in Northern Finland. METHODS: This study on male military recruits (n = 1151, mean age 19.4 years; response rate 80%) investigated association of snus use with self-reported tobacco use, nicotine dependence and attempts to quit smoking. RESULTS: Overall, 15.6% (n = 179) reported daily snus use, and almost half of them were dual users who used both products, i.e. cigarettes and snus, daily. Daily smokers were often occasional snus users (66.3%), and those with dual use smoked equal number of cigarettes per day as daily smokers who were not snus users. In addition, dual snus use seemed to increase the dependence to cigarettes, although this trend did not reach statistical significance. Dual users tried to quit less likely than exclusive smokers. Very few snus users were 'switchers' (ex-smokers) [3.2% (n = 22) of all snus users]. CONCLUSIONS: Dual use of snus and cigarettes is common among young in Finland, despite the sales ban on snus. The role of snus in reducing cigarette smoking is unclear, but it is likely that snus use complicates the attempts to quit smoking.

Distribution and levels of alpha-1-antitrypsin in the lung and plasma in smokers and chronic obstructive pulmonary disease.

Our recent non-biased proteomic screening study revealed elevated SerpinA1 i.e. alpha-1-antitrypsin (AAT) levels in induced sputum of smokers with Chronic obstructive pulmonary disease (COPD). This study was designed to further investigate the role of AAT in smokers and subjects with COPD. The expression/distribution of AAT was studied by immunohistochemistry/digital image morphometry in the lung, by Western blot in the lung and sputum, and by ELISA in the plasma at baseline (n = 349) and after a 2-year follow-up (n = 58). AAT was localized mainly in airway and alveolar epithelium and endothelium, especially in smokers and in those with COPD. AAT was elevated in smokers and in subjects with COPD in the lung endothelial cells. Total lung AAT immunoreactivity was elevated in subjects with moderate COPD compared with smokers and with non-smokers. AAT showed elevated tendency in sputum of smokers with COPD compared with 'healthy' smokers. Plasma AAT levels were elevated in smokers with/without COPD compared with non-smokers. In the follow-up, plasma AAT concentrations decreased significantly after quitting smoking. Chronic smoking/COPD leads to AAT elevation especially in the endothelium of the lung periphery; these changes reflect only modestly to the AAT in sputum, while plasma AAT significantly reflects smoking-related systemic manifestations, and decreases after smoking cessation.

Young male daily smokers are nicotine dependent and experience several unsuccessful quit attempts.

OBJECTIVE: Previous studies on smoking cessation have generally been conducted with adolescents or adults. Very little is known about the cessation attempts, their success, and/or use of pharmacological aids in young adult smokers who want to quit. The present study aimed to investigate quitting attempts in a group of both young male daily and occasional smokers. DESIGN AND SUBJECTS: 614 male smokers aged 18-26 years completed a standardized questionnaire about their smoking habits, quit attempts, and aids used in smoking cessation. RESULTS: Nearly all daily smokers (95.3%, 95% CI 93.1-96.8) were nicotine addicted to some extend according to the standardized questionnaire, and the more addicted they were, the more often they had tried to quit (p = 0.025). Of the daily smokers, 55.6% (95% CI 51.3-59.9) had made quit attempts and 36.2% (95% CI 32.1-40.4) had used nicotine replacement therapy (NRT). In all, 34.1% (95% CI 25.2-44.3) of all occasional smokers reported having intended to quit but they had seldom made more than one attempt whereas 20.2% of daily smokers had made at least three attempts. The stronger the nicotine dependence in daily smokers was, the more likely the subject was to have attempted to use NRT (quite dependent 23.8% vs. totally dependent 48.9%) (p < 0.001). CONCLUSIONS: A high proportion of young male daily smokers were nicotine addicted. Young smokers make many unsuccessful attempts to stop smoking using nicotine replacement therapy (NRT) on their own. A better availability of professional cessation services directed to young adult smokers is needed.

Peroxiredoxins and tropomyosins as plasma biomarkers for lung cancer and asbestos exposure.

The prognosis of lung cancer is poor due to late diagnosis, the lack of established screening programs, and the paucity of early biomarkers for high-risk populations. Plasma proteome analysis was used to identify novel biomarkers for diagnosing lung cancer, and to unravel the mechanisms of underlying pathogenesis. Plasma proteins obtained from asbestos-exposed lung cancer cases detected by CT screening, asbestos-exposed subjects, clinical lung cancer patients, and healthy tobacco smokers, 5-6 cases in each group, were separated by two-dimensional gel electrophoresis, and identified with tandem mass spectrometry (LC-MS/MS). Nine proteins were selected for immunological confirmation in a test or validation set of plasma samples from an additional 49 clinical lung cancer cases, 66 asbestos-exposed patients, and 107 healthy tobacco smokers. Twenty-eight unique proteins were differentially expressed between the four study groups (p<0.05). Peroxiredoxin 1 (PRX1) was detected as a novel plasma marker for lung cancer (p=0.001). We also confirmed the previously found association of serum amyloid A with lung cancer (p<0.001). High plasma levels of tropomyosin 4 (TPM4: p<0.001) and peroxiredoxins 1 and 2 (PRX2: p<0.001) correlated with asbestos exposure or a diagnosis of asbestosis. PRX1 and PRX2 exhibited an inverse correlation with tobacco smoking (p<0.001). Plasma peroxiredoxins 1 and 2, and tropomyosin 4 were shown to associate with asbestos-exposure, and peroxiredoxin 1 with lung cancer. High plasma levels of peroxiredoxin 1 may result from genetic damage caused by reactive oxygen species. This study has identified several biomarkers worthy of further investigation in lung cancer and asbestos-related diseases.

Sputum proteomics identifies elevated PIGR levels in smokers and mild-to-moderate COPD.

Chronic obstructive pulmonary disease (COPD) is one of the leading causes of morbidity and mortality around the world. However, the exact mechanisms leading to COPD and its progression are still poorly understood. In this study, induced sputum was analyzed by cysteine-specific two-dimensional difference gel electrophoresis (2D-DIGE) coupled with mass spectrometry to identify proteins involved in COPD pathogenesis. The comparison of nonsmokers, smokers, and smokers with moderate COPD revealed 15 changed proteins with the majority, including polymeric immunoglobulin receptor (PIGR), being elevated in smokers and subjects with COPD. PIGR, which is involved in specific immune defense and inflammation, was further studied in sputum, lung tissue, and plasma by Western blot, immunohistochemistry/image analysis, and/or ELISA. Sputum PIGR was characterized as glycosylated secretory component (SC). Lung PIGR was significantly elevated in the bronchial and alveolar epithelium of smokers and further increased in the alveolar area in mild to moderate COPD. Plasma PIGR was elevated in smokers and smokers with COPD compared to nonsmokers with significant correlation to obstruction. In conclusion, new proteins in smoking-related chronic inflammation and COPD could be identified, with SC/PIGR being one of the most prominent not only in the lung but also in circulating blood.

Smoking and COPD increase sputum levels of extracellular superoxide dismutase.

Extracellular superoxide dismutase (ECSOD) is the major superoxide-scavenging enzyme in the lung. Certain ECSOD polymorphisms are protective against COPD. We postulated that smokers and COPD subjects would have altered levels of ECSOD in the lung, airway secretions, and/or plasma. Lung tissue ECSOD was evaluated from nonsmokers, smokers, and subjects with mild to very severe COPD by Western blot, immunohistochemistry, and ELISA. ECSOD levels in plasma, bronchoalveolar lavage fluid (BALF), and induced-sputum supernatants were analyzed by ELISA and correlated with smoking history and disease status. Immunohistochemistry identified ECSOD in extracellular matrix around bronchioles, arteries, and alveolar walls, with decreases seen in the interstitium and vessels of severe COPD subjects using digital image analysis. Plasma ECSOD did not differ between COPD subjects and controls nor based on smoking status. ECSOD levels in induced sputum supernatants were elevated in current smokers and especially in COPD subjects compared to nonsmokers, whereas corresponding changes could not be seen in the BALF. ECSOD expression was reduced around vessels and bronchioles in COPD lungs. Substantial increases in sputum ECSOD in smokers and COPD is interpreted as an adaptive response to increased oxidative stress and may be a useful biomarker of disease activity in COPD.

Ageing and long-term smoking affects KL-6 levels in the lung, induced sputum and plasma.

BACKGROUND: KL-6 is a high-molecular-weight glycoprotein classified as a human MUC1 mucin. It was hypothesized that KL-6 could be detectable in the circulating blood and especially in airway secretions in lung diseases associated with mucus production such as chronic obstructive pulmonary disease (COPD). Additional aims of this study were to investigate whether the levels of KL-6 in plasma and sputum are related to ageing and smoking history. METHODS: The concentrations of KL-6 in plasma and induced sputum supernatants from young and/or middle aged/elderly non-smokers, smokers and patients with COPD were assayed by ELISA (n = 201). The subjects were classified into five groups according to age, smoking status and presence of COPD. In addition, KL-6 expression in control and diseased lung i.e. samples from patients with COPD (n = 28), were analyzed by immunohistochemistry and digital image analysis. RESULTS: The plasma levels of KL-6 increased with age both in non-smokers and smokers. Among middle aged/elderly subjects, plasma KL-6 levels in all smokers regardless of COPD were significantly higher than in non-smokers, whereas sputum levels of KL-6 were significantly higher in COPD compared not only to non-smokers but also to smokers. KL-6 was more prominently expressed in the bronchiolar/alveolar epithelium in COPD than in the control lungs. Plasma and sputum KL-6 levels correlated inversely with obstruction and positively with smoking history and ageing. The linear multiple regression analysis confirmed that age and cigarette smoking had independent effects on plasma KL-6. CONCLUSIONS: KL-6 increases with ageing and chronic smoking history, but prospective studies will be needed to elucidate the significance of KL-6 in chronic airway diseases.

Ageing and smoking contribute to plasma surfactant proteins and protease imbalance with correlations to airway obstruction.

BACKGROUND: A significant number of young people start smoking at an age of 13-15, which means that serious smoking-evoked changes may have been occurred by their twenties. Surfactant proteins (SP) and matrix metalloproteinases (MMPs) and their tissue inhibitors (TIMPs) have been linked to cigarette smoke induced lung remodelling and chronic obstructive pulmonary disease (COPD). However, the level of these proteins has not been examined during ageing or in young individuals with short smoking histories. METHODS: Plasma levels of SP-A, SP-D, MMP-9, and TIMP-1 were measured by EIA/ELISA from young (18-23 years) non-smoking controls (YNS) (n = 36), smokers (YS) (n = 51), middle aged/elderly (37-77 years) non-smoking controls (ONS) (n = 40), smokers (OS) (n = 64) (FEV1/FVC >0.7 in all subjects) and patients with COPD (n = 44, 35-79 years). RESULTS: Plasma levels of SP-A increased with age and in the older group in relation to smoking and COPD. Plasma SP-D and MMP-9 levels did not change with age but were elevated in OS and COPD as compared to ONS. The TIMP-1 level declined with age but increased in chronic smokers when compared to ONS. The clearest correlations could be detected between plasma SP-A vs. age, pack years and FEV1/FVC. The receiver operating characteristic (ROC) curve analysis revealed SP-A to be the best marker for discriminating between patients with COPD and the controls (area under ROC curve of 0.842; 95% confidence interval, 0.785-0.899; p < 0.001). CONCLUSIONS: Age has a significant contribution to potential markers related to smoking and COPD; SP-A seems to be the best factor in differentiating COPD from the controls.

Attitudes to new smoking restrictions and second-hand smoke among young Finnish males.

AIMS: Relatively little is known about the attitudes of young people to restrictions on smoking in public places and to environmental second-hand smoke in housing estates. The objective was to explore the attitudes of young male adults after the new smoke-free legislation was implemented in Finland. METHODS: A survey of 1167 Finnish male military conscripts was performed. The main outcome variables were their attitudes to the new restrictions on smoking in public places and concerns about second-hand smoke in the home originating from their neighbours. RESULTS: Almost half of the youths (43.5%) reported that they supported the more restrictive smoking regulations, with 44.8% having a neutral view. Only 16.0% of the respondents were irritated about the second-hand smoke entering to their house from outside and 48.6% were not concerned about smoking in their neighbourhood. A total of 555 (47.6%) conscripts were current smokers. Current smokers were more often totally opposed to the legislation and had less negative views about the exposure to second-hand smoke than non-smokers. Strong nicotine dependence increased the feelings of anxiety and stigmatisation when the new restrictions were introduced. CONCLUSIONS: Finnish young men do accept new smoking restrictions. However, smoking with high nicotine dependence was surprisingly common among these young men and the negative attitude to the legislation can be traced to this group of smokers. The repulsion felt towards second-hand smoke by non-smokers represents an opportunity for public health initiatives to guarantee a smoke-free environment in public and private places.

High frequency of chronic cough and sputum production with lowered exercise capacity in young smokers.

OBJECTIVES: The aim was to evaluate how cigarette smoking is associated with respiratory symptoms, fitness, and anthropometric measures in young smokers. METHODS: The prevalence of smoking was investigated in a cohort of young military draftees (n = 1130; 98% between 18­21 years of age) in Northern Finland. The associations of smoking with respiratory symptoms, physical fitness (12-min running test), education, and anthropometric measures were analysed using a self-reported questionnaire with high response rate (80%). RESULTS: Almost half (46.5%) of the young males were daily smokers, 17.4% being occasional smokers. The prevalence of self-reported chronic cough and sputum production was high in daily smokers (40.7%) and occasional smokers (26.9%) compared to non-smokers (12%). These symptoms were significantly associated with the smoking history. Aerobic fitness was worse in regular smokers compared to non-smokers (P < 0.001). Smokers had a higher body mass index than non-smokers (P = 0.035). In the regular smokers, the more active the subjects were in sports, the less they smoked when evaluated by pack year history (P < 0.001). Smokers had a lower educational level than occasional smokers or, especially, non-smokers (P < 0.001). CONCLUSIONS: The frequency of young smokers with chronic cough and sputum production was very high, posing a serious risk to their future health.

Early detection of COPD combined with individualized counselling for smoking cessation: a two-year prospective study.

OBJECTIVE: Though the prevalence of COPD is related to the definition, even with this proviso COPD remains under-diagnosed. Screening can detect many new COPD cases, but its effects on smoking cessation remain unknown. DESIGN: To evaluate symptoms in "healthy" cigarette smokers, to screen new COPD cases using international and national guidelines, and to assess the success of a smoking cessation. SUBJECTS: Healthy asymptomatic smokers with a >20 pack-years smoking history were recruited. The first visit included a standardized personal interview, Fagerstom nicotine dependence test (FNDT) and individualized smoking counselling by Motivational Interviewing. At the follow-up visit two years later, the same analyses were repeated and smoking status assessed. To avoid bias in the counselling attributable to spirometry, the test was evaluated at the two-year follow-up assessment. RESULTS: Almost all, 93.2%, of 584 participants attended the second visit. Spirometry revealed COPD by GOLD criteria in 11.0% and by national guidelines in 15.3%, mid-expiratory flow (MEF50) had significantly declined in 19.5%, chronic cough or sputum production was detected in 62% of the subjects. After two years, 23.3% had succeeded in giving up smoking. There were four predictors of successful quitting, i.e. positive attitude to the intervention, pharmacotherapy, older age, and higher BMI, whereas other factors such as cough, obstruction, gender, pack-years, or nicotine dependence showed no association with ability to achieve successful cessation. CONCLUSION: Significant numbers of "healthy" smokers experience symptoms, according to detailed questionnaires, and have COPD. Motivation is the most significant factor in determining the chance of stopping smoking.

Proteomics of human lung tissue identifies surfactant protein A as a marker of chronic obstructive pulmonary disease.

Chronic Obstructive Pulmonary Disease (COPD), a lung disease related to smoking, is one of the leading causes of chronic morbidity and mortality around the world. One goal in COPD research is the identification of biomarkers for early diagnosis of the disease. Here, we sought COPD-specific changes in the proteome from human lung tissue. This revealed increased levels of surfactant protein A (SP-A) in COPD but not in the normal or fibrotic lung. The results were confirmed by immunohistochemistry, morphometry and Western blotting. Furthermore, elevated SP-A protein levels were detected from the induced sputum supernatants of COPD patients. The levels of other surfactant proteins (SP-B, SP-C, SP-D) were not altered. Our results suggest that SP-A is linked to the pathogenesis of COPD and could be considered as a potential COPD biomarker.

Copy number gains on 5p15, 6p11-q11, 7p12, and 8q24 are rare in sputum cells of individuals at high risk of lung cancer.

UNLABELLED: Lung cancer specimens display recurrent copy number aberrations in distinguished chromosomal regions as compared with normal lung cells. Such alterations have been utilized in design of fluorescence in situ hybridization (FISH) probe sets in attempts to improve the cytological diagnosis of lung cancer. One of such probe sets, LAVysion, detects copy number changes in the centromeric region of chromosome 6 (CEP6), and regions 5p15, 8q24, and 7p12, often gained in lung cancer. METHODS: We evaluated the feasibility of the LAVysion multi-color probe set in detection of individuals at high risk of lung cancer by applying the FISH probe set on smears prepared of induced sputa obtained from 20 lung cancer patients, 43 asbestos-exposed workers, 21 heavy tobacco smokers, and 15 healthy never-smokers. The hybridized sputum smears were examined using fluorescence microscopy and the number of signals in epithelial cells was examined throughout the hybridized area. Additionally, we review here the previous studies using LAVysion probe set. RESULTS: The FISH probe set was slightly more sensitive than cytology alone in detecting lung cancer. No significant differences in copy number gain were found between high-risk individuals and healthy never-smokers. The proportions of individuals with copy number gains in sputa among the lung cancer patients, asbestos-exposed workers, tobacco smokers, and never-smokers were 50, 20, 12, and 27%, respectively, when three or more cells with a copy number gain detected by at least two different probes was used as the cut-off point. In comparison, the sensitivity of cytology in detecting lung cancer was 44%. In the lung cancer patients the number of abnormal cells by FISH correlated well with the cytologic atypia class (Spearman rank correlation coefficient 0.77, p<0.01). Using multivariant variance analysis, gains in CEP6, 5p15, 8q24 and 7p12 were not associated with smoking or asbestos exposure. CONCLUSIONS: FISH did not significantly exceed the sensitivity of sputum cytology in finding lung cancers. Significant differences were not found between sputa of asbestos-exposed individuals, heavy-smokers and never-smokers. More sensitive methods are needed for the follow-up of populations at high risk of contracting lung cancer.