Healthy Ex-smokers Research Articles

Impact of Short-Term Diesel Exhaust Exposure on Prothrombotic Markers in COPD: A Randomized, Double-blinded, Crossover Study.

Rationale: Growing evidence suggests that air pollution exposure is a major risk factor in chronic obstructive pulmonary disease (COPD) that is associated with an increased prothrombotic state and adverse cardiovascular outcomes. However, much of this work is based on observational data or human exposure studies involving younger participants. The biological causality and mechanism of air pollution-induced prothrombotic response in patients with COPD remain to be explored. Objective: The main aim of this work was to investigate the impact of short-term diesel exhaust (DE) exposure on circulating prothrombotic markers-fibrinogen and plasminogen activator inhibitor-1 (PAI-1)-and urinary eicosanoids in patients with COPD. Methods: Twenty-nine research participants were recruited in this randomized, double-blinded, crossover, controlled human exposure study to DE. Participants included former smokers with and without mild or moderate COPD (ES and COPD group) and healthy never-smokers without COPD (NS group). Each participant was exposed to DE (300 µg/m3 of PM2.5) and filtered air (FA) for 2 hours on different occasions, in randomized order, separated by a 4-week washout. Blood and urine samples were collected prior to and 24 hours after each exposure. Plasma fibrinogen and serum PAI-1 concentrations were quantified using ELISAs. Urinary eicosanoid concentrations were quantified using ultra- performance liquid chromatography coupled to tandem mass spectrometry. Linear mixed-effects models were used for statistical comparisons. Results: Participants with COPD showed an increase in plasma fibrinogen (effect estimate: 1.27 [1.06 to 1.53], p=0.01) after DE relative to FA, but no significant DE-associated change in serum PAI-1 (0.95 [0.87 to 1.04], p=0.26). In never-smokers and ex-smokers without COPD, fibrinogen (NS group: 1.10 [0.99 to 1.23], p=0.08; ES group: 0.86 [0.68 to 1.09], p=0.08] and PAI-1 (NS group: 1.12 [ 0.96 to 1.32], p=0.15; ES group: 0.90 [0.79 to 1.03], p=0.13) were not changed after DE exposure. COPD participants showed a DE-attributable increase in urinary thromboxane B2 (TXB2) metabolites concentrations as follows: 11-dehydro TXB2 (1.45 [1.02 to 2.08], p=0.04); 2,3-dinor-TXB2 (1.45 [1.05 to 2.00], p=0.03). Conclusions: Participants with COPD had increased plasma fibrinogen and urinary TXB2 metabolites after short-term DE exposure, suggesting they may be more susceptible to pollution-attributable prothrombotic response compared to healthy controls or ex-smokers without COPD. Clinical trial registration available at www.clinicaltrials.gov, ID: NCT02236039.

Pulmonary EV miRNA profiles identify disease and distinct inflammatory endotypes in COPD.

Chronic obstructive pulmonary disease (COPD) is a heterogeneous condition without effective disease modifying therapies. Identification of novel inflammatory endotype markers such as extracellular vesicles (EVs), which are important intercellular messengers carrying microRNA (miRNA), may enable earlier diagnosis and disease stratification for a targeted treatment approach. Our aim was to identify differentially expressed EV miRNA in the lungs of COPD patients compared with healthy ex-smokers and determine whether they can help define inflammatory COPD endotypes. EV miRNA were isolated and sequenced from ex-smoking COPD patients and healthy ex-smoker bronchoalveolar lavage fluid. Results were validated with RT-qPCR and compared to differential inflammatory cell counts. Expression analysis identified five upregulated miRNA in COPD (miR-223-3p, miR-2110, miR-182-5p, miR-200b-5p and miR-625-3p) and three downregulated miRNA (miR-138-5p, miR-338-3p and miR-204-5p), all with a log2 fold change of >1/-1, FDR < 0.05. These miRNAs correlated with disease defining characteristics such as FEF 25-75% (a small airways disease measure) and DLCO% (a surrogate measure of emphysema). Receiver operator curve analysis demonstrated miR-2110, miR-223-3p, and miR-182-5p showed excellent combinatory predictive ability (AUC 0.91, p < 0.0001) in differentiating between health and mild COPD. Furthermore, miR-223-3p and miR-338-3p correlated with airway eosinophilia and were able to distinguish "pure eosinophilic" COPD from other airway inflammatory subtypes (AUC 0.94 and 0.85, respectively). This is the first study to identify differentially expressed miRNA in COPD bronchoalveolar lavage fluid EVs. These findings suggest specific lung derived EV miRNA are a strong predictor of disease presence even in mild COPD. Furthermore, specific miRNA correlated with inflammatory cell numbers in COPD, and may have a role in defining inflammatory endotypes for future treatment stratification.

Mitochondrial Transfer Regulates Bioenergetics in Healthy and Chronic Obstructive Pulmonary Disease Airway Smooth Muscle.

Mitochondrial dysfunction has been reported in chronic obstructive pulmonary disease (COPD). Transfer of mitochondria from mesenchymal stem cells to airway smooth muscle cells (ASMCs) can attenuate oxidative stress-induced mitochondrial damage. It is not known whether mitochondrial transfer can occur between structural cells in the lungs or what role this may have in modulating bioenergetics and cellular function in healthy and COPD airways. Here, we show that ASMCs from both healthy ex-smokers and subjects with COPD can exchange mitochondria, a process that happens, at least partly, via extracellular vesicles. Exposure to cigarette smoke induces mitochondrial dysfunction and leads to an increase in the donation of mitochondria by ASMCs, suggesting that the latter may be a stress response mechanism. Healthy ex-smoker ASMCs that receive mitochondria show increases in mitochondrial biogenesis and respiration and a reduction in cell proliferation, irrespective of whether the mitochondria are transferred from healthy ex-smoker or COPD ASMCs. Our data indicate that mitochondrial transfer between structural cells is a homeostatic mechanism for the regulation of bioenergetics and cellular function within the airways and may represent an endogenous mechanism for reversing the functional consequences of mitochondrial dysfunction in diseases such as COPD.

Study to Assess the Immunogenicity and Safety of GSK's Investigational Vaccine (GSK3277511A) When Given to Healthy Smokers and Ex-smokers After Administration of Shingrix Vaccine

Study to Assess the Immunogenicity and Safety of GSK's Investigational Vaccine (GSK3277511A) When Given to Healthy Smokers and Ex-smokers After Administration of Shingrix Vaccine

Permanence of Modifications in Oral Microcirculation in Ex-Smokers.

BackgroundThe aim of this study was to assess the long-term effects of smoking and to investigate the permanence of this damage to the oral microcirculation.Material/MethodsWe recruited 75 patients and divided them into 3 groups: group 1 was composed of 25 healthy non-smokers, group 2 was composed of 25 healthy current smokers, and group 3 was composed of 25 healthy ex-smokers. Video-capillaroscopic examination was performed on all patients.The video-capillaroscopic investigation was performed on patients in sitting position, always with the same light source, at the same room temperature (23°C), in the morning, with the same operator (GAS), and was repeated many times for every area under investigation. An enlargement of 200× allowed us to explore point-by-point all the morpho-structural characteristics of the capillaroscopic field. For non-parametric data, we evaluated the visibility of the loops and their position in relation to the surface of the mucosa. The evaluated parametric data were length of capillary loop, diameter of the loop, capillary tortuosity, and capillary density.ResultsOur study clearly shows there was no remission of vascular damage, even 13 years after smoking cessation.ConclusionsOur research shows that that the effects of smoking are still visible in ex-smokers, even at 13 years after cessation and also that ex-smokers are still subject to the risk of oral pathologies in the interval of time that we considered.

Exhaled and non-exhaled non-invasive markers for assessment of respiratory inflammation in patients with stable COPD and healthy smokers

We aimed at comparing exhaled and non-exhaled non-invasive markers of respiratory inflammation in patients with chronic obstructive pulmonary disease (COPD) and healthy subjects and define their relationships with smoking habit. Forty-eight patients with stable COPD who were ex-smokers, 17 patients with stable COPD who were current smokers, 12 healthy current smokers and 12 healthy ex-smokers were included in a cross-sectional, observational study. Inflammatory outcomes, including prostaglandin (PG) E2 and 15-F2t-isoprostane (15-F2t-IsoP) concentrations in exhaled breath condensate (EBC) and sputum supernatants, fraction of exhaled nitric oxide (FENO) and sputum cell counts, and functional (spirometry) outcomes were measured. Sputum PGE2 was elevated in both groups of smokers compared with ex-smoker counterpart (COPD: P < 0.02; healthy subjects: P < 0.03), whereas EBC PGE2 was elevated in current (P = 0.0065) and ex-smokers with COPD (P = 0.0029) versus healthy ex-smokers. EBC 15-F2t-IsoP, a marker of oxidative stress, was increased in current and ex-smokers with COPD (P < 0.0001 for both) compared with healthy ex-smokers, whereas urinary 15-F2t-IsoP was elevated in both smoker groups (COPD: P < 0.01; healthy subjects: P < 0.02) versus healthy ex-smokers. FENO was elevated in ex-smokers with COPD versus smoker groups (P = 0.0001 for both). These data suggest that the biological meaning of these inflammatory markers depends on type of marker and biological matrix in which is measured. An approach combining different types of outcomes can be used for assessing respiratory inflammation in patients with COPD. Large studies are required to establish the clinical utility of this strategy.

Ventilation Heterogeneity in Ex-smokers without Airflow Limitation

Hyperpolarized (3)He magnetic resonance imaging (MRI) ventilation abnormalities are visible in ex-smokers without airflow limitation, but the clinical relevance of this is not well-understood. Our objective was to phenotype healthy ex-smokers with normal and abnormally elevated ventilation defect percent (VDP). Sixty ex-smokers without airflow limitation provided written informed consent to (3)He MRI, computed tomography (CT), and pulmonary function tests in a single visit. (3)He MRI VDP and apparent diffusion coefficients (ADCs) were measured for whole-lung and each lung lobe as were CT measurements of emphysema (relative area [RA] with attenuation≤-950 HU, RA950) and airway morphology (wall area percent [WA%], lumen area [LA] and LA normalized to body surface area [LA/BSA]). In 42 ex-smokers, there was abnormally elevated VDP and no significant differences for pulmonary function, RA950, or airway measurements compared to 18 ex-smokers with normal VDP. Ex-smokers with abnormally elevated VDP reported significantly greater (3)He ADC in the apical lung (right upper lobe [RUL], P=.02; right middle lobe [RML], P=.04; and left upper lobe [LUL], P=.009). Whole lung (r=0.40, P=.001) and lobar VDP (RUL, r=0.32, P=.01; RML, r=0.46, P=.002; right lower lobe [RLL], r=0.38, P=.003; LUL, r=0.35, P=.006; and left lower lobe, r=0.37, P=.004) correlated with regional (3)He ADC. Although whole-lung VDP and CT airway morphology measurements were not correlated, regional VDP was correlated with RUL LA (r=-0.37, P=.004), LA/BSA (r=-0.42, P=.0008), RLL WA% (r=0.28, P=.03), LA (r=-0.28, P=.03), and LA/BSA (r=-0.37, P=.004). Abnormally elevated VDP in ex-smokers without airflow limitation was coincident with very mild emphysema detected using MRI and regional airway remodeling detected using CT representing a subclinical obstructive lung disease phenotype.

Quantification of plasma microRNAs in a group of healthy smokers, ex-smokers and non-smokers and correlation to biomarkers of tobacco exposure

The stability of circulating miRNAs, their non-invasive sampling techniques and deregulation in diseases make them potential candidate biomarkers of biological effect. Here, we profiled the level of 84 plasma miRNAs in 30 smokers, 20 non-smokers and 20 ex-smokers. A robust statistical strategy was applied with replicate samples to account for reproducibility of the results. We identified differential expression of miR-124 and let-7a between the smoking and control groups. We further explored the dose–response relationship of miR-124 and let-7a with two biomarkers of tobacco exposure and found that this relationship was affected by adjustments based on age, pack-year and gender.

Análisis de la proteína C reactiva en la población fumadora sana y con EPOC e influencia de las comorbilidades y del tiempo de abandono del tabaco

ObjectiveThe smoking habit increases the C reactive protein in the serum. Values are studied in different populations: healthy (exsmokers, smokers and nonsmokers), chronic bronchitis and chronic obstructive pulmonary disease (COPD) in different stages; in addition the influence according to the time of abandonment of the tobacco and the associate comorbidities. Material and methodsDescriptive-transversal analysis. 401 persons we studied: 106 healthy not smokers (HNS), 104 healthy smokers (HS), 95 healthy nonsmoker (HN), 30 with chronic bronchitis, 30 with incipient COPD (COPDi) and 36 with advanced COPD (COPDa), with ages included between 45 and 80 years old, being detrmined CRP and the associate comorbidities. ResultsCRP's values were: 1.98 (2.1) mg/l in HN; 3.35 (4.39) mg/l in HS; 2 (2.2) mg/l in HE; 3 (3.8) mg/l in chronic bronchitis; 3.40 (2.23) in COPDi and 5.94 (1.76) in COPDa. The CRP in chronic bronchitis and COPD falls to 2.7 (6.8) after five years of abandonment of the tobacco, remaining constant after. There exist significant differences between the HS and HN populations, and between chronic bronchitis and COPD after five years of abstinence with the population HN (p=0.003). There are not significant differences between HE and HN (p>0.05); between population HS and the population with chronic bronchitis and COPDi (p>0.05), and between COPD's different stages and the indexes of comorbiditie. ConclusionsThe value of the CRP in the HS population is similar to that on the chronic bronchitis and COPDi population, but higher to that of the HN. After the abandon of the smoking habit, in HS the CRP returns to the value of the HN population. In the populations with pathologies is significantly elevated as compared to HN and not return to the HN level after five years of abstinence. Their level is independent of comorbidity index. The detection level of inflammatory disease is at a value of PCR: 3mg/l.

Sputum and nasal lavage lung-specific biomarkers before and after smoking cessation

BackgroundLittle is known about the effect of smoking cessation on airway inflammation. Secretory Leukocyte Protease Inhibitor (SLPI), Clara Cell protein 16 (CC16), elafin and human defensin beta-2 (HBD-2) protect human airways against inflammation and oxidative stress. In this longitudinal study we aimed to investigate changes in sputum and nasal lavage SLPI, CC16, elafin and HBD-2 levels in healthy smokers after 6 and 12 months of smoking cessation.MethodsInduced sputum and nasal lavage was obtained from healthy current smokers (n = 76) before smoking cessation, after 6 months of smoking cessation (n = 29), after 1 year of smoking cessation (n = 22) and from 10 healthy never smokers. SLPI, CC16, elafin and HBD-2 levels were measured in sputum and nasal lavage supernatants by commercially available ELISA kits.ResultsSputum SLPI and CC-16 levels were increased in healthy smokers before smoking cessation versus never-smokers (p = 0.005 and p = 0.08 respectively). SLPI and CC16 levels did not differ before and 6 months after smoking cessation (p = 0.118 and p = 0.543 respectively), neither before and 1 year after smoking cessation (p = 0.363 and p = 0.470 respectively). Nasal lavage SLPI was decreased 12 months after smoking cessation (p = 0.033). Nasal lavage elafin levels were increased in healthy smokers before smoking cessation versus never-smokers (p = 0.007), but there were no changes 6 months and 1 year after smoking cessation.ConclusionsOnly nasal lavage SLPI decrease after 1 year after smoking cessation. We may speculate that there is an ongoing inflammatory process stimulating the production of counter-regulating proteins in the airways of healthy ex-smokers.

Leukotriene B4 Contributes to Exhaled Breath Condensate and Sputum Neutrophil Chemotaxis in COPD

Neutrophils have been implicated in the pathogenesis of COPD. Several chemoattractants for neutrophils have been measured in samples of exhaled breath condensate (EBC) and induced sputum (IS) from patients with COPD. The aims of this study were to compare EBC and IS supernatant neutrophil chemotactic activity (NCA) from ex-smoking subjects with COPD and healthy ex-smokers, and to assess the contribution of leukotriene B(4) (LTB(4)) to this activity. Thirty-four subjects with COPD were compared to 24 control subjects. EBC and IS chemotactic activity for neutrophils was assessed by using Boyden microchambers. The chemotactic index was used to evaluate cell migration. LTB(4) was measured by a specific enzyme immunoassay. The contribution of LTB(4) to EBC and sputum neutrophil chemotaxis was assessed by an LTB(4) receptor antagonist (U-75302; Cayman Chemical Company; Ann Arbor, MI). EBC and IS samples from both COPD patients and healthy subjects displayed significant NCA, but this activity was raised in COPD patients compared to healthy subjects. The chemotactic activity contained in sputum, however, failed to correlate with that in EBC. In COPD patients, there was a significant correlation between EBC NCA and sputum neutrophil counts. LTB(4) levels were raised in EBC samples, but not in sputum samples, from COPD subjects compared to those from healthy subjects. LTB(4) receptor antagonist concentrations (2.5 x 10(-4) mol/L) reduced by 44.6% and by 44.4%, respectively, the chemotactic activity contained in the EBC and sputum samples. EBC and IS from COPD patients have a raised NCA to which LTB(4) contributes.

Granulocyte Chemotactic Activity in Exhaled Breath Condensate of Healthy Subjects and Patients With COPD

Several chemoattractants have been measured in exhaled breath condensate (EBC) from patients with COPD. The aim of this study was to compare the eosinophil and neutrophil chemotactic activity contained in EBC from healthy subjects and patients with COPD. EBC collected using a commercially available condenser (EcoScreen; Erich Jaeger Viasys; Hoechberg, Germany) was compared in 45 COPD patients and 65 healthy subjects. EBC chemotactic activity for eosinophils and neutrophils was assessed using microchambers (Boyden; Neuro Probe; Cabin John, MD). Chemotactic index (CI) was used to evaluate cell migration. EBC from patients with COPD (CI, 2.21 +/- 0.16 [mean +/- SEM]) and healthy subjects (CI, 1.67 +/- 0.11) displayed significant neutrophil chemotactic activity (p < 0.0001 for both), which was however higher in patients with COPD (p < 0.001). Healthy smokers had a significantly raised CI for neutrophils by comparison with healthy nonsmokers (p < 0.01) and ex-smokers (p < 0.05). Likewise, current COPD smokers tended to have greater neutrophil CI than COPD who stopped smoking (p = 0.08). COPD ex-smokers had raised chemotactic activity by comparison with healthy ex-smokers (p < 0.05). Anti-interleukin-8 (10(-6) g/mL) antibodies reduced neutrophil chemotactic activity by 35.2% (p < 0.05). EBC also contained significant eosinophil chemotactic activity in healthy subjects (CI, 1.68 +/- 0.09; p < 0.0001) and patients with COPD (CI, 1.23 +/- 0.07; p < 0.01), with a significantly lower CI in patients with COPD as compared to healthy subjects (p < 0.001). Smoking did not influence eosinophil chemotactic activity in healthy subjects or patients with COPD. Current smoking favors neutrophil chemotactic activity. As compared to healthy subjects, EBC from patients with COPD displays a skewed chemotactic activity toward neutrophils vs eosinophils.

Airway Blood Flow Reactivity in Healthy Smokers and in Ex-Smokers With or Without COPD

Cigarette smoking has been associated with impaired endothelium-dependent relaxation responses in the brachial and coronary arteries (endothelial dysfunction). The aim of the present study was to determine whether the airway circulation is also affected and whether pharmacologic treatment has an effect on endothelial function in patients with COPD. Airway blood flow (Qaw) responses to therapy with inhaled albuterol, which causes endothelium-dependent vasodilation, were measured with a noninvasive soluble-gas-uptake technique in age-matched healthy current smokers (n = 10), healthy ex-smokers (n = 10), ex-smokers with COPD (n = 10), and healthy lifetime nonsmokers. In the ex-smokers with COPD, the albuterol responsiveness measurement was repeated after 4 weeks of treatment with fluticasone/salmeterol and after a drug washout period of 4 or 8 weeks. The mean (+/- SE) baseline Qaw values ranged between 40.7 +/- 3.9 and 50.9 +/- 2.8 microL/min/mL anatomic dead space in the four groups (differences were not significant). The mean FEV(1) was 53.4 +/- 2.3% predicted in the ex-smokers with COPD. Albuterol inhalation increased mean Qaw significantly in lifetime nonsmokers (50.1 +/- 8.3% predicted; p < 0.05) and healthy ex-smokers (37.2 +/- 3.4% predicted; p < 0.05), but not in healthy current smokers (13.9 +/- 3.2% predicted; difference was not significant) and ex-smokers with COPD (9.7 +/- 4.5% predicted; difference was not significant). While fluticasone/salmeterol did not change Qaw significantly, it restored albuterol responsiveness (67.6 +/- 11.1% predicted; p < 0.05) in the ex-smokers with COPD; this effect was no longer seen after the drug washout period. Cigarette smoking is associated with a blunted vasodilator response to inhaled albuterol in the airway as an expression of endothelial dysfunction, with a partial recovery of albuterol responsiveness after smoking cessation in healthy ex-smokers but not in ex-smokers with COPD. In the latter group, combined glucocorticoid/long-acting beta(2)-adrenergic agonist treatment restores albuterol responsiveness. The role of endothelial dysfunction in the physiopathology of COPD remains to be examined.

Treatment With AM3 Restores Defective T-Cell Function in COPD Patients

Lymphocyte alterations have been associated with an increased prevalence of acute respiratory infections in COPD patients. AM3 is an oral immunomodulator that normalizes the defective functions of peripheral blood natural killer and phagocytic cells in COPD patients and improves their health-related quality of life. To characterize putative systemic abnormalities of the T-cell compartment in COPD patients, and to investigate whether AM3 can restore such abnormalities. The study was a randomized, prospective, double-blind, placebo-controlled trial in a cohort of COPD patients. The results were also compared to those of nonsmoker and ex-smoker healthy control subjects. Outpatient departments of four hospitals. Seventy COPD patients were randomized to receive either AM3 or a placebo orally for 90 consecutive days. Populations of 36 healthy nonsmokers and 36 healthy ex-smokers were used as control subjects. Peripheral blood mononuclear cell (PBMC) proliferation and production of interleukin (IL)-2, IL-4, IL-12p40, tumor necrosis factor-alpha, and interferon (IFN)-gamma proteins in response to the T-cell polyclonal mitogens were assessed at baseline and at the end of treatment. The proliferative response was significantly decreased in COPD patients. Decreased production of IFN-gamma was the only defect in the profiles of the cytokine measures, and was selectively observed in COPD patients, but not in nonsmoker and ex-smoker healthy control subjects. Treatment with AM3 significantly restored the PBMC proliferative response to polyclonal mitogens and significantly promoted stimulated IFN-gamma production in these patients. The normalization of these proliferative responses was not related to significant variations in the numbers of peripheral blood monocytes, CD3+, CD4+, CD8+ cells or of any major naïve/memory/activated T-cell subset. The increased IFN-gamma production in the AM3 study arm was associated with an increase in the mean of number of IFN-gamma molecules produced per CD8+ T cells. PBMCs of COPD patients showed clear functional T-lymphocyte abnormalities that are rescued by AM3 treatment.

Airway blood flow reactivity in smokers

Cigarette smoking has been associated with impaired endothelium-dependent relaxation responses in the brachial and coronary arteries (endothelial dysfunction). The aim of the present study was to determine if the airway circulation is also affected and if airway treatment has an effect on endothelial function. Airway blood flow ( Q aw) responses to inhaled albuterol as an index of endothelial function were measured in age-matched healthy current smokers, healthy ex-smokers, ex-smokers with COPD and healthy lifetime non-smokers; in the ex-smokers with COPD, the albuterol responsiveness was repeated after a 4-week treatment with an inhaled glucocorticoid/ β 2-adrenergic agonist combination drug. Mean baseline Q aw was similar in the four groups. Albuterol inhalation increased mean Q aw in lifetime non-smokers (50.1±8.3%; p < 0.0 5 ) and in healthy ex-smokers (37.2±3.4%; p < 0.0 5 ) but not in healthy current smokers (13.9±3.2%; p=NS) and ex-smokers with COPD (9.7±4.5%; p=NS). While drug treatment per se did not change Q aw significantly, it restored albuterol responsiveness (+67.6±11.1%; p < 0.0 5 ) in the ex-smokers with COPD. Thus, cigarette smoking is associated with endothelial dysfunction in the airway, with a partial recovery of endothelial function after smoking cessation in healthy ex-smokers but not in ex-smokers with COPD. In the latter, combined glucocorticoid/ β 2-adrenergic agonist treatment restores albuterol responsiveness.

Screening, Early Detection, and Early Intervention Strategies for Lung Cancer

Screening for lung cancer has been utilized for several decades without demonstrating overall survival benefit. However, recent advances in treatment of lung cancer, improvements in our biologic understanding of lung cancer development, and an increasing population of healthy ex-smokers provide cause for optimism. Several chemoprevention trials suggest that it may be possible to intervene in the oncologic process prior to the development of invasive malignancy, resulting in a delay or reversal of these changes.

Cigarette smoking and ethane exhalation in humans.

The time course of exhaled ethane gas was determined in the alveolar expirate of healthy, fasting smokers and nonsmokers after smoking a cigarette. Baseline ethane was measured by gas chromatography and corrected for background ethane after a 2-min washout using purified air. Ethane was measured immediately after smoking and hourly thereafter. Ethane was highest immediately after smoking, reflecting ethane in cigarette smoke. An exponential decline of ethane in smokers returned ethane to baseline within 3 h. Ethane in nonsmokers also peaked immediately after smoking but returned to baseline by 1 h. Ethane from smokers, measured 3 h after the last cigarette, was compared with ethane from healthy ex-smokers and nonsmokers. Mean (+/- SEM) baseline ethane in smokers was 2.90 +/- 0.52 pmol/min/kg, 1.55 +/- 0.36 pmol/min/kg in ex-smokers and 1.11 +/- 0.26 pmol/min/kg in nonsmokers (p < 0.05). Ethane in two smokers measured before and after a week of oral beta carotene supplementation (60 mg/d) fell by 80 and 35%. We conclude that cigarette smokers have increased baseline ethane in exhaled breath compared with non-smokers. Trials with antioxidant agents are warranted to assess their ability to reduce expired ethane levels.

Issues in the Prevention of Weight Gain after Smoking Cessation

Abstract Although commonly accepted, there is essentially no direct support for the assumption that preventing weight gain after smoking cessation will improve the likelihood of remaining abstinent from smoking. First, developing interventions to prevent this weight gain has proven to be extremely difficult. To date, no adjunct behavioral treatment has been shown to be successful in attenuating cessation-induced weight gain in healthy ex-smokers. Reasons for this failure may stem from inadequate intensity of interventions, poor compliance due to the complexity of interventions aimed at both eliminating smoking and controlling weight, or to biological pressures for weight to increase after removal of the weight suppressing effects of smoking (i.e. altered energy regulation). Pharmacological interventions, despite being successful during brief periods of active use, have not been studied beyond several months' duration of treatment. Second and more importantly, prospective studies have not reported that weight gain after cessation directly predicts relapse, and results of a recent intervention indicate that adjunct weight control treatment may be associated with greater smoking relapse. Although contrary to common belief these findings are very consistent with a large body of basic animal research showing that food or weight restriction increases drug intake. In light of these observations, a more prudent and fruitful approach for basic and clinical research may be to re-examine the fundamental relationships among smoking, eating, body weight, and perhaps weight-related attitudes, rather than developing intensive strategies for combating weight gain after smoking cessation. If further study continues to find no positive relationship between this weight gain and risk of subsequent smoking relapse, it may be necessary to consider developing treatments designed to help ex-smokers accept, rather than fight, weight gain after cessation.

Plasma protein-bound sialic acid in patients with colorectal polyps of known histology

Protein-bound sialic acid (PBSA) was measured in serial plasma specimens from 62 healthy subjects, 48 patients with colorectal polyps, and 30 patients with colorectal adenocarcinomas. The mean plasma PBSA concentration in healthy smokers was significantly greater than that in healthy nonsmokers and healthy ex-smokers (P less than 0.0001). Villoglandular polyps were associated with higher plasma PBSA values than were the most benign hyperplastic polyps (P less than 0.025). Patients with the most neoplastic villoglandular and villous polyps had significantly greater (P less than 0.010-0.050) plasma PBSA values than healthy subjects. Polypectomy decreased the mean PBSA value significantly to the mean value for healthy subjects only for patients with villoglandular (P less than 0.010) or villous (P less than 0.050) polyps. Colorectal cancer patients had mean plasma PBSA concentrations significantly greater than those for the healthy subjects (P much less than 0.001) and the polyp patients (P much less than 0.001). Surgery significantly reduced (P less than 0.025) the mean PBSA value for the cancer patients to the mean PBSA value observed for the healthy subjects.

Sperm quality of healthy smokers, ex-smokers, and never-smokers

The possible effects of cigarette smoking on sperm quality were investigated in a blind study of 333 healthy male volunteers 19 to 40 years of age. All subjects with clinically proven abnormalities, operations, or inflammatory diseases of the genital organs, exposure to radiation exceeding routine x-ray examination, or medication were excluded, and the data from 150 smokers, 37 ex-smokers, and 52 never-smokers were evaluated. There was a small but insignificant decrease in sperm density from never-smokers to ex-smokers and to smokers. Eight smokers (6%) had sperm counts less than 1 X 10(6)/ml, whereas none of the ex-smokers or never-smokers fell into this category. This difference, however, is not statistically significant (P = 0.084). No statistically significant effect of smoking habits on sperm density, motility, and morphologic features was detected. It is concluded that smoking does not affect the motility and morphologic features of sperm in healthy adult men. The diminished sperm density in heavy smokers may be related to factors associated with smoking.