Lifetime Nonsmokers Research Articles

Wound-Management of Complex Wounds

INTRODUCTION: Patients undergoing hyperbaric oxygen therapy (HBOT) have had inconsistent changes in pulmonary mechanics as reported in the literature. Additionally, there are no studies thus far comparing former smokers versus lifetime nonsmokers undergoing HBOT to determine whether it contributes to decrements in lung function. The objective of this study is to examine physiological changes in lung function of smokers versus nonsmokers with chronic wounds undergoing HBOT. METHOD: Standard pulmonary spirometric parameters were collected on patients before and after their HBOT courses, which ranged from 20–60 treatments per patient. Former smokers were considered if they had a minimum of 10 pack-year smoking history. Patients were treated for the following wound conditions: Diabetic foot ulcer, refractory osteomyelitis and compromised graft/flap. Standard wound care practices were provided by a wound/HBOT specialist throughout the study period. RESULTS: Thirty-four patients, 24 males and 10 females, with an average age of 60, were enrolled. Sixteen were former smokers and 18 were lifetime nonsmokers. Results were analyzed with the Mann-Whitney test for statistical analysis. P-values were not significant in both groups. CONCLUSION: There is no statistical significant change in any of the lung mechanics of former smokers and lifetime nonsmokers patients undergoing long-term HBOT for treatment of chronic wounds.

Clinical Characteristics of Subjects With Symptoms of α 1 -Antitrypsin Deficiency Older Than 60 Years

The clinical characteristics of elderly subjects with alpha(1)-antitrypsin deficiency (AATD)-associated COPD have not been described. The clinical, demographic, health-related quality of life (HRQoL) characteristics and 1-year exacerbation rates of 275 subjects with AATD and COPD receiving augmentation therapy aged > 59 years (mean [+/- SD] age, 66.3 +/- 5.7 years) were compared to those of 354 subjects aged 50 to 59 years (mean age, 54.3 +/- 2.8 years) and 293 subjects < 50 years (mean age, 43.9 +/- 3.8 years). Older subjects received diagnoses later in life (mean age at diagnosis, 55.0 +/- 8.5 years) and had a longer diagnostic delay (mean age at diagnosis, 12.9 +/- 14.3 years) than subjects in the other two age groups. Although the proportion of lifetime nonsmokers was higher in the older group, the majority (64%) had significant tobacco exposure but with a longer interval of tobacco abstinence. The mean FEV(1) values (n = 641) were similar between the three age groups, suggesting a slower disease progression in the oldest group. Subjects in the older group were less symptomatic, had less concomitant asthma, and had significantly better scores in most domains of two HRQoL instruments. During follow-up, older subjects had fewer acute exacerbations. Subjects with AATD-associated COPD who reach an older age exhibit a more indolent clinical course than younger affected individuals, possibly related in part to differences in tobacco exposure. This finding supports current guidelines that recommend screening of all patients with COPD for AATD, regardless of their age and prior smoking history.

Menstrual and Reproductive Factors in Association With Lung Cancer in Female Lifetime Nonsmokers

Menstrual and Reproductive Factors in Association With Lung Cancer in Female Lifetime Nonsmokers

Menstrual and Reproductive Factors in Association With Lung Cancer in Female Lifetime Nonsmokers

Menstrual and Reproductive Factors in Association With Lung Cancer in Female Lifetime Nonsmokers

Menstrual and Reproductive Factors in Association With Lung Cancer in Female Lifetime Nonsmokers

Menstrual and Reproductive Factors in Association With Lung Cancer in Female Lifetime Nonsmokers

Menstrual and Reproductive Factors in Association With Lung Cancer in Female Lifetime Nonsmokers

Cigarette smoking is irrefutably the strongest risk factor for lung cancer; however, approximately 25% of cases worldwide occur among nonsmokers. The age-adjusted annual incidence rate of lung cancer in Shanghai, a region where relatively few women smoke cigarettes, is one of the highest in the world. To help further elucidate the etiology of lung cancer among nonsmokers, the authors examined hormonal factors among women who were lifetime nonsmokers. They analyzed data from the prospective Shanghai Women's Health Study, which recruited Chinese women aged 40-70 years between 1996 and 2000 from selected urban communities. The current analysis included 71,314 women (n = 220 cases) who were lifetime nonsmokers and had no history of cancer at baseline. Later age at menopause (> or =51 vs. <46 years; hazard ratio (HR) = 0.63, 95% confidence interval (CI): 0.40, 1.00), longer reproductive period (> or =36 vs. <31 years; HR = 0.60, 95% CI: 0.39, 0.93), higher parity (> or =4 vs. 0 children; HR = 0.42, 95% CI: 0.19, 0.90), and intrauterine device use (HR = 0.59, 95% CI: 0.41, 0.86) were associated with decreased risks of lung cancer. This large prospective study suggests a potential role for hormonal factors in the etiology of lung cancer among nonsmoking women.

The association between depressive symptoms and smoking in pregnant adolescents

There have been no studies that have specifically examined the relationship between smoking and depressive symptoms in Australian pregnant adolescents. Eighty one pregnant adolescents completed an adapted version of Lawson's (1994) Smoking Questionnaire and the Edinburgh Postnatal Depression Scale. Smoking status (smokers vs. non-smokers) and depressive symptoms remained stable during pregnancy. However, comparisons of depressive symptoms across smoking categories revealed that pregnant adolescent smokers were more likely to be depressed than pregnant adolescent lifetime non-smokers, particularly in the later stages of pregnancy. There was a weak association between the number of cigarettes smoked and depressive symptoms, but only in the third trimester. Recommendations include further examination of the association between depression or depressive symptoms and smoking, and investigation of how change in smoking status during pregnancy may effect depression.

Pulmonary Nontuberculous Mycobacterial Disease

Pulmonary nontuberculous mycobacterial (PNTM) disease is increasing, but predisposing features have been elusive. To prospectively determine the morphotype, immunophenotype, and cystic fibrosis transmembrane conductance regulator genotype in a large cohort with PNTM. We prospectively enrolled 63 patients with PNTM infection, each of whom had computerized tomography, echocardiogram, pulmonary function, and flow cytometry of peripheral blood. In vitro cytokine production in response to mitogen, LPS, and cytokines was performed. Anthropometric measurements were compared with National Health and Nutrition Examination Survey (NHANES) age- and ethnicity-matched female control subjects extracted from the NHANES 2001-2002 dataset. Patients were 59.9 (+/-9.8 yr [SD]) old, and 5.4 (+/-7.9 yr) from diagnosis to enrollment. Patients were 95% female, 91% white, and 68% lifetime nonsmokers. A total of 46 were infected with Mycobacterium avium complex, M. xenopi, or M. kansasii; 17 were infected with rapidly growing mycobacteria. Female patients were significantly taller (164.7 vs. 161.0 cm; P < 0.001) and thinner (body mass index, 21.1 vs. 28.2; P < 0.001) than matched NHANES control subjects, and thinner (body mass index, 21.1 vs. 26.8; P = 0.002) than patients with disseminated nontuberculous mycobacterial infection. A total of 51% of patients had scoliosis, 11% pectus excavatum, and 9% mitral valve prolapse, all significantly more than reference populations. Stimulated cytokine production was similar to that of healthy control subjects, including the IFN-gamma/IL-12 pathway. CD4(+), CD8(+), B, and natural killer cell numbers were normal. A total of 36% of patients had mutations in the cystic fibrosis transmembrane conductance regulator gene. Patients with PNTM infection are taller and leaner than control subjects, with high rates of scoliosis, pectus excavatum, mitral valve prolapse, and cystic fibrosis transmembrane conductance regulator mutations, but without recognized immune defects.

Smoking differently modifies suicide risk of affective disorders, substance use disorders, and social factors

BackgroundAlthough an association between smoking and suicide has repeatedly been shown, information about a modifying influence of smoking on other risk factors for suicide is lacking. MethodsAxis I and Axis II disorders, sociodemographic factors, and tobacco use were assessed by a semi-structured interview including the Structured Clinical Interview for DSM-IV Axis I (SCID-I) and Personality Disorders (SCID-II) in 163 suicides (mean age 49.6+/−19.3 years; 64.4% men;) by psychological autopsy method and by personal interview in 396 living population-based control persons (mean age 51.6+/−17.0 years; 55.8% men). ResultsSmoking status (current smokers, lifetime non-smokers, and former smokers) differently modifies the effects of psychiatric disorders and sociodemographic variables on suicide risk. Former and current smoking modified suicide risk associated with affective disorders, but only current smoking increased suicide risk for substance use disorders. Ex-smokers with affective disorders, particularly with major depression, had less increased suicide risk than current smokers and non-smokers with affective disorders. Estimated suicide risks for personality disorders and ‘no professional training’ were strongly increased by smoking. LimitationsDue to the small size of some of the subgroups, confidence intervals are wide. Therefore, precise risk estimation is not possible. ConclusionsClinicians should interpret smoking as an indicator of increased risk of suicide for individuals with substance use disorders, personality disorders, and adverse social factors. Further studies are needed to investigate the effects of smoking cessation on suicide risk of patients with psychiatric disorders such as major depression and substance use disorders.

Second-Line Treatment of Advanced Non-small Cell Lung Cancer

After failure of first-line chemotherapy for advanced non-small cell lung cancer, many patients remain candidates to receive further antitumor treatment. To guide clinical management of these patients and to suggest priorities for clinical research, an International Panel of Experts met in Naples (Italy) in April 2007. Results and evidence-based conclusions are presented in this article. Single-agent chemotherapy with docetaxel or pemetrexed is the recommended option for unselected patients with performance status 0 to 2 who are candidates for second-line chemotherapy for advanced non-small cell lung cancer. Docetaxel has demonstrated superiority compared with best supportive care. Pemetrexed has been shown to be noninferior to docetaxel, with a more favorable toxicity profile. Erlotinib is effective in pretreated patients, and can be given second-line in patients not suitable or intolerant to chemotherapy, and in all patients as third-line treatment after failure of second-line chemotherapy. Gefitinib failed to show superiority to placebo as second- or third-line treatment, but it has been shown to be noninferior to docetaxel. In selected patients such as lifetime nonsmokers or those of East-Asian ethnicity, erlotinib, or gefitinib (where licensed) may be considered as second-line treatment even if they are fit for chemotherapy. Best supportive care in addition to active treatment remains important for all patients, but may be the exclusive option for patients unsuitable for more aggressive therapy. Further research is mandatory, to find better treatments, and to identify clinical and molecular predictive markers of efficacy, both for chemotherapy and for novel biologic agents.

Exposure to traffic emissions throughout life and risk of breast cancer: the Western New York Exposures and Breast Cancer (WEB) study

We previously reported that total suspended particulates exposure (a measure of air pollution) at the time of birth was related to increased postmenopausal breast cancer risk. In this study, we examined breast cancer risk in relation to exposure to air pollution from traffic emissions throughout life. We conducted a case-control study of breast cancer. Participants were women, aged 35-79, residents of Erie and Niagara Counties. Cases had incident, primary, histologically confirmed breast cancer. Controls were randomly selected from the population, frequency-matched on age and race. Using lifetime residential histories, exposure to traffic emissions was modeled for each woman using her residence as a proxy. Estimates were calculated for residence at menarche, her first birth, and 20 and 10 years before interview. Unconditional logistic regression was used to calculate odds ratios (OR) and 95% confidence intervals (CI). Higher exposure to traffic emissions at the time of menarche was associated with increased risk of premenopausal breast cancer (OR 2.05, 95% CI 0.92-4.54, p for trend 0.03); and at the time of a woman's first birth for postmenopausal breast cancer (OR 2.57, 95% CI 1.16-5.69, p for trend 0.19). Statistically significant associations were limited to lifetime non-smokers; there was a significant interaction between exposure at time of menarche and smoking for premenopausal women. Our findings add to accumulating evidence that early life exposures impact breast cancer risk and provide indication of potential importance of traffic emissions in risk of breast cancer.

Identification of current smokers among renal transplant recipients

In renal transplant recipients, smoking is associated with a high burden of cardiovascular disease and a higher risk of graft loss. Surprisingly, the results of measurement of cotinine serum level, the gold standard for the detection of active smoking, have not been confronted with self-reported smoking history in this group. The aim of our study was to identify and characterize the smoking group of renal transplant recipients. Cotinine serum level was measured and all patients were asked to fill out an anonymous questionnaire on smoking history. Out of 233 renal transplant recipients, 106 (45%) reported to be lifetime and current non-smokers: cotinine serum level was below detection limit in all; among the 127 renal transplant recipients (55%) with a lifetime history of smoking, cotinine level was diagnostic of current smoking in 32 (25%). Only 21 of the current smokers (66%) declared to the nephrologist that they had continued smoking whereas 11 (34%) claimed to be non-smokers. Current smokers were younger (P=0.01) than former smokers. The identification of current smokers among renal transplant recipients should start with questioning about lifetime history of smoking and if positive, measurement of cotinine serum level. Indeed up to 34% of current smokers do not acknowledge they are active smokers and would otherwise not offer to participate in programmes to stop smoking.

Changes in markers of epithelial permeability and inflammation in chronic smokers switching to a nonburning tobacco device (Eclipse)

Eclipse, produced by R. J. Reynolds Tobacco Company, is a potential reduced exposure product (PREP) that heats rather than burns tobacco. We hypothesized that switching to Eclipse would result in relative normalization of pulmonary epithelial permeability, airway inflammation, and blood leukocyte activation in current smokers. We assessed 10 healthy smokers (aged 21-50 years, 19+/-8 pack-years) at baseline and after 2 and 4 weeks of switching to Eclipse, for symptoms, pulmonary function, airway inflammation, lung clearance of (99m)technicium-diethylenetriaminepentaacetic acid, and blood leukocyte activation and production of reactive oxygen species. Values were compared before and after Eclipse use and with those of healthy, lifetime nonsmokers (aged 18-53 years). Compared with baseline values before switching to Eclipse, lung permeability half-time increased from 33+/-3 to 43+/-6 min (p = .017) after 2 weeks and to 44+/-7 min (p = .10) after 4 weeks of Eclipse use. Carboxyhemoglobin levels increased from 5%+/-2% to 7%+/-2% (p<.01) at 4 weeks. Compared with smoking the usual brand of cigarettes, after smoking Eclipse the percentage of natural killer cells, the expression of intercellular adhesion molecule-1 on monocytes, and the expression of CD45RO on T cells showed significant improvement. However, expression of other surface markers, notably CD23 on monocytes, became more abnormal. Production of reactive oxygen species by smokers' neutrophils and monocytes increased further with Eclipse use. We found no significant effects on pulmonary function, cells in induced sputum, or exhaled nitric oxide. Switching to Eclipse reduces alveolar epithelial injury in some smokers but may increase carboxyhemoglobin levels and oxidative stress.

The μ-opioid receptor gene and smoking initiation and nicotine dependence

The gene encoding the mu-opioid receptor (OPRM1) is reported to be associated with a range of substance dependence. Experiments in knockout mice indicate that the mu-opioid receptor may mediate reinforcing effects of nicotine. In humans, opioid antagonist naltrexone may reduce the reinforcing effects of tobacco smoking. Additionally, the OPRM1 gene is located in a region showing linkage to nicotine dependence. The OPRM1 is thus a plausible candidate gene for smoking behavior. To investigate whether OPRM1 contributes to the susceptibility of smoking initiation and nicotine dependence, we genotyped 11 SNPs in the gene for 688 Caucasian subjects of lifetime smokers and nonsmokers. Three SNPs showed nominal significance for smoking initiation and one reached significance for nicotine dependence. The global test for three-marker (rs9479757-rs2075572-rs10485057) haplotypes was significant for smoking initiation (p = 0.0022). The same three-marker haplotype test was marginal (p = 0.0514) for nicotine dependence. These results suggest that OPRM1 may be involved in smoking initiation and nicotine dependence.

Treatment of tobacco use in preconception care.

Treatment of tobacco use in preconception care.

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.

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.

Clinical Charicteristics of Primary Lung Cancer Patients in a Tertiary Hospital

Background : To evaluate the clinical characteristics of lung cancer patients in Korea, where there is a higher number of smokers than in Western countries. Methods : A retrospective study was performed on 1655 lung cancer patients, who were diagnosed at a university hospital between September 1996 and August 2005. Age, gender, cell types and clinical stage were analysed. Of 941 patients, who responded to a questionnaire at the time of diagnosis, the smoking habits, occupational history, family history of lung cancer in the first-degree relatives, coexisting diseases (diabetes mellitus and cardiovascular disease), body weight loss, ECOG performance status and presenting symptoms, were examined prospectively. In addition, coexisting diseases including chronic obstructive pulmonary disease, idiopathic pulmonary fibrosis and active pulmonary tuberculosis were evaluated. Results : Of the 1655 patients, the male to females ratio was 3.6. Squamous cell carcinoma was the most common cancer whereas adenocarcinoma was more common in lifetime nonsmokers or women. 19.9% of the patients were non smokers and 80.1% ever smokers. Since 2000, there was an increase in the incidence of adenocarcinoma with a corresponding decrease in the incidence of squamous cell carcinoma. 6.2% of patients were asymptomatic. A coincident diagnosis of chronic obstructive pulmonary disease, cardiovascular disease, diabetes mellitus, active pulmonary tuberculosis, and idiopathic pulmonary fibrosis was made in: 44.1%, 22.2%, 10.7%, 3.9%, and 1.6% of patients, respectively. A positive family history of lung cancer in the first-degree relatives was identified in 4.4% of patients. An occupational history relevant to lung cancer was identified in 12.2% of patients. Conclusion : There is a high proportion of cigarette smokers in Korean lung cancer patients. The most common cell type was squamous cell carcinoma. However, a more detailed, prospective study of the clinical characteristics will be needed to better characterize lung cancer in Korea.

Passive smoking exposure among adults and the dynamics of respiratory symptoms in a prospective multicenter cohort study

The aim of this study was to measure the effects of past exposure to environmental tobacco smoke on the day-to-day dynamics of four respiratory-symptom classes in a diary study including adult never-smokers. As part of SAPALDIA (Swiss study on air pollution and lung diseases in adults), a prospective multicenter cohort study, 1421 life-time adult nonsmokers were followed for 2 years with the use of daily questionnaires filled out during one to six periods of 4 weeks spread over 2 years (1992-1993). The hazard ratios (HR) of getting or losing respiratory symptoms from one day to another were determined in association with past exposure to environmental tobacco smoke. In a sample of adult never-smokers, an association between self-reported past exposure to environmental tobacco smoke and deteriorated average symptom dynamics was found for all of the outcomes considered, showing HR values from 1.09 to 1.21 for developing symptoms and HR values from 0.91 to 0.83 for getting rid of them. Exposure to environmental tobacco smoke, including the workplace, was negatively associated with the length of intervals without symptoms of bronchitis (HR 1.33) and asthma (HR 1.27), while exposure to environmental tobacco smoke confined to places outside work was positively associated with the length of episodes of any respiratory symptom and lower-respiratory-tract symptoms (HR 0.78-0.77). The results suggest that exposure to environmental tobacco smoke has adverse effects on the dynamics of respiratory symptoms, and the size (magnitude) and type of effects appear to depend on the place of exposure.

Environmental Tobacco Smoke and Risk of Adult Leukemia

The role of environmental tobacco smoke (ETS) in the causation of lung and breast cancer has been repeatedly evaluated over recent years. In contrast, its impact on the risk of adult leukemia has received little attention. We used the lifetime residential and occupational ETS exposure histories from a population-based sample of 1068 incident and histologically confirmed adult leukemia cases and 5039 population controls age 20 to 74 years to evaluate the relationship between ETS exposure and adult leukemia risk among nonsmokers in Canada. The duration of exposure and smoker-years index were used as indices of ETS exposure. We restricted our analysis to the 266 case and 1326 control subjects who reported being lifetime nonsmokers and provided residential ETS exposure history for at least 75% of their lifetime. No association was found for most leukemia subtypes, and in particular for acute myeloid leukemia. In contrast, the risk for chronic lymphocytic leukemia was clearly associated with ETS exposure, with an adjusted odds ratio of 2.3 (95% confidence interval = 1.2-4.5) for more than 83 smoker-years of residential exposure and 2.4 (1.3-4.3) for more than 72 smoker-years of occupational exposure. There was a dose-response relationship for chronic lymphocytic leukemia with both indices of exposure. Risk was not higher with recent exposure, using time-window-exposure analyses. Regular long-term ETS exposure may be a risk factor for chronic lymphocytic leukemia.