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1.  Influence of current or former smoking on asthma management and control 
In patients with asthma, smoking has been associated with accelerated decline in pulmonary function, poor disease control and reduced responsiveness to corticosteroids.
To assess the influence of current and former smoking on self-reported asthma control and health care use in a large population of asthma patients.
The present analysis was conducted following a telephone survey of adult Canadians aged 18 to 54 years who had physician-diagnosed asthma and a smoking history of less than 20 pack-years.
Of 893 patients, 268 were former smokers and 108 were current smokers. Daytime and nighttime symptoms, absenteeism from work or school, emergency care use for asthma in the past year, and use of a short-acting bronchodilator without controller medication were reported more frequently by current smokers than non-smokers and former smokers. Former smokers were not significantly different from nonsmokers with respect to most asthma outcomes.
Current smokers with asthma show evidence of poorer asthma control and greater acute care needs than lifelong nonsmokers or former smokers. These observations stress the importance of smoking cessation to help achieve asthma control.
PMCID: PMC2679551  PMID: 18716691
Asthma; Asthma control; Asthma management; Smoking
2.  Smoking in Asthma Is Associated with Elevated Levels of Corticosteroid Resistant Sputum Cytokines—An Exploratory Study 
PLoS ONE  2013;8(8):e71460.
Current cigarette smoking is associated with reduced acute responses to corticosteroids and worse clinical outcomes in stable chronic asthma. The mechanism by which current smoking promotes this altered behavior is currently unclear. Whilst cytokines can induce corticosteroid insensitivity in-vitro, how current and former smoking affects airway cytokine concentrations and their responses to oral corticosteroids in stable chronic asthma is unclear.
To examine blood and sputum cytokine concentrations in never, ex and current smokers with asthma before and after oral corticosteroids.
Exploratory study utilizing two weeks of oral dexamethasone (equivalent to 40 mg/day prednisolone) in 22 current, 21 never and 10 ex-smokers with asthma. Induced sputum supernatant and plasma was obtained before and after oral dexamethasone. 25 cytokines were measured by multiplex microbead system (Invitrogen, UK) on a Luminex platform.
Smokers with asthma had elevated sputum cytokine interleukin (IL) -6, -7, and -12 concentrations compared to never smokers with asthma. Few sputum cytokine concentrations changed in response to dexamethasone IL-17 and IFNα increased in smokers, CCL4 increased in never smokers and CCL5 and CXCL10 reduced in ex-smokers with asthma. Ex-smokers with asthma appeared to have evidence of an ongoing corticosteroid resistant elevation of cytokines despite smoking cessation. Several plasma cytokines were lower in smokers with asthma compared to never smokers with asthma.
Cigarette smoking in asthma is associated with a corticosteroid insensitive increase in multiple airway cytokines. Distinct airway cytokine profiles are present in current smokers and never smokers with asthma and could provide an explanatory mechanism for the altered clinical behavior observed in smokers with asthma.
PMCID: PMC3739804  PMID: 23951170
3.  Smoking, respiratory symptoms and likely asthma in young people: evidence from postal questionnaire surveys in the Wythenshawe Community Asthma Project (WYCAP) 
Although it is recognised that smoking is a major risk factor for subjects with chronic obstructive pulmonary disease and is associated with respiratory symptoms, there is less agreement concerning the relationship between asthma and smoking. This study aims to examine the relationship between cigarette smoking and asthma prevalence.
Data were used from two postal questionnaire surveys (1999 and 2001) in two general practice populations, using a respiratory questionnaire based on the ECRHQ and a generic quality of life questionnaire (EQ-5D). Only subjects less than 45 years old were included in the survey. An empirical definition of likely asthma was used based on respiratory questionnaire responses. Smoking was examined according to three categories, current smoker, ex smoker and never smoker.
Almost 3500 subjects were included in the analyses. Current smokers had a higher prevalence of likely asthma compared to never smokers, odds ratio (OR) 1.59 (95% confidence interval (CI) 1.24 to 2.04). and also compared to ex smokers OR 1.79 (CI 1.25 to 2.56), but there was no difference between ex smokers and never smokers (OR 1.00 (0.75–1.35)). Current smoking was also positively associated with all symptoms but not with a history of hayfever/eczema.
Although the positive association found between current smoking and obstructive airways disease is likely to be due to the effect of cigarettes on asthma, it could reflect an association with early COPD (GOLD stages 0 or 1). Smoking cessation has a beneficial effect on the prevalence of respiratory symptoms and is therefore of paramount importance among these young adults.
PMCID: PMC1489948  PMID: 16716223
4.  Smoking, allergy, and the differential white blood cell count. 
Thorax  1985;40(1):17-22.
Dutch workers have proposed that people with asthma and those smokers who develop chronic airflow obstruction share a common allergic constitution. To study whether smoking itself is associated with indicators of allergy, we have examined 237 men aged 51-61 years (120 smokers, 73 ex-smokers, and 44 non-smokers) who were recruited to a long term study of lung function in 1974, at which time men with a clinical diagnosis of asthma were excluded. Smokers, ex-smokers, and non-smokers did not differ in personal or family history of allergic disease, but the prevalence of positive responses to skinprick tests was greater in ex-smokers (59%) than in the other two groups (33% and 34%). In men with negative responses to skinprick tests total serum IgE was greater in smokers (log10 mean 1.41 IU/ml) and in ex-smokers (log10 mean 1.53 IU/ml) than in non-smokers (log10 mean 1.12 IU/ml). In men with positive skin test responses serum IgE was similar in the three groups (log10 mean ranging from 1.68 to 1.78 IU/ml). Geometric mean total white cell counts in the peripheral blood were higher in smokers (7.34 X 10(9)/l) than in non-smokers (5.82 X 10(9)/l); the value in ex-smokers (6.16 X 10(9)/l) was intermediate. Absolute blood eosinophil counts were increased in smokers disproportionately to the increase in total white cell count. Thus smoking is associated with small increases in some markers of allergy. These changes are probably acquired after the onset of smoking but sequential studies are required to amplify these cross sectional observations. Smokers whose skin test responses are positive appear more likely to give up smoking.
PMCID: PMC459971  PMID: 3969651
5.  Smoking and prevalence of allergic disorders in Japanese pregnant women: baseline data from the Kyushu Okinawa Maternal and Child Health Study 
Environmental Health  2012;11:15.
Studies on the associations between smoking and allergic diseases have mostly focused on asthma. Epidemiological studies in adults on the effects of smoking on allergic diseases other than asthma, such as eczema and rhinoconjunctivitis, have been limited, and the information that is available has been inconsistent. The aim of this study was to investigate the association between smoking status and environmental tobacco smoke (ETS) exposure and the prevalence of allergic diseases.
Study subjects were 1743 pregnant Japanese women. The definitions of wheeze and asthma were based on criteria from the European Community Respiratory Health Survey whereas those of eczema and rhinoconjunctivitis were based on criteria from the International Study of Asthma and Allergies in Childhood. Adjustment was made for age; region of residence; family history of asthma, atopic eczema, and allergic rhinitis; household income; and education.
Compared with never smoking, current smoking and ≥ 4 pack-years of smoking were independently positively associated with the prevalence of wheeze. There were no associations between smoking status and the prevalence of asthma, eczema, or rhinoconjunctivitis. When subjects who had never smoked were classified into four categories based on the source of ETS exposure (never, only at home, only at work, and both), exposure occurring both at home and at work was independently associated with an increased prevalence of two outcomes: wheeze and rhinoconjunctivitis. No relationships were observed between exposure to ETS and the prevalence of asthma or eczema.
Our results provide evidence that current smoking and ETS exposure may increase the likelihood of wheeze. The possibility of a positive association between ETS exposure and rhinoconjunctivitis was also suggested.
PMCID: PMC3317840  PMID: 22413964
Asthma; Cross-sectional studies; Eczema; Environmental tobacco smoke; Smoking; Wheeze; Rhinoconjunctivitis
6.  Greater risk of incident asthma cases in adults with Allergic Rhinitis and Effect of Allergen Immunotherapy: A Retrospective Cohort Study 
Respiratory Research  2005;6(1):153.
Asthma and rhinitis are often co-morbid conditions. As rhinitis often precedes asthma it is possible that effective treatment of allergic rhinitis may reduce asthma progression.
The aim of our study is to investigate history of allergic rhinitis as a risk factor for asthma and the potential effect of allergen immunotherapy in attenuating the incidence of asthma.
Hospital-referred non-asthmatic adults, aged 18–40 years between 1990 and 1991, were retrospectively followed up until January and April 2000. At the end of follow up, available subjects were clinically examined for asthma diagnosis and history of allergen specific immunotherapy, second-hand smoking and the presence of pets in the household. A total of 436 non-asthmatic adults (332 subjects with allergic rhinitis and 104 with no allergic rhinitis nor history of atopy) were available for final analyses.
The highest OR (odds ratio) associated with a diagnosis of asthma at the end of follow-up was for the diagnosis of allergic rhinitis at baseline (OR, 7.8; 95%CI, 3.1–20.0 in the model containing the covariates of rhinitis diagnosis, sex, second-hand smoke exposure, presence of pets at home, family history of allergic disorders, sensitization to Parietaria judaica; grass pollen; house dust mites; Olea europea: orchard; perennial rye; and cat allergens). Female sex, sensitization to Parietaria judaica and the presence of pets in the home were also significantly predictive of new onset asthma in the same model. Treatment with allergen immunotherapy was significantly and inversely related to the development of new onset asthma (OR, 0.53; 95%CI, 0.32–0.86).
In the present study we found that allergic rhinitis is an important independent risk factor for asthma. Moreover, treatment with allergen immunotherapy lowers the risk of the development of new asthma cases in adults with allergic rhinitis.
PMCID: PMC1351177  PMID: 16381607
7.  Quantitative analysis of high-resolution computed tomography scans in severe asthma subphenotypes 
Thorax  2010;65(9):775-781.
Severe asthma is a heterogeneous condition. Airway remodelling is a feature of severe asthma and can be determined by the assessment of high-resolution computed tomography (HRCT) scans. The aim of this study was to assess whether airway remodelling is restricted to specific subphenotypes of severe asthma.
A retrospective analysis was performed of HRCT scans from subjects who had attended a single-centre severe asthma clinic between 2003 and 2008. The right upper lobe apical segmental bronchus (RB1) dimensions were measured and the clinical and sputum inflammatory characteristics associated with RB1 geometry were assessed by univariate and multivariate regression analyses. Longitudinal sputum data were available and were described as area under the time curve (AUC). Comparisons were made in RB1 geometry across subjects in four subphenotypes determined by cluster analysis, smokers and non-smokers, and subjects with and without persistent airflow obstruction.
Ninety-nine subjects with severe asthma and 16 healthy controls were recruited. In the subjects with severe asthma the RB1 percentage wall area (%WA) was increased (p=0.009) and lumen area (LA)/body surface area (BSA) was decreased (p=0.008) compared with controls but was not different across the four subphenotypes. Airway geometry was not different between smokers and non-smokers and RB1 %WA was increased in those with persistent airflow obstruction. RB1 %WA in severe asthma was best associated with airflow limitation and persistent neutrophilic airway inflammation (model R2=0.27, p=0.001).
Airway remodelling of proximal airways occurs in severe asthma and is associated with impaired lung function and neutrophilic airway inflammation.
PMCID: PMC2975950  PMID: 20805170
Severe asthma; airway remodelling; computed tomography; airway inflammation; quantitative analysis; asthma phenotypes; cluster analysis; imaging/CT MRI etc
8.  Regular Smoking and Asthma Incidence in Adolescents 
Rationale: Although involuntary exposure to maternal smoking during the in utero period and to secondhand smoke are associated with occurrence of childhood asthma, few studies have investigated the role of active cigarette smoking on asthma onset during adolescence.
Objectives: To determine whether regular smoking is associated with the new onset of asthma during adolescence.
Methods: We conducted a prospective cohort study among 2,609 children with no lifetime history of asthma or wheezing who were recruited from fourth- and seventh-grade classrooms and followed annually in schools in 12 southern California communities. Regular smoking was defined as smoking at least seven cigarettes per day on average over the week before and 300 cigarettes in the year before each annual interview. Incident asthma was defined using new cases of physician-diagnosed asthma.
Measurements and Main Results: Regular smoking was associated with increased risk of new-onset asthma. Children who reported smoking 300 or more cigarettes per year had a relative risk (RR) of 3.9 (95% confidence interval [95% CI], 1.7–8.5) for new-onset asthma compared with nonsmokers. The increased risk from regular smoking was greater in nonallergic than in allergic children. Regular smokers who were exposed to maternal smoking during gestation had the largest risk from active smoking (RR, 8.8; 95% CI, 3.2–24.0).
Conclusions: Regular smoking increased risk for asthma among adolescents, especially for nonallergic adolescents and those exposed to maternal smoking during the in utero period.
PMCID: PMC2648110  PMID: 16973983
asthma; epidemiology; smoking
9.  Rhinitis Symptoms and Asthma among Parents of Preschool Children in Relation to the Home Environment in Chongqing, China 
PLoS ONE  2014;9(4):e94731.
Risk factors for rhinitis and asthma in the home environment were studied by a questionnaire survey. Parents of 4530 1–8 year old children (one parent per child) from randomly selected kindergartens in Chongqing, China participated. 70.4% were females; 47.1% had rhinitis symptoms in the last three months (current rhinitis, CR); 1.6% reported a history of allergic asthma (AA); 2.7% reported a history of allergic rhinitis (AR); 16.4% were current smokers; 50.8% males and 2.4% females were current smokers. Stuffy odor, unpleasant odor, tobacco smoke odor and dry air were associated with CR (adjustment for gender, current smoking and other perceptions of odor or humidity). Associations between home environment and CR, AR, and AA were studied by multiple logistic regression analyses, adjusting for gender, current smoking and other significant home factors. Living near a main road or highway was a risk factor for both CR (OR(95%CI): 1.31(1.13,1.52)) and AR (OR(95%CI): 2.44(1.48,4.03)). Other risk factors for CR included living in rural areas (OR(95%CI): 1.43(1.10,1.85)), new furniture (OR(95%CI): 1.28(1.11,1.49)), water damage (OR(95%CI): 1.68(1.29,2.18)), cockroaches (OR(95%CI): 1.46(1.23,1.73)), and keeping pets (OR(95%CI): 1.24(1.04,1.49)). Other risk factors for AR included redecoration (OR(95%CI): 2.14(1.34,3.41)), mold spots (OR(95%CI): 2.23(1.06,4.68)), window pane condensation (OR(95%CI): 2.04(1.28,3.26)). Water damage was the only home factor associated with AA (2.56(1.34,4.86)). Frequently put bedding to sunshine was protective for CR (OR(95%CI): 0.79(0.68,0.92); cleaning every day was protective for AR (OR(95%CI): 0.40(0.22,0.71)). In conclusion, parents' CR and AR were related to a number of factors of the home environment.
PMCID: PMC3986232  PMID: 24733290
10.  The Wage Effects of Personal Smoking History 
Why do we observe a wage differential between smokers and non-smokers? Pooling reports of current and prior smoking activity across 15 years from the Panel Study of Income Dynamics (PSID) allows the reconstruction of individual smoking histories. Dividing the sample into smoking history groups, the four largest of which are: persistent smokers, never smokers, former smokers, and future quitters reveals that there is no observed wage gap between former smokers and those who have never smoked. There is, however, a wage gap between those smokers who will continue smoking and three other groups of individuals: (1) those smokers who will quit smoking in the future, (2) those smokers who have quit smoking already, and (3) those who never smoked. The wage gap between smokers and non-smokers, observed in the 1986 cross-section, is largely driven by those who persist as smokers, 1986–2001. These results support the hypothesis that the cross-sectional wage differential is not driven by smoking per se, but may be driven by a non-causal explanation. One plausible interpretation is that a common factor such as myopia, leads to reduced investment in both health capital or firm-specific or other human capital.
PMCID: PMC3717362  PMID: 23882133
smoking; wages; health capital
11.  Smoking Status as a Predictor of Hip Fracture Risk in Postmenopausal Women of Northwest Texas 
Preventing Chronic Disease  2007;5(1):A09.
The purpose of this study was to determine the effect of cigarette smoking on the risk of hip fracture for postmenopausal women living in rural and urban areas of Northwest Texas.
Using an unmatched case-control design, we compared postmenopausal women who had recently experienced osteoporotic hip fracture with women who had not. Both study groups completed a questionnaire on demographic, clinical, and behavioral risk factors for osteoporotic hip fracture. We categorized smoking status as never smoked, former smoker, and current smoker. Covariates included age, weight, age at menopause, physical activity, estrogen replacement, calcium supplementation, and rurality. We used univariate and multivariate logistic regressions to test the associations between hip fracture and the independent variables of interest.
We found an increased risk of hip fracture for former smokers (adjusted odds ratio [OR], 2.27; 95% confidence interval [CI], 1.22–4.21) and current smokers (adjusted OR, 3.72; 95% CI, 1.59–8.70). Residence in a rural county (population <100,000) also was associated with increased risk (adjusted OR, 2.71; 95% CI, 1.48–4.95).
Former and current smoking increased the risk of hip fracture in this population of postmenopausal women.
PMCID: PMC2248794  PMID: 18081998
12.  Childhood exposure to environmental tobacco smoke and chronic respiratory symptoms in non-smoking adults: The Singapore Chinese Health Study 
Thorax  2005;60(12):1052-1058.
Background: Childhood exposure to environmental tobacco smoke has been extensively associated with childhood respiratory illness; fewer studies have addressed the effects on adults.
Methods: Childhood environmental tobacco smoke exposure in relation to chronic cough, phlegm, and asthma diagnosis was studied in never smokers from a cohort of Singaporeans of Chinese ethnicity aged 45–74 years at enrolment from 1993 to 1998. From 1999 to 2004 subjects were interviewed regarding environmental tobacco smoke exposure before and after the age of 18 and the presence and duration of current symptoms of chronic cough and phlegm production and asthma diagnosis.
Results: Among 35 000 never smokers, fewer had smoking mothers (19%) than fathers (48%). Although few subjects currently lived (20%) or worked (4%) with smokers, 65% reported living with a daily smoker before the age of 18 years. Living with a smoker before the age of 18 increased the odds of chronic dry cough (149 cases, odds ratio 2.1, 95% CI 1.4 to 3.3) and, to a lesser extent, phlegm, after adjustment for age, sex, dialect group, and current and past exposure to smokers at home and at work after the age of 18. Associations strengthened with higher numbers of smokers in childhood. There was no association with asthma or chronic bronchitis. There was evidence to suggest a stronger association among subjects with a lower adult intake of fibre which has previously been found to be protective for respiratory symptoms.
Conclusions: In this large study of non-smokers, living with a smoker in childhood was associated with chronic dry cough and phlegm in adulthood, independent of later exposures to environmental tobacco smoke.
PMCID: PMC1414787  PMID: 16131525
13.  Childhood smoking is an independent risk factor for obstructive airways disease in women 
Thorax  2004;59(8):682-686.
Objective: To assess whether starting to smoke in childhood increases the risk of obstructive airways disease (OAD) in adult life.
Methods: A retrospective cohort analysis was undertaken of 12 504 current and ex-smokers in the EPIC-Norfolk cohort. The main exposure was starting to smoke during childhood (age <16 years). Three definitions of OAD were used: doctor diagnosed asthma, doctor diagnosed bronchitis/emphysema, and "any OAD" (doctor diagnosed asthma or bronchitis/emphysema, or taking medication used in the treatment of OAD).
Results: Childhood smokers had significantly more pack years of exposure and poorer lung function than subjects who started to smoke in adulthood (⩾16 years). Compared with starting in adulthood, starting to smoke in childhood was associated with a greater risk of bronchitis/emphysema in female smokers (OR 1.79, 95% CI 1.25 to 2.56) and ex-smokers of both sexes (OR 1.29, 95% CI 1.07 to 1.55 in men and OR 1.40, 95% CI 1.05 to 1.85 in women), and of "any OAD" in female smokers (OR 1.72, 95% CI 1.24 to 2.38) and male and female ex-smokers (OR 1.20, 95% CI 1.03 to 1.40 in men and 1.34, 95% CI 1.07 to 1.57 in women). After adjustment for pack years, childhood smoking was associated with poorer lung function (FEV1 92.3% predicted in adult smokers and 89.5% in childhood smokers, p = 0.03) and a greater risk of bronchitis/emphysema (adjusted OR 1.55, 95% CI 1.08 to 2.24) and for "any OAD" (OR 1.54, 95% CI 1.10 to 2.13) in female smokers but not in male and female ex-smokers.
Conclusion: Starting to smoke in childhood is associated with an increased risk of airways disease because of the extra pack years smoked. In women, childhood smoking is itself an independent risk factor for the development of airways disease.
PMCID: PMC1747099  PMID: 15282389
14.  Prevalence of chronic cough and phlegm among male cigar and pipe smokers: results of the Scottish Heart Health Study. 
Thorax  1993;48(11):1163-1167.
BACKGROUND--Previous studies investigating the effect of cigar or pipe smoking on the occurrence of chronic cough and chronic phlegm have reported prevalences among cigar and pipe smokers lying between those of non-smokers and current cigarette smokers. This study uses data on previous cigarette consumption, current cigar or pipe consumption, and biochemical markers of smoking to provide a detailed analysis of chronic cough and chronic phlegm among cigar and pipe smokers. METHODS--A total of 10,359 men and women aged 40-59 years were sampled for the Scottish Heart Health Study between 1984 and 1986. Prevalence of chronic cough and chronic phlegm among male cigar and pipe smokers (non-cigarette smokers) was compared with those who had never smoked, between ex-smokers of cigarettes and those who had never smoked cigarettes, between cigar-only and pipe-only smokers, and by cigar or pipe consumption levels. RESULTS--In all, 463 ex-smokers of cigarettes and 154 who had never smoked cigarettes were cigar or pipe smokers; 1080 had never smoked any form of tobacco. Ex-cigarette smokers smoked and inhaled more than those who had never smoked cigarettes. Among the ex-cigarette smokers, cigar or pipe smokers had 1.63-1.71 times the prevalence of both chronic cough and chronic phlegm than those who had never smoked (1.31-1.36 among cigar only smokers; 2.23-2.84 among pipe only smokers). A strong positive dose-response effect was found between the prevalence of symptoms and cigar or pipe consumption. CONCLUSIONS--Cigar and pipe smokers have a higher prevalence of chronic cough and phlegm than those who have never smoked, and the difference is more marked in pipe-only smokers than in cigar-only smokers. Both categories show a positive dose-response effect. Among cigar and pipe smokers, ex-cigarette smokers have a higher prevalence of symptoms than those who have never smoked cigarettes, which may be because they inhale more or may be attributable to previous cigarette smoking.
PMCID: PMC464910  PMID: 8296263
15.  Damage to DNA in cervical epithelium related to smoking tobacco. 
BMJ : British Medical Journal  1993;306(6890):1444-1448.
OBJECTIVE--To determine whether tobacco smoking causes increased DNA modification (adducts) in human cervical epithelium. DESIGN--Comparison of DNA adducts measured by the technique of postlabelling with phosphorus-32 in normal ectocervical epithelium of smokers and non-smokers. A questionnaire on smoking habit and a urinary cotinine assay were used to identify smokers and non-smokers. SETTING--Cytology unit in large teaching hospital. SUBJECTS--39 women (11 current smokers, seven former smokers, and 21 who had never smoked) undergoing gynaecological treatment (colposcopy or hysterectomy). Nineteen members of staff who did not smoke as controls. INTERVENTIONS--Biopsy of normal ectocervical epithelium. Urine sample. MAIN OUTCOME MEASURES--Measurement of DNA adducts in cervical epithelial tissue of smokers and non-smokers. Smoking habit derived from results of questionnaire and urinary cotinine:creatinine ratio. Proportion of adducts in women with abnormal and normal results of cervical smear test. RESULTS--DNA samples from smokers (identified from questionnaire) had significantly higher median proportions of DNA adducts that non-smokers (4.62 (95% confidence interval 4.04 to 7.74) v 3.47 (2.84 to 4.78) adducts/10(8) nucleotides; p = 0.048). Exclusion of women whose urinary cotinine:creatinine ratio did not confirm their self reported smoking habit (smoker or non-smoker) increased this difference (4.7 (3.85 to 8.08) v 3.52 (2.32 to 4.95) adducts/10(8) nucleotides; p = 0.03). Women who had abnormal results of cervical smear tests had significantly higher proportions of adducts than those with normal results (4.7 (3.90 to 8.13) v 3.47 (3.06 to 5.36) adducts/10(8) nucleotides; p = 0.03). CONCLUSIONS--Tobacco smoking by women leads to increased modification of DNA in cervical epithelium, suggesting biochemical evidence consistent with smoking as a cause of cervical cancer.
PMCID: PMC1677905  PMID: 8257490
16.  Cigarette Smoking and Serum Bilirubin Subtypes in Healthy Korean Men: The Korea Medical Institute Study 
Cigarette smoking is a modifiable risk factor for cardiovascular disease. Bilirubin is a potent antioxidant and its concentration decreases in smokers. However, studies about the association between cigarette smoking and bilirubin are scarce and most are limited to total bilirubin. Additionally, bilirubin is highly related to hemoglobin. Therefore, this study evaluates the association between bilirubin subtypes and cigarette smoking in healthy Korean men independently of hemoglobin.
This study included 48 040 Korean men aged 30 to 87 years who visited the Korea Medical Institute for routine health examinations from January to December, 2007. The association of smoking with total, direct, and indirect bilirubin was assessed by logistic regression analysis taking into consideration differences in subjects and smoking characteristics.
Current smokers had lower bilirubin concentrations than never-smokers and ex-smokers. Smoking amount and duration were inversely significantly associated with total, direct, and indirect bilirubin. In a multivariable adjusted model, compared to never-smokers, the odds ratios (ORs) and 95% confidence intervals (CIs) of current smokers with the highest number of pack-years were 1.7 (1.6 to 1.9) for total, 1.5 (1.4 to 1.6) for direct, and 1.7 (1.6 to 1.9) for indirect bilirubin. After further adjustment for hemoglobin, this association became stronger (OR [95% CI], 2.1 [1.9 to 2.2] for total; 1.9 [1.8 to 2.0] for direct; 2.0 [1.9 to 2.2] for indirect bilirubin).
In this study, bilirubin subtypes are inversely associated with smoking status, smoking amount, and smoking duration in healthy Korean men independently of hemoglobin. Further studies are needed to investigate this association in healthy Korean women.
PMCID: PMC3324713  PMID: 22509451
Bilirubin; Bilirubin subtypes; Hemoglobins; Pack-years; Smoking
17.  Prospective study of asthma in relation to smoking habits among 14,729 adults. 
Thorax  1988;43(7):534-539.
The prevalence and incidence of asthma in relation to cigarette smoking habits was studied in a population of 14,729 Finnish adult men and women who participated in a postal health survey in 1975. Of those invited to participate in a new survey in 1981, 89.7% replied. Asthma was diagnosed on the basis of self reporting of asthma diagnosed by a physician and by record linkage to a national register of hospital admissions to all general and tuberculosis hospitals during 1972 and 1983. The prevalence of diagnosed asthma in 1975 was significantly higher among male smokers than among male non-smokers (relative risk (RR) = 1.73); no significant difference was observed for women (RR = 1.33). People with asthma were slightly but not significantly more likely to stop smoking during the six year follow up period (RR = 1.23). The incidence of asthma among those who had neither reported asthma in 1975 nor been admitted to hospital for asthma before the 1975 questionnaire study was not significantly higher among smokers than among non-smokers during follow up. Although possible mechanisms exist to explain how smoking could have a role in the aetiology of asthma, this study suggests that smoking is not a strong risk factor for asthma.
PMCID: PMC461360  PMID: 3269222
18.  The relationship between age and duration of asthma and the presence of persistent obstruction in asthma. 
Postgraduate Medical Journal  1988;64(752):422-425.
Persistent obstruction was assessed in 630 asthmatic subjects by measurement after bronchodilator of the maximum potential peak flow rate and forced vital capacity. Persistent obstruction was directly related to duration of asthma. The fit was slightly better after logarithmic transformation, suggesting that the early stages of asthma may be as important as the later ones in the development of persistent obstruction. On multivariate analysis age was an additional factor in males, but made no significant difference to females. Atopy did not prove relevant. Measurements of peak flow suggested a more rapid deterioration in males of social classes III, IV and V than classes I and II. Although current smokers had lower peak flow rate and vital capacity than non-smokers, there was no evidence of a steeper decline in smokers than non-smokers suggesting that the effect of cigarette smoking was at most additive to that of duration of asthma.
PMCID: PMC2428859  PMID: 3211818
19.  Quality of Life in Adolescents With Mild Asthma 
Pediatric pulmonology  2003;36(6):536-543.
The majority of individuals with asthma have mild disease, often in conjunction with allergic rhinitis and exercise-induced bronchoconstriction (EIB). Although health-related quality-of-life (HRQoL) is reduced in moderate to severe asthma and allergic rhinitis, little is known about the effect of mild asthma, mild allergic rhinitis, and EIB on HRQoL outcomes. The objective of this study was to determine the effect of mild asthma, allergic rhinitis, and EIB on HRQoL. A cross-sectional study was conducted of 160 adolescent athletes participating in a screening program to detect EIB. Generic HRQoL was assessed with the teen version of the pediatric quality-of-life inventory (PedsQL™). Prior diagnoses of asthma, allergic rhinitis, and EIB, and current symptoms of dyspnea during exercise and asthma, were recorded. Lung function and the presence of EIB were determined by spirometry before and after an exercise challenge test. Adolescent athletes with a prior physician diagnosis of asthma had a lower HRQoL scale summary score (P < 0.01) and lower physical functioning, emotional functioning, and school functioning domain scores (P values, 0.01–0.02) in comparison to adolescent athletes with no prior diagnosis of these disorders. Athletes with a prior diagnosis of asthma reported dyspnea during exercise more frequently than did those without asthma (P < 0.001). Adolescent athletes with dyspnea during exercise had a lower scale summary score, and lower physical functioning, general well-being, and emotional functioning domain scores (P values, 0.02–0.03). These data show that mild asthma and dyspnea without asthma significantly affect HRQoL. Symptoms of dyspnea during exercise are common in asthma and are associated with lower HRQoL. The clinical significance of these differences in HRQoL is unclear.
PMCID: PMC2002508  PMID: 14618647
asthma; allergic rhinitis; exercise-induced bronchoconstriction; health-related quality of life; spirometry
20.  Multi-symptom asthma is closely related to nasal blockage, rhinorrhea and symptoms of chronic rhinosinusitis-evidence from the West Sweden Asthma Study 
Respiratory Research  2010;11(1):163.
We have previously shown that approximately 25% of those with asthma in West Sweden have multiple asthma symptoms, which may describe a group of patients with more severe disease. Furthermore, asthma is associated with several co-morbid diseases, including rhinitis and chronic rhinosinusitis. The aim of this study was to determine whether multi-symptom asthma is related to signs of severe asthma, and to investigate the association between multi-symptom asthma and different symptoms of allergic and chronic rhinosinusitis.
This study analyzed data on asthma symptoms, rhinitis, and chronic rhinosinusitis from the 2008 West Sweden Asthma Study, which is an epidemiologically based study using the OLIN and GA2LEN respiratory and allergy focused questionnaires.
Multi-symptom asthma was present in 2.1% of the general population. Subjects with multi-symptom asthma had more than double the risk of having night-time awakenings caused by asthma compared with those with fewer asthma symptoms (P < 0.001). The prevalence of allergic rhinitis was similar in the fewer- and multi-symptom asthma groups, but nasal blockage and rhinorrhea were significantly increased in those with multi- versus fewer-symptom asthma (odds ratio 2.21; 95% confidence interval 1.64-2.97, versus 1.49; 1.10-2.02, respectively). Having any, or one to four symptoms of chronic rhinosinusitis significantly increased the risk of having multi- versus fewer-symptom asthma (P < 0.01).
An epidemiologically identified group of individuals with multiple asthma symptoms harbour to greater extent those with signs of severe asthma. The degree of rhinitis, described by the presence of symptoms of nasal blockage or rhinorrhea, as well as the presence of any or several signs of chronic rhinosinusitis, significantly increases the risk of having multi-symptom asthma.
PMCID: PMC3004848  PMID: 21110834
21.  The effect of smoking on the development of allergic disease and specific immunological responses in a factory workforce exposed to humidifier contaminants. 
The effects of smoking on the development of work related asthma and on the production of specific IgE and IgG antibodies to antigen from a contaminated humidifier are described for a sample of 258 workers from a printing factory. Current smoking was associated with low production of IgG antibody but with higher production of IgE antibody. No dose response for either antibody was found when numbers of cigarettes or pack-years smoked were considered. Work related asthma was detected in 12 workers by peak flow recordings. Six were current smokers and one was an ex-smoker. One subject with work related asthma had a high (and one a marginal) concentration of specific IgE to humidifier antigen.
PMCID: PMC1035308  PMID: 1993157
22.  Cigarette tar yields in relation to mortality from lung cancer in the cancer prevention study II prospective cohort, 1982-8 
BMJ : British Medical Journal  2004;328(7431):72.
Objective To assess the risk of lung cancer in smokers of medium tar filter cigarettes compared with smokers of low tar and very low tar filter cigarettes.
Design Analysis of the association between the tar rating of the brand of cigarette smoked in 1982 and mortality from lung cancer over the next six years. Multivariate proportional hazards analyses used to assess hazard ratios, with adjustment for age at enrolment, race, educational level, marital status, blue collar employment, occupational exposure to asbestos, intake of vegetables, citrus fruits, and vitamins, and, in analyses of current and former smokers, for age when they started to smoke and number of cigarettes smoked per day.
Setting Cancer prevention study II (CPS-II).
Participants 364 239 men and 576 535 women, aged ≥ 30 years, who had either never smoked, were former smokers, or were currently smoking a specific brand of cigarette when they were enrolled in the cancer prevention study.
Main outcome measure Death from primary cancer of the lung among participants who had never smoked, former smokers, smokers of very low tar (≤ 7 mg tar/cigarette) filter, low tar (8-14 mg) filter, high tar (≥ 22 mg) non-filter brands and medium tar conventional filter brands (15-21 mg).
Results Irrespective of the tar level of their current brand, all current smokers had a far greater risk of lung cancer than people who had stopped smoking or had never smoked. Compared with smokers of medium tar (15-21 mg) filter cigarettes, risk was higher among men and women who smoked high tar (≥ 22 mg) non-filter brands (hazard ratio 1.44, 95% confidence interval 1.20 to 1.73, and 1.64, 1.26 to 2.15, respectively). There was no difference in risk among men who smoked brands rated as very low tar (1.17, 0.95 to 1.45) or low tar (1.02, 0.90 to 1.16) compared with those who smoked medium tar brands. The same was seen for women (0.98, 0.80 to 1.21, and 0.95, 0.82 to 1.11, respectively).
Conclusion The increase in lung cancer risk is similar in people who smoke medium tar cigarettes (15-21 mg), low tar cigarettes (8-14 mg), or very low tar cigarettes (≤ 7 mg). Men and women who smoke non-filtered cigarettes with tar ratings ≥ 22 mg have an even higher risk of lung cancer.
PMCID: PMC314045  PMID: 14715602
23.  Smoking decreases the response of human lung macrophages to double-stranded RNA by reducing TLR3 expression 
Respiratory Research  2013;14(1):33.
Cigarette smoking is associated with increased frequency and duration of viral respiratory infections, but the underlying mechanisms are incompletely defined. We investigated whether smoking reduces expression by human lung macrophages (Mø) of receptors for viral nucleic acids and, if so, the effect on CXCL10 production.
We collected alveolar macrophages (AMø) by bronchoalveolar lavage of radiographically-normal lungs of subjects undergoing bronchoscopies for solitary nodules (n = 16) and of volunteers who were current or former smokers (n = 7) or never-smokers (n = 13). We measured expression of mRNA transcripts for viral nucleic acid receptors by real-time PCR in those AMø and in the human Mø cell line THP-1 following phorbol myristate acetate/vitamin D3 differentiation and exposure to cigarette smoke extract, and determined TLR3 protein expression using flow cytometry and immunohistochemistry. We also used flow cytometry to examine TLR3 expression in total lung Mø from subjects undergoing clinically-indicated lung resections (n = 25). Of these, seven had normal FEV1 and FEV1/FVC ratio (three former smokers, four current smokers); the remaining 18 subjects (14 former smokers; four current smokers) had COPD of GOLD stages I-IV. We measured AMø production of CXCL10 in response to stimulation with the dsRNA analogue poly(I:C) using Luminex assay.
Relative to AMø of never-smokers, AMø of smokers demonstrated reduced protein expression of TLR3 and decreased mRNA for TLR3 but not TLR7, TLR8, TLR9, RIG-I, MDA-5 or PKR. Identical changes in TLR3 gene expression were induced in differentiated THP-1 cells exposed to cigarette smoke-extract in vitro for 4 hours. Among total lung Mø, the percentage of TLR3-positive cells correlated inversely with active smoking but not with COPD diagnosis, FEV1% predicted, sex, age or pack-years. Compared to AMø of never-smokers, poly(I:C)-stimulated production of CXCL10 was significantly reduced in AMø of smokers.
Active smoking, independent of COPD stage or smoking duration, reduces both the percent of human lung Mø expressing TLR3, and dsRNA-induced CXCL10 production, without altering other endosomal or cytoplasmic receptors for microbial nucleic acids. This effect provides one possible mechanism for increased frequency and duration of viral lower respiratory tract infections in smokers.
Trial registration NCT00281190, NCT00281203 and NCT00281229.
PMCID: PMC3599854  PMID: 23497334
Lung; Cigarette smoking; Effects; Toll-like receptors; Macrophages; Alveolar
24.  Occupational asthma due to chrome and nickel electroplating 
Thorax  1997;52(1):28-32.
BACKGROUND: Exposure to chromium during electroplating is a recognised though poorly characterised cause of occupational asthma. The first series of such patients referred to a specialist occupational lung disease clinic is reported. METHODS: The diagnosis of occupational asthma was made from a history of asthma with rest day improvement and confirmed by specific bronchial provocation testing with potassium dichromate and nickel chloride. RESULTS: Seven workers had been exposed to chrome and nickel fumes from electroplating for eight months to six years before asthma developed. One subject, although exposed for 11 years without symptoms, developed asthma after a single severe exposure during a ventilation failure. This was the only subject who had never smoked. The diagnosis was confirmed by specific bronchial challenges. Two workers had isolated immediate reactions, one a late asthmatic reaction, and four a dual response following exposure to nebulised potassium dichromate at 1-10 mg/ml. Two of the four subjects were also challenged with nebulised nickel chloride at 0.1-10 mg/ml. Two showed isolated late asthmatic reactions, in one at 0.1 mg/ml, where nickel was probably the primary sensitising agent. Four workers carried out two hourly measurements of peak expiratory flow over days at and away from work. All were scored as having occupational asthma using OASYS-2. Breathing zone air monitoring was carried out in 60 workers from four decorative and two hard chrome plating shops from workers with similar jobs to those sensitised. No measurement exceeded the current occupational exposure standard for chromate or nickel, the mean levels of chromate exposure for jobs similar to those of the affected workers were 9-15 micrograms/m3. CONCLUSION: Chrome used in electroplating is a potential cause of occupational asthma. Sensitivity to chrome in electroplaters may occur in situations where exposure levels are likely to be within the current exposure standards. There may be cross reactivity with nickel. Inhalation challenge with nebulised potassium dichromate solution is helpful in making the specific diagnosis where doubt exists. 

PMCID: PMC1758409  PMID: 9039236
25.  Personality, psychiatric disorders, and smoking in middle-aged adults 
Nicotine & Tobacco Research  2009;11(7):833-841.
A number of personality traits have been associated with cigarette smoking. Current smokers generally show higher levels of negative emotionality and lower levels of behavioral constraint than former smokers and those who never smoked. However, prior investigations have not examined thoroughly whether these smoking–personality associations are unique to smoking status or simply reflect the fact that these personality traits tend to be elevated across numerous forms of psychopathology. Likewise, prior studies have not addressed whether personality shows differential associations with smoking based on the presence or absence of lifetime psychiatric disorders.
The present study examined these questions using data from 472 current, 311 former, and 324 never-smokers aged 34–44 years.
Current smokers reported being more reactive to stress, more aggressive, more alienated, and less harm avoidant than both former smokers and never-smokers, whereas former smokers and never-smokers showed similar personality profiles overall. Psychiatric disorder history did not interact with smoking status in predicting personality. Controlling for differences in four major lifetime psychiatric disorders (major depression, alcohol dependence, drug dependence, and conduct disorder) reduced the differences in personality traits associated with smoking status. However, smoking status continued to relate uniquely and significantly to higher levels of negative emotionality and behavioral undercontrol with the most robust effect observed for trait alienation.
These results provide the most comprehensive depiction to date of interrelations among personality, psychopathology, and smoking and suggest an important role of personality in smoking that is not redundant with or conditional upon lifetime psychopathology.
PMCID: PMC2699929  PMID: 19470795

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