Cigarette Smoke Exposure Increases Myeloid Cell Production and Lung Bacterial Clearance in Mice

Pneumonia is a leading cause of hospitalization in patients with chronic obstructive pulmonary disease (COPD). Although most COPD patients are smokers, the effects of cigarette smoke exposure on clearance of lung bacterial pathogens and on immune and inflammatory responses are incompletely defined. Here, clearance of Streptococcus pneumoniae and Pseudomonas aeruginosa and associated immune responses were examined in mice exposed to cigarette smoke or following smoking cessation. Mice exposed to cigarette smoke for 6 weeks or 4 months demonstrated decreased lung bacterial burden compared to air-exposed mice when infected 16-24 hours post-exposure. When infection was performed after smoke cessation, bacterial clearance kinetics of mice previously exposed to smoke reversed to comparable levels as those of control mice suggesting that the observed defects were not dependent on adaptive immunological memory to bacterial determinants found in smoke. Comparing cytokine levels and myeloid cell production prior to infection in mice exposed to cigarette smoke relative to mice never exposed or following smoke cessation revealed that reduced bacterial burden was most strongly associated with higher levels of IL-1β and GM-CSF in the lungs and with increased neutrophil reserve and monocyte turnover in the bone marrow. Using serpinb1a-deficient mice with reduced neutrophil numbers and treatment with G-CSF showed that increased neutrophil numbers contribute only in part to the effect of smoke on infection. Our findings indicate that cigarette smoke induces a temporary and reversible increase in clearance of lung pathogens, which correlates with local inflammation and increased myeloid cell output from the bone marrow.

High Rates of Smoking Especially in Female Crohn's Disease Patients and Low Use of Supportive Measures to Achieve Smoking Cessation--Data from the Swiss IBD Cohort Study

BACKGROUND AND AIMS Smoking is a crucial environmental factor in inflammatory bowel disease [IBD]. However, knowledge on patient characteristics associated with smoking, time trends of smoking rates, gender differences and supportive measures to cease smoking provided by physicians is scarce. We aimed to address these questions in Swiss IBD patients. METHODS Prospectively obtained data from patients participating in the Swiss IBD Cohort Study was analysed and compared with the general Swiss population [GSP] matched by age, sex and year. RESULTS Among a total of 1770 IBD patients analysed [49.1% male], 29% are current smokers. More than twice as many patients with Crohn's disease [CD] are active smokers compared with ulcerative colitis [UC] [UC, 39.6% vs CD 15.3%, p < 0.001]. In striking contrast to the GSP, significantly more women than men with CD smoke [42.8% vs 35.8%, p = 0.025], with also an overall significantly increased smoking rate compared with the GSP in women but not men. The vast majority of smoking IBD patients [90.5%] claim to never have received any support to achieve smoking cessation, significantly more in UC compared with CD. We identify a significantly negative association of smoking and primary sclerosing cholangitis, indicative of a protective effect. Psychological distress in CD is significantly higher in smokers compared with non-smokers, but does not differ in UC. CONCLUSIONS Despite well-established detrimental effects, smoking rates in CD are alarmingly high with persistent and stagnating elevations compared with the GSP, especially in female patients. Importantly, there appears to be an unacceptable underuse of supportive measures to achieve smoking cessation.

Associations Between Cardiovascular Risk Factors, Inflammation, and Progression of Carotid Atherosclerosis Among Smokers

INTRODUCTION The high risk of cardiovascular events in smokers requires adequate control of other cardiovascular risk factors (CVRFs) to curtail atherosclerosis progression. However, it is unclear which CVRFs have the most influence on atherosclerosis progression in smokers. METHODS In 260 smokers aged 40-70 included in a smoking cessation trial, we analyzed the association between traditional CVRFs, high-sensitivity C-reactive protein (hs-CRP), smoking cessation and 3-year progression of carotid intima-media thickness (CIMT, assessed by repeated ultrasound measurements) in a longitudinal multivariate model. RESULTS Participants (mean age 52 years, 47% women) had a mean smoking duration of 32 years with a median daily consumption of 20 cigarettes. Baseline CIMT was 1185 μm (95% confidence interval [CI]: 1082-1287) and increased by 93 μm (95% CI: 25-161) and 108 μm (95% CI: 33-183) after 1 and 3 years, respectively. Age, male sex, daily cigarette consumption, systolic blood pressure (SBP), but neither low-density lipoprotein cholesterol nor hs-CRP, were independently associated with baseline CIMT (all P ≤ .05). Baseline SBP, but neither low-density lipoprotein cholesterol nor hs-CRP, was associated with 3-year atherosclerosis progression (P = .01 at 3 years). The higher the SBP at baseline, the steeper was the CIMT increase over 3-year follow-up. We found an increase of 26 μm per each 10-mmHg raise in SBP at 1 year and an increase of 39 μm per each 10 mmHg raise in SBP at 3 years. Due to insufficient statistical power, we could not exclude an effect of smoking abstinence on CIMT progression. CONCLUSION Control of blood pressure may be an important factor to limit atherosclerosis progression in smokers, besides support for smoking cessation. IMPLICATIONS Among 260 smokers aged 40-70 years with a mean smoking duration of 32 years, baseline SBP was associated with atherosclerosis progression over 3 years, as measured by CIMT (P = .01 at 3 years), independently of smoking variables and other CVRFs. The higher the SBP at baseline, the steeper was the CIMT increase over 3-year follow-up. Our findings emphasize the importance of focusing not only on smoking cessation among smokers, but to simultaneously control other CVRFs, particularly blood pressure, in order to prevent future cardiovascular disease.

Sociodemographic characteristics as predictors of successful smoking cessation among a group of Hispanic Spanish speaking smokers

Few studies have examined predictors of smoking abstinence among Hispanic groups. The purpose of this dissertation was to examine the relations of sociodemographic characteristics and smoking related factors with smoking abstinence among a group of Hispanic Spanish speaking smokers. This study utilized previously collected data from Hispanic Spanish-speaking smokers (N = 246) who participated in a study entitled Smoking Cessation Services for Hispanic Smokers in Texas. ^ The first study examined sociodemographic characteristics and smoking related mechanisms that predicted smoking abstinence among this group. Two of the characteristics were related to smoking abstinence, marital status and acculturation level. Being unmarried increased the likelihood of being abstinent at the 12 week assessment (OR = 1.80). Those in the high acculturation group were twice as likely to be abstinent (OR = 2.24). Of the smoking related mechanisms, those with higher positive reinforcement expectancies were less likely to be abstinent (OR = .86), as were those with a higher level of affiliative attachment (OR = .86), a higher level of craving (OR = .78) and a higher tolerance to the effect of smoking (OR = .74). The second study was to examine the relationship of objective measures of socioeconomic status (SES) (income, education, or employment) with smoking abstinence among this group. This study also compared the relationship of a subjective measure of SES (Social Status Ladder) to smoking abstinence. None of the objective measures of SES were related to smoking abstinence at the 12 week assessment. The subjective measure of SES did predict smoking abstinence (OR = 1.9) indicting that those that rated themselves ≤4 on the SES scale were more likely to be abstinent. ^ Although this group was recruited using various methods across the state of Texas, the fact that they preferred to interact with the counselor in Spanish may limit the study findings. The results of this study highlight the need for research to examine specific subgroups of people and understand the special circumstances that influence their health behaviors. Furthering our knowledge of the relations between sociodemographic characteristics and smoking cessation could lead to interventions that reduce disparities in smoking cessation. ^

The role of smoking status on postoperative complications and survival in lung cancer patients presenting to M.D. Anderson Cancer Center

It is estimated that 50% of all lung cancer patients continue to smoke after diagnosis. Many of these lung cancer patients who are current smokers often experience tremendous guilt and responsibility for their disease, and feel it might be too late for them to quit smoking. In addition, many oncologists may be heard to say that it is 'too late', 'it doesn't matter', 'it is too difficult', 'it is too stressful' for their patients to stop smoking, or they never identify the smoking status of the patient. Many oncologists feel unprepared to address smoking cessation as part of their clinical practice. In reality, physicians can have tremendous effects on motivating patients, particularly when patients are initially being diagnosed with cancer. More information is needed to convince patients to quit smoking and to encourage clinicians to assist patients with their smoking cessation. ^ In this current study, smoking status at time of lung cancer diagnosis was assessed to examine its impact on complications and survival, after exploring the reliability of smoking data that is self-reported. Logistic Regression was used to determine the risks of smoking prior to lung resection. In addition, survival analysis was performed to examine the impact of smoking on survival. ^ The reliability of how patients report their smoking status was high, but there was some discordance between current smokers and recent quitters. In addition, we found that cigarette pack-year history and duration of smoking cessation were directly related to the rate of a pulmonary complication. In regards to survival, we found that current smoking at time of lung cancer diagnosis was an independent predictor of early stage lung cancer. This evidence supports the idea that it is "never too late" for patients to quit smoking and health care providers should incorporate smoking status regularly into their clinical practice.^

Illicit drug use, alcohol use and nicotine dependence as predictors of antiretroviral adherence in a sample of HIV positive smokers

Objective. Predictors of non-adherence to antiretroviral medications in a population of low-income, multiethnic, HIV-positive smokers were investigated. ^ Methods. A secondary analysis was conducted using baseline data collected from 326 patients currently prescribed antiretrovirals enrolled in a randomized clinical trial assessing smoking outcomes. Variables evaluated included demographics, stress, depression, nicotine dependence, illicit drug use and alcohol use. ^ Results. The average age of participants was 45.9 years (SD=7.6). The majority of participants were male (72.1%), Black (76.7%), reported sexual contact as the method of HIV exposure (heterosexual (43%) and MSM (27%)) and were antiretroviral adherent (60.4%). Results from unadjusted analyses indicated depression (OR=1.02; 95% CI=1.00-1.04), illicit drug use (OR=2.39; 95% CI=1.51-3.79) and alcohol consumption (OR=2.86; 95% CI=1.79-4.57) were associated with non-adherence. Multivariate analyses indicated nicotine dependence (OR=1.13; 95% CI=1.02-1.25), illicit drug use (OR=2.10; 95% CI=1.27-3.49) and alcohol use (OR=2.50; 95% CI=1.52-4.12) were associated with nonadherence. ^ Conclusions. Illicit drug use, alcohol use and nicotine dependence are formidable barriers to antiretroviral adherence in this population. Future research is needed to assess how to address these variables in the context of improving antiretroviral adherence for individuals living with HIV/AIDS.^

Investigating the epidemic of heroin use in Dar es Salaam, Tanzania: Recognizing the issues of heroin smokers

Since heroin was introduced to East Africa during the 1980s, heroin use practices have changed rapidly in response to various internal and external pressures. The aim of this study was to identify and describe the population of heroin users and locations of heroin use in Dar es Salaam, Tanzania, in order to understand recent contexts of heroin use. The study took place between June 30 and August 19, 2011, in all three districts (Kinondoni, Ilala, and Temeke) of Dar es Salaam. We mapped sites using a Global Positioning System device, counted numbers of heroin users, and conducted informal interviews with heroin users. The mixed-methods analyses of the data included quantifying the basic demographic and aggregate information about the sites and heroin users, as well as qualitative analysis and coding of fieldnotes from observations and responses to interviews which was used to identify themes and characteristics of heroin users. ^ We identified a total of 150 sites and counted a total of 1046 male and 46 female non-injecting drug users and 78 male and 9 female injecting drug users (IDUs) of heroin. We found that social organization existed at some of the sites, with 31% (n=47) of sites reporting having a leader and 44% (n=66) of sites reporting mutual aid between users frequenting the site. We had difficulty locating IDUs and female drug users, and the majority of users we encountered were heroin smokers of kokteli, a mixture of heroin, cannabis, and/or tobacco which is smoked like a cigarette. ^ This research highlighted heroin smokers’ desire for access to drug treatment services. The current methadone-based medication assisted treatment (MAT) program is funded and operates as an HIV prevention program for IDUs to reduce HIV infection in this population and slow or stop the spread of a second wave of HIV infection in the general population. However, smokers perceived MAT to be primarily a drug use prevention or cessation program and felt unjustly neglected from the intervention, leading to a tense relationship with IDUs. From a public health standpoint, future interventions should include heroin smokers to prevent HIV transmission. ^

Factors associated with HPV16 status and survival among patients with squamous cell carcinoma of the oropharynx

Background: Squamous cell carcinoma of the oropharynx (SCCOP) is characterized by local tumor aggressiveness, high recurrence rates, a high incidence of second primary tumors, and medical comorbidities. Significant trends in demographic and clinical characteristics as well as survival among SCCOP patients have been observed over time, likely owing to the changing etiology of the disease. Human papillomavirus type 16 (HPV16) infection is associated with a significant proportion of these cancers. Biomarkers that may aid in identifying patients that are at higher risk of recurrence and death are important so that these patients may be followed more closely to improve their quality of life. ^ Study population and methods: The retrospective review (Specific Aim 2) included 3891 newly diagnosed, previously untreated patients presenting to our institution between 1955 and 2004. A total of 2299 patients treated at our institution were included in survival and recursive partitioning analysis. The prospective cohort study (Specific Aim 3) included 266 patients presenting to our institution between January 2006 and September 2009. ^ Results: The results from the retrospective review showed that over time, patients presented at younger ages and were more likely to have base of tongue/tonsil tumors and to be never/former smokers and moreover survival improved significantly over time. In survival and recursive partitioning analyses, the TNM staging system was efficient in prognosticating patients prior to 1995. However, in the recent decade, the TNM staging system was completely inadequate. The factors having the greatest positive effect on overall survival since 1995 were those common to HPV-associated SCCOP. The results from the prospective cohort study indicate that patients with high nodal stage and those with late stage disease have increased levels of pretreatment serum HPV DNA. ^ Conclusions: We saw a distinct improvement in survival among SCCOP patients over the past 50 years at our institution. The main factors contributing to this were changes in clinical characteristics, in particular surrogates for HPV status. The current TNM staging system for SCCOP is inadequate and incorporation of HPV status (and perhaps smoking status) is encouraged. Furthermore, although pretreatment circulating levels of HPV DNA was associated with higher N category and overall disease stage, it has limited utility as a marker for recurrence among SCCOP patients.^

Thomas Van Nortwick. Somewhere I Have Never Travelled. The Hero's Journey. New York-Oxford, Oxford University Press, 1996, 204 pp.

Fil: Errecalde, Alejandro Martín. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.

Thomas Van Nortwick. Somewhere I Have Never Travelled. The Hero's Journey. New York-Oxford, Oxford University Press, 1996, 204 pp.

Fil: Errecalde, Alejandro Martín. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.

Thomas Van Nortwick. Somewhere I Have Never Travelled. The Hero's Journey. New York-Oxford, Oxford University Press, 1996, 204 pp.

Fil: Errecalde, Alejandro Martín. Universidad Nacional de La Plata. Facultad de Humanidades y Ciencias de la Educación; Argentina.