The human lung mucosa drives differential Mycobacterium tuberculosis infection outcome in the alveolar epithelium.

Mycobacterium tuberculosis (M.tb) is deposited into the alveolus where it first encounters the alveolar lining fluid (ALF) prior contacts host cells. We demonstrated that M.tb-exposure to human ALF alters its cell surface, driving better M.tb infection control by professional phagocytes. Contrary to these findings, our results with non-professional phagocytes alveolar epithelial cells (ATs) define two distinct subsets of human ALFs; where M.tb exposure to Low (L)-ALF or High(H)-ALF results in low or high intracellular bacterial growth rates in ATs, respectively. H-ALF exposed-M.tb growth within ATs was independent of M.tb-uptake, M.tb-trafficking, and M.tb-infection induced cytotoxicity; however, it was associated with enhanced bacterial replication within LAMP-1+/ABCA1+ compartments. H-ALF exposed-M.tb infection of ATs decreased AT immune mediator production, decreased AT surface adhesion expression, and downregulated macrophage inflammatory responses. Composition analysis of H-ALF vs. L-ALF showed H-ALF with higher protein tyrosine nitration and less functional ALF-innate proteins important in M.tb pathogenesis. Replenishment of H-ALF with functional ALF-innate proteins reversed the H-ALF-M.tb growth rate to the levels observed for L-ALF-M.tb. These results indicate that dysfunctionality of innate proteins in the H-ALF phenotype promotes M.tb replication within ATs, while limiting inflammation and phagocyte activation, thus potentiating ATs as a reservoir for M.tb replication and survival.

Regional Rural-Urban Differences in E-Cigarette Use and Reasons for Use in the United States.

PURPOSE: To determine whether there are rural/urban differences in e-cigarette use and reasons for use that vary across the 10 Health & Human Services (HHS) regions. METHODS: Age-adjusted bivariate and multivariable analyses were conducted for n = 225,413 respondents to the 2014-2015 Tobacco Use Supplement-Current Population Survey to estimate the prevalence of e-cigarette use. Reasons for e-cigarette use were collected from n = 16,023 self-respondents who reported ever using e-cigarettes. FINDINGS: While nationally rural residents appeared more likely to use e-cigarettes, adjusted results indicated that current e-cigarette use was significantly less likely across the northern and western regions (New England, East North Central, Heartland, North Central Mountain, Northwest, and Southwest Pacific regions). Reasons for e-cigarette use differed by urban/rural status and region; for example, the rationale to use e-cigarettes as a smoking cessation aid was significantly more common among rural compared to urban adults in the New England and New York/New Jersey regions, but less common in the Southeast. CONCLUSIONS: For several regions, there were no significant rural/urban differences in e-cigarette use and reasons for use. Yet those regions that present differences face the need to develop public health approaches to minimize urban/rural disparities in health education, services, and outcomes related to tobacco use, particularly where access to health care is limited. Public health campaigns and guidance for clinical care within HHS regions should be tailored to reflect regional differences in beliefs about e-cigarettes.

Exposure to human alveolar lining fluid enhances Mycobacterium bovis BCG vaccine efficacy against Mycobacterium tuberculosis infection in a CD8+ T-cell-dependent manner.

Current tuberculosis (TB) treatments include chemotherapy and preventative vaccination with Mycobacterium bovis Bacillus Calmette-Guérin (BCG). In humans, however, BCG vaccination fails to fully protect against pulmonary TB. Few studies have considered the impact of the human lung mucosa (alveolar lining fluid (ALF)), which modifies the Mycobacterium tuberculosis (M.tb) cell wall, revealing alternate antigenic epitopes on the bacterium surface that alter its pathogenicity. We hypothesized that ALF-induced modification of BCG would induce better protection against aerosol infection with M.tb. Here we vaccinated mice with ALF-exposed BCG, mimicking the mycobacterial cell surface properties that would be present in the lung during M.tb infection. ALF-exposed BCG-vaccinated mice were more effective at reducing M.tb bacterial burden in the lung and spleen, and had reduced lung inflammation at late stages of M.tb infection. Improved BCG efficacy was associated with increased numbers of memory CD8+ T cells, and CD8+ T cells with the potential to produce interferon-γ in the lung in response to M.tb challenge. Depletion studies confirmed an essential role for CD8+ T cells in controlling M.tb bacterial burden. We conclude that ALF modifications to the M.tb cell wall in vivo are relevant in the context of vaccine design.

A growing geographic disparity: Rural and urban cigarette smoking trends in the United States.

Rural areas of the United States have a higher smoking prevalence than urban areas. However, no recent studies have rigorously examined potential changes in this disparity over time or whether the disparity can be explained by demographic or psychosocial characteristics associated with smoking. The present study used yearly cross sectional data from the National Survey on Drug Use and Health from 2007 through 2014 to examine cigarette smoking trends in rural versus urban areas of the United States. The analytic sample included 303,311 respondents. Two regression models were built to examine (a) unadjusted rural and urban trends in prevalence of current smoking and (b) whether differences remained after adjusting for demographic and psychosocial characteristics. Results of the unadjusted model showed disparate and diverging cigarette use trends during the 8-year time period. The adjusted model also showed diverging trends, initially with no or small differences that became more pronounced across the 8-year period. We conclude that differences reported in earlier studies may be explained by differences in rural versus urban demographic and psychosocial risk factors, while more recent and growing disparities appear to be related to other factors. These emergent differences may be attributable to policy-level tobacco control and regulatory factors that disproportionately benefit urban areas such as enforcement of regulations around the sale and marketing of tobacco products and treatment availability. Strong federal policies and targeted or tailored interventions may be important to expanding tobacco control and regulatory benefits to vulnerable populations including rural Americans.

Cigarette and waterpipe smoking associated knowledge and behaviour among medical students in Lebanon.

As future physicians capable of controlling tobacco dependence in the population, medical students are considered a main target for tobacco control interventions. This cross-sectional study reported on the prevalence of tobacco use (cigarettes and waterpipes) and associated knowledge and behaviour among 6th-year medical students in 2009-2010 from 6 medical schools in Lebanon. The self-administered questionnaire based on the Global Health Professional Survey (GHPSS) core questions also enquired about training in tobacco cessation approaches. All enrolled students were asked to participate; the response rate was 191/354 (54.3%). The prevalence of tobacco use was 26.3% for cigarettes and 29.5% for waterpipes. Smoking waterpipes was the only significant predictor for cigarette smoking and there was no difference by sex and socioeconomic status. A minority reported ever receiving any formal training in treatment approaches for tobacco dependence. Medical schools should include tobacco dependence treatment training programmes in their curriculum and discourage tobacco use.

Treatment adherence in a lay health adviser intervention to treat tobacco dependence.

Lay health advisers (LHAs) are increasingly used to deliver tobacco dependence treatment, especially with low-socioeconomic status (SES) populations. More information is needed about treatment adherence to help interpret mixed evidence of LHA intervention effectiveness. This study examined adherence to behavioral counseling and nicotine patches in an LHA intervention with 147 Ohio Appalachian female daily smokers. Participants were randomly selected from clinics and randomized to the intervention condition of a randomized controlled trial. Overall, 75.5% of participants received all seven planned LHA visits, 29.3% used patches for >7 weeks and approximately half received high average ratings on participant responsiveness. Depressive symptoms and low nicotine dependence were associated with lower patch adherence while high poverty-to-income ratio was associated with high responsiveness. Compared with those with fewer visits, participants who received all visits were more likely to be abstinent (22.5 versus 2.8%, P=0.026) or have attempted quitting (85.0 versus 47.4%, P=0.009) at 3 months. High participant responsiveness was associated with 12-month abstinence. LHA interventions should focus on improving adherence to nicotine patches and managing depression because it is an independent risk factor for low adherence.

Cigarette and waterpipe smoking associated knowledge and behaviour among medical students in Lebanon

As future physicians capable of controlling tobacco dependence in the population, medical students are considered a main target for tobacco control interventions. This cross-sectional study reported on the prevalence of tobacco use [cigarettes and waterpipes] and associated knowledge and behaviour among 6th-year medical students in 2009-2010 from 6 medical schools in Lebanon. The self-administered questionnaire based on the Global Health Professional Survey [GHPSS] core questions also enquired about training in tobacco cessation approaches. All enrolled students were asked to participate; the response rate was 191/354 [54.3%]. The prevalence of tobacco use was 26.3% for cigarettes and 29.5% for waterpipes. Smoking waterpipes was the only significant predictor for cigarette smoking and there was no difference by sex and socioeconomic status. A minority reported ever receiving any formal training in treatment approaches for tobacco dependence. Medical schools should include tobacco dependence treatment training programmes in their curriculum and discourage tobacco use

Tobacco policy in American prisons, 2007.

OBJECTIVE: To examine current tobacco policy in US prisons and explore changes in prison tobacco policies over time. DATA SOURCE: Telephone survey of the 52 US departments of correction. MAIN OUTCOME MEASURES: Current tobacco policy; distribution of free tobacco; availability of smoking cessation programming and cessation aids. PARTICIPANTS: Complete responses were received from 51 of 52 (98%) departments, while one provided partial information. RESULTS: The majority of correctional systems (60%) reported total tobacco bans on prison grounds, with most remaining facilities (27%) having an indoor ban on tobacco use. No prisons distributed free tobacco. No major violence was reported relating to the implementation of stricter tobacco policies; however many respondents noted that tobacco became a major contraband item following the implementation of a total ban. While most prison systems with an indoor tobacco ban (86%) reported having tobacco cessation programmes, few of those with total bans (39%) continued such programmes after the initial transition period. CONCLUSION: Total tobacco bans have often been accompanied by the termination of tobacco cessation programmes. Such actions undermine efforts to promote long-term cessation resulting in a missed public health opportunity.

Pulmonary defense and the human cathelicidin hCAP-18/LL-37.

Antimicrobial peptides form an important component of the innate immune system. The cathelicidin family, a key member of the antimicrobial peptide defenses, has been highly conserved throughout evolution. Though widespread in mammals, there is currently only one identified human example, hCAP-18/LL-37. The cathelicidins have been found to have multiple functions, in addition to their known antimicrobial and lipopolysaccharide-neutralizing effects. As a result, they profoundly affect both innate and adaptive immunity. Currently, antimicrobial peptides are being evaluated as therapeutic drugs in disease states as diverse as oral mucositis, cystic fibrosis, and septic shock. One such peptide, the cathelicidin hCAP-18/LL-37, is reviewed in detail in the context of its role in lung physiology and defense.

Preparing the "Ground War" against tobacco among Chinese Americans in New York City: baseline data.

OBJECTIVES: The objective of this paper is to report on data on the perceptions regarding smoking and environmental tobacco smoke as well as the health communication patterns of a representative sample of 715 adult Chinese families with children under age 18 who had not banned smoking in the home. METHODS: We selected a representative sample of Chinese American families residing in New York's five boroughs: Brooklyn, Bronx, Manhattan, Queens, and Staten Island based on Chinese family surnames and interviewed them by telephone between December 2000-March 2001. All except 4% of the interviews were conducted in English; most respondents chose to speak Cantonese and lesser numbers chose Mandarin. FINDINGS: For the most part, respondents believed in the hazards of smoking, especially as it harms children living at home. To address smoking, respondents believed the physicians is the most trustworthy source of health information and the sources of health information consulted would be overwhelmingly the Chinese language newspaper, followed by Chinese language radio and television. CONCLUSIONS: This study represents the first systematic assessment of Chinese Americans in New York with regard to selected tobacco control issues. The findings provide the empirical base for developing potential messages using the source considered most trustworthy (the physician) and the vehicle most consulted (Chinese language media).

Sequential processing of human ProIL-1beta by caspase-1 and subsequent folding determined by a combined in vitro and in silico approach.

PURPOSE: Interleukin-1beta is a multifunctional cytokine produced by activated monocytes and macrophages that requires caspase-1 (IL-1 converting enzyme/ICE) to process the 31kDa inactive precursor protein to the biologically active 17kDa peptide. This activation event involves ICE cleavage at Asp27 (site 1) and Asp116 (site 2). To address the sequential processing at ICE cut sites we combined in vitro analysis and molecular modeling to investigate the sequence of molecular events. METHODS: Pulse chase labeling followed by immunoprecipitation of IL-1beta in activated human monocyte lysates demonstrated sequential cutting by ICE at site 1 before site 2 in vitro. To corroborate these findings, we constructed a homology model of proIL-1beta after the crystal structure of another ICE substrate, human alpha1-antitrypsin (23% sequence identity). RESULTS: Comparative modeling revealed that site 1 on proIL-1beta is accessible to ICE but site 2 is not. Molecular dynamics simulations following ICE cleavage at site 1 and removal of the 3kDa amino-terminal fragment, rendered site 2 accessible to ICE. CONCLUSIONS: The close agreement between the in vitro and modeled behavior of IL-1beta support our contention that IL-1beta may be structurally related to alpha1-antitrypsin and also predicts that proIL-1beta requires sequential processing for activation. These findings may facilitate the development of novel pharmacological agents that control posttranslational proIL-1beta modification, thereby preventing excessive production of this potent inflammatory cytokine.

Barriers to tobacco cessation in clinical practice: report from a National Survey of Oncology Nurses.

This study describes the survey results of a national random sample of members of the Oncology Nursing Society who reported the greatest number of barriers to delivering a tobacco cessation intervention with their patients. Nurses who perceived the greatest number of barriers were more likely to be current smokers and to be young and were less likely to have an advanced degree, to be a nurse practitioner, or to have administrative responsibilities. Those with greater barriers were less likely to deliver tobacco cessation interventions.

Interleukin-1beta costimulates interferon-gamma production by human natural killer cells.

Natural killer (NK) cells are an early source of immunoregulatory cytokines during the innate immune response to viruses, bacteria, and parasites. NK cells provide requisite IFN-gamma to monocytes for the elimination of obligate intracellular pathogens. IL-1beta is a pro-inflammatory cytokine produced by monocytes (i.e. a monokine) during the early immune response to infection, but its role in promoting human NK cell IFN-gamma production is unknown. The current study examines the ability of the monokine IL-1beta, plus IL-12, to costimulate IFN-gamma production by resting CD56(bright) and CD56(dim) human NK cell subsets. CD56(bright) NK cells stimulated with IL-1beta plus IL-12 produced abundant IFN-gamma protein, while little IFN-gamma was produced in identical cultures of CD56(dim) cells. In addition, upon activation with IL-1beta, CD56(bright) NK cells exhibited considerably greater phosphorylation of extracellular signal-regulated kinases p42/44 as compared to CD56(dim) NK cells. Quantitative PCR analysis showed brisk induction of IFN-gamma gene expression following costimulation with IL-1beta plus IL-12 in CD56(bright) NK cells, but intracellular flow cytometry revealed that only a fraction (42+/-2.3%) of CD56(bright) NK cells account for this high IFN-gamma production. These data suggest that the monokine IL-1beta is a potent costimulus of IFN-gamma production by a subset of NK cells following infectious insult.

BAL and serum IgG levels in healthy asymptomatic HIV-infected patients.

OBJECTIVES: To determine if the increased susceptibility to bacterial infection in asymptomatic HIV-infected patients is associated with decreased total IgG or IgG2 levels in lung epithelial lining fluid. BACKGROUND: A decrease in lung IgG levels or subtypes has been proposed as contributing to the increased risk of bacterial lung infections in HIV-infected patients. Previous studies measuring lung lavage IgG concentrations have been inconsistent. METHODS: Twenty-three HIV patients and 25 control subjects underwent BAL. Both patient groups were of similar age, and had similar pulmonary function studies and body mass index. Smokers were equally represented in both groups, and the majority of subjects in both groups were male. Total IgG and IgG2 levels in lavage fluid were assayed in both cohorts and compared using a two-tailed Student's t test. RESULTS: The lung lining fluid IgG level in HIV-infected patients was 0.19 +/- 0.13 microg/microg of protein (mean +/- SD) vs 0.11 +/- 0.09 microg/microg of protein in control subjects (p < 0.05). The IgG(2) level in HIV patients was 0.034 +/- 0.038 microg/microg of protein and 0.014 +/- 0.01 microg/microg of protein in control subjects (p = 0.054). Lavage IgG levels reflected serum IgG values (correlation coefficient, 0.56; p < 0.001) but did not correlate with lung immunoglobulin-producing cells. CONCLUSIONS: The increased susceptibility to bacterial pneumonia in asymptomatic HIV-infected individuals is neither explained by depressed total IgG levels nor a deficiency in IgG(2) levels in the lungs. The strong correlation between serum and lavage IgG levels suggests that lavage IgG derives from serum.

ATP-stimulated release of interleukin (IL)-1beta and IL-18 requires priming by lipopolysaccharide and is independent of caspase-1 cleavage.

Interleukin (IL)-1beta and IL-18 are structurally similar proteins that require caspase-1 processing for activation. Both proteins are released from the cytosol by unknown pathway(s). To better characterize the release pathway(s) for IL-1beta and IL-18 we evaluated the role of lipopolysaccharide priming, of interleukin-1beta-converting enzyme (ICE) inhibition, of human purinergic receptor (P2X(7)) function, and of signaling pathways in human monocytes induced by ATP. Monocytes rapidly processed and released both IL-1beta and IL-18 after exogenous ATP. Despite its constitutive cytosolic presence, IL-18 required lipopolysaccharide priming for the ATP-induced release. Neither IL-1beta nor IL-18 release was prevented by ICE inhibition, and IL-18 release was not induced by ICE activation itself. Release of both cytokines was blocked completely by a P2X7 receptor antagonist, oxidized ATP, and partially by an antibody to P2X(7) receptor. In evaluating the signaling components involved in the ATP effect, we identified that the protein-tyrosine kinase inhibitor, AG126, produced a profound inhibition of both ICE activation as well as release of IL-1beta/IL-18. Taken together, these results suggest that, although synthesis of IL-1beta and IL-18 differ, ATP-mediated release of both cytokines requires a priming step but not proteolytically functional caspase-1.

Tobacco-control attitudes, advocacy, and smoking behaviors of oncology nurses.

PURPOSE/OBJECTIVES: To describe oncology nurses' attitudes, smoking behaviors, and involvement in tobacco-control policy and legislation. DESIGN: Descriptive, cross-sectional survey. SAMPLE: Responses from 1,508 (38% return) of 4,000 randomly selected members of the Oncology Nursing Society (ONS). The typical respondent was female, age 44, a staff nurse, had practiced as an oncology nurse for 12 years, and was certified as an OCN. METHODS: A mailed survey with specific questions about smoking status and the importance of nursing involvement in healthcare policy and legislation for tobacco control. MAIN RESEARCH CONCEPTS: Attitudes about tobacco-control policies and legislation; sociodemographic, professional, and institutional variables; and tobacco use. FINDINGS: The majority (85%) of members stated that nursing involvement in tobacco-control healthcare policy and legislation was important. More than 90% of respondents supported prevention of youth access to tobacco and providing information about health effects of tobacco and cessation. Seven percent (n = 106) were current smokers. Significantly fewer smokers valued involvement in tobacco-control activities. Respondents with personal experience of tobacco-related illnesses were more likely to value involvement in advocacy activities. Educational programs to prevent tobacco use among youth and to help patients stop smoking received the most support (80%). IMPLICATIONS FOR NURSING PRACTICE: This sample of ONS members strongly supported involvement in tobacco-control policies and legislation. Smoking was associated with more negative attitudes about the importance of actively engaging in tobacco control. These oncology nurses recognized the need for additional educational programs to prevent tobacco initiation by youth.

Cotinine levels in Southeast Asian smokers.

Understanding the contribution of race to factors associated with cigarette smoking and nicotine metabolism is essential for the characterization of patterns of tobacco use, nicotine dependence and incidence of tobacco-related diseases. This paper reports an investigation of cotinine levels among Southeast Asian smokers in two separate studies. Study 1 included 327 male and female smokers who participated in community-based interviews where smoking history information was obtained and a saliva continine sample was collected. Results indicated that subjects smoked an average of 11.2 cigarettes/day, with men reporting significantly higher consumption rates as compared to women (p < 0.0001). Subjects' mean cotinine level was 65 ng/ml with an average cotinine/cigarette ratio of 8.2. In Study 2, plasma and saliva cotinine in six Southeast Asian adult smokers were measured during 2 days of smoking followed by 6 days of abstinence. On day 1, mean plasma and saliva continine levels were 268 and 235 ng/ml, respectively. After 6 days of abstinence, mean levels had dropped to 12 ng/ml for plasma and 8 ng/ml in saliva. On average, it required at least 4.7 days for saliva continine levels to reach < 14 ng/ml. Mean cotinine concentrations during smoking differed in these two separate studies. Implications of these findings are discussed and future research recommendations are presented.

The feasibility of a nurse-managed, peer-led tobacco cessation intervention among HIV-positive smokers.

The purpose of this pilot study was to examine the effectiveness of an 8-week, nurse-managed, peer-led smoking cessation intervention among HIV-positive smokers. The intervention was based on the Agency for Health Care Policy and Research Smoking Cessation Clinical Practice Guideline and was delivered by an ex-smoker who was HIV positive and had been trained by an advanced practice nurse to deliver cessation counseling. Eight male HIV-positive smokers were assigned to the intervention group and received (a) 21 mg nicotine patch therapy for 6 weeks, (b) weekly face-to-face or telephone counseling, and (c) skills training that included substitute strategies for dealing with not smoking. Those participants assigned to the control group received written self-help materials for smoking cessation. Abstinence rates at end of intervention and 8 months were compared between groups. At end of treatment, 62.5% of intervention group participants were biochemically confirmed as abstinent from smoking compared with 0% in the control group. Eight-month abstinence rates were 50% among the intervention group compared with 0% in the control group.

Implementing the Agency for Health Care Policy and Research's Smoking Cessation Guideline in a lung cancer surgery clinic.

PURPOSE/OBJECTIVES: To determine the effectiveness of a nurse-managed smoking cessation intervention based on the Agency for Health Care Policy and Research's (AHCPR's) Smoking Cessation Guideline in a lung cancer surgery clinic. DESIGN: Quasi-experimental. SETTING: Urban, Midwest, academic, and tertiary care. SAMPLE: 25 adult male and female smokers with a confirmed diagnosis of lung cancer that had been surgically managed. Subjects were assigned to an intervention group (n = 14) or a usual-care group (n = 11). METHODS: Participants in the intervention group received a nurse-delivered, AHCPR-based smoking cessation intervention that included face-to-face and phone follow-up contact beginning with the first preoperative clinic consultation. Usual-care participants received routine care provided at the institution. MAIN RESEARCH VARIABLES: Self-reported smoking status with expired air carbon monoxide confirmation six months postsurgery. FINDINGS: Seventy-one percent of the intervention group was biochemically confirmed to be abstinent by expired air carbon monoxide, as compared to 55% in the usual-care group. CONCLUSIONS: Smokers diagnosed with lung cancer desired to quit smoking and may benefit from an intensive smoking cessation intervention at time of diagnosis. IMPLICATIONS FOR NURSING PRACTICE: Further research should include continuing evaluation of an intensive smoking cessation intervention with this population, and all clinicians should be trained to implement AHCPR's Smoking Cessation Guideline in practice.

Tobacco use characteristics among rural Ohio Appalachians.

Appalachians remain at high risk for cancer, heart and lung disease, in part because of their high prevalence of tobacco use; yet, information about their tobacco consumption patterns is limited. The purpose of this study was to describe tobacco consumption variables among rural adult Appalachian tobacco users. Subjects, aged 18 and older (N = 249), participated in a face-to-face interview about tobacco consumption variables and knowledge regarding the health effects of tobacco at fairs in two rural Ohio Appalachian counties. The majority of participants were categorized as precontemplators, although 21 percent were classified in preparation stage of change. Mean age of initiation was 16.6 years and number of cigarettes smoked per day (cpd) was significantly higher for men, as compared to women. One-third of males reported the use of smokeless tobacco. The majority had not tried to quit for more than a year and the average number of previous quit attempts was low. One-half of the sample had been advised in the past to quit by their physician. Few had used nicotine replacement with past quit attempts but greater than half would consider this approach with future attempts. Knowledge about the health effects of smoking indicated that most were aware of the relationship between smoking and cancer but less than one-half recognized its association with heart disease. Those with less education were less informed about the health effects to self and non-smokers. While a sizeable portion expressed interest in quitting, knowledge about the health effects of smoking is lacking, especially with regard to heart disease and among those with less education.