Proangiogenic and Profibrotic Markers in Pulmonary Sarcoidosis.

The aim of our study was to determine the blood levels of vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß1, fibroblast growth factor (FGF)-2, and platelet-derived growth factor (PDGF)-AB in different stages of pulmonary sarcoidosis. There were 92 patients in sarcoidosis stages I + II, III, and IV enrolled into the study. All the patients underwent lung diffusing capacity and blood sampling. We found that VEGF levels differed significantly between the stage groups with the peak VEGF concentrations in stage III. TGF-ß1 levels were similar in stages I + II and III, and tended to be lower in stage IV. The analysis of the subgroups showed increased VEGF and FGF-2, and reduced TGF-ß1 concentration in stages I + II patients with relevantly reduced lung diffusing capacity or increased sarcoidosis activity compared to patients with normal lung diffusing capacity or inactive sarcoidosis. A tendency towards increased VEGF, PDGF-AB and TGF-ß1 levels was observed in the analogical subgroup analysis within the stage III. We conclude that proangiogenic VEGF, and profibrotic FGF-2 and PDGF-AB may contribute to the progression of sarcoidosis, whereas TGF-ß1, with its dual anti-inflammatory and profibrotic actions, may play a dichotomous protective or deleterious role. Reduced diffusing capacity and active sarcoidosis are associated with an unfavorable constellation of the markers studied, which predicts a progressive disease course.

Impaired Vascular Function in Sarcoidosis Patients.

A common feature of sarcoidosis and atherosclerosis is a chronic systemic inflammatory reaction. Our hypothesis was that sarcoidosis may negatively influence the vessel status. We addressed the issue by examining preatherosclerotic vascular alternations using an ultrasound-based speckle-tracking method in 72 sarcoidosis patients and 15 matched controls. To find potential factors which may have a deleterious influence on arterial performance, different subgroups of sarcoidosis, such as sarcoidosis with or without cortisone therapy, pulmonary sarcoidosis in early and advanced stages, pulmonary sarcoidosis alone or combined with extrapulmonary sarcoidosis, and sarcoidosis with or without elevated blood levels of angiotensin converting enzyme (ACE)/soluble interleukin 2 receptor (sIL-2R) were investigated. We found in the general collective of sarcoidosis patients that circumferential strain (2.68 ± 0.19%), circumferential strain rate (0.21 ± 0.01 1/s), and radial displacement (0.10 ± 0.01 mm) were significantly decreased compared to controls (3.77 ± 0.35%, 0.28 ± 0.02 1/s, and 0.14 ± 0.02 mm, respectively). Vascular strains were more impaired in patients with cortisone therapy, pulmonary sarcoidosis in stages III-IV, and in pulmonary sarcoidosis accompanied by extrapulmonary involvement. The level of ACE/sIL-2R had no relevant influence on the angiological parameters. In conclusion, sarcoidosis is associated with increased vascular stiffness. Cortisone therapy and advanced stages of pulmonary sarcoidosis with extrapulmonary manifestations may account for the impaired vascular function in this patient collective.

Atherosclerotic Vessel Changes in Sarcoidosis.

Sarcoidosis is a systemic granulomatous disease. Atherosclerosis is a chronic inflammatory vessel disease. The aim of our present study was to investigate whether sarcoidosis could be associated with increased risk of atherosclerotic vessel changes. Angiological analysis and blood tests were performed in 71 sarcoidosis patients and 12 matched controls in this prospective cross-sectional study. Specifically, angiological measurements comprised ankle brachial index (ABI), central pulse wave velocity (cPWV), pulse wave index (PWI), and duplex sonography of central and peripheral arteries. Sarcoidosis activity markers (angiotensin converting enzyme, soluble interleukin-2 receptor) and cardiovascular risk parameters such as cholesterol, lipoprotein(a), C-reactive protein, interleukin 6, fibrinogen, d-dimer, and blood count were analyzed in blood. We found no relevant differences in ABI, cPWV, and plaque burden between the sarcoidosis and control groups (1.10 ± 0.02 vs. 1.10 ± 0.02, 6.7 ± 0.5 vs. 6.1 ± 1.2, 53.7 % vs. 54.5 %, respectively). However, PWI was significantly higher in sarcoidosis patients (146.2 ± 6.8) compared with controls (104.9 ± 8.8), irrespectively of the activity of sarcoidosis and immunosuppressive medication. Except for increased lipoprotein(a) and d-dimer in sarcoidosis, the remaining cardiovascular markers were similar in both groups. We conclude that sarcoidosis is associated with increased pulse wave index, which may indicate an early stage of atherosclerosis.

[Chronic obstructive pulmonary disease (COPD): eosinophilia and novel drug therapies]. / Chronisch-obstruktive Lungenerkrankung (COPD) ­ Eosinophilie und neue Arzneimitteltherapien.

BACKGROUND: The phenotyping of chronic obstructive pulmonary disease (COPD) has increasingly gained attention in recent years, as it leads to new and individualized therapeutic concepts. OBJECTIVE: The aim is to provide an overview of the heterogeneity of COPD and to summarize current drug therapy concepts, particularly in the context of eosinophilic airway inflammation. DATA: Several prospective, randomized, placebo-controlled studies have shown a reduction in exacerbations and overall mortality with inhaled triple therapy using an inhaled corticosteroid and dual bronchodilation. The higher the eosinophils in the blood, the greater the expected effect. In addition, a reduction in exacerbations with biologics in COPD with eosinophilia has been demonstrated for dupilumab. Eosinophil-guided therapy for acute exacerbations is the subject of current research. CONCLUSION: For COPD without exacerbations, dual bronchodilation forms the basis of inhaled therapy. With exacerbations, inhaled triple therapy is indicated for patients with a blood eosinophil count of ≥ 300/µl. This type of treatment may also be useful when eosinophils are between 100 and 300/µl. Therapy with dupilumab is a possible option for the eosinophilic phenotype in the near future.

Association of proangiogenic and profibrotic serum markers with lung function and quality of life in sarcoidosis.

BACKGROUND: Sarcoidosis is a systemic inflammatory granulomatous disease, frequently affecting the lung. If left untreated, it may end in lung fibrosis. Proangiogenic and profibrotic vascular endothelial growth factor (VEGF), transforming growth factor (TGF)-ß1, fibroblast growth factor (FGF)-2 and platelet-derived growth factor (PDGF)-AB are a known therapeutical target in pulmonary fibrosing diseases, e.g. IPF, but there is no targeted therapy option for pulmonary fibrosis in sarcoidosis. OBJECTIVES: The aim of our study was to determine the association of these markers' serum levels on lung function and the patients' quality of life in a long-term follow-up of sarcoidosis patients, to provide further information for finding targeted therapy options for pulmonary sarcoidosis. METHODS: 54 patients with sarcoidosis underwent blood sampling, pulmonary function testing and answered the King's Brief Interstitial Lung Disease (K-BILD) questionnaire at baseline and at three-years follow-up. Serum levels of profibrotic and angiogenic markers were assessed at baseline by enzyme-linked immunosorbent assay. RESULTS: Between 2015 and 2018, 54 patients with biopsy proven sarcoidosis were enrolled. Throughout the observation period, there was a significant decrease in the diffusion capacity for carbon monoxide (DLCO) [%] (-6.5504 ± 13,39, p = 0.001) and forced expiratory volume in one second predicted (FEV1) [%] (-6.07 ± 12.09, p = 0.001). Patients with greater impairment of forced vital capacity (FVC) did have significantly higher serum levels of VEGF (p = 0.03) and PDGF-AB (p<0.001). The K-BILD questionnaire did not change significantly during follow-up. However, patients with worsening K-BILD scores did have significantly higher serum-levels of PDGF-AB (2.67 pg/ml ± 0.93 vs. 1.88 pg/ml ± 0.60, p = 0.004) at baseline, compared to those with unchanged or increasing K-BILD scores. CONCLUSIONS: Among patients with pulmonary sarcoidosis, baseline serum levels of VEGF and PDGF-AB were associated with pulmonary function impairment. Furthermore, PDGF-AB was associated with worsening K-BILD scores. No such association was observed for FGF-2 and TGF-ß1. VEGF and PDGF-AB may be possible prognostic and therapeutic targets in sarcoidosis as a fibrosing ILD beyond IPF.

Impact of parental home smoking policies on policy choices of independently living young adults.

OBJECTIVE: To determine whether adolescents living in parental homes where smoking is banned are more likely to move into smoke-free living quarters when they leave home. METHODS: We analysed data on 693 youths from a 4-year, three-wave prospective study of a representative sample of Massachusetts adolescents (aged 12-17). All youths resided in independent living quarters at follow-up. The primary outcome was presence of a smoking ban in the living quarters at follow-up. The primary predictor was presence of a household smoking ban in the parental home, assessed 2 years before the outcome. Generalised linear mixed effects models examined the effect of a parental household smoking ban on the odds of moving into smoke-free living quarters at follow-up overall and stratified by smoking status at follow-up. RESULTS: Youths leaving home had much higher odds of moving to smoke-free living quarters if their parental household had had a smoking ban (odds ratio (OR) = 12.70, 95% CI, 6.19 to 26.04). Other independent predictors included moving into a school or college residence (OR = 3.88, 95% CI 1.87 to 8.05), and not living with smokers at follow-up (OR = 3.91, 95% CI 1.93 to 7.92). CONCLUSIONS: A household smoking ban in the parental home appears to lead youths to prefer smoke-free living quarters once they leave home.

Effect of local restaurant smoking regulations on progression to established smoking among youths.

BACKGROUND: While smoke-free restaurant laws are intended to protect the public from secondhand smoke exposure, they may also discourage smoking among adolescents. There is no evidence from longitudinal studies to test this hypothesis. OBJECTIVE: To examine the effect of local restaurant smoking regulations on progression to established smoking among adolescents. DESIGN, SETTING, AND SUBJECTS: A cohort of 2623 Massachusetts youths, ages 12-17 years at baseline, was interviewed via random digit dial telephone survey in 2001-2002 and followed up two years later. A generalised estimating equations (GEE) logistic regression analysis was used and controlled for potential individual, household, and town level confounding factors. MAIN OUTCOME MEASURE: Progression to established smoking during the two year follow up period (defined as having smoked 100 or more cigarettes in one's life). RESULTS: Compared to youths living in towns with weak regulations, those living in towns with strong regulations (complete restaurant smoking bans) had less than half the odds of progression to established smoking (odds ratio (OR) 0.39, 95% confidence interval (CI) 0.24 to 0.66). The association was stronger for youths in towns with strong regulations in effect for two or more years (OR 0.11, 95% CI 0.03 to 0.37), although it was still present for those in towns with strong regulations in effect for less than two years (OR 0.55, 95% CI 0.33 to 0.90). No relationship was found between living in a town with a medium restaurant smoking regulation (restriction of smoking to enclosed, separately ventilated areas) and rates of progression to established smoking. CONCLUSIONS: Local restaurant smoking bans may be an effective intervention to prevent youth smoking.

Disclosure of familial genetic information: perceptions of the duty to inform.

BACKGROUND: The familial implications of genetic information can lead to a conflict between a physician's duties to maintain patient confidentiality and to inform at-risk relatives about susceptibility to genetic diseases. As genes are discovered that can identify patients at risk of adverse outcomes, this conflict has become the subject of discussion and debate. METHODS: We performed a one-time telephone survey of a population-based sample of 200 Jewish women to assess knowledge and attitudes about genetic testing. Attitudes toward sharing genetic test results with family members were evaluated using three hypothetical scenarios that described an easily preventable disease, a disease (breast cancer) in which the only option for prevention was prophylactic mastectomies, and a nonpreventable disease. RESULTS: Nearly all respondents believed that a patient should inform at-risk family members when the disease was preventable (100% and 97% in the relevant scenarios), compared with only 85% who felt a duty to inform at-risk family members about a nonpreventable disease (P <0.001). The proportions of respondents who believed that physicians should seek out and inform at-risk family members against a patient's wishes was much lower: only 18% of respondents to the easily preventable disease scenario, 22% of respondents to the breast cancer scenario, and 16% of respondents to the nonpreventable disease scenario. CONCLUSIONS: Most women surveyed believed that genetic information should be shared within families, unless it violated a patient's wishes. These sorts of opinions should be considered in the debate over the confidentiality of genetic information.

The Contemplation Ladder: validation of a measure of readiness to consider smoking cessation.

Presents evidence for the validity of the Contemplation Ladder, a measure of readiness to consider smoking cessation. Analyses of data collected from more than 400 smokers at two worksites before and during a 10-month intervention indicate that Ladder scores were significantly associated with reported intention to quit, number of previous quit attempts, perceived co-worker encouragement to quit, and socioeconomic status. Ladder scores predicted subsequent participation in programs designed to educate workers about their smoking habit and its contingent risks. The Ladder did not predict biochemically validated abstinence of 24 hr or more. To assess its ability to distinguish between groups known a priori to differ in readiness, we administered the Ladder to 36 participants in a clinic-based smoking cessation program. As predicted, clinic patients scored significantly higher than the workers on the Ladder. The importance of distinguishing between smokers at the lowest stages of readiness to quit is discussed.

Debunking myths about self-quitting. Evidence from 10 prospective studies of persons who attempt to quit smoking by themselves.

This article examines data from 10 longterm prospective studies (N greater than 5,000) in relation to key issues about the self-quitting of smoking, especially those discussed by Schachter. When a single attempt to quit was evaluated, self-quitters' success rates were no better than those reported for formal treatment programs. Light smokers (20 or less cigarettes per day) were 2.2 times more likely to quit than heavy smokers. The cyclical nature of quitting was also examined. There was a moderate rate (mdn = 2.7%) of long-term quitting initiated after the early months (expected quitting window) of these studies, but also a high rate (mdn = 24%) of relapsing for persons abstinent for six months. The number of previous unsuccessful quit attempts was unrelated to success in quitting. Finally, there were few occasional smokers (slips) among successful long-term quitters. We argue that quitting smoking is a dynamic process, not a discrete event.

Adults only: the prevalence of tobacco promotions in bars and clubs in the Boston area.

OBJECTIVE: To document the nature and prevalence of tobacco promotions in bars and clubs in a major US city. DESIGN: We conducted systematic observations in a representative sample of 38 establishments in the Boston area, half of which had been advertised in a tobacco company ad. We also observed seven events in six additional clubs hosting Camel Casbah promotions. Telephone interviews were later completed with club managers. MAIN OUTCOME MEASURE: Use of branded give-away items, distribution of free cigarette samples, managers' reports of costs and benefits of hosting promotions. RESULTS: The majority of the 38 clubs were observed to use bar paraphernalia including matchbooks with tobacco brand logos, regardless of their history of appearing in tobacco sponsored ads. Free cigarette samples were not observed at any of the sampled clubs, but were a feature of every Casbah event. Managers of clubs in the advertised group were somewhat more likely to report having hosted promotions, but 44% of managers of non-advertised clubs indicated that tobacco promotions had occurred in their establishments in the past. Approximately one third of club managers viewed public links with a tobacco company as a negative feature of hosting promotions. CONCLUSIONS: Based on managers' reports, tobacco promotions occurred in more than 50% of the Boston area entertainment venues frequented by young adults. Cigarette companies should be required to inform the attorney general of plans to conduct promotions in adult-only venues to facilitate monitoring of compliance with the Master Settlement Agreement. The negative health and business consequences of hosting promotions should be communicated to bar owners.

Relation between local restaurant smoking regulations and attitudes towards the prevalence and social acceptability of smoking: a study of youths and adults who eat out predominantly at restaurants in their town.

OBJECTIVE: To examine the relation between strength of local restaurant smoking regulations and smoking related social norms among youths and adults. DESIGN: We used generalised estimating equations logistic regression analysis to examine the relation between regulation strength and youths' and adults' perceptions of adult smoking prevalence and the social acceptability of smoking in their town, while controlling for baseline anti-smoking sentiment in the town. SETTING: Each of the 351 Massachusetts towns were classified as having strong (complete smoking ban), medium (restriction of smoking to enclosed, separately ventilated areas), or weak (all others) restaurant smoking regulations. SUBJECTS: 1147 Massachusetts youths ages 12-17 years and 2116 adults who reported that they often or always eat out in their own town, drawn from a random digit dial survey. MAIN OUTCOME MEASURES: Perceived adult smoking prevalence and perceived social acceptability of smoking in restaurants, in bars, or in general. RESULTS: Compared to youths from towns with weak regulations, youths from towns with strong regulations were more likely to perceive lower adult smoking prevalence (odds ratio (OR) 1.71; 95% confidence interval (CI) 1.02 to 2.84) and social unacceptability of adult smoking (OR 2.00, 95% CI 1.29 to 3.08) in their town. Adults from towns with strong regulations were not more likely to perceive lower adult smoking prevalence, but had more than twice the odds of perceiving that smoking was unacceptable in restaurants (OR 2.19, 95% CI 1.58 to 3.02) or bars (OR 2.51, 95% CI 1.90 to 3.31). CONCLUSIONS: Strong local restaurant smoking regulations are associated with favourable smoking related social norms among youths and adults.

Effect of workplace smoking policies on smoking cessation: results of a longitudinal study.

Studies of worksite smoking bans often find that they fail to increase the rate of smoking cessation. To see whether duration of exposure to restrictive policies was an important element, we surveyed workers by phone to examine the effect of being continuously employed at a smokefree worksite for 3 years. Results showed that worksite policy was unrelated to smoking cessation. However, 12% of respondents at smokefree worksites reported that smoking had taken place in their work area, and over 20% reported at least 2 hours of worksite environmental tobacco smoke (ETS) exposure during the prior week. When minimal ETS exposure is used as an indicator of an effectively enforced smoking ban, logistic regression demonstrates that continuous employment at such a worksite strongly predicts smoking cessation. Failure to demonstrate a significant impact of worksite smoking bans on cessation in this and other studies may be due to poor enforcement of smoking policies.

The impact of organizational characteristics on smoking policy restrictions in midwestern hospitals.

Purpose. The relationship between hospitals' organizational characteristics and adoption of restrictive smoking policies was examined. Design. Self-administered questionnaires and telephone interviews were conducted prior to and following the target date for policy implementation. Setting. The Director of Regional Medical Services of a community network of hospitals requested in the summer of 1989 that the 57 member hospitals voluntarily implement a policy prohibiting all smoking in hospital buildings as of January 1, 1990. Subjects. Subjects were the 49 hospital CEOs (86%) who provided data at both time points. Intervention. The Director of Regional Medical Services made a personal request of the CEO during a routine visit at each hospital. Measures. Measures included structural aspects of the hospitals (e.g., number of employees, number of beds, presence of chemical dependency and psychiatric units); orientation toward employee health; support for smoking restrictions among various groups; and extent of CEO authority to set smoking policy. Results. Fifty-one percent of hospitals increased the restrictiveness of their smoking policy; 35% adopted a complete indoor smoking ban. Stepwise multiple regression analysis demonstrated that adoption of additional smoking restrictions was related to CEOs' and perceived board of directors' support of smoking restrictions, absence of a chemical dependency unit, and experience of financial difficulties in the previous two years. Conclusions. It is important to educate top decision makers as to the necessity of restrictive smoking policies. Barriers to smoking restrictions in organizations with chemical dependency units deserve particular attention from health promotion practitioners and researchers.

Researching and preventing alcohol problems at work: toward an integrative model.

PURPOSE OF PROPOSAL. A consolidated framework is proposed to highlight modifiable factors in work organizations that may contribute to alcohol-related problems. This research model serves to organize existing knowledge, highlight pathways for new research initiatives, and offer insights into the design of primary and secondary preventive strategies. CONTRIBUTING INFLUENCES. Current research on problem drinking in the workplace either locates problems in individual drinkers or looks to the social environment to understand how drinking problems unfold. There is a clear need for a more complete theoretical model which incorporates social, cultural, organizational, and personal factors. PROPOSAL SUMMARY. This article elaborates on a model for examining problem drinking at work which integrates policy, normative, and psychosocial influences. It emphasizes the structures within which health-related decisions and actions are contained and constrained. The focus here on the connections between alcohol use and work builds on the premise that health is socially produced.

The relationship between organizational characteristics and the adoption of workplace smoking policies.

Organizational-level variables that are hypothesized to influence the level of smoking policy restrictions and the prevalence of smoking control activities were tested in a sample of 1 14 worksites that participated in the Working Well Trial, a national trial of worksite health promotion. Predictors related to more restrictive policies included smaller size, larger percentage of white-collar workers, larger number of complaints about environmental tobacco smoke, less complexity, more formalization, and having a CEO who valued health and employees' well-being. The number of smoking control activities offered in a worksite was predicted by having a larger blue-collar workforce, a higher percentage of female employees, higher levels of workforce stability, and a CEO who valued health and employees' well-being. Efforts to identify predictors of companies' adoption and implementation of workplace-based policies and interventions are an important part of tobacco control efforts and will enhance future intervention and research efforts.

Impact of the Working Well Trial on the worksite smoking and nutrition environment.

This article reports the effect of a worksite cancer control intervention on aspects of the physical and social environment related to dietary and smoking behaviors of employees. Data are from 111 intervention and control worksites that participated in the Working Well Trial. Employee surveys and interviews with key organizational informants assessed environmental and normative changes relevant to nutrition and tobacco use. Results indicated significant effects of the intervention on all nutrition outcomes: access to healthy food, nutritional information at work, and social norms regarding dietary choice. Significant benefits were not found for smoking norms or smoking policies. However, changes occurred in both the control and intervention sites on these variables. This first large analysis of environmental and normative effects of a worksite intervention is consistent with the employee behavior change findings for the trial and serves as a model for future analyses of multilevel worksite health promotion programs.

Determinants of physicians' preferences for alternative treatments in women with early breast cancer.

To learn about factors, that influence a physician's decision making, a mail survey was conducted asking physicians about their preferences for radical mastectomy vs. local excision plus irradiation, and for adjuvant chemotherapy vs. no adjuvant treatment for two hypothetical women with operable, clinical stage I breast cancer - one 35 years old and the other 60 years old. Two hundred and sixty-one physicians from varied specialties in Connecticut and Massachusetts returned the questionnaire. Approximately half of the respondents would accept either mastectomy or limited surgery plus radiation therapy for either patient. Adjuvant chemotherapy was recommended by 97% of respondents for the younger patient and by 66% for the older patient. Several factors appeared to be related to therapeutic preferences. An individual physician's attitude towards patient involvement in decision making was the most important predictor of surgical preference for both the patients, whereas the role of specialty (i.e., surgeons vs. other providers) was more important for the surgical management of the older patient. For the decision involving adjuvant chemotherapy, specialty, hospital size, and presence of radiotherapy equipment on site were important predictors. Factors other than survival (such as disease-free interval and cosmetic results) were viewed as important standards of effectiveness by some physicians.

Impact of the Massachusetts tobacco control programme: population based trend analysis.

OBJECTIVE: To assess the impact of the Massachusetts tobacco control programme, which, since its start in January 1993, has spent over $200m-"the highest per capita expenditure for tobacco control in the world"-funded by an extra tax of 25 cents per pack of cigarettes. DESIGN: Population based trend analysis with comparison group. SUBJECTS: Adult residents of Massachusetts and other US states excluding California. MAIN OUTCOME MEASURES: Per capita consumption of cigarettes as measured by states' sales tax records; prevalence of smoking in adults as measured by several population-based telephone surveys. RESULTS: From 1988 to 1992, decline in per capita consumption of cigarettes in Massachusetts (15%) was similar to that in the comparison states (14%), corresponding to an annual decline of 3-4% for both groups. During 1992-3, consumption continued to decline by 4% in the comparison states but dropped 12% in Massachusetts in response to the tax increase. From 1993 onward, consumption in Massachusetts showed a consistent annual decline of more than 4%, whereas in the comparison states it levelled off, decreasing by less than 1% a year. From 1992, the prevalence of adult smoking in Massachusetts has declined annually by 0.43% (95% confidence interval 0.21% to 0.66%) compared with an increase of 0. 03% (-0.06% to 0.12%) in the comparison states (P<0.001). CONCLUSIONS: These findings show that a strongly implemented, comprehensive tobacco control programme can significantly reduce tobacco use.