[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.

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.

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.

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.

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.

Trends in cigar smoking and perceptions of health risks among Massachusetts adults.

OBJECTIVE: To track trends in cigar smoking and assess perceptions of cigar related health risks among Massachusetts adults. DESIGN: A random digit dial telephone survey conducted in 1993 and a subsequent monthly random digit dial survey conducted March 1995 to June 2000. PARTICIPANTS: 4733 adults who completed the 1993 survey and 14 868 adults who completed the monthly survey between 1995 and 2000. MAIN OUTCOME MEASURES: Trends in current and experimental cigar use and perceptions of health risks. RESULTS: Current cigar usage increased significantly among men aged 18-34 years between 1993 (5.8%) and 1997-98 (18.2%), but began to decrease in 1999-2000 (13.5%). Young men were much more likely than older men or women of any age to have experimented with cigars in the year before interview, but this trend appears to have decreased slightly since 1998. Young male cigar smokers were increasingly those who never smoked cigarettes. Former cigarette smokers were not smoking cigars in greater numbers. Cigar smokers were roughly three times as likely as those who do not smoke cigars to believe cigars are a safer alternative to cigarettes, and that perception did not appear to change much over time. CONCLUSION: Cigar usage increased dramatically among young men in Massachusetts in conjunction with national increases in sales and marketing of cigars, but now appears to be decreasing.

Bidi Smoking among Massachusetts Teenagers.

OBJECTIVES: This article presents the prevalence of bidi use among Massachusetts adolescents. METHODS: Questions on bidi use were included in a statewide telephone survey of a population-based sample of youth 14 to 17 years of age (N = 733). RESULTS: Past-month use rates were below 2.0% for all demographic subgroups. Minority respondents were more likely than white respondents to have ever smoked a bidi. Males and current cigarette smokers were more likely than their female and nonsmoking counterparts to have ever smoked a bidi or to have smoked one in the past year. CONCLUSIONS: The demographic distributions of bidi smoking suggest the need for monitoring bidi use trends among adolescent subgroups.

Adults' response to Massachusetts anti-tobacco television advertisements: impact of viewer and advertisement characteristics.

OBJECTIVE: To assess adults' receptivity to the Massachusetts television anti-tobacco campaign. Reactions were examined as a function of respondents' demographics, baseline tobacco control attitudes, changes in smoking status during the campaign, and advertisements' affective qualities. DESIGN: A random digit dial telephone survey in 1993 at the start of the media campaign and re-interview in 1996 of respondents to the baseline survey. PARTICIPANTS: Respondents were 1544 adults who completed the baseline and follow up interview. INTERVENTION: By the time the follow up survey was completed, approximately $49 million had been spent on the media campaign. Approximately 66 spots had been aired. MAIN OUTCOME MEASURES: Reported exposure to television advertisements; perceived effectiveness of nine specific advertisements each. RESULTS: 56% of respondents reported seeing anti-tobacco advertisements at least once a week during the preceding three years. The average effectiveness rating for all advertisements recalled on a 0-10 scale was 7.29, and did not differ by smoking status group. Advertisements eliciting strong negative emotions (sadness and fear) were rated most effective by quitters, non-smokers, and by smokers who at baseline were planning to quit soon. Humorous, entertaining advertisements were seen as ineffective by all groups. CONCLUSION: The Massachusetts anti-tobacco campaign achieved high levels of penetration into the population and was well received by both smokers and non-smokers. The results suggest that advertisements depicting suffering as a result of tobacco use may be instrumental in promoting cessation or reinforcing the decision to quit. Further research is needed to lend additional support to the link between perceived effectiveness and smoking behaviour change.

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 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.

Adult and youth response to the Massachusetts anti-tobacco television campaign.

This article is a response to DeJong and Hoffman's critique of the Massachusetts anti-tobacco television advertisements. It presents data on the recall and perceived effectiveness of the advertisements by a representative sample of adults and youth, and summarizes a previously published analysis of the impact of exposure to the advertisements on progression to regular smoking among youth. These data indicate that the campaign has achieved high levels of penetration into the population, that the advertisements are seen by the public to be effective, and that high levels of reported exposure are associated with reductions in teen smoking.

The impact of an antismoking media campaign on progression to established smoking: results of a longitudinal youth study.

OBJECTIVES: We examined the impact of a statewide antismoking media campaign on progression to established smoking among Massachusetts adolescents. METHODS: We conducted a 4-year longitudinal survey of 592 Massachusetts youths, aged 12 to 15 years at baseline in 1993. We examined the effect of baseline exposure to television, radio, and outdoor antismoking advertisements on progression to established smoking (defined as having smoked 100 or more cigarettes), using multiple logistic regression and controlling for age; sex; race; baseline smoking status; smoking by parents, friends, and siblings; television viewing; and exposure to antismoking messages not related to the media campaign. RESULTS: Among younger adolescents (aged 12 to 13 years at baseline), those reporting baseline exposure to television antismoking advertisements were significantly less likely to progress to established smoking (odds ratio = 0.49, 95% confidence interval = 0.26, 0.93). Exposure to television antismoking advertisements had no effect on progression to established smoking among older adolescents (aged 14 to 15 years at baseline), and there were no effects of exposure to radio or outdoor advertisements. CONCLUSIONS: These results suggest that the television component of the Massachusetts antismoking media campaign may have reduced the rate of progression to established smoking among young adolescents.

Tobacco marketing and adolescent smoking: more support for a causal inference.

OBJECTIVES: This prospective study examined the effect of tobacco marketing on progression to established smoking. METHODS: Massachusetts adolescents (n = 529) who at baseline had smoked no more than 1 cigarette were reinterviewed by telephone in 1997. Analyses examined the effect of receptivity to tobacco marketing at baseline on progression to established smoking, controlling for significant covariates. RESULTS: Adolescents who, at baseline, owned a tobacco promotional item and named a brand whose advertisements attracted their attention were more than twice as likely to become established smokers (odds ratio = 2.70) than adolescents who did neither. CONCLUSIONS: Participation in tobacco marketing often precedes, and is likely to facilitate, progression to established smoking. Hence, restrictions on tobacco marketing and promotion could reduce addiction to tobacco.

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.