Development and external validation of a head and neck cancer risk prediction model.

BACKGROUND: Head and neck cancer (HNC) incidence is on the rise, often diagnosed at late stage and associated with poor prognoses. Risk prediction tools have a potential role in prevention and early detection. METHODS: The IARC-ARCAGE European case-control study was used as the model development dataset. A clinical HNC risk prediction model using behavioral and demographic predictors was developed via multivariable logistic regression analyses. The model was then externally validated in the UK Biobank cohort. Model performance was tested using discrimination and calibration metrics. RESULTS: 1926 HNC cases and 2043 controls were used for the development of the model. The development dataset model including sociodemographic, smoking, and alcohol variables had moderate discrimination, with an area under curve (AUC) value of 0.75 (95% CI, 0.74-0.77); the calibration slope (0.75) and tests were suggestive of good calibration. 384 616 UK Biobank participants (with 1177 HNC cases) were available for external validation of the model. Upon external validation, the model had an AUC of 0.62 (95% CI, 0.61-0.64). CONCLUSION: We developed and externally validated a HNC risk prediction model using the ARCAGE and UK Biobank studies, respectively. This model had moderate performance in the development population and acceptable performance in the validation dataset. Demographics and risk behaviors are strong predictors of HNC, and this model may be a helpful tool in primary dental care settings to promote prevention and determine recall intervals for dental examination. Future addition of HPV serology or genetic factors could further enhance individual risk prediction.

Risk prediction models for head and neck cancer: A rapid review.

Background: Cancer risk assessment models are used to support prevention and early detection. However, few models have been developed for head and neck cancer (HNC). Methods: A rapid review of Embase and MEDLINE identified n = 3045 articles. Following dual screening, n = 14 studies were included. Quality appraisal using the PROBAST (risk of bias) instrument was conducted, and a narrative synthesis was performed to identify the best performing models in terms of risk factors and designs. Results: Six of the 14 models were assessed as "high" quality. Of these, three had high predictive performance achieving area under curve values over 0.8 (0.87-0.89). The common features of these models were their inclusion of predictors carefully tailored to the target population/anatomical subsite and development with external validation. Conclusions: Some existing models do possess the potential to identify and stratify those at risk of HNC but there is scope for improvement.

Head and neck cancer in the UK: what was the stage before COVID-19? UK cancer registries analysis (2011-2018).

Introduction People who present with more advanced stage head and neck cancer (HNC) are associated with poorer outcomes and survival. The burden and trends of advanced stage HNC are not fully known at the population level. The UK national cancer registries routinely collect data on HNC diagnoses.Aims To describe trends in stage of diagnosis of HNCs across the UK before the COVID-19 pandemic.Methods Aggregated HNC incidence data were requested from the national cancer registries of the four UK countries for the ten most recent years of available data by subsite and American Joint Commission on Cancer stage at diagnosis classification. Additionally, data for Scotland were available by age group, sex and area-based socioeconomic deprivation category.Results Across the UK, rates of advanced stage HNC had increased, with 59% of patients having advanced disease at diagnosis from 2016-2018. England had a lower proportion of advanced disease (58%) than Scotland, Wales or Northern Ireland (65-69%) where stage data were available. The completeness of stage data had improved over recent years (87% by 2018).Conclusion Prior to the COVID-19 pandemic, diagnoses of HNC at an advanced stage comprised the majority of HNCs in the UK, representing the major challenge for the cancer healthcare system.

Cancer mortality 1981-2016 and contribution of specific cancers to current socioeconomic inequalities in all cancer mortality: A population-based study.

BACKGROUND: In many high-income countries cancer mortality rates have declined, however, socioeconomic inequalities in cancer mortality have widened over time with those in the most deprived areas bearing the greatest burden. Less is known about the contribution of specific cancers to inequalities in total cancer mortality. METHODS: Using high-quality routinely collected population and mortality records we examine long-term trends in cancer mortality rates in Scotland by age group, sex, and area deprivation. We use the decomposed slope and relative indices of inequality to identify the specific cancers that contribute most to absolute and relative inequalities, respectively, in total cancer mortality. RESULTS: Cancer mortality rates fell by 24 % for males and 10 % for females over the last 35 years; declining across all age groups except females aged 75+ where rates rose by 14 %. Lung cancer remains the most common cause of cancer death. Mortality rates of lung cancer have more than halved for males since 1981, while rates among females have almost doubled over the same period. CONCLUSION: Current relative inequalities in total cancer mortality are dominated by inequalities in lung cancer mortality, but with contributions from other cancer sites including liver, and head and neck (males); and breast (females), stomach and cervical (younger females). An understanding of which cancer sites contribute most to inequalities in total cancer mortality is crucial for improving cancer health and care, and for reducing preventable cancer deaths.

Occupational socioeconomic risk associations for head and neck cancer in Europe and South America: individual participant data analysis of pooled case-control studies within the INHANCE Consortium.

BACKGROUND: The association between socioeconomic disadvantage (low education and/or income) and head and neck cancer is well established, with smoking and alcohol consumption explaining up to three-quarters of the risk. We aimed to investigate the nature of and explanations for head and neck cancer risk associated with occupational socioeconomic prestige (a perceptual measure of psychosocial status), occupational socioeconomic position and manual-work experience, and to assess the potential explanatory role of occupational exposures. METHODS: Pooled analysis included 5818 patients with head and neck cancer (and 7326 control participants) from five studies in Europe and South America. Lifetime job histories were coded to: (1) occupational social prestige-Treiman's Standard International Occupational Prestige Scale (SIOPS); (2) occupational socioeconomic position-International Socio-Economic Index (ISEI); and (3) manual/non-manual jobs. RESULTS: For the longest held job, adjusting for smoking, alcohol and nature of occupation, increased head and neck cancer risk estimates were observed for low SIOPS OR=1.88 (95% CI: 1.64 to 2.17), low ISEI OR=1.74 (95% CI: 1.51 to 1.99) and manual occupations OR=1.49 (95% CI: 1.35 to 1.64). Following mutual adjustment by socioeconomic exposures, risk associated with low SIOPS remained OR=1.59 (95% CI: 1.30 to 1.94). CONCLUSIONS: These findings indicate that low occupational socioeconomic prestige, position and manual work are associated with head and neck cancer, and such risks are only partly explained by smoking, alcohol and occupational exposures. Perceptual occupational psychosocial status (SIOPS) appears to be the strongest socioeconomic factor, relative to socioeconomic position and manual/non-manual work.

Inequality in survival of people with head and neck cancer: Head and Neck 5000 cohort study.

BACKGROUND: Explanations for socioeconomic inequalities in survival of head and neck cancer (HNC) patients have had limited attention and are not well understood. METHODS: The UK Head and Neck 5000 prospective clinical cohort study was analyzed. Survival relating to measures of socioeconomic status was explored including area-based and individual factors. Three-year overall survival was determined using the Kaplan-Meier method. All-cause mortality was investigated via adjusted Cox Proportional Hazard models. RESULTS: A total of 3440 people were included. Three-year overall survival was 76.3% (95% CI 74.9, 77.7). Inequality in survival by deprivation category, highest education level, and financial concerns was explained by age, sex, health, and behavioral factors. None of the potential explanatory factors fully explained the inequality associated with annual household income or the proportion of income of benefits. CONCLUSION: These results support the interventions to address the financial issues within the wider care and support provided to HNC patients.

Determinants of long-term survival in a population-based cohort study of patients with head and neck cancer from Scotland.

BACKGROUND: We investigated long-term survival from head and neck cancer (HNC) using different survival approaches. METHODS: Patients were followed-up from the Scottish Audit of Head and Neck Cancer. Overall survival and disease-specific survival were calculated using the Kaplan-Meier method. Net survival was calculated by the Pohar-Perme method. Mutually adjusted Cox proportional hazards models were used to determine the predictors of survival. RESULTS: A total of 1820 patients were included in the analyses. Overall survival at 12 years was 26.3% (24.3%, 28.3%). Disease-specific survival at 12 years was 56.9% (54.3%, 59.4%). Net survival at 12 years was 41.4% (37.6%, 45.1%). CONCLUSION: Determinants associated with long-term survival included age, stage, treatment modality, WHO performance status, alcohol consumption, smoking behavior, and anatomical site. We recommend that net survival is used for long-term outcomes for HNC patients-it disentangles other causes of death, which are overestimated in overall survival and underestimated in disease-specific survival.

Trends of oral cavity, oropharyngeal and laryngeal cancer incidence in Scotland (1975-2012) - A socioeconomic perspective.

AIM: To examine current incidence trends (1975-2012) of oral cavity (OCC), oropharyngeal (OPC) and laryngeal cancer in Scotland by socioeconomic status (SES). METHODS: We included all diagnosed cases of OCC (C00.3-C00.9, C02-C06 excluding C2.4), OPC (C01, C2.4, C09-C10, C14) and laryngeal cancer (C32) on the Scottish Cancer Registry (1975-2012) and annual midterm population estimates by age, sex, geographic region and SES indices (Carstairs 1991 and Scottish Index of Multiple Deprivation 2009). Age-standardized incidence rates were computed and adjusted Poisson regression rate-ratios (RR) compared subsites by age, sex, region, SES and year of diagnosis. RESULTS: We found 28,217 individuals (19,755 males and 8462 females) diagnosed with head and neck cancer (HNC) over the study period. Between 1975 and 2012, relative to the least deprived areas, those living in the most deprived areas exhibited the highest RR (>double) of OCC, OPC and laryngeal cancer, and an almost dose-like response was observed between SES and HNC incidence. Between 2001 and 2012, this socioeconomic inequality tended to increase over time for OPC and laryngeal cancer but remained relatively unchanged for OCC. Incidence rates increased markedly for OPC, decreased for laryngeal cancer and remained stable for OCC, particularly in the last decade. Males exhibited significantly higher RRs compared to females, and the peak age of incidence of OPC was slightly lower than the other subsites. CONCLUSION: Contrary to reports that OPC exhibits an inverse socioeconomic profile, Scotland country-level data show that those from the most deprived areas consistently have the highest rates of head and neck cancers.

Estimating and explaining the effect of education and income on head and neck cancer risk: INHANCE consortium pooled analysis of 31 case-control studies from 27 countries.

Low socioeconomic status has been reported to be associated with head and neck cancer risk. However, previous studies have been too small to examine the associations by cancer subsite, age, sex, global region and calendar time and to explain the association in terms of behavioral risk factors. Individual participant data of 23,964 cases with head and neck cancer and 31,954 controls from 31 studies in 27 countries pooled with random effects models. Overall, low education was associated with an increased risk of head and neck cancer (OR = 2.50; 95% CI = 2.02 - 3.09). Overall one-third of the increased risk was not explained by differences in the distribution of cigarette smoking and alcohol behaviors; and it remained elevated among never users of tobacco and nondrinkers (OR = 1.61; 95% CI = 1.13 - 2.31). More of the estimated education effect was not explained by cigarette smoking and alcohol behaviors: in women than in men, in older than younger groups, in the oropharynx than in other sites, in South/Central America than in Europe/North America and was strongest in countries with greater income inequality. Similar findings were observed for the estimated effect of low versus high household income. The lowest levels of income and educational attainment were associated with more than 2-fold increased risk of head and neck cancer, which is not entirely explained by differences in the distributions of behavioral risk factors for these cancers and which varies across cancer sites, sexes, countries and country income inequality levels.

Oral health, dental care and mouthwash associated with upper aerodigestive tract cancer risk in Europe: the ARCAGE study.

OBJECTIVE: We aimed to assess the association of oral health (OH), dental care (DC) and mouthwash with upper-aerodigestive tract (UADT) cancer risk, and to examine the extent that enzymes involved in the metabolism of alcohol modify the effect of mouthwash. MATERIALS AND METHODS: The study included 1963 patients with incident cancer of the oral cavity, oropharynx, hypopharynx, larynx or esophagus and 1993 controls. Subjects were interviewed about their oral health and dental care behaviors (which were converted to scores of OH and DC respectively), as well as smoking, alcohol drinking, diet, occupations, medical conditions and socio-economic status. Blood samples were taken for genetic analyses. Mouthwash use was analyzed in relation to the presence of polymorphisms of alcohol-metabolizing genes known to be associated with UADT. Adjusted odds ratios (ORs) and 95%-confidence intervals [CI] were estimated with multiple logistic regression models adjusting for multiple confounders. RESULTS: Fully adjusted ORs of low versus high scores of DC and OH were 2.36[CI=1.51-3.67] and 2.22[CI=1.45-3.41], respectively, for all UADT sites combined. The OR for frequent use of mouthwash use (3 or more times/day) was 3.23[CI=1.68-6.19]. The OR for the rare variant ADH7 (coding for fast ethanol metabolism) was lower in mouthwash-users (OR=0.53[CI=0.35-0.81]) as compared to never-users (OR=0.97[CI=0.73-1.29]) indicating effect modification (pheterogeneity=0.065) while no relevant differences were observed between users and non-users for the variant alleles of ADH1B, ADH1C or ALDH2. CONCLUSIONS: Poor OH and DC seem to be independent risk factors for UADT because corresponding risk estimates remain substantially elevated after detailed adjustment for multiple confounders. Whether mouthwash use may entail some risk through the alcohol content in most formulations on the market remains to be fully clarified.

Association between socioeconomic factors and cancer risk: a population cohort study in Scotland (1991-2006).

BACKGROUND: Lung and upper aero-digestive tract (UADT) cancer risk are associated with low socioeconomic circumstances and routinely measured using area socioeconomic indices. We investigated effect of country of birth, marital status, one area deprivation measure and individual socioeconomic variables (economic activity, education, occupational social class, car ownership, household tenure) on risk associated with lung, UADT and all cancer combined (excluding non melanoma skin cancer). METHODS: We linked Scottish Longitudinal Study and Scottish Cancer Registry to follow 203,658 cohort members aged 15+ years from 1991-2006. Relative risks (RR) were calculated using Poisson regression models by sex offset for person-years of follow-up. RESULTS: 21,832 first primary tumours (including 3,505 lung, 1,206 UADT) were diagnosed. Regardless of cancer, economically inactivity (versus activity) was associated with increased risk (male: RR 1.14, 95% CI 1.10-1.18; female: RR 1.06, 95% CI 1.02-1.11). For lung cancer, area deprivation remained significant after full adjustment suggesting the area deprivation cannot be fully explained by individual variables. No or non degree qualification (versus degree) was associated with increased lung risk; likewise for UADT risk (females only). Occupational social class associations were most pronounced and elevated for UADT risk. No car access (versus ownership) was associated with increased risk (excluding all cancer risk, males). Renting (versus home ownership) was associated with increased lung cancer risk, UADT cancer risk (males only) and all cancer risk (females only). Regardless of cancer group, elevated risk was associated with no education and living in deprived areas. CONCLUSIONS: Different and independent socioeconomic variables are inversely associated with different cancer risks in both sexes; no one socioeconomic variable captures all aspects of socioeconomic circumstances or life course. Association of multiple socioeconomic variables is likely to reflect the complexity and multifaceted nature of deprivation as well as the various roles of these dimensions over the life course.

Facial injuries in Scotland 2001-2009: epidemiological and sociodemographic determinants.

To our knowledge, sociodemographic determinants of facial injuries in children have not previously been reported in Scotland. We analysed the pattern, time trends, and key sociodemographic determinants of facial injuries in children and adolescents using Scottish morbidity records for inpatient care (2001-2009) which were retrieved from the Information Services Division of National Health Services (NHS) Scotland. We calculated annual incidences by age, sex, health board, Scottish Index of Multiple Deprivation (SIMD), and mechanism of injury. A Poisson regression analysis model was used to incorporate the variables. A total of 45388 patients aged from birth to 17 years sustained a facial injury (4.7/1000 population over nine years); 60% (27101) of injuries were unintentional, 15% (6726) resulted from motor vehicle accidents, and 9% (4149) resulted from alleged assaults; 5% (2058) were alcohol related. The incidence decreased over time from 5.5/1000 in 2001 to 4.0/1000 in 2009. The rate ratio for boys was 1.94 times greater than for girls (p<0.001), and it varied significantly between health board areas (0.68 in Dumfries and Galloway and 1.76 in Grampian) (p<0.001). There was a significant association between facial injury and increasing deprivation (p<0.001). The incidence of facial injury is highest among boys living in areas of high socioeconomic deprivation so education and resources should be directed towards prevention in these areas.

Socioeconomic inequalities in incidence of lung and upper aero-digestive tract cancer by age, tumour subtype and sex: a population-based study in Scotland (2000-2007).

BACKGROUND: Lung and upper aero-digestive tract (UADT) cancer risk is associated with socioeconomic inequality (SEI) but the degree of socioeconomic burden by age, tumour subtype, and sex is not known. METHODS: We reviewed 216,305 cases excluding non melanoma skin cancer (All Cancer) comprising 37,274 lung; 8216 head and neck; and 6534 oesophageal cancers from 2000 to 2007 classified into anatomical or morphology subtypes. Deprivation was measured using the Scottish Index of Multiple Deprivation and SEI was measured using the Slope Index of Inequality and the Relative Index of Inequality (RII). Analyses were partitioned by 5-year age group and sex. RII was adapted to rank tumour type contribution to All Cancer SEI and to examine subtype by age and sex simultaneously. Rank was defined as proportion of All Cancer SEI. RESULTS: All Cancer SEI was greater for males (RII=0.366; female RII=0.279); the combination of lung and UADT SEI contributed 91% and 81% respectively to All Cancer SEI. For both sexes lung and UADT subtypes showed significant SEI (P<0.001) except oesophageal adenocarcinoma in males (P=0.193); for females, SEI was borderline significant (P=0.048). Although RII rank differed by sex, all lung and larynx subtypes contributed most to All Cancer SEI with RII rank for oral cavity, oesophagus-squamous cell, and oropharynx following. For males 40-44 years, SEI increased abruptly peaking at 55-59 years. For females, SEI gradually peaked 10 years later. In both sexes, the SEI peak preceded peak incidence. CONCLUSION: SEI in lung and UADT cancers vary greatly by age, tumour subtype and sex; these variations are likely to largely reflect differences between the sexes in risk behaviours which vary by birth cohort and are socioeconomically patterned.

Components of socioeconomic risk associated with head and neck cancer: a population-based case-control study in Scotland.

The complex associations between socioeconomic circumstances and risk for head and neck cancer are under-explored. We investigated components of social class and their relative influence on the risk of head and neck cancers by studying 103 patients (age range 24-80 years) who had been diagnosed with cancer of the head and neck between April 2002 and December 2004, and 91 controls who were randomly selected from general practitioners' lists. Information about occupation, education, smoking, and alcohol consumption was collected at personal interview. Socioeconomic circumstances were measured at an individual level (education, occupational social class, unemployment), and by area-based measures of deprivation. Odds ratios (OR) and 95% confidence intervals (CI) were computed using unconditional logistic regression and multivariate analyses. People living in the most deprived areas (OR=4.66, 95% CI 1.79-12.18); and those who were unemployed (OR=2.27, 95% CI 1.21-4.26) had a significantly higher risk of cancer than those with high levels of educational attainment (OR=0.17, 95% CI 0.05-0.58). Significance was lost for all measures of social class when adjustments were made for smoking and consumption of alcohol. Smoking was the only significant risk factor (OR=15.53, 95% CI 5.36-44.99) in the multivariate analysis. A high risk of head and neck cancer was consistently associated with poor socioeconomic circumstances, and there were strong links for specific components however smoking dominated the overall profile of risk. We propose a framework for future socioeconomic analyses.

Socioeconomic factors influence selection and participation in a population-based case-control study of head and neck cancer in Scotland.

OBJECTIVE: We aimed to investigate the association between socioeconomic factors and selection and participation biases in a population-based case-control study of head and neck cancer conducted in the city of Glasgow, UK. METHODS: General Practices (GP) of the case subjects were the sampling frame from which age and sex-matched controls were randomly selected. Participant and nonparticipant postcodes of cases and controls were linked to the area-based Scottish Index of Multiple Deprivation. Comparisons of study selection and participation were made with the Glasgow study-base population. RESULTS: Cases were from significantly more deprived areas than controls. Overall, participation was low for both cases (34.9%) and controls (34.7%). Our overall control sample was not similar to the general population of Glasgow having "over selected" from deprived areas. Individuals from more affluent areas were more likely to participate providing a set of interviewed participants reflecting the socioeconomic distribution of Glasgow. CONCLUSIONS: Low participation rates in case-control studies remain a problem and socioeconomic factors strongly affect participation. A control sample selection biased in one direction was offset by participation bias in the opposite direction -- fortuitously providing a representative control sample. Selecting controls from case GP lists needs to be implemented with care with attention paid to obtaining evidence on the underlying socioeconomic characteristics of GP populations, especially for diseases with a skewed socioeconomic distribution.

Comparative study of modified release alpha-blocker exposure in elderly patients with fractures.

PURPOSE: Standard formulation alpha-blocker use has been associated with an increased risk of hypotension-related adverse events, particularly with cardiovascular indications and on treatment initiation. We investigated the association between those fractures that are commonly due to falls and modified-release doxasozin exposure. METHODS: A case-control study using UK primary care records (the THIN database) showed that 6540 cases aged 50 years or older had a record of first fracture of the hip/femur, humerus or wrist after May 2001; 26 495 controls had no fracture and were matched on practice, year of birth and sex. Exclusions for the primary analysis were previous benign prostatic hypertrophy (BPH), lower urinary tract symptoms (LUTS) or prostate cancer, major trauma at the time of the case's fracture, or a history of falls. Conditional logistic regression estimated the association between modified-release doxasozin treatment and the occurrence of fractures. RESULTS: No increased risk of fractures was associated with current use of modified-release doxasozin, adjusted odds ratios (ORs) 0.90 (95%CI 0.68, 1.19); previous use, adjusted OR 0.92 (95%CI 0.73, 1.16) or the start of a treatment episode (

Effects of smoking cessation on lung function and airway inflammation in smokers with asthma.

RATIONALE: Active smoking in asthma is associated with worsening of symptoms, accelerated decline in lung function, and impaired response to corticosteroids. OBJECTIVES: To examine the short-term effects of smoking cessation on lung function, airway inflammation, and corticosteroid responsiveness in smokers with asthma. METHODS AND MEASUREMENTS: Smokers with asthma were given the option to quit or continue smoking. Both groups underwent spirometry and induced sputum at baseline and at 1, 3, and 6 wk. Cutaneous vasoconstrictor response to topical beclometasone, airway response to oral prednisolone, and sensitivity of peripheral blood lymphocytes to corticosteroids were measured before smoking cessation and at 6 wk. MAIN RESULTS: Of 32 subjects recruited, 11 opted to continue smoking (smoking control group). Of 21 subjects who opted for smoking cessation, 10 quit smoking for 6 wk (quit group). In the comparison of quitters with smokers at 6 wk, the mean (confidence interval [CI]) difference in FEV(1) was 407 ml (21, 793), p = 0.040, and the proportion of sputum neutrophils was reduced by 29 (51, 8), p = 0.039. Total cutaneous vasoconstrictor response score to topical beclometasone improved after smoking cessation with a mean (CI) difference of 3.56 (0.84, 6.28), p = 0.042, between quitters and smokers. There was no change in airway corticosteroid responses after smoking cessation. CONCLUSIONS: By 6 wk after smoking cessation, subjects who quit smoking had achieved considerable improvement in lung function and a fall in sputum neutrophil count compared with subjects who continued to smoke. These findings highlight the importance of smoking cessation in asthma.

Effect of inhaled corticosteroids on symptom severity and sputum mediator levels in chronic persistent cough.

BACKGROUND: Chronic cough often lasts for more than 1 year and is associated with airway inflammation. The effect of inhaled corticosteroids on symptom severity and inflammatory mediator levels in these patients is unknown. OBJECTIVE: We sought to determine whether inhaled corticosteroids reduce cough severity and sputum mediator concentrations in patients with chronic persistent cough. METHODS: We performed a double-blind, randomized, placebo-controlled crossover study with inhaled fluticasone, 500 microg twice daily, and placebo for 14 days in 88 patients with cough for more than 1 year, with normal chest radiography and spirometry results. Outcome measures were a daily cough visual analogue scale and induced sputum concentrations of eosinophilic cationic protein (ECP), myeloperoxidase, leukotriene B(4) (LTB(4)), leukotrienes C(4)/D(4)/E(4) (cysteinyl leukotrienes [Cys-LTs]), prostaglandin E(2) (PGE(2)), IL-8, and TNF-alpha. Sputum cell counts, exhaled nitric oxide levels, and carbon monoxide levels were also measured. RESULTS: There was a significant improvement in the cough visual analogue scale after inhaled fluticasone compared with placebo (mean difference, 1.0; 95% CI, 0.4-1.5; P <.001). LTB(4), Cys-LT, and PGE(2) levels were increased in all causes of cough. Sputum ECP counts, exhaled nitric oxide levels, and carbon monoxide levels decreased significantly after inhaled fluticasone. There was no change in sputum cell counts and other mediator concentrations. CONCLUSION: Cough severity and sputum ECP levels are modestly reduced by inhaled corticosteroids in patients with chronic cough persisting for more than 1 year. LTB(4), Cys-LT, PGE(2), IL-8, myeloperoxidase, and TNF-alpha levels are unaltered by this therapy. This raises the possibility that drugs targeted to reduce the effects of these mediators might be of benefit in chronic persistent cough.

Interleukin-6, fibrin D-dimer, and coagulation factors VII and XIIa in prediction of coronary heart disease.

OBJECTIVE: Activated inflammation and activated blood coagulation are believed to increase the risk of coronary thrombosis and are related. We therefore compared plasma IL-6 (a key cytokine in the inflammatory process), fibrin D-dimer (a marker of fibrin turnover), and coagulation factors VII and XIIa (initiators of extrinsic and intrinsic blood coagulation, respectively) as predictors of coronary risk in the West of Scotland Coronary Prevention Study of pravastatin in men with hypercholesterolemia. METHODS AND RESULTS: 485 men who had had a coronary event (nonfatal myocardial infarction, death from coronary heart disease, or revascularization) were matched for age and smoking status with 934 controls. Baseline IL-6 and D-dimer were strong univariate predictors of coronary risk (relative risk in the highest quintile approximately twice that in the lowest quintile) and were associated with each other and with C-reactive protein. On multivariate analyses, D-dimer retained a significant association with coronary risk (relative risk, 1.86; 95% CI, 1.24 to 2.80), whereas IL-6 (1.47; 0.95 to 2.28) and C-reactive protein (1.33; 0.85 to 2.08) did not. Neither factor VII nor factor XIIa antigens were predictors of coronary events. CONCLUSIONS: Fibrin D-dimer may be a stronger predictor of coronary risk than inflammatory markers, perhaps through its ability to stimulate monocyte release of IL-6.