Biological responses of midge (Chironomus riparius) and lamprey (Lampetra fluviatilis) larvae in ecotoxicity assessment of PCDD/F-, PCB- and Hg-contaminated river sediments.

We evaluated the utility of chironomid and lamprey larval responses in ecotoxicity assessment of polychlorinated dibenzo-p-dioxins, dibenzofurans (PCDD/F)-, polychlorinated biphenyls (PCB)- and mercury (Hg)-contaminated river sediments. Sediment samples were collected from the River Kymijoki with a known industrial pollution gradient. Sediment for the controls and lamprey larvae were obtained from an uncontaminated river nearby. Contamination levels were verified with sediment and tissue PCDD/F, PCB and Hg analyses. Behaviour of sediment-exposed chironomid and lamprey larvae were measured with Multispecies Freshwater Biomonitor© utilizing quadrupole impedance conversion technique. In addition, mortality, growth and head capsule deformity incidence of chironomids were used as ecotoxicity indicators. WHOPCDD/F+PCB-TEQ in the R. Kymijoki sediments ranged from the highest upstream 22.36 ng g(-1) dw to the lowest 1.50 ng g(-1) near the river mouth. The sum of PCDD/Fs and PCBs correlated strongly with Hg sediment concentrations, which ranged from <0.01 to 1.15 µg g(-1). Lamprey tissue concentrations of PCDD/Fs were two orders and PCBs one order of magnitude higher in the R. Kymijoki compared to the reference. Chironomid growth decreased in contaminated sediments and was negatively related to sediment ∑PCDD/Fs, WHOPCDD/F+PCB-TEQ and Hg. There were no significant differences in larval mortality or chironomid mentum deformity incidence between the sediment exposures. The distinct behavioural patterns of both species indicate overall applicability of behavioural MFB measurements of these species in sediment toxicity bioassays. Chironomids spent less and lampreys more time in locomotion in the most contaminated sediment compared to the reference, albeit statistically significant differences were not detected. Lamprey larvae had also a greater activity range in some of the contaminated sediments than in the reference. High pollutant levels in lamprey indicate risks for biomagnification in the food webs, with potential health risks to humans consuming fish.

Impact of physicians' adherence to treat-to-target strategy on outcomes in early rheumatoid arthritis in the NEO-RACo trial.

OBJECTIVES: It is well recognized that medication adherence of rheumatoid arthritis (RA) patients is often poor. As less attention has been paid to physicians' adherence to targeted treatment, we aimed to investigate how it affects outcomes in aggressively treated early RA patients. METHOD: In the new Finnish RA Combination Therapy (NEO-RACo) trial, 99 patients with early active RA were treated, targeting remission, with a combination of methotrexate, sulfasalazine, hydroxychloroquine, and low-dose prednisolone for 2 years, and randomized to receive infliximab or placebo for the initial 6 months. After 2 years, therapy was unrestricted while remission was still targeted. Patients were divided into tertiles by physicians' adherence to treat-to-target, which was evaluated with a scoring system during the initial 2 years. After 5 years of follow-up, the between-tertile differences in remission rates, 28-joint Disease Activity Score (DAS28) levels, radiological changes, cumulative days off work, and the use of anti-rheumatic medication were assessed. RESULTS: Follow-up data were available for 93 patients. Physicians' good adherence was associated with improved remission rates at 2-4 years and lower DAS28 levels throughout the follow-up. In a multivariable model, physicians' adherence was the most important predictor of remission at 3 months and 2 years (p < 0.001 for both). Between 2 and 5 years, biologics were used more often in the tertile of low adherence compared with the other two groups (p = 0.024). No significant differences were observed in radiological progression and cumulative days off work. CONCLUSIONS: Physicians' good adherence is associated with improved remission rates and lesser use of biologics in early RA.

Pollutant concentrations in placenta.

Unborn children are exposed to environmental pollutants via the placenta, and there is a causal relationship between maternal intake of pollutants and fetal exposure. Placental examination is an effective way for acquiring data for estimating fetal exposure. We analyzed the concentrations of 104 congeners of persistent organic pollutants, seven organotin compounds, five heavy metals, and methylmercury in 130 randomly selected placentas. Additionally, we examined similarities between pollutant concentrations by analyzing correlations between their placental concentrations. Our results yield new information for conducting contaminant risk assessments for the prenatal period. Out of the 117 individual persistent organic pollutants or metals assayed, 46 could be detected in more than half of the placentas. Moreover, dichlorodiphenyldichloroethylene (p,p'-DDE) was found in all placentas. The data indicates that fetal exposure to dioxins and furans (PCDD/Fs), polychlorinated biphenyls (PCBs), p,p'-DDE, and methylmercury depends on the mother's parity, and age. We also conclude that sources of the above four pollutants are similar but differ from the sources of polybrominated diphenyl ethers.

Effects of docosahexaenoic acid and methylmercury on child's brain development due to consumption of fish by Finnish mother during pregnancy: a probabilistic modeling approach.

Fish contains both beneficial substances e.g. docosahexaenoic acids but also harmful compounds e.g. methylmercury. Importantly, the health effects caused by these two substances can be evaluated in one common end point, intelligence quotient (IQ), providing a more transparent analysis. We estimated health effects of maternal fish consumption on child's central nervous system by creating a model with three alternative maternal fish consumption scenarios (lean fish, fatty fish, and current fish consumption). Additionally, we analyzed impacts of both regular fish consumption and extreme fish consumption habits. At the individual level, the simulated net effects were small, encompassing a range of one IQ point in all scenarios. Fatty fish consumption, however, clearly generated a beneficial net IQ effect, and lean fish consumption evoked an adverse net IQ effect. In view of the current fish consumption pattern of Finnish mothers the benefits and risks seem to more or less compensate each other. This study clearly shows the significance of which fish species are consumed during pregnancy and lactation, and the results can be generalized to apply to typical western population fish consumption habits.

Renal safety of initial combination versus single DMARD therapy in patients with early rheumatoid arthritis: an 11-year experience from the FIN-RACo Trial.

OBJECTIVE: To evaluate the renal safety of traditional disease-modifying antirheumatic drugs (DMARDs) in early rheumatoid arthritis (RA). METHODS: One hundred and ninety-five DMARD-naïve patients with recent-onset RA were randomised to receive combination DMARD therapy (n=97) starting with sulfasalazine, methotrexate, hydroxychloroquine, and prednisolone (COMBI) or monotherapy (n=98), initially with sulfasalazine, with or without prednisolone (SINGLE). After two years, the choice and dosing of DMARDs and prednisolone were not restricted, but the treatment was still targeted to achieve or maintain remission. Urinalysis, serum creatinine and glomerular filtration rate (GFR; estimated according to the Cockcroft-Gault formula [eGFRCG]) were analysed at baseline and at months 6, 9, 12, 18, 24 and thereafter yearly up to 11 years. RESULTS: The cumulative incidence of repeated (>or=3 times) abnormal renal findings during the 11-year follow-up period were as follows (COMBI versus SINGLE; p-values adjusted for age and sex): proteinuria (dipstick positive) 4.8% (95%CI 1.8-12.2) vs. 5.3% (95%CI 2.0-13.7, p=0.93), haematuria (dipstick positive) 14.1% (95%CI 8.0-24.2) vs. 22.1 % (95%CI 14.5-33.0, p=0.14), raised serum creatinine (>or=100 micromol/l in females and >or=115 micromol/l in males) 4.4% (95%CI 1.7-11.4) vs. 6.7% (3.0-14.3, p=0.87) and eGFRGC<60 ml/min/1.73 m2 11.9% (95%CI 6.8-20.5) vs. 10.5% (95%CI 5.8-18.7, p=0.85). CONCLUSION: Initial remission targeted therapy with the FIN-RACo DMARD combination in early RA is safe for kidneys and does not induce more short- or long-term renal complications compared to traditional therapy with a single DMARD.

DNA copy number loss and allelic imbalance at 2p16 in lung cancer associated with asbestos exposure.

Five to seven percent of lung tumours are estimated to occur because of occupational asbestos exposure. Using cDNA microarrays, we have earlier detected asbestos exposure-related genomic regions in lung cancer. The region at 2p was one of those that differed most between asbestos-exposed and non-exposed patients. Now, we evaluated genomic alterations at 2p22.1-p16.1 as a possible marker for asbestos exposure. Lung tumours from 205 patients with pulmonary asbestos fibre counts from 0 to 570 million fibres per gram of dry lung, were studied by fluorescence in situ hybridisation (FISH) for DNA copy number alterations (CNA). The prevalence of loss at 2p16, shown by three different FISH probes, was significantly increased in lung tumours of asbestos-exposed patients compared with non-exposed (P=0.05). In addition, a low copy number loss at 2p16 associated significantly with high-level asbestos exposure (P=0.02). Furthermore, 27 of the tumours were studied for allelic imbalances (AI) at 2p22.1-p16.1 using 14 microsatellite markers and also AI at 2p16 was related to asbestos exposure (P=0.003). Our results suggest that alterations at 2p16 combined with other markers could be useful in diagnosing asbestos-related lung cancer.

Gene expression and copy number profiling suggests the importance of allelic imbalance in 19p in asbestos-associated lung cancer.

Asbestos is a pulmonary carcinogen known to give rise to DNA and chromosomal damage, but the exact carcinogenic mechanisms are still largely unknown. In this study, gene expression arrays were performed on lung tumor samples from 14 heavily asbestos-exposed and 14 non-exposed patients matched for other characteristics. Using a two-step statistical analysis, 47 genes were revealed that could differentiate the tumors of asbestos-exposed from those of non-exposed patients. To identify asbestos-associated regions with DNA copy number and expressional changes, the gene expression data were combined with comparative genomic hybridization microarray data. As a result, a combinatory profile of DNA copy number aberrations and expressional changes significantly associated with asbestos exposure was obtained. Asbestos-related areas were detected in 2p21-p16.3, 3p21.31, 5q35.2-q35.3, 16p13.3, 19p13.3-p13.1 and 22q12.3-q13.1. The most prominent of these, 19p13, was further characterized by microsatellite analysis in 62 patients for the differences in allelic imbalance (AI) between the two groups of lung tumors. 79% of the exposed and 45% of the non-exposed patients (P=0.008) were found to be carriers of AI in their lung tumors. In the exposed group, AI in 19p was prevalent regardless of the histological tumor type. In adenocarcinomas, AI in 19p appeared to occur independently of the asbestos exposure.

Polymorphism at position +896 of the toll-like receptor 4 gene interferes with rapid response to treatment in rheumatoid arthritis.

The aim of this study was to determine whether the +896 A-->G substitution of the Toll-like receptor 4 (TLR4) gene, causing the Asp299-->Gly change in the extracellular domain of TLR4, influences treatment response in recent-onset rheumatoid arthritis. 169 patients with rheumatoid arthritis were genotyped from the Finnish Rheumatoid Arthritis Combination Therapy trial, in which they were treated either with only one disease-modifying antirheumatic drug (DMARD) with or without prednisolone (single group), or with three DMARDs and prednisolone (combination group). Patients homozygotic for the wild-type +896A allele were compared with those having the polymorphic G allele in terms of early clinical response (at 6 months) by the 28-joint Disease Activity Score (DAS28). 1 of 20 (5%; (95% (confidence interval (CI) 1 to 5)) patients of the single group with TLR4 +896AG or GG and 29 of 67 (43%; (95% CI 31 to 56)) patients with AA were in remission (p = 0.001). DAS28 of the single group with TLR4 +896AG or GG was higher than with AA (p = 0.019). In the combination group, remission rates and DAS28 values were comparable between the genotypes. The polymorphic TLR4 +896G allele may impair treatment response to single DMARD treatment in recent-onset rheumatoid arthritis.

Inhibitory characteristics of citrullinated telopeptides of type I and II collagens for autoantibody binding in patients with rheumatoid arthritis.

OBJECTIVE: To study how soluble citrullinated telopeptides of type I and II collagens inhibit the binding of autoantibodies to the respective antigens immobilized onto solid phase, and to use modifications of previous methods to re-analyse rheumatoid arthritis (RA) and control serum samples. METHODS: Autoantibody binding was inhibited with normal or citrullinated carboxytelopeptides using enzyme-linked immunosorbent assay (ELISA) methods. Serum samples were available from 120 patients with RA and 81 controls. RESULTS: Autoantibodies that bind normal C-telopeptides were not inhibited with soluble normal or citrullinated telopeptides. However, the antibodies that bind only citrullinated telopeptides could be inhibited with corresponding citrullinated telopeptides. Thus, it is not necessary to study the binding of autoantibodies to normal collagens if the specificity of their binding is assessed by immunological inhibition. For type I telopeptide, there are two arginines, the latter of which, when citrullinated, is important for binding. For type II telopeptide, there is one arginine, which is important when citrullinated. The other amino acids, e.g. the last alanine, have only a slight effect on binding. These improved methods differentiate better between RA patients, who have specific citrullinated autoantibodies, and controls than previous ELISA methods. CONCLUSIONS: Based on inhibition assay, it is possible to measure the autoantibodies binding specifically to citrullinated telopeptides of type I and II collagens. When only one assay is involved, variance is decreased and the overall performance is easier than before.

Increased expression of high mobility group A proteins in lung cancer.

High mobility group A (HMGA) proteins play an important role in the regulation of transcription, differentiation, and neoplastic transformation. In this work, the expression of HMGA 1 and 2 in 152 lung carcinomas of mainly non-small-cell histological type has been studied by immunohistochemistry in order to evaluate their feasibility as lung cancer markers. In 17 lung cancer cases, the related bronchial epithelial changes were also studied for HMGA1 and 2 expression. RNA expression of HMGA1a and b isoforms and of HMGA2 was determined by real-time semi-quantitative RT-PCR in 23 lung carcinomas. High expression of HMGA1 and HMGA2 at both mRNA and protein levels was detected in lung carcinomas, compared with normal lung tissue. Nuclear immunostaining for HMGA1 and 2 proteins also occurred in hyperplastic, metaplastic, and dysplastic bronchial epithelium. Increased nuclear expression of HMGA1 and 2 correlated with poor survival (for adenocarcinomas, HMGA1, p=0.006; HMGA2, p=0.05). While the expression of HMGA2 was significantly associated with cell proliferation (p=0.008), HMGA1 expression did not show any association with proliferation or apoptotic index. Sequencing of HMGA2 transcripts from tumours with very high expression showed a normal full-length transcript. As HMGA proteins were expressed in about 90% of lung carcinomas and their expression was inversely associated with survival, they may provide useful markers for lung cancer diagnosis and prognosis.

Biological treatment in rheumatic diseases: results from a longitudinal surveillance: adverse events.

The objective of this study was to assess the long-term safety and tolerability of biologicals in a clinical setting. Data on adverse events (AEs) have been collected over a 5-year period by means of detailed reports sent in to the National Register of Biological Treatment in Finland (ROB-FIN) and validated by information collected by the National Agency for Medicines. Three hundred and eight reports on AEs were filed, concerning a total of 248 patients; this corresponds to 17% of all patients in the ROB-FIN register who started biological treatments. Skin reactions and infections comprised 35 and 28% of the AEs, respectively. Some cases of tuberculosis and other infections, heart failure and demyelinating conditions were seen. Our work demonstrates no unexpected AEs in a Finnish patient cohort consisting of rheumatoid arthritis and spondylarthropathy patients, although many of them were treated with combination treatments in common use in Finland. Biological treatment appears safe in the hands of the Finnish rheumatologists.

Are there autoantibodies reacting against citrullinated peptides derived from type I and type II collagens in patients with rheumatoid arthritis?

OBJECTIVES: To assess the possible presence in patients with rheumatoid arthritis (RA) of autoantibodies recognising citrullinated peptides derived from type I and II collagens. METHODS: Firstly, the binding of four pairs of synthetic peptides (arginine-containing and artificially citrullinated forms) related to different regions of human type II collagen were tested with sera from 120 patients with RA and 81 controls. Secondly, two similar pairs of peptides related to the carboxy terminal telopeptides of the alpha1 and alpha2 chains of human type I collagen were tested. RESULTS: 42-53% of the RA sera showed increased binding of arginine peptides related to type II collagen. However, 12 RA sera bound the citrullinated form of the alpha1(II) telopeptide more strongly than the corresponding arginine peptide. 20 RA sera bound the citrullinated carboxytelopeptide from the alpha1 chain of type I collagen (alpha1(I) telopeptide) more strongly than the respective arginine peptide. The correlation between the autoantibodies to type I and II collagen telopeptides was r(s) = 0.576, p < 0.001. Anti-cyclic citrullinated peptide (anti-CCP) assay was positive in 71/120 (59%) patients with RA. An anti-CCP assay detects a different subgroup of antibodies than anti-telopeptide assays. However, both anti-telopeptide and anti-CCP antibodies were increased in patients with RA. CONCLUSION: Some patients with RA were identified whose sera contained antibodies that specifically bound citrullinated peptides related to the carboxy terminal telopeptides of the alpha1 and alpha2 chains of type I collagen and the alpha1 chains of type II collagen (sequences YYXA, FYXA, and YMXA, where X stands for citrulline).

Prevalence of work-aggravated symptoms in clinically established asthma.

This population-based cross-sectional survey assessed the prevalence of work-aggravated asthma symptoms and the effect of the work environment on the aggravation of symptoms of established asthma. A questionnaire was sent to 2,613 persons (aged 20-65 yrs) with asthma. The analyses were restricted to the 969 respondents who were currently employed. The effect of occupational exposure on the aggravation of asthma symptoms at work was assessed according to both self-reported and expert-evaluated exposure. Approximately 21% of the respondents reported work-aggravated asthma symptoms at least weekly during the past month. The prevalence of those with work-aggravated symptoms increased by age, self-reported occupational exposure to dusts, abnormal temperatures or poor indoor air quality, physically strenuous work, and chemicals, and expert-evaluated probability of daily occupational exposure to airborne dusts, gases or fumes. Aggravation of asthma symptoms at work is common among employed adults with asthma. Both self-reported and expert-evaluated exposure to dusts, abnormal temperatures or poor indoor air quality, physically strenuous work, and chemicals explained the significant worsening of symptoms. The findings suggest a marked role of the work environment in the aggravation of symptoms of established asthma.

Excess incidence of asthma among Finnish cleaners employed in different industries.

The incidence and risk of asthma among female cleaners employed in different industries was explored. An increased risk of asthma has been associated with the cleaning profession, in some but not all studies. All Finnish females employed as cleaners and all those employed in administrative work were followed for asthma incidence through a record linkage in 1986-1998. An individual was defined as an "incident case of asthma" if they received rights for special reimbursement of asthma medication from the national health insurance or were recognized as having occupational asthma. Age-adjusted relative risks (RR) were estimated for cleaners in comparison with those employed in administrative work. There were 2,414 and 5,235 cases of asthma among the cleaners and administrative workers, respectively. The RR was 1.50 (95% confidence interval (CI) 1.43-1.57) in cleaners. The risk was increased in cleaners working in nearly all major sectors of economic activity, but cleaners employed by companies concerned with the manufacture of basic metals (RR 2.47; 95% CI 1.68-3.64) and food products (RR 2.19; 95% CI 1.69-2.85) had the highest risk. Only 25 of the "cases of asthma" among cleaners had been recognized as being occupational asthma. It could be concluded that cleaners have an increased risk of persistent adult-onset asthma. Factors inherent to the environment where cleaning is performed or differences in the cleaning agents used may explain the observed differences between industries.

CYP1A1 levels in lung tissue of tobacco smokers and polymorphisms of CYP1A1 and aromatic hydrocarbon receptor.

Induction of a polycyclic aromatic hydrocarbon-metabolizing cytochrome P450 isoform CYP1A1 is regulated by aromatic hydrocarbon receptor (AHR). High inducibility of CYP1A1, possibly due to genetic polymorphisms, has been considered to be a risk factor for lung cancer in tobacco smokers. The relationship between low or high pulmonary expression of CYP1A1 and polymorphic genotypes of CYP1A1 and AHR was investigated in 73 active smokers. CYP1A1 expression was determined in surgical lung samples by measuring ethoxyresorufin O-deethylase (EROD) activity and by immunostaining for CYP1A1 protein. The most common allelic variants of CYP1A1 and AHR in Finns, i.e. the MspI variant (CYP1A1*2A), I462V variant (CYP1A1*2B), and -459C to T variant of CYP1A1 and the R554K variant (AHR*2) of AHR were studied using polymerase chain reaction based methods. EROD activity correlated positively with the daily cigarette consumption (r = 0.45). There was additional variation in EROD activity independent of the amount of smoking e.g. among those who smoked one pack per day until the day of operation, EROD activity ranged from 4-142 (median 48) pmol/min/mg. The frequencies of the MspI, 462V, and -459T variant alleles of CYP1A1 and 554K variant allele of AHR were 0.158, 0.055, 0.055 and 0.075, respectively. No differences were observed in the frequencies of polymorphic genotypes between the smokers with low and those with high expression, when the relationship was studied using a regression analysis adjusted for cigarette consumption. Our results thus indicate that the interindividual variation of CYP1A1 levels in smokers' lung tissue is not attributable to genetic polymorphisms of CYP1A1 or AHR tested in this study.

Work is related to a substantial portion of adult-onset asthma incidence in the Finnish population.

There are no population-based follow-up studies to estimate the fraction of asthma incidence that is attributable to work. In Finland, individuals with clinically well-established persistent asthma are registered for reimbursement of medication from the national health insurance scheme. We combined, at an individual level, these data with the population census data of 1985, 1990, and 1995 to estimate the attributable fraction of work in adult-onset persistent asthma. Our follow-up study covered the entire 25- to 59-yr-old employed population of Finland in 1986-1998. Relative risks (RR) for occupational categories were estimated in comparison to those employed in administrative work. There were 49,575 incident cases of asthma. The attributable fraction of occupation was 29% (95% CI 25-33%) for men and 17% (95% CI 15-19%) for women. The risk was increased especially in agricultural work, manufacturing work, and service work. In addition to already established risk occupations of occupational asthma, such as food and beverage work, the analysis identified a large number of occupations with significant excess of asthma incidence. The results indicate that the impact of occupational factors in the inception of adult-onset persistent asthma, and consequently the potential for prevention, is much larger and more widely spread than generally assumed.

Epidemiologic estimate of the proportion of fatalities related to occupational factors in Finland.

OBJECTIVES: This study attempts to estimate the proportion of annual deaths related to occupational factors in Finland and considers related methodological issues and associated uncertainties. METHODS: Statistics on causes of death, numbers of subjects exposed, and risk ratios obtained from the epidemiologic literature were used to estimate the population attributable fraction and disease burden for causes of death from work-related diseases. Gender-, age- and disease-specific numbers of deaths were provided by Statistics Finland for 1996. Information on the size of the population, broken down by gender, age, occupation, and industry, was acquired from population censuses. A Finnish job-exposure matrix supplied data on the prevalence of exposure for specific agents and the level of exposure among exposed workers. RESULTS: The attributable fraction of work-related mortality in the relevant disease and age categories was estimated to be 7% (10% for men and 2% for women), and for all diseases and ages the fraction was 4%. For the main cause-of-death categories, the attributable fraction became 12% for circulatory system diseases, 8% for malignant neoplasms, 4% for respiratory system diseases, 4% for mental disorders, 3% for nervous system diseases, and 3% for accidents and violence. The following estimates were obtained for specific important diseases: 24% for lung cancer, 17% for ischemic heart disease, 12% for chronic obstructive pulmonary disease, and 11% for stroke. Based on these fractions, the total number of work-related deaths that occurred in Finland in 1996 was calculated to be on the order of 1800 (employed work force of 2.1 million); 86% involved men. CONCLUSIONS: High-quality epidemiologic studies and national survey data are essential for obtaining reliable estimates of the proportion of deaths attributable to occupational factors. The magnitude of work-related mortality is an insufficiently recognized contributor to total mortality in Finland, especially from circulatory diseases and other diseases caused by exposure to agents other than asbestos.

Association between pleural plaques and coronary heart disease.

OBJECTIVE: The aim of this study was to verify a clinical impression that patients with coronary heart disease disproportionately frequently have calcified pleural plaques. METHODS: Chest X-rays were collected from 148 patients referred consecutively to the Helsinki University Central Hospital for coronary angiography and from 100 consecutive lung cancer patients seen at the same hospital. The radiographs were analyzed for the presence of calcified pleural plaques according to the classification the International Labour Office. A generalized linear model with binomial distribution and log link was used to estimate the relative risks and their 95% confidence intervals (95% CI). RESULTS: The prevalence of calcified pleural plaques was 35% for the coronary patients and 19% for the lung cancer patients. Calcified pleural plaques were more common among the men than the women, and the risk increased with age. The relative risk of calcified pleural plaques, adjusted for age and gender, was 2.19 (95% CI 1.44-3.32) for the coronary patients as compared with the lung cancer patients. CONCLUSIONS: Further studies with better information on past exposure to asbestos and other potential risk factors are warranted to confirm the observations and to examine whether the association between coronary heart disease and calcified pleural plaques is related to an etiologic or an individual susceptibility factor common to both of these conditions.