Overview of biological mechanisms of human carcinogens.

This review summarizes the carcinogenic mechanisms for 109 Group 1 human carcinogens identified as causes of human cancer through Volume 106 of the IARC Monographs. The International Agency for Research on Cancer (IARC) evaluates human, experimental and mechanistic evidence on agents suspected of inducing cancer in humans, using a well-established weight of evidence approach. The monographs provide detailed mechanistic information about all carcinogens. Carcinogens with closely similar mechanisms of action (e.g. agents emitting alpha particles) were combined into groups for the review. A narrative synopsis of the mechanistic profiles for the 86 carcinogens or carcinogen groups is presented, based primarily on information in the IARC monographs, supplemented with a non-systematic review. Most carcinogens included a genotoxic mechanism.

Development of a database on tumors and tumor sites in humans and in experimental animals for 'Group 1 agents identified through volume 109 of the IARC Monographs.

Volume 100 in the series of IARC Monographs on the Evaluation of Carcinogenic Risks to Humans comprises an update and review of relevant information on all agents determined to induce cancer in humans. These Group 1 agents are categorized in 6 Monographs (Volumes 100A-F) published in 2012. This paper describes the methodology and stringent criteria used in the creation of a comprehensive database on tumors noted in animals and humans for the carcinogens reviewed in Volume 100, and for additional Group 1 agents that were identified in subsequent Monographs through Volume 109. The development of this database involved the systematic collection of relevant data on tumors detected in humans and experimental animals identified by the Working Groups that conducted evaluations reported in the IARC Monographs. The database includes all human tumor sites identified by the Working Groups, along with all tumor sites for which there was sufficient evidence in experimental animals. This database provides a basis for assessing the degree of concordance between tumor sites observed in humans and experimental animals for Group 1 agents identified through Volume 109.

Development of a database on key characteristics of human carcinogens.

A database on mechanistic characteristics of human carcinogenic agents was developed by collecting mechanistic information on agents identified as human carcinogens (Group 1) by the International Agency for Research on Cancer (IARC) in the IARC Monographs on the Evaluation of Carcinogenic Risks to Humans. A two-phase process is described for the construction of the database according to 24 toxicological endpoints, derived from appropriate test systems that were acquired from data obtained from the mechanisms sections of the IARC Monographs (Section 4) and a supplementary PubMed search. These endpoints were then aligned with 10 key characteristics of human carcinogens that reflect the broader attributes of these agents relating to the development of cancer in humans. The considerations involved in linking of toxicological endpoints to key characteristics are described and specific examples of the determination of key characteristics for six specific agents (tamoxifen, hepatitis B virus, arsenic, ultraviolet and solar radiation, tobacco smoking, and dioxin) are provided. Data for humans and animals were tabulated separately, as were results for in-vivo and for in-vitro sources of information. The database was constructed to support a separate analysis of the expression of these endpoints by 86 Group 1 carcinogens, in-vivo and in-vitro along with an analysis of the key characteristics of these agents.

Concordance between sites of tumor development in humans and in experimental animals for 111 agents that are carcinogenic to humans.

Since the inception of the IARC Monographs Programme in the early 1970s, this Programme has developed 119 Monograph Volumes on more than 1000 agents for which there exists some evidence of cancer risk to humans. Of these, 120 agents were found to meet the criteria for classification as carcinogenic to humans (Group 1). Volume 100 of the IARC Monographs, compiled in 2008-2009 and published in 2012, provided a review and update of the 107 Group 1 agents identified as of 2009. These agents were divided into six broad categories: (I) pharmaceuticals; (II) biological agents; (III) arsenic, metals, fibers and dusts; (IV) radiation; (V) personal habits and indoor combustions; and (VI) chemical agents and related occupations. The Group I agents reviewed in Volume 100, as well as five additional Group 1 agents defined in subsequent Volumes of the Monographs, were used to assess the degree of concordance between sites where tumors originate in humans and experimental animals including mice, rats, hamsters, dogs, and non-human primates using an anatomically based tumor nomenclature system, representing 39 tumor sites and 14 organ and tissue systems. This evaluation identified 91 Group 1 agents with sufficient evidence (82 agents) or limited evidence (9 agents) of carcinogenicity in animals. The most common tumors observed in both humans and animals were those of the respiratory system including larynx, lung, and lower respiratory tract. In humans, respiratory system tumors were noted for 31 of the 111 distinct Group 1 carcinogens identified up to and including Volume 109 of the IARC Monographs, comprising predominantly 14 chemical agents and related occupations in category VI; seven arsenic, metals, fibers, and dusts in category III, and five personal habits and indoor combustions in category V. Subsequent to respiratory system tumors, those in lymphoid and hematopoietic tissues (26 agents), the urothelium (18 agents), and the upper aerodigestive tract (16 agents) were most often seen in humans, while tumors in digestive organs (19 agents), skin (18 agents), and connective tissues (17 agents) were frequently seen in animals. Exposures to radiation, particularly X- and γ-radiation, and tobacco smoke were associated with tumors at multiple sites in humans. Although the IARC Monographs did not emphasize tumor site concordance between animals and humans, substantial concordance was detected for several organ and tissue systems, even under the stringent criteria for sufficient evidence of carcinogenicity used by IARC. Of the 60 agents for which at least one tumor site was identified in both humans and animals, 52 (87%) exhibited tumors in at least one of the same organ and tissue systems in humans and animals. It should be noted that some caution is needed in interpreting concordance at sites where sample size is particularly small. Although perfect (100%) concordance was noted for agents that induce tumors of the mesothelium, only two Group 1 agents that met the criteria for inclusion in the concordance analysis caused tumors at this site. Although the present analysis demonstrates good concordance between animals and humans for many, but not all, tumor sites, limitations of available data may result in underestimation of concordance.

Key characteristics of 86 agents known to cause cancer in humans.

Since the inception of the International Agency for Research on Cancer (IARC) in the early 1970s, the IARC Monographs Programme has evaluated more than 1000 agents with respect to carcinogenic hazard; of these, up to and including Volume 119 of the IARC Monographs, 120 agents met the criteria for classification as carcinogenic to humans (Group 1). Volume 100 of the IARC Monographs provided a review and update of Group 1 carcinogens. These agents were divided into six broad categories: (I) pharmaceuticals; (II) biological agents; (III) arsenic, metals, fibers, and dusts; (IV) radiation; (V) personal habits and indoor combustions; and (VI) chemical agents and related occupations. Data on biological mechanisms of action (MOA) were extracted from the Monographs to assemble a database on the basis of ten key characteristics attributed to human carcinogens. After some grouping of similar agents, the characteristic profiles were examined for 86 Group 1 agents for which mechanistic information was available in the IARC Monographs up to and including Volume 106, based upon data derived from human in vivo, human in vitro, animal in vivo, and animal in vitro studies. The most prevalent key characteristic was "is genotoxic", followed by "alters cell proliferation, cell death, or nutrient supply" and "induces oxidative stress". Most agents exhibited several of the ten key characteristics, with an average of four characteristics per agent, a finding consistent with the notion that cancer development in humans involves multiple pathways. Information on the key characteristics was often available from multiple sources, with many agents demonstrating concordance between human and animal sources, particularly with respect to genotoxicity. Although a detailed comparison of the characteristics of different types of agents was not attempted here, the overall characteristic profiles for pharmaceutical agents and for chemical agents and related occupations appeared similar. Further in-depth analyses of this rich database of characteristics of human carcinogens are expected to provide additional insights into the MOA of human cancer development.

Indoor air quality, ventilation and respiratory health in elderly residents living in nursing homes in Europe.

Few data exist on respiratory effects of indoor air quality and comfort parameters in the elderly. In the context of the GERIE study, we investigated for the first time the relationships of these factors to respiratory morbidity among elderly people permanently living in nursing homes in seven European countries. 600 elderly people from 50 nursing homes underwent a medical examination and completed a standardised questionnaire. Air quality and comfort parameters were objectively assessed in situ in the nursing home. Mean concentrations of air pollutants did not exceed the existing standards. Forced expiratory volume in 1 s/forced vital capacity ratio was highly significantly related to elevated levels of particles with a 50% cut-off aerodynamic diameter of <0.1 µm (PM0.1) (adjusted OR 8.16, 95% CI 2.24-29.3) and nitrogen dioxide (aOR 3.74, 95% CI 1.06-13.1). Excess risks for usual breathlessness and cough were found with elevated PM10 (aOR 1.53 (95% CI 1.15-2.07) and aOR 1.73 (95% CI 1.17-10.3), respectively) and nitrogen dioxide (aOR 1.58 (95% CI 1.15-2.20) and aOR 1.56 (95% CI 1.03-2.41), respectively). Excess risks for wheeze in the past year were found with PM0.1 (aOR 2.82, 95% CI 1.15-7.02) and for chronic obstructive pulmonary disease and exhaled carbon monoxide with formaldehyde (aOR 3.49 (95% CI 1.17-10.3) and aOR 1.25 (95% CI 1.02-1.55), respectively). Breathlessness and cough were associated with higher carbon dioxide. Relative humidity was inversely related to wheeze in the past year and usual cough. Elderly subjects aged ≥80 years were at higher risk. Pollutant effects were more pronounced in the case of poor ventilation. Even at low levels, indoor air quality affected respiratory health in elderly people permanently living in nursing homes, with frailty increasing with age. The effects were modulated by ventilation.

Causes of deaths in COPD patients in primary care setting--a 6-year follow-up.

INTRODUCTION: COPD is one of the most frequent respiratory diseases responsible for patients' disability and mortality. In 2005 a single primary care practice, COPD was diagnosed in 183 out of 1,960 eligible subjects ≥ 40 years (9.3%). The aim of this study was to assess mortality rate and causes of deaths in this group after 6 years. MATERIAL AND METHODS: In 2011 we invited all 183 patients with COPD recognised in 2005. We performed spirometry, physical examination, questionnaire of respiratory symptoms, smoking habits, concomitant diseases and treatment. Information about deaths was taken from primary care register, furthermore, family members were asked to deliver medical documentation or death certificate. RESULTS: In 2011 we studied only 74 subjects (40.4%), 43 subjects died (23.5%) and 66 subjects were lost from the follow-up (36.1%). Cardiovascular diseases were the most frequent causes of deaths - 21 subjects (48.8%) (heart attack - 8 patients and stroke - 8 patients). Respiratory failure in the course of COPD exacerbation was the cause of 10 deaths (23.3%). Neoplastic diseases lead to 9 deaths (20.9%) (lung cancer 7 patients). Renal insufficiency was responsible for one death (2.325%), and the causes of 2 deaths remained unknown (4.65%). Subjects who died (predominantly males) were older, had higher MRC score and lower FEV1. CONCLUSIONS: Study performed six years after COPD diagnosis revealed that 23.5% of subjects died. The main causes of deaths were the following: cardiovascular diseases (mainly heart attack and stroke), COPD exacerbations and lung cancer (more than 75%). Death risk in COPD patients was associated with age, male sex, dyspnoea and severity of the disease.

Identification of a chronic obstructive pulmonary disease genetic determinant that regulates HHIP.

Multiple intergenic single-nucleotide polymorphisms (SNPs) near hedgehog interacting protein (HHIP) on chromosome 4q31 have been strongly associated with pulmonary function levels and moderate-to-severe chronic obstructive pulmonary disease (COPD). However, whether the effects of variants in this region are related to HHIP or another gene has not been proven. We confirmed genetic association of SNPs in the 4q31 COPD genome-wide association study (GWAS) region in a Polish cohort containing severe COPD cases and healthy smoking controls (P = 0.001 to 0.002). We found that HHIP expression at both mRNA and protein levels is reduced in COPD lung tissues. We identified a genomic region located ∼85 kb upstream of HHIP which contains a subset of associated SNPs, interacts with the HHIP promoter through a chromatin loop and functions as an HHIP enhancer. The COPD risk haplotype of two SNPs within this enhancer region (rs6537296A and rs1542725C) was associated with statistically significant reductions in HHIP promoter activity. Moreover, rs1542725 demonstrates differential binding to the transcription factor Sp3; the COPD-associated allele exhibits increased Sp3 binding, which is consistent with Sp3's usual function as a transcriptional repressor. Thus, increased Sp3 binding at a functional SNP within the chromosome 4q31 COPD GWAS locus leads to reduced HHIP expression and increased susceptibility to COPD through distal transcriptional regulation. Together, our findings reveal one mechanism through which SNPs upstream of the HHIP gene modulate the expression of HHIP and functionally implicate reduced HHIP gene expression in the pathogenesis of COPD.

Prevalence of metabolic syndrome diagnosis in patients with obstructive sleep apnoea syndrome according to adopted definition.

INTRODUCTION: Metabolic syndrome (MS), which is connected with enlarged cardiovascular risk, is common in patients with OSAS. The aim of the study was to estimate the prevalence of MS in patients with OSAS according to two definitions of MS (criteria from NCEP-ATP III from 2001 versus criteria from IDF 2005). MATERIAL AND METHODS: Materials consisted of 155 males and 18 females with OSAS (mean AHI 44 ± 22 h-1), obesity (BMI 31.8 ± 5.0 kg/m2), aged 53.9 ± 9.3 years (mean ± SD). Serum lipids, glucose, body mass index (BMI), waist circumference (WC) and waist-to-hip ratio (WHR) were measured in all patients. RESULTS: According to first definition (NCEP - ATP III from 2001), MS was diagnosed in 98 patients (56% of the whole group - MS1 group) compared to 120 patients (69% of the whole group - MS2 group) diagnosed according to the second definition (IDF from 2005), p < 0.05. No differences in BMI and WC between the groups were found. Significant differences in WHR were noted (MS1 group: 1.005 ± 0.05 vs. MS2 group: 1.027 ± 0.06, p < 0.05). Patients from the MS2 group had higher cholesterol HDL compared to the MS1 group (52.3 ± 12.1 mg/dl vs. 42.3 ± 12.1 mg/dl, p < 0.05). Serum triglyceride concentrations were significantly higher in the MS1 group than in the MS2 group (228 ± 122 mg/dl vs. 122 ± 49 mg/dl, p < 0.05). There were no differences in OSAS severity between the MS1 and MS2 group. In both groups weak correlations between diagnosis of MS and AHI were found (r = 0.19 for MS1 and r = 0.21 for MS2, p < 0.05) They are, however, clinically insignificant. CONCLUSIONS: The IDF definition from 2005 of metabolic syndrome indeed increases the frequency of diagnosis of metabolic syndrome in patients with OSAS. We did not observe essential clinical correlation among the degree of OSAS severity and recognition of metabolic syndrome in the MS1 or in the MS2 group.

CHRNA3/5, IREB2, and ADCY2 are associated with severe chronic obstructive pulmonary disease in Poland.

We examined the association between single-nucleotide polymorphisms (SNPs) previously associated with chronic obstructive pulmonary disease (COPD) and/or lung function with COPD and COPD-related phenotypes in a novel cohort of patients with severe to very severe COPD. We examined 315 cases of COPD and 330 Caucasian control smokers from Poland. We included three SNPs previously associated with COPD: rs7671167 (FAM13A), rs13180 (IREB2), and rs8034191 (CHRNA 3/5), and four SNPs associated with lung function in a genome-wide association study of general population samples: rs2070600 (AGER), rs11134242 (ADCY2), rs4316710 (THSD4), and rs17096090 (INTS12). We tested for associations with severe COPD and COPD-related phenotypes, including lung function, smoking behavior, and body mass index. Subjects with COPD were older (average age 62 versus 58 years, P < 0.01), with more pack-years of smoking (45 versus 33 pack-years, P < 0.01). CHRNA3/5 (odds ratio [OR], 1.89; 95% confidence interval [CI], 1.5-2.4; P = 7.4 × 10(-7)), IREB2 (OR, 0.69; 95% CI, 0.5-0.9; P = 3.4 × 10(-3)), and ADCY2 (OR, 1.35; 95% CI, 1.1-1.7; P = 0.01) demonstrated significant associations with COPD. FAM13A (OR, 0.8; 95% CI, 0.7-1.0; P = 0.11) approached statistical significance. FAM13A and ADCY2 also demonstrated a significant association with lung function. Thus, in severe to very severe COPD, we demonstrate a replication of association between two SNPs previously associated with COPD (CHRNA3/5 and IREB2), as well as an association with COPD of one locus initially associated with lung function (ADCY2).

Database of radiogenic cancer in experimental animals exposed to low doses of ionizing radiation.

For decades, there have been debates regarding the nature of the relationship between exposure to low doses of ionizing radiation and cancer risk. Under the linear no-threshold hypothesis, which serves as a theoretical basis for current radiation protection standards, the risk of cancer at low levels of exposure is presumed to be directly proportional to dose. Opponents of this hypothesis claim that there are threshold doses for radiation carcinogenesis, or even a reduction in cancer risk at low doses (a phenomenon referred to as "radiation hormesis"). Epidemiological, animal, molecular, and cellular studies were conducted to resolve this controversy, although each of these study types has its strengths and limitations. Although the results of animal experiments are not directly applicable to humans, data can substantially add to our knowledge on the form of relationship between radiation dose and cancer risk in a wide range of doses. Laboratory animals are a homogeneous population with little biological variability; animal experiments are conducted under controlled conditions with good estimates of radiation doses. In order to address the question of whether or not the dose-response curve for radiation carcinogens is linear at low doses, a comprehensive database of animal carcinogenesis experiments was assembled involving exposure to different types of ionizing gradation. The database includes virtually all publicly accessible data on the induction of radiogenic cancer in laboratory mammals. This review provides a descriptive overview of the experiments included in the database, along with a qualitative assessment of the shape of the dose-response relationship for radiation carcinogenesis at low doses in experimental animals.

A meta-analysis of evidence for hormesis in animal radiation carcinogenesis, including a discussion of potential pitfalls in statistical analyses to detect hormesis.

A database containing 800 datasets on the incidence of specific tumor types from 262 radiation carcinogenicity experiments identified in a comprehensive literature search through September 2000 was analyzed for evidence of hormesis. This database includes lifetime studies of tumorigenic responses in mice, rats, and dogs to exposures to alpha, beta, gamma, neutron, or x-ray radiation. A J-shaped dose response, in the form of a significant decreased response at some low dose followed by a significant increased response at a higher dose, was found in only four datasets from three experiments. Three of these datasets involved the same control animals and two also shared dosed animals; the J shape in the fourth dataset appeared to be the result of an outlier within an otherwise monotonic dose response. A meta-analysis was conducted to determine whether there was an excess of dose groups with decreases in tumor response below that in controls at doses below no-observed-effect levels (NOELs) in individual datasets. Because the probability of a decreased response is generally not equal to the probability of an increased response even in the null case, the meta-analysis focused on comparing the number of statistically significant diminished responses to the number expected, assuming no dose effect below the NOEL. Only 54 dose groups out of the total of 2579 in the database had doses below the dataset-specific NOEL and that satisfied an a priori criterion for sufficient power to detect a reduced response. Among these 54, a liberal criterion for defining a significant decreases identified 15 such decreases, versus 54 × 0.2 = 10.8 expected. The excess in significant reductions was accounted for almost entirely by the excess from neutron experiments (10 observed, 6.2 expected). Nine of these 10 dose groups involved only 2 distinct control groups, and 2 pairs from the 10 even shared dosed animals. Given this high degree of overlap, this small excess did not appear remarkable, although the overlap prevented a formal statistical analysis. A comprehensive post hoc evaluation using a range of NOEL definitions and alternative ways of restricting the data entering the analysis did not produce materially different results. A second meta-analysis found that, in every possible low dose range ([0, d] for every dose, d) of each of the radiation types, the number of dose groups with significantly increased tumorigenic responses was either close to or exceeded the number showing significantly reduced responses. This meta-analysis was considered to be the more definitive one. Not only did it take dose into account by looking for consistent evidence of hormesis throughout defined low-dose ranges, it was also potentially less susceptible to limitations in experimental protocols that would cause individual animals to respond in a non-independent fashion. Overall, this study found little evidence in a comprehensive animal radiation database to support the hormesis hypothesis. However, the ability of the database to detect a hormetic effect was limited both by the small number of dose groups with doses below the range where positive effects have been found in epidemiological studies (≤ 0.1 Gy) and by the limited power of many of these dose groups for detecting a decrease in response.

[Morbid obesity as a cause of respiratory failure]. / Chorobliwa otylosc jako przyczyna niewydolnosci oddychania.

World epidemic of obesity reached Poland. Obesity may result in hypercapnic respiratory failure. This complication may be expected in morbidly obese subjects, with BMI 〉 35. Diagnosis is confirmed by arterial blood gas analysis showing PaO(2) 〈 60 mm Hg and PaCO(2) 〉 45 mm Hg. The most frequent cause of respiratoty failure is severe form of obstructive sleep apnea. In approximately 10% of patients obesity hypoventilation syndrome is diagnosed. Diagnosis is established during polysomnographic examination. Patients are treated with nocturnal ventilatory suport CPAP or BiPAP. Causative treatment is based on weight reduction. Low - calorie diet is ineffective. Bariatric surgery available in Poland is effective.

[Three month continuous positive airway pressure (CPAP) therapy decreases serum total and LDL cholesterol, but not homocysteine and leptin concentration in patients with obstructive sleep apnea syndrome (OSAS)]. / Trzymiesieczne leczenie za pomoca ciaglego dodatniego cisnienia w drogach oddechowych (CPAP) obniza stezenie cholesterolu calkowitego oraz cholesterolu frakcji LDL we krwi, ale nie wplywa na stezenie homocysteiny i leptyny w surowicy u chorych z obturacyjnym bezdechem podczas snu (OBPS) bez wspólistniejacej choroby niedokrwiennej serca (ChNS).

INTRODUCTION: In OSAS patients CPAP therapy decreases cardiovascular morbidity and mortality. Homocysteine and leptin may play a role in development of ischaemic heart disease (IHD) in patients with OSAS. The aim of the study was to assess the influence of 3 month CPAP therapy on cardiovascular risk factors in patients with OSAS without IHD (pure OSAS) and with OSAS and IHD. MATERIAL AND METHODS: Therapy with CPAP was started in 42 OSAS without IHD (pure OSAS) and 23 OSAS and IHD patients. Plasma concentration of homocysteine, serum concentration of leptin, C-reactive protein (CRP), fibrinogen, lipids, and markers of visceral adiposity (MVA) were measured before and after treatment. RESULTS: There were no significant changes in homocysteine, leptin, fibrinogen and CRP concentrations in neither group. In OSAS and IHD no change in serum lipids and MVA were found. In pure OSAS group total cholesterol and LDL cholesterol concentrations significantly decreased (202.5 ± 38.5 mg/dl v. 186.7 ± 33.5 mg/dl, p = 0.001 and 127.3 ± 32.9 mg/dl v. 116.4 ± 26.9 mg/dl, p = 0.02, respectively). Triglycerides did not significantly change (p = 0.09). There were no significant changes in BMI (30.4 ± 3.8 v. 30.6 ± 3.6, p = 0.5), waist circumference (108.5 ± 8.0 cm v. 107.0 ± 7.5 cm, p = 0.09) and waist to hip ratio (1.03 ± 0.04 v. 1.01 ± 0.03, p = 0.07). CONCLUSIONS: Three month CPAP therapy did not change homocysteine and leptin concentration in neither group. However, it significantly decreased serum lipids concentration in patients with pure OSAS, but not in patients with OSAS and IHD, suggesting beneficial effects of CPAP therapy on cardiovascular risk factors.

Screening for and early detection of chronic obstructive pulmonary disease.

Chronic obstructive pulmonary disease (COPD) is a substantially underdiagnosed disorder, with the diagnosis typically missed or delayed until the condition is advanced. Spirometry is the most frequently used pulmonary function test and enables health professionals to make an objective measurement of airflow obstruction and assess the degree to which it is reversible. As a diagnostic test for COPD, spirometry is a reliable, simple, non-invasive, safe, and non-expensive procedure. Early diagnosis of COPD should provide support for smoking cessation initiatives and lead to reduction of the societal burden of the disease, but definitive confirmation of both proves elusive. Despite substantial effort and investment, implementation of quality spirometry is deficient because of several hurdles and limitations, described in this Review. All in all, spirometry is recognised as the essential test for diagnosis and monitoring of COPD.

Evolution of upper airway resistance syndrome.

The question of whether upper airway resistance syndrome (UARS) is a distinct disease or an initial feature of obstructive sleep apnoea syndrome is still a matter of debate. We evaluated a retrospective group of UARS patients to determine the evolution of UARS over time and the relationship between clinical evolution and subjects' phenotype. Investigations were performed in 30 patients, in whom UARS was diagnosed between 1995 and 2000 by the use of full polysomnography (PSG) without oesophageal pressure (Pes) measurement. The time between initial and follow-up investigations was 6.6 +/- 2.6 years. All subjects had full PSG with Pes measurement and completed a sleep questionnaire, including the Epworth Sleepiness Scale. In 19 subjects, PSG results were compatible with UARS. In nine subjects, obstructive sleep apnoea-hypopnoea syndrome (OSAHS) was diagnosed. In two subjects, PSG did not demonstrate breathing abnormalities. The mean +/- SD apnoea-hypopnoea index in the UARS group was 1.5 +/- 1.7 h(-1) and 25.2 +/- 19 h(-1) in the OSAHS group (P < 0.01). The increase in body mass index (BMI) between initial and follow-up investigations in the UARS group was from 29.4 +/- 4 to 31 +/- 5.7 kg m(-2) (P = 0.014) and in the OSAHS group from 30 +/- 4.1 to 32.4 +/- 4.7 kg m(-2)(P = 0.004). Amplitude of Pes swings during respiratory events was significantly higher in OSAHS than that in UARS (P = 0.014). Our results suggest that UARS is part of a clinical continuum from habitual snoring to OSAHS. Progression from UARS to OSAHS seems to be related to an increase in the BMI.

Continuous positive airway pressure treatment increases bronchial reactivity in obstructive sleep apnea patients.

BACKGROUND: The effects of continuous positive airway pressure (CPAP) treatment on the function of the lower airways are poorly understood. One of the methods used to determine the influence of positive pressure breathing on lower airways is the bronchial hyperreactivity test. Some authors report that CPAP increases bronchial hyperreactivity, while others report decreases. OBJECTIVES: To assess the influence of CPAP treatment on bronchial reactivity and the effects of bronchial hyperreactivity on compliance to CPAP treatment. METHODS: The study group consisted of 101 obstructive sleep apnea syndrome patients (88 men and 13 women) with a mean age of 51 ± 11 years, mean apnea-hypopnea index of 53 ± 20 and mean body mass index of 32.6 ± 5.4. Patients were randomly assigned to a treatment group that received 3 weeks of CPAP therapy (group 1) or to a nontreatment control group (group 2). Pulmonary function tests and the methacholine bronchial provocation test were performed at baseline and 3 weeks later. RESULTS: There were no statistically significant differences between treated and control groups in anthropometry and polysomnography variables. At baseline, bronchial hyperreactivity was found in 6 patients from group 1 and 5 patients from group 2. A significant increase in bronchial reactivity was observed after CPAP treatment. Log PC20M decreased from 1.38 ± 0.30 at baseline to 1.26 ± 0.50 (p < 0.05). In group 2, changes were statistically insignificant. Patients with bronchial hyperreactivity during CPAP treatment were characterized by significantly lower FEV1, FVC and MEF50 values. CONCLUSIONS: CPAP produces statistically significant bronchial hyperreactivity. However, there were no clinical symptoms and it is not necessary to withdraw previous therapies.

Low dose ionizing radiation exposure and cardiovascular disease mortality: cohort study based on Canadian national dose registry of radiation workers.

OBJECTIVES: The purpose of our study was to assess the risk of cardiovascular disease (CVD) mortality in a Canadian cohort of 337 397 individuals (169 256 men and 168 141 women) occupationally exposed to ionizing radiation and included in the National Dose Registry (NDR) of Canada. MATERIAL AND METHODS: Exposure to high doses of ionizing radiation, such as those received during radiotherapy, leads to increased risk of cardiovascular diseases. The emerging evidence of excess risk of CVDs after exposure to doses well below those previously considered as safe warrants epidemiological studies of populations exposed to low levels of ionizing radiation. In the present study, the cohort consisted of employees at nuclear power stations (nuclear workers) as well as medical, dental and industrial workers. The mean whole body radiation dose was 8.6 mSv for men and 1.2 mSv for women. RESULTS: During the study period (1951-1995), as many as 3 533 deaths from cardiovascular diseases have been identified (3 018 among men and 515 among women). In the cohort, CVD mortality was significantly lower than in the general population of Canada. The cohort showed a significant dose response both among men and women. Risk estimates of CVD mortality in the NDR cohort, when expressed as excess relative risk per unit dose, were higher than those in most other occupational cohorts and higher than in the studies of Japanese atomic bomb survivors. CONCLUSIONS: The study has demonstrated a strong positive association between radiation dose and the risk of CVD mortality. Caution needs to be exercised when interpreting these results, due to the potential bias introduced by dosimetry uncertainties, the possible record linkage errors, and especially by the lack of adjustment for non-radiation risk factors.

Health outcomes of low-dose ionizing radiation exposure among medical workers: a cohort study of the Canadian national dose registry of radiation workers.

BACKGROUND: Medical workers can be exposed to low-dose ionizing radiation from various sources. The potential cancer risks associated with ionizing radiation exposure have been derived from cohort studies of Japanese atomic bomb survivors who had experienced acute, high-level exposure. Since such extrapolations are subject to uncertainty, direct information is needed on the risk associated with chronic low-dose occupational exposure to ionizing radiation. OBJECTIVES: To determine the occupational doses of ionizing radiation and examine possible associations with mortality rates and cancer incidence in a cohort of medical workers deriving from the National Dose Registry of Canada (NDR) over the period of 1951-1987. METHODS: Standardized mortality and incidence ratios (SMR and SIR, respectively) were ascertained by linking NDR data for a cohort of 67 562 medical workers (23 580 males and 43 982 females) with the data maintained by the Canadian Mortality, and Cancer Incidence databases. Dosimetry information was obtained from the National Dosimetry Services. RESULTS: During the follow-up period, 1309 incident cases of cancer (509 in males, 800 in females) and 1325 deaths (823 in males, 502 in females) were observed. Mortality from cancer and non-cancer causes was generally below expected as compared to the general Canadian population. Thyroid cancer incidence was significantly elevated both among males and females, with a combined SIR of 1.74 and 90% CI: 1.40-2.10. CONCLUSIONS: The findings confirm previous reports on an increased risk of the thyroid cancer among medical workers occupationally exposed to ionizing radiation. Over the last 50 years, radiation protection measures have been effective in reducing radiation exposures of medical workers to the current very low levels.

[Smoking habits in a family physician's practice]. / Palenie tytoniu wsród podopiecznych lekarza rodzinnego.

INTRODUCTION: Poland is the one of the countries in the European Union with the highest prevalence of smokers. The involvement of family physicians in smoking cessation activity could improve this situation. The aim of this study was to estimate smoking habits, their intensity and nicotine dependence in a family physician's practice (urban and rural population). An additional aim was to estimate smoking habits in relation to the presence of smoking-related disease, gender, location and motivation to stop smoking. MATERIAL AND METHODS: This study was part of an investigation into the prevalence and severity of chronic obstructive pulmonary disease (COPD) in the same population. Statistical analysis of questionnaires about smoking and history of respiratory diseases, Fagerström's nicotine dependence test and a motivation to quit test were performed. RESULTS: Questionnaires were filled in by 1960 subjects (87% of those eligible). There were 29.6% current smokers, 24.9% ex-smokers, and 45.5% never-smokers. There were 39.4% current smokers among men, and 23.3% among women. Current smokers were more numerous in the rural population. 54% of women urban dwellers and 73% of women from rural population never smoked. There were no significant differences in the motivation to stop smoking or in the nicotine dependence among smokers with and without COPD nor according to the severity of COPD. CONCLUSIONS: Smoking habits among the studied population were comparable with national and regional data. The intensity of smoking habits among female town dwellers is especially alarming.