Systematic review and meta-analysis of epidemiological literature evaluating the association between exposure to man-made vitreous fibers and respiratory tract cancers.

We conducted a systematic review and meta-analysis of epidemiological studies that evaluated occupational exposure to man-made vitreous fibers (MMVF) including glass, rock, and slag wools, and respiratory tract cancers (RTC) including cancers of the larynx, trachea, bronchus, and lung. The MEDLINE/PubMed and Web of Science databases were searched in order to identify epidemiological studies that evaluated the association between occupational MMVF exposure and RTCs. We performed random-effects meta-analyses of relevant studies identified by our literature search, and evaluated sources of between-study heterogeneity. The pooled relative risk (RR) of RTC among workers exposed to MMVFs was 1.09 (95% CI = 0.97, 1.22). The RR was closer to 1.0 when limiting the analysis to effect estimates from studies that accounted for the main a priori risk factors for RTC, asbestos exposure and smoking (RR = 1.03, 95% CI = 0.90, 1.18). Overall, our synthesis of the epidemiological literature suggests that occupational MMVF exposure is not associated with risk of RTC.

[Influence of vehicular traffic density on hospital admissions due to respiratory tract cancer in the city of São Paulo, Brazil]. / Influência da densidade de tráfego veicular na internação por câncer do aparelho respiratório no Município de São Paulo, Brasil.

Pollution related to traffic is a major problem in urban centers and a large portion of the population is vulnerable to its health effects. This study sought to identify a potential association between hospital admissions due to respiratory tract cancer and vehicular traffic density in the city of São Paulo, Brazil. It is an ecological study of the public (Hospital Inpatient Authorization - AIH, in Portuguese) and private (Hospital Inpatient Communication - CIH, in Portuguese) health care systems, from 2004 to 2006, geocoded by individuals' residential addresses. Using a Besag-York-Mollié ecological model, we initially evaluated the relationship between number of cases of hospital admission due to respiratory tract cancer in each weighting area and the standardized co-variables: traffic density and Municipal Human Development Index (MHDI) as indicator of socioeconomic status. Using a classic Poisson model, we then evaluated the risk associated with growing traffic density categories. The Besag-York-Mollié model estimated a RR = 1.09 (95%CI: 1.02-1.15) and RR = 1.19 (95%CI: 1.10-1.29) of admission due to respiratory tract cancer for each increase of one standard deviation of traffic and MHDI, respectively. The Poisson model also showed a clear exposure-response gradient for admission due to respiratory tract cancer (IRR = 1.11; 95%CI: 1.07-1.15, for each 10 units of added traffic density). This study suggests that there is an association between residing in areas with high traffic density and hospital admissions due to respiratory tract cancer in the city of São Paulo.

A poluição relacionada ao tráfego é um grande problema nos centros urbanos, e uma grande parcela da população fica vulnerável aos seus efeitos à saúde. Este trabalho teve como objetivo identificar potencial associação entre as internações hospitalares por câncer do aparelho respiratório com a densidade de tráfego veicular no Município de São Paulo, Brasil. É um estudo ecológico com dados de internações hospitalares por câncer dos sistemas público (Autorização de Internação Hospitalar - AIH) e particular (Comunicação de Internação Hospitalar - CIH), de 2004 a 2006, geocodificados por endereço de residência do indivíduo. Mediante um modelo ecológico de Besag-York-Mollié foi avaliada inicialmente a relação entre o número de casos de internação por câncer do aparelho respiratório em cada área de ponderação e as covariáveis padronizadas: densidade de tráfego e Índice de Desenvolvimento Humano Municipal (IDHM) como indicador de status socioeconômico. Sequencialmente, com um modelo clássico de Poisson, procedeu-se uma avaliação do risco associado às categorias crescentes de densidade de tráfego. O modelo de Besag-York-Mollié estimou um RR = 1,09 (IC95%: 1,02-1,15) e RR = 1,19 (IC95%: 1,10-1,29) de internação por câncer do aparelho respiratório, para cada aumento de um desvio padrão da densidade de tráfego e IDHM, respectivamente. Foi também evidenciado pelo modelo de Poisson um claro gradiente de exposição-resposta para internação por câncer respiratório (IRR = 1,11; IC95%: 1,07-1,15, para cada dez unidades de acréscimo da densidade de tráfego). Este trabalho sugere que há associação entre residir em áreas com alta densidade de tráfego e internação por câncer do aparelho respiratório no Município de São Paulo.

La contaminación relacionada con el tráfico es un gran problema en los centros urbanos, y una gran parte de la población es vulnerable a sus efectos para la salud. El objetivo de este trabajo fue identificar la potencial asociación entre los internamientos hospitalarios por cáncer del aparato respiratorio con la densidad del tráfico vehicular en el Municipio de São Paulo, Brasil. Es un estudio ecológico con datos de internamientos hospitalarios por cáncer de los sistemas público (Autorización de Internación Hospitalaria - AIH) y particular (Comunicación de Internación Hospitalaria - CIH), de 2004 a 2006, geocodificados por dirección de residencia del individuo. Mediante el modelo ecológico de Besag-York-Mollié se evaluó inicialmente la relación entre el número de casos de internamiento por cáncer del aparato respiratorio en cada área de ponderación y covariables estandarizadas: densidad de tráfico e Índice de Desarrollo Humano Municipal (IDHM), como indicador de estatus socioeconómico. Secuencialmente, con un modelo clásico de Poisson, se procedió a una evaluación del riesgo asociado a las categorías crecientes de densidad de tráfico. El modelo de Besag-York-Mollié estimó un RR = 1,09 (IC95%: 1,02-1,15) y RR = 1,19 (IC95%: 1,10-1,29) de internamiento por cáncer del aparato respiratorio, para cada aumento de un desvío estándar de la densidad de tráfico e IDHM, respectivamente. Se evidenció también, a través del modelo de Poisson, un claro gradiente de exposición-respuesta para el internamiento por cáncer respiratorio (IRR = 1,11; IC95%: 1,07-1,15, para cada 10 unidades de incremento de la densidad de tráfico). Este trabajo sugiere que existe una asociación entre residir en áreas con alta densidad de tráfico y el internamiento por cáncer del aparato respiratorio en el Municipio de São Paulo.

Influência da densidade de tráfego veicular na internação por câncer do aparelho respiratório no Município de São Paulo, Brasil / Influence of vehicular traffic density on hospital admissions due to respiratory tract cancer in the city of São Paulo, Brazil / Influencia de la densidad de tráfico vehicular en el internamiento por cáncer del aparato respiratorio en el Municipio de São Paulo, Brasil

A poluição relacionada ao tráfego é um grande problema nos centros urbanos, e uma grande parcela da população fica vulnerável aos seus efeitos à saúde. Este trabalho teve como objetivo identificar potencial associação entre as internações hospitalares por câncer do aparelho respiratório com a densidade de tráfego veicular no Município de São Paulo, Brasil. É um estudo ecológico com dados de internações hospitalares por câncer dos sistemas público (Autorização de Internação Hospitalar - AIH) e particular (Comunicação de Internação Hospitalar - CIH), de 2004 a 2006, geocodificados por endereço de residência do indivíduo. Mediante um modelo ecológico de Besag-York-Mollié foi avaliada inicialmente a relação entre o número de casos de internação por câncer do aparelho respiratório em cada área de ponderação e as covariáveis padronizadas: densidade de tráfego e Índice de Desenvolvimento Humano Municipal (IDHM) como indicador de status socioeconômico. Sequencialmente, com um modelo clássico de Poisson, procedeu-se uma avaliação do risco associado às categorias crescentes de densidade de tráfego. O modelo de Besag-York-Mollié estimou um RR = 1,09 (IC95%: 1,02-1,15) e RR = 1,19 (IC95%: 1,10-1,29) de internação por câncer do aparelho respiratório, para cada aumento de um desvio padrão da densidade de tráfego e IDHM, respectivamente. Foi também evidenciado pelo modelo de Poisson um claro gradiente de exposição-resposta para internação por câncer respiratório (IRR = 1,11; IC95%: 1,07-1,15, para cada dez unidades de acréscimo da densidade de tráfego). Este trabalho sugere que há associação entre residir em áreas com alta densidade de tráfego e internação por câncer do aparelho respiratório no Município de São Paulo.

Pollution related to traffic is a major problem in urban centers and a large portion of the population is vulnerable to its health effects. This study sought to identify a potential association between hospital admissions due to respiratory tract cancer and vehicular traffic density in the city of São Paulo, Brazil. It is an ecological study of the public (Hospital Inpatient Authorization - AIH, in Portuguese) and private (Hospital Inpatient Communication - CIH, in Portuguese) health care systems, from 2004 to 2006, geocoded by individuals' residential addresses. Using a Besag-York-Mollié ecological model, we initially evaluated the relationship between number of cases of hospital admission due to respiratory tract cancer in each weighting area and the standardized co-variables: traffic density and Municipal Human Development Index (MHDI) as indicator of socioeconomic status. Using a classic Poisson model, we then evaluated the risk associated with growing traffic density categories. The Besag-York-Mollié model estimated a RR = 1.09 (95%CI: 1.02-1.15) and RR = 1.19 (95%CI: 1.10-1.29) of admission due to respiratory tract cancer for each increase of one standard deviation of traffic and MHDI, respectively. The Poisson model also showed a clear exposure-response gradient for admission due to respiratory tract cancer (IRR = 1.11; 95%CI: 1.07-1.15, for each 10 units of added traffic density). This study suggests that there is an association between residing in areas with high traffic density and hospital admissions due to respiratory tract cancer in the city of São Paulo.

La contaminación relacionada con el tráfico es un gran problema en los centros urbanos, y una gran parte de la población es vulnerable a sus efectos para la salud. El objetivo de este trabajo fue identificar la potencial asociación entre los internamientos hospitalarios por cáncer del aparato respiratorio con la densidad del tráfico vehicular en el Municipio de São Paulo, Brasil. Es un estudio ecológico con datos de internamientos hospitalarios por cáncer de los sistemas público (Autorización de Internación Hospitalaria - AIH) y particular (Comunicación de Internación Hospitalaria - CIH), de 2004 a 2006, geocodificados por dirección de residencia del individuo. Mediante el modelo ecológico de Besag-York-Mollié se evaluó inicialmente la relación entre el número de casos de internamiento por cáncer del aparato respiratorio en cada área de ponderación y covariables estandarizadas: densidad de tráfico e Índice de Desarrollo Humano Municipal (IDHM), como indicador de estatus socioeconómico. Secuencialmente, con un modelo clásico de Poisson, se procedió a una evaluación del riesgo asociado a las categorías crecientes de densidad de tráfico. El modelo de Besag-York-Mollié estimó un RR = 1,09 (IC95%: 1,02-1,15) y RR = 1,19 (IC95%: 1,10-1,29) de internamiento por cáncer del aparato respiratorio, para cada aumento de un desvío estándar de la densidad de tráfico e IDHM, respectivamente. Se evidenció también, a través del modelo de Poisson, un claro gradiente de exposición-respuesta para el internamiento por cáncer respiratorio (IRR = 1,11; IC95%: 1,07-1,15, para cada 10 unidades de incremento de la densidad de tráfico). Este trabajo sugiere que existe una asociación entre residir en áreas con alta densidad de tráfico y el internamiento por cáncer del aparato respiratorio en el Municipio de São Paulo.

Mortality among Coast Guard Shipyard workers: A retrospective cohort study of specific exposures.

In a previous analysis of a cohort of shipyard workers, we found excess mortality from all causes, lung cancer, and mesothelioma for longer work durations and in specific occupations. Here, we expand the previous analyses by evaluating mortality associated with 5 chemical exposures: asbestos, solvents, lead, oils/greases, and wood dust. Data were gathered retrospectively for 4,702 workers employed at the Coast Guard Shipyard, Baltimore, MD (1950-1964). The cohort was traced through 2001 for vital status. Associations between mortality and these 5 exposures were calculated via standardized mortality ratios (SMRs). We found all 5 substances to be independently associated with mortality from mesothelioma, cancer of the respiratory system, and lung cancer. Findings from efforts to evaluate solvents, lead, oils/greases, and wood dust in isolation of asbestos suggested that the excesses from these other exposures may be due to residual confounding from asbestos exposure.

[The opponent you do not just imagine. The case of Falconara Marittima (Marche Region, Central Italy)]. / EPICHANGE/2. L'avversario che non ti aspetti. Il caso di Falconara Marittima.

Falconara Marittima (Marche Region, Central Italy) is declared to be an area at high risk of environmental crisis, due to the presence of a refinery plant. In 2004, Marche Region funded an epidemiological survey to assess atmospheric risks linked to the refinery. This survey was conducted by the Italian National Cancer Institute of Milan, and citizens actively contributed. An excess for leukaemias and an increase in non-Hodgkin lymphomas were showed. These results were confirmed also by the Regional Environmental Protection Agency and the Regional Health Authority. But Marche Region and the Municipalities chose to not report the situation: the same Institutions, which at the beginning sided the citizens, became an opponent for health protection.

[Respiratory cancers attributable to occupational exposures: what is the cost to society in France]. / Cancers des voies respiratoires attribuables aux expositions professionnelles : quels coûts pour la société française ?

OBJECTIVE: To estimate the social cost of respiratory cancers attributable to occupational risk factors in France in 2010. METHODS: We estimated the number of cases of respiratory cancers attributable to each identified occupational risk factor according to the attributable fractions method. We also estimated direct (costs of hospital stays, drugs, outpatient care) and indirect costs (production losses) related to morbidity (absenteeism and presenteeism) and mortality (years of lost production). Production losses for paid work and unpaid domestic activities were taken into account. RESULTS: The social cost of respiratory cancers (lung, larynx, sinonasal, pleural mesothelioma) attributable to exposure to asbestos, chromium, diesel engine exhaust, polycyclic aromatic hydrocarbons, painting occupations (unidentified carcinogen), crystalline silica, wood and leather dust in France in 2010 was estimated to be between €960 and 1,866 million. The cost of lung cancer represents between €804 and 1,617 million. The three risk factors with the greatest impact are asbestos (€530 to 890 million), diesel engine exhaust (€227 to 394 million), and crystalline silica (€116 to 268 million). CONCLUSION: These results provide a conservative estimate of the public health and economic burden of respiratory cancers attributable to occupational risk factors from a societal perspective.

Re-evaluation of the WHO (2010) formaldehyde indoor air quality guideline for cancer risk assessment.

In 2010, the World Health Organization (WHO) established an indoor air quality guideline for short- and long-term exposures to formaldehyde (FA) of 0.1 mg/m3 (0.08 ppm) for all 30-min periods at lifelong exposure. This guideline was supported by studies from 2010 to 2013. Since 2013, new key studies have been published and key cancer cohorts have been updated, which we have evaluated and compared with the WHO guideline. FA is genotoxic, causing DNA adduct formation, and has a clastogenic effect; exposure-response relationships were nonlinear. Relevant genetic polymorphisms were not identified. Normal indoor air FA concentrations do not pass beyond the respiratory epithelium, and therefore FA's direct effects are limited to portal-of-entry effects. However, systemic effects have been observed in rats and mice, which may be due to secondary effects as airway inflammation and (sensory) irritation of eyes and the upper airways, which inter alia decreases respiratory ventilation. Both secondary effects are prevented at the guideline level. Nasopharyngeal cancer and leukaemia were observed inconsistently among studies; new updates of the US National Cancer Institute (NCI) cohort confirmed that the relative risk was not increased with mean FA exposures below 1 ppm and peak exposures below 4 ppm. Hodgkin's lymphoma, not observed in the other studies reviewed and not considered FA dependent, was increased in the NCI cohort at a mean concentration ≥0.6 mg/m3 and at peak exposures ≥2.5 mg/m3; both levels are above the WHO guideline. Overall, the credibility of the WHO guideline has not been challenged by new studies.

Respiratory cancer mortality and incidence in an updated cohort of Canadian nickel production workers.

Respiratory cancer mortality and incidence were examined in an updated cohort of >56,000 Canadian nickel mining and refining workers. There was little evidence to suggest increased lung cancer risk in workers who had no experience in high-risk sintering operations that were closed by 1972, apart from that which would be expected from probable increased smoking prevalence relative to the comparison population. There was no substantive evidence of increased laryngeal cancer risk in the cohort, nor was there evidence of increased pharyngeal cancer risk in nonsinter workers. Nasal cancer incidence was elevated in nonsinter workers, but excess risks appeared to be confined to those hired prior to 1960. These findings lead us to tentatively conclude that occupationally-related respiratory risks in workers hired over the past 45 years are either very low or nonexistent.

IMPACT OF SOME ENVIRONMENTAL FACTORS ON HUMAN HEALTH.

This paper presents statistical data of 2012-2015 on the diseases caused by the atmospheric air and water pollutions in Ajara region. The research on the content of dust, sulfur dioxide and nitrogen dioxide as well as carbon monoxide in the atmospheric air was held together with the National Environment Agency Ajara Monitoring Service. The results of the research have shown that the average content of the dust reached its maximum in 2012 (0.60 mg/m3) and it dropped to the minimum in 2015 (0.441 mg/m3). As for average content of carbon monoxide the maximum was observed in 2013 (3.1 mg/m3) and minimum in 2015 (2.1 mg/m3). Average content of the sulfur dioxide was at maximum in 2015 (0.159 mg/m3) and at minimum in 2012 (0.07 mg/m3). The average content of nitrogen dioxide reached its maximum in 2015 (0.153 mg/m3) and was found to be at its minimum in 2012 (0.13 mg/m3). In parallel statistical research of the registered diseases (chronic and undetermined bronchitis, asthma, allergic rhinitis and trachea/bronchi/lung malignant cancer) in Ajara during 2012-2015 has been performed. These diseases were especially common among the population over the age of 40. It may be concluded that in 2015 the cases of diseases caused by the atmospheric air pollution in Ajara have become more frequent compared to the previous years. Therefore, it is evident that monitoring of atmosphere air should be improved and corresponding preventive measures should be undertaken.

Genotoxic properties of XLR-11, a widely consumed synthetic cannabinoid, and of the benzoyl indole RCS-4.

Aim of this study was the investigation of the genotoxic properties of XLR-11 [1-(5-fluoropentyl)-1H-indol-3-yl](2,2,3,3-tetramethylcyclopropyl)methanone, a widely consumed synthetic cannabinoid (SC), and of the benzoyl indole RCS-4 (4-methoxyphenyl)(1-pentyl-1H-indol-3-yl)methanone). We characterized the DNA-damaging properties of these drugs in different experimental systems. No evidence for induction of gene mutations was detected in bacterial (Salmonella/microsome) tests, but clear dose-dependent effects were found in in vitro single cell gel electrophoresis (SCGE) assays with human lymphocytes and with buccal- and lung-derived human cell lines (TR-146 and A-549). These experiments are based on the determination of DNA migration in an electric field and enable the detection of single- and double-strand breaks and apurinic sites. Furthermore, we found that both drugs induce micronuclei which are formed as a consequence of chromosomal aberrations. The lack of effects in SCGE experiments with lesion-specific enzymes (FPG, Endo III) shows that the DNA damage is not caused by formation of oxidatively damaged bases; experiments with liver enzyme homogenates and bovine serum albumin indicate that the drugs are not converted enzymatically to DNA-reactive intermediates. Furthermore, results with buccal- and lung-derived human cells show that gaseous treatment of the cells under conditions which reflect the exposure situation in drug users may cause damage of the genetic material in epithelia of the respiratory tract. Since DNA instability is involved in the etiology of cancer, these findings can be taken as an indication that consumption of the SCs may cause tumors in the respiratory tract of consumers.

Use of sleep medications and risk of cancer: a matched case-control study.

BACKGROUND: Previous research suggests a possible link between sleep-medication use and mortality, especially cancer deaths, but findings are mixed, and large population-based studies are lacking. METHODS: Data from the Finnish Public Sector study were linked to the Finnish Cancer Register and the Drug Prescription Register of Finland. A total of 5053 cancer cases (mean age of 57.4 years) diagnosed in 2002-2011, and their 24,388 controls free of cancer and matched for sex, age, socioeconomic status, employer, and geographical area, were identified. The use of sleep medications was defined as purchases of prescribed sleep medications. RESULTS: Both quantity and duration of prior sleep-medication use during the seven years studied were associated with increased odds of having cancer. Compared with participants not using sleep medications, the odds ratio was 1.18-fold (95% confidence interval (CI): 1.01-1.39) for those who used >100 defined daily doses per year and 1.16-fold (95% CI: 1.01-1.34) for those who had such a medication for >3 years. Site-specific analyses showed a more pronounced association of quantity and duration of sleep-medication use with subsequent cancer of the respiratory system (odds ratio for >100 defined daily doses per year vs. no use: 3.47; 95% CI: 1.97-6.11). No associations were found with other cancer sites. CONCLUSION: In this register-based study, sleep-medication use was associated with an increased cancer incidence of the respiratory system. Further studies are needed to examine potential carcinogenic mechanisms associated with hypnotic medications.

Aspirin and non-steroidal anti-inflammatory drug use and the risk of upper aerodigestive tract cancer.

BACKGROUND: Aspirin and other non-steroidal anti-inflammatory drugs (NSAIDs) are widely used as analgesics and preventative agents for vascular events. It is unclear whether their long-term use affects cancer risk. Data on the chemopreventative role of these drugs on the risk of the upper aerodigestive tract cancer (UADT) are insufficient and mostly refer to oesophageal cancer. The aim of this study was to investigate the effect of aspirin and other NSAIDs on the risk of UADT cancers. METHODS: A nested case-control study using the Primary Care Clinical Informatics Unit (PCCIU) database. Conditional logistics regression was used for data analysis. RESULTS: There were 2392 cases of UADT cancer diagnosed between 1996 and 2010 and 7165 age-, gender- and medical practice-matched controls from 131 general medical practices. Mean age of cases was 66 years (s.d. 12) and most were male (63%). Aspirin was prescribed in a quarter of cases and controls, COX-2 inhibitors in 4% of cases and 5% of controls and other NSAIDs in 33% of cases and 36% of controls. Aspirin prescription was associated with a nonsignificant risk reduction of cancer of UADT (adjusted OR=0.9, 95% CI=0.8, 1.0), head and neck (HN; adjusted OR=0.9, 95% CI=0.7, 1.1) or the oesophagus (adjusted OR=0.8, 95% CI=0.7, 1.0). Similar results were found for COX-2 inhibitors prescription. Prescription of other NSAIDs was associated with significantly reduced risk of cancer of UADT (adjusted OR=0.8, 95% CI=0.7, 0.9), HN (adjusted OR=0.8, 95% CI=0.7, 0.9) and the oesophagus (adjusted OR=0.8, 95% CI=0.7, 0.9). An increased volume of aspirin prescriptions was associated with a significant risk reduction (test for trend P<0.001). CONCLUSIONS: The decreased risk of cancer of the UADT associated with the use of non-COX-2 inhibitors, NSAIDs and long-term aspirin therapy warrants further exploration of the benefits vs risks of the use of these agents.

Occupational exposures to polycyclic aromatic hydrocarbons and respiratory and urinary tract cancers: an updated systematic review and a meta-analysis to 2014.

Exposure to polycyclic aromatic hydrocarbons (PAHs) has been associated with an excess risk of respiratory tract and bladder cancers in several industries, but the issue requires further quantification. We updated a previous systematic review by reviewing in details cohort studies on workers employed in selected industries with potential PAH exposure published between 2006 and 2014, and we summarized through a meta-analytic approach the main results of all available cohort studies published between 1958 and 2014 investigating cancers of the respiratory and urinary tracts. Thirteen papers on cohort studies investigating cancer risk in workers exposed to PAHs were retrieved through the literature search. These included workers from aluminum production industries (seven studies), iron and steel foundries (two studies), asphalt workers (two studies), and carbon black production (two studies). In the meta-analysis, an excess risk of respiratory tract cancers (mainly lung cancer) was found in iron and steel foundries [pooled relative risk (RR) 1.31, 95 % confidence interval (CI) 1.08-1.59 from 14 studies], while a weak excess risk (pooled RR 1.08, 95 % CI 0.95-1.23 from 11 studies) emerged for aluminum production. A borderline increase risk was also observed for cancer of the bladder in the aluminum production (pooled RR 1.28, 95 % CI 0.98-1.68 from 10 studies) and in iron and steel foundries (pooled RR 1.38, 95 % CI 1.00-1.91 from 9 studies). This updated review and meta-analysis confirm the increased risk from respiratory tract and bladder cancers in selected PAH-related occupations. It cannot be ruled out whether such excesses are due, at least in part, to possible bias or residual confounding.

Degrees of dysplasia based on viral typing in patients with cidofovir use and recurrent respiratory papillomatosis.

OBJECTIVES/HYPOTHESIS: To evaluate the degree of dysplasia following cidofovir injections while documenting human papillomavirus (HPV) type in patients with recurrent respiratory papillomatosis (RRP). STUDY DESIGN: Retrospective chart review. METHODS: Demographic data, operative reports, and pathology results were reviewed from 25 patients with RRP who had had cidofovir injections. All patients included had adult onset RRP, no history of immunosuppression, well-controlled laryngopharyngeal reflux, and no current smoking history. Eight patients were excluded because they did not meet the inclusion criteria. RESULTS: Seventeen patients had adequate data for analysis and 40 subsites were identified with sufficient data for analysis. Patients negative for both low and high risk did not have progressive dysplasia at the conclusion of the study. Of the patients with positive viral typing, 70% had progressive disease at the conclusion of the study. No patients progressed to carcinoma or carcinoma in situ. The average pre- and post-treatment dysplasia scores were analyzed using a Student paired t test. There was no difference in mean dysplasia score, indicating that there was no increased risk of dysplasia following cidofovir treatment. CONCLUSIONS: To our knowledge, this is the first study looking at the degree of dysplasia while documenting HPV types in RRP. Our study suggests that HPV type appears to be relevant in the disease progression of RRP and that cidofovir does not increase the risk of dysplasia.

Evaluation of propargyl alcohol toxicity and carcinogenicity in F344/N rats and B6C3F1/N mice following whole-body inhalation exposure.

Propargyl alcohol (PA) is a high production volume chemical used in synthesis of many industrial chemicals and agricultural products. Despite the potential for prolonged or accidental exposure to PA in industrial settings, the toxicity potential of PA was not well characterized. To address the knowledge gaps relevant to the toxicity profile of PA, the National Toxicology Program (NTP) conducted 2-week, 14-week and 2-year studies in male and female F344/N rats and B6C3F1/N mice. For the 2-week inhalation study, the rats and mice were exposed to 0, 31.3, 62.5, 125, 250 or 500ppm. Significant mortality was observed in both rats and mice exposed to ≥125ppm of PA. The major target organ of toxicity in both mice and rats was the liver with exposure-related histopathological changes (250 and 500ppm). Based on the decreased survival in the 2-week study, the rats and mice were exposed to 0, 4, 8, 16, 32 or 64ppm of PA in the 14-week study. No treatment-related mortality was observed. Mean body weights of male (≥8ppm) and female mice (32 and 64ppm) were significantly decreased (7-16%). Histopathological changes were noted in the nasal cavity, and included suppurative inflammation, squamous metaplasia, hyaline droplet accumulation, olfactory epithelium atrophy, and necrosis. In the 2-year inhalation studies, the rats were exposed to 0, 16, 32 and 64ppm of PA and the mice were exposed to 0, 8, 16 and 32ppm of PA. Survival of male rats was significantly reduced (32 and 64ppm). Mean body weights of 64ppm male rats were significantly decreased relative to the controls. Both mice and rats showed a spectrum of non-neoplastic changes in the nose. Increased neoplastic incidences of nasal respiratory/transitional epithelial adenoma were observed in both rats and mice. The incidence of mononuclear cell leukemia was significantly increased in male rats and was considered to be treatment-related. In conclusion, the key findings from this study indicated that the nose was the primary target organ of toxicity for PA. Long term inhalation exposure to PA led to nonneoplastic changes in the nose, and increased incidences of respiratory/transitional epithelial adenomas in both mice and rats. Increased incidences of harderian gland adenoma may also have been related to exposure to PA in male mice.

Assessing specific causation of mesothelioma following exposure to chrysotile asbestos-containing brake dust.

BACKGROUND: The question of whether chrysotile asbestos-containing brake dust can plausibly serve as a cause of mesothelioma in an exposed individual has become a matter of heated debate in the medical literature despite multiple international, federal, and state governmental agencies acknowledging a causal association. OBJECTIVES: We describe and provide an analysis of various industry and academic perspectives contributing to the debate. METHODS: A framework is presented for evaluating the general and specific causal relationship between brake dust exposure and mesothelioma utilizing the principles of forensic epidemiology, and by applying the Bradford-Hill criteria. RESULTS AND CONCLUSIONS: We conclude that there is a "net" of evidence favoring a causal relationship between brake dust-associated chrysotile exposure and mesothelioma. The industry-sponsored position that there is insufficient evidence to support a contiguous "chain" of causation is specious from both a methodologic and evidentiary perspective. Finally, we suggest a semiquantitative approach for the evaluation of individual causation in putative cases of mesothelioma with a history of significant brake dust exposure.

Mesothelioma associated with use of drywall joint compound: a case series and review of literature.

BACKGROUND: Drywall joint compound contained asbestos fibers, primarily chrysotile, in the 1950s through the 1970s. Workers in a variety of construction trades and homeowners were exposed to respirable asbestos from the use of these products, including during handling, mixing, sanding, and sweeping. Disturbance of in-place asbesto-containing joint compound continues to be a potential source of exposure during demolition or repair of wallboard. Studies from the 1970s and 1980s report air fiber measurements above current and historic regulatory limits during intended usage, and typical asbestos-related disease in drywall construction workers. OBJECTIVES: We present three cases of mesothelioma in which the only known exposure to asbestos was from joint compound and review the literature on exposure circumstances, dose and fiber types. CONCLUSIONS: Physicians treating mesothelioma patients should obtain a history of exposure to these products during work or home remodeling.

Treatment of kidney transplant recipients with ACEi/ARB and risk of respiratory tract cancer: a collaborative transplant study report.

Whether treatment with angiotensin-converting enzyme inhibitors (ACEi) and/or angiotensin receptor blockers (ARB) increases the risk of cancer is controversial. Collaborative transplant study data were analyzed according to whether kidney transplant recipients were treated with ACEi/ARB at year 1. Twenty-four thousand and ninety patients were studied of whom 9079 (38%) patients received ACEi/ARB. There were 872 nonskin malignancies during years 2-8 posttransplant, including 107 respiratory/intrathoracic tumors. The standardized incidence ratio (SIR) for all nonskin malignancies was similar between the ACEi/ARB (1.91) and no ACEi/ARB (1.81) groups (p = 0.42). For respiratory/intrathoracic tumors, however, SIR was significantly higher with ACEi/ARB (1.65 vs. 1.09 for no ACEi/ARB, p = 0.033). Multivariate Cox regression analysis showed that ACEi/ARB treatment was not associated with an increased risk of respiratory/intrathoracic tumors in nonsmokers. In patients with a history of smoking, however, the risk of respiratory/intrathoracic tumors was 2.77 (95% CI 1.19-6.43, p = 0.018) in patients without ACEi/ARB treatment as compared to 7.10 (95% CI 3.27-15.4, p < 0.001) in patients treated with ACEi/ARB. Our data indicate that in kidney transplant recipients, ACEi/ARB treatment is associated with a significant increase in the rate of respiratory/intrathoracic tumors in the subpopulation of patients with a history of smoking.