Robert J. McCunney

Asthma, genes, and air pollution.

Objective: The objective of this article is to evaluate genetic risks associated with the pulmonary response to air pollutants, including particulates and ozone. Methods: A comprehensive review of articles related to the genetics of asthma with particular attention to air pollution was conducted through a search of the National Library of Medicine’s PubMed database. Results: Asthma, which affects over 15 million people in the United States, is characterized by inflammation leading to reversible airflow obstruction. Triggered by exposure to numerous occupational and environmental agents, asthma has long been considered to occur more frequently in families, with upwards of a 50% higher rate in the offspring of parents with asthma. Asthma genetic studies have used two major methods: mapping techniques that pinpoint gene loci and studies that identify genes and polymorphisms associated with various asthma mechanisms such as inflammatory mediators. The most consistently replicated chromosomal regions associated with asthma have been chromosomes 2q, 5q, 6p, 12q, and 13q. Because the formation of reactive oxygen species is a major aspect of the inflammatory process of asthma, genetic aberrations associated with antioxidants such as glutathione S-transferase (GST) may shed light on reasons why some people with asthma seem more at risk of exacerbations as a result of air pollution. People with a polymorphism at the GSTP 1 locus, which codes for GST, one of a family of pulmonary antioxidants, have higher rates of asthma. Children in Mexico City with the GSTM1 null genotype demonstrated significant ozone-related decrements in lung function. Animal studies support the key role of antioxidants in reducing the inflammatory response associated with exposure to diesel exhaust particles. Conclusions: Oxidative stress is a key mechanism underlying the toxic effects of exposure to some types of air pollution. Asthmatics with the null genotype for the antioxidant, GST, seem more at risk of the pulmonary effects of air pollution.

Response to the Reply on behalf of the ‘Permanent Senate Commission for the Investigation of Health Hazards of Chemical Compounds in the Work Area’ (MAK Commission) by Andrea Hartwig Karlsruhe Institute of Technology (KIT)

Calculation error in the MAK Commission’s document on GBS [3] when using the rule of three in Pauluhn’s volumetric model (we emphasize that the comment did not dispute the arithmetical error lowering Model B’s GBS limit value erroneously from 2.0 mg/m to 0.5 mg/m). Use of an MPPD2 program version in [3] that is outdated and no longer available to enable to replicate the MAK Commission’s conclusions. Input values in [3] that cannot be reproduced from the references listed in [3] or are not state-of-the-art. Inconsistent use of varying input data by the MAK Commission in [3] although explicitly specified as guideline in the same document [3].

Radiation Risks in Lung Cancer Screening Programs

The National Lung Cancer Screening Trial (NLST) demonstrated that screening with low-dose CT (LDCT) scan reduced lung cancer and overall mortality by 20% and 7%, respectively. The LDCT scanning involves an approximate 2-mSv dose, whereas full-chest CT scanning, the major diagnostic study used to follow up nodules, may involve a dose of 8 mSv. Radiation associated with CT scanning and other diagnostic studies to follow up nodules may present an independent risk of lung cancer. On the basis of the NLST, we estimated the incidence and prevalence of nodules detected in screening programs. We followed the Fleischner guidelines for follow-up of nodules to assess cumulative radiation exposure over 20- and 30-year periods. We then evaluated nuclear worker cohort studies and atomic bomb survivor studies to assess the risk of lung cancer from radiation associated with long-term lung cancer screening programs. The findings indicate that a 55-year-old lung screening participant may experience a cumulative radiation exposure of up to 280 mSv over a 20-year period and 420 mSv over 30 years. These exposures exceed those of nuclear workers and atomic bomb survivors. This assessment suggests that long-term (20-30 years) LDCT screening programs are associated with nontrivial cumulative radiation doses. Current lung cancer screening protocols, if conducted over 20- to 30-year periods, can independently increase the risk of lung cancer beyond cigarette smoking as a result of cumulative radiation exposure. Radiation exposures from LDCT screening and follow-up diagnostic procedures exceed lifetime radiation exposures among nuclear power workers and atomic bomb survivors.The National Lung Cancer Screening Trial (NLST) demonstrated that screening with low-dose CT (LDCT) scan reduced lung cancer and overall mortality by 20% and 7%, respectively. The LDCT scanning involves an approximate 2-mSv dose, whereas full-chest CT scanning, the major diagnostic study used to follow up nodules, may involve a dose of 8 mSv. Radiation associated with CT scanning and other diagnostic studies to follow up nodules may present an independent risk of lung cancer. On the basis of the NLST, we estimated the incidence and prevalence of nodules detected in screening programs. We followed the Fleischner guidelines for follow-up of nodules to assess cumulative radiation exposure over 20- and 30-year periods. We then evaluated nuclear worker cohort studies and atomic bomb survivor studies to assess the risk of lung cancer from radiation associated with long-term lung cancer screening programs. The findings indicate that a 55-year-old lung screening participant may experience a cumulative radiation exposure of up to 280 mSv over a 20-year period and 420 mSv over 30 years. These exposures exceed those of nuclear workers and atomic bomb survivors. This assessment suggests that long-term (20-30 years) LDCT screening programs are associated with nontrivial cumulative radiation doses. Current lung cancer screening protocols, if conducted over 20- to 30-year periods, can independently increase the risk of lung cancer beyond cigarette smoking as a result of cumulative radiation exposure. Radiation exposures from LDCT screening and follow-up diagnostic procedures exceed lifetime radiation exposures among nuclear power workers and atomic bomb survivors.

Bronchiolitis obliterans from exposure to incinerator fly ash.

Inhalation of toxic substances in the workplace can result in a variety of respiratory disorders. One relatively rare sequela of the inhalation of toxic fumes is bronchiolitis obliterans, a condition characterized by fibrosis and narrowing of the small airways. Several substances have been reported to cause bronchiolitis obliterans, including ammonia, chlorine, hydrogen fluoride, hydrogen sulfide, nitrogen dioxide, ozone, phosgene, and other irritant fumes. Little has been reported on the pulmonary effects of fly ash produced by the incineration of coal and oil. We report a case of bronchiolitis obliterans with a component of partially reversible airway obstruction in a 39-year-old male occupationally exposed to incinerator fly ash.

Pulmonary alveolar proteinosis and cement dust: a case report.

Pulmonary alveolar proteinosis developed in a 29-year-old white man within 2 years of working as a cement truck driver. Pulmonary alveolar proteinosis (PAP), an uncommon respiratory disorder characterized by the accumulation of phospholipid material within the alveoli, has been described in association with exposure to silica, aluminum oxide, and a variety of dusts and fumes. Although a link between exposure to Portland cement and PAP has not been previously noted, this type of cement contains nearly 20% silica. Lung biopsy material, originally used to diagnose PAP, was reviewed under electron dispersive spectroscopy. Analysis indicated the presence of silica particles within the alveolar fluid and macrophages. A number of items support a causal relationship between exposure to cement dust and PAP: (1) the temporal sequence between assuming job duties and the development of the illness, (2) improvement following removal from further exposure, (3) dusty, unprotected working conditions, (4) the presence of silica within the cement, and (5) the alveolar fluid from periodic acid-Schiff-positive lung tissue.

What component of coal causes coal workers' pneumoconiosis?

Objective: To evaluate the component of coal responsible for coal workers’ pneumoconiosis (CWP). Methods: A literature search of PubMED was conducted to address studies that have evaluated the risk of CWP based on the components of coal. Results: The risk of CWP (CWP) depends on the concentration and duration of exposure to coal dust. Epidemiology studies have shown inverse links between CWP and quartz content. Coal from the USA and Germany has demonstrated links between iron content and CWP; these same studies indicate virtually no role for quartz. In vitro studies indicate strong mechanistic links between iron content in coal and reactive oxygen species, which play a major role in the inflammatory response associated with CWP. Conclusions: The active agent within coal appears to be iron, not quartz. By identifying components of coal before mining activities, the risk of developing CWP may be reduced.

Health and productivity: a role for occupational health professionals.

The impressive economic gains achieved by many nations within the past decade have been attributed primarily to improvements in productivity from technological changes. The resultant low unemployment levels, however, emphasize the importance of human capital in the success of any enterprise. Concurrently, some economists have proposed an alternative economic view regarding the relationship between health and income, postulating that improvements in the health of the nation’s population have a substantial effect on its economic viability. Such a view directly pertains to occupational health professionals, who are often charged with promoting the health of the worker. Although studies relating the beneficial impact of occupational health on productivity and human performance are limited, some efforts have shown impressive effects, as measured primarily by reduced absenteeism. The prompt, assertive management of occupational injuries and illnesses and their treatment have been well documented. Illnesses not considered traditional occupational ailments, such as migraine headaches, allergic disorders, infectious diseases, and depression, offer opportunities for occupational health professionals to ensure an accurate diagnosis and proper treatment for minimizing the impact on work performance. Considerable opportunities exist for occupational health professionals to demonstrate the importance of certain services to productivity.

Diverse manifestations of trichloroethylene

Trichloroethylene, a solvent used in a variety of industrial settings for more than 60 years, has caused adverse health effects on the central and peripheral nervous system, the skin, liver, kidney, and heart. Three men have shown relatively unusual manifestations secondary to exposure to trichloroethylene in degreasing operations in the jewelry industry. Toxic encephalopathy, hepatitis, and carpal spasm occurred among young, healthy workers. Clinical and laboratory data, including measurement of urinary trichloroacetic acid concentrations, are presented.

Translational toxicology in setting occupational exposure limits for dusts and hazard classification – a critical evaluation of a recent approach to translate dust overload findings from rats to humans

BackgroundWe analyze the scientific basis and methodology used by the German MAK Commission in their recommendations for exposure limits and carcinogen classification of “granular biopersistent particles without known specific toxicity” (GBS). These recommendations are under review at the European Union level. We examine the scientific assumptions in an attempt to reproduce the results. MAK’s human equivalent concentrations (HECs) are based on a particle mass and on a volumetric model in which results from rat inhalation studies are translated to derive occupational exposure limits (OELs) and a carcinogen classification.MethodsWe followed the methods as proposed by the MAK Commission and Pauluhn 2011. We also examined key assumptions in the metrics, such as surface area of the human lung, deposition fractions of inhaled dusts, human clearance rates; and risk of lung cancer among workers, presumed to have some potential for lung overload, the physiological condition in rats associated with an increase in lung cancer risk.ResultsThe MAK recommendations on exposure limits for GBS have numerous incorrect assumptions that adversely affect the final results. The procedures to derive the respirable occupational exposure limit (OEL) could not be reproduced, a finding raising considerable scientific uncertainty about the reliability of the recommendations. Moreover, the scientific basis of using the rat model is confounded by the fact that rats and humans show different cellular responses to inhaled particles as demonstrated by bronchoalveolar lavage (BAL) studies in both species.ConclusionClassifying all GBS as carcinogenic to humans based on rat inhalation studies in which lung overload leads to chronic inflammation and cancer is inappropriate. Studies of workers, who have been exposed to relevant levels of dust, have not indicated an increase in lung cancer risk. Using the methods proposed by the MAK, we were unable to reproduce the OEL for GBS recommended by the Commission, but identified substantial errors in the models. Considerable shortcomings in the use of lung surface area, clearance rates, deposition fractions; as well as using the mass and volumetric metrics as opposed to the particle surface area metric limit the scientific reliability of the proposed GBS OEL and carcinogen classification.

Wind turbines and health: a critical review of the scientific literature.

Objective: This review examines the literature related to health effects of wind turbines. Methods: We reviewed literature related to sound measurements near turbines, epidemiological and experimental studies, and factors associated with annoyance. Results: (1) Infrasound sound near wind turbines does not exceed audibility thresholds. (2) Epidemiological studies have shown associations between living near wind turbines and annoyance. (3) Infrasound and low-frequency sound do not present unique health risks. (4) Annoyance seems more strongly related to individual characteristics than noise from turbines. Discussion: Further areas of inquiry include enhanced noise characterization, analysis of predicted noise values contrasted with measured levels postinstallation, longitudinal assessments of health preand postinstallation, experimental studies in which subjects are “blinded” to the presence or absence of infrasound, and enhanced measurement techniques to evaluate annoyance.