Traffic-related air pollution, chronic stress, and changes in exhaled nitric oxide and lung function among a panel of children with asthma living in an underresourced community.

We examined associations between short-term exposure to traffic-related air pollutants (TRAP) and airway inflammation and lung function in children with asthma, and whether these associations are modified by chronic psychological stress. Residents of underresourced port-adjacent communities in New Jersey were concerned about the cumulative impacts of exposure to TRAP, particularly diesel-engine truck emissions, and stress on exacerbation of asthma among children. Children with asthma aged 9-14 (n = 35) were recruited from non-smoking households. We measured each participant's (1) continuous personal exposure to black carbon (BC, a surrogate of TRAP) at 1-min intervals, (2) 24-h integrated personal exposure to nitrogen dioxide (NO2), (3) daily fractional exhaled nitric oxide (FeNO), and (4) lung function for up to 30 consecutive days. Personal BC was recorded by micro-aethalometers. We measured daily FeNO using the NIOX MINO, forced expiratory volume in one second (FEV1), and forced vital capacity (FVC) using Easy One Frontline spirometers. Chronic stress was measured with the UCLA Life Stress Interview for Children. The association was examined using linear mixed-effect models. In the fully adjusted model, an interquartile range (IQR) increase in BC at lag 0-6 h before the FeNO measurement was associated with 8 % (95 % CI: 3 % - 12 %) increase in FeNO, whereas an IQR increase in BC at lag 7-12 h and lag 0-24 h were associated with 6 % (95 % CI: 2 % - 11 %) and 7 % (2 % - 12 %) FeNO increases, respectively. There were no significant lung function changes per IQR increase in BC. No interactions were observed between chronic stress and BC on FeNO. Chronic stress was negatively associated with individual average FeNO levels. Our findings suggest that higher levels of BC exposure within the prior 24 h increased airway inflammation levels in children with asthma, with the strongest effect observed within the first 6 h.

Exposure to traffic-related air pollution and changes in exhaled nitric oxide and DNA methylation in arginase and nitric oxide synthase in children with asthma.

BACKGROUND: Traffic-related air pollution (TRAP) has been associated with increased risk of airway inflammation in children with asthma. While epigenetic changes could potentially modulate TRAP-induced inflammatory responses, few studies have assessed the temporal pattern of exposure to TRAP, epigenetic changes and inflammation in children with asthma. Our goal was to test the time-lag patterns of personal exposure to TRAP, airway inflammation (measured as fractional exhaled nitric oxide, FeNO), and DNA methylation in the promoter regions of genes involved in nitric oxide synthesis among children with asthma. METHODS: We measured personal exposure to black carbon (BC) and FeNO for up to 30 days in a panel of children with asthma. We collected 90 buccal cell samples for DNA methylation analysis from 18 children (5 per child). Methylation in promoter regions of nitric oxide synthase (NOS1, NOS2A, NOS3) and arginase (ARG1, ARG2) was assessed by bisulfite pyrosequencing. Linear-mixed effect models were used to test the associations of BC at different lag periods, percent DNA methylation at each site and FeNO level. RESULTS: Exposure to BC was positively associated with FeNO, and negatively associated with DNA methylation in NOS3. We found strongest association between FeNO and BC at lag 0-6 h while strongest associations between methylation at positions 1 and 2 in NOS3 and BC were at lag 13-24 h and lag 0-24 h, respectively. The strengths of associations were attenuated at longer lag periods. No significant associations between exposure to TRAP and methylation levels in other NOS and ARG isoforms were observed. CONCLUSIONS: Exposure to TRAP was associated with higher levels of FeNO and lower levels of DNA methylation in the promoter regions of the NOS3 gene, indicating that DNA methylation of the NOS3 gene could be an important epigenetic mechanism in physiological responses to TRAP in children with asthma.

Human symptom responses to bioeffluents, short-chain carbonyls/acids, and long-chain carbonyls in a simulated aircraft cabin environment.

Occupants of aircraft have reported an array of symptoms related to general discomfort and irritation. Volatile organic compounds (VOCs) have been suggested to contribute to the reported symptoms. VOCs are from products used, bioeffluents from people and oxidation reaction products. Thirty-six healthy, young female subjects rated symptoms and environmental quality during an eight-hour exposure to groups of compounds often present in aircraft: (i) long-chain carbonyls, (ii) simulated bioeffluents, and (iii) short-chain carbonyls/organic acids. Statistically more symptoms were identified for the simulated bioeffluents and, to a lesser extent, short-chain carbonyls/organic acids compared to a control condition, although they remained in the acceptable range. There were three temporal patterns in the environmental quality and symptom reports: (i) an adaptive response (immediate increases followed by a decline); (ii) an apparent physiological effect (increases one to three hours into the exposure that remained elevated); and (iii) no statistical differences in reported environmental quality or symptom severity compared to the control air conditions. Typical concentrations found in aircraft can cause transitory symptoms in healthy individuals questioning the adequacy of current standards. Understanding the effects on individuals sensitive to air pollutants and methods to remove the compounds causing the greatest symptom responses are needed.

Development of solvent exposure index for construction painters.

This article describes methodological approaches for reconstructing long-term occupational exposure to organic solvents among construction painters. A detailed exposure questionnaire was administered to 125 painters to develop a job exposure matrix (JEM). The questionnaire inquired about painting activities with solvent-based paints and use of protection equipment for the previous 25 years in 5-year intervals. Current and historical distributions of solvent air concentrations were assessed for the same time period based on the following information: industrial hygiene measurements, paint composition changes, and VOC emission rate changes from architectural and industrial maintenance coatings. Changes in protection factors of respirators were also assessed. A cumulative solvent exposure index was calculated for each painter through Monte Carlo simulations by combining appropriate input distributions of solvent air concentrations and protection factors of respirators with JEM. Sensitivity simulations revealed that the historical variations in solvent air concentrations had a higher impact on the cumulative solvent exposure index than changes in protection factors for respirators. Fifty-eight percent of painters were classified with a different exposure quartile when the solvent exposure index was used vs. an exposure based only on years using solvent-based paints, suggesting the need for more detailed exposure analysis than just years working when conducting epidemiologic studies for this worker population.

Effect of vehicle use and maintenance patterns of a self-described group of sensitive individuals and nonsensitive individuals to methyl tertiary-butyl ether in gasoline.

The objective of this study was to compare the driving habits and vehicle maintenance patterns of individuals who report symptoms when exposed to methyl tertiary-butyl ether (MTBE) and those who are asymptomatic when exposed to the oxygenate. Participants were healthy volunteers (CON) and self-reported MTBE-sensitive individuals (SRS) who participated in a controlled exposure study of MTBE in gasoline. A questionnaire was developed to gather information about each participant's automobile usage, engine maintenance habits and fueling and driving patterns. Results showed that the individuals who had self-reported heightened sensitivity to the oxygenate drove their vehicles more often and fueled their vehicles more frequently than asymptomatic individuals. In addition, the self-reported symptomatic individuals in this study were shown to be more likely to drive vehicles with some form of body damage and carbureted engines.

Cognitive functioning in Gulf War Illness.

A comprehensive neuropsychological battery was administered to 48 veterans with Gulf War Illness (GWI) characterized by severe fatigue (GV-F) and 39 healthy veterans (GV-H). Subjects were matched on intelligence and did not differ on age, gender, race, and alcohol consumption. Compared to GVs-H, GVs-F were significantly impaired on four tasks: three attention, concentration, information processing tasks and one measure of abstraction and conceptualization. After considering the presence of post-war Axis I psychopathology, GWI remained a significant predictor of cognitive performance on one of the attention, concentration, and information processing tasks and one abstraction and conceptualization measure. Performance on the remaining two attention, concentration, and information processing tasks was only significantly predicted by Axis I psychopathology with post-war onset. The results suggest that Gulf War Illness is associated with some aspects of cognitive dysfunction in Gulf Veterans, over and above the contribution of psychopathology.

Controlled exposures to volatile organic compounds in sensitive groups.

Sensitivities to chemicals are characterized by symptoms in multiple organ systems in response to low-level chemical exposures. This paper reviews studies of controlled exposures to odorants and to mixtures of volatile organic compounds. Sensitive subgroups include subjects who met Cullen's 1987 criteria for multiple chemical sensitivity (MCS), Gulf War veterans with chronic fatigue syndrome and chemical sensitivity (CFS/CS), and subjects with specific self-reported sensitivities to methyl terbutyl ether (MTBE) in gasoline (MTBE-sensitive). All studies include comparison of age- and sex-matched healthy controls. Studies of olfaction did not support unusual sensitivity, defined as lower odor thresholds, among MCS subjects; however, a dose-response pattern of symptoms was observed in response to suprathreshold concentrations of phenyl ethyl alcohol. In blinded, controlled exposures to clean air, gasoline, gasoline/11% MTBE, and gasoline/15% MTBE, a threshold effect was observed with MTBE-sensitive subjects reporting significantly increased symptoms to gasoline/15% MTBE exposure. Autonomic arousal (heart and respiration rate; end-tidal CO2) in response to odor of chemical mixtures may mediate symptoms for subjects with generalized chemical sensitivities, but not for those whose sensitivities are confined to specific chemicals. For example, Gulf War veterans with CFS/CS experienced reduced end-tidal CO2 when exposed to diesel fumes, while exposure to MTBE did not produce any psychophysiologic changes in MTBE-sensitive subjects. Controlled olfactory and exposure studies reveal that significant responses can be observed in chemically sensitive subjects even when de-adaptation has not occurred. However, these studies suggest that symptoms are not necessarily accompanied by changes in physiologic arousal. Subject characteristics play a critical role in outcomes.

Optimised conditions for the production of hepatitis B virus from cell culture.

In chronically infected patients, hepatitis B virus (HBV) particles reach numbers as large as >10(9) genome equivalents (GE)/ml of serum. However, expression of infectious HBV particles in cell culture only yields 10(5)-10(6) GE/ml, which is insufficient for many studies. HBV transcription and possibly replication is dependent on hepatocyte-specific differentiation. Thus, we tested several cell culture parameters that have been reported to enhance the expression of hepatocyte-specific markers, such as growth on different extracellular matrices, different cell culture media, low concentrations of fetal calf serum (FCS) and the addition of dimethyl sulfoxide (DMSO) to the medium. Lower concentrations of FCS, growth on collagen and inclusion of DMSO in the medium only moderately enhanced HBV production in vitro when applied individually. However, combinations of these parameters optimised cell culture conditions and reproducibly increased the release of HBV particles about 100-fold to titres >10(8) GE/ml of culture medium.

Medical follow-up of Persian Gulf War Veterans with severe medically unexplained fatigue: a preliminary study.

An important question for researchers interested in long-term consequences of military service is the health outcome of symptomatic Persian Gulf War Veterans. From an original group of 76 Gulf War Veterans who received the diagnosis of severe fatiguing illness, we attempted to get 58 veterans to return to our center for a second evaluation. Thirteen returned. Two had recovered by the time of revisit, but the rest remained ill; however, only one was so ill as to be unable to work. The data suggest that the medical consequences of serving in the Persian Gulf are not transient. The difficulty in getting veterans to return to our center suggests potential problems in the proposed nation-wide longitudinal health outcome study of Persian Gulf War Veterans.

Stressors, personality traits, and coping of Gulf War veterans with chronic fatigue.

OBJECTIVES: preliminary surveys of Persian Gulf veterans revealed a significant prevalence of self-reported symptoms consistent with chronic fatigue syndrome (CFS). The purpose of this study was to compare self-reported life stressors, combat, and chemical exposures, personality and coping between Gulf War veterans with CFS and healthy veterans. METHODS: following a complete physical, psychiatric, and neuropsychological evaluation, 45 healthy veterans, 35 veterans with CFS and co-morbid psychiatric disorder, and 23 veterans with CFS and no co-morbid psychiatric disorder completed questionnaires assessing war and non-war-related life stressors, self-reports of environmental exposure (e.g. oil well fires, pesticides), personality, and coping. RESULTS: measures of personality, self-reported combat and chemical exposures, and negative coping strategies significantly differentiated healthy veterans from those with CFS. CONCLUSION: a biopsychosocial model of veterans' illness was supported by the fact that personality, negative coping strategies, life stress after the war, and environmental exposures during the war were significant predictors of veterans' current physical function.

Controlled human exposure to methyl tertiary butyl ether in gasoline: symptoms, psychophysiologic and neurobehavioral responses of self-reported sensitive persons.

The 1990 Clean Air Act mandated oxygenation of gasoline in regions where carbon monoxide standards were not met. To achieve this standard, methyl tertiary butyl ether (MTBE) was increased to 15% by volume during winter months in many locations. Subsequent to the increase of MTBE in gasoline, commuters reported increases in symptoms such as headache, nausea, and eye, nose, and throat irritation. The present study compared 12 individuals selected based on self-report of symptoms (self-reported sensitives; SRSs) associated with MTBE to 19 controls without self-reported sensitivities. In a double-blind, repeated measures, controlled exposure, subjects were exposed for 15 min to clean air, gasoline, gasoline with 11% MTBE, and gasoline with 15% MTBE. Symptoms, odor ratings, neurobehavioral performance on a task of driving simulation, and psychophysiologic responses (heart and respiration rate, end-tidal CO(2), finger pulse volume, electromyograph, finger temperature) were measured before, during, and immediately after exposure. Relative to controls, SRSs reported significantly more total symptoms when exposed to gasoline with 15% MTBE than when exposed to gasoline with 11% MTBE or to clean air. However, these differences in symptoms were not accompanied by significant differences in neurobehavioral performance or psychophysiologic responses. No significant differences in symptoms or neurobehavioral or psychophysiologic responses were observed when exposure to gasoline with 11% MTBE was compared to clean air or to gasoline. Thus, the present study, although showing increased total symptoms among SRSs when exposed to gasoline with 15% MTBE, did not support a dose-response relationship for MTBE exposure nor the symptom specificity associated with MTBE in epidemiologic studies.

A controlled short-term exposure study to investigate the odor differences among three different formulations of gasoline.

Control subjects (CON) and self-reported methyl tertiary butyl ether (MTBE)-sensitive subjects (SRS) were evaluated to distinguish between the following gasoline blends: gasoline versus gasoline + MTBE (15% MTBE v/v); and gasoline versus gasoline + MTBE + reodorant. The study also investigated the ability of a reodorant to conceal the odor of MTBE in a gasoline mixture. In each of two separate sessions, seven men (four CON, three SRS) and seven women (four CON, three SRS) were asked, in a forced-choice format, to sniff 28 randomized bottle pairs to determine if the odors in each pair were the same or different. Chi-square analyses revealed that, with the exception of one male CON, subjects were unable to distinguish between gasoline and gasoline with MTBE or gasoline with MTBE and the reodorant. Thus, a reodorant is of limited value as an additive which alters the ability of an individual to detect MTBE in a blended gasoline. The results suggest that at the level used in the experiment, no mask would be required to blind a participant from the odor of MTBE if that level is used in a controlled human health effects study of the additive.

Odor perception: multiple chemical sensitivities, chronic fatigue, and asthma.

Patients with multiple chemical sensitivities (MCS) often report heightened sensitivity to odors. Odor detection thresholds to phenyl ethyl alcohol (PEA) and pyridine (PYR) were evaluated as a measure of odor sensitivity for 33 MCS subjects, 13 chronic fatigue syndrome subjects, 16 asthmatic subjects, and 27 healthy controls. Odor identification ability (based on University of Pennsylvania Smell Identification Test results) and ratings in response to four suprathreshold levels of PEA and PYR were also assessed. Odor detection thresholds for PEA and PYR and odor identification ability were equivalent for all groups; however, when exposed to suprathreshold concentrations of PEA, MCS subjects reported significantly more trigeminal symptoms and lower esthetic ratings of PEA. No group differences were found in response to suprathreshold concentrations of PYR. In summary, MCS subjects did not demonstrate lower olfactory threshold sensitivity or enhanced ability to identify odors accurately. Furthermore, they were differentiated from the other groups in their symptomatic and esthetic ratings of PEA, but not PYR.

A 37-year-old mechanic with multiple chemical sensitivities.

A 37-year-old heating, ventilation, and air-conditioning mechanic developed respiratory, musculoskeletal, and central nervous system symptoms associated with a variety of odorous environmental chemicals. Organic disease was not evident, but the patient was distressed by these symptoms and was at risk for becoming disabled by them. His symptoms fit broadly into the condition recognized as multiple chemical sensitivity. Multiple chemical sensitivity is a diagnostic term for a group of symptoms without demonstrated organic basis. The symptoms are characteristic of dysfunction in multiple organ systems, they increase and decrease according to exposure to low levels of chemical agents in the patient's environment, and they sometimes occur after a distinct environmental change or insult such as an industrial accident or remodeling. Although traditional medical organizations have not agreed on a definition for this syndrome, it is being increasingly recognized and makes up an increasing percentage of the caseload at occupational and environmental medicine clinics. Although there is often dispute about whether the symptoms have a functional or organic basis, an informed approach to evaluation, diagnosis, and management and a careful assessment of impairment, disability, and work relatedness are necessary. Careful exclusion of organic causes is critical, and this should be followed by a judicious approach to coping with symptoms.

Prevalence of chronic fatigue and chemical sensitivities in Gulf Registry Veterans.

More than 68000 of the 700000 veterans of the Gulf War have become members of the Veteran Affairs' Gulf War Registry. In 1995, we undertook a questionnaire study of the symptoms and medical histories reported by a randomly selected subsample of 1935 of these veterans to characterize their complaints. All results reported were based on questionnaire responses without face-to-face evaluation or physical examinations. Inasmuch as initial registry symptoms overlapped those of Chronic Fatigue Syndrome and Multiple Chemical Sensitivities, we also included standard questions for these syndromes in the questionnaire. A total of 1161 (60%) individuals responded, and there were no major demographic biases; therefore, 15.7% of registry veterans qualified for Chronic Fatigue Syndrome in accordance with the 1994 Centers for Disease Control definition. In addition, 13.1% qualified for multiple chemical sensitivities in accordance with a widely used definition, and 3.3% of the respondents had both conditions. There were no effects of gender, race, branch, duty status (active or reserve), or rank, although Multiple Chemical Sensitivities was somewhat more prevalent in women and African Americans. The data gleaned in this study suggested that the unexplained symptom syndromes of Chronic Fatigue and Multiple Chemical Sensitivities may characterize an appreciable portion of the complaints of those who volunteered for the Veterans Affairs' Gulf War Registry, and further investigation is warranted.

Urinary biomarkers as indicators of renal disease.

Using modern technology, minute quantities of LMWP, prostanoids, growth factors, intra-renal and extra-renal enzymes can be measured in urine. Excretory patterns that are characteristic for site and mechanism of renal injury often can be found. It is possible to recognise urinary biomarker patterns that suggest the putative environmental nephrotoxin. Our own studies performed in subjects with low level occupational and environmental exposures in New Jersey confirm the pattern specificity and threshold effects for Cr, Hg and Pb. In addition, we have been able to show that increased NAG and IAP excretion following Pb exposure correlates with current (blood Pb) but not with the cumulative Pb burden (bone Pb). The relatively specific characteristic patterns of biomarker excretion are lost as renal failure progresses. Moreover, renal injury that results in tubular proteinuria may not progress to renal failure. Nevertheless, urine biomarkers can help to establish acceptable levels and identify the need for long term surveillance to ascertain when clinical renal disease may result.

Neuropsychological and stress evaluation of a residential mercury exposure.

Residents of a former factory building converted to apartments were exposed to mercury over a 2-year period. The neurobehavioral and emotional health effects of this exposure and subsequent evacuation are presented. Urine mercury levels were measured before (urine1) and 3-10 weeks after evacuation (urine2) of the building, when neurobehavioral and psychological measures were also completed. Performance on neurobehavioral and psychologic measures were compared between subjects above and below the median for urine1 (>=19 microg/g creatinine) and were correlated with urine1 mercury levels. The high urine mercury group made more errors on a test of fine motor function and 84% of the residents reported clinically significant elevations in somatic and psychologic symptoms. Although subclinical tremor from mercury exposure may have affected subtle hand-eye coordination, other tests of motor function were not affected. Therefore, the observation of reduced hand-eye coordination may be due to chance. Significant levels of psychosocial stress were more closely associated with the evacuation necessitated by mercury exposure rather than a direct effect of mercury exposure.

Psychiatric diagnoses in Gulf War veterans with fatiguing illness.

The purpose of this study was to determine whether Gulf War Illness (GWI) can be explained by the presence of psychiatric disorders as assessed by DSM-III-R. To reduce the heterogeneity amongst Persian Gulf War veterans with GWI (PGV-F), only those were studied who presented with severe fatigue as a major complaint and also fulfilled clinical case definitions for Chronic Fatigue Syndrome, Idiopathic Chronic Fatigue, and/or Multiple Chemical Sensitivity. A total of 95 Registry PGVs were examined; 53 presented with GWI and 42 did not report any post-war health problems (PGV-H). All subjects were assessed for the presence of DSM-III-R Axis I psychiatric disorders. Compared to PGV-Hs, 49% of PGV-Fs had similar post-war psychiatric profiles: either no, or only one, psychiatric disorder was diagnosed. Psychiatric profiles of the remaining 51% of PGV-Fs were significantly different from PGV-Hs in that most of these veterans suffered from multiple post-war psychiatric diagnoses. The presence of psychiatric disorders as assessed by DSM-III-R criteria cannot explain symptoms of Gulf War Illness among all Persian Gulf veterans with severe fatiguing illness.