Axel Muttray

Effect of nighttime aircraft noise exposure on endothelial function and stress hormone release in healthy adults

Aims Aircraft noise disturbs sleep, and long-term exposure has been shown to be associated with increases in the prevalence of hypertension and an overall increased risk for myocardial infarction. The exact mechanisms responsible for these cardiovascular effects remain unclear. Methods and results We performed a blinded field study in 75 healthy volunteers (mean age 26 years), who were exposed at home, in random order, to one control pattern (no noise) and two different noise scenarios [30 or 60 aircraft noise events per night with an average maximum sound pressure level (SPL) of 60 dB(A)] for one night each. We performed polygraphy during each study night. Noise caused a worsening in sleep quality (P < 0.0001). Noise60, corresponding to equivalent continuous SPLs of 46.3 dB (Leq) and representing environmental noise levels associated with increased cardiovascular events, caused a blunting in FMD (P = 0.016). As well, although a direct comparison among the FMD values in the noise groups (control: 10.4 ± 3.8%; Noise30: 9.7 ± 4.1%; Noise60: 9.5 ± 4.3%, P = 0.052) did not reach significance, a monotone dose-dependent effect of noise level on FMD was shown (P = 0.020). Finally, there was a priming effect of noise, i.e. the blunting in FMD was particularly evident when subjects were exposed first to 30 and then to 60 noise events (P = 0.006). Noise-induced endothelial dysfunction (ED) was reversed by the administration of Vitamin C (P = 0.0171). Morning adrenaline concentration increased from 28.3 ± 10.9 to 33.2 ± 16.6 and 34.1 ± 19.3 ng/L (P = 0.0099). Pulse transit time, reflecting arterial stiffness, was also shorter after exposure to noise (P = 0.003). Conclusion In healthy adults, acute nighttime aircraft noise exposure dose-dependently impairs endothelial function and stimulates adrenaline release. Noise-induced ED may be in part due to increased production in reactive oxygen species and may thus be one mechanism contributing to the observed association of chronic noise exposure with cardiovascular disease.

The impact of solvent mixtures on neurobehavioral performance: conclusions from epidemiological data.

The review of epidemiological studies investigating the neurobehavioral effects of occupational exposure to solvent mixtures sought to contribute to the following issues: (1) Identification of affected cognitive and motor functions. (2) Identification of sensitive neuropsychological tests. (3) Analysis of exposure-effect relationships. The approach was based on the meta-analytical method of effect size estimates. Fifty-three groups from occupational studies were included in the meta-analysis. Forty-eight neuropsychological performance variables could be analyzed as they were included in at least three studies. Seventeen articles provided detailed information on the constituents of mixtures, thereby enabling the computation of an exposure index that allowed the comparison of different mixtures. Significant negative effect sizes were obtained for 12 test variables measuring attention, memory, motor performance and constructional abilities. The greatest proportion of lower performance scores in the exposed groups was shown by different tests of attention: significant effect sizes between d=-0.16 and -0.46 were calculated. Tests of cognitive processing speed, response alternation and inhibition seemed to be sensitive tools for the detection of poorer performance. Exposure-effect relationships were mainly characterized by inconsistent patterns. Crude and inappropriately calculated exposure measures were blamed for this outcome. A healthy worker effect was suggested more consistently: studies examining groups with longer exposure duration obtained smaller effect sizes. Indications of confounding were observed; however, they did not seem sufficient to question consistent effect size patterns. Paying greater attention to the measurement of exposure and including measures of confounding is advisable for future studies and would enhance the explanatory power of cross-sectional studies and meta-analyses.

Effects of high doses of toluene on color vision.

High exposure to toluene may cause optic neuropathy and retinopathy, both associated with dyschromatopsia. Another solvent, ethanol, is known to induce acute blue-yellow dyschromatopsia. This study investigated the acute effects of high doses of toluene on color vision. Eight male printshop workers were examined before and after cleaning printing containers with pure toluene. After cleaning, concentrations of toluene in blood were between 3.61 and 7.37 mg/l. Color vision was tested with the Farnsworth panel D-15 test, the Lanthony desaturated panel D-15 test, and the Standard Pseudoisochromatic Plates part 2. For control of possible acute effects, eight workers of a metal-working factory without any neurotoxic exposure were tested according to the same procedure. Acute exposure to toluene did not cause impairment of color vision. However, statistical power is limited due to the small number of exposed subjects. Color vision of the printshop workers tested before cleaning was slightly impaired (statistically not significant) when compared with unexposed subjects.

Exposure to 200 ppm of methanol increases the concentrations of interleukin-1β and interleukin-8 in nasal secretions of healthy volunteers

This study was designed to investigate subclinical irritating effects of methanol on functional and immunologic parameters in human respiratory epithelia. Twelve healthy, nonsmoking individuals were exposed to concentrations of 20 and 200 ppm of methanol in an exposure chamber. The concentrations of interleukin (IL)-8, IL-1β, IL-6, and prostaglandin E2 (PGE2) were monitored. The saccharin transport time test was used to evaluate mucociliary transport. Video interference contrast microscopy was used to determine the ciliary beat frequency of nasal epithelial cells. Subjective symptoms were assessed with a questionnaire. The median concentrations of IL-8 and IL-1β were significantly elevated after exposure to 200 ppm of methanol as compared to exposure to 20 ppm (IL-1β, 21.4 versus 8.3 pg/mL, p = .001; IL-8, 424 versus 356 pg/mL, p = .02). The release of IL-6 and PGE2 did not change significantly (IL-6, 10.3 versus 6.5 pg/mL, p = .13; PGE2, 13.6 versus 13.4 pg/mL), nor did the ciliary beat frequency or the saccharin transport time. Both IL-8 and IL-1β proved to be sensitive indicators for subclinical irritating effects of methanol in vivo. The German threshold limit of 200 ppm of methanol does not prevent subclinical inflammatory reactions of the nasal respiratory mucosa.

Measuring mechanical pain: The refinement and standardization of pressure pain threshold measurements

Pain thresholds are widely used in behavioral research, but unlike other pain modalities, a standardized assessment of pressure pain remains a challenge. In this research, we describe the application of an automatic pressure algometer with a linear increase in force. Ergonomically designed fixation devices were developed to increase the accuracy and to shorten the time of each measurement. Ten healthy volunteers were included in a pilot study to test the algometry method. Pressure pain thresholds (PPTs) were investigated over 2 experimental days in three nonconsecutive runs at 29 measurement sites. During the experiment, subjects reported their subjective sleepiness, level of state-anxiety, psychological status and the perceived pain intensity of each measurement. Pain intensity ratings indicate that instructions were followed. State-anxiety and subjective sleepiness levels were low throughout the experiment. The method has proven to be suitable for standardized PPT measurements across the body in an ergonomic, safe, and user-friendly fashion.

Acute effects of low doses of methyl parathion on human EEG.

Biological monitoring of workers exposed to organophosphates consists mainly of measuring serum or erythrocyte cholinesterase activity. However, animal experiments and a field study suggest that quantitative analysis of EEG may be more sensitive. In a parallel group design, 25 farmers were investigated, spraying methyl parathion or water for 50min. EEG was recorded before and after spraying. Serum and erythrocyte cholinesterase activity was compared with intraindividual pre-exposure values. Plasma methyl parathion concentrations ranged up to 12.1μg/l, methyl paraoxon was not detectable. Based on plasma concentrations, two exposed subgroups were defined. In EEG recorded with closed eyes, α(1)-power increased insignificantly (Kruskal-Wallis test) in both subgroups. β(1)-power was enhanced in both exposed subgroups, reaching significance (p≤0.05) at five of 17 electrodes. Spearmans rank correlation showed a significant association between methyl parathion plasma concentration and the median of β(1)-band power of the 17 electrodes (rho=0.48, p=0.015). Cholinesterase activity did not decrease. On a group basis, EEG is possibly more sensitive than cholinesterase. EEG changes suggest brain cholinesterase inhibition following low exposure to methyl parathion.

Porphyrin studies in TCDD-exposed workers

Abstract2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin (TCDD) has been shown to inhibit uroporphyrinogen decarboxylase activity resulting in chronic hepatic porphyria. From a cross-sectional study of 170 workers in chemical industry 68 showed elevated coproporphyrin levels, interpreted as secondary coproporphyrinuria. Three persons suffered from chronic hepatic porphyria in subclinical stages. None of the workers showed an overt porphyria cutanea tarda. A lowgrade zinc protoporphyrinemia was observed in three persons. Forty-three of the 170 workers were evaluable for investigating the effect of TCDD on porphyrin levels. No significant correlation was found between TCDD concentration in adipose tissue and the level of uroporphyrin and coproporphyrin. The influence of a chloracne history is described.

mRNA Induction and Cytokine Release of Inflammatory Mediators During In Vitro Exposure of Human Nasal Respiratory Epithelia to Acetaldehyde

Acetaldehyde has been shown to be cytotoxic and carcinogenic to the upper respiratory tract epithelium of rodents following long-term exposure. Most animal studies have concentrated on carcinogenicity and DNA–protein cross-link formation, while less is known about potential dose- and time-dependent induction of aldehyde-induced rhinitis in humans. In this in vitro study, 22 primary cell cultures established from inferior turbinate tissue of healthy individuals were exposed to acetaldehyde concentrations of 50 (German MAK value) or 500 ppm for 4 or 24 h. mRNA expression and protein levels of cytokines and other inflammatory mediators were quantified at the end of the 4- and 24-h exposures. Controls were exposed to synthetic air. Quantitative polymerase chain reaction (Q-PCR) analysis was performed for interleukin (IL)-6, IL-8, IL-1β, monocyte chemotactic protein (MCP)-1, tumor necrosis factor (TNF)-alpha, GMCSF, Cox-1, and Cox-2. Enzyme-linked immunosorbent assay (ELISA) was performed from culture supernatants for IL-6, IL-8, IL-1β, MCP-1, TNF-alpha, and GMCSF. Significant inductions of IL-1β, TNF-alpha, and Cox-1 and Cox-2 mRNA were observed following exposure to ≥50 ppm acetaldehyde for 4 h. IL-6 and MCP-1 were also induced following a 4-h exposure to 500 ppm acetaldehyde. For all these parameters, effects were significantly stronger at the higher concentration. After 24-h of exposure only Cox-2 remained significantly elevated at 500 ppm but not at 50 ppm, while all other mediators had been downregulated. The obtained data suggest that with exposure to 500 ppm and remarkably also at the level of the occupational exposure limit of 50 ppm, an immediate transient upregulation of inflammatory mediator mRNA is induced, possibly leading to subclinical inflammatory effects.

The Candy Smell Test in clinical routine.

Background The “Candy Smell Test” (CST) has been introduced as a new testing method for the evaluation of the human sense of smell. In contrast to other established orthonasal smell tests, the CST addresses the retronasal application of odors, typical for food aroma effects during mastication and swallowing. The aim of this study was to evaluate the CST in a clinical setting in patients with olfactory dysfunction and normal controls against the Sniffin’ Sticks test. Furthermore, cutoff points for normal and pathological results in the CST should be determined. Methods The olfactory performance of 96 patients presenting with olfactory disorders and 71 healthy controls was evaluated with the CST—comprised of 23 different aromatized smell candies and the extended Sniffin’ Sticks test (threshold, discrimination, and identification). The control group was gender matched but included also younger persons. Results The tested subjects could easily understand the procedures and were motivated to participate. The CST correlated well with the Sniffin’ Sticks for all tested subjects and for patients (n = 96) and controls (n = 71). The proposed cutoff value to differentiate normosmia from hyposmia in the CST was a score of <16 (i.e., 16 correctly identified odors) of 23. A score below 13 in the CST was the cutoff value for anosmia. Conclusion The CST is an easy-to-handle reliable tool to investigate retronasal olfaction suited for clinical determination of normosmia, hyposmia, and ansomia. In addition, it can be used for investigation where self-application is necessary such as in large survey studies.

Acute effects of 1,1,1-trichloroethane on human olfactory functioning.

Background Animal experiments indicate that 1,1,1-trichloroethane can cause degeneration of the olfactory epithelium. The effects of 1,1,1-trichloroethane on human odor perception still have not been investigated. The goal of this study was to learn more about acute effects of 1,1,1-trichloroethane. Methods Twelve healthy, nonsmoking students were exposed to 200 and 20 ppm (control) 1,1,1-trichloroethane in an exposure chamber for 4 hours according to a crossover design. Olfactory functioning was investigated with the Sniffin’ Sticks. The test includes the determination of the detection threshold for n-butanol and an odor identification test. Results After 1 hour of exposure to 200 ppm 1,1,1-trichloroethane, no effects on olfactory functioning were observed. After 4 hours, the olfactory threshold for n-butanol was slightly (p = 0.04) elevated. Conclusion The threshold shift may be caused by different mechanisms, including inflammation of the olfactory mucosa or degeneration of receptor cells.