Hyena (German) 8.8 serial key or number

Associated Data

Supplementary Materials

Additional file 1: Table S1. Linear regression coefficient after exponentiation for the relation between cortisol outcomes and aircraft noise levels removing in turn one country from the HYENA study. Table S2. Linear regression coefficient after exponentiation for the relation between cortisol outcomes and aircraft noise levels in women under and above 50&#x;years old.

GUID: 30AFA8AF-8C3EE-CE

Data Availability Statement

Not applicable.

Abstract

Introduction

Aircraft noise exposure represents a major issue for public health policies. Impacts on human health are of growing concern, and many adverse effects have been evidenced [1]. Extensive information is available to quantify the burden of disease from aircraft noise exposure associated with annoyance, sleep disturbances, cardiovascular disease including hypertension [2&#x;7], and altered cognitive performance among children [8, 9]. A proposed biological process is the release of stress hormones with noise exposure, leading to disruption of hormonal rhythms by activating the Sympathetic-Adrenal-Medullary (SAM) axis and the Hypothalamic-Pituitary-Adrenal (HPA) axis [10, 11]. Cortisol can be viewed as a stress indicator, and is easy to measure non-invasively [12]. Its concentration may be a clinical indicator of disturbed HPA axis activity, and therefore can be used to assess chronic stress effects due to noise exposure [13]. Specific roles of cortisol include regulation of blood glucose levels, lipolysis, immune suppression, and regulation of blood pressure [14]. The cortisol secretion follows a circadian rhythm in the absence of stimuli: levels decline slowly throughout the day, from a peak in the early morning (20&#x;30&#x;min after awakening) to a nadir in the evening [15]. Cortisol can easily be measured in saliva and this reliably reflects the serum-free cortisol concentration [16].

The majority of the studies have focused on average levels of cortisol at specific times of the day [17, 18]. However, when subjects are chronically exposed to high levels of energy mobilization after exposure to a stressor, the regulation of the cortisol response could be disturbed. This may be in the form of inability to lower cortisol during the calmer part of the day with no decrease in cortisol when the subject is expected to fall asleep. After long intensive periods without possibility to recuperate, the subject may develop a low flat curve, which is associated with inability to mobilize cortisol when it is needed [19]. Several studies showed an association between long-term stress exposure and a flattening of the diurnal cortisol rhythm across the day [20&#x;22]. The variability of cortisol during the day could therefore be used as an indicator of a disturbed HPA axis regulation.

Many studies have been carried out on the relationship between noise exposure and cortisol levels, but conclusions are still unclear [12]. Biological responses may differ depending on the source (occupation, road traffic, rail or air) and characteristics of the study population (gender, age) [23]. Studies on aircraft noise exposure and cortisol levels have mainly focused on children&#x;s populations. The main studies to date on adults were a subset of HYENA (HYpertension and Exposure to Noise near Airports) [24] and DEBATS (Discussion on the health effects of aircraft noise) [5] projects. The HYENA study analysis found increases in morning saliva concentrations with aircraft noise exposure in women only [17], while DEBATS found higher evening but not morning cortisol in both men and women [25].

The present HYDE (HYENA&#x;+&#x;DEBATS) project aims to combine both HYENA and DEBATS datasets in order to elucidate the effects of aircraft noise exposure on saliva cortisol levels. The HYENA study included persons living near one of seven major European airports [London Heathrow (United Kingdom), Berlin Tegel (Germany), Amsterdam Schiphol (the Netherlands), Stockholm Arlanda and Bromma (Sweden), Milan Malpensa (Italy), and Athens International Airport Eleftherios Venizelos (Greece) Airports]. Specifically, the HYDE present project added to the HYENA study the three French airports included in the DEBATS study: Lyon Saint Exupéry, Toulouse-Blagnac, and Paris-Charles de Gaulle &#x; the latter being a major European airports in term of passenger numbers [26]. Combination of HYENA and DEBATS enabled a higher number of participants to be included in the analyses, resulting in an increase in statistical power, and extending the scope of the results. As gender differences in production of corticosteroid-binding globulin have been shown [27], the higher number of participants in the HYDE study allowed us to investigate the association between aircraft noise exposure and cortisol secretion for male and female separately. Moreover, the HYDE study also provided an opportunity to consider a new approach based on the relative variation in cortisol levels per hour taking into account time between measurements as well as morning and evening levels.

Methods

Results

Participation rates differed between countries, from approximately 30% in France, Germany, Italy, and the UK to 46% in the Netherlands, 56% in Greece, and 78% in Sweden. Figure 2 shows noise exposure levels by country and gender. The four noise indicators were highly correlated (correlation coefficients between and ). Participants from the UK were more likely to be exposed to higher noise levels compared to participants from other countries (p&#x;&#x;). Characteristics of the study population, stratified by categories of noise exposure in terms of L_den are presented in the Table 1. Few differences appeared between noise categories. They are related to alcohol intake in men (p&#x;=&#x;) and physical activity in women (p&#x;=&#x;).

There was no statistically significant gender difference for the cortisol levels (Table 2): geometric means for morning levels were slightly higher for men compared to women (&#x;nmol. L^&#x;&#x;1 and &#x;nmol. L^&#x;&#x;1 respectively), whereas geometric means for evening levels were slightly lower for men compared to women (&#x;nmol. L^&#x;&#x;1 and &#x;nmol. L^&#x;&#x;1 respectively). Men showed a slightly higher geometric mean for the variation per hour than women (&#x;nmol. L^&#x;&#x;1.H^&#x;&#x;1 and &#x;nmol. L^&#x;&#x;1.H^&#x;&#x;1 for men and women respectively.) The geometric means for the average relative-variation per hour in men and in women were statistically and significantly different ( and respectively (p&#x;=&#x;)).

Crude and adjusted linear regression coefficients after exponentiation for each of the cortisol outcomes (morning and evening cortisol levels, variation per hour, and relative-variation per hour) in relation to aircraft noise levels are shown in Table 3. Analyses were performed for each noise indicator separately. No statistically significant association was found in men, for any of the cortisol outcomes, or noise indicators, both for univariate and multivariate analyses. Statistically significant crude estimates were shown in women only for the L_night in relation to the evening level, and for all the noise indicators in relation to the relative variation. For multivariate analyses, aircraft noise levels were not related to the morning concentration of cortisol, but were associated with an increase in evening cortisol concentration (exp(²)&#x;=&#x;, CI95% &#x; for a dB(A) increase in LA_eq,16h; exp.(²)&#x;=&#x;, CI95% &#x; for a dB(A) increase in L_den; exp.(²)&#x;=&#x;, CI95% &#x; for a dB(A) increase in L_night &#x; while the relation between evening level and LA_{eq, 24h} was borderline significant exp.(²)&#x;=&#x;, CI95% &#x; per dB(A) increase) in women. For cortisol variation per hour, an association at the borderline of the statistical significance was found with L_night suggesting a 11%-decrease in the average difference between both samplings (exp(²)&#x;=&#x;, CI95% &#x; per dB(A) increase). Considering the relative-variation per hour, statistically significant associations were seen for a decrease of the relative difference between both samplings, whatever the noise indicator (a decrease of 8 to 11% according to the considered noise indicator). The strongest association was found for the L_night exposure (exp(²)&#x;=&#x;, CI95% &#x; per dB(A) increase).

No obvious differences were observed when noise annoyance or noise sensitivity were included in the model. When these factors were included in the models as factor of interest instead of noise levels, results did not show statistically significant association with cortisol outcomes, except an association between aircraft noise annoyance and the relative variation of cortisol in women only (exp(²)&#x;=&#x;, CI95% &#x; for highly annoyed women compared to not annoyed women).

When analyses were carried out removing one country from the HYENA study in turn from the study population, results were similar to those found for the whole study population (See Additional file 1: Table S1).

Analyses carried for women under or above 50&#x;years of age showed statistically significant associations between aircraft noise exposure and cortisol outcomes in women under 50, whereas no statistically significant association was found in women 50 and older (See Additional file 1: Table S2).

Finally, the results of the sensitivity analyses with the adjusted cortisol levels (results not shown) to overcome differences in the cortisol determination method (ELISA versus RIA method) were similar to the results in Table Table

Discussion

This study provides some support for the hypothesis that psychological stress induced by aircraft noise exposure, results in disturbed cortisol regulation, with an increase in evening cortisol levels and a flattening of the usual (absolute or relative) variation per hour. The results of the present study are partly in line with those found based on the DEBATS participants only [25], where similar conclusions were drawn, but in that study no difference were shown between gender subgroups. Considering the HYENA participants only, statistically significant associations were found only in women, but for an increase in the morning cortisol levels [17]. The HYDE pooled-analyses, providing a greater statistical power, found statistically significant associations between aircraft noise exposure and modification of the cortisol stress-hormone secretion for women only. Moreover, the main finding of this study was the statistically significant associations between noise levels and noise annoyance and the average relative-variation per hour.

The use of relative-variation per hour contributes to a new approach to analysis of cortisol in relation to noise exposure. It also allows for potential measurement differences between HYENA and DEBATS related to sampling and laboratory analysis: the ELISA (enzyme-linked immunosorbent) method in the DEBATS study and the RIA (radioimmunoassay) method in the HYENA. For morning and evening cortisol levels, the use of the linear relationship between ELISA and RIA methods [35] makes levels of cortisol concentrations directly comparable for the HYDE study. Regression conclusions were similar to those presented in Table Table3,3, carried out without the use of this equation.

Although procedures in samplings were similar, differences occurred in the morning sampling which was requested to be collected 30&#x;min after awakening in HYENA, and directly at awakening in DEBATS. It has been shown that cortisol levels rapidly rise by 50&#x;75% within the first 30&#x;min after awakening, and remain elevated for the next 30&#x;min after the peak. This pattern in cortisol secretion has been shown to be independent of time of awakening, sleep quality, sleep duration, and age [42]. However, it seems quite difficult to define precisely when the awakening occurred. If morning cortisol samples were collected before the cortisol peak in the DEBATS study, it is likely that these cortisol levels were lower than the peak level. However, this measurement bias is independent from the noise levels, and could stand for a non-differential measurement error. Thus, it could have led to biased results toward the null value and could explain the fact that no association was observed for morning concentrations. Despite this, a statistically significant association was still observed for morning-evening cortisol variation and average relative cortisol variation per hour.

The present study found statistically significant associations between aircraft noise levels and cortisol outcomes only in women. Even if they were closer to 1, the estimates for males were not so different from that of females, especially for the relative variation per hour. This can either be explained by the fact that the men sample was smaller than the female study sample or by the fact that there was no association in men.

These results are in line with those showing that women were more sensitive to stressors in general [43, 44]. But they are not in line with those of previous studies considering gender-differences and showing statistically significant associations between aircraft or traffic noise exposure and hypertension only in men [5, 36, 45]. As statistically significant associations in women were stronger considering aircraft noise levels during the night with the L_night, the hypothesis that women have a higher susceptibility to noise during sleep could be relevant. Recent research has pointed out different physiological characteristics in both men and women, leading to differences in the pathogenesis of cardiovascular diseases. Indeed, several studies on the effects of traffic noise exposure on the risk of hypertension showed stronger associations for men [1, 46&#x;48]. This interaction could also explain the findings of the present study concerning the results of analyses in women under and over 50&#x;years of age. Indeed, the associations were stronger in women under 50&#x;years of age, while there was no statistically significant relationship in women over 50&#x;years of age. After 50&#x;years of age, with the disappearance of oestrogens, women&#x;s hormonal systems tend to get closer to those of men, thus could explain that the results were almost similar in men and in women after 50&#x;years of age in this study.

Statistically significant associations in women were stronger for aircraft noise levels during the night. These results support the hypothesis that susceptibility to noise would be higher during the night [49]. Sleep duration could be regarded as a confounder or as a mediator in the relation between aircraft noise exposure and the cortisol secretion [40, 50], since night-time noise can impact on sleep latency and induce early morning awakenings. Nevertheless, when this variable was included in the models, the results remained very similar, thus excluding the role of confounder or of mediator of sleep duration in the association between aircraft noise levels and cortisol secretion. As restrictions in night traffic concerned every airport except London&#x;s Heathrow and Amsterdam Schiphol, we added an interaction term between country and noise exposure levels in multivariate models. Nevertheless, no substantial difference between countries was seen (results not shown). In sensitivity analyses, the results remained similar when the HYENA countries were removed one at a time from analyses. Associations were even stronger when the UK, the country with the highest noise exposure levels, was removed.

Selection bias cannot be excluded in the present study. The low response rate in most of the participating countries may be a potential weakness of this study. However, only minor differences were found between the characteristics of the participants and those of the nonresponders according to aircraft noise exposure categories [5, 36]. Aircraft noise levels were estimated at home address of each participant, but this may result in some exposure misclassification. It was not possible to take into account their noise exposure outside their home because no information was collected on time schedule and the work or leisure places of each participant. It is more likely that people are in their home at night, so night-time exposure is more likely to be close to the estimated noise level and may be the reason that the strongest associations were observed for L_night. However, as the four noise indicators were highly correlated, this did not allow the effects of noise exposure during the day or at night to be disentangled.

When annoyance from aircraft noise or noise sensitivity were included as confounders in the models, no obvious differences were seen in results. These findings suggest that cortisol variations may be directly connected to aircraft noise exposure rather than mediated through noise annoyance and noise sensitivity.

Noise has been assumed to be a non-specific stress factor activating the autonomic nervous system and endocrine pathway [12, 51]. Stress is biologically distinguished by the secretion of hormones: catecholamines (norepinephrine, adrenaline) and cortisol [52]. The use of saliva cortisol in this study rather than blood cortisol or cortisol in the urine has been motivated by the fact that it is easy to measure in the general population, by its reliability, rapidity to sample, and non-invasiveness [53]. However, cortisol secretion can be influenced by season, time and week day of sampling [54], sex, age, BMI, physical activity, alcohol consumption, smoking, medication, high food intake, sleep quality, occupational activity, female hormonal contraception, and pregnancy [50] - all factors that affect hormonal balance [55]. All of these factors may moderate the association between aircraft noise exposure and cortisol secretion. Residual confounding bias cannot be excluded in this study but we have tried to minimize it by including all the information we have about these factors in the models.

The findings of the present study support a hypothesis that noise induces stress and are coherent with previous studies finding associations between aircraft noise exposure and hypertension or antihypertensive and anxiolytic medication intake [5, 36, 37]. There is evidence suggesting a role for cortisol in hypertension [56, 57], and other stated for an increase in the cortisol stress response responding to mental stress tasks, thus leading to incident hypertension [58].

Conclusions

The present results support the hypothesis that exposure to aircraft noise, at night in particular, could make the HPA axis less flexible, especially in women, resulting in higher average values for the evening cortisol concentration, and therefore a flattening of the difference between morning and evening levels. The cause/effect relations and the biological process between noise exposure and HPA dysregulation are of major importance and need to be further elucidated.

Acknowledgements