[show abstract][hide abstract] ABSTRACT: Indoor air pollution (IAP) that constitutes a major global public health problem requiring increasing efforts in research and policymaking and it may have special significance for elderly that are likely to spend most of their day indoors and appear to be particularly susceptible to adverse effects of chemical pollutants and bio-contaminants. Yet, evidence existing on the effects of IAP in elderly is scanty. The Geriatric study in Europe on health effects of air quality in nursing homes (GERIE) study aims to assess health effects of major indoor air pollutants and thermal conditions in elderly (> 70 years) living stably in nursing homes (NH) across Europe. Respiratory effects were particularly considered as airways and lung constitute the first target of air pollutants.Objectives: We describe here the rationale and the methods of the GERIE Study.
8 nursing homes were randomly selected in 7 European countries. Twenty individuals were randomly selected in each nursing home, 20 individuals were randomly selected. Major indoor and outdoor air chemical pollutants (PM10, PM2.5, PM0.1, formaldehyde, NO2; O3, VOC, CO2) and bio-contaminants (moulds, allergens) were assessed objectively with standardized procedures. Major health status indicators were assessed through a standardized questionnaire, non-invasive clinical tests and blood and urine biomarkers as well as saliva for ADN.
The GERIE study has given the opportunity to publish two reviews on respiratory health effects of indoor and outdoor air pollution in elderly. In addition it has provided the inventory of air quality and thermal conditions in 50 nursing homes across Europe and data on respiratory health status in 600 elderly aged 82 years in mean. Major future results will include the relationships between NH environment and health in elderly.
The main long-term purpose of the GERIE study is to improve the health of elderly who permanently reside in nursing homes or of those who are exposed to indoor air pollution because of reduced mobility.
Multidisciplinary respiratory medicine 11/2013; 8(1):71. · 0.05 Impact Factor
[show abstract][hide abstract] ABSTRACT: To examine the value of urinary 5-hydroxy-N-methyl-2-pyrrolidone (5-HNMP) and 2-hydroxy-N-methylsuccinimide (2-HMSI) in a population of workers exposed to N-methyl-2-pyrrolidone (NMP) and to look for health effects of exposure to this organic solvent.
Airborne NMP was determined according to the NIOSH method. Urinary 5-HNMP and 2-HMSI (after and before next shift) were determined by liquid chromatography with tandem mass spectrometry. Outcomes were effects on lung, kidney, skin and mucous membranes, nervous system, haematopoiesis and liver determined by clinical examination and laboratory measurements. Univariate statistical methods and multiple regressions were used to analyse results. Skin resorption, smoking and other potential confounders were taken into account.
Three hundred twenty-seven workers were eligible out of which 207 workers (63 %) participated. Ninety-one of these worked with NMP. Occupational exposure to NMP did often not occur daily and ranged from non-detectable to 25.8 mg/m(3) (median = 0.18). Urinary 2-HMSI (mg/l; before next shift) was the best biomarker of exposure to NMP, explaining about 70 % of the variance, but most likelihood ratios did not allow for ruling exposure in or out, at these low levels of exposure. Creatinine adjustment did not improve the results clearly. No clear and consistent health effects could be associated with NMP exposure. No indication for a bias due to non-participation was found.
Biological monitoring, primarily urinary 2-HMSI (mg/l; before next shift), is of value to estimate exposure to NMP even when exposure is irregular and low. Likelihood ratios of urinary 5-HMNP or 2-HMSI are, however, not quite satisfactory at these low levels. No irritant or other health effects were found.
International Archives of Occupational and Environmental Health 09/2013; · 2.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: BACKGROUND: The current risk assessment for environmental Cd largely relies on the assumption that urinary Cd (U-Cd) is a reliable biomarker of the Cd body burden. Recent studies increasingly question the validity of this assumption. OBJECTIVES: We studied the lifetime trend of U-Cd as a function of diuresis, gender, smoking status and protein tubular reabsorption. We also analyzed the associations between U-Cd and urinary proteins. METHODS: Cd, retinol-binding protein and albumin were measured in the urine of six cohorts of the general population of Belgium with a mean age ranging from 5.7 to 88.1 years (N=1,567). Variations of U-Cd with age were modeled by using natural cubic splines. RESULTS: In both genders, U-Cd in μg/L decreased to a minimum (around 0.20) at the end of adolescence, then increased till the age 60-70 (around 0.60 in never-smokers) before leveling off or decreasing. Expression in µg/g creatinine amplified these variations (minimum, 0.15; maximum, 0.70) and also caused much higher U-Cd values in women. There was no difference in U-Cd levels between never- and former smokers and the difference with current smokers did not increase over lifetime. Lifetime curves of U-Cd were shifted to higher values with increasing urinary retinol-binding protein or albumin, a consequence of the co-excretion of Cd with proteins. CONCLUSIONS: At low exposure levels, U-Cd and age are associated through nonlinear and non-monotonous relationships that appear to be mainly driven by the recent Cd intake and physiological variations in the excretion of creatinine and proteins.
Environmental Health Perspectives 06/2013; · 7.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: RATIONALE: Irritant chlorination products in swimming pools can cause respiratory problems in swimmers but their possible implication in allergies development is still unclear. OBJECTIVES: To assess prospectively whether early-life attendance at chlorinated pools increases the risks of IgE sensitization and of airways inflammation later during childhood. METHODS: We conducted a two-year prospective study among 196 kindergarten children (mean age of 5.7 years, 54% of boys). We measured exhaled nitric oxide (eNO) and aeroallergen-specific IgE in nasal mucosa. Parents completed a questionnaire about the child's health, chlorinated pool attendance and potential confounders. MAIN RESULTS: Ever swimming at indoor or outdoor chlorinated pools before the age of three years was associated with higher odds for new-onset IgE sensitization to house dust mite (adjusted odds ratio [aOR] 2.93, 95% confidence interval [CI] 1.14-7.55) and for new-onset increased eNO (>15ppb; aOR, 4.54, 95% CI 1.48-13.9). For both outcomes, aORs increased dose-dependently with time spent in chlorinated pools with values reaching, respectively, 3.60 (95% CI 1.21-10.7) and 5.92 (95% CI 1.72-20.5) when the cumulative pool attendance exceeded 60h These risks appeared independently of each other, of parental history of allergies and of pre-existing diseases, including eczema, which at baseline was more prevalent in early swimmers (aOR, 2.91; 95% CI 1.23-6.89). Such associations were not seen with IgE sensitization to pollen or cat allergens. CONCLUSION: Attendance at chlorinated swimming pools in early life is associated with higher risks of new-onset airways inflammation and IgE sensitization to house dust mite, independently of other risk factors.
International journal of hygiene and environmental health 03/2013; · 2.64 Impact Factor
[show abstract][hide abstract] ABSTRACT: Recent studies suggest that domestic water hardness and swimming in chlorinated pools may increase the prevalence of childhood eczema. The combined influence of these two factors as well as their interaction with atopic status has not been investigated.
We conducted a cross-sectional study on 358 children aged 5-6 years (54% of boys) in 30 kindergarten schools. Parents completed a questionnaire about the child's health, chlorinated pool attendance and potential confounders. Data about tap water quality were provided by water companies. Atopy was defined as a sensitization to at least one aeroallergen or as a medication for allergy. The effect of water hardness and infant swimming practice were assessed by multivariate logistic models. In addition, the effects of these risk factors combined with atopy were evaluated using two measures of biological interaction: the attributable proportion of interaction (AP) and the synergy index (S). AP>0 and S>1 indicate biological interaction between the two risk factors.
Water hardness was linearly associated to the prevalence of eczema whereas the relationship of eczema with infant swimming was not linear. We observed a biological interaction between hard water (>150 mg/L CaCO(3)L(-1)) and atopic status that increases the prevalence of eczema with an odds ratio (OR) of 3.30 and a 95% confidence interval (CI) of 1.34-8.15 (AP, 0.41; 95% CI 0.15-0.66 and S, 2.4; 95% CI 0.96-6.01). Infant swimming practice combined with atopy also increased the prevalence of eczema (OR, 2.72; 95% CI 1.29-5.74) although none of the interaction measures was significant. However, when water hardness and infant swimming were combined, there was no further increase of the eczema prevalence due to some form of antagonistic interaction between these two factors (AP, -0.56; 95% CI -1.12 to -0.01 and S, 0.54; 95% CI 0.33-0.87).
Our study shows that exposure to hard water and infant swimming interact with atopic status to increase the prevalence of childhood eczema. A breaching of the epidermal barrier by detergents or salts in hard water and by chlorine-based oxidants in swimming pool water might explain these interactions.
Environmental Research 05/2012; 116:52-7. · 3.24 Impact Factor
[show abstract][hide abstract] ABSTRACT: Changes in the airways epithelium caused by environmental insults might play a role in the development of allergic rhinitis. We measured albumin and Clara cell protein (CC16) in the nasal lavage fluid (NALF) from 474 adolescents (263 girls and 211 boys). The NALF CC16/albumin ratio, integrating the permeability and cellular integrity of the nasal epithelium, decreased mostly with time spent in chlorinated pools. In boys, a lower CC16/albumin ratio in NALF was associated with an increased risk of house dust mite sensitization. The results suggest that the CC16/albumin ratio in NALF can be used to detect nasal epithelium alterations linked to allergic sensitization.
[show abstract][hide abstract] ABSTRACT: Heavy metals can cause renal effects on vulnerable populations but it is uncertain whether these metals still pose health risks at the low exposure levels now prevailing in most industrialized countries. In a cross-sectional study performed on 736 adolescents, we assessed the associations between the concentrations of cadmium and lead in blood and urine and the urinary concentrations of albumin and of low-molecular-weight (LMW) proteins, retinol-binding protein (RBP) and β(2)-microglobulin. Multiple regression analyses were tested using urinary markers normalized to urinary creatinine or specific gravity. Median metal concentrations were in blood (μg/L): lead, 15.1, cadmium, 0.18 and in urine (μg/g creatinine): cadmium, 0.09 and lead, 0.82. Multivariate analyses revealed significant associations in urine between RBP and cadmium as well as between β(2)-microglobulin and lead whereas no associations were seen with metals in blood. These associations were completely abolished in subjects with increased urinary albumin, which may be explained by the competitive inhibition of LMW protein reabsorption by albumin. Given the evidence that cadmium and lead circulate mainly bound to LMW proteins, these associations observed at low exposure might simply reflect the interindividual variations in the renal uptake of proteins sharing the same affinity for tubular binding sites.
[show abstract][hide abstract] ABSTRACT: Long-term exposure to cadmium (Cd) causes renal dysfunction, but the change in renal function with exposure is unknown. We assessed the evolution of Cd-induced renal effects after a reduction in dietary exposure to Cd in rice.
Four hundred twelve residents in previously Cd-polluted and nonpolluted areas were examined twice, in 1998 and in 2006. Changes in blood Cd, urinary Cd, and kidney function [N-acetyl-β-d-glucosaminidase (NAG), β2-microglobulin, and albumin in urine] were measured.
In the most polluted area, mean blood Cd was 8.9 μg/L and 3.3 μg/L in 1998 and in 2006, respectively, and urinary Cd was 11.6 and 9.0 μg/g creatinine. Urinary albumin in 1998 increased with urinary Cd, but no such exposure-response relation appeared for 2006 albumin versus urinary Cd 1998, indicating recovery. Other biomarkers of kidney function were also elevated in 1998. Partial recovery was observed for NAG among women and was suggested for β2-microglobulin among young individuals. The probability of having β2-microglobulin levels above the 95th percentile in 2006 was high in those with elevated β2-microglobulin in 1998 [odds ratio (OR) = 24.8; 95% confidence interval (CI): 11.2, 55.3] compared with albumin (OR = 3.0; 95% CI: 1.2, 7.5) and NAG (OR = 2.6; 95% CI: 1.6, 4.4).
Results suggest that a Cd-mediated increase in urinary albumin excretion is reversible upon substantial reduction of exposure. For markers of tubular effects, we observed a tendency toward improvement but not complete recovery. Data from repeated observations suggest that β2-microglobulin may be more informative than NAG as an indicator for an individual's future tubular function.
Environmental Health Perspectives 02/2012; 120(2):223-8. · 7.26 Impact Factor
[show abstract][hide abstract] ABSTRACT: Exposure to trichloramine (NCl(3)) in indoor swimming-pool environments is known to cause mucous membrane irritation, but if it gives rise to changes in lung function or asthma in adults is not known. (1) We determined lung function in volunteers before and after exposure to indoor pool environments. (2) We studied the occurrence of respiratory symptoms and asthma in a cohort of pool workers. DESIGN/METHODS/PARTICIPANTS: (1) We studied two groups of volunteers, 37 previously non-exposed healthy persons and 14 pool workers, who performed exercise for 2 h in an indoor pool environment. NCl(3) in air was measured during pool exposures and in 10 other pool environments. Filtered air exposures were used as controls. Lung function and biomarkers of pulmonary epithelial integrity were measured before and after exposure. (2) We mailed a questionnaire to 1741 persons who indicated in the Swedish census 1990 that they worked at indoor swimming-pools.
(1) In previously non-exposed volunteers, statistically significant decreases in FEV(1) (forced expiratory volume) and FEV(%) (p=0.01 and 0.05, respectively) were found after exposure to pool air (0.23 mg/m(3) of NCl(3)). In pool workers, a statistically significant decrease in FEV(%) (p=0.003) was seen (but no significant change of FEV(1))(.) In the 10 other pool environments the median NCl(3) concentration was 0.18 mg/m(3). (2) Our nested case/control study in pool workers found an OR for asthma of 2.31 (95% CI 0.79 to 6.74) among those with the highest exposure. Exposure-related acute mucous membrane and respiratory symptoms were also found.
This is the first study in adults showing statistically significant decreases in lung function after exposure to NCl(3). An increased OR for asthma among highly exposed pool workers did not reach statistical significance, but the combined evidence supports the notion that current workroom exposures may contribute to asthma development. Further research on sensitive groups is warranted.
[show abstract][hide abstract] ABSTRACT: The use of wood as heating and cooking fuel can result in elevated levels of indoor air pollution, but to what extent this is related to respiratory diseases and allergies is still inconclusive. Here, we report a cross-sectional study among 744 school adolescents (median age 15 years) using as main outcomes respiratory symptoms and diseases, exhaled nitric oxide, total and aeroallergen-specific IgE in serum, and two epithelial biomarkers in nasal lavage fluid (NALF) or serum, that is, Clara cell protein (CC16) and surfactant-associated protein D (SPD). Information about the wood fuel use and potential confounders was collected via a personal interview of the adolescent and a questionnaire filled out by the parents. Two approaches were used to limit the possible influence of confounders, that is, multivariate analysis using the complete study population or pairwise analysis of matched sub-populations obtained using an automated procedure. Wood fuel use was associated with a decrease of CC16 and an increase of SPD in serum, which resulted in a decreased serum CC16/SPD ratio (median -9%, P = 0.001). No consistent differences were observed for the biomarkers measured in exhaled breath or NALF. Wood fuel use was also associated with increased odds for asthma [odds ratio (OR) 2.2, 95% CI: 1.1-4.4, P = 0.02], hay fever (OR = 2.4, 95% CI: 1.4-4.3, P = 0.002), and sensitization against pollen allergens (OR = 2.1, 95% CI: 1.3-3.4, P = 0.002). The risks of respiratory tract infections, self-reported symptoms, and sensitization against house-dust mite were not increased by wood fuel use. The increased risks of asthma, hay fever and aeroallergen sensitization, and the changes of lung-specific biomarkers consistently pointed towards respiratory effects associated with the use of wood fuel.
[show abstract][hide abstract] ABSTRACT: To prospectively assess respiratory health in wastewater workers and garbage collectors over 5 years.
Exposure, respiratory symptoms and conditions, spirometry and lung-specific proteins were assessed yearly in a cohort of 304 controls, 247 wastewater workers and 52 garbage collectors. Results were analysed with random coefficient models and linear regression taking into account several potential confounders.
Symptoms, spirometry and lung-specific proteins were not affected by occupational exposure.
In this population no effects of occupational exposure to bioaerosols were found, probably because of good working conditions.
Occupational and environmental medicine 05/2011; 68(11):856-9. · 3.64 Impact Factor
[show abstract][hide abstract] ABSTRACT: Associations of proteinuria with low-level urinary cadmium (Cd) are currently interpreted as the sign of renal dysfunction induced by Cd. Few studies have considered the possibility that these associations might be non causal and arise from confounding by factors influencing the renal excretion of Cd and proteins.
We examined 184 healthy male workers (mean age, 39.5 years) from a zinc smelter (n = 132) or a blanket factory (n = 52). We measured the concentrations of Cd in blood (B-Cd) and the urinary excretion of Cd (U-Cd), retinol-binding protein (RBP), protein HC and albumin. Associations between biomarkers of metal exposure and urinary proteins were assessed by simple and multiple regression analyses.
The medians (interquartile range) of B-Cd (μg/l) and U-Cd (μg/g creatinine) were 0.80 (0.45-1.16) and 0.70 (0.40-1.3) in smelter workers and 0.66 (0.47-0.87) and 0.55 (0.40-0.90) in blanket factory workers, respectively. Occupation had no influence on these values, which varied mainly with smoking habits. In univariate analysis, concentrations of RBP and protein HC in urine were significantly correlated with both U-Cd and B-Cd but these associations were substantially weakened by the adjustment for current smoking and the residual influence of diuresis after correction for urinary creatinine. Albumin in urine did not correlate with B-Cd but was consistently associated with U-Cd through a relationship, which was unaffected by smoking or diuresis. Further analyses showed that RBP and albumin in urine mutually distort their associations with U-Cd and that the relationship between RBP and Cd in urine was almost the replicate of that linking RBP to albumin
Associations between proteinuria and low-level urinary Cd should be interpreted with caution as they appear to be largely driven by diuresis, current smoking and probably also the co-excretion of Cd with plasma proteins.
Environmental Health 01/2011; 10:37. · 2.71 Impact Factor
[show abstract][hide abstract] ABSTRACT: OBJECTIVE: To evaluate the threshold value of urinary cadmium (CdU) for renal dysfunction on the basis of relationships unconfounded by protein degradation, diuresis and the renal effects associated with chronic smoking. Methods We studied 599 workers (451 men, mean age 45.4 years) who were employed in four nickel-cadmium battery plants for 18.8 years on average. After adjustment for covariates by multiple regression, the CdU threshold values for increased concentrations of retinol-binding protein (RBPU) and b(2)-microglobulin (b(2)-mU) were assessed by logistic regression and benchmark dose analyses using as referents workers with CdU<1 μg/g creatinine. Results Relationships between urinary proteins and CdU (μg/g creatinine) were influenced by sex, age, diuresis and especially smoking. When considering all workers, odds for abnormal RBPU and b(2)-mU were significantly increased from CdU of 6-10 and >10, respectively. The benchmark dose (BMD5) and the benchmark dose lower limit (BMDL5) for a 5% excess in the background prevalence of abnormal RBPU and b(2)-mU were estimated at 5.1/3.0 and 9.6/5.9. When excluding ever smokers, odds for abnormal RBPU and b(2)-mU were both increased only among workers with CdU>10 (OR, 21.8, 95% CI, 6.4-74.4 and OR, 15.1, 95% CI, 3.6-63.1, respectively). In never smokers, these BMD5/BMDL5 of CdU were estimated at 12.6/6.6 and 12.2/5.5 while in ever smokers they were 6.2/4.9 and 4.3/3.5. Conclusions On the basis of associations undistorted by smoking and adjusted for covariates, the BMDL5 of CdU for low-molecular-weight proteinuria induced by occupational exposure to Cd can be reliably estimated between 5.5 and 6.6 μg/g creatinine.
Occupational and environmental medicine 10/2010; 68(4):257-64. · 3.64 Impact Factor
[show abstract][hide abstract] ABSTRACT: Bioaerosols and their constituents, such as endotoxins, are capable of causing an inflammatory reaction at the level of the lung-blood barrier, which becomes more permeable. Thus, it was hypothesized that occupational exposure to bioaerosols can increase leakage of surfactant protein-D (SP-D), a lung-specific protein, into the bloodstream.
SP-D was determined by ELISA in 316 wastewater workers, 67 garbage collectors, and 395 control subjects. Exposure was assessed with four interview-based indicators and by preliminary endotoxin measurements using the Limulus amoebocyte lysate assay. Influence of exposure on serum SP-D was assessed by multiple linear regression considering smoking, glomerular function, lung diseases, obesity, and other confounders.
Overall, mean exposure levels to endotoxins were below 100 EU/m(3). However, special tasks of wastewater workers caused higher endotoxin exposure. SP-D concentration was slightly increased in this occupational group and associated with the occurrence of splashes and contact to raw sewage. No effect was found in garbage collectors. Smoking increased serum SP-D. No clinically relevant correlation between spirometry results and SP-D concentrations appeared.
These results support the hypothesis that inhalation of bioaerosols, even at low concentrations, has a subclinical effect on the lung-blood barrier, the permeability of which increases without associated spirometric changes.
International Archives of Occupational and Environmental Health 03/2010; 83(8):879-86. · 2.10 Impact Factor
[show abstract][hide abstract] ABSTRACT: Clara cell protein (CC16), the main secretory product of bronchiolar Clara cells, plays an important protective role in the respiratory tract against oxidative stress and inflammation. The purpose of the study was to investigate the role of elemental carbon ultrafine particles (EC-UFP)-induced oxidative stress on Clara cells and CC16 in a mouse model of allergic lung inflammation.
Ovalbumin (OVA)-sensitized mice were exposed to EC-UFP (507 microg/m(3) for 24 h) or filtered air immediately prior to allergen challenge and systemically treated with N-acetylcysteine (NAC) or vehicle prior and during EC-UFP inhalation. CC16 was measured up to one week after allergen challenge in bronchoalveolar lavage fluid (BALF) and in serum. The relative expression of CC16 and TNF-alpha mRNA were measured in lung homogenates. A morphometrical analysis of mucus hypersecretion and electron microscopy served to investigate goblet cell metaplasia and Clara cell morphological alterations.
In non sensitized mice EC-UFP inhalation caused alterations in CC16 concentration, both at protein and mRNA level, and induced Clara cell hyperplasia. In sensitized mice, inhalation of EC-UFP prior to OVA challenge caused most significant alterations of BALF and serum CC16 concentration, BALF total protein and TNF-alpha relative expression compared to relevant controls; their Clara cells displayed the strongest morphological alterations and strongest goblet cell metaplasia occurred in the small airways. NAC strongly reduced both functional and morphological alterations of Clara cells.
Our findings demonstrate that oxidative stress plays an important role in EC-UFP-induced augmentation of functional and morphological alterations of Clara cells in allergic lung inflammation.
Particle and Fibre Toxicology 01/2010; 7:11. · 9.18 Impact Factor