Noninvasive integrative approach applied to children in the context of recent air pollution exposure demonstrates association between fractional exhaled nitric oxide (FeNO) and urinary CC16.

Exposure to the air pollutant particulate matter (PM) is associated with increased risks of respiratory diseases and enhancement of airway inflammation in children. In the context of large scale air pollution studies, it can be challenging to measure fractional exhaled nitric oxide (FeNO) as indicator of lung inflammation. Urinary CC16 (U-CC16) is a potential biomarker of increased lung permeability and toxicity, increasing following short-term PM2.5 exposure. The single nucleotide polymorphism (SNP) CC16 G38A (rs3741240) affects CC16 levels and respiratory health. Our study aimed at assessing the use of U-CC16 (incl. CC16 G38A from saliva) as potential alternative for FeNO by investigating their mutual correlation in children exposed to PM. Samples from a small-scale study conducted in 42 children from urban (n = 19) and rural (n = 23) schools examined at two time points, were analysed. When considering recent (lag1) low level exposure to PM2.5 as air pollution measurement, we found that U-CC16 was positively associated with FeNO (ß = 0.23; 95% CI [-0.01; 0.47]; p = 0.06) in an adjusted analysis using a linear mixed effects model. Further, we observed a positive association between PM2.5 and FeNO (ß = 0.56; 95% CI [0.02; 1.09]; p = 0.04) and higher FeNO in urban school children as compared to rural school children (ß = 0.72; 95% CI [0.12; 1.31]; p = 0.02). Although more investigations are needed, our results suggest that inflammatory responses evidenced by increased FeNO are accompanied by potential increased lung epithelium permeability and injury, evidenced by increased U-CC16. In future large scale studies, where FeNO measurement is less feasible, the integrated analysis of U-CC16 and CC16 G38A, using noninvasive samples, might be a suitable alternative to assess the impact of air pollution exposure on the respiratory health of children, which is critical for policy development at population level.

Urinary CC16, a potential indicator of lung integrity and inflammation, increases in children after short-term exposure to PM2.5/PM10 and is driven by the CC16 38GG genotype.

Particular matter (PM) exposure is a big hazard for public health, especially for children. Serum CC16 is a well-known biomarker of respiratory health. Urinary CC16 (U-CC16) can be a noninvasive alternative, albeit requiring adequate adjustment for renal handling. Moreover, the SNP CC16 G38A influences CC16 levels. This study aimed to monitor the effect of short-term PM exposure on CC16 levels, measured noninvasively in schoolchildren, using an integrative approach. We used a selection of urine and buccal DNA samples from 86 children stored in an existing biobank. Using a multiple reaction monitoring method, we measured U-CC16, as well as RBP4 (retinol binding protein 4) and ß2M (beta-2-microglobulin), required for adjustment. Buccal DNA samples were used for CC16 G38A genotyping. Linear mixed-effects models were used to find relevant associations between U-CC16 and previously obtained data from recent daily PM ≤ 2.5 or 10 µm exposure (PM2.5, PM10) modeled at the child's residence. Our study showed that exposure to low PM at the child's residence (median levels 18.9 µg/m³ (PM2.5) and 23.6 µg/m³ (PM10)) one day before sampling had an effect on the covariates-adjusted U-CC16 levels. This effect was dependent on the CC16 G38A genotype, due to its strong interaction with the association between PM levels and covariates-adjusted U-CC16 (P = 0.024 (PM2.5); P = 0.061 (PM10)). Only children carrying the 38GG genotype showed an increase of covariates-adjusted U-CC16, measured 24h after exposure, with increasing PM2.5 and PM10 (ß = 0.332; 95% CI: 0.110 to 0.554 and ß = 0.372; 95% CI: 0.101 to 0.643, respectively). To the best of our knowledge, this is the first study using an integrative approach to investigate short-term PM exposure of children, using urine to detect early signs of pulmonary damage, and taking into account important determinants such as the genetic background and adequate adjustment of the measured biomarker in urine.

Health effects of exposure to chlorination by-products in swimming pools.

Concerns have been raised regarding the potential negative effects on human health of water disinfectants used in swimming pools. Among the disinfection options, the approaches using chlorine-based products have been typically preferred. Chlorine readily reacts with natural organic matter that are introduced in the water mainly through the bathers, leading to the formation of potentially harmful chlorination by-products (CBPs). The formation of CBPs is of particular concern since some have been epidemiologically associated with the development of various clinical manifestations. The higher the concentration of volatile CBPs in the water, the higher their concentration in the air above the pool, and different routes of exposure to chemicals in swimming pools (water ingestion, skin absorption, and inhalation) contribute to the individual exposome. Some CBPs may affect the respiratory and skin health of those who stay indoor for long periods, such as swimming instructors, pool staff, and competitive swimmers. Whether those who use chlorinated pools as customers, particularly children, may also be affected has been a matter of debate. In this article, we discuss the current evidence regarding the health effects of both acute and chronic exposures in different populations (work-related exposures, intensive sports, and recreational attendance) and identify the main recommendations and unmet needs for research in this area.

Short halt in vaping modifies cardiorespiratory parameters and urine metabolome: a randomized trial.

Propylene glycol and glycerol are e-cigarette constituents that facilitate liquid vaporization and nicotine transport. As these small hydrophilic molecules quickly cross the lung epithelium, we hypothesized that short-term cessation of vaping in regular users would completely clear aerosol deposit from the lungs and reverse vaping-induced cardiorespiratory toxicity. We aimed to assess the acute effects of vaping and their reversibility on biological/clinical cardiorespiratory parameters [serum/urine pneumoproteins, hemodynamic parameters, lung-function test and diffusing capacities, transcutaneous gas tensions (primary outcome), and skin microcirculatory blood flow]. Regular e-cigarette users were enrolled in this randomized, investigator-blinded, three-period crossover study. The periods consisted of nicotine-vaping (nicotine-session), nicotine-free vaping (nicotine-free-session), and complete cessation of vaping (stop-session), all maintained for 5 days before the session began. Multiparametric metabolomic analyses were used to verify subjects' protocol compliance. Biological/clinical cardiorespiratory parameters were assessed at the beginning of each session (baseline) and after acute vaping exposure. Compared with the nicotine- and nicotine-free-sessions, a specific metabolomic signature characterized the stop-session. Baseline serum club cell protein-16 was higher during the stop-session than the other sessions (P < 0.01), and heart rate was higher in the nicotine-session (P < 0.001). Compared with acute sham-vaping in the stop-session, acute nicotine-vaping (nicotine-session) and acute nicotine-free vaping (nicotine-free-session) slightly decreased skin oxygen tension (P < 0.05). In regular e-cigarette-users, short-term vaping cessation seemed to shift baseline urine metabolome and increased serum club cell protein-16 concentration, suggesting a decrease in lung inflammation. Additionally, acute vaping with and without nicotine decreased slightly transcutaneous oxygen tension, likely as a result of lung gas exchanges disturbances.

Fourth generation e-cigarette vaping induces transient lung inflammation and gas exchange disturbances: results from two randomized clinical trials.

When heated by an electronic cigarette, propylene glycol and glycerol produce a nicotine-carrying-aerosol. This hygroscopic/hyperosmolar aerosol can deposit deep within the lung. Whether these deposits trigger local inflammation and disturb pulmonary gas exchanges is not known. The aim of this study was to assess the acute effects of high-wattage electronic cigarette vaping with or without nicotine on lung inflammation biomarkers, transcutaneous gas tensions, and pulmonary function tests in young and healthy tobacco smokers. Acute effects of vaping without nicotine on arterial blood gas tensions were also assessed in heavy smokers suspected of coronary artery disease. Using a single-blind within-subjects study design, 25 young tobacco smokers underwent three experimental sessions in random order: sham-vaping and vaping with and without nicotine at 60 W. Twenty heavy smokers were also exposed to sham-vaping (n = 10) or vaping without nicotine (n = 10) in an open-label, randomized parallel study. In the young tobacco smokers, compared with sham-vaping: 1) serum club cell protein-16 increased after vaping without nicotine (mean ± SE, -0.5 ± 0.2 vs. +1.1 ± 0.3 µg/l, P = 0.013) and vaping with nicotine (+1.2 ± 0.3 µg/l, P = 0.009); 2) transcutaneous oxygen tension decreased for 60 min after vaping without nicotine (nadir, -0.3 ± 1 vs. -15.3 ± 2.3 mmHg, P < 0.001) and for 80-min after vaping with nicotine (nadir, -19.6 ± 2.8 mmHg, P < 0.001). Compared with sham vaping, vaping without nicotine decreased arterial oxygen tension for 5 min in heavy-smoking patients (+5.4 ± 3.3 vs. -5.4 ± 1.9 mmHg, P = 0.012). Acute vaping of propylene glycol/glycerol aerosol at high wattage with or without nicotine induces airway epithelial injury and sustained decrement in transcutaneous oxygen tension in young tobacco smokers. Intense vaping conditions also transiently impair arterial oxygen tension in heavy smokers.

Continuous exercise induces airway epithelium damage while a matched-intensity and volume intermittent exercise does not.

BACKGROUND: While continuous exercise (CE) induces greater ventilation ([Formula: see text]E) when compared to intermittent exercise (IE), little is known of the consequences on airway damage. Our aim was to investigate markers of epithelial cell damage - i.e. serum levels of CC16 and of the CC16/SP-D ratio - during and following a bout of CE and IE of matched work. METHODS: Sixteen healthy young adults performed a 30-min continuous (CE) and a 60-min intermittent exercise (IE; 1-min work: 1-min rest) on separate occasions in a random order. Intensity was set at 70% of their maximum work rate (WRmax). Heart rate (HR) and [Formula: see text]E were measured throughout both tests. Blood samples were taken at rest, after the 10th min of the warm-up, at the end of both exercises, half way through IE (matched time but 50% work done for IE) as well as 30- and 60-min post-exercise. Lactate and CC16 and SP-D were determined. RESULTS: Mean [Formula: see text]E was higher for CE compared to IE (85 ± 17 l.min- 1 vs 50 ± 8 l.min- 1, respectively; P < 0.001). Serum-based markers of epithelial cell damage remained unchanged during IE. Interaction of test × time was observed for SP-D (P = 0.02), CC16 (µg.l- 1) (P = 0.006) and CC16/SP-D ratio (P = 0.03). Maximum delta CC16/SP-D was significantly correlated with mean [Formula: see text]E sustained (r = 0.83, P < 0.001) during CE but not during IE. CONCLUSION: The 30-min CE performed at 70% WRmax induced mild airway damage, while a time- or work-matched IE did not. The extent of the damage during CE was associated with the higher ventilation rate.

Nasal epithelium injury by chlorination products and other stressors predicts persistent sensitization to aeroallergens in young schoolchildren.

BACKGROUND: Allergic sensitization during childhood is a dynamic process with a substantial rate of remission. Factors influencing this process are largely unknown. METHODS: We conducted a two-year prospective study among 121 schoolchildren (mean age, 5.8 years; 64 boys). We measured urea, club cell protein (CC16), ß2-microglobulin and albumin in nasal lavage fluid (NALF) and IgE to cat, pollen or house dust mite (HDM) in nasal mucosa fluid. RESULTS: Odds of persistent sensitization to any aeroallergen increased across baseline ascending tertiles of urea-adjusted ß2-microglobulin or albumin and descending tertiles of albumin- or ß2-microglobulin-adjusted CC16 (P-trend = 0.006, 0.02, 0.044 and 0.006, respectively). Persistent HDM sensitization also increased with baseline descending tertiles of raw or urea-adjusted CC16 (both P-trend = 0.007). Such strong associations were not observed with new-onset or remitted sensitization to any aeroallergen or with raw NALF concentrations of urea, albumin or ß2-microglobulin. At baseline, house cleaning with bleach and chlorinated pool attendance emerged among the strongest and most consistent determinants of NALF biomarkers, being both associated with higher urea and lower CC16 in NALF. CONCLUSION: In young children, a defective nasal epithelium attributable to immaturity or stressors such as chlorination products is predictive of more persistent aeroallergen sensitization.

The physiological determinants of low-level urine cadmium: an assessment in a cross-sectional study among schoolchildren.

BACKGROUND: Recent studies in children have reported associations of urinary cadmium (U-Cd), used as biomarker of Cd body burden, with renal dysfunction, retarded growth and impaired cognitive development in children. Little is known, however, about factors influencing U-Cd in children and likely to act as confounders. METHODS: In a cross-sectional study involving 249 schoolchildren (mean age, 5.72 years; 138 boys), we measured the urine concentrations of cadmium, zinc, lead, albumin, alpha1-microglobulin (A1M), retinol-binding protein, ß2-microglobulin and club cell protein (CC16). Determinants of U-Cd expressed per creatinine or adjusted to specific gravity were identified by multiple regression analyses. RESULTS: Girls and boys had similar median concentrations of U-Cd (0.22 and 0.24 µg/L, 0.33 and 0.35 µg/g creatinine, respectively). When models were run without including creatinine or specific gravity among independent variables, urinary zinc, urinary A1M and age emerged as the strongest predictors of U-Cd expressed per g creatinine or adjusted to SG. When adding creatinine among predictors, urinary creatinine emerged as an additional strong predictor correlating negatively with U-Cd per g creatinine. This strong residual influence of diuresis, not seen when adding specific gravity among predictors, linked U-Cd to U-A1M or U-CC16 through secondary associations mimicking those induced by Cd nephrotoxity. CONCLUSIONS: In young children U-Cd largely varies with diuresis, zinc metabolism and urinary A1M. These physiological determinants, unrelated to Cd body burden, may confound the child renal and developmental outcomes associated with low-level U-Cd.

Inflammation induced by inhaled lipopolysaccharide depends on particle size in healthy volunteers.

AIMS: In drug development, the anti-inflammatory properties of new molecules in the lung are currently tested using the inhaled lipopolysaccharide (LPS) model. The total and regional lung bioavailability of inhaled particles depends significantly on their size. The objective of the present study was to compare inflammatory responses in healthy volunteers after the inhalation of LPS of varying droplet size. METHODS: Three nebulizers were characterized by different droplet size distributions [mean mass median aerodynamic diameters: Microcirrus (2.0 µm), MB2 (3.2 µm) and Pari (7.9 µm)]. Participants inhaled three boluses of a 20 µg (technetium 99 m-labelled) solution of LPS, randomly delivered by each nebulizer. We measured the lung deposition of the nebulized LPS by gamma-scintigraphy, while blood and sputum biomarkers were evaluated before and after challenges. RESULTS: MB2 and Pari achieved greater lung deposition than Microcirrus [171.5 (±72.9) and 217.6 (±97.8) counts pixel-1 , respectively, vs. 67.9 (±20.6) counts pixel-1 ; P < 0.01]. MB2 and Pari caused higher levels of blood C-reactive protein and more total cells and neutrophils in sputum compared with Microcirrus (P < 0.05). C-reactive protein levels correlated positively with lung deposition (P < 0.01). CONCLUSIONS: Inhalation of large droplets of LPS gave rise to greater lung deposition and induced a more pronounced systemic and bronchial inflammatory response than small droplets. The systemic inflammatory response correlated with lung deposition. NCT01081392.

Indoor air quality, ventilation and respiratory health in elderly residents living in nursing homes in Europe.

Few data exist on respiratory effects of indoor air quality and comfort parameters in the elderly. In the context of the GERIE study, we investigated for the first time the relationships of these factors to respiratory morbidity among elderly people permanently living in nursing homes in seven European countries. 600 elderly people from 50 nursing homes underwent a medical examination and completed a standardised questionnaire. Air quality and comfort parameters were objectively assessed in situ in the nursing home. Mean concentrations of air pollutants did not exceed the existing standards. Forced expiratory volume in 1 s/forced vital capacity ratio was highly significantly related to elevated levels of particles with a 50% cut-off aerodynamic diameter of <0.1 µm (PM0.1) (adjusted OR 8.16, 95% CI 2.24-29.3) and nitrogen dioxide (aOR 3.74, 95% CI 1.06-13.1). Excess risks for usual breathlessness and cough were found with elevated PM10 (aOR 1.53 (95% CI 1.15-2.07) and aOR 1.73 (95% CI 1.17-10.3), respectively) and nitrogen dioxide (aOR 1.58 (95% CI 1.15-2.20) and aOR 1.56 (95% CI 1.03-2.41), respectively). Excess risks for wheeze in the past year were found with PM0.1 (aOR 2.82, 95% CI 1.15-7.02) and for chronic obstructive pulmonary disease and exhaled carbon monoxide with formaldehyde (aOR 3.49 (95% CI 1.17-10.3) and aOR 1.25 (95% CI 1.02-1.55), respectively). Breathlessness and cough were associated with higher carbon dioxide. Relative humidity was inversely related to wheeze in the past year and usual cough. Elderly subjects aged ≥80 years were at higher risk. Pollutant effects were more pronounced in the case of poor ventilation. Even at low levels, indoor air quality affected respiratory health in elderly people permanently living in nursing homes, with frailty increasing with age. The effects were modulated by ventilation.

Chlorinated pool attendance, airway epithelium defects and the risks of allergic diseases in adolescents: Interrelationships revealed by circulating biomarkers.

It has been suggested that allergic diseases might be epithelial disorders driven by various environmental stressors but the epidemiological evidence supporting this concept is limited. In a cross-sectional study of 835 school adolescents (365 boys; mean age, 15.5 yr), we measured the serum concentrations of Club cell protein (CC16), surfactant-associated protein D (SP-D) and of total and aeroallergen-specific IgE. We used the serum CC16/SP-D concentration ratio as an index integrating changes in the permeability (SP-D) and secretory function (CC16) of the airway epithelium. In both sexes, early swimming in chlorinated pools emerged as the most consistent and strongest predictor of low CC16 and CC16/SP-D ratio in serum. Among girls, a low CC16/SP-D ratio was associated with increased odds (lowest vs. highest tertile) for pet sensitization (OR 2.97, 95% CI 1.19-8.22) and for hay fever in subjects sensitized to pollen (OR 4.12, 95% CI 1.28-14.4). Among boys, a low CC16/SP-D ratio was associated with increased odds for house-dust mite (HDM) sensitization (OR 2.01, 95% CI 1.11-3.73), for allergic rhinitis in subjects sensitized to HDM (OR 3.52, 95% CI 1.22-11.1) and for asthma in subjects sensitized to any aeroallergen (OR 3.38, 95% CI 1.17-11.0), HDM (OR 5.20, 95% CI 1.40-24.2) or pollen (OR 5.82, 95% CI 1.51-27.4). Odds for allergic sensitization or rhinitis also increased with increasing SP-D or decreasing CC16 in serum. Our findings support the hypothesis linking the development of allergic diseases to epithelial barrier defects due to host factors or environmental stressors such as early swimming in chlorinated pools.

Serum club cell protein 16 is associated with asymptomatic airway responsiveness in adults: Findings from the French epidemiological study on the genetics and environment of asthma.

BACKGROUND AND OBJECTIVE: Club cell secretory protein (CC-16) is a sensitive biomarker of airways epithelium integrity. It has gained interest as a biological marker in chronic lung diseases because of its presumed relationship to inflammation. Little is known about the association between CC-16 serum level and asthma, lung function and airway responsiveness (AR). METHODS: Serum CC-16 level was determined by latex immunoassay in 1298 participants from the French Epidemiological case-control and family-based study on Genetics and Environment of Asthma (EGEA) (mean age 43 years; 49% men, 38% with asthma). Pre-bronchodilator lung function (forced expiratory volume in 1 s (FEV1 ), forced vital capacity (FVC) and FEV1 /FVC) and degree of AR, expressed as a function of the dose-response slope to methacholine test were measured. Standardized residuals CC-16 z-scores were obtained by regressing CC-16 level on the glomerular filtration rate. CC-16 z-scores were correlated with asthma, lung function and AR in participants with and without asthma. RESULTS: CC-16 geometric mean level was 12.4 µg/L (range: 2.2-70.6 µg/L). In participants without asthma, lower CC-16 z-scores was associated with impaired FEV1 /FVC% (ß = 0.50 (95% CI: 0.06, 0.95) and with higher degree of AR (ß = 0.24 (95% CI: 0.09, 0.39)). CC-16 was not associated with impaired lung function or AR in participants with asthma. CONCLUSIONS: Lower CC-16 serum level was associated with impaired lung function and AR, suggesting that serum CC-16 level may reflect early damages to the lung epithelium in adults without asthma.

Biological monitoring and health effects of low-level exposure to N-methyl-2-pyrrolidone: a cross-sectional study.

PURPOSE: 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. METHODS: 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. RESULTS: 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/m3 (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. CONCLUSIONS: 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.

Update of the human secretoglobin (SCGB) gene superfamily and an example of 'evolutionary bloom' of androgen-binding protein genes within the mouse Scgb gene superfamily.

The secretoglobins (SCGBs) comprise a family of small, secreted proteins found in animals exclusively of mammalian lineage. There are 11 human SCGB genes and five pseudogenes. Interestingly, mice have 68 Scgb genes, four of which are highly orthologous to human SCGB genes; the remainder represent an 'evolutionary bloom' and make up a large gene family represented by only six counterparts in humans. SCGBs are found in high concentrations in many mammalian secretions, including fluids of the lung, lacrimal gland, salivary gland, prostate and uterus. Whereas the biological activities of most individual SCGBs have not been fully characterised, what already has been discovered suggests that this family has an important role in the modulation of inflammation, tissue repair and tumorigenesis. In mice, the large Scgb1b and Scgb2b gene families encode the androgen-binding proteins, which have been shown to play a role in mate selection. Although much has been learned about SCGBs in recent years, clearly more research remains to be done to allow a better understanding of the roles of these proteins in human health and disease. Such information is predicted to reveal valuable novel drug targets for the treatment of inflammation, as well as designing biomarkers that might identify tissue damage or cancer.

Nasal epithelium integrity, environmental stressors, and allergic sensitization: a biomarker study in adolescents.

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.

Interactions between domestic water hardness, infant swimming and atopy in the development of childhood eczema.

AIM: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Dermal Exposure to Hazardous Chemicals in Baby Diapers: A Re-Evaluation of the Quantitative Health Risk Assessment Conducted by The French Agency for Food, Environmental and Occupational Health and Safety (ANSES).

In January 2019, the French Agency for Food, Environmental and Occupational Health and Safety (ANSES) published an opinion on risks related to the presence of hazardous chemicals in infant diapers. ANSES found that health reference values were largely exceeded for polycyclic aromatic hydrocarbons (PAHs), dioxins (PCCD/Fs) and dioxin-like polychlorobiphenyls (DL-PCBs). The levels of formaldehyde and some fragrances were also considered potentially unsafe. Therefore, ANSES concluded that actions have to be taken to restrict levels of these contaminants in diapers. Under the exposure scenario deemed the most reliable by ANSES, estimates of cancer risks of the most potent PAHs detected in diapers exceeded 10-3 and hazard quotients for neurobehavioral effects attained values up to 66. Regarding dioxins and DL-PCBs, ANSES derived a hazard quotient of 12 for the risk of decreased sperm count at adult age. The aim of this study was to examine whether the exposure and risk assessment conducted by ANSES contained potential flaws that could explain such a high exceedance of health reference values. This study also put into perspective the exposure from diapers with that from breast milk whose benefits for children's health are undisputable despite contamination by PAHs, dioxins and DL-PCBS.

Health Risk Assessment of Dermal Exposure to Polycyclic Aromatic Hydrocarbons from the Use of Infant Diapers.

In September 2021, the European Chemicals Agency evaluated a dossier for restricting polycyclic aromatic hydrocarbons (PAHs) in infant diapers and concluded that risks were not demonstrated, because of inconclusive exposure data. To fill this gap, we measured the 16 priority PAHs of the U.S. Environmental Protection Agency in the diaper core of four brands and in the sheets and fastening tapes of six brands of commercially available diapers. Health risks were conservatively assessed by assuming that dermally absorbed PAHs can cause both local (skin cancer) and systemic critical effects (neurobehavioral changes). Total concentrations of PAHs in the diaper core and top sheet, the only significant contributors to skin exposure, averaged 26.5 µg/kg and 66.6 µg/kg, respectively. Excess skin cancer risks and hazard quotients for neurobehavioral effects calculated with the daily dose of total PAHs from the combined diaper core and top sheet averaged 1.44 × 10-7 and 1.19 × 10-2, respectively. The median daily doses of total PAHs and of its benzo[a]pyrene-equivalent from breast milk estimated worldwide are 171 and 30 times greater than that from the combined diaper core and top sheet, respectively. Altogether, these findings indicate that trace levels of PAHs found in infant diapers are unlikely to pose health risks.