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.

Risks of new-onset allergic sensitization and airway inflammation after early age swimming in chlorinated pools.

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 (>15 ppb; 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 60 h 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.

Associations of urinary cadmium with age and urinary proteins: further evidence of physiological variations unrelated to metal accumulation and toxicity.

BACKGROUND: The current risk assessment for environmental cadmium (Cd) largely relies on the assumption that urinary Cd (U-Cd) is a reliable biomarker of the Cd body burden. Recent studies have questioned 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 using natural cubic splines. RESULTS: In both genders, U-Cd decreased to a minimum (~ 0.20 µg/L) at the end of adolescence, then increased until 60-70 years of age (~ 0.60 µg/L in never-smokers) before leveling off or decreasing. When U-Cd was expressed in micrograms per gram of creatinine, these variations were amplified (minimum, 0.15 µg/g creatinine; maximum, 0.70 µg/g creatinine) and much higher U-Cd values were observed in women. We observed no difference in U-Cd levels between never-smokers and former smokers, and the difference with current smokers did not increase over time. Lifetime curves of U-Cd were higher with increasing urinary retinol-binding protein or albumin, a consequence of the coexcretion of Cd with proteins. CONCLUSIONS: At low Cd exposure levels, U-Cd and age are associated through nonlinear and nonmonotonic relationships that appear to be driven mainly by recent Cd intake and physiological variations in the excretion of creatinine and proteins.

Nasal epithelium biomarkers in young children: associations with allergic sensitization and environmental stressors.

BACKGROUND: Recent studies suggest that allergic diseases might have their onset in early epithelial barrier defects. To test this hypothesis, we assessed associations between nasal epithelium biomarkers, environmental stressors, and the risks of allergic sensitization. METHODS: In a cross-sectional study of 288 kindergarten children (mean age, 5.7 years), we measured aeroallergen-specific IgE in nasal mucosa and the concentrations of urea, albumin, and Clara cell protein (CC16) in nasal lavage fluid (NALF). Albumin and CC16 in NALF were expressed per liter or as a ratio to urea. We also calculated the NALF CC16/albumin ratio as an index integrating the permeability and the secretory function of the nasal epithelium. RESULTS: Median NALF concentrations of CC16 and albumin were 8.2 µg/L and 34.5 mg/L, respectively. While there were no significant gender differences when proteins were expressed per liter, the CC16 to albumin and CC16 to urea ratios in NALF were higher in girls than in boys (P = 0.02 and 0.055, respectively. The nasal epithelial barrier function, as reflected by these NALF biomarkers, was positively influenced by probiotics and age, and negatively by environmental stressors such as pool chlorine. The risk of house dust mite (HDM) sensitization increased with decreasing log NALF CC16 concentration, whether expressed per liter (2.59, 95% CI: 1.15-5.82, P = 0.02), as a ratio to urea (1.98, 95% CI: 0.96-4.06, P = 0.06), or as a ratio to albumin (OR, 2.03, 95% CI: 1.10-3.74, P = 0.02). Children in the highest and intermediate tertiles of the NALF albumin/urea ratio were three times more likely to be sensitized to HDM than those in the lowest tertile (both P = 0.04). CONCLUSION: Defects in the nasal epithelium barrier function of young children, as reflected by the concentrations of CC16 and albumin in NALF, are associated with environmental factors, including pool chlorine, and with increased risks of HDM 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.

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.

Impact of chlorinated swimming pool attendance on the respiratory health of adolescents.

OBJECTIVE: The goal was to estimate the burden of allergic diseases associated with chlorinated pool exposure among adolescents. METHODS: We examined 847 students, 13 to 18 years of age, who had attended outdoor or indoor chlorinated pools at various rates. Of them, 114 had attended mainly a copper-silver pool and served as a reference group. We measured total and aeroallergen-specific immunoglobulin E (IgE) levels in serum and screened for exercise-induced bronchoconstriction. Outcomes were respiratory symptoms, hay fever, allergic rhinitis, and asthma that had been diagnosed at any time (ever asthma) or was being treated with medication and/or was associated with exercise-induced bronchoconstriction (current asthma). RESULTS: Among adolescents with atopy with serum IgE levels of>30 kIU/L or aeroallergen-specific IgE, the odds ratios (ORs) for asthma symptoms and for ever or current asthma increased with the lifetime number of hours spent in chlorinated pools, reaching values of 7.1 to 14.9 when chlorinated pool attendance exceeded 1000 hours. Adolescents with atopy with chlorinated pool attendance of >100 hours had greater risk of hay fever (OR: 3.3-6.6), and those with attendance of >1000 hours had greater risk of allergic rhinitis (OR: 2.2-3.5). Such associations were not found among adolescents without atopy or with copper-silver pool attendance. The population attributable risks for chlorinated pool-related ever-diagnosed asthma, hay fever, and allergic rhinitis were 63.4%, 62.1%, and 35.0%, respectively. CONCLUSION: Chlorinated pool exposure exerts an adjuvant effect on atopy that seems to contribute significantly to the burden of asthma and respiratory allergies among adolescents.