Use of a Cumulative Exposure Index to Estimate the Impact of Tap Water Lead Concentration on Blood Lead Levels in 1- to 5-Year-Old Children (Montréal, Canada).

BACKGROUND: Drinking water is recognized as a source of lead (Pb) exposure. However, questions remain about the impact of chronic exposure to lead-contaminated water on internal dose. OBJECTIVE: Our goal was to estimate the relation between a cumulative water Pb exposure index (CWLEI) and blood Pb levels (BPb) in children 1-5 years of ages. METHODS: Between 10 September 2009 and 27 March 2010, individual characteristics and water consumption data were obtained from 298 children. Venous blood samples were collected (one per child) and a total of five 1-L samples of water per home were drawn from the kitchen tap. A second round of water collection was performed between 22 June 2011 and 6 September 2011 on a subsample of houses. Pb analyses used inductively coupled plasma mass spectroscopy. Multiple linear regressions were used to estimate the association between CWLEI and BPb. RESULTS: Each 1-unit increase in CWLEI multiplies the expected value of BPb by 1.10 (95% CI: 1.06, 1.15) after adjustment for confounders. Mean BPb was significantly higher in children in the upper third and fourth quartiles of CWLEI (0.7-1.9 and ≥ 1.9 µg/kg of body weight) compared with the first (< 0.2 µg/kg) after adjusting for confounders (19%; 95% CI: 0, 42% and 39%; 95% CI: 15, 67%, respectively). The trends analysis yielded a p-value < 0.0001 after adjusting for confounders suggesting a dose-response relationship between percentiles of CWLEI and BPb. CONCLUSIONS: In children 1-5 years of age, BPb was significantly associated with water lead concentration with an increase starting at a cumulative lead exposure of ≥ 0.7 µg Pb/kg of body weight. In this age group, an increase of 1 µg/L in water lead would result in an increase of 35% of BPb after 150 days of exposure.

The impact of drinking water, indoor dust and paint on blood lead levels of children aged 1-5 years in Montréal (Québec, Canada).

Lead is neurotoxic at very low dose and there is a need to better characterize the impact of domestic sources of lead on the biological exposure of young children. A cross-sectional survey evaluated the contribution of drinking water, house dust and paint to blood lead levels (BLLs) of young children living in old boroughs of Montréal (Canada). Three hundred and six children aged 1 to 5 years and currently drinking tap water participated in the study. For each participant, residential lead was measured in kitchen tap water, floor dust, windowsill dust and house paint and a venous blood sample was analyzed. Multivariate logistic regression was used to evaluate the association between elevated BLL in the children (≥ 75th percentile) and indoor lead contamination by means of odds ratios (OR) using 95% confidence intervals (CI). There was an association between BLL ≥75th percentile (1.78 µg/dL) and water lead when the mean water concentration was >3.3 µg/L: adjusted OR=4.7 (95% CI: 2.1-10.2). Windowsill dust loading >14.1 µg/ft(2) was also associated with BLL ≥1.78 µg/dL: adjusted OR=3.2 (95% CI: 1.3-7.8). Despite relatively low BLLs, tap water and house dust lead contribute to an increase of BLLs in exposed young children.

Leptin and adiponectin in obese and non-obese subjects with asthma.

OBJECTIVE: To understand the role of leptin and adiponectin in obese asthmatics. METHODS: We compared serum leptin, adiponectin and sputum leptin levels in 44 non-obese and 44 obese subjects. RESULTS: We found higher serum leptin (P < 0.0001) and lower adiponectin (P = 0.0002) levels in obese asthmatics. Sputum leptin was correlated with body mass index (BMI; r = 0.34, P = 0.03) and serum leptin (r = 0.43, P = 0.005); however, this last correlation was not significant after adjusting for BMI (r = 0.26, P = 0.11). CONCLUSION: Airway inflammation in obese asthmatics may present a different pattern involving leptin. Sputum leptin levels may partially originate from systemic circulation, with other contributing mechanisms.

Comparison of two in vitro models of cigarette smoke exposure.

Cigarette smoke is associated with a high morbidity and mortality, and affects particularly the respiratory tract. Various in vitro models have been developed to study the effects of cigarette smoke on bronchial epithelial cells. To identify an adequate exposure model of cigarette smoke, we analysed the effects of cigarette smoke extract (CSE) and a smoking chamber on bronchial epithelial cells. The release of monocyte chemoattractant protein (MCP)-1, interleukin (IL)-10, and vascular endothelial growth factor (VEGF) was measured. Bronchial epithelial cells isolated from Sprague-Dawley rat (NRBE) were exposed to 3% CSE or air control every day for 3 days. In the second model, NRBE were placed in an air/liquid interface and exposed, in a smoking chamber, to whole smoke from 2 cigarettes, twice daily for 3 days. Levels of MCP-1, IL-10, and VEGF were measured by enzyme-linked immunosorbent assay (ELISA), 24 h after the last exposure. The pattern of MCP-1 production by bronchial epithelial cells was different between the two models. MCP-1 release was increased after 3 days of exposure in the CSE model, but was inhibited using the smoking chamber model. Production of IL-10 by NRBE was reduced after 3 days in both models. Finally, no difference was observed in the production of VEGF between the two models. CSE and the smoking chamber differently modulate bronchial epithelial cell mediator production, demonstrating that the model of cigarette smoke exposure used can influence the data obtained.

Cigarette smoke differently alters normal and ovalbumin-sensitized bronchial epithelial cells from rat.

BACKGROUND: Smoking is a common habit in the general population, even in asthmatic patients. Bronchial epithelial cells are the first cellular elements exposed to environmental stimuli such as cigarette smoke. These cells produce a wide range of mediators involved in inflammation and remodeling processes. However, the effects of chronic smoke exposure on the release and production of these mediators remain unclear. OBJECTIVES: To investigate the effects of repeated exposure to cigarette smoke extract on mediator released by bronchial epithelial cells isolated from control and asthmatic rats. METHODS: Bronchial epithelial cells were isolated from normal (NRBE) and asthmatic rats (ARBE) (ovalbumin (OVA)-sensitized rat). Cells were exposed to cigarette smoke extract (CSE) obtained by impacting cigarette smoke with an AGI-30. A concentration of 3% CSE was added in the medium daily, for 5 consecutive days. Supernatant was recovered at baseline and after the 5 days. Levels of macrophage chemoattractant protein (MCP)-1, interleukin (IL)-10, vascular endothelial growth factor (VEGF), tumor necrosis factor (TNF), IL-1alpha, and interferon (IFN)-gamma were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: TNF, IL-1alpha, and IFN-gamma were lower than the detection limit of our methods. At the baseline, NRBE produced less MCP-1 but more IL-10 and VEGF when compared with ARBE. CSE exposure reduced NRBE IL-10 production but did not significantly alter MCP-1 and VEGF production. Interestingly, bronchial epithelial cells of asthmatic rats responded differently to CSE. MCP-1 level was decreased and VEGF increased after CSE exposure, whereas IL-10 level did not change in ARBE. CONCLUSION: Cells isolated from asthmatic rats produced distinct levels of mediators compared with cells isolated from control rats. Furthermore, these cells react differently to CSE exposure.

Alveolar macrophage subpopulations in bronchoalveolar lavage and induced sputum of asthmatic and control subjects.

BACKGROUND: Alveolar macrophages (AM) are the most numerous immune cells in the airways and are involved in the immunological homeostasis of the lung. Intriguingly, their role in asthma remains unclear probably, in part, because of their heterogeneity. OBJECTIVE: To characterize AM population from bronchoalveolar lavage (BAL) and induced sputum (IS) of asthmatic and normal subjects using specific biomarkers. METHODS: Non-asthmatic non-allergic and allergic mild asthmatic subjects were recruited for this study. AM were obtained from BAL and IS and cytospins were prepared. Immunocytochemistry was performed for nine cellular markers (CD68, RFD7, CD14, CD11b, CD83, CD64, CD80, CD86, and FIZZ1). RESULTS: Asthmatic subjects had more AM RFD7(+) in BAL compared with IS, whereas control subjects had more AM RFD7(+) in IS than in BAL. Consequently, there was an increased number of AM RFD7(+) in BAL of asthmatic subjects compared with BAL of control subjects. AM CD11b(+) was higher in BAL than in IS in both groups. The expression of FIZZ1, marker of macrophage alternative activation, was similar in asthmatic and normal subjects. CONCLUSION: The expression of cellular markers on AM differs according to their localization in the lung. Subpopulations of AM may contribute to the inflammatory profile observed in asthmatic subjects.

Effects of protease inhibitors on mediator preservation in the supernatant of induced sputum.

Addition of protease inhibitors in induced sputum samples may help improve the recovery of mediators. The effect of protease inhibitors, in induced sputum, on the measurement of fibronectin, VEGF, IL-5, IL-6, and IL-8 was assessed. Protease inhibitors were added to sputum supernatant of atopic asthmatic subjects. Mediators were measured by ELISA or EIA. No differences were found in VEGF, IL-5, and IL-8 levels between protease inhibitors studied. Concentrations of IL-6 and fibronectin were higher when using, respectively, the commercial cocktail, and aprotinin. Protease inhibitors, if added, should be carefully chosen at the beginning of each study, to optimize the results.

Comparison of cell fixation methods of induced sputum specimens: an immunocytochemical analysis.

Induced sputum (IS) is a non-invasive method to evaluate airway inflammation. Various techniques are used to fix IS cells but their respective value has never been compared. We aimed to determine the best IS cell fixation technique for cellular markers staining. Cells were fixed using four methods: 1) periodate-paraformaldehyde-lysine (PLP)-sucrose, 2) paraformaldehyde 4% on slide and 3) in solution and 4) acetone-methanol. Analysis was based on percentage of positive cells compared to total cell counts stained by hematoxylin and quality of staining. Using PLP-sucrose resulted in a higher percentage of positive cells for CD3 and a better quality of staining. Acetone-methanol showed a lower percentage of positive cells for CD68 and a poor quality. PLP-sucrose gives the best results for the preservation of the studied cell markers and acetone-methanol the worst.