Short-term changes in respiratory biomarkers after swimming in a chlorinated pool.
ABSTRACT: BACKGROUND: Swimming in chlorinated pools involves exposure to disinfection by-products (DBPs) and has been associated with impaired respiratory health. OBJECTIVES: We evaluated short-term changes in several respiratory biomarkers to explore mechanisms of potential lung damage related to swimming pool exposure. METHODS: We measured lung function and biomarkers of airway inflammation [fractional exhaled nitric oxide (FeNO), eight cytokines, and vascular endothelial growth factor (VEGF) in exhaled breath condensate], oxidative stress (8-isoprostane in exhaled breath condensate), and lung permeability [surfactant protein D (SP-D) and the Clara cell secretory protein (CC16) in serum] in 48 healthy nonsmoking adults before and after they swam for 40 min in a chlorinated indoor swimming pool. We measured trihalomethanes in exhaled breath as a marker of individual exposure to DBPs. Energy expenditure during swimming, atopy, and CC16 genotype (rs3741240) were also determined. RESULTS: Median serum CC16 levels increased from 6.01 to 6.21 microg/L (average increase, 3.3%; paired Wilcoxon test p = 0.03), regardless of atopic status and CC16 genotype. This increase was explained both by energy expenditure and different markers of DBP exposure in multivariate models. FeNO was unchanged overall but tended to decrease among atopics. We found no significant changes in lung function, SP-D, 8-isoprostane, eight cytokines, or VEGF. CONCLUSIONS: We detected a slight increase in serum CC16, a marker of lung epithelium permeability, in healthy adults after they swam in an indoor chlorinated pool. Exercise and DBP exposure explained this association, without involving inflammatory mechanisms. Further research is needed to confirm the results, establish the clinical relevance of short-term serum CC16 changes, and evaluate the long-term health impacts.
Project description:BACKGROUND: Exposure to disinfection by-products (DBPs) in drinking water has been associated with cancer risk. A recent study (Villanueva et al. 2007; Am J Epidemiol 165:148-156) found an increased bladder cancer risk among subjects attending swimming pools relative to those not attending. OBJECTIVES: We evaluated adults who swam in chlorinated pools to determine whether exposure to DBPs in pool water is associated with biomarkers of genotoxicity. METHODS: We collected blood, urine, and exhaled air samples from 49 nonsmoking adult volunteers before and after they swam for 40 min in an indoor chlorinated pool. We estimated associations between the concentrations of four trihalomethanes (THMs) in exhaled breath and changes in micronuclei (MN) and DNA damage (comet assay) in peripheral blood lymphocytes before and 1 hr after swimming; urine mutagenicity (Ames assay) before and 2 hr after swimming; and MN in exfoliated urothelial cells before and 2 weeks after swimming. We also estimated associations and interactions with polymorphisms in genes related to DNA repair or to DBP metabolism. RESULTS: After swimming, the total concentration of the four THMs in exhaled breath was seven times higher than before swimming. The change in the frequency of micronucleated lymphocytes after swimming increased in association with higher exhaled concentrations of the brominated THMs (p = 0.03 for bromodichloromethane, p = 0.05 for chlorodibromomethane, p = 0.01 for bromoform) but not chloroform. Swimming was not associated with DNA damage detectable by the comet assay. Urine mutagenicity increased significantly after swimming, in association with the higher concentration of exhaled bromoform (p = 0.004). We found no significant associations with changes in micronucleated urothelial cells. CONCLUSIONS: Our findings support potential genotoxic effects of exposure to DBPs from swimming pools. The positive health effects gained by swimming could be increased by reducing the potential health risks of pool water.
Project description:BACKGROUND:Exposure to disinfection by-products (DBPs) in drinking water and chlorinated swimming pools are associated with adverse health outcomes, but biological mechanisms remain poorly understood. OBJECTIVES:Evaluate short-term changes in metabolic profiles in response to DBP exposure while swimming in a chlorinated pool. MATERIALS AND METHODS:The PISCINA-II study (EXPOsOMICS project) includes 60 volunteers swimming 40min in an indoor pool. Levels of most common DBPs were measured in water and in exhaled breath before and after swimming. Blood samples, collected before and 2h after swimming, were used for metabolic profiling by liquid-chromatography coupled to high-resolution mass-spectrometry. Metabolome-wide association between DBP exposures and each metabolic feature was evaluated using multivariate normal (MVN) models. Sensitivity analyses and compound annotation were conducted. RESULTS:Exposure levels of all DBPs in exhaled breath were higher after the experiment. A total of 6,471 metabolic features were detected and 293 features were associated with at least one DBP in exhaled breath following Bonferroni correction. A total of 333 metabolic features were associated to at least one DBP measured in water or urine. Uptake of DBPs and physical activity were strongly correlated and mutual adjustment reduced the number of statistically significant associations. From the 293 features, 20 could be identified corresponding to 13 metabolites including compounds in the tryptophan metabolism pathway. CONCLUSION:Our study identified numerous molecular changes following a swim in a chlorinated pool. While we could not explicitly evaluate which experiment-related factors induced these associations, molecular characterization highlighted metabolic features associated with exposure changes during swimming.
Project description:Acute exposure to chlorine gas results in respiratory impairment, but few data are available on the pathobiology of the underlying lung damage.To assess lung function and potential lung damage pathways in the acute phase and longitudinally over a 15-mo follow-up after acute chlorine exposure.Ten previously healthy children were accidentally exposed to chlorine gas at a swimming pool because of an erroneous servicing procedure. The fraction of nitric oxide in exhaled air (Fe(NO)), exhaled breath condensate compounds, and serum Clara cell-specific protein CC16 were repeatedly measured.In the acute phase, all patients had respiratory distress (one child required mechanical ventilation) and reduced lung function (median and interquartile range: FVC, 51 [43-60]% predicted; FEV(1), 51 [46-60]% predicted). This was accompanied by low Fe(NO) (4.7 [3.9-7.9] ppb), high exhaled breath condensate leukotriene B(4) (LTB(4)) levels (24.4 [22.5-24.9] pg/ml), and increased serum CC16 levels (mean +/- SEM, 23.4 +/- 2.5 microg/L). Lung function returned to normal in 15 d (FVC, 97% predicted [82-108], and FEV(1), 92% predicted [77-102]). Fe(NO) reached normal values after 2 mo (12.6 [11.4-15] ppb), whereas LTB(4) levels were still increased (12 [9.3-17.1] pg/ml).Children acutely exposed to chlorine in a swimming pool presented a substantial lung function impairment associated with biochemical exhaled breath alterations, represented mainly by an increase in LTB(4) and a reduction in Fe(NO). Although lung function and Fe(NO) improved within a few weeks, the increased levels of exhaled LTB(4) persisted for several months.
Project description:Trihalomethanes (THM) are a class of disinfection by-products in chlorinated waters linked to deleterious health effects in humans although biological mechanisms are unclear. We aimed to study short-term changes in blood gene expression of adult recreational swimmers associated with physical activity and THM exposure. Adult volunteers (18-50 years, non-smokers, non-asthmatics) swam 40 minutes in an indoor chlorinated pool in Barcelona. Blood samples and THM measurements in exhaled breath were collected before and 5 min/1h after swimming, respectively. Physical activity intensity was calculated as metabolic equivalents (METs). Gene expression in whole blood RNA was evaluated using Illumina HumanHT-12v3 Expression-BeadChip. Linear mixed models, Gene Set Enrichment Analyses-GSEA and mediation analyses were used. The study population comprised 37 before-after pairs, with mean age 31 years (SD: 6.0), 60% female, and average changes before-after swimming of 1.75 METs (SD: 1.36) and 0.23 µg/m3 of exhaled bromoform (SD: 0.23). Among THM, bromoform yielded the strongest effect on gene expression changes. Eighty eight probes were associated with bromoform, 326 probes with MET and 77 probes overlapped. In mutually adjusted models, 15 probes remained significant for MET after False Discovery Rate (FDR). Although not FDR significant, in 23 nominally significant probes (p-value <0.05), fulfilling criteria for exploring mediation, 29.5 to 53.4% of MET effect was mediated by exhaled bromoform. Individual genes in this subset and the GSEA of the mutually adjusted gene lists of bromoform and MET were associated with pathways related to inflammatory/immune response and to several cancers. In this first study evaluating short-term gene expression changes associated with swimming in a chlorinated pool, changes in gene expression were observed in association with physical activity with part of this effect mediated through bromoform exposure. Identified genes were correlated with inflammatory, immune response and cancer pathways. These results need replication in larger studies. Expression profile differences were determined between total RNA extracted before and after exposure to trihalomethanes present in swimming pool water for 40 minute from whole blood samples from 33 healthy human individuals.
Project description:Chlorination is the most popular method for disinfecting swimming pool water; however, although pathogens are being killed, many toxic compounds, called disinfection by-products (DBPs), are formed. Numerous epidemiological publications have associated the chlorination of pools with dysfunctions of the respiratory system and with some other diseases. However, the findings concerning these associations are not always consistent and have not been confirmed by toxicological studies. Therefore, the health effects from swimming in chlorinated pools and the corresponding stress reactions in organisms are unclear. In this study, we show that although the growth and behaviors of experimental rats were not affected, their health, training effects and metabolic profiles were significantly affected by a 12-week swimming training program in chlorinated water identical to that of public pools. Interestingly, the eyes and skin are the organs that are more directly affected than the lungs by the irritants in chlorinated water; instead of chlorination, training intensity, training frequency and choking on water may be the primary factors for lung damage induced by swimming. Among the five major organs (the heart, liver, spleen, lungs and kidneys), the liver is the most likely target of DBPs. Through metabolomics analysis, the corresponding metabolic stress pathways and a defensive system focusing on taurine were presented, based on which the corresponding countermeasures can be developed for swimming athletes and for others who spend a lot of time in chlorinated swimming pools.
Project description:Exposures to ambient diesel exhaust particles have been associated with respiratory symptoms and asthma exacerbations in children; however, epidemiologic evidence linking short-term exposure to ambient diesel exhaust particles with airway inflammation is limited. We conducted a panel study with asthmatic and nonasthmatic adolescents to characterize associations between ambient diesel exhaust particle exposures and exhaled biological markers of airway inflammation and oxidative stress. Over four weeks, exhaled breath condensate was collected twice a week from 18 asthmatics and 18 nonasthmatics (ages 14-19 years) attending two New York City schools and analyzed for pH and 8-isoprostane as indicators of airway inflammation and oxidative stress, respectively. Air concentrations of black carbon, a diesel exhaust particle indicator, were measured outside schools. Air measurements of nitrogen dioxide, ozone, and fine particulate matter were obtained for the closest central monitoring sites. Relationships between ambient pollutants and exhaled biomarkers were characterized using mixed effects models. Among all subjects, increases in 1- to 5-day averages of black carbon were associated with decreases in exhaled breath condensate pH, indicating increased airway inflammation, and increases in 8-isoprostane, indicating increased oxidative stress. Increases in 1- to 5-day averages of nitrogen dioxide were associated with increases in 8-isoprostane. Ozone and fine particulate matter were inconsistently associated with exhaled biomarkers. Associations did not differ between asthmatics and nonasthmatics. The findings indicate that short-term exposure to traffic-related air pollutants may increase airway inflammation and/or oxidative stress in urban youth and provide mechanistic support for associations documented between traffic-related pollutant exposures and respiratory morbidity.
Project description:Background: New biomarkers are urgently needed to facilitate diagnosis in Interstitial Lung Diseases (ILD), thus reducing the need for invasive procedures, and to enable tailoring and monitoring of medical treatment. Methods: In this study we investigated if patients with idiopathic pulmonary fibrosis (IPF; n = 21), non-IPF ILDs (n = 57) and other lung diseases (chronic obstructive pulmonary disease (COPD) n = 24, lung cancer (LC) n = 16) as well as healthy subjects (n = 20) show relevant differences in exhaled NO (FeNO; Niox MINO), or in eicosanoid (PGE2, 8-isoprostane; enzyme-linked immunosorbent assay (ELISA)) levels as measured in exhaled breath condensates (EBC) and bronchoalveolar lavage fluids (BALF). Results: There was no significant difference in FeNO values between IPF, non-IPF ILDs and healthy subjects, although some individual patients showed highly elevated FeNO. On the basis of the FeNO signal, it was neither possible to differentiate between the kind of disease nor to detect exacerbations. In addition, there was no correlation between FeNO values and lung function. The investigation of the eicosanoids in EBCs was challenging (PGE2) or unreliable (8-isoprostane), but worked out well in BALF. A significant increase of free 8-isoprostane was observed in BALF, but not in EBCs, of patients with IPF, hypersensitivity pneumonitis (HP) and sarcoidosis, possibly indicating severity of oxidative stress. Conclusions: FeNO-measurements are not of diagnostic benefit in different ILDs including IPF. The same holds true for PGE2 and 8-isoprostane in EBC by ELISA.
Project description:Exposure to airborne black carbon (BC) has been associated with asthma development, respiratory symptoms and decrements in lung function. However, the mechanism through which BC may lead to respiratory symptoms has not been completely elucidated. Oxidative stress has been suggested as a potential mechanism through which BC might lead to adverse health outcomes. Exhaled breath condensate (EBC) allows for the non-invasive collection of airway lining fluid containing biomarkers of oxidative stress like 8-isoprostane, a stable by-product of lipid peroxidation. Therefore, we sought to characterize the association between domestic airborne BC concentrations and 8-isoprostane in EBC.Seven- and eight-year-old children participated in an asthma case-control study in New York City. During home visits, air samples and EBC were collected. Seven day averages of domestic levels of particulate matter <2.5?m (PM2.5), BC and environmental tobacco smoke (ETS) were measured. Urea and 8-isoprostane were measured by liquid chromatography tandem mass spectrometry (LC/MS/MS) in EBC.In univariate models, PM2.5 and BC, but not ETS, were significantly associated with increases in 8-isoprostane in the EBC (?=0.006 and ?=0.106 respectively, p<0.05 for both). These associations remained statistically significant for both PM2.5 and BC after adjustment for covariates. In a co-pollutant model including PM2.5, BC and ETS, only BC remained a statistically significant predictor of 8-isoprostane (p<0.05).Our findings suggest the BC fraction of PM might contain exposure relevant to increased oxidative stress in the airways.
Project description:Early detection of lung cancer is a key factor for increasing the survival rates of lung cancer patients. The analysis of exhaled breath is promising as a noninvasive diagnostic tool for diagnosis of lung cancer. We demonstrate the quantitative analysis of carbonyl volatile organic compounds (VOCs) and identification of lung cancer VOC markers in exhaled breath using unique silicon microreactor technology. The microreactor consists of thousands of micropillars coated with an ammonium aminooxy salt for capture of carbonyl VOCs in exhaled breath by means of oximation reactions. Captured aminooxy-VOC adducts are analyzed by nanoelectrospray Fourier transform-ion cyclotron resonance (FT-ICR) mass spectrometry (MS). The concentrations of 2-butanone, 2-hydroxyacetaldehyde, 3-hydroxy-2-butanone, and 4-hydroxyhexenal (4-HHE) in the exhaled breath of lung cancer patients (n = 97) were significantly higher than in the exhaled breath of healthy smoker and nonsmoker controls (n = 88) and patients with benign pulmonary nodules (n = 32). The concentration of 2-butanone in exhaled breath of patients (n = 51) with stages II though IV non-small cell lung cancer (NSCLC) was significantly higher than in exhaled breath of patients with stage I (n = 34). The carbonyl VOC profile in exhaled breath determined using this new silicon microreactor technology provides for the noninvasive detection of lung cancer.
Project description:BACKGROUND:The mechanisms of chronic cough are unclear. Many reactive oxygen species affect airway sensory C-fibres which are capable to induce cough. Several chronic lung diseases are characterised by cough and oxidative stress. In asthma, an association between the cough severity and airway oxidative stress has been demonstrated. The present study was conducted to investigate whether airway oxidative stress is associated with chronic cough in subjects without chronic lung diseases. METHODS:Exhaled breath condensate samples were obtained in 43 non-smoking patients with chronic cough and 15 healthy subjects. Exclusion criteria included a doctor's diagnosis of any lung disorders and any abnormality in lung x-ray. The concentration of 8-isoprostane was measured. In addition, the patients filled in Leicester Cough Questionnaire and underwent hypertonic saline cough provocation test, spirometry, ambulatory peak flow monitoring, nitric oxide measurement, and histamine airway challenge. In a subgroup of patients the measurements were repeated during 12 weeks' treatment with inhaled budesonide, 800 ug/day. RESULTS:The 8-isoprostane concentrations were higher in the cough patients than in the healthy subjects (24.6?±?1.2 pg/ml vs. 10.1?±?1.7 pg/ml, p?=?0.045). The 8-isoprostane concentration was associated with the Leicester Cough Questionnaire total score (p?=?0.044) but not with the cough sensitivity to saline or other tests. Budesonide treatment did not affect the 8-isoprostane concentrations. CONCLUSIONS:Chronic cough seems to be associated with airway oxidative stress in subjects with chronic cough but without chronic lung diseases. This finding may help to develop novel antitussive drugs. TRIAL REGISTRATION:The study was registered in ClinicalTrials.gov database (KUH5801112), identifier NCT00859274.