Interaction between Occupational and Non-Occupational Arsenic Exposure and Tobacco Smoke on Lung Cancerogenesis: A Systematic Review.

Although a higher lung cancer risk has been already associated with arsenic exposure, the contribution of arsenic and its compounds to the carcinogenic effects of other agents, such as tobacco smoke, is not well characterized. This systematic review examined the relationship between occupational and non-occupational arsenic exposure and tobacco smoking on lung cancer risk using papers published from 2010 to 2022. Two databases, PUBMED and Scifinder, were used for the searches. Among the sixteen human studies included, four were about occupational exposure, and the others were about arsenic in drinking water. Furthermore, only three case-control studies and two cohort studies evaluated an additive or multiplicative interaction. The interaction between arsenic exposure and tobacco smoke seems to be negligible at low arsenic concentrations (<100 µg/L), while there is a synergistic effect at higher concentrations. Finally, it is not yet possible to assess whether a linear no-threshold (LNT) model for lung cancer risk can be applied to the co-exposure to arsenic and tobacco smoke. Although the methodological quality of the included studies is good, these findings suggest that rigorous and accurate prospective studies on this topic are highly needed.

Interaction between occupational radon exposure and tobacco smoke: a systematic review.

INTRODUCTION: The risk of lung cancer from radon exposure was small compared to tobacco smoking (BEIR VI), but the relationship between these two carcinogenic agents has yet to be quantitatively estimated. The objective of this systematic review was to evaluate the last evidences on the role of radon occupational exposures and tobacco smoke on lung cancer risk. AREAS COVERED: Thirteen articles were selected using two different databases, PubMed and Scifinder, and were limited to those published from 2010 to 2021. The reference list of selected studies was reviewed to identify other relevant papers. EXPERT OPINION: Seven papers included in this systematic review did not deal with the multiplicative or the additive type of interaction between radon exposure and smoking habit. Six papers discussed the nature of this interaction with a prevalence of the sub-multiplicative model compared to the additive one. Altogether, smoking adjustment did not significantly change lung cancer risk. The included studies might constitute a starting point for updating the models for risk assessment in occupational and residential scenarios, promoting concomitantly the exposure reduction to radon and other cofactors, as recently introduced by Italian Legislative Decree number 101 of 31 July 2020, an application of Euratom Directive 59/2013.

This paper offers an updated overview on lung cancer risk due to occupational exposure to radon together with tobacco smoking habits. It evidences the quantitative role of smoking on radon exposure and discusses their interaction. The results show that smoking adjustments do not significantly modify lung cancer risk at both high and low radon concentrations.

Occupational exposure to graphene and silica nanoparticles. Part II: pilot study to identify a panel of sensitive biomarkers of genotoxic, oxidative and inflammatory effects on suitable biological matrices.

The available biomonitoring studies on workers producing/handling nanomaterials (NMs) focused on potential effects on respiratory, immune and cardio-vascular system. Aim of this study was to identify a panel of sensitive biomarkers and suitable biological matrices to evaluate particularly genotoxic and oxidative effects induced on workers unintentionally exposed to graphene or silica nanoparticles during the production process. These nanomaterials have been chosen for 'NanoKey' project, integrating the workplace exposure assessment (reported in part I) with the biomonitoring of exposed workers reported in the present work. Simultaneously to workplace exposure characterization, we monitored the workers using: Buccal Micronucleus Cytome (BMCyt) assay, fpg-comet test (lymphocytes), oxidized DNA bases 8-oxoGua, 8-oxoGuo and 8-oxodGuo measurements (urine), analysis of oxidative stress biomarkers in exhaled breath condensate (EBC), FENO measurement and cytokines release detection (serum). Since buccal cells are among the main targets of NM occupational exposure, particular attention was posed to the BMCyt assay that represents a noninvasive assay. This pilot study, performed on 12 workers vs.11 controls, demonstrates that BMCyt and fpg-comet assays are the most sensitive biomarkers of early, still reparable, genotoxic and oxidative effects. The findings suggest that these biomarkers could represent useful tools for the biomonitoring of workers exposed to nanoparticles, but they need to be confirmed on a high number of subjects. However, such biomarkers don't discriminate the effects of NM from those due to other chemicals used in the NM production process. Therefore, they could be suitable for the biomonitoring of workers exposed to complex scenario, including nanoparticles exposure.

Non-invasive techniques to assess restrictive lung disease in workers exposed to free crystalline silica.

OBJECTIVES: To compare the reliability of spirometry and body plethysmography in detecting restrictive lung disease in clay excavation workers exposed to free crystalline silica (FCS). The exhaled breath condensate (EBC) biomarkers of oxidative stress were also assessed in order to evaluate early lung damage. METHODS: The study involved 62 workers (58 males and 4 females) at a company that extracts and processes clay. RESULTS: Body plethysmography (total lung capacity below the lower normal limit) and spirometry respectively indicated restrictive pattern prevalence rates of 22.6% and 1.6%. EBC 4-hydroxynonenale levels were not sufficiently sensitive to highlight a restrictive deficit, but did distinguish low and high rates of occupational exposure. There was no correlation between plethysmography values and the intensity or duration of exposure. CONCLUSIONS: Only one out of 14 cases of restrictive deficit diagnosed on the basis of body plethysmography values was also identified by means of spirometry. This finding supports the need to use body plethysmography in the health surveillance of clay workers exposed to FCS.

The influence of maternal and paternal history on stone composition and clinical course of calcium nephrolithiasis in subjects aged between 15 and 25.

Our aim was to compare the influence of maternal history of stones (MHS) and paternal history of stones (PHS) on composition of calculi and disease course in a group of patients with calcium nephrolithiasis (CN) aged between 15 and 25, the age range with the maximal influence of family history on disease expression. One-hundred thirty-five patients (68 F) with CN and one stone-forming parent were retrospectively selected from the database of our outpatient stone clinic, and categorized according to MHS or PHS. Data about stone disease course and composition of passed calculi, determined by chemical analysis or Fourier-transformed infrared spectrophotometry, were collected together with information on blood chemistry and 24-h urinary profile of lithogenic risk. The characteristics of disease course and stone composition were compared using logistic regression tests adjusted for age, sex, and BMI or analysis of covariance where appropriate. Patients with MHS (n = 46) had significantly higher urinary calcium/creatinine ratio and ammonium, a higher prevalence of urological treatments (57 vs 27 %, p < 0.001) and mixed calcium oxalate/calcium phosphate stone composition (69 vs 35 %, p = 0.002) than those with PHS. At multivariate logistic regression models, MHS was independently associated with urological treatments (OR 4.5, 95 %CI 1.9-10.7, p < 0.001) and the formation of calculi with mixed calcium oxalate/calcium phosphate composition (OR 5.8, 95 %CI 1.9-17.9, p = 0.002). The method of stone analysis did not affect this result. In conclusion, in subjects aged 15-25, MHS is associated with mixed calcium stones and with a higher risk for urological procedures, and should be, therefore, considered in the management of urolithiasis.

The association of serum procalcitonin and high-sensitivity C-reactive protein with pneumonia in elderly multimorbid patients with respiratory symptoms: retrospective cohort study.

BACKGROUND: Serum procalcitonin and high-sensitivity C-reactive protein (hs-CRP) elevations have been associated with pneumonia in adults. Our aim was to establish their diagnostic usefulness in a cohort of hospitalized multimorbid patients ≥65 years old admitted to hospital with acute respiratory symptoms. METHODS: With a retrospective cohort study design, all multimorbid patients ≥65 years-old with acute respiratory symptoms admitted to an internal medicine hospital ward in Italy from January to August 2013 were evaluated. Pneumonia diagnosis, comorbidities expressed through Cumulative Illness Rating Scale (CIRS), setting of living, length of stay, serum hs-CRP and procalcitonin at admission were collected for each patient. Data were analyzed with Mann-Whitney's U test and multivariate Cox logistic regression analysis. A Receiver Operating Characteristic (ROC) curve was used to verify each biomarker's association with pneumonia diagnosis. RESULTS: Four hundred fifty five patients (227 M) were included in the study, of whom 239 with pneumonia (138 M, mean age 80 ± 13) and 216 without pneumonia (89 M, mean age 80 ± 14). After adjustment for age and sex, median levels of hs-CRP were significantly higher in patients with pneumonia (116 mg/L, IQR 46.5-179.0, vs 22.5 mg/dl, IQR 6.9-84.4, p < 0.0001), while procalcitonin median levels were not (0.22 ng/ml IQR 0.12-0.87, vs 0.15 ng/ml, IQR 0.10-0.35, p = 0.08). The ROC analysis showed that, unlike procalcitonin, hs-CRP values were predictive of pneumonia (AUC 0.76, 95% CI 0.72-0.79, p < 0.0001, cut-off value 61 mg/L), even after adjustment for possible confounders including nursing home residence and dementia. Serum hs-CRP levels >61 mg/L were independently associated with a 3.59-fold increased risk of pneumonia (OR 3.59, 95% CI 2.35-5.48, p < 0.0001). CONCLUSION: In elderly multimorbid patients who require hospital admission for respiratory symptoms, serum hs-CRP testing seems to be more useful than procalcitonin for guiding the diagnostic process when clinical suspicion of pneumonia is present. Procalcitonin testing might hence be not recommended in this setting.

Idiopathic Calcium Nephrolithiasis and Hypovitaminosis D: A Case-control Study.

OBJECTIVE: To investigate the association between vitamin D deficiency (25-hydroxyvitamin D <20 ng/mL) and idiopathic calcium nephrolithiasis (ICN). METHODS: A total of 884 patients with ICN (363 males, mean age of 51 ± 14) and 967 controls (162 males, mean age of 59 ± 15) from an area with no food fortification policy were considered following a case-control study design. Patients were enrolled at a third-level outpatient stone clinic. Controls were selected from a laboratory database after exclusion of those with nephrolithiasis, bone, endocrine, liver, and kidney diseases. Serum 25-hydroxyvitamin-D (25-OH-D), date of test, presence/history of diabetes, and cardiovascular disease including hypertension were recorded for all subjects. Serum parathormone, calcium, phosphorus, and urinary factors of lithogenic risk were available in stone formers (SF). After univariate statistical analysis, propensity score matching with conditional logistic regression was used to control for the possible effects of covariates. RESULTS: The prevalence of 25-OH-D <20 ng/mL was 56% in SF and 44% in controls (P <.001), with median levels of 18 ng/mL [interquartile range (IQR) of 12-24)] versus 23 ng/mL (IQR of 14-30) (age and sex adjusted P <.001). After a fully adjusted conditional logistic regression analysis, performed on propensity-matched cohorts (442 SF, 442 controls), there was a statistically significant association between vitamin D deficiency and odds of nephrolithiasis (estimated odds ratio of 2.29, confidence interval 95% 1.74-3.02, P <.001). 25-OH-D levels were not different in hypercalciuric and normocalciuric SF (median and IQR of 18 ng/mL and 13-23 vs 19 ng/mL and 13-26, respectively, P = .2). CONCLUSIONS: SF have lower serum 25-OH-D levels than controls. The role of hypovitaminosis D in the onset of ICN should be better reconsidered.

Family history influences clinical course of idiopathic calcium nephrolithiasis: case-control study of a large cohort of Italian patients.

AIM: To evaluate the contribution of family history of stones (FHS), up to second-degree relatives, on clinical course (age of first renal colic, bilateral disease, retained calculi, recurrences, urological procedures) of idiopathic calcium nephrolithiasis (ICN) and urinary parameters of lithogenic risk, a case-control study was carried out. METHOD: Clinical records of 2080 patients with ICN were evaluated and categorized according to FHS. Data about clinical course of disease and urinary parameters of lithogenic risk were collected. Student's t, Chi square tests and binary logistic regression were applied to discriminate groups with vs. without FHS. RESULTS: FHS was associated with an earlier onset of stone disease (age at first episode 32 ± 13 vs. 37 ± 15 years, p <0.001), particularly in females. After adjustment for multiple covariates, FHS was significantly associated to a higher risk of recurrence [odds ratio (OR) 1.2, 95 % confidence interval (1.1-1.4), p = 0.04], retained stones [OR 1.3, CI (1.1-1.5), p = 0.004], bilateral stones [OR 1.2, 95 % CI (1.1-1.5), p = 0.022] and urological procedures [OR 1.2, 95 % CI (1.1-1.5), p = 0.034]. FHS did not influence urinary parameters of lithogenic risk, except for calcium excretion in females. CONCLUSION: A positive family history influences the clinical course of ICN with some significant gender-related differences, substantially irrespective of urinary parameters of lithogenic risk.

An investigation of multimorbidity measures as risk factors for pneumonia in elderly frail patients admitted to hospital.

OBJECTIVES: To investigate the association of different chronic comorbidities, considered singularly and together in Cumulative Illness Rating Scale (CIRS) indexes, with pneumonia diagnosis in a group of elderly frail hospitalized patients. DESIGN AND METHODS: With a retrospective cohort design, all clinical records of frail (Rockwood ≥ 5) nonterminal patients ≥ 65 years old acutely admitted over a 8-month span in an internal medicine ward were evaluated. Pneumonia status and its categorization (community-acquired, CAP, vs healthcare-associated, HCAP) were defined according to chest radiology findings and validated criteria. Chronic comorbidities, CIRS Comorbidity Score and CIRS Severity Index were collected for each participant through a standardized methodology. Multivariate logistic regression models were applied to assess the association of each comorbid condition or scores with pneumonia. RESULTS: 1199 patients (546 M, median age 81.9, IQR 72.8-87.9 years), of whom 239 with pneumonia (180 CAP, 59 HCAP) were evaluated. CIRS Comorbidity Score was significantly associated with pneumonia, both at an age- and sex-adjusted model and at a multivariate model (OR for each unitary increase 1.03, 95% CI 1.001-1.062, p=0.04), together with provenience from nursing home (OR 1.96, 95% CI 1.41-2.73, p<0.001). Among single comorbidities, only COPD (OR 2.7, 95% CI 1.9-3.6, p<0.001) and dementia (OR 2.3, 95% CI 1.7-3.3, p<0.001) were associated with pneumonia, while stroke, cancer, cardiovascular, chronic liver and kidney disease were not. CONCLUSIONS: In a small cohort of elderly frail hospitalized patients, measures of multimorbidity, like CIRS, are significantly associated with the risk of pneumonia. COPD and dementia are the main conditions concurring to define this risk.

Multimorbidity in elderly hospitalised patients and risk of Clostridium difficile infection: a retrospective study with the Cumulative Illness Rating Scale (CIRS).

OBJECTIVES: To identify the role of chronic comorbidities, considered together in a literature-validated index (Cumulative Illness Rating Scale, CIRS), and antibiotic or proton-pump inhibitor (PPI) treatments as risk factors for hospital-acquired Clostridium difficile infection (CDI) in elderly multimorbid hospitalised patients. DESIGN: Retrospective cohort study. SETTING: Subacute hospital geriatric care ward in Italy. PARTICIPANTS: 505 (238 male (M), 268 female (F)) elderly (age≥65) multimorbid patients. MAIN OUTCOME MEASURES: The relationship between CDI and CIRS Comorbidity Score, number of comorbidities, antibiotic, antifungal and PPI treatments, and length of hospital stay was assessed through age-adjusted and sex-adjusted and multivariate logistic regression models. The CIRS Comorbidity Score was handled after categorisation in quartiles. RESULTS: Mean age was 80.7±11.3 years. 43 patients (22 M, 21 F) developed CDI. The prevalence of CDI increased among quartiles of CIRS Comorbidity Score (3.9% first quartile vs 11.1% fourth quartile, age-adjusted and sex-adjusted p=0.03). In the multivariate logistic regression analysis, patients in the highest quartile of CIRS Comorbidity Score (≥17) carried a significantly higher risk of CDI (OR 5.07, 95% CI 1.28 to 20.14, p=0.02) than patients in the lowest quartile (<9). The only other variable significantly associated with CDI was antibiotic therapy (OR 2.62, 95% CI 1.21 to 5.66, p=0.01). PPI treatment was not associated with CDI. CONCLUSIONS: Multimorbidity, measured through CIRS Comorbidity Score, is independently associated with the risk of CDI in a population of elderly patients with prolonged hospital stay.

Hippuric acid in 24 h urine collections as a biomarker of fruits and vegetables intake in kidney stone formers.

This work aimed to underline the prospects of hippuric acid, a product of the metabolism of polyphenols, as a new biomarker of fruits and vegetables intake associated with lithogenic risk. Biochemical parameters of lithogenic risk and hippuric acid were measured in the 24 h urine collections of a cohort of 696 Italian kidney stone formers divided into two subgroups according to their different dietary habits. The link between lithogenic risk parameters and hippuric acid was assessed and this compound was revealed as a valuable biomarker of fruits and vegetables intake in kidney stone formers. A cut-off value of urinary excretion of hippuric acid, 300 mg/24 h, was set as the threshold of discrimination between low and high intake of fruits and vegetables for these patients. These results highlight the importance of monitoring of the excretion hippuric acid in urine to address proper dietary guidelines for the management of stone former patients.

Airway acidification in childhood asthma exacerbations.

Exhaled breath condensate (EBC) is being used increasingly to sample airway lining fluid. In asthmatic patients, the concentration of pH in EBC has been found to be decreased and to be related to airway inflammation. The aim of this study was to determine exhaled pH levels during acute asthma exacerbations in relation to pharmacologic treatment in asthmatic children and compare these with control subjects. Twelve asthmatic children with asthma exacerbation and 27 healthy children were enrolled. Clinical observations and pH in EBC before and after standard treatment for asthma attack, based administration of inhaled beta2-agonist, and corticosteroid, according to international Global Initiative for Asthma guidelines, were compared with those in healthy subjects. All children performed skin-prick tests to aeroallergens. Asthmatic children underwent spirometry. Exhaled pH levels were significantly lower in children with asthma exacerbation before treatment (mean ± SD = 7.87 ± 0.66; p = 0.03) but not after treatment (8.11 ± 0.06; p = 0.40) compared with controls (8.12 + 0.19). Intragroup analyses found that condensate pH levels in asthmatic children before treatment were lower, but not significantly, than those after treatment. No correlation was found between pH values and treatment with systemic corticosteroids or lung function. Asthmatic children were atopic in 75% of cases. Levels of pH are decreased in EBC of asthmatic children with exacerbation before treatment. Larger studies are required to determine whether EBC pH levels may be a useful noninvasive biomarker to guide treatment of asthma exacerbations in childhood.

Influence of lean and fat mass on bone mineral density and on urinary stone risk factors in healthy women.

BACKGROUND: The role of body composition (lean mass and fat mass) on urine chemistries and bone quality is still debated. Our aim was therefore to determine the effect of lean mass and fat mass on urine composition and bone mineral density (BMD) in a cohort of healthy females. MATERIALS AND METHODS: 78 female volunteers (mean age 46 ± 6 years) were enrolled at the Stone Clinic of Parma University Hospital and subdued to 24-hour urine collection for lithogenic risk profile, DEXA, and 3-day dietary diary. We defined two mathematical indexes derived from body composition measurement (index of lean mass-ILM, and index of fat mass-IFM) and the cohort was split using the median value of each index, obtaining groups differing only for lean or fat mass. We then analyzed differences in urine composition, dietary intakes and BMD. RESULTS: The women with high values of ILM had significantly higher excretion of creatinine (991 ± 194 vs 1138 ± 191 mg/day, p = 0.001), potassium (47 ± 13 vs 60 ± 18 mEq/day, p < 0.001), phosphorus (520 ± 174 vs 665 ± 186 mg/day, p < 0.001), magnesium (66 ± 20 vs 85 ± 26 mg/day, p < 0.001), citrate (620 ± 178 vs 807 ± 323 mg/day, p = 0.002) and oxalate (21 ± 7 vs 27 ± 11 mg/day, p = 0.015) and a significantly better BMD values in limbs than other women with low values of ILM. The women with high values of IFM had similar urine composition to other women with low values of IFM, but significantly better BMD in axial sites. No differences in dietary habits were found in both analyses. CONCLUSIONS: Lean mass seems to significantly influence urine composition both in terms of lithogenesis promoters and inhibitors, while fat mass does not. Lean mass influences bone quality only in limb skeleton, while fat mass influences bone quality only in axial sites.

Prealbumin improves death risk prediction of BNP-added Seattle Heart Failure Model: results from a pilot study in elderly chronic heart failure patients.

BACKGROUND: An accurate prognosis prediction represents a key element in chronic heart failure (CHF) management. Seattle Heart Failure Model (SHFM) prognostic power, a validated risk score for predicting mortality in CHF, is improved by adding B-type natriuretic peptide (BNP). We evaluated in a prospective study the incremental value of several biomarkers, linked to different biological domains, on death risk prediction of BNP-added SHFM. METHODS: Troponin I (cTnI), norepinephrine, plasma renin activity, aldosterone, high sensitivity-C reactive protein (hs-CRP), tumor necrosis factor-α (TNF-α), interleukin 6 (IL-6), interleukin 2 soluble receptor, leptin, prealbumin, free malondialdehyde, and 15-F2t-isoprostane were measured in plasma from 142 consecutive ambulatory, non-diabetic stable CHF (mean NYHA-class 2.6) patients (mean age 75±8years). Calibration, discrimination, and risk reclassification of BNP-added SHFM were evaluated after individual biomarker addition. RESULTS: Individual addition of biomarkers to BNP-added SHFM did not improve death prediction, except for prealbumin (HR 0.49 CI: (0.31-0.76) p=0.002) and cTnI (HR 2.03 CI: (1.20-3.45) p=0.009). In fact, with respect to BNP-added SHFM (Harrell's C-statistic 0.702), prealbumin emerged as a stronger predictor of death showing the highest improvement in model discrimination (+0.021, p=0.033) and only a trend was observed for cTn I (+0.023, p=0.063). These biomarkers showed also the best reclassification statistic (Integrated Discrimination Improvement-IDI) at 1-year (IDI: cTnI, p=0.002; prealbumin, p=0.020), 2-years (IDI: cTnI, p=0.018; prealbumin: p=0.006) and 3-years of follow-up (IDI: cTnI p=0.024; prealbumin: p=0.012). CONCLUSIONS: Individual addition of prealbumin allows a more accurate prediction of mortality of BNP enriched SHFM in ambulatory elderly CHF suggesting its potential use in identifying those at high-risk that need nutritional surveillance.

Concentration of exhaled breath condensate biomarkers after fractionated collection based on exhaled CO2 signal.

A standard procedure for exhaled breath condensate (EBC) collection is still lacking. The aim of this study was to compare the concentration of several biomarkers in whole (W-EBC) and fractionated EBC (A-EBC), the latter collected starting from CO2 ≥ 50% increase during exhalation. Forty-five healthy non-smokers or asymptomatic light smokers were enrolled. Total protein concentrations in W-EBC and A-EBC were overlapping (median: 0.7 mg l(-1) in both cases), whereas mitochondrial DNA was higher in A-EBC (0.021 versus 0.011 ng ml(-1)), indicating a concentration rather than a dilution of lining fluid droplets in the last portion of exhaled air. H2O2 (0.13 versus 0.08 µM), 8-isoprostane (4.9 versus 4.4 pg ml(-1)), malondialdehyde (MDA) (4.2 versus 3.2 nM) and 4-hydroxy-2-nonhenal (HNE) (0.78 versus 0.66 nM) were all higher in W-EBC, suggesting a contribution from the upper airways to oxidative stress biomarkers in apparently healthy subjects. NH4(+) was also higher in W-EBC (median: 590 versus 370 µM), with an estimated increase over alveolar and bronchial air by a factor 1.5. pH was marginally, but significantly higher in W-EBC (8.05 versus 8.01). In conclusion, the fractionation of exhaled air may be promising in clinical and occupational medicine.

Effect of exposure to detergents and other chemicals on biomarkers of pulmonary response in exhaled breath from hospital cleaners: a pilot study.

PURPOSE: The main aim of the study was to provide evidence whether professional cleaning was associated with biomarkers of lung damage in non-invasively collected biological fluids (exhaled air and exhaled breath condensate--EBC). MATERIALS AND METHODS: This cross-sectional study involved 40 cleaners regularly exposed to cleaning detergents and 40 controls. The subjects completed a standard questionnaire from European Community Respiratory Health Survey (ECRHS II) and underwent a spirometry. Fractional exhaled nitric oxide (F(E)NO) was measured online, and pH, ammonium (NH(4) (+)), H(2)O(2) and 4-hydroxynonenal (4-HNE) were assayed in EBC. RESULTS: Among the cleaners, the frequency of asthma and rhinitis was, respectively, 2.5 and 20%. The most frequently reported symptoms were sneezing (27.5%), nasal and/or pharyngeal pruritus (25%), ocular pruritus (22.5%) and cough (22.5%). There were no significant differences in comparison with the control group. Median F(E)NO levels were higher in African than in Caucasian cleaners (21.5 [16.5-30.0] ppb and 18.0 [13.5-20.5] ppb; p < 0.05). H(2)O(2)-EBC (0.26 [0.09-0.53] µM vs. 0.07 [0.04-0.15] µM; p < 0.01), NH(4) (+)-EBC (857 [493-1,305] µM vs. 541 [306-907] µM; p < 0.01) and pH-EBC (8.17 [8.09-8.24] vs. 8.06 [7.81-8.10]; p < 0.01) were higher in the cleaners than in the controls. Finally, the cleaners showed significant correlations between pH-EBC and NH(4) (+)-EBC (r = 0.33, p < 0.05) and a weak correlation between 4-HNE-EBC and H(2)O(2)-EBC (r = 0.37, p < 0.05). CONCLUSION: The promising role of EBC analysis in biomonitoring of exposed workers was confirmed. It was also possible to identify the potential biomarkers of exposure to alkaline products (increased ammonium-EBC and pH-EBC levels) and potential biomarkers of oxidative stress (increased H(2)O(2)-EBC levels correlated with 4-HNE-EBC levels) in workers with no signs of airway diseases.

Urea in exhaled breath condensate of uraemics and patients with chronic airway diseases.

Exhaled breath condensate (EBC) is composed mainly by water and also contains non-volatile mediators, which are expired in small droplets of airway fluid. Urea has been proposed as a normalization factor for EBC non-volatile biomarkers. Aim of this study was to assess volatility and diffusivity of urea ex vivo and to measure its EBC concentrations in different clinical conditions. Volatility was assessed quantifying EBC concentrations collected at 4 different temperatures, whereas diffusivity was tested by measuring urea concentrations in both plasma and EBC from uraemic patients on intermittent haemodialysis. Urea was also measured in EBC from patients with chronic airway diseases, i.e., chronic obstructive pulmonary disease, asthma, and cystic fibrosis. The concentration of urea but not its absolute amount in EBC increased with condensation temperature. Haemodialysis influenced EBC and plasma urea concentrations in a similar way. The concentrations of urea in chronic airway diseases did not significantly differ from those of controls. Urea is a non-volatile molecule ex vivo and EBC urea depends on its concentrations in plasma. Urea concentrations in EBC are unaffected by three chronic airway diseases. We suggest that there is no need to normalize non-volatile biomarkers in EBC for urea concentrations to account for inter-individual variability. However, in repeated measurements within the same individual, the use of urea either as a normalizing factor or as covariate variable could be proposed to control intra-individual variability.

Collecting exhaled breath condensate (EBC) with two condensers in series: a promising technique for studying the mechanisms of EBC formation, and the volatility of selected biomarkers.

Exhaled breath condensate (EBC) consists mainly of water, but also contains semivolatile and nonvolatile compounds. The aim of this study was to develop a system in which two condensers are simultaneously used in series to clarify the mechanisms of EBC condensation. Two aliquots of EBC (EBC1 and EBC2) were collected from 20 asymptomatic smokers and 20 healthy young nonsmokers using a specifically designed device having two condensers in series in which total volume, hydrogen peroxide (H(2)O(2)), ammonium (NH(4)(+)), and conductivity before and after lyophilization were measured. Water, NH(4)(+) levels and conductivity before lyophilization were significantly lower in the EBC2 than in the EBC1 of smokers and nonsmokers; the contrary was true for H(2)O(2) levels. Almost all nonvolatile salts were collected in the first condenser, because more than 50% of postlyophilization conductivity was below the detection limit in EBC2. The recovery of volatile molecules and their derivatives (water and NH(4)(+)) was partial in the first condenser, but appreciable amounts of both were measured in the second; however, the condenser immediately in contact with exhaled air was more efficient in terms of water, NH(4)(+) and conductivity before lyophilization. On the contrary, nonvolatile ions (conductivity after lyophilization) were mainly collected in the first condenser. Finally, the behavior of H(2)O(2) cannot be explained on the basis of its chemical and physical properties, and the most probable explanation is that some was byproduced by a radical reaction in the gas phase or during the condensation process in water.

Environmental and biological monitoring of benzene exposure in a cohort of Italian taxi drivers.

An integrated approach based on ambient and biological monitoring, the latter including both biomarkers of exposure and susceptibility, was applied to characterize benzene exposure in a group of 37 taxi drivers of the city of Parma (Italy). Airborne benzene concentrations were assessed by 24 h personal sampling and work-shift sampling inside the taxicab using passive samplers (Radiello). Benzene metabolites, trans,trans-muconic acid (t,t-MA) and S-phenylmercapturic acid (S-PMA), and urinary cotinine as biomarker of smoking habits were measured by isotopic dilution liquid chromatography tandem mass spectrometry in both pre-shift (PS) and end-of-shift (EOS) samples. Urinary benzene (U-B) levels were determined by solid-phase microextraction gas chromatography-mass spectrometry in EOS samples. Relevant polymorphisms of microsomal epoxide hydrolase, NAD(P)H:quinone oxidoreductase, glutathione S-transferases M1-1 (GSTM1), T1-1, and A1 were characterized by PCR-based methods. Mean airborne benzene concentration was 5.85 +/- 1.65 microg/m3, as assessed by 24 h personal sampling integrating for work-shift, indoor or general environment activities. Significantly, higher benzene concentrations were detected in the taxicab during the work-shift (7.71 +/- 1.95 microg/m3, p < 0.005). Smokers eliminated significantly higher concentrations of U-B and S-PMA than non-smokers in EOS samples [geometric mean (geometric S.D.): 2.58 (4.23) versus 0.44 (1.79) microg/l for U-B; 3.79 (1.50) versus 2.14 (1.87) microg/gcreat. for S-PMA, p < 0.002]. Within smokers, S-PMA concentrations significantly increased at the end of the work-shift compared to pre-shift values (p < 0.05). t,t-MA showed a similar behaviour, although differences were not significant. In the narrow range examined, no correlation was observed between air benzene concentration and urinary biomarkers. All benzene biomarkers but EOS t,t-MA were correlated with U-cotinine (p < 0.05). GSTM1 polymorphism significantly modulated S-PMA excretion, as subjects bearing the GSTM1pos genotype [3.61 (1.15) microg/gcreat.] excreted significantly higher S-PMA concentrations than GSTM1null subjects [2.19 (1.18) microg/gcreat., p < 0.05].

Longitudinal monitoring of lung injury in children after acute chlorine exposure in a swimming pool.

RATIONALE: Acute exposure to chlorine gas results in respiratory impairment, but few data are available on the pathobiology of the underlying lung damage. OBJECTIVES: 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. METHODS: 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. MAIN RESULTS: 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). CONCLUSION: 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.