Does exposure to inflammatory particles modify the pattern of anion in exhaled breath condensate?

Exposure to environmental and occupational particulate matter (PM) induces health effects on the cardio-pulmonary system. In addition, associations between exposure to PM and metabolic syndromes like diabetes mellitus or obesity are now emerging in the literature. Collection of exhaled breath condensate (EBC) is an appealing non-invasive technique to sample pulmonary fluids. This hypothesis-generating study aims to (1) validate an ion chromatography method allowing the robust determination of different metabolism-related molecules (lactate, formate, acetate, propionate, butyrate, pyruvate, nitrite, nitrate) in EBC; (2) apply this method to EBC samples collected from workers exposed to quartz (a known inflammatory particle), to soapstone (a less inflammatory particle than quartz), as well as to controls. A multi-compound standard solution was used to determine the linearity range, detection limit, repeatability and bias from spiked EBC. The biological samples were injected without further treatment into an ion chromatograph with a conductivity detector. RTube® were used for field collection of EBC from 11 controls, 55 workers exposed to soapstone and 12 volunteers exposed to quartz dust. The analytical method used proved to be adequate for quantifying eight anions in EBC samples. Its sub-micromolar detection limits and repeatability, combined with a very simple sample preparation, allowed an easy and fast quantification of different glycolysis or nitrosative stress metabolites. Using multivariate discriminant analysis to maximize differences between groups, we observed a different pattern of anions with a higher formate/acetate ratio in the EBC samples for quartz exposed workers compared to the two other groups. We hypothesize that a modification of the metabolic signature could be induced by exposure to inflammatory particles like quartz and might be observed in the EBC via a change in the formate/acetate ratio.

Elevated alveolar nitric oxide is linked to poor aerobic capacity and chronotropic incompetence in liver transplant candidates.

BACKGROUND & AIMS: Increased nitric oxide is involved in abnormal hemodynamic parameters and respiratory function of cirrhotic patients. We aimed to quantify partitioning exhaled nitric oxide measurements in exhaled air in liver transplantation (LT) candidates and evaluate their relationships with chronotropic incompetence and aerobic capacity. METHODS: We compared exhaled nitric oxide (NO) measurements, heart rate response and peak oxygen uptake during incremental exercise in liver transplantation candidates to those of controls. RESULTS: As opposed to healthy control subjects, LT candidates displayed elevated alveolar NO, blunted chronotropic response and reduced V'O2 at maximal exercise. In LT candidates, median peak V'O2 was 18.7 ml kg-1 min-1 (interquartile range (IQR) 16.2; 21.8), corresponding to 65% (IQR 57; 72) of the predicted value. Compared with controls, LT candidates had increased levels of alveolar NO (median (IQR) 2.0 (1.2; 2.2) versus 3.1 (2.3; 4.5), p < 0.001). In controls, no relations were found between alveolar NO and V'O2 peak or heart rate reserve whereas in cirrhotic patients, negative correlations and negative slopes were found between alveolar NO and V'O2 peak and heart rate reserve decrease. CONCLUSIONS: Increasing alveolar NO could be a specific pathophysiological condition limiting aerobic capacity in LT candidates.

Method validation of nanoparticle tracking analysis to measure pulmonary nanoparticle content: the size distribution in exhaled breath condensate depends on occupational exposure.

A particle exposure assessment based on the dose deposited in the lungs would be the gold standard for the evaluation of any resulting health effects. Measuring particles in exhaled breath condensate (EBC)-a matrix containing water and airway lining fluid-could help to evaluate particle retention in the lungs. This study aimed to (1) validate a nanoparticle tracking analysis (NTA) method for determining the particle number concentration and their hydrodynamic size distribution in EBC, and (2) apply this method to EBC collected from workers exposed to soapstone (n = 55) or quartz dust (n = 12) and controls (n = 11). A standard latex bead solution was used to determine the linear range, limit of detection (LOD), repeatability (coefficient of variation, CV), and bias in spiked EBC. An LM10 NanoSight instrument with NTA version 3.1 software was used for measurement. RTubes® were used for field collection of EBC. The repeatability obtained for a D50 size distribution in EBC showed less than 8% variability, with a bias <7%. The particle concentration was linear in the range ≤2.5 × 108 particles ml-1 with a LOD of 4 × 106 particles ml-1. A recovery of 117 ± 20% at 6.2 × 107 particles ml-1 was obtained with a CV <10% and a bias <20%. EBC from workers exposed to quartz, who experienced the largest exposure to silica particles, consistently exhibited a statistically significant (p < 0.01) higher concentration of particles in their EBC, with a size distribution shift towards larger values than the other groups. Results showed that the NTA technique performed well for characterizing the size distribution and concentrations of particles in EBC. The technique needs to be corroborated with a larger population of workers.

Prognostic implications of preoperative aerobic capacity and exercise oscillatory ventilation after liver transplantation.

Our aim was to determine preoperative aerobic capacity (oxygen uptake [V'O2 ]) and prevalence of exercise oscillatory ventilation (EOV), underlying clinical characteristics of patients with EOV, and significance of reduced aerobic capacity and EOV in predicting mortality after liver transplantation. We prospectively studied 263 patients who underwent elective liver transplantation. Patients were followed up for 1 year. Despite minor impairment of resting cardiopulmonary function, preoperative aerobic capacity was reduced (peak V'O2 : 64 ± 19% predicted). EOV occurred in 10% of patients. Model for End-Stage Liver Disease score tended to be higher in patients with EOV compared to patients without, but failed to reach significance (p = 0.09). EOV patients had lower peak V'O2 and higher ventilatory drive. EOV was more frequent in nonsurvivors than in survivors (30% vs. 9%, p = 0.01) and was independently associated with posttransplant all-cause 1-year mortality. Reduced peak V'O2 best predicted the primary composite endpoint defined as 1-year mortality and/or prolonged hospitalization and early in-hospital mortality. Multivariate analysis revealed EOV (χ(2), 3.96; p = 0.04) and V'O2 (χ(2), 4.28; p = 0.04) as independent predictors of mortality and so-called primary composite endpoint, respectively. EOV and reduced peak V'O2 may identify high-risk candidates for liver transplantation, which would motivate a more aggressive treatment when detected.

Emphysema in asymptomatic smokers: quantitative CT evaluation in correlation with pulmonary function tests.

PURPOSE: To provide quantitative information on emphysema in asymptomatic smokers in correlation with pulmonary function tests (PFT). PATIENTS AND METHODS: The study population included 75 smokers (current smokers: n=39; ex-smokers: n=36) and 25 nonsmokers who underwent volumetric high-resolution CT of the chest with automated quantification of emphysema and PFTs. RESULTS: Current smokers had a higher percentage of emphysema in the right lung (P=0.041) and right upper lobe (P=0.037). The overall percentage of emphysema did not differ according to the Gold stage (P=0.77). Smokers with emphysema had significantly higher mean values of FRC (P=0.012), RV (<0.0001) and TLC (P=0.0157) than smokers without emphysema but no significant differences were found in neither the mean values of TLCO nor in expiratory flows (P>0.05). Correlations were found between the percentage of emphysema and (a) cigarette consumption of current (r=0.34215; P=0.0330) and ex-smokers (r=0.44104; P=0.0071); and (b) alterations of TLC, FRC, RV and DLCO of smokers. CONCLUSION: Quantitative CT allows recognition of regional specificities and subclinical functional alterations in smokers with emphysema.

Interest of exhaled biomarkers in occupational asthma to latex: a case report.

New methods for exploring pulmonary inflammation might be useful: measurements of exhaled nitric oxide (NO) and hydrogen peroxide (H(2)O(2)) in exhaled breath condensate (EBC). The authors describe the application and utility of these methods in a case report of pediatric nurse presenting an occupational asthma to latex. Despite compliance with avoidance measures, respiratory discomfort had worsened during work. Classical tests (spirometry, monitoring of peak expiratory flow) were not contributing to objectify the discomfort. Exhaled NO and H(2)O(2) in EBC increased immediately after work periods, compared with rest periods. Application of these new methods, at the same time, in workplace appears useful in the objective demonstration of a temporal relation between work and respiratory problems. The results allowed the occupational physician to transfer the patient to a new work station more appropriate for her respiratory health status.

Home telemonitoring (forced expiratory volume in 1 s) in children with severe asthma does not reduce exacerbations.

Some children with severe asthma develop frequent exacerbations despite intensive treatment. We sought to assess the outcome (severe exacerbations and healthcare use, lung function, quality of life and maintenance treatment) of a strategy based on daily home spirometry with teletransmission to an expert medical centre and whether it differs from that of a conventional strategy. 50 children with severe uncontrolled asthma were enrolled in a 12-month prospective study and were randomised into two groups: 1) treatment managed with daily home spirometry and medical feedback (HM) and 2) conventional treatment (CT). The children's mean age was 10.9 yrs (95% confidence interval 10.2-11.6). 44 children completed the study (21 in the HM group and 23 in the CT group). The median number of severe exacerbations per patient was 2.0 (interquartile range 1.0-4.0) in the HM group and 3.0 (1.0-4.0) in the CT group (p=0.38 with adjustment for age). There were no significant differences between the two groups for unscheduled visits (HM 5.0 (3.0-7.0), CT 3.0 (2.0-7.0); p=0.30), lung function (pre-ß(2)-agonist forced expiratory volume in 1 s (FEV(1)) p=0.13), Paediatric Asthma Quality of Life Questionnaire scores (p=0.61) and median daily dose of inhaled corticosteroids (p=0.86). A treatment strategy based on daily FEV(1) monitoring with medical feedback did not reduce severe asthma exacerbations.

Relationship between psychosocial factors at work and incidence of perceived health problems in the GERICOTS cohort.

BACKGROUND: The objective of this study was to investigate the relationship between the incidence of health problems and the psychosocial work environment in a French occupational cohort. METHODS: Among the 2062 employees in the North of France who participated in the GERICOTS survey between 1999 and 2004, 1154 subjects who kept the same full-time shift in the same firm during the study period (797 men and 357 women) were included. Job strain was assessed using Karasek's model--the strain profile (high psychological demand and low decision latitude) and the iso-strain profile (strain profile and low social support)--and Siegrist's model, Effort-Reward Imbalance (ERI) (high effort and low rewards). Perceived health status was assessed using the four dimensions of the Nottingham Health Profile (emotional reactions, sleep, social isolation, pain). The results are given by the odds ratio adjusted for age, occupational category, and size of firm. RESULTS: At baseline, higher prevalence of health problems was found in workers with job strain, e.g., between emotional reactions and iso-strain for men, OR=3.50 (2.19-5.60) and for women, 2.64 (1.39-5.04) or between sleep disorders and ERI for men, OR=2.41 (1.71-3.40) and for women, OR=2.41 (1.39-4.20). Longitudinal analysis showed a significant relationship between incidence of health problems and level of job strain in 1999, e.g., between sleep disorder incidence and strain profile, OR=1.89 (1.16-3.06) and ERI, OR=2.20 (1.43-3.38). CONCLUSION: These results show a significant relationship between perceived health and job stress in 1999 but also between incidence of health problems between 1999 and 2004 and job strain in 1999.

Cytokine concentrations in exhaled breath condensates in systemic sclerosis.

BACKGROUND: Pulmonary fibrosis in systemic sclerosis (SSc) involves inflammatory processes in the lower respiratory tract. Analysis of exhaled breath condensate (EBC) is a non-invasive method for studying inflammatory mediators, such as cytokines, which are of interest from both physiological and therapeutic perspectives. The aim of this study was to assess and compare cytokine concentrations in the EBC of SSc patients and controls. MATERIAL AND METHODS: EBC was collected from 19 SSc patients and 19 controls. We used a multiplex assay test kit to assay interleukin (IL)-2, -4, -6, -10, tumour necrosis factor-alpha, and interferon-gamma in samples concentrated by lyophilization. RESULTS: Cytokine concentrations in EBC were higher in SSc patients than in controls. The stepwise analyses showed that IL-4 was the biomarker which contributed most to the discrimination between controls and patients (Wilk's Lambda = 0.55, p < 0.001). We observed significant negative correlations of EBC cytokines with total lung capacity and diffusion capacity of the lung for carbon monoxide. CONCLUSIONS: These findings suggest that EBC sampling permits the non-invasive study of inflammation in SSc patients, and may be correlated with the severity of interstitial lung disease.

Long-term assessment of a sanitary education and lumbar rehabilitation program for health care workers with chronic low back pain at the University Hospital of Lille.

A back school was established in 1992 at the University Hospital of Lille (France) for employees with low back pain. We report its medical and socioeconomic benefits with a mean time to follow-up of 4 years. Our retrospective study included 108 health care workers and provides objective data (absenteeism, use of health care) and subjective information (progression of pain and disorder, social and professional impact) before training and a mean of 4 years after training. We found that 92% of the participants were satisfied with the training and that back pain had regressed or resolved for 55% of them. Both the frequency and duration of pain had decreased significantly. Seventy percent continue to apply the advice they received in their everyday life. Dealing with the problems specific to professional activities contributed to reduce the strain experienced on the job by the health care workers and improved their satisfaction at work. Global absenteeism was reduced by 57.8%, whereas it was reduced by 33% for back pain alone 4 years after implementing this program. Our study provides evidence of the positive impact of this type of training on the way back pain is perceived and on everyday life. The assessment of the cost/efficiency ratio completes the list of durable benefits reported here.

Thin-section CT finding in 250 volunteers: assessment of the relationship of CT findings with smoking history and pulmonary function test results.

PURPOSE: To evaluate the frequency and morphologic characteristics of air trapping in volunteers with various smoking habits. MATERIALS AND METHODS: Two hundred fifty volunteers (133 women, 117 men; mean age, 39 years), including 144 smokers, 47 ex-smokers, and 59 nonsmokers, prospectively underwent inspiratory and expiratory high-spatial-resolution computed tomography (CT) and pulmonary function tests (PFTs). The frequency and characteristics of air trapping were evaluated according to the population's smoking habits and PFT results. RESULTS: The overall frequency of air trapping was 62% (155 of 250 subjects). Lobular air trapping was depicted in 117 (47%) of 250 subjects, without significant differences among smokers (n = 91), ex-smokers (n = 33), and nonsmokers (n = 31) (P =.118). Segmental and lobar air trapping (38 [15%] of 250) were more frequent among smokers (24 [26%] of 91) and ex-smokers (nine [27%] of 33) (P <.001). No relationship was found between air trapping and functional indexes of small-airway disease when the CT pattern of air trapping was considered. The strongest relationship between CT abnormalities and functional alterations at the small-airways level was between inspiratory CT features of bronchiolitis: ground-glass opacity, ill-defined micronodules, bronchiolectasis, and air flow at low lung volumes. CONCLUSION: Whereas a significant relationship was observed between segmental and lobar air trapping and cigarette consumption, lobular air trapping was not found to reflect functional impairment at the small-airways level.

Prevalence of cytomegalovirus infection among health care workers in pediatric and immunosuppressed adult units.

The prevalence of cytomegalovirus (CMV) infection varies not only from one country to another, but also with social, economic, and environmental conditions and with professional activity. Health care workers in contact with the main vectors of the CMV (i.e., children and immunosuppressed patients) are particularly exposed to the infection. We assessed the prevalence of the virus among health care personnel in light of CMV epidemiology and the recent shift in living conditions and family size. Our study was included in a broader program evaluating the risk of infection among female hospital workers of childbearing age. The goal of the program was to implement appropriate preventive measures for personnel who were not immune to the infection. Consequently, we included only female caregivers who worked with children or immunosuppressed patients. The study was based on a clinical examination, a medical and occupational questionnaire, the assessment of tasks performed; and CMV serologic testing. The overall seroprevalence was 44.25% in our population (n = 400) and was comparable regardless of the place of work. Prevalence differed significantly with age and parity, and we also found that it was higher among personnel who worked in closer contact with the patients (nurse's aides, pediatric nurse's aides) than among those whose tasks required more technical skills (nurses, pediatric nurses) (57.3% vs 34.5%, P < 0.01). The logistic regression analysis between prevalence of CMV antibodies, age, parity, and type of job showed that "contact job" was as significant a factor as parity to explain immunization in our population (odds ratio, 2.2). We also determined a correlation between the prevalence of CMV antibodies and tasks performed. In addition, we found a non-negligible group of non-immune personnel (55.75%) and young workers (mean age: 33.4) who were potentially exposed to infection. This points to the need to establish a prevention program.

Acute respiratory effects of exposure to stainless steel and mild steel welding fumes.

Over the past few years, many studies, including one on our previous work, have examined the chronic effects of fumes from stainless steel (SS) welding on the health of welders. These chronic effects have been related to concentrations of chromium and nickel in SS welding fumes. The present study examined the acute respiratory effects of welding fumes in the workplace by measuring the across-shift changes in a population of 144 SS and mild steel (MS) welders and 223 controls. Manual Metal Arc, Metal Inert Gas, and Tungsten Inert Gas welding processes were studied. Pulmonary function tests were performed at the start (ante, or A) and at the end (post, or P) of the work shift. The study of sensitization to harmful respiratory effects of welding was based on the study of the (P-A)/A ratio (%) of the spirometric variations during the shift. The means of these ratios in the control subjects were used to account for the circadian effect. In SS welders we observed a significant decrease in forced vital capacity (FVC) during the shift. Significant across-shift decrements in forced expiratory volume in 1 second (FEV1) and FVC were related to the SS welding exposure compared with MS welding. Moreover, the across-shift decreases in FEV1, FVC, and peak expiratory flow (PEF) were significantly related to the Manual Metal Arc welding process, compared with Metal Inert Gas techniques (respectively, PEF = -2.7% of baseline values [SD, 11.9] vs 2.0% of baseline values [SD, 7.7] P = 0.04; FVC = -1.5% of baseline values [SD, 4.8] vs 0.2% of baseline values [SD, 4.5] P = 0.05). We also demonstrated the influence of duration of SS welding exposure on the course of lung function during the work shift. After 20 years of SS welding activity, SS welders had more significant across-shift decreases than MS welders with a similar MS exposure duration (respectively, FEV1 = -2.7% of baseline values [SD, 5.9] vs 0.7% of baseline values [SD, 4.2] P = 0.008; PEF = -3.8% of baseline values [SD, 9.6] vs 2.3% of baseline values [SD, 6.5] P = 0.04). We concluded that welding-related lung function responses are seen in SS compared with MS welders and in those with a longer lifetime welding history.

Short term response of circulating leptin to feeding and fasting in man: influence of circadian cycle.

OBJECTIVE: To investigate whether acute feeding induces changes in circulating leptin levels in humans and whether these changes vary according to nycthemeral cycle. METHODS: First experiment. Eighteen male subjects were given a fatty meal at 08.00 h. Blood sampling was performed for 10 h following this meal. Second experiment. Thirteen male subjects were given either a mixed meal or remained fasting either at night (starting at 01.00 h) or during the day (starting at 13.00 h). Blood samples were drawn every hour for a period of 8 h. RESULTS: First experiment. Serum leptin levels increased progressively from a mean (s.d.) baseline of 3.8 +/- 2.2 ng/ml to a value of 4.5 +/- 2.7 ng/ml (P < 0.01) 8 h after the fatty meal. Second experiment. During the day, serum leptin levels increased progressively from 2.65 +/- 1.7 to 3.34 +/- 2.2 ng/ml (P < 0.001) 6 h after the test-meal and decreased from 2.68 +/- 1.5 to 1.9 +/- 1.1 ng/ml (P < 0.001) 8 h after the beginning of the fasting experiment. Similar results were obtained at night. No statistically significant differences in leptin levels were observed between day and night sessions in response to feeding (mean area under the curve: 3.0 +/- 4.1 vs 4.1 +/- 4.1 ng/ml) and fasting (-2.9 +/- 2.2 vs -1.5 +/- 2.2 ng/ml). CONCLUSION: In two independent experiments, human serum leptin levels increase following food intake. This response is not influenced by nycthemeral cycle.

Respiratory symptoms and pulmonary function among stainless steel welders.

In the last few years, many studies have been carried out concerning the effects of fumes from stainless steel (SS) welding on the health of welders. The respiratory effects of exposure to SS welding fumes have already been studied, but the results of lung function investigations have not been consistent. However, the main factor of risk for the welders' health seems to be related to the great concentration of chromium and nickel contained in fumes coming from SS welding. The aim of this study was to detect the chronic effects of SS welding exposure on pulmonary symptoms and ventilatory function tests. Respiratory symptoms and lung function tests were studied in 134 SS welders and 252 controls (C). Welders and controls were of similar average age, height, and duration in employment. The smoking habits of the groups were also similar. The medical questionnaire on respiratory symptoms was a version of the Medical Research Council questionnaire, modified by the British Occupational Hygiene Society. The flow-volume curves were performed with a calibrated pneumotachograph spirometer before each subject started working. After adjustment for tobacco habits, the SS welders presented a higher prevalence of bronchial irritative symptoms such as cough (P = 0.01) or sputum production (P = 0.02) than the controls. On the other hand, chronic bronchitis appeared to be significantly linked to tobacco consumption. The pulmonary function analysis underscored no significant difference between stainless steel welders and controls (forced expiratory volume in one second, observed/predicted: SS = 0.99 vs C = 0.98; maximal midexpiratory flow, observed/predicted: SS = 0.90 vs C = 0.92; maximal expiratory flow at 50 % of the forced vital capacity, observed/predicted: SS = 0.95 vs C = 0.95). On the other hand, by the mean of the two-ways analysis, a significant tobacco effect was found, without exposure or interaction of tobacco-exposure effects. There was no influence of the specific welding processes on the spirographic parameters, but a decrease in spirographic values after 25 years of welding activity was evident. The results of multiple regression indicated that age was not a confounding factor.

Circadian variation of postprandial lipemia.

The goal of the present study was to assess the influence of mealtime on postprandial lipemia. Thirteen healthy subject aged 19-32 y were given the same meal at night (0100) or during the day (1300) in random order: the meal contained 40% of estimated daily energy expenditure. Blood samples were drawn at baseline and hourly for 8 h after the meal. Serum total cholesterol, very-low-density-lipoprotein cholesterol (VLDL-C), low-density-lipoprotein cholesterol (LDL-C), high-density-lipoprotein cholesterol (HDL-C), triacylglycerols, VLDL-triacylglycerols, apolipoprotein (apo) A-I, and apo B were measured at each time point. In a subgroup of seven subjects a control fasting reference line was measured according to the same nocturnal and diurnal time schedule. The mean postprandial concentrations of triacylglycerol (P < 0.001), VLDL-triacylglycerol (P < 0.001), and VLDL-C (P < 0.001) were higher at night than during the day. In contrast, mean cholesterol (P < 0.01), LDL-C (P < 0.01), HDL-C (P < 0.001), apo A-I (P < 0.001), and apo B (P < 0.001) concentrations were lower after the night meal than after the day meal. The magnitude of the postprandial response was estimated by the area between the fasting and postprandial curves. The triacylglycerol and VLDL-triacylglycerol responses were not significantly different between night and day. The VLDL-C (P < 0.01) response was greater and LDL-C (P < 0.0001) and HDL-C (P < 0.01) responses were lower at night than during the day. These results indicate that circadian factors specifically affect serum cholesterol transport. Apo B (P < 0.01) and apo A-I (P < 0.01) responses followed LDL-C and HDL-C changes during the day but were dissociated from lipoprotein responses at night, suggesting that circadian apolipoprotein regulation is dissociated from that of serum lipids. The results of the present study indicate that postprandial lipid, lipoprotein, and apolipoprotein concentrations are affected by circadian factors.