Sébastien Hulo

Analysis of nitrogen oxides (NOx) in the exhaled breath condensate (EBC) of subjects with asthma as a complement to exhaled nitric oxide (FeNO) measurements: a cross-sectional study

BackgroundThe study of pulmonary biomarkers with noninvasive methods, such as the analysis of exhaled breath condensate (EBC), provides a useful approach to the pathophysiology of asthma. Although many recent publications have applied such methods, numerous methodological pitfalls remain. The first stage of our study consisted of validating methods for the collection, storage and analysis of EBC; we next sought to clarify the utility of analysing nitrogen oxides (NOx) in the EBC of asthmatics, as a complement to measuring exhaled nitric oxide (FeNO).MethodsThis hospital-based cross-sectional study included 23 controls matched with 23 asthmatics. EBC and FeNO were performed and respiratory function measured. Intra-assay and intra-subject reproducibility were assessed for the analysis of NOx in the EBC of 10 healthy subjects.ResultsThe intraclass correlation coefficient (ICC) was excellent for intra-assay reproducibility and was moderate for intra-subject reproducibility (Fermanians classification). NOx was significantly higher in asthmatics (geometric mean [IQR] 14.4 μM [10.4 - 19.7] vs controls 9.9 μM [7.5 - 15.0]), as was FeNO (29.9 ppb [17.9 - 52.4] vs controls 9.6 ppb [8.4 - 14.2]). FeNO also increased significantly with asthma severity.ConclusionsWe validated the procedures for NOx analysis in EBC and confirmed the need for assays of other biomarkers to further our knowledge of the pathophysiologic processes of asthma and improve its treatment and control.

Non-invasive collection of exhaled breath condensate in rats: Evaluation of pH, H2O2 and NOx in lipopolysaccharide-induced acute lung injury

The analysis of exhaled breath condensate (EBC) offers the potential for identifying lung disease markers in humans and animals, but methodological issues and standardised procedures need to be addressed before the technique can be considered for use in applications to help understand the role of environmental pollution in respiratory diseases. The purpose of this study was to develop and implement a new device using a glass-chamber for collecting EBC non-invasively from rats in order to analyse EBC markers in lipopolysaccharide (LPS)-induced acute lung injury. Eighty-four adult rats were used in five different series of experiments to determine the source of EBC formation, intra-day and inter-day variability, and the influence of environmental parameters on EBC markers. The hypothesis that inflammation induces an oxidative stress was assessed by measuring pH, nitrogen oxides (NOx) and hydrogen peroxide (H(2)O(2)) in EBC. The results confirmed that EBC fluid was generated at the level of the respiratory tract. The repeatability studies of disease markers indicated higher concentrations of NOx and H(2)O(2) at midday compared to the morning, but there were no significant difference between measurements on consecutive days. EBC volume was influenced by both ambient temperature and humidity. Moreover, 3h after LPS challenge, significantly increased concentrations of both NOx and H(2)O(2) were observed in EBC of the LPS group compared with controls (P=0.005 and P=0.027, respectively). These results suggested that EBC collection may be a valuable tool to monitor the presence of markers, such as NOx and H(2)O(2), in an animal model of LPS-induced acute lung injury.

Both exhaled nitric oxide and blood eosinophil count were associated with mild allergic asthma only in non-smokers.

The fractional exhaled nitric oxide (FENO) and the blood eosinophil count (B‐eos) are markers of eosinophilic inflammation used in the diagnosis and management of asthma. The relationships between smoking cigarette and both FENO and B‐eos are complex and raise questions about the association between these markers and asthma in smokers.

Global Lung Function Initiative reference equations better describe a middle-aged, healthy French population than the European Community for Steel and Coal values

Spirometry plays a pivotal role in the clinical evaluation and management of respiratory diseases. Pulmonary function varies with age, height, sex and ethnicity, and test results need to be compared with predicted values and lower limits of normal (LLN) and upper limits of normal (ULN), that are appropriate for the individual being tested [1]. The European Community for Steel and Coal (ECSC) first published reference spirometric values for healthy non-smokers in 1983 based on a collation of regression equations [2]. In 2012, the Global Lung Function Initiative (GLI) presented prediction equations derived from measured values of a large population [1]. These newer statistical procedures provided us for the first time with a single equation for ages from 3 years through to 95 years. Measured values are converted to z-scores which describe how many standard deviations a measured value differs from the predicted value and these are independent of sex, age and height. GLI reference equations better describe a middle-aged, healthy French population than the ECSC values http://ow.ly/xF773022Xhy

Manganese in exhaled breath condensate: A new marker of exposure to welding fumes

OBJECTIVE To evaluate manganese in exhaled breath condensate (Mn-EBC) as an indicator of exposure to fumes from metal inert gas welding process. METHODS We collected EBC and urine from 17 welders and 16 unexposed control subjects after 5 days exposure. Concentrations of manganese (Mn), nickel (Ni), iron (Fe) and chromium (Cr) were measured in EBC and urine samples and correlated with cumulative exposure indices for the working week (CIW) and for the total welding years (WY), based on duration of welding activity and atmospheric metal measurements. RESULTS Concentrations of Mn and Ni in EBC were significantly higher among welders than controls whereas this difference was not significant for Mn in urine. Levels of Mn and Ni in EBC were not correlated with their respective levels in urine. The linear regressions found significant positive coefficients between Mn-EBC, Ni-EBC, Ni-U and Cr-U concentrations and the cumulative exposure indices. Taking into account tobacco use, statistical analysis showed the same trends except for the relationship between Mn-U and CIW. CONCLUSION This pilot study showed that Mn-EBC, as well as Ni-EBC, can serve as reliable indices of occupational exposure to welding fumes and provide complimentary toxicokinetic information to that provided by urine analyses.

Knowledge and attitudes towards influenza vaccination of health care workers in emergency services

Annual vaccination rates among French health care workers (HCWs) are in decline even in Emergency Services to which patients at highest risk of influenza complications are admitted, and in which HCWs have the greatest risk of exposure to influenza from patients. We aimed here to identify knowledge and attitudes towards influenza vaccination of HCWs in Emergency Services. We collected 344 self-administered questionnaires of 1060 HCWs. Only 18% of HCWs were vaccinated against influenza. Physicians were vaccinated more often (55%) than nurses (16%) or aid nurses (11%). The most important barriers to vaccination were reported as being a lack of time (33%), lack of safety of the vaccine (31%), fear of contracting influenza due to vaccination (29%), and lack of effectiveness (23%). Being vaccinated was significantly related to a higher knowledge score based on epidemiological influenza items (OR (95% CI)) (1.63 (1.08-2.46)) and vaccine features items (2.36 (1.36-4.10)).

Mica Dust and Pneumoconiosis Example of a Pure Occupational Exposure in a Muscovite Milling Unit

Objective: We present pulmonary disorders of four employees who were exposed to high concentration of pure mica dust in a muscovite milling unit. Method: All cases underwent traditional examinations with a dual-energy chest computed tomographic scan. An analysis of exhaled breath condensate by Raman microspectrometry and of mineralogical content of a lung biopsy was performed for one case. Results: All cases showed bilateral micronodular ground glass opacities and mediastinal and hilar hyperdense lymph nodes consistent with the nodal sequestration of mineral particles. Histological analysis showed giant cell granulomas without typical silicotic nodule with high concentration of birefringent particles consistent with mica. Mica particles found in the exhaled breath condensate were identical to particles in ambient air at the company. Conclusion: Occupational exposure to mica dust is responsible for diffuse infiltrative lung disease by overload processes.

Interest of Exhaled Biomarkers in Occupational Asthma to Latex: A Case Report

ABSTRACT New methods for exploring pulmonary inflammation might be useful: measurements of exhaled nitric oxide (NO) and hydrogen peroxide (H2O2) 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 H2O2 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.

Exhaled breath NOx levels in a middle-aged adults population-based study: reference values and association with the smoking status

BACKGROUND Biomarkers in exhaled breath condensate (EBC) are potentially sensitive indicators of early biochemical changes in airways following exposure to pneumotoxic substances, particularly in susceptible subjects. NOx are the stable end products of the nitrite-nitrate-NO oxidative stress pathway and can be used to monitor airway inflammatory diseases, especially in asthma. Nevertheless, population-based surveys are needed to better interpret EBC NOx levels in clinical studies. The aim of this study was to establish reference values of EBC NOx in a large group of middle-aged, healthy adults of a sample of the general population with particular focus on the smoking status. METHODS The EBC NOx levels were analysed from 2872 subjects among the ELISABET population-based cross sectional study including a representative sample of men and women aged from 40 to 66 years olds conducted in northern France, which included comprehensive questionnaires by interview and spirometry data. Healthy participants were defined as participants with no self-reported respiratory disease. RESULTS For the healthy subjects (n = 1251), the median NOx concentration (IQR) was equal to 7.2  μM (3.12) and concentrations of NOx in EBC did not differ significantly according to smoking status. The upper fifth percentile (95%) (ULN) of NOx concentrations among healthy subjects was equal to 13.6  μM, ranging from 12.7  μM (smokers) to 14.4  μM (ex smokers). Among subjects with EBC NOx values higher than the ULN and compared with subjects that had EBC NOx values lower than the ULN, we found a significant higher proportion of subjects with current asthma (10.5% vs 6.5%) or with chronic bronchitis symptoms (7.6% vs 3.3%). CONCLUSION This population-based study has provided the distribution and the upper limit reference value of a nitrosative stress biomarker (NOx) in EBC of middle aged, healthy adults. EBC NOx levels were not associated with smoking status.

Predictive value of exhaled nitric oxide and aerobic capacity for sepsis complications after liver transplantation.

Our objective was to investigate the predictive value of fractional nitric oxide (NO) concentration in exhaled breath (FeNO) and aerobic capacity (peak VO2) for postoperative sepsis in liver transplantation candidates. Patients were identified and charts of all consecutive patients were prospectively reviewed. Bacterial sepsis represented the commonest postoperative complications (30%), which was attributed to peritonitis, pneumonia, and catheter‐related infections. Preoperative FeNO and peak VO2 values were lower in patients with postoperative sepsis. Patients with sepsis required higher needs for mechanical ventilation and ICU length of stay. Inverse correlation was found between logarithmically FeNO‐transformed data and systolic pulmonary artery pressure (r = −0.348; P = 0.018). Multivariate analyses using bootstrap sampling method indicated that odds of sepsis were associated with lower values of peak exercise VO2 [OR = 0.790 (0.592; 0.925)] and reduced log(FeNo) [OR = 0.027 (0.001; 0.451)], but not with higher MELD scores [OR = 1.141 (0.970; 1.486)]. By evaluating the cutoff for the ROC curves in each bootstrap resampling, median and 95% confidence interval were calculated for peak VO2: 17 [16.2; 22] ml/kg/min and FeNO: 17.2 [13.0; 33.9] ppb. We conclude that low peak exercise VO2 and reduced FeNO may help identify patients who are at risk to develop perioperative sepsis.