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

<p>Abstract</p> <p>Background</p> <p>The 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).</p> <p>Methods</p> <p>This 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.</p> <p>Results</p> <p>The intraclass correlation coefficient (ICC) was excellent for intra-assay reproducibility and was moderate for intra-subject reproducibility (Fermanian's 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.</p> <p>Conclusions</p> <p>We 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.</p

Le condensat d'air exhalé : une nouvelle matrice pour évaluer l'exposition pulmonaire professionnelle

Medical follow-up of employees in occupational medicine requires the use of biological exposure indices that are frequently measured in urine or blood and thus reflect the result of purification by multiple organs. It seems appropriate to evaluate the internal pulmonary dose of occupational toxins to detect their potential early impact. This internal dose could previously only be known after performing invasive techniques such as bronchoalveolar lavage. The exhaled breath condensate (EBC) is a liquid obtained non-invasively after cooling the exhaled air of a subject at rest. It consists of the aerosolization of the liquid that covers the respiratory epithelium of the alveolar compartment and the tracheobronchial or bronchial compartment. Many studies have investigated the markers of inflammation in this matrix but very few have studied the markers of exposure. The current clearance lung models show that the clearance of inhaled particles is variable depending on the region (tracheobronchial , bronchiolar or alveolar region) and a significant proportion of these particles has a slow clearance. Therefore, we hypothesize that EBC could be a matrix that should reflect the pulmonary exposure of inhaled particles during occupational exposure.AimsThe first aim of our study was to assess the feasibility to detect mineral or metallic particles in the EBC of exposed workers. The second objective was to correlate the EBC concentration of these particles with their atmospheric concentrations measured during work.We analyzed EBC from employees engaged in three occupational activities.The first study involved an employee of a milling unit of muscovite suffering from diffuse infiltrative lung disease who underwent a collection of condensate, a lung biopsy, and a dual-source, dual-energy computed tomography. A mineralogical analysis was performed on the EBC, lung tissue, and atmospheric dust collected at the plant.The second study was an exposed-unexposed study on a group of welders using a technique called "metal inert gas" (MIG) welding for assembling steel structures during the production of rail transport (in collaboration with the Association Santé Travail de l’Arrondissement de Valenciennes - ASTAV). Metals of interest in this study were manganese (Mn), nickel (Ni), iron (Fe), and chromium (Cr). Air samples were performed at the plant in order to calculate a cumulative exposure index for the week and thence the welding history for each metal of interest.The third study was a national exposed-unexposed study of workers exposed to soluble beryllium compounds in an aluminum smelter (in collaboration with the Institut National de Recherche et de Sécurité - INRS). The recruitment of exposed subjects was carried out in the electrolysis area production (Area “A”) and in the area of anodes repair (area “B”). Metals of interest in this study were the beryllium (Be), and aluminum (Al). A task-exposure matrix allowed us to calculate a cumulative exposure index of beryllium.Groups (exposed and control) of the second and third study underwent a collection of condensate, a urine collection (U), and pulmonary function tests (PFT) including measurement of exhaled NO. Cumulative exposure indices were correlated with metal concentrations in EBC.The use of new techniques was necessary for the determination of particles in the EBC as Raman spectroscopy for mineral muscovite particles (collaboration with EA 4490 Faculty of Dental Surgery) and inductively coupled plasma mass spectrometry (ICP- MS) for the metal particles in the EBC (in collaboration with the Ultra Trace Analyse Aquitaine - UT2A ) and urine (in collaboration with the Centre Universitaire de Mesures et d’Analyses – CUMA, Lille 2 ). [...]Dans le cadre d’une action préventive, la mesure de la dose interne pulmonaire est plus pertinenteque la mesure de l’exposition atmosphérique car la dose interne est la quantité de toxique pouvantinteragir avec les cellules de l’épithélium respiratoire. En santé-travail, le dosage urinaire est fréquemmentutilisé mais il ne représente que le résultat final de l’épuration de multiples organes. Lecondensat d’air exhalé (EBC) est le liquide obtenu de façon non invasive après refroidissement del’air expiré d’un sujet au repos. Ce liquide est constitué de l’aérosolisation du liquide recouvrantl’épithélium respiratoire du compartiment alvéolaire et aussi du compartiment trachéobronchique oubronchique. Nous proposons d’utiliser l’EBC comme une approche alternative pour la surveillancebiologique des salariés. Les modèles cinétiques d’épuration pulmonaire actuels montrent que lesparticules déposées dans le compartiment alvéolaire ont une épuration très lente. Nous avons doncvoulu savoir si l’EBC était une matrice reflétant l’exposition pulmonaire en particules inhalées.Objectifs : 1) évaluer la faisabilité de la détection de particules minérales ou métalliques dans l’EBCde salariés exposés, 2) corréler la concentration de ces particules dans l’EBC avec les concentrations atmosphériques de ces particules obtenues pendant le poste de travail et avec les dosages urinaires.Matériel et Méthode : Nous avons analysé les EBC de salariés issus de trois secteurs d’activité professionnelle. La 1ère étude concernait un salarié d’une unité de broyage de muscovite atteint d’une infiltration pulmonaire diffuse. La 2ème étude était une étude « exposé/non-exposé »concernant un groupe de soudeurs utilisant la technique « metal inert gaz » (MIG). La 3ème étudeétait une étude « exposé/non-exposé » de salariés exposés à des composés solubles de bérylliumdans le secteur de l’aluminerie dans 2 entreprises différentes.Résultats Etude n°1 : L’analyse minéralogique de l’EBC a retrouvé des particules ayant le même profil spectral en spectrométrie Raman que les particules prélevées dans l’atmosphère de l’entreprise. L’analyse minéralogique du parenchyme pulmonaire a montré la présence d’une concentration élevée de particules compatibles avec des particules de muscovite.Etude n°2 : Les concentrations de manganèse et de nickel dans l’EBC (Mn-EBC, Ni-EBC) dosées par ICP-MS étaient significativement plus élevées chez les soudeurs que chez les témoins alors que cette différence n'était pas significative pour le Mn urinaire (Mn-U). Les concentrations de Mn-EBC et de Ni-EBC ne sont pas corrélées avec leur concentration respective dans l'urine. Les régressions linéaires ont trouvé des coefficients significativement positifs entre les concentrations de Mn-EBC,Ni-EBC, Ni-U et Cr-U et les indices d’exposition cumulée.Etude n°3 : Les concentrations de béryllium et d’aluminium dans l’EBC (Be-EBC, Al-EBC) étaient significativement plus élevées chez les sujets de l’entreprise n°1 que chez les témoins alors que leurs concentrations dans les urines ne l’étaient pas. Les régressions linéaires ont trouvé des coefficients significativement positifs entre les concentrations de Be-EBC et celle d’Al-EBC mais aussi entre les concentrations de Be-EBC et l’indice d’exposition cumulée. Les concentrations d’Al-EBC et Al-U étaient significativement plus élevées chez les sujets de l’entreprise n°2 que chez les témoins. [...

Exhaled breath condensate : a new matrix for evaluating pulmonary occupational exposure

Dans le cadre d’une action préventive, la mesure de la dose interne pulmonaire est plus pertinenteque la mesure de l’exposition atmosphérique car la dose interne est la quantité de toxique pouvantinteragir avec les cellules de l’épithélium respiratoire. En santé-travail, le dosage urinaire est fréquemmentutilisé mais il ne représente que le résultat final de l’épuration de multiples organes. Lecondensat d’air exhalé (EBC) est le liquide obtenu de façon non invasive après refroidissement del’air expiré d’un sujet au repos. Ce liquide est constitué de l’aérosolisation du liquide recouvrantl’épithélium respiratoire du compartiment alvéolaire et aussi du compartiment trachéobronchique oubronchique. Nous proposons d’utiliser l’EBC comme une approche alternative pour la surveillancebiologique des salariés. Les modèles cinétiques d’épuration pulmonaire actuels montrent que lesparticules déposées dans le compartiment alvéolaire ont une épuration très lente. Nous avons doncvoulu savoir si l’EBC était une matrice reflétant l’exposition pulmonaire en particules inhalées.Objectifs : 1) évaluer la faisabilité de la détection de particules minérales ou métalliques dans l’EBCde salariés exposés, 2) corréler la concentration de ces particules dans l’EBC avec les concentrations atmosphériques de ces particules obtenues pendant le poste de travail et avec les dosages urinaires.Matériel et Méthode : Nous avons analysé les EBC de salariés issus de trois secteurs d’activité professionnelle. La 1ère étude concernait un salarié d’une unité de broyage de muscovite atteint d’une infiltration pulmonaire diffuse. La 2ème étude était une étude « exposé/non-exposé »concernant un groupe de soudeurs utilisant la technique « metal inert gaz » (MIG). La 3ème étudeétait une étude « exposé/non-exposé » de salariés exposés à des composés solubles de bérylliumdans le secteur de l’aluminerie dans 2 entreprises différentes.Résultats Etude n°1 : L’analyse minéralogique de l’EBC a retrouvé des particules ayant le même profil spectral en spectrométrie Raman que les particules prélevées dans l’atmosphère de l’entreprise. L’analyse minéralogique du parenchyme pulmonaire a montré la présence d’une concentration élevée de particules compatibles avec des particules de muscovite.Etude n°2 : Les concentrations de manganèse et de nickel dans l’EBC (Mn-EBC, Ni-EBC) dosées par ICP-MS étaient significativement plus élevées chez les soudeurs que chez les témoins alors que cette différence n'était pas significative pour le Mn urinaire (Mn-U). Les concentrations de Mn-EBC et de Ni-EBC ne sont pas corrélées avec leur concentration respective dans l'urine. Les régressions linéaires ont trouvé des coefficients significativement positifs entre les concentrations de Mn-EBC,Ni-EBC, Ni-U et Cr-U et les indices d’exposition cumulée.Etude n°3 : Les concentrations de béryllium et d’aluminium dans l’EBC (Be-EBC, Al-EBC) étaient significativement plus élevées chez les sujets de l’entreprise n°1 que chez les témoins alors que leurs concentrations dans les urines ne l’étaient pas. Les régressions linéaires ont trouvé des coefficients significativement positifs entre les concentrations de Be-EBC et celle d’Al-EBC mais aussi entre les concentrations de Be-EBC et l’indice d’exposition cumulée. Les concentrations d’Al-EBC et Al-U étaient significativement plus élevées chez les sujets de l’entreprise n°2 que chez les témoins. [...]Medical follow-up of employees in occupational medicine requires the use of biological exposure indices that are frequently measured in urine or blood and thus reflect the result of purification by multiple organs. It seems appropriate to evaluate the internal pulmonary dose of occupational toxins to detect their potential early impact. This internal dose could previously only be known after performing invasive techniques such as bronchoalveolar lavage. The exhaled breath condensate (EBC) is a liquid obtained non-invasively after cooling the exhaled air of a subject at rest. It consists of the aerosolization of the liquid that covers the respiratory epithelium of the alveolar compartment and the tracheobronchial or bronchial compartment. Many studies have investigated the markers of inflammation in this matrix but very few have studied the markers of exposure. The current clearance lung models show that the clearance of inhaled particles is variable depending on the region (tracheobronchial , bronchiolar or alveolar region) and a significant proportion of these particles has a slow clearance. Therefore, we hypothesize that EBC could be a matrix that should reflect the pulmonary exposure of inhaled particles during occupational exposure.AimsThe first aim of our study was to assess the feasibility to detect mineral or metallic particles in the EBC of exposed workers. The second objective was to correlate the EBC concentration of these particles with their atmospheric concentrations measured during work.We analyzed EBC from employees engaged in three occupational activities.The first study involved an employee of a milling unit of muscovite suffering from diffuse infiltrative lung disease who underwent a collection of condensate, a lung biopsy, and a dual-source, dual-energy computed tomography. A mineralogical analysis was performed on the EBC, lung tissue, and atmospheric dust collected at the plant.The second study was an exposed-unexposed study on a group of welders using a technique called "metal inert gas" (MIG) welding for assembling steel structures during the production of rail transport (in collaboration with the Association Santé Travail de l’Arrondissement de Valenciennes - ASTAV). Metals of interest in this study were manganese (Mn), nickel (Ni), iron (Fe), and chromium (Cr). Air samples were performed at the plant in order to calculate a cumulative exposure index for the week and thence the welding history for each metal of interest.The third study was a national exposed-unexposed study of workers exposed to soluble beryllium compounds in an aluminum smelter (in collaboration with the Institut National de Recherche et de Sécurité - INRS). The recruitment of exposed subjects was carried out in the electrolysis area production (Area “A”) and in the area of anodes repair (area “B”). Metals of interest in this study were the beryllium (Be), and aluminum (Al). A task-exposure matrix allowed us to calculate a cumulative exposure index of beryllium.Groups (exposed and control) of the second and third study underwent a collection of condensate, a urine collection (U), and pulmonary function tests (PFT) including measurement of exhaled NO. Cumulative exposure indices were correlated with metal concentrations in EBC.The use of new techniques was necessary for the determination of particles in the EBC as Raman spectroscopy for mineral muscovite particles (collaboration with EA 4490 Faculty of Dental Surgery) and inductively coupled plasma mass spectrometry (ICP- MS) for the metal particles in the EBC (in collaboration with the Ultra Trace Analyse Aquitaine - UT2A ) and urine (in collaboration with the Centre Universitaire de Mesures et d’Analyses – CUMA, Lille 2 ). [...

Utilité du condensat d'air exhalé chez des soudeurs pour la quantification de l'imprégnation en particules métalliques et l'évaluation de l'inflammation de leur parenchyme pulmonaire

LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Dispositifs français et étrangers de suivi post-professionnel après exposition à l'amiante

Résumé : L exposition professionnelle à l amiante est responsable de pathologies bénignes et malignes qui se révèlent après de nombreuses années : asbestose, plaques pleurales, atteintes de la plèvre viscérale, mésothéliome pleural malin et cancer broncho-pulmonaire. La question du suivi post-professionnel des travailleurs exposés fait l objet de dispositifs pilotes en France et à l étranger, principalement en Europe, selon des modalités différentes. L analyse de ces dispositifs peut permettre d appréhender les avantages et les inconvénients de la généralisation de ce type de suivi.LILLE2-BU Santé-Recherche (593502101) / SudocSudocFranceF

Intérêt d'un questionnaire professionnel systématique chez des patients atteints de néoplasie pulmonaire ou pleurale

LILLE2-BU Santé-Recherche (593502101) / SudocPARIS-BIUM (751062103) / SudocSudocFranceF

Extracellular vesicles as actors in the air pollution related cardiopulmonary diseases

International audienceMany associations were reported between air pollution and daily mortality rates for cardiopulmonary diseases. Humans are exposed to a mixture of oxidizing gases and particles, both anthropogenic and natural. Exposure to air toxics causes or exacerbates cardiovascular damages and respiratory diseases. Numerous studies have identified the induction of oxidative stress and sustained inflammatory response as among the main known underlying pathophysiological mechanisms of air pollutants. More recently, the relationship between these mechanisms of action and the secretion of extracellular vesicles (EVs) by lung cells has been revealed. EVs have been shown to be important mediators of cellular communication in the body. The purpose of this review is to first recall the main air pollutants. Then, the cardiopulmonary diseases caused by exposure to air pollution and the pathophysiological mechanisms are presented before showing, through an exhaustive review of the literature, the involvement of EVs in the toxicity of air pollutants and the initiation of cardiopulmonary diseases

Short-term exposure to air pollution: Associations with lung function and inflammatory markers in non-smoking, healthy adults

Introduction: Air pollution impacts health by increasing mortality and the incidence of acute events in unhealthy individuals. In contrast, the acute effects of pollution in healthy individuals are less obvious. The present study was designed to evaluate the associations between short-term exposure to air pollution on one hand and lung function, and inflammatory markers on the other in middle-aged, non-smoking adults with no respiratory disease, in two urban areas in northern France.Methods: A sample of 1506 non-smoking adults (aged from 40 to 65) with no respiratory disease was selected from the participants in the 2011-2013 cross-sectional Enquête Littoral Souffle Air Biologie Environnement (ELISABET) survey in two urban areas in the northern France. We evaluated the associations between (i) mean levels of particulate matter with aerodynamic diameter < 10 μm (PM10), nitrogen dioxide (NO2) and ozone (O3) exposure on the day and the day before the study examination for each participant, and (ii) spirometry data and levels of inflammatory markers. Coefficients of multiple linear regression models were expressed (except for the forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio) as the percentage change [95% confidence interval] per 10 μg increment in each pollutant.Results: Levels of PM10, NO2 and O3 exposure were below or only close to the World Health Organization's recommended limits in our two study areas. An increment in NO2 levels was significantly associated with a lower FEV1/FVC ratio (-0.38 [-0.64; -0.12]), a lower forced expiratory flow between 25% and 75% of FVC (FEF25-75%) (-1.70 [-3.15; -0.23]), and a lower forced expiratory flow measured at 75% of FVC (FEF75%) (-3.07 [-4.92; -1.18]). An increment in PM10 levels was associated with lower FEF75% (-1.41 [-2.79; -0.01]) and a non-significant elevation in serum levels of high-sensitivity C-reactive protein (+3.48 [-0.25; 7.36], p = 0.07). Lastly, an increment in O3 levels was associated with a significantly higher blood eosinophil count (+2.41 [0.10; 4.77]) and a non-significant elevation in fractional exhaled nitric oxide (+2.93 [-0.16; 6.13], p = 0.06).Conclusion: A short-term exposure to air pollution was associated with a subclinical decrement in distal lung function and increment in inflammatory markers in healthy inhabitants of two urban areas in France. If these exploratory results are confirmed, this could suggest that even moderate levels of air pollution could have an impact on respiratory health on the general population, and not solely on susceptible individuals

Assessing the applicability of the new Global Lung Function Initiative reference values for the diffusing capacity of the lung for carbon monoxide in a large population set.

BackgroundThe single-breath diffusing capacity of the lung for carbon monoxide (DLCO) interpretation needs the comparison of measured values to reference values. In 2017, the Global Lung Function Initiative published new reference values (GLI-2017) for DLCO, alveolar volume (VA) and transfer coefficient of the lung for carbon monoxide (KCO). We aimed to assess the applicability of GLI-2017 reference values for DLCO on a large population by comparing them to the European Community of Steel and Coal equations of 1993 (ECSC-93) widely used.MethodsIn this retrospective study, spirometric indices, total lung capacity, DLCO, VA and KCO were measured in adults classified in 5 groups (controls, asthma, chronic bronchitis, cystic fibrosis, and interstitial lung diseases (ILD)). Statistical analysis comparing the 2 equations sets were stratified by sex.Results4180 tests were included. GLI-2017 z-scores of the 3 DLCO indices of the controls (n = 150) are nearer to 0 (expected value in a normal population) than ECSC-93 z-scores. All groups combined, in both genders, DLCO GLI-2017 z-scores and %predicted are significantly higher than ECSC z-scores and %predicted. In the ILD group, differences between the 2 equation sets depend on the DLCO impairment severity: GLI-2017 z-scores are higher than ECSC z-scores in patients with no or "mild" decrease in DLCO, but are lower in "moderate" or "severe" decrease.ConclusionGLI-2017 reference values for DLCO are more suitable to our population and influence the diagnostic criteria and severity definition of several lung diseases