Relationship between Occupational Exposure to Airborne Nanoparticles, Nanoparticle Lung Burden and Lung Diseases

Valérie Forest, Jérémie Pourchez, Carole Pélissier, Sabyne Audignon Durand, Jean-Michel Vergnon, Luc Fontana, Valérie Forest, Jérémie Pourchez, Carole Pélissier, Sabyne Audignon Durand, Jean-Michel Vergnon, Luc Fontana

Abstract

The biomonitoring of nanoparticles in patients' broncho-alveolar lavages (BAL) could allow getting insights into the role of inhaled biopersistent nanoparticles in the etiology/development of some respiratory diseases. Our objective was to investigate the relationship between the biomonitoring of nanoparticles in BAL, interstitial lung diseases and occupational exposure to these particles released unintentionally. We analyzed data from a cohort of 100 patients suffering from lung diseases (NanoPI clinical trial, ClinicalTrials.gov Identifier: NCT02549248) and observed that most of the patients showed a high probability of exposure to airborne unintentionally released nanoparticles (>50%), suggesting a potential role of inhaled nanoparticles in lung physiopathology. Depending on the respiratory disease, the amount of patients likely exposed to unintentionally released nanoparticles was variable (e.g., from 88% for idiopathic pulmonary fibrosis to 54% for sarcoidosis). These findings are consistent with the previously performed mineralogical analyses of BAL samples that suggested (i) a role of titanium nanoparticles in idiopathic pulmonary fibrosis and (ii) a contribution of silica submicron particles to sarcoidosis. Further investigations are necessary to draw firm conclusions but these first results strengthen the array of presumptions on the contribution of some inhaled particles (from nano to submicron size) to some idiopathic lung diseases.

Keywords: biomonitoring; lung diseases; mineralogical analysis of broncho-alveolar lavages; nanoparticles; occupational exposure.

Conflict of interest statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Figures

Figure 1
Figure 1
The mineralogical analysis of metal load extracted from pulmonary fluids could be used as an indicator of exposure to nanoparticles and could contribute to the assessment of potential causal links between the presence of inhaled biopersistent nanoparticles in the lungs and respiratory diseases.
Figure 2
Figure 2
(A) Si particles concentration in bronchial wash (BW) and broncho-alveolar lavages (BAL) of patients suffering either from sarcoidosis or another type of ILD. (B) Ti particles concentration in BW and BAL of patients suffering either from idiopathic pulmonary fibrosis or another type of ILD. Comparison between the fractions containing either the submicron particles and the nanoparticles and ions. The median (in bold), minimal and maximal values, as well as the first and third quartiles are indicated. The number of patients (n) from each group is reported (please note that some data are missing because for technical reasons some BW and BAL samples could not be analyzed).
Figure 3
Figure 3
Distribution of the patients depending on their probability of exposure to unintentionally released nanoparticles.
Figure 4
Figure 4
(A) Distribution of patients depending on the probability of exposure to unintentionally released nanoparticles and depending on the origin of their disease. (B) Distribution of patients depending on the probability of exposure to unintentionally released nanoparticles and depending on the nature of their disease.

References

    1. Stone V., Miller M.R., Clift M.J.D., Elder A., Mills N.L., Møller P., Schins R.P.F., Vogel U., Kreyling W.G., Alstrup Jensen K., et al. Nanomaterials Versus Ambient Ultrafine Particles: An Opportunity to Exchange Toxicology Knowledge. Environ. Health Perspect. 2017;125:106002. doi: 10.1289/EHP424.
    1. Manno M., Viau C., Cocker J., Colosio C., Lowry L., Mutti A., Nordberg M., Wang S. Biomonitoring for occupational health risk assessment (BOHRA) Toxicol. Lett. 2010;192:3–16. doi: 10.1016/j.toxlet.2009.05.001.
    1. Silins I., Högberg J. Combined Toxic Exposures and Human Health: Biomarkers of Exposure and Effect. Int. J. Environ. Res. Public Health. 2011;8:629–647. doi: 10.3390/ijerph8030629.
    1. De Vuyst P., Karjalainen A., Dumortier P., Pairon J.-C., Monsó E., Brochard P., Teschler H., Tossavainen A., Gibbs A. Guidelines for mineral fibre analyses in biological samples: Report of the ERS Working Group. European Respiratory Society. Eur. Respir. J. 1998;11:1416–1426. doi: 10.1183/09031936.98.11061416.
    1. Case B.W., Abraham J.L., Meeker G., Pooley F.D., Pinkerton K.E. Applying Definitions of “Asbestos” to Environmental and “Low-Dose” Exposure Levels and Health Effects, Particularly Malignant Mesothelioma. J. Toxicol. Environ. Health B Crit. Rev. 2011;14:3–39. doi: 10.1080/10937404.2011.556045.
    1. Mossman B.T., Lippmann M., Hesterberg T.W., Kelsey K.T., Barchowsky A., Bonner J.C. Pulmonary Endpoints (Lung Carcinomas and Asbestosis) Following Inhalation Exposure to Asbestos. J. Toxicol. Environ. Health B Crit. Rev. 2011;14:76–121. doi: 10.1080/10937404.2011.556047.
    1. Bargagli E., Lavorini F., Pistolesi M., Rosi E., Prasse A., Rota E., Voltolini L. Trace metals in fluids lining the respiratory system of patients with idiopathic pulmonary fibrosis and diffuse lung diseases. J. Trace Elem. Med. Biol. 2017;42:39–44. doi: 10.1016/j.jtemb.2017.04.001.
    1. Bergamaschi E., Poland C., Guseva Canu I., Prina-Mello A. The role of biological monitoring in nano-safety. Nano Today. 2015;10:274–277. doi: 10.1016/j.nantod.2015.02.001.
    1. Bitounis D., Pourchez J., Forest V., Boudard D., Cottier M., Klein J.-P. Detection and analysis of nanoparticles in patients: A critical review of the status quo of clinical nanotoxicology. Biomaterials. 2016;76:302–312. doi: 10.1016/j.biomaterials.2015.10.061.
    1. Rapport de l’Anses—Anses Particules de l’air Ambiant Extérieur—Impact Sur La Pollution Atmosphérique Des Technologies et de La Composition Du Parc de Véhicules Automobiles Circulant En France. 2019. [(accessed on 9 July 2021)]. Available online: .
    1. Groopman J.D., Kensler T.W. The light at the end of the tunnel for chemical-specific biomarkers: Daylight or headlight? Carcinogenesis. 1999;20:1–11. doi: 10.1093/carcin/20.1.1.
    1. Angerer J., Ewers U., Wilhelm M. Human biomonitoring: State of the art. Int. J. Hyg. Environ. Health. 2007;210:201–228. doi: 10.1016/j.ijheh.2007.01.024.
    1. Rinaldo M., Andujar P., Lacourt A., Martinon L., Canal Raffin M., Dumortier P., Pairon J.-C., Brochard P. Perspectives in Biological Monitoring of Inhaled Nanosized Particles. Ann. Occup. Hyg. 2015;59:669–680. doi: 10.1093/annhyg/mev015.
    1. Forest V., Vergnon J.-M., Pourchez J. Biological Monitoring of Inhaled Nanoparticles in Patients: An Appealing Approach To Study Causal Link between Human Respiratory Pathology and Exposure to Nanoparticles. Chem. Res. Toxicol. 2017;30:1655–1660. doi: 10.1021/acs.chemrestox.7b00192.
    1. Bitounis D., Klein J.-P., Mery L., El-Merhie A., Forest V., Boudard D., Pourchez J., Cottier M. Ex vivo detection and quantification of gold nanoparticles in human seminal and follicular fluids. Analyst. 2018;143:475–486. doi: 10.1039/C7AN01641G.
    1. Rinaldi L., Barabino G., Klein J.-P., Bitounis D., Pourchez J., Forest V., Boudard D., Leclerc L., Sarry G., Roblin X., et al. Metals distribution in colorectal biopsies: New insight on the elemental fingerprint of tumour tissue. Dig. Liver Dis. 2015;47:602–607. doi: 10.1016/j.dld.2015.03.016.
    1. Raia-Barjat T., Prieux C., Leclerc L., Sarry G., Grimal L., Chauleur C., Pourchez J., Forest V. Elemental fingerprint of human amniotic fluids and relationship with potential sources of maternal exposure. J. Trace Elem. Med. Biol. 2020;60:126477. doi: 10.1016/j.jtemb.2020.126477.
    1. Forest V., Vergnon J.-M., Guibert C., Bitounis D., Leclerc L., Sarry G., Pourchez J. Metal load assessment in patient pulmonary lavages: Towards a comprehensive mineralogical analysis including the nano-sized fraction. Nanotoxicology. 2017;11:1211–1224. doi: 10.1080/17435390.2017.1406170.
    1. Forest V., Pourchez J., Guibert C., Bitounis D., Leclerc L., Sarry G., Vergnon J.-M. Nano to micron-sized particle detection in patients’ lungs and its pathological significance. Environ. Sci. Nano. 2019;6:1343–1350. doi: 10.1039/C8EN01301B.
    1. Bitounis D., Barnier V., Guibert C., Pourchez J., Forest V., Boudard D., Hochepied J.-F., Chelle P., Vergnon J.-M., Cottier M. A method for the quantitative extraction of gold nanoparticles from human bronchoalveolar lavage fluids through a glycerol gradient. Nanoscale. 2018;10:2955–2969. doi: 10.1039/C7NR04484D.
    1. Mikolasch T.A., Garthwaite H.S., Porter J.C. Update in diagnosis and management of interstitial lung disease. Clin. Med. (Lond.) 2017;17:146–153. doi: 10.7861/clinmedicine.17-2-146.
    1. National Institute for Statistics and Economic Studies (INSEE) Nomenclature d’Activités Françaises. 2000. [(accessed on 7 July 2021)]. Available online: .
    1. International Labour Organization . International Standard Classification of Occupations. ILO; Geneva, Switzerland: 1968. [(accessed on 7 July 2021)]. Available online: .
    1. Song Y., Li X., Du X. Exposure to nanoparticles is related to pleural effusion, pulmonary fibrosis and granuloma. Eur. Respir. J. 2009;34:559–567. doi: 10.1183/09031936.00178308.
    1. Song Y., Li X., Wang L., Rojanasakul Y., Castranova V., Li H., Ma J. Nanomaterials in Humans: Identification, Characteristics, and Potential Damage. Toxicol. Pathol. 2011;39:841–849. doi: 10.1177/0192623311413787.
    1. Andujar P., Simon-Deckers A., Galateau-Sallée F.G., Fayard B., Beaune G., Clin B., Billon-Galland M.-A., Durupthy O., Pairon J.-C., Doucet J., et al. Role of metal oxide nanoparticles in histopathological changes observed in the lung of welders. Part. Fibre Toxicol. 2014;11:23. doi: 10.1186/1743-8977-11-23.
    1. Leprince M., Sancey L., Coll J.-L., Motto-Ros V., Busser B. Elemental imaging using laser-induced breakdown spectroscopy: Latest medical applications. Med. Sci. MS. 2019;35:682–688. doi: 10.1051/medsci/2019132.
    1. Viitanen A.-K., Uuksulainen S., Koivisto A.J., Hämeri K., Kauppinen T. Workplace Measurements of Ultrafine Particles-A Literature Review. Ann. Work. Expo. Health. 2017;61:749–758. doi: 10.1093/annweh/wxx049.
    1. Audignon-Durand S., Gramond C., Ducamp S., Manangama G., Garrigou A., Delva F., Brochard P., Lacourt A. Development of a Job-Exposure Matrix for Ultrafine Particle Exposure: The MatPUF JEM. Ann. Work Expo. Health. 2021;65:516–527. doi: 10.1093/annweh/wxaa126.
    1. Manangama G., Migault L., Audignon-Durand S., Gramond C., Zaros C., Bouvier G., Brochard P., Sentilhes L., Lacourt A., Delva F. Maternal occupational exposures to nanoscale particles and small for gestational age outcome in the French Longitudinal Study of Children. Environ. Int. 2019;122:322–329. doi: 10.1016/j.envint.2018.11.027.
    1. Manangama G., Gramond C., Audignon-Durand S., Baldi I., Fabro-Peray P., Gilg Soit Ilg A., Guénel P., Lebailly P., Luce D., Stücker I., et al. Occupational exposure to unintentionally emitted nanoscale particles and risk of cancer: From lung to central nervous system—Results from three French case-control studies. Environ. Res. 2020;191:110024. doi: 10.1016/j.envres.2020.110024.
    1. Abramson M.J., Murambadoro T., Alif S.M., Benke G.P., Dharmage S.C., Glaspole I., Hopkins P., Hoy R.F., Klebe S., Moodley Y., et al. Occupational and environmental risk factors for idiopathic pulmonary fibrosis in Australia: Case-control study. Thorax. 2020;75:864–869. doi: 10.1136/thoraxjnl-2019-214478.
    1. Andersson M., Blanc P.D., Torén K., Järvholm B. Smoking, occupational exposures, and idiopathic pulmonary fibrosis among Swedish construction workers. Am. J. Ind. Med. 2021;64:251–257. doi: 10.1002/ajim.23231.
    1. Jonsson E., Järvholm B., Andersson M. Silica dust and sarcoidosis in Swedish construction workers. Occup. Med. 2019;69:482–486. doi: 10.1093/occmed/kqz118.
    1. Graff P., Larsson J., Bryngelsson I.-L., Wiebert P., Vihlborg P. Sarcoidosis and silica dust exposure among men in Sweden: A case–control study. BMJ Open. 2020;10:e038926. doi: 10.1136/bmjopen-2020-038926.
    1. Rafnsson V., Ingimarsson O., Hjalmarsson I., Gunnarsdottir H. Association between exposure to crystalline silica and risk of sarcoidosis. Occup. Environ. Med. 1998;55:657–660. doi: 10.1136/oem.55.10.657.
    1. Taskar V., Coultas D. Exposures and Idiopathic Lung Disease. Semin. Respir. Crit. Care Med. 2008;29:670–679. doi: 10.1055/s-0028-1101277.
    1. Vincent M., Lievre M. Sarcoidosis and pulmonary dust exposure, a plausible pathogenic link. Rev. Mal. Respir. 2002;19:103–104.
    1. Nanoparticle Task Force ACOEM Nanotechnology and Health. J. Occup. Environ. Med. 2011;53:687–689. doi: 10.1097/JOM.0b013e31820568ef.
    1. Yokel R.A., MacPhail R.C. Engineered nanomaterials: Exposures, hazards, and risk prevention. J. Occup. Med. Toxicol. 2011;6:7. doi: 10.1186/1745-6673-6-7.

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