Metal load assessment in patient pulmonary lavages: towards a comprehensive mineralogical analysis including the nano-sized fraction

Our plain-English summary of Metal load assessment in patient pulmonary lavages: towards a comprehensive mineralogical analysis including the nano-sized fraction, by V. Forest, J.M. Vergnon, C. Guibert, et al (Nanotoxicology, 2017).

The study

• Authors: V. Forest, J.M. Vergnon, C. Guibert, D. Bitounis, L. Leclerc, G. Sarry, J. Pourchez
• Journal: Nanotoxicology
• Published: 2017;11(9-10):1211-1224
• Cited by: 7 articles, as counted by NIH iCite
• Read it: PubMed · Publisher

Abstract

Mineralogical analyses of clinical samples have been proved useful to identify causal relationship between exposure to airborne particles and pulmonary diseases. The most striking example is asbestosis where the assessment of asbestos bodies in patient lung samples has allowed defining values specific of pathologies. However, this type of analyses only considers the micro-sized fraction of the particles, neglecting the specific impact of nano-sized particles which have been otherwise shown to be reactive and able to induce biological effects. Similarly, in nanotoxicology, the mineralogical analysis of pulmonary fluids could be used as an indicator of exposure to inhaled nanoparticles and could help investigations on the relationship between exposure to these nanoparticles and lung diseases. We designed this study first to demonstrate the technical feasibility of this approach, then to get a clear picture of the metals present, and in what form, in patient lungs and finally to determine if indeed it is worth investigating separately the micro, sub-micro and nano fractions. Broncho-alveolar lavages were recovered from 100 patients suffering from interstitial lung diseases. A protocol was specifically developed to isolate three fractions containing respectively microparticles, sub-microparticles and nanoparticles with ions. The metal content in each fraction was qualitatively and quantitatively characterized. Results showed significant differences between the three fractions in terms of metal load confirming that the separate analysis of the fractions is relevant. It also means that the assessment of the micro-sized fraction alone, as commonly done in clinical practice, only gives a partial view of the mineralogical analysis.

In plain English

This exploratory study looked at metals in lung washings from 100 adults with diffuse interstitial lung disease who needed a bronchoscopy as part of their care at the University Hospital of Saint-Etienne, France, over 2 years. Asbestos appears only as background in the article. The study did not measure asbestos fibers or asbestos bodies. The authors developed a method to split each bronchial wash and broncho-alveolar lavage sample into three size fractions: microparticles, sub-microparticles, and nanoparticles with dissolved ions. In each fraction they measured twelve elements, including aluminum, chromium, iron, silicon and zinc. Checks showed that the size separation worked. Silicon was found mainly in the micro and sub-micro fractions. Chromium was found mainly in the sub-micro and nano/ion fractions. The authors reported no obvious correlation between the three fractions. They named aluminum, chromium and silicon as the main metals of outside origin. The authors concluded that analysing only the micro fraction, as is commonly done, gives a partial view. They noted that iron and zinc may come from the body itself, and that the results have not yet been compared with patients' clinical data.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Prospective, single-centre, exploratory laboratory analysis of lung lavage samples (registered as NanoPI, NCT02549248)
• Who was studied: 100 adult patients with diffuse interstitial lung disease (for example sarcoidosis, idiopathic pulmonary fibrosis, hypersensitivity pneumonitis) who needed bronchoscopy with lavage for clinical reasons, Chest Diseases and Thoracic Oncology Department, University Hospital of Saint-Etienne, France, over 2 years
• Exposure: Metal load in bronchial wash (BW) and broncho-alveolar lavage (BAL) samples, split into micro, sub-micro and nano/ion fractions. Elements measured: aluminum, beryllium, cobalt, chromium, copper, iron, nickel, silicon, titanium, tungsten, zinc and zirconium. No asbestos fibers were measured, and patients' occupational or environmental exposures were not analysed.
• Main results:
  • Dynamic light scattering showed that the three size fractions were successfully separated. No nanoparticles were found in the micro fraction, and no microparticles were found in the sub-micro or nano/ion fractions.
  • Chromium was mostly found in the sub-micro and nano/ion fractions and almost never in the micro fraction. In bronchial washes, chromium was above the detection limit in 3 patients in the micro fraction, 93 in the sub-micro fraction and 90 in the nano/ion fraction. Silicon was found in the micro and sub-micro fractions (52 and 54 patients in bronchial washes) but in the nano/ion fraction of only 1 patient's bronchial wash and of no patient's BAL.
  • No obvious correlation was found between the micro, sub-micro and nano/ion fractions for any metal, in either type of sample. The authors state that further patient-by-patient statistical analyses confirmed this.
  • BW and BAL mostly showed the same metals in terms of the number of patients with levels above the detection limit. However, when metal concentrations were compared patient by patient, no clear correlations appeared between BW and BAL.
  • Aluminum was the only metal of necessarily outside origin found in all sample types and all fractions. The main metals of outside origin found in the lavages were aluminum, chromium and silicon.
• The authors' conclusion: The authors concluded that a comprehensive mineralogical analysis of clinical samples must consider the micro, sub-micro and nano/ion fractions. In their view, analysing only the micro fraction, as is commonly done, gives only a partial view and could lead to misleading conclusions.
• Limitations the authors state:
  • Some metals, such as iron and zinc, may come from the body itself (endogenous sources), so their content is difficult to interpret.
  • The results have not yet been compared with patients' clinical data, diagnoses, or environmental and occupational exposures. The authors say this is the next step.
  • The cutoff of 10 patients used to classify which metals were mainly found in each fraction or sample type was chosen arbitrarily.

Topics

Medical terms in this study, explained in our Lexicon: Asbestos Bodies, Interstitial Lung Disease.

Related studies

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• Predicting EMP hazard: Lessons from studies with inhaled fibrous and non-fibrous nano- and micro-particles — G. Oberdörster, U. Graham (2018)
• Alveolar fiber load in asbestos workers and in subjects with no occupational asbestos exposure: an electron microscopy study — G. Chiappino, K.H. Friedrichs, et al. (1988)
• Gender differences in murine pulmonary responses elicited by cellulose nanocrystals — A.A. Shvedova, E.R. Kisin, et al. (2016)
• Assessment of environmental asbestos exposure in Turkey by bronchoalveolar lavage — P. Dumortier, L. Coplü, et al. (1998)

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