Relationship between human biomonitoring of inhaled biopersistent nanoparticles in broncho-alveolar lavages, lung diseases and occupational exposure

Because of the tremendous development of nanotechnologies and the subsequent potential exposure of humans to nanomaterials, nanotoxicology is a rapidly evolving research field. In a context of health risk assessment the biological monitoring (or biomonitoring) of nanoparticles in human biological samples could be a particularly useful approach to get new insights into the role of inhaled biopersistent nanoparticles in the etiology/development of some respiratory diseases. Biomonitoring has been widely used in pulmonology, especially in the case of pneumoconiosis. It can bring critical information on the relationship between exposure to a harmful substance and biological/pathological effects.

Our objective was to investigate the relationship between the biomonitoring of nanoparticles in patients’ broncho-alveolar lavages (BAL), interstitial lung diseases and occupational exposure to these particles released unintentionally.

We conducted a clinical trial on a cohort of 100 patients suffering from lung diseases (NanoPI clinical trial, ClinicalTrials.gov Identifier: NCT02549248). We separated micron-sized particles (>1 µm) from submicron (100 nm-1 µm) and nano-sized particles (<100 nm) contained in BAL from patients who suffered from interstitial lung diseases (ILD). We then determined the metal load in each of these size-fractions. We evidenced a concentration of submicron silica particles higher in patients suffering from sarcoidosis than in patients suffering from other ILD, suggesting a potential role of these inhaled particles in the etiology and/or development of sarcoidosis. Similarly, we observed a concentration of titanium nanoparticles higher in patients suffering from idiopathic fibrosis than in patients suffering from other ILD allowing suspecting a relationship between titanium nanoparticles and idiopathic pulmonary fibrosis. To complement mineralogical analyses of BAL and offer a comprehensive vision of the events from exposure to airborne nanoparticles to the biological response induced, we investigated associations between respiratory diseases and occupational exposures. To that purpose, we estimated the exposure to inhaled unintentionally released nanoparticles of the patients for each job held in their working life. 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 were consistent with the mineralogical analyses. 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.