Early Exposure to Nanoparticles: A Risk Factor to Develop Chronic Obstructive Pulmonary Disease?

International audienceRATIONALE OF THE STUDY Chronic obstructive pulmonary disease (COPD) is a disease ofincreasing incidence characterized by progressive airflow limitation and inflammation. COPD riskis strongly related to tobacco smoking, but environmental and genetic factors are also involved inits pathogenesis. There is increasing evidence that adverse exposures (cigarette smoke,pollution, nanoparticles (NP)) occurring during foetal and early infant life can impair thedevelopment of the lungs and may finally increase risks of COPD at adulthood. Using a mousemodel, we have recently shown that respiratory exposure of pregnant mice to metal NP leads toalterations in lung morphology in pups, with a persistent alveolar airspace enlargement. In orderto determine if such modifications represent a susceptibility factor to develop a COPD-likephenotype in later life, we exposed the progeny to cigarette smoke and analysed the morphologyof the lungs. METHODS Three metal nanoparticles were used in the study: Cerium oxide, Silverand Gold (diameter 15 to 30 nm). We performed weekly non-surgical intratracheal instillation of100µg nanoparticles on C57BL/6 pregnant mice during the entire course of gestation. At the ageof two months, the progeny was exposed to cigarette smoke for 7 and 12 weeks. The lungmorphology was analysed at different stages of alveolar development (E17.5, P23 and P60) andafter cigarette smoke exposure. RESULTS The number of pups per pregnant mother, as well astheir weight was similar between the 4 experimental groups. Respiratory exposure of pregnantmice to metal nanoparticles induce persistent lung morphological abnormalities in the progeny,demonstrated by enlargement of the alveolar airspace already at P23 and which remains at P60.The mean linear intercept (MLI), of 151.3 +/- 7.2 µm in controls lungs, is increased to 171.8 +/- 8.2µm with Silver, 166.0 +/-3.9 with Cerium and 166.4 +/-3.9 with Gold NP (p<0.005). Cigarettesmoke exposure induces an alveolar enlargement in control lungs (MLI = 172.8 +/- 9.3 µm),which is increased in all the NP groups, with MLI of 191.7 +/- 6.5 with Silver, 190.9 +/- 5.8 withCerium and 191.3 +/- 7.6 with Gold NP (p