Use of Lung Weight as Biomarker for Assessment of Lung Toxicity in Rat Inhalation Studies

Abstract

Subacute inhalation study (1 week or 2 weeks) is an important process for screening out inhaled compounds causing lung irritation. To investigate whether the lung weight can be used as an indicator for acute lung injury, we have analyzed retrospectively the lung weight data from 30 studies in rats exposed to dry powder inhalation. The lung weight change was correlated with lung histopathology in the majority of studies (25 of 30), showing as either both changed or both unchanged. The sensitivity and specificity of using the weight change in lungs as biomarker for predicting lung histopathology in these studies were over 80%. The pattern of lung weight change was often similar in the 1- to 2- week studies and the 4-week studies. Our analysis of covariance model showed that a study with 40 rats (5 males + 5 females/group and 4 groups) could detect lung weight change greater than 10% to 20% of control value. These results suggested that lung weight is a useful indicator for identifying acute lung toxic effect by inhaled compounds in these subacute inhalation studies.