Interstitial lung disease induced by exogenous agents: factors governing susceptibility.

ABSTRACT: The purpose of this review is to describe the present state of knowledge regarding host susceptibility factors that may determine the occurrence, development and severity of interstitial lung disease (ILD) caused by exogenous agents. First, host susceptibility may pertain to differences in the delivery and/or persistence of the noxious agent in the lung. The deposition and clearance of inhaled particles or fibres may vary depending on innate anatomical or physiological characteristics, and on acquired changes, such as nasal disease or smoking-induced alterations. Genetically- or environmentally-induced interindividual differences in the expression of pulmonary biotransformation enzymes may form the basis for, or contribute to the risk of, drug-induced interstitial lung disease. Secondly, there are genetic and acquired variations in various enzymatic and nonenzymatic defence systems that protect cells and tissues against oxidative stress, which is often involved in the pathogenesis of interstitial lung disease caused by particles, fibres, metals, organic agents and drugs. Thirdly, the occurrence of immunological sensitization is dependent on both geneti