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Interstitial lung disease induced by exogenous agents: factors governing susceptibility

¹ Laboratory of Pneumology (Lung Toxicology), Katholieke Universiteit Leuven, Leuven, Belgium. ² Dept of Pharmacology, University of Maastricht, Maastricht, the Netherlands. ³ Dept of Internal Medicine I, Division for Pulmonary Diseases, University of Munich, Munich, Germany. ⁴ Dept of Fibre and Particle Toxicology, Medical Institute for Environmental Hygiene, Düsseldorf, Germany. ⁵ Dept of Respiratory Medicine, Royal Victoria Infirmary, Newcastle upon Tyne, UK. ⁶ Division of Pneumology and Critical Care, Centre Hospitalier Universitaire de Dijon, Dijon, France. ⁷ Division of Pneumology, Hôpital Erasme, Université Libre de Bruxelles, Brussels, Belgium. ⁸ Dept of Pulmonology, Academic Medical Centre, Amsterdam, the Netherlands. ⁹ Dept of Internal Medicine, Division of Pulmonary Medicine, University of Oulu, Oulu, Finland. ¹⁰ Unit of Industrial Toxicology and Occupational Medicine, Louvain Catholic University, Belgium. ¹¹ Dept of Pharmacology and Toxicology, University of Oulu, Oulu, Finland. ¹² Division of Respiratory Diseases, Università di Roma "Tor Vergata", Ospedale L. Spallanzani-IRCCS, Rome, Italy

CORRESPONDENCE: B. Nemery, Laboratorium voor Pneumologie (Longtoxicologie), K.U. Leuven, Herestraat 49, B-3000, Leuven, Belgium. Fax: 32 16347124

Keywords: drug-induced lung disease, environment, genetics, hypersensitivity pneumonitis, oxidative stress, pneumoconioses

Received: March 8, 2001
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 genetic and environmental factors. This has been demonstrated in chronic beryllium lung disease and in hypersensitivity pneumonitis.

Fourthly, the propensity of individuals to develop particular types of inflammation, such as granulomas, is probably under genetic control. The regulation and resolution of inflammation and fibrogenesis caused by dust particles are also partly determined by genetic factors, involving cytokine networks and growth factors.

In conclusion, although the issue of genetics pervades the entire discussion of host susceptibility, genes are not the only determinants of health and disease. Environmental factors may be equally important in shaping host susceptibility. Therefore, research must be focused on both the genetic bases and the environmental determinants of interstitial lung disease, in order to provide mechanism-based prevention strategies, early detection of, and improved therapy for these conditions.