Interstitial Lung Disease: Pathophysiology and Genetic Predisposition

Penelope A. Lympany, PhD, and Roland M. du Bois, MD, Imperial College of Science, Technology and Medicine, London, UK

In This Article

Abstract and Introduction


Diffuse (interstitial) lung disease includes a wide variety of relatively uncommon conditions presenting with characteristic clusters of clinical features and marked by an immune response. There are over 200 specific diffuse lung diseases, many of unknown etiology. The combined incidence is 50 per 100,000, or 1 in 2000 people. Because these conditions cause aberrant lung function, morbidity and mortality due to lung injury and fibrosis are not uncommon. Both environmental and genetic factors are believed to contribute to the development of diffuse lung disease. Antigen processing and presentation are important in the development of the immune response seen in the disease, and it is thought that the likely candidate genes predisposing patients to this category of disease are those of the major histocompatibility complex. Genes that affect the immune, inflammatory, and fibrotic processes may also influence who develops the disease. If we can identify the genes that cause diseases characterized by lung injury and fibrosis, we can eventually develop genetic interventional approaches to treatment.


Diffuse (interstitial) lung disease includes a wide variety of conditions, individually relatively uncommon, but collectively found in approximately 50 people per 100,000 population. There are over 200 specific diffuse lung diseases including those characterized by fibrosing and granulomatous histopathology. Only some are of known etiology. It has been suggested that exposure to environmental agents is a major contributory factor in the development of diffuse interstitial lung disease. For example, occupational exposure to beryllium can cause a chronic granulomatous disease that is clinically and histologically indistinguishable from sarcoidosis.[1] A disease resembling cryptogenic fibrosing alveolitis (CFA) or idiopathic pulmonary fibrosis (IPF) results from asbestos exposure,[2] and exposure to cobalt may cause interstitial pneumonia and fibrosis.[3] Other agents that are known to produce diffuse lung disease include some therapeutic drugs, such as amiodarone and radiation. Identified risk factors include exposure to dust,[4] cigarette smoking,[4,5] gender, age, and race.[6] For example, sarcoidosis occurs predominantly in the 30- to 40-year age range and is more aggressive in patients of Afro-Caribbean descent than in Caucasians. In addition, the male to female ratio is 1:1.5. It has been hypothesized that, because not all individuals exposed to a common environment develop the disease and because apparently trivial exposure to common environmental agents can result in disease, genetics may play a role.

Diffuse interstitial lung disease causes major morbidity and mortality due to lung injury and fibrosis. If we can identify individuals who are genetically predisposed to develop diseases characterized by lung injury and fibrosis, we can treat the disease earlier by using genetic interventional therapies.


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