Exposure-Related Diffuse Lung Diseases

In this issue we bring together a group of articles addressing the complex relationship between environmental exposures and diffuse lung diseases (DLDs). These disorders are recognized as a growing global problem; however, we have only a limited understanding of their clinical spectrum and underlying pathophysiology. Although studies of chronic obstructive pulmonary disease (COPD) and asthma have estimated that 15% or more of adult-onset disease is attributable to occupational exposures, there are no good estimates of the attributable risk due to exposures in the DLDs, making it difficult to appreciate the size and scope of the problem. Part of the difficulty is that clinical recognition, phenotyping, and confirmation of the relationship to a particular exposure are challenging for even the best clinician. Add to this complexity the large and expanding list of pertinent exposures one must consider, for example, flavor manufacturing, the use of biomass for fuel in the home, and World Trade Center dust are all newly identified sources of concern. Just as important, although in many developed countries specific exposure reduction has occurred for some of the best-recognized potentially harmful exposures (e.g., asbestos), in developing countries there may be a rising exposure burden.

Drs. Goldyn, Condos, and Rom address the problems associated with determining the overall burden of disease, including the lack of good estimates of prevalence and the downstream impact on health care costs, morbidity and mortality, and economic costs. Drs. Brass, Wise, and Schwartz outline the pathogenic and genetic studies in idiopathic pulmonary fibrosis (IPF). They note that genomic, animal, and human studies all support the importance of an epithelial response in the fibroproliferative process in IPF and other fibrosing DLDs, even if the inciting exposure or agent is unknown. In their article, Drs. Spagnolo, Richeldi, and du Bois review the pathogenic and genetic evidence linking sarcoidosis with potential etiologic agents. The evidence from genetic studies demonstrates that the strongest association to date is with human leukocyte antigen (HLA) complex genes. Drs. Rose, Lynch, and Cool address our limited clinical insight by providing a clinical approach to the recognition and confirmation of exposure-related lung disease. Drs. Lacasse, Assayag, and Cormier highlight the common problems in hypersensitivity pneumonitis (HP), including the difficulties with diagnosis and classification. They remind us that HP is not limited to granulomatous lung disease; a spectrum of disease may result from bioaerosols and chemicals, including both parenchymal fibrosis and airways disease. Finally, Drs. Vassallo and Ryu review our most common exposure, tobacco smoke, and its ability to lead to or promote the development of desquamative interstitial pneumonitis, respiratory bronchiolitis-interstitial lung disease, and pulmonary Langerhans cell histiocytosis, among others. Several of the well-recognized exposure-related DLDs are reviewed in greater detail. Drs. Cohen, Patel, and Green address the DLD resulting from coal and silica, including coal workers' pneumoconiosis, silicosis. They review the varied disease manifestations, underlining the importance of considering coal and silica exposures not only in parenchymal disease but also in obstructive airways disease. Metal exposure can result in a variety of clinical manifestations, and Drs. Fontenot and Amicosante review our understanding of the clinical and pathogenetic features of cobalt and beryllium exposure, focusing on hard metal lung disease and chronic beryllium disease (CBD). Because the immunopathogenesis of CBD is well understood, including the importance of a genetic susceptibility factor, HLA-DPB1, it may serve as a model for understanding other exposure-related DLDs.

Essentially all lung disease is idiopathic if the important clinical and pathophysiological connections are not made, and Drs. Taskar and Coultas review the epidemiological literature conducted to date that supports an etiologic role for specific exposures in the development of otherwise idiopathic DLDs. Finally, Drs. Nuernberg and Christiani discuss the new trends in identifying populations at particularly high risk of disease after exposure. These include the study of gene–environment interactions, including genome-wide association and candidate gene studies, as well as biomarker investigation. However, control of exposure remains the time-tested and preferred method of disease prevention.

Each of these articles should remind us of the critical link between our environment and the development of diffuse lung disease. They give us an appreciation of the size and scope of the problem, increase our awareness of the clinical clues that should prompt us to consider an environmental contribution in individual patients, and encourage us to find ways to reduce relevant exposures in ways to limit morbidity and mortality and ultimately prevent disease. This appreciation of the importance of host–environmental exposure interaction is a first step in reducing the global burden of these important diseases.