tobacco smoke exposure, environmental exposures (eg, metal and wood dusts), occupational exposures (in farming and agriculture), and chronic viral infections. Beyond environmental exposures, recent studies clearly implicate both common and rare variant genetic alterations in the development of IPE. The common variants account for approximately one-third of the risk for developing IPF and include the MUCSB and TOLLIP genes. Associations with other disorders, including emphysema, gastroesophageal reflux disease, and obesity, remain undefined. The clinical, imaging, and histopathologic features of IPF can be indistinguishable from diffuse parenchymal lung diseases of known etiology. Therefore, it is critical that a thorough history and physical examination are performed on each patient, since the treatment and prognosis differ between IPF and these other interstitial disorders. The natural history of IPF is classically one of unremittingiprogressionyand the median survival is approximately 3 years from the time of diagnosis. The clinical course is nonetheless very heterogeneous and may reflect separate phenotypes of the disease rather than variable progression. Risk factors for accelerated progression include gender, older age at diagnosis (®20;years), cumulativedobaccorsmokerexposure, and severityrofidiseaseibyrsymproms (dyspnea score) or standardizedrassessment (extent of radiographic disease, severity of pulmonary restriction on pulmonary function tests, presence of pulmonaryshyperension). Combining these predictive variables into scoring algorithms such as the GAP index (Gender, Age, Physiology [including FVC and DLCO}) can aid the clinician in estimating the 1-year mortality rate for a patient with IPF. Further attempts to improve such predictions have examined the utility of IPF biomarkers. One example is the serum concentration of matrix metalloproteinase 7, with increasing levels portending a worse outcome. Other less well-established prognostic biomarkers include serum levels of monomeric periostin, YKL-40, and CCL18. A subset (515%) of patients with IPF will also experience an acute exacerbation of their disease characterized by an abrupt deterioration in symptoms, lung function, and radiographic abnormalities. Pathologic specimens from such patients reveal diffuse alveolar damage in addition to findings of UIP. These episodes are associated with a poor prognosis, with an associated median survival of 3-4 months. Pathophysiology The pathophysiology of IPF and its histopathologic correlate UIP is an active area of research with the promise that a better understanding of the basic