Interstitial lung disease (ILD) is a heterogenous group of inflammatory and scarring conditions of the lung. Idiopathic pulmonary fibrosis (IPF) is a distinct form of ILD and represents a specific clinical entity defined by a constellation of clinical, radiographic, and pathophysiologic features. Other forms of cryptogenic ILD that do not fit into the diagnostic criteria for IPF are referred to as “unclassifiable” ILD, although some may, in fact, show a clinical trajectory that matches IPF.
IPF is the most common ILD with heterogenous and complex pathophysiology without a clear causative etiology (except in the case of familial disease). A diagnosis of IPF is made most confidently when a high-resolution computed tomography (HRCT) or histopathologic pattern of usual interstitial pneumonia (UIP) is observed in the absence of an identifiable trigger. Such etiologies include connective tissue disease, environmental exposures leading to hypersensitivity reactions, and drug-induced fibrosis. In other words, UIP is not synonymous with IPF; other etiologies of UIP must be excluded for the diagnosis of IPF.
Considered a disease of aging, IPF usually presents in the seventh decade of life. The symptoms and physical examination findings of IPF are nonspecific and can thus lead to substantial delays in diagnosis, especially as there are far more common pulmonary and cardiac abnormalities that present similarly. As will be discussed further, the scope of current therapies for IPF render them of greatest benefit earlier in the course of disease, so timely diagnosis is of importance from a therapeutic standpoint. Diagnostic delays also contribute to patient distress, and as depression and anxiety are common comorbidities in IPF, earlier establishment of a definitive diagnosis can contribute to a patient’s peace of mind and ability to cope with chronic illness.
The clinical course of IPF is one of certain, yet unpredictable, progression. Long-term observational studies of patients with IPF reveal that while decline in lung function is inevitable, there is a paucity of reliable predictors to identify which patients are at risk for progression. Similarly, there are no reliable means to identify which patients are at risk for acute exacerbations of disease or when such exacerbations are likely to occur, which provides a challenge in counseling patients on prognosis and determining the ideal timing for what remains the only definitive “cure” for IPF: lung transplantation.
Biomedical research in recent years has yielded new insights into the genetic predisposition to IPF, the pathogenic pathways that are potentially targetable with experimental therapies, and molecular markers to discriminate IPF from non-IPF ILD. However, there remains an unmet need to develop medications that not only slow disease progression, but halt progression of disease entirely.
A brief review of the evolution in our understanding of IPF illustrates the contributions made by earlier investigators but also reveals the reasons for the confusion that many clinicians have regarding IPF. One of the challenges ...