© 2007 American Thoracic Society doi: 10.1164/rccm.200612-1873ED
Identifying Patients with Idiopathic Pulmonary FibrosisQuality or Quantity?University of Modena & Reggio Emilia Center for Rare Lung Diseases, Modena, Italy
University of Alabama at Birmingham School of Medicine, Birmingham, Alabama Although idiopathic pulmonary fibrosis (IPF) is likely to be more common than previously thought, with an estimated prevalence ranging from 14 to 43 per 100,000 persons in the United States (1), it still is a rare disease. However, rare does not mean unimportant. In the last decade, both in the United States and in Europe, there were increased efforts among pulmonary specialists to identify patients with IPF (2). This new energy has been mainly fuelled by the recognition of the inefficacy of the "traditional" antiinflammatory therapeutic approach (3, 4) and by innovative drugs made available in randomized controlled trials (5–7). There were at least two important consequences of this increased interest in IPF: first, our basic knowledge about the pathogenesis of this clinical entity greatly advanced, providing insights into novel therapeutic targets and prognostic markers (8); second, there was the realization that medical treatments seem to preserve lung function better in patients with mild to moderate disease (as measured by simple functional parameters such as forced vital capacity) (9), whereas the more advanced stages of IPF seem to be less responsive to therapy and should probably be the main reservoir of candidates for lung transplantation (10). Although a lower rate of decrease in lung function does not necessarily translate into longer survival, changes in forced vital capacity have been shown to be predictive of survival in at least one large trial (9). As a consequence of these advances in the understanding of IPF, early diagnosis is now seen as an important constituent of good clinical practice for these patients. A key question is therefore how to identify early IPF cases, ideally when only few symptoms are present. These patients may feel perfectly healthy for a long period when pulmonary fibrosis is limited to the peripheral lung. During this time, it is highly unlikely that they will be in contact with a specialized IPF center. Early diagnosis is often difficult in respiratory medicine, and there are some unique characteristics of IPF that make diagnosis even more difficult for this disorder. IPF isn't characterized by a single genetic defect, such as cystic fibrosis, and therefore an approach based on genetic screening is unfeasible. Chest imaging is probably the most informative and least invasive diagnostic aid in IPF (11), but the low incidence of the disease makes unrealistic the concept of computed tomography scan–based screening for case finding. On the other hand, history, symptoms, and physical examination should, at least in theory, be reasonably sensitive (although poorly specific) to identify early IPF cases. In fact, at least all four "minor" diagnostic criteria (age > 50, a gradual onset of dyspnea, a duration of illness of at least 3 mo, and the presence of bibasilar "Velcro type" inspiratory crackles) (12) may be identified or excluded by nonspecialist, community-based physicians: their presence make the diagnosis of IPF more likely, and the exclusion of known causes of interstitial lung disorders (e.g., drugs) may further sharpen the diagnostic suspicion. This issue of the Journal (pp. 1054–1060) presents a report showing that the diagnostic accuracy for idiopathic interstitial pneumonia is higher among academic as compared with community physicians (13). In particular, the authors clearly demonstrate how the main diagnostic challenge for nonexpert community doctors is the differential diagnosis between IPF and other forms of diffuse parenchymal lung disorders, such as hypersensitivity pneumonia or nonspecific interstitial pneumonia. These findings are probably not surprising, but they highlight an important new step in the complex process leading to diagnosis of idiopathic interstitial lung disease, and particularly IPF. If a dynamic, academic-based, multidisciplinary approach is the basis for a confident diagnosis of IPF (and therefore might be proposed as essential in the design of randomized controlled trials), a strong relationship between academic experts and community physicians is likely to play a key role in a strategy aimed at the identification of the maximum number of patients with early disease. Although the study by Flaherty and coworkers indicates that community-based diagnosis will likely have low specificity, it should nonetheless allow expert academic centers to become involved in sophisticated iterative diagnostic processes in a prescreened population of a reasonable size. To design an effective strategy for the identification of IPF cases (and, in general, patients with rare lung disorders), it is worth knowing that academic and community-based physicians have a different level of expertise in the diagnosis of rare lung diseases; and for a disease as rare as IPF, it's also not bad to know that the community-based physicians are more, rather than less, likely to assign a diagnosis of IPF. In principle, this should increase the sensitivity of a diagnostic approach that begins with community identification of likely cases of IPF. So, although we know that a specialist multidisciplinary approach is definitely needed for an accurate diagnosis and proper treatment (14), if we also want to identify patients with IPF in the early stages of the disease (i.e., when medical treatments seem to be more effective), we need to build a two-way network connecting academic reference centers and community-based physicians. With this approach, academic physicians should be prepared to accept some reduction in the specificity of the diagnosis made in the community, but with a likely increased sensitivity of the whole approach. As an example, among the 750,000 inhabitants of San Francisco, an effective network connecting community and academic physicians could identify something like 100 new IPF cases each year; obviously, this will be feasible only at the cost of examining a much higher number of patients who eventually turn out not to be affected by IPF. Physicians need to be vigilant about a condition that is rare but important, like IPF. To achieve the ideal goal of identifying as many cases as possible at early phases of disease, quantity and quality need to be well balanced in the diagnostic approach to this important lung disease. FOOTNOTES Conflict of Interest Statement: L.R. has participated in advisory board meetings for Intermune, Inc. ($2,000 in 2003), and Boehringer-Ingelheim ($2,000 in 2007). E.A. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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