© 2009 American Thoracic Society
Understanding Nonspecific Interstitial Pneumonia: The Need for a Diagnostic Gold StandardTo the Editor:The article by Dr. Travis and colleagues based on an American Thoracic Society project (1) highlights the difficulties encountered by a physician treating a patient with the histological lesion of nonspecific interstitial pneumonia (NSIP). Of 305 cases reviewed by the multidisciplinary workshop, each presumably considered an exemplar case of idiopathic NSIP by the submitting clinician, less than 6% fulfilled a consensus classification of definite idiopathic NSIP. Furthermore, of the 67 patients with definite or probable NSIP, a significant number had symptoms or serum markers suggestive of undifferentiated connective tissue disease (CTD) (2). Two of the patients later developed overt CTD. A large proportion of patients initially considered to have idiopathic NSIP were subsequently reclassified as having hypersensitivity pneumonitis (HP), idiopathic pulmonary fibrosis (IPF), or organizing pneumonia (OP). There is considerable overlap between the histological entities that fall within the spectrum of the idiopathic interstitial pneumonias (3). In individual patients with a single disease (e.g., IPF), NSIP may be found coexistent with either usual interstitial pneumonia (UIP), OP, or diffuse alveolar damage. Furthermore, the same disease (e.g., CTD, HP) may give rise to either UIP or NSIP in different patients. The difficulties inherent in trying to identify a discrete clinical, histological, and radiological phenotype for NSIP arise because NSIP represents the common histological lesion of a range of diseases (3). These include CTD, HP, IPF, drug-induced lung disease, familial interstitial lung disease, and fibrosing OP. It seems likely that the remaining cases of apparently idiopathic NSIP simply represent occult manifestations of these other diseases. This is borne out by microarray studies. Selman and colleagues found cases of NSIP with transcription profiles indistinguishable from either HP or IPF (4). Yang and colleagues failed to detect any clear differences in transcription profile between idiopathic NSIP and IPF (5). It remains to be seen whether classification of patients by gene profile predicts prognosis or response to treatment. Attempts to better classify and understand NSIP are hampered by the lack of a clear diagnostic gold standard. Consensus diagnosis is the current best diagnostic standard but carries definite limitations (6). Emerging technologies, including transcription microarrays, metabolomics, and high-throughput proteomics, should produce candidate biomarkers and novel disease insights. Given this, the search for a true diagnostic gold standard for fibrosing lung disease should be a priority for the fibrosis research community, as finding one promises the opportunity to better classify, diagnose, and treat this group of debilitating diseases.
Royal Brompton Hospital FOOTNOTES Conflict of Interest Statement: T.M.M. has no financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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