© 2008 American Thoracic Society
A Unique Spirometric Phenotype in COPDTo the Editor:We enjoyed the editorial by Drs. Fabbri, Boschetto, and Mapp (1) commenting on the Global Initiative for Chronic Obstructive Lung Disease (GOLD) guidelines (2). We agree that classification based on the FEV1 and FEV1/FVC criteria established by the GOLD guidelines underemphasizes the potential significance of the "unclassified" subgroup of patients with low FEV1 but normal FEV1/FVC ratio. We would suggest further expansion of this subgroup to include patients with a disproportionately high FEV1/FVC ratio relative to FEV1. This group, currently classified within GOLD II, III, or IV, may share biological characteristics with the "unclassified" subgroup and may thus represent a unique COPD subphenotype with characteristics independent of the current GOLD severity classification schema. We further evaluated the distribution of 1,678 GOLD II, III, and IV patients selected from a population consisting of 4,504 subjects combined from both a COPD registry and large tobacco-exposed computed tomography (CT) screening cohort. Our population distribution (Figure 1) is similar to that of Kohler and colleagues (3). We determined the regression equation and 90% prediction intervals of the relationship between FEV1/FVC and FEV1% predicted for patients categorized as GOLD II, III, and IV (4). The upper limit of the prediction interval isolates a subset of 124 patients with severity of FEV1 impairment below that which would be expected given their FEV1/FVC ratio. Compared with others within their assigned GOLD category, this group may represent a unique COPD phenotype with unique pathogenic characteristics, clinical symptoms, therapeutic responsiveness, and prognosis. For example, it is not known whether this characteristic is most likely related to asymmetric air trapping versus synchronous parenchymal lung disease resulting in combined restriction. We believe that, by describing this subgroup, focused investigation can now be directed to better elucidate any unique clinical and biological attributes of this population.
The heterogeneous nature of COPD is exemplified by the variability of anatomic phenotypes, symptomatology, and systemic manifestations. Research efforts aim to further refine disease phenotypes for the purpose of understanding molecular mechanisms, developing novel therapies, and predicting disease prognosis. We must go beyond broadly classifying our patients according to current guidelines and continue to refine the characterization of those individuals falling outside the boundaries of the population distribution. Indeed, the important thing is not to stop questioning.
University of Pittsburgh FOOTNOTES Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. Sources of support for this research were the University of Pittsburgh SCCOR in COPD:NHLBI 1P50 HL084948 and P50-CA90440. REFERENCES
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