"GOLD or lower limit of normal definition? A comparison with expert-based diagnosis of chronic obstructive pulmonary disease in a prospective cohort-study"

Abstract

Background: The Global initiative for chronic Obstructive Lung Disease (GOLD) defines COPD as a fixed post-bronchodilator ratio of forced expiratory volume in 1 second and forced vital capacity (FEV1/FVC) below 0.7. Age-dependent cut-off values below the lower fifth percentile (LLN) of this ratio derived from the general population have been proposed as an alternative. We wanted to assess the diagnostic accuracy and prognostic capability of the GOLD and LLN definition when compared to an expert-based diagnosis.

Methods: In a prospective cohort study, 405 patients aged ≥ 65 years with a general practitioner's diagnosis of COPD were recruited and followed up for 4.5 (median; quartiles 3.9; 5.1) years. Prevalence rates of COPD according to GOLD and three LLN definitions and diagnostic performance measurements were calculated. The reference standard was the diagnosis of COPD of an expert panel that used all available diagnostic information, including spirometry and bodyplethysmography.

Results: Compared to the expert panel diagnosis, 'GOLD-COPD' misclassified 69 (28%) patients, and the three LLNs misclassified 114 (46%), 96 (39%), and 98 (40%) patients, respectively. The GOLD classification led to more false positives, the LLNs to more false negative diagnoses. The main predictors beyond the FEV1/FVC ratio for an expert diagnosis of COPD were the FEV1 % predicted, and the residual volume/total lung capacity ratio (RV/TLC). Adding FEV1 and RV/TLC to GOLD or LLN improved the diagnostic accuracy, resulting in a significant reduction of up to 50% of the number of misdiagnoses. The expert diagnosis of COPD better predicts exacerbations, hospitalizations and mortality than GOLD or LLN.

Conclusions: GOLD criteria over-diagnose COPD, while LLN definitions under-diagnose COPD in elderly patients as compared to an expert panel diagnosis. Incorporating FEV1 and RV/TLC into the GOLD-COPD or LLN-based definition brings both definitions closer to expert panel diagnosis of COPD, and to daily clinical practice.

Figure 1

Flow chart for diagnostic algorithm. In clinical practice the diagnosis of COPD is based on multiple variables. As the simplest model we chose a three PFT parameters approach in which an initial COPD YES/NO diagnosis based on FEV/FVC levels was corrected if FEV1 and RV/TLC levels were altered counterintuitively*. * As thresholds for FEV1 and RV/TLC levels different cut-off levels were used and kappa statistics calculated for all alternatives. Each change in COPD diagnosis only materializes if both parameters deviate by ≤ 5/7.5/10/12.5/15/20% from 100% of the predicted value. Example: If deviations of 10% (from 100%) are chosen as thresholds for both FEV1 and RV/TLC (as % of predicted) in order to change the GOLD-COPD diagnosis from ¹⁾ 'yes' into 'no' (i.e., FEV1 ≥ 90% and RV/TLC ≤ 110%; [²⁾ or vice versa, from 'no' into 'yes', FEV1 < 90% and RV/TLC > 110%]), then the number of misclassified patients (false positives + false negatives) is reduced from 69 to 33, and κ- statistics improve from 0.64 to 0.83. Abbreviations: as in table 1.

Figure 2

Change of the threshold of FEV1/FVC ratio will change the amount of misdiagnosis in both directions. Application of the LLN definition in elderly patients which generally results in FEV1/FVC levels smaller than 0.7 reduces the number of FP diagnoses but subsequently increases the FN.