Discriminative Accuracy of FEV₁:FVC Thresholds for COPD-Related Hospitalization and Mortality

Abstract

IMPORTANCE According to numerous current guidelines, the diagnosis of chronic obstructive pulmonary disease (COPD) requires a ratio of the forced expiratory volume in the first second to the forced vital capacity (FEV 1 :FVC) of less than 0.70, yet this fixed threshold is based on expert opinion and remains controversial. OBJECTIVE To determine the discriminative accuracy of various FEV 1 :FVC fixed thresholds for predicting COPD-related hospitalization and mortality. DESIGN, SETTING, AND PARTICIPANTS The National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study harmonized and pooled data from 4 US general population-based cohorts (Atherosclerosis Risk in Communities Study; Cardiovascular Health Study; Health, Aging, and Body Composition Study; and Multi-Ethnic Study of Atherosclerosis). Participants aged 45 to 102 years were enrolled from 1987 to 2000 and received follow-up longitudinally through 2016. EXPOSURES Presence of airflow obstruction, which was defined by a baseline FEV 1 :FVC less than a range of fixed thresholds (0.75 to 0.65) or less than the lower limit of normal as defined by Global Lung Initiative reference equations (LLN). MAIN OUTCOMES AND MEASURES The primary outcome was a composite of COPD hospitalization and COPD-related mortality, defined by adjudication or administrative criteria. The optimal fixed FEV 1 :FVC threshold was defined by the best discrimination for these COPD-related events as indexed using the Harrell C statistic from unadjusted Cox proportional hazards models. Differences in C statistics were compared with respect to less than 0.70 and less than LLN thresholds using a nonparametric approach. RESULTS Among 24 207 adults in the pooled cohort (mean [SD] age at enrollment, 63 [10.5] years; 12 990 [54%] women; 16 794 [69%] non-Hispanic white; 15 181 [63%] ever smokers), complete follow-up was available for 11 077 (77%) at 15 years. During a median follow-up of 15 years, 3925 participants experienced COPD-related events over 340 757 person-years of follow-up (incidence density rate, 11.5 per 1000 person-years), including 3563 COPD-related hospitalizations and 447 COPD-related deaths. With respect to discrimination of COPD-related events, the optimal fixed threshold (0.71; C statistic for optimal fixed threshold, 0.696) was not significantly different from the 0.70 threshold (difference, 0.001 [95% CI, −0.002 to 0.004]) but was more accurate than the LLN threshold (difference, 0.034 [95% CI, 0.028 to 0.041]). The 0.70 threshold provided optimal discrimination in the subgroup analysis of ever smokers and in adjusted models. CONCLUSIONS AND RELEVANCE Defining airflow obstruction as FEV 1 :FVC less than 0.70 provided discrimination of COPD-related hospitalization and mortality that was not significantly different or was more accurate than other fixed thresholds and the LLN. These results support the use of FEV 1 :FVC less than 0.70 to identify individuals at risk of clinically significant COPD.

Low FVC/TLC in Preserved Ratio Impaired Spirometry (PRISm) is associated with features of and progression to obstructive lung disease

“…We acknowledge that the fixed threshold FEV1/FVC < 0.7 diagnostic criterion for COPD endorsed by Global Initiative for Chronic Obstructive Lung Disease(GOLD) may have also misclassified individuals with obstructive lung disease as PRISm. In a recent large population-based sample (n = 24,207), Bhatt and colleagues showed that the discriminative accuracy of FEV 1 /FVC < 0.7 to predict COPD-related death and/or hospitalization was not inferior to FEV 1 /FVC < LLN 36 . We assert that because the majority of our findings remained robust on sensitivity analyses using LLN-defined lung function categories.…”

Pulmonary Function Reference Equations: A Brief History to Explain All the Confusion

“…Research using hospital administrative data or fixed cutoffs for spirometric indices introduces biases and risk of misclassification of COPD, although this topic remains controversial. [32][33][34] Use of statistically valid LLN for lung function measures, along with prior probability of disease, clinical signs, and symptoms reduces the risk of both false positives and false negatives. Using the LLN rather than 0.70 in younger adults with symptoms of airway obstruction (eg, asthma) also avoids false-negative interpretations when the LLN is above the fixed threshold.…”

Canadian Thoracic Society Clinical Practice Guideline on pharmacotherapy in patients with COPD – 2019 update of evidence

“…Recent results support the use of fixed ratio less than 0.70 as appropriate to identify individuals at risk of clinically significant COPD. 5,6 However, more than a single postbronchodilator spirometric assessment may be necessary for diagnosing COPD for patients with mild airway obstruction at baseline. 7 We suggest post-bronchodilator FEV 1 /FVC ratio should be confirmed by a repeat spirometry on a separate occasion if the value is between 0.6 and 0.8, because the ratio may change as a result of biological variation.…”