Chronic obstructive pulmonary disease (COPD) diagnosis based on current guidelines was a more accurate predictor of clinically significant disease than assessment of airflow obstruction using the lower limit of normal (LLN), pooled data from four large population-based cohort studies indicated.
In the analysis of more than 24,000 individuals, the forced expiratory volume in the first second to forced vital capacity (FEV1:FVC) threshold of 0.70 provided better discrimination of COPD-related hospitalizations or death than LLN, as well as optimal discrimination in ever smokers, Surya P. Bhatt, MD, MSPH, of the University of Alabama at Birmingham, and colleagues reported in JAMA.
GOLD guidelines and those of leading respiratory groups identify COPD as presence of FEV1:FVC of less than 0.70 on spirometry, but this fixed threshold had not been previously validated in population-based studies, Bhatt told MedPage Today.
“The 0.70 fixed rate was derived from expert opinion in the late 1990s,” he said. “There really hasn’t been research to support using this fixed ratio, but it has been used clinically for the past two decades.”
Within pulmonary medicine, the clinical community is divided about how to best diagnose airflow obstruction, said Bhatt, as the FEV1:FVC threshold does not take demographic factors into account, while defining airflow obstruction as less than the LLN does.
In their newly published study, Bhatt and colleagues compared the efficacy of various fixed FEV1:FVC thresholds for predicting COPD-related events (hospitalizations and deaths) in a large, multi-ethnic cohort.
The optimal threshold of 0.71, defined as that which yielded the highest Harrell C statistic (0.696), was more accurate in discrimination of COPD-related events than the LLN threshold (0.034 difference, 95% CI 0.028-0.041, P<0.001) but no different than the 0.70 threshold (0.001 difference, 95% CI -0.002 to 0.004, P=0.57).
“Defining airflow obstruction as an FEV1:FVC of less than 0.70 provided discrimination of COPD-related hospitalization and mortality that was not significantly different than or was more accurate than other fixed thresholds and the LLN,” the authors concluded. “These results support use of an FEV1:FVC of less than 0.70 to identify individuals at risk of clinically significant COPD.”
In an accompanying editorial, Jørgen Vestbo, DMSc, of the University of Manchester in England, and Peter Lange, DMSc, of Copenhagen University in Denmark, wrote that the use of both a fixed threshold, which is not adjusted for patient characteristics, and an adjusted measure like LLN offers advantages and disadvantages.
“A fixed threshold will invariably be biased by age,” they wrote. “Undoubtedly, LLN for the FEV1:FVC ratio is a better measure of airflow limitation in general because LLN adjusts for the strong association between increasing age and decreasing FEV1:FVC ratio in healthy individuals. However, for use as a diagnostic criterion in a symptomatic individual with an exposure history relevant to COPD (most often smoking), this advantage of LLN may not be that important.”
They added that while COPD is heterogeneous “with several different components and likely many different pathways leading to disease,” the identification of disease subsets that can inform diagnosis and treatment will require additional research.
“While waiting, clinicians may be best advised to continue to use an old simple measurement, FEV1:FVC of less than 0.70, as an indicator of this complex disorder,” Vestbo and Lange wrote. “Now, based on the findings reported in the study of Bhatt [and colleagues], this simple measurement has better evidence backing its prognostic value.”
For their study, Bhatt’s team analyzed data from four trials included in the National Heart, Lung, and Blood Institute Pooled Cohorts Study that included 24,207 participants enrolled from 1987 to 2000 and followed until 2016.
Airflow obstruction was defined as baseline FEV1:FVC less than a range of fixed thresholds (0.75 to 0.65) or less than the LLN as defined by Global Lung Initiative reference equations. At enrollment, mean subject age was 63 years, and 54% were women. Non-Hispanic whites made up 69% of the cohort and 63% were ever smokers.
Among 11,077 subjects who were followed for at least 15 years, 3,925 had COPD-related events, 3,563 were hospitalized for COPD-related causes, and 447 died of COPD.
The researchers used pre-bronchodilator spirometry values to confirm airway obstruction, even though GOLD guidelines recommend using post-bronchodilator values. But they noted that multiple studies have shown close correlation between the two values. Other study limitations cited by the researchers included the lack of adjustment for medication use, baseline differences in demographics across studies, and significant loss to follow-up.
Funding for this study was provided by the National Institutes of Health (NIH). The studies included in the analysis were funded by the NIH; the National Heart, Lung, and Blood Institute; the Department of Health and Human Services; the National Institute on Aging; and others.
Bhatt reported consulting fees from Sunovion and funds from ProterixBio unrelated to this study. Co-authors reported fees from industry outside the submitted work.
Vestbo reported relationships with Boehringer Ingelheim, GlaxoSmithKline, Chiesi Pharmaceuticals, Novartis, and AstraZeneca. Lange disclosed fees from Boehringer Ingelheim, AstraZeneca, Novartis, and GlaxoSmithKline.