In the Journals

FEV1:FVC ratio diagnostic threshold optimal for predicting COPD prognosis

Use of a ratio of FEV1 to FVC less than 0.7 to define airflow obstruction was at least as accurate as other thresholds for predicting COPD-related hospitalizations and mortality, according to a study published in JAMA.

“The selection of a threshold for defining airflow obstruction has major implications for patient care and public health, as the prevalence of the condition could vary by more than a third depending on the metric used,” Elizabeth C. Oelsner, MD, MPH, the Herbert Irving Assistant Professor of Medicine at Columbia University in New York City, said in a press release. “Defining ‘normal’ lung function is very challenging in diverse and changing populations, and certain approaches might interpret low levels of lung function as normal in women, nonwhites or the elderly. We were able to show that a simple fixed threshold worked well in our study’s very diverse sample, which improves the generalizability of our results.”

For the National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study, Oelsner and colleagues sought to determine the accuracy of airflow at baseline of FEV1:FVC less than various fixed thresholds — 0.75 to 0.65 — or less than the Global Lung Initiative reference equations-defined lower limit of normal (LLN) for predicting the primary outcome of a composite of hospitalization and mortality related to COPD.

They evaluated pooled data from four large U.S. population-based cohorts, including the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), the Health, Aging and Body Composition Study (Health ABC) and the Multi-Ethnic Study of Atherosclerosis (MESA).

The pooled cohort was composed of 24,207 adults (mean age, 63 years; 54% women; 69% white; 63% ever smokers) — of whom 77% had complete follow-up at 15 years. The studies enrolled participants from 1987 to 2000 and included follow-up through 2016.

Most accurate threshold

A total of 3,925 participants experienced COPD-related events during 340,757 person-years of follow-up, translating to an incidence density rate of 11.5 per 1,000 person-years. During follow-up, COPD accounted for 3,563 hospitalizations and 447 deaths, with data demonstrating an inverse relationship between the incidence density rate and FEV1:FVC.

An FEV1:FVC of 0.71 was the optimal fixed threshold for discrimination of COPD-related events and was not significantly different from the 0.7 threshold (difference, 0.001; 95% CI, –0.002 to 0.004). However, the 0.7 threshold proved to be more accurate than the LLN threshold (difference, 0.034; 95% CI, 0.028-0.041), the researchers reported.

Additionally, the sensitivity and specificity for the LLN, which approximated results for a fixed threshold of 0.66, were 52% and 89%, respectively, whereas the sensitivity and specificity for the 0.7 threshold were 66% and 79%, respectively.

In sensitivity analyses, the optimal fixed threshold did not differ significantly from a fixed-ratio threshold of 0.7 and remained significantly more accurate than the LLN, except in groups with relatively low event rates.

In a subgroup analysis of ever smokers and in adjusted models, the 0.7 threshold was optimal for discrimination of COPD-related events.

A simple approach

James Kiley, PhD, director of the NHLBI Division of Lung Diseases, noted that the study bolsters confidence in use of the spirometry for COPD diagnosis.

“Diagnosis of airflow obstruction remains a major hurdle to improving care for patients with COPD,” he said in the press release. “This validation of a fixed threshold confirms the usefulness of a simple approach for assessment of the disease. As we celebrate the 50th anniversary of the Division of Lung Diseases, this rigorous analysis of populations-based, multiethnic studies is yet another example of research we fund that improves clinical practice, public health and patient care.”

Moreover, the use of this threshold may be best for diagnosing COPD until more is known about this complex disease, according to Jørgen Vestbo, DMSc, from the Manchester Academic Health Science Centre, Division of Infection, Immunity and Respiratory Medicine, University of Manchester and the NorthWest Lung Centre at Manchester University NHS Foundation Trust in the United Kingdom, and Peter Lange, DMSc, from the Institute of Public Health, Section of Epidemiology, Copenhagen University and the medical department, respiratory section, Herlev-Gentofte Hospital, Copenhagen University in Herlev, Denmark.

“Like most other common chronic diseases, COPD is heterogeneous with several different components and likely many different pathways leading to the disease, as illustrated by the different trajectories of FEV1 leading to COPD. In addition, although a better understanding is emerging of the genetics of COPD and the interactions of small airways disease and emphysema, further research is needed to define subsets of COPD based on mechanisms,” they wrote in an accompanying editorial. “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. Now, based on the findings reported in the study by Bhatt et al, this simple measurement has better evidence backing its prognostic value.”– by Melissa Foster

Disclosure s: Oelsner reports she has received grants from the NIH/NHLBI. Please see the study for all other authors’ relevant financial disclosures. Lange reports he has received grants from AstraZeneca and GlaxoSmithKline and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Novartis. Vestbo reports he has received a grant from Boehringer Ingelheim and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi Pharmaceuticals and Novartis.

 

Use of a ratio of FEV1 to FVC less than 0.7 to define airflow obstruction was at least as accurate as other thresholds for predicting COPD-related hospitalizations and mortality, according to a study published in JAMA.

“The selection of a threshold for defining airflow obstruction has major implications for patient care and public health, as the prevalence of the condition could vary by more than a third depending on the metric used,” Elizabeth C. Oelsner, MD, MPH, the Herbert Irving Assistant Professor of Medicine at Columbia University in New York City, said in a press release. “Defining ‘normal’ lung function is very challenging in diverse and changing populations, and certain approaches might interpret low levels of lung function as normal in women, nonwhites or the elderly. We were able to show that a simple fixed threshold worked well in our study’s very diverse sample, which improves the generalizability of our results.”

For the National Heart, Lung, and Blood Institute (NHLBI) Pooled Cohorts Study, Oelsner and colleagues sought to determine the accuracy of airflow at baseline of FEV1:FVC less than various fixed thresholds — 0.75 to 0.65 — or less than the Global Lung Initiative reference equations-defined lower limit of normal (LLN) for predicting the primary outcome of a composite of hospitalization and mortality related to COPD.

They evaluated pooled data from four large U.S. population-based cohorts, including the Atherosclerosis Risk in Communities Study (ARIC), the Cardiovascular Health Study (CHS), the Health, Aging and Body Composition Study (Health ABC) and the Multi-Ethnic Study of Atherosclerosis (MESA).

The pooled cohort was composed of 24,207 adults (mean age, 63 years; 54% women; 69% white; 63% ever smokers) — of whom 77% had complete follow-up at 15 years. The studies enrolled participants from 1987 to 2000 and included follow-up through 2016.

Most accurate threshold

A total of 3,925 participants experienced COPD-related events during 340,757 person-years of follow-up, translating to an incidence density rate of 11.5 per 1,000 person-years. During follow-up, COPD accounted for 3,563 hospitalizations and 447 deaths, with data demonstrating an inverse relationship between the incidence density rate and FEV1:FVC.

An FEV1:FVC of 0.71 was the optimal fixed threshold for discrimination of COPD-related events and was not significantly different from the 0.7 threshold (difference, 0.001; 95% CI, –0.002 to 0.004). However, the 0.7 threshold proved to be more accurate than the LLN threshold (difference, 0.034; 95% CI, 0.028-0.041), the researchers reported.

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Additionally, the sensitivity and specificity for the LLN, which approximated results for a fixed threshold of 0.66, were 52% and 89%, respectively, whereas the sensitivity and specificity for the 0.7 threshold were 66% and 79%, respectively.

In sensitivity analyses, the optimal fixed threshold did not differ significantly from a fixed-ratio threshold of 0.7 and remained significantly more accurate than the LLN, except in groups with relatively low event rates.

In a subgroup analysis of ever smokers and in adjusted models, the 0.7 threshold was optimal for discrimination of COPD-related events.

A simple approach

James Kiley, PhD, director of the NHLBI Division of Lung Diseases, noted that the study bolsters confidence in use of the spirometry for COPD diagnosis.

“Diagnosis of airflow obstruction remains a major hurdle to improving care for patients with COPD,” he said in the press release. “This validation of a fixed threshold confirms the usefulness of a simple approach for assessment of the disease. As we celebrate the 50th anniversary of the Division of Lung Diseases, this rigorous analysis of populations-based, multiethnic studies is yet another example of research we fund that improves clinical practice, public health and patient care.”

Moreover, the use of this threshold may be best for diagnosing COPD until more is known about this complex disease, according to Jørgen Vestbo, DMSc, from the Manchester Academic Health Science Centre, Division of Infection, Immunity and Respiratory Medicine, University of Manchester and the NorthWest Lung Centre at Manchester University NHS Foundation Trust in the United Kingdom, and Peter Lange, DMSc, from the Institute of Public Health, Section of Epidemiology, Copenhagen University and the medical department, respiratory section, Herlev-Gentofte Hospital, Copenhagen University in Herlev, Denmark.

“Like most other common chronic diseases, COPD is heterogeneous with several different components and likely many different pathways leading to the disease, as illustrated by the different trajectories of FEV1 leading to COPD. In addition, although a better understanding is emerging of the genetics of COPD and the interactions of small airways disease and emphysema, further research is needed to define subsets of COPD based on mechanisms,” they wrote in an accompanying editorial. “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. Now, based on the findings reported in the study by Bhatt et al, this simple measurement has better evidence backing its prognostic value.”– by Melissa Foster

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Disclosure s: Oelsner reports she has received grants from the NIH/NHLBI. Please see the study for all other authors’ relevant financial disclosures. Lange reports he has received grants from AstraZeneca and GlaxoSmithKline and personal fees from AstraZeneca, Boehringer Ingelheim, GlaxoSmithKline and Novartis. Vestbo reports he has received a grant from Boehringer Ingelheim and personal fees from AstraZeneca, Boehringer Ingelheim, Chiesi Pharmaceuticals and Novartis.