As advances are made in the understanding of normal vs abnormal lung function, practitioners must not only use the right tests but also apply up-to-date information about how to interpret the results.
A CHEST 2022 session, Pulmonary Function Testing in 2022: Key Updates and Best Practices, on Monday, October 17, highlighted important changes recommended in a technical standard on interpretive strategies for routine lung function tests, updated in 2021 by the European Respiratory Society and the American Thoracic Society (ATS) for the first time since 2005. Presenters also focused on the use of reference values, methods of grading severity of impairment, and the fractional exhaled nitric oxide (FeNO) test.
Assessing bronchodilator response: a controversial change
Thomas DeCato, MD, FCCP, assistant clinical professor of medicine at the David Geffen School of Medicine at UCLA and Harbor-UCLA Medical Center, discussed the new guideline’s definition of bronchodilator responsiveness (BDR). Previously, responsiveness was defined as a forced vital capacity (FVC) of 12% or more and a gain of at least 200 mL from baseline measured by FVC or forced expiratory volume in the first second (FEV1). Now, BDR positivity constitutes improvement in lung function reaching 10% or more of the predicted value of FVC or FEV1.
The change is controversial because it shrinks the proportion of patients classified as responders across the board. In addition, while those with severe COPD are likely to be deemed BDR-positive, patients with severe asthma—whose condition responds less meaningfully to bronchodilators—are not.
Dr. DeCato said the 10% cutoff was chosen because it approximates the 95th percentile for response. He added that evidence supports predicted value rather than baseline score as a guidepost because it minimizes bias associated with age, height, and gender.
Regardless of methodology, Dr. DeCato cautioned that BDR cannot differentiate asthma from COPD.
Which reference values are best?
Although the previous guideline did not recommend a specific set of reference values in most cases, the update encourages the use of Global Lung Function Initiative (GLI) measurements to assess spirometry, lung volume, and diffusing capacity (DLCO) results, said Matthew Hegewald, MD, FCCP, adjunct associate professor of internal medicine at the University of Utah and Intermountain Medical Center.
The best reference criteria rely on high-quality testing methods—including appropriate statistical limits of the upper and lower normal ranges, such as Z scores, that allow for age-related variation because they are not fixed, Dr. Hegewald said. Values should also be based on large global study populations that are biologically similar to the patients being evaluated and include healthy nonsmokers—criteria met by the GLI, he said.
“GLI equations are probably the best for spirometry, DLCO, and lung volumes,” he said. “If you use them as a package, you will have consistent methods for determining the predicted values of the lower limit of normal. But, there are some shortcomings: The ethnic and racial diversity for DLCO and lung volumes is lacking, and there may be some significant differences between GLI and other previous reference equations, especially for DLCO.”
Switching to Z scores
The guideline recommends that clinicians describe the severity of lung obstruction through Z scores, which quantify the divergence of pulmonary function from predicted value. Z scores are expressed in standard deviations after accounting for age, height, sex, and—in some cases—race and ethnicity, said Meredith McCormack, MD, MHS, associate professor of pulmonary and critical care medicine at Johns Hopkins University.
In the earlier guideline, the extent of airflow obstruction was expressed as a percentage comparing test results with predicted FEV1.
With Z scores, the lower limit of normal is typically set at the fifth percentile and expressed as a standard deviation of -1.645 from the mean. But with “normal” defined as the middle 95% of values in a healthy, nonsmoking population, a “zone of uncertainty” at either end of the scale can lead to misdiagnoses.
“Our goal is to minimize that,” Dr. McCormack said. “In a borderline case, we’d want to get more information from the patient about their history, more testing, and follow their lung function more closely.”
Adding FeNO testing to usual care
Nitric oxide promotes healthy blood flow and smooth muscle relaxation, but too much of it can lead to hyper-responsiveness that exacerbates asthma. Because that excess is detectable in the breath of affected patients, FeNO testing can play a role in asthma management.
The strategy warranted an ATS guideline published in 2011 and another in 2021, which provided evidence that including FeNO testing in treatment planning reduces asthma exacerbation and oral steroid use.
Sumita Khatri, MD, MS, FCCP, professor of medicine, vice chair of the Respiratory Institute, and director of the Asthma Center at the Cleveland Clinic, was the lead author of the 2021 FeNO guideline. She advised that FeNO testing is most useful in those with steroid-naive asthma, children, and nonsmokers but should never be used alone to control asthma or predict its development. Considering FeNO levels and asthma exacerbation rates together can help doctors determine when treatment needs adjustment, she added.
“In patients with asthma in whom treatment is being considered,” Dr. Khatri said, “we suggest the use of FeNO testing in addition to usual care, over usual care alone.”