COMMENTARY

The Latest on ERS/ATS Lung Function Interpretation Guidelines and Bronchodilator Testing

Aaron B. Holley, MD

Disclosures

December 08, 2022

The European Respiratory Society (ERS) and the American Thoracic Society (ATS) just published an updated technical standard on lung function interpretation. It's a critically important document written by a "Who's Who" in the lung function world. It's impossible to review in its entirety without more space, so I'll settle for covering what the authors say about bronchodilator testing. But before I do that, it's worth reviewing what we think we know about having a patient perform spirometry, inhale a bronchodilator, and then repeat it. This is colloquially referred to as pre- and post-bronchodilator testing.

Administering a bronchodilator and measuring changes in lung function seems simple and intuitive. It is biologically plausible that improvement would predict treatment response. It should allow for phenotyping airways diseases and quantifying exacerbation risk. It is easy to perform and can be done in the clinic. But in practice it falls short of its purpose, in part because of technical factors but also because it doesn't really have a purpose.

The last interpretative strategies document from the ERS/ATS was published in 2005. Reading it many years ago, I was struck by the contrast between our reliance on bronchodilator response and its lack of standardization. It seemed that there was none. After making statements like, "There is no consensus on what constitutes reversibility in subjects with airflow obstruction" and "There is no consensus on how a bronchodilator response should be expressed, the variables to be used, and finally, the kind, dose, and inhalation mode of bronchodilator agent," the 2005 ERS/ATS authors suggest using the criteria most clinicians are familiar with: A change of 12% and 200 cc in FEV1 or FVC marks a "significant" bronchodilator response. Four puffs of albuterol (100 µg each for a total of 400 µg) with a 15- to 20-minute wait before repeat spirometry is also suggested.

The 2005 iteration acknowledges that a significant bronchodilator response isn't a very accurate predictor of, well, anything. It doesn't reliably differentiate COPD from asthma and it's never been as sensitive as bronchoprovocation testing for diagnosing airway reactivity. The absence of a significant bronchodilator response does not preclude a 2-month trial of the same medicine used to test for response. Given these problems with standardization and accuracy, I was left wondering why anyone bothers ordering the test at all.

In my own practice, I continued to order, conduct, and interpret bronchodilator response according to the suggestions made by the ERS/ATS in 2005 when trying to diagnose asthma. I recognized that a nonsignificant response meant nothing, but bronchodilator response testing was easier to obtain than bronchoprovocation at my hospital. It was a matter of convenience for me and the patient. According to the Global Initiative for Asthma (GINA) Guidelines, a significant bronchodilator response conducted and interpreted as recommended by the ERS/ATS 2005 standard provides objective confirmation of asthma in the presence of characteristic clinical symptoms.

The headline from the ERS/ATS 2022 Technical Standard is that the 12% and 200 cc criteria suggested in 2005 are being retired. Why? Well, much of the variability in the 2005 criteria is explained by height, age, sex, and baseline lung function. These factors obscure change related to intrinsic airway abnormalities. Instead, the authors suggest using a threshold change in the predicted values of FEV1 and FVC to determine a significant response. Because predicted values incorporate age, height, and sex, the impact from these variables is minimized. Using a percent predicted (PPD) threshold will also minimize the effect from the inverse relationship between measured values and bronchodilator response.

A 10% change in the PPD value for either FEV1 or FVC constitutes a significant bronchodilator response. Ten percent was chosen because it represents the statistically defined upper limit of normal response; and a greater than 8% change in bronchodilator response is associated with mortality, implying that values above this threshold connote disease. The technical standard seems to be on solid ground here; the rationale is mathematically appropriate and evidence based. The new definition will certainly improve precision.

There's really no progress on accuracy, though. There are no comments on the protocol to be followed or clinical indications. The reader is referred to the ERS/ATS 2019 technical statement on standardization of spirometry. The statement on standardization is short on details too and refers the reader to an online supplement for a suggested protocol. The suggested protocol is identical to that suggested in 2005.

In summary, not a lot is different in the world of bronchodilator response testing. The definition is different now, and though it's likely to be more precise, we still don't know enough about accuracy. It's nice to know that the new criteria will predict mortality, but in clinical practice we don't use the test for that purpose. The 2022 technical standard acknowledges this and other limitations in a "future directions" paragraph. Perhaps we'll know more when the next iteration is published.

Aaron B. Holley, MD, is a professor of medicine at Uniformed Services University in Bethesda, Maryland, and a pulmonary medicine/critical care physician at MedStar Washington Hospital Center in Washington, DC. He covers a wide range of topics in pulmonary, critical care, and sleep medicine.

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