Pharmacologic Therapy for COPD: GOLD or ATS Guidelines?

Aaron B. Holley, MD


October 08, 2020

Chronic obstructive pulmonary disease (COPD) is a major cause of morbidity and mortality worldwide. It is a chronic disease that affects quality of life and mobility, and can lead to respiratory compromise and exacerbations that require hospitalization. While prevention is key, inhalers are the mainstay of therapy once disease is established.

The Global Strategy for the Diagnosis, Management, and Prevention of Chronic Obstructive Pulmonary Disease (GOLD) Report provides recommendations for COPD management. Its ABCD algorithm for prescribing inhaler therapy — driven by patient symptoms and exacerbation history — is well known and widely used. If symptoms such as dyspnea continue to occur despite initial inhaler therapy, step-up is recommended. The same is true for exacerbations.

The American Thoracic Society (ATS) just released its clinical practice guideline on pharmacologic management of COPD online in the form of a physician summary. The recommendations on using inhalers for dyspnea and respiratory-related quality of life come from a systematic review and meta-analysis, also published online. They examined whether switching from long-acting bronchodilator monotherapy (either long-acting beta-agonist [LABA] or long-acting muscarinic antagonist [LAMA]) to dual (inhaled corticosteroid [ICS]/LABA or LABA/LAMA) or triple (LABA/LAMA/ICS) therapy would improve dyspnea or respiratory-related quality of life. Turns out, there's no significant benefit beyond initial monotherapy.

It would appear, then, that the new ATS guidelines contradict GOLD. GOLD specifically recommends going to dual and then triple therapy for patients on monotherapy with persistent symptoms. In fact, the 2020 GOLD document has a separate flow chart for dyspnea that seems to directly contradict the ATS clinical practice guideline.

This wouldn't be the first time that recommendations from different organizations offer conflicting guidance, but they usually differ over minor points. Managing dyspnea and exercise intolerance is key for all patients with COPD, so ideally it would be something we'd agree on.

The reasons for the difference may lie, at least in part, within the design of the GOLD report. It is not a guideline; it is a self-described "strategy document." The processes are outlined in the introduction, and while they are certainly "scientific," they do not follow the GRADE criteria the way other practice guidelines (including the ATS guideline on pharmacologic therapy) do. Data are not combined systematically using a meta-analytic technique.

In fact, when discussing their ABCD recommendations for treatment escalation, the GOLD authors specifically state, "[W]e are aware that treatment escalation has not been systematically tested." But with the release of the ATS clinical practice guideline, it seems that's no longer true. It's important to note that the ATS guideline did find clear evidence that going from monotherapy to dual or triple therapy does reduce acute exacerbations of COPD (AECOPD) in those patients with frequent AECOPDs at baseline. So by no means are dual and triple therapy dead.

Physicians should think twice, however, before chasing symptoms by adding inhaler therapies. Pulmonary rehab has great data for dyspnea and quality of life and is underutilized. While GOLD endorses pulmonary rehab, its ABCD algorithm seems overly simplistic. More emphasis on pulmonary rehab could reduce inhaler overprescription and increase pulmonary rehab referrals.

Aaron B. Holley, MD, is an associate professor of medicine at Uniformed Services University and program director of pulmonary and critical care medicine at Walter Reed National Military Medical Center. He covers a wide range of topics in pulmonary, critical care, and sleep medicine.

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