Two sets of experts addressed questions surrounding the use of single and dual bronchodilators as first-line therapy, and the need to measure peak inspiratory flow (PIF) prior to prescribing a dry powder inhaler in the Pro/Con Debate: Uncertainties in Treating COPD. The session is available for viewing on the virtual CHEST 2020 meeting platform through February 1, 2021, for registered attendees.

LABA/LAMA should be first-line therapy for symptomatic patients with COPD (Group B)

The first debate examined the Global Initiative for Chronic Obstructive Lung Disease (GOLD) committee recommendation that a single bronchodilator be the initial therapy for symptomatic patients with COPD (Group B).

“We know that long-acting bronchodilators are key pharmacologic agents in treatment of COPD patients who have symptoms,” said Nicola A. Hanania, MD, MS, FCCP, associate professor of pulmonary medicine and director of Airways Clinical Research Center, Baylor College of Medicine. “They not only improve lung function, but they decrease dyspnea as well as increase exercise tolerance and potentially reduce exacerbation.” He challenged the GOLD recommendation and presented support for using a long-acting beta-agonist (LABA) and long-acting muscarinic antagonist (LAMA) combination as first-line treatment for Group B patients.

Dr. Hanania said there is sufficient evidence that the LABA/LAMA combination is more effective and as safe as monotherapy as the first therapy for patients with COPD. The recently released American Thoracic Society Clinical Practice Guideline on Pharmacologic Management of Chronic Obstructive Pulmonary Disease also strongly recommends LABA/LAMA combination therapy for patients with COPD who complain of dyspnea or exercise intolerance.

“The rationale for combining bronchodilators came because of the need, because patients on one long-acting bronchodilator often continue to have symptoms,” Dr. Hanania said.

Sanjay Sethi, MBBS, professor and division chief of pulmonary, critical care, and sleep medicine; assistant vice president for health sciences; director of clinical research; and deputy director of the Clinical and Translational Science Institute, University at Buffalo, acknowledged the efficacy of dual long-acting bronchodilators for patients who do not respond to a single long-acting bronchodilator, but he added a caveat.

“If you’ve never been at one, then you will never know where you are between one and two if you were to start at two,” he said.

Dr. Sethi characterized initial therapy with a dual long-acting bronchodilator in COPD as a life sentence.

“Once you get that on those patients, you’re done,” he said. “You’re not going to be able to take away a bronchodilator with any level of confidence, so basically you never had the chance to see if a single long-acting bronchodilator was enough and if the second long-acting bronchodilator did really make a difference.”

Peak inspiratory flow should be measured before prescribing a dry powder inhaler

Dry powder inhalers each have their own unique internal resistance as well as unique minimal and optimal PIFs, or the maximum flow rate that can be generated during the inspiratory cycle. This means drug delivery is affected significantly by PIF, as seen by the residual drug left in a capsule after a dose has been administered.

“There is a lot more in the capsule if you had a low PIF measurement than a high PIF measurement,” said Jill Ohar, MD, FCCP, professor of medicine, Wake Forest University, who made the case for measuring PIF before prescribing a dry powder inhaler.

A retrospective study of patients admitted to the hospital for an acute exacerbation of COPD showed statistically significant evidence that patients with a suboptimal PIF are more likely to be readmitted with COPD within 90 days compared to patients with an optimal PIF, Dr. Ohar explained. Between 32% and 52% of admitted patients with an exacerbation of COPD have a suboptimal PIF.

M. Bradley Drummond, MD, MHS, associate professor of medicine, University of North Carolina at Chapel Hill, contends that we don’t know how to measure PIF well or what PIF means for the patient.

PIF measurement can be impacted by numerous factors, such as whether the patient is sitting or standing and even instructions for the inhalation maneuver. Dr. Drummond suggested patients should be asked to approach an inspiratory maneuver like they do their inhalers.

“We’re trying to see if the patient can actually use the dry powder inhaler in a sufficient manner, and so certainly taking that deep breath in, if it’s going to be a false equivalence, if they’re doing it in an experimental setting, it doesn’t reflect what they’re doing in the real world,” he said. “I think that that may give us false comfort in using that device.”