Kevin Kunzmann

Halpin reviews the state of triple therapy inhaler prescribing strategies in the era of new biologic options.

COPD Inhaler Use in the Biologic Era, with David Halpin, MBBS, DPhil

Single inhaler triple therapy options reached the US market in the last decade, providing clinicians a number of options to effectively treat the common symptoms of 

 without tasking a patient to adhere to multiple devices; options like fluticasone furoate / umeclidinium / vilanterol (Trelegy Ellipta)

 and budesonide / glycopyrrolate / formoterol (Breztrai Aerosphere)

 have simplified a patient’s means to receive a regular dose of inhaled corticosteroid (ICS), long-acting beta agonist (LABA) and long-acting muscarinic antagonist (LAMA).

But this drug class hasn’t come without its own practical hang-ups.

Chronic Obstructive Lung Disease (GOLD) International COPD Conference

 in Philadelphia, PA, this month, David Halpin, MBBS, DPhil, Clinical Lead of Respiratory Medicine at the University of Exeter, discussed the advantages and challenges alike that have emerged in the era of multiple-therapy inhaler devices to treat COPD.

While there are more opportunities to now fit a suitable device to a patient with COPD, the amplification of choices warrants an adequate understanding of each option.

“It's confusing for clinicians about how you should use them optimally,” Halpin said. “And so even though many devices are available, many clinicians default to a limited number that they're familiar with.”

There’s even differing methodology between single inhaler multiple therapy options — some warrant a twice-daily administration, others only one. Some do require an add-on treatment, others do not.

“Patients get very confused, and as a result, don't take it as well as they should and are more likely to have exacerbations and not get as good symptom control as they could achieve,” Halpin said. “There’s still a lot of work to do to educate the prescribers and to train the patients that having a single inhaler is much more convenient — patients are going to be more adherent and more likely to get the benefits from that treatment.”

Halpin also discussed general prescribing strategy trends in COPD. He noted that some of his colleagues may initiate a long-acting bronchodilator, wait to assess its benefit, then add a second bronchodilator, wait again, and finally add an ICS to a patient’s regimen. He stressed that this strategy is only delaying the time to optimal care — and time is everything in COPD treatment.

“The evidence suggests that if a patient needs the treatment, the sooner you start all of the components together, the better the outcomes will be,” he said.

The advent of biologic therapies to treat COPD further evidences the need to start timely, robust maintenance treatment as soon as the patient needs it; an add-on biologic is now available for most patients with severe cases.

“Biologics offer an opportunity to add on to the triple therapy, to further reduce those exacerbation rates,” Halpin said. “And they have to be tailored to the individual patient. But if you've got the right patients with the right biomarkers to indicate the need for a biologic, the biologics really offer something new.”

Walter K. FDA Approves COPD Triple Therapy. 

. Published July 24, 2020. https://www.hcplive.com/view/fda-approves-copd-triple-therapy

Hoffman M. FDA Grants New Indication to Trelegy Ellipta for COPD. 

. Published online April 24, 2018. https://www.hcplive.com/view/fda-grants-new-indication-to-trelegy-ellipta-for-copd

Videos

Vogelmeier discusses major changes to the annual COPD report, including a broader threshold for escalating treatment after exacerbation.

Breaking Down the 2026 GOLD Report, with Claus Vogelmeier, MD

The Global Initiative for Obstructive Lung Disease (GOLD) released its 

 earlier this week, adding more than 300 relevant references from clinical research to the organization’s annually updated guidance on the definition, diagnosis, assessment, prevention, and management of 

This year’s report made several significant alterations to the clinical definitions that comprise COPD, including the shift to constitute any patient who has experienced ≥1 moderate or severe exacerbation in the last year to be classified as “exacerbated.” Previously, patients were required to have ≥2 exacerbations to reach this mark. This update was based on observational research showing that just 1 exacerbation prior to initiating maintenance pharmacotherapy could increase the risk of subsequent events — thereby warranting that clinicians consider treatment escalation at the threshold of 1 exacerbation in order to achieve low disease acidity state.

"If we are able to identify patients earlier in a state where not most of the lung is destroyed, and then select the right patient based on their endotype and give them the drugs that are targeted to this endotype...then we have a very high likelihood that we are able to change the natural cause the disease, and that that was not possible 20-30 years ago. We didn't have the management strategies, we didn't have the assessment strategies, we weren't able to diagnose earlier. I think this is the time to try."

The 2026 report additionally provided recommendations for goal-setting, monitoring, and prescribing / maintaining therapy for “stable COPD” — a previously less-defined state of disease without worsening markers nor symptoms.

Further, the report introduced the role of artificial intelligence (AI) in COPD detection, management, and research — setting the groundwork for further organization-level recommendations surrounding large language models (LLMs) and other AI tools to optimize COPD care.

 in Philadelphia, PA, this week, Claus Vogelmeier, MD, a professor at the University of Marburg and chair of the GOLD science committee, discussed the biggest updates to the annual report and what it means for the current and future priorities in COPD care progression.

Regarding the updated exacerbation classification, Vogelmeier noted the change does not affect initial COPD treatment — patients will still likely be initiated on long-acting beta agonist (LABA) plus an anticholinergic. But it will implicate future treatment, as it qualifies patients immediately for care escalation.

“We have learned over time that having an exacerbation, even moderate ones, can be very risky for the patients,” Vogelmeier said. “They may go to the hospital, they may need to be treated with steroids and/or antibiotics, they may lose lung function, they may lose quality of life. So with this as a background, we decided that we have to change the system.”

Vogelmeier explained that increasingly robust data on the clinical efficacy and safety of newer therapies to treat COPD, including triple-therapy inhaler devices and the recently approved biologic mepolizumab, gives him and the committee assurance that treatment escalation is worthwhile for patients after their first COPD exacerbation.

Regarding the addition of a second biologic to the annual GOLD report — following dupilumab — Vogelmeier acknowledged that more biomarkers need to become established in COPD, in order to reflect the metrics of treatment success with modern therapy.

“Most of the treatment decisions that we make are based on clinical parameters,” Vogelmeier said. “We have to move on to biological parameters, so we have to go from phenotype to endotype.”

The concept of “disease stability,” added to the GOLD report, reflects the increasing opportunity to reduce COPD activity in patients with the wider armamentarium of treatments now available.

“There are now the first data suggesting when patients are stable over certain periods of time, their prognosis will get better,” Vogelmeier said. “And this is not only good as an end point for future studies, that we try to have a composite endpoint that tells us about disease stability or control — but in addition to that, it also tells us how we can communicate better with patients. If they are doing well, we should tell them. And as you know, wording is extremely important.”

Global Initiative for Chronic Obstructive Lung Disease. 2026 GOLD Report and Pocket Guide. Web page. Accessed November 14, 2025. https://goldcopd.org/2026-gold-report-and-pocket-guide/

Johnson V. FDA Approves Mepolizumab for Eosinophilic COPD. 

. Published online May 22, 2025. https://www.hcplive.com/view/fda-approves-mepolizumab-for-eosinophilic-copd

COPD is not a complex disease, Polverino explains. It's only complex to treat because of limited understanding.

The Practical Hurdles in COPD Detection, with Francesca Polverino, MD, PhD

 is heterogeneous and often laden with confounding symptoms and severe comorbidities. But that doesn’t mean it’s a complicated disease — its treatment is complicated because of our clinical shortcomings.

In the second segment of an interview with 

2025 Global Initiative for Chronic Obstructive Lung Disease (GOLD) International COPD Conference

 in Philadelphia, PA, this week, Francesca Polverino, MD, PhD, professor of pulmonary medicine at Baylor College of Medicine discussed the issue of practical limitations in refining the diagnosis, treatment, maintenance, and monitoring of COPD.

“We call COPD a complex disease because we don't understand it,” Polverino said. “But COPD is not a complex disease. We make it complex because we don't understand that all these phenotypes or endotypes that we observe in the clinic are all different diseases with different pathologies that should be treated all in different ways. And this is the importance of the biomarkers.”

 and utility; she also noted that there’s a lack of understanding around the disease’s clinical drivers and manifestations at the primary care level. She stressed that non-smokers and younger patients are being missed at the frontline because of common misconceptions around COPD risk.

“Usually when we get a patient [from primary care] after an exacerbation, that patient has been through a couple of rounds of oral corticosteroids already, which is a problem for the pulmonologist,” Polverino said.

Another recurring issue is the patient’s lack of urgency to get a diagnosis and initiate care — not always due to the common stigma associated with COPD, but sometimes because the disease is a slow burn.

Polverino has high expectations for COPD advancement in the coming decade. She believes Th1 inflammation-based biomarkers that correlate with the majority of patients with COPD — versus the more specific eosinophil biomarker — will emerge in research. The introduction of targeted therapies like dupilumab and mepolizumab have already shifted the perception of COPD from “untreatable” to potentially alterable. An influx of biomarkers may raise the bar for treatment even higher.

“We’re going to have radiology and radiomics to be used as a valid biomarker in COPD, together with other [new biomarkers] like CC16, and we are going to start paying attention to milder stages of the disease,” she said. “We are going to start including these people more in our trials, as well as non-smoking patients.”

Polverino F, Kunzmann K. Eosinophils, CC16, and the Role of COPD Biomarkers, with Francesca Polverino, MD, PhD. 

. Published online November 14, 2025. https://www.hcplive.com/view/eosinophils-cc16-copd-biomarkers-francesca-polverino-md-phd

Terzikhan N, Verhamme KM, Hofman A, Stricker BH, Brusselle GG, Lahousse L. Prevalence and incidence of COPD in smokers and non-smokers: the Rotterdam Study. Eur J Epidemiol. 2016;31(8):785-792. doi:10.1007/s10654-016-0132-z

Polverino stresses the need for prospective analysis to validate CC16 and mucus plugs as viable biomarkers for COPD status.

Eosinophils, CC16, and the Role of COPD Biomarkers, with Francesca Polverino, MD, PhD

It's a common misconception that there are no biomarkers available to determine 

 disease status. Both blood eosinophils and fraction exhaled nitric oxide (FeNO) serve as viable, if not each slightly limited, biomarkers in COPD. The real issue is the lack of clinical investigation into more potential biomarkers — an impasse that can delay the development of targeted therapies to treat COPD.

 in Philadelphia, PA, this week, Francesca Polverino, MD, PhD, professor of pulmonary medicine at Baylor College of Medicine, reviewed her session presentation on clinical markers of COPD that dictate therapeutic strategy. As Polverino explained, the simplistic measures of COPD type and status are currently robust: blood eosinophils, spirometry-based tests like forced vital capacity (FVC) and forced expiratory volume in 1 second (FEV

), FeNO , and radiomics help determine a patients’ classification and severity of COPD at any point of assessment.

But a lack of investigation into more promising biomarkers like mucus plugs and club cell protein (CC16) — both of which may help determine a patient’s true response to diverse therapy strategies — stalls targeted therapy development.

“I think [CC16] is next in line,” Polverino said. “All we need is a clinical trial in which CC16 is used prospectively…I think it’s going to be probably the most powerful biomarker in COPD, just because it relates to all patients with COPD, not just a subset of [type 2] COPD patients like eosinophils.”

Polverino referenced very recently published analysis from her and a team of colleagues showing a correlation between lowered CC16 levels and accelerated lung function decline and progression of emphysema. The findings even showed the biomarker’s ability to determine pediatric disease progression: children with lowered levels had correlative obstructive physiology and early small airway impairment.

There has been ample early data supporting the potential of CC16 and mucus plugs in determining COPD status; Polverino wants to see that potential be finally met.

Rojas-Quintero J, Faner R, Chiu CY, et al. Maternal Smoking and CC-16: Implications for Lung Development and COPD Across the Lifespan. Am J Respir Crit Care Med. Published online October 7, 2025. doi:10.1164/rccm.202504-0854OC

Lugugo N. Dupilumab Reduces Mucus Burden in Uncontrolled Asthma, with Njira Lugogo, MD. 

. Published October 22, 2025. https://www.hcplive.com/view/dupilumab-reduces-mucus-burden-uncontrolled-asthma-njira-lugogo-md

Kevin Kunzmann

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