New therapies and devices for chronic obstructive pulmonary disease (COPD) were approved in 2020 and researchers continued to explore expanding the definition of disease beyond spirometry.
But 2020 was dominated by the struggles managing the care of highly vulnerable COPD patients during the COVID-19 pandemic.
COVID Paradox
The delivery of routine components of COPD care, such as lung function testing and pulmonary rehabilitation, came to a virtual halt in the spring as medical offices closed. Connecting patients to these services remained a challenge throughout the year even after those offices reopened.
“Almost all of my COPD patients have refused to come into the office. I see them remotely if I see them at all,” said David Mannino III, MD, of the University of Kentucky HealthCare in Lexington.
Pulmonary and critical care specialist MeiLan Han, MD, of Michigan Medicine in Ann Arbor, said that while telemedicine has plugged some of the gaps, remote access to key COPD services has not been available for the vast majority of patients.
“I have been struggling to find remote pulmonary rehabilitation for my patients. It has been a huge problem,” she told MedPage Today.
But despite these challenges, emerging research suggests patients with COPD may be doing better than expected during the pandemic.
A pooled analysis of studies examining COVID-19 prevalence in patients with chronic conditions found COPD patients to be under-represented among COVID-19 patients.
The analysis of 22 observational studies involving more than 11,000 patients hospitalized with COVID-19 found the prevalence of hypertension and diabetes (42% and 23%, respectively) to be much higher than COPD, which was reported in just 5% of patients.
COPD was associated with higher COVID-19 mortality in the study, presented at the CHEST 2020 virtual meeting.
“While one would expect patients with prior lung disease to have greater mortality with COVID-19, it is curious to see that the prevalence of COPD was lower than the general population and may reflect greater measures taken by COPD patients to avoid coronavirus exposure,” according to Vikramaditya Venkata and Gerard Kiernan, MD, of Dartmouth-Hitchcock Hospital in Keene, New Hampshire.
“We are seeing fewer patients hospitalized for COPD exacerbations, and, surprisingly, COPD patients also seem to be underrepresented among patients dying of COVID-19,” Han told MedPage Today. “This is certainly not because these patients are less susceptible. It is probably because they are being really, really cautious. They aren’t going anywhere right now. They aren’t seeing their grand-kids as much or socializing much in general.”
It has also been suggested that a treatment commonly used by patients with asthma and COPD may help protect them from developing severe COVID-19 when they become infected with SARS-CoV-2, said Mannino, who is also co-founder and a medical director for the COPD Foundation.
Inhaled corticosteroids are routinely used in the management of the chronic airway diseases, and systemic corticosteroids have been used to suppress the hyper-inflammatory state known as cytokine storm in patients with COVID-19.
“There is debate about whether inhaled steroids are protecting COPD patients,” Mannino said. “They may be, but I suspect it has more to do with the fact that patients with COPD are being extremely cautious and doing what they need to do to avoid getting COVID-19.”
FDA OKs Another Triple Tx; Rejects Mortality Claim
New treatments available for COPD patients in 2020 include a second fixed-dose, triple therapy, approved by the FDA in July.
AstraZeneca’s Breztri Aerosphere (budesonide/glycopyrrolate/formoterol fumarate) was approved based on the phase III ETHOS clinical trial findings, which showed a reduction in COPD exacerbations among symptomatic patients who had experienced exacerbations within the past year.
GlaxoSmithKline’s (GSK) Trelegy Ellipta (fluticasone furoate, umeclidinium, vilanterol) became the first fixed-dose, triple therapy available for use by COPD patients in the U.S., with its FDA approval in the fall of 2017.
While increasing survival was not a primary endpoint in clinical trials of either drug, a post-hoc analysis of IMPACT trial data showed signals of reduced all-cause mortality in patients treated with Trelegy Ellipta versus fluticasone furoate/vilanterol dual therapy (hazard ratio 0.72 for death, 95% CI 0.53-0.99, P=0.042 vs HR 8.89, 95% CI 0.67-1.16, P=0.387).
Based on these findings, GSK petitioned the FDA to include an all-cause mortality-risk reduction claim on the labeling of it’s COPD fixed-dose, triple therapy, but an advisory committee for the agency voted 14-1 against the move in August, citing lack of evidence supporting the claim.
In January, the FDA approved a novel lung expansion tandem therapy developed by Monaghan Medical Corporation that combines positive expiratory pressure and positive airway pressure devices into a single, handheld device for airway clearance.
Approval was also granted for NuvoAir’s Air Next hand-held, home-use spirometer, which can be connected to iOS and Android devices via Bluetooth.
In June, the FDA granted breakthrough therapy status to a novel lung denervation system developed by Nuvaira. The bronchoscopic treatment is designed to disrupt pulmonary nerve input to the lung with the aim of reducing the neural hyperactivity associated with airway hyper-responsiveness.
The non-surgical procedure involves mechanical disruption of the vagus nerves of the lung using a specialized catheter delivered via bronchoscope to the distal mainstem bronchi. After confirmation of positioning, the catheter is repeatedly rotated to achieve ablation along the external wall of the main airways.
In the AIRFLOW clinical trial, patients with symptomatic COPD treated with targeted lung denervation combined with optimal pharmacotherapy had fewer study-defined respiratory adverse events, including hospitalizations for COPD exacerbation.
Rethinking the Definition of COPD
The emphasis on identifying COPD subtypes has the potential to transform diagnosis and treatment of the disease, Mannino said.
“There has been a lot of talk over the last year about new approaches to how we define COPD,” Mannino said. “Measuring lung function has worked well for many, but we also see patients regularly who don’t necessarily fit that strict spirometric definition. They have a lot of symptoms, but don’t have spirometric impairment.”
The COPDGene Study is the largest study ever to examine the genetic factors associated with COPD susceptibility, with a goal of better characterizing specific COPD subtypes.
Researchers have enrolled more than 10,000 COPD patients from 21 sites located across the U.S.
An analysis of a decade’s worth of chest imaging, spirometry, and molecular data from the COPDGene cohort using machine learning, was a leap forward for characterizing COPD subtypes.
Among the main findings:
- The analysis suggested that most manifestations of COPD “occur along a continuum, which explains why continuous aspects of COPD or disease axes may be more accurate and reproducible than subtypes identified through clustering methods,” the researchers wrote.
- COPD phenotypes identified or prioritized through machine learning methods have led to novel biological discoveries, including novel emphysema genetic risk variants and systemic inflammatory subtypes of COPD.
- Trajectory-based COPD subtyping “captures differences in the longitudinal evolution of COPD, addressing a major limitation of clustering analyses that are confounded by disease severity.”
“Ongoing longitudinal characterization of subjects in COPDGene will provide useful insights about the relationship between lung imaging parameters, molecular markers, and COPD progression that will enable the identification of subtypes based on underlying disease processes and distinct patterns of disease progression, with the potential to improve the clinical relevance and reproducibility of COPD subtypes,” wrote COPDGene investigator Peter Castaldi, MD, of Brigham and Women’s Hospital in Boston, and colleagues.
Last Updated December 04, 2020