1 of 5 | Dr. Norman Edelman, a pulmonologist and professor of internal medicine at Stony Brook University in Stony Brook, N.Y., describes how lungs function using a 3D model at the pulmonary clinic at Advanced Specialty Care at Lake Grove, N.Y. Photo by John Griffin/Stony Brook University
NEW YORK, Sept. 20 (UPI) -- Recent advances in chronic obstructive pulmonary disease offer patients more hope in easing discomfort from a condition that can cause severe airflow blockage and breathing-related problems.
The umbrella of diseases, which includes emphysema and bronchitis, is the third-leading cause of global mortality, accounting for more than 3 million deaths in 2019, according to the latest statistics from the World Health Organization.
"COPD makes breathing difficult for the 16 million Americans who have this disease. Millions more people suffer from COPD, but have not been diagnosed and are not being treated. Although there is no cure for COPD, it can be treated," according to the Centers for Disease Control and Prevention.
The progressive damage to lung tissue from COPD can't be repaired with current treatments, but it can be alleviated with bronchodilators -- medicines that widen the airways to improve airflow. Newer formulations of drugs have appeared in recent years, while others are in late-stage clinical trials.
And now, transplanting patients' own lung cells offers hope of a cure for COPD. In a recent early-stage clinical trial, 17 patients with COPD who underwent this experimental treatment could breathe better, walk farther and enjoy a better quality of life.
"For the first [time] in human history, we showed that the extremely severe COPD patients could be treated by lung progenitor cell transplantation. [Progenitor cells are early descendants of stem cells.] And the efficacy looks quite promising in this Phase I trial," the study's corresponding author, Wei Zuo, told UPI via email.
Zuo is a professor in the School of Medicine at Tongji University in Shanghai and the chief scientist at Regend Therapeutics Ltd. in China.
Cells infused into lungs
In the study, researchers removed lung cells with a brush from COPD patients by passing a scope into the lungs. The specific kind of lung stem cell, p63+, was isolated and cultured. From the cultures, millions of these stem cells were infused back into lungs of the patients.
"We are currently working on a Phase II clinical trial in China, and we are also looking for collaborators in U.S. and Europe," Zuo said. "Hopefully, the first COPD cell therapy could be approved by authorities within two to three years."
Despite its prevalence, COPD is "an underappreciated health problem," said Dr. Norman Edelman, a pulmonologist at Stony Brook Medicine, professor of internal medicine and core member of the public health program at Stony Brook University in Stony Brook, N.Y.
"Before COVID-19, COPD and other less important diseases of the lung were actually the third-leading cause of death after cancer and heart disease. I'm not sure the general public sees it as threatening as heart attacks or cancer," Edelman told UPI in a telephone interview.
Some scientists consider stem cell therapy to be "the holy grail of modern medicine," Edelman said. Stem cells are "an exciting idea if we can actually regrow new lung tissue," but "this is really, really early stuff. I'm not ready to call this a breakthrough."
Older therapies studied
A number of trials are examining the efficacy of new formulations of older types of therapies, as well as novel options, Dr. Joshua Malo, a pulmonologist and an associate professor at the University of Arizona College of Medicine-Tucson. told UPI via email.
"COPD is a complex disease, and many inflammatory pathways have been identified as potential therapeutic targets and are currently being studied. Some of these studies involve medications that are already approved for other diseases such as asthma," Malo said.
Among the asthma medications studied for COPD is Dupixent, which had been used off-label in COPD patients with a specific type of inflammation as evaluated by a common blood test.
This specific subtype of inflammatory COPD accounts for roughly 20% to 40% of COPD cases, Dr. Jessica Kuppy told UPI via email.
Kuppy is a pulmonologist and critical care specialist at Rush University System for Health and an assistant professor at Rush Medical College in Chicago. She also is associate director of the critical care medicine fellowship training program.
A major Phase 3 trial of Dupixent involving patients with "smoker's lung" demonstrated a 30% decrease in episodes of worsening symptoms associated with COPD.
Dupixent also improved lung function, quality of life and respiratory symptoms, its joint manufacturers, Sanofi and Regeron Pharmaceuticals, said in seeking Food and Drug Administration approval for the COPD indication.
The results were presented at the 2023 American Thoracic Society International Conference and published in the New England Journal of Medicine.
Another tool for treatment
Although Malo said Dupixent "is unlikely to be a major game-changer," he noted that the drug adds "another tool for the treatment of COPD for patients with symptoms and exacerbations that are difficult to control."
Kuppy was more enthusiastic about Dupixent's potential for that purpose. "It is exciting to see how much promise it has shown in patients with COPD," she said.
Similarly, ensifentrine by Verona Pharma, is described as a novel, inhaled therapeutic aimed at blocking certain inflammatory pathways that may lead to airway spasm and mucus production.
A Phase III trial showed that blocking these pathways decreases exacerbations, and some patients even had a slight improvement in lung function.
"I hope both dupilumab and ensifentrine will be making their way to market soon for patients with COPD," Kuppy said. She noted that the chance to reverse damage with lung cell transplantation also sounds appealing.
Daliresp, a once-daily tablet approved by the Food and Drug Administration in 2011, "operates in a similar fashion" to ensifentrine, Malo said.
"There certainly is promise that we may have an expanded armamentarium of medications available to help manage COPD, although it remains unclear how many of these therapies will be effective and to what degree they will be effective," he said.
"It is likely that many of these will have some role in minimizing symptoms and reducing exacerbations. Identifying who will benefit and to what degree is the goal" of clinical trials.
Triple-therapy inhalers an option
Other options include triple-therapy inhalers -- Trelegy Ellipta, approved by the FDA in 2017 for the treatment of appropriate patients with COPD and Breztri Aerosphere, approved in 2020.
The combination of three medications in one inhaler helps control symptoms of COPD when taken regularly. But they aren't a substitute for a rescue inhaler and don't relieve sudden breathing problems, doctors warn.
"In general, triple therapy using two bronchodilators and a steroid has been shown to give improved control of symptoms and a decreased amount of COPD exacerbations-that is, flare-ups," pulmonologist Edelman said.
Even though these inhalers use new formulations of older classes of medicine, they "are very useful in simplifying the regimen for patients." Acting as controller medicines, they previously required at least two different inhalers, often multiple times daily, Malo said.
"By combining those into medications into a single inhaler, these combinations make it more likely that patients will be able to adhere to and benefit from these controller medications," he said.
Beyond these options, "drugs that have revolutionized the treatment of cystic fibrosis, called CFTR modulators, also are an intriguing option for the treatment of certain patients with COPD," pulmonologist Malo said.
According to Cystic Fibrosis News Today, "these therapies work to increase the functionality of a protein, known as CFTR, whose production is disrupted in cystic fibrosis."
Current treatment is still aimed at managing symptoms and improving quality of life. Often, patients can be managed with inhalers and chronic oxygen use, pulmonologists said.
"For some patients with a lot of emphysema, we used to cut away severely affected parts of the lung to help them breathe better," Kuppy said.
However, "more recently, we have developed one-way valves placed within the airway itself to close off those highly affected parts of the lung, greatly reducing the need for surgery. Sometimes, lung transplant may be considered for certain highly affected individuals who meet eligibility requirements."
COPD is more common in older individuals. But "older" is a relative term because lung age can differ from someone's actual age, Dr. Charlie Strange, a professor of pulmonary medicine at the Medical University of South Carolina in Charleston. told UPI via email.
"I think of this concept [as] similar to wrinkles on the skin. If we stay out of the sun and use sunscreen, then the skin at age 70 can still look great," he said. "If the lungs see lots of smoke and particles of dust and fumes, then premature aging is the disease of COPD. "
Cigarette smoke is responsible for most cases of COPD. "Compared to never smokers, COPD rates are seven times higher among current smokers and five times higher among former smokers," according to the American Lung Association. Vaping can cause COPD as well, Kuppy noted.
Premature birth, childhood respiratory infections and genetics also contribute to the lung and airway injury of COPD, Strange said.
He added that the lungs continue to grow in size until age 20. "If there is lung disease, the push to grow new lung structure would be a great advance," he said of the new study. "This report in 17 patients is a first step that adds some excitement."