Bronchodilators do not improve smoking-related respiratory symptoms in people without COPD

News release

Sunday, September 4, 2022

Researchers supported by the National Institutes of Health found that dual bronchodilators — long-acting inhalers that relax the airways and make breathing easier — don’t help much in people who don’t have chronic obstructive pulmonary disease (COPD) but who have respiratory symptoms and a history of smoking.

COPD, a lung disease that blocks the airways and causes coughing, wheezing and shortness of breath, affects about 15 million Americans. However, millions of others who smoke or have smoked and have some symptoms of COPD are also prescribed bronchodilators.

“We hypothesized that these drugs worked in patients who did not meet the lung function criteria for COPD, but we had never tested,” said MeiLan K. Han, MD, principal investigator and first author of the study. “Now we know that these existing drugs don’t work for these patients.”

The results of the study, funded by the National Heart, Lung, and Blood Institute (NHLBI), were published in New England Journal of Medicine and simultaneously presented at the International Congress of the European Respiratory Society.

According to scientists, the consequences are significant. First, they show the importance of diagnosing lung conditions through spirometry, a lung function test that Hahn noted is underutilized in clinical practice. Second, they demonstrate the need for new, effective therapies for patients without COPD.

Inhalers have long been the main treatment for these patients, she explained, because doctors either assume the patient has COPD or, if they don’t, that their smoking-related symptoms can be helped by inhalers. But while smoking causes a wide range of lung damage, the study showed that bronchodilator therapy only helped patients with enough lung damage that would cause abnormal spirometry readings.

In the 12-week, randomized, double-blind trial, which was part of the Redefining Early COPD Therapy for the Lung Research Collaborative (RETHINC), researchers enrolled 535 adults with COPD symptoms, aged 40-80 years, on one of 20 American Medical Centers. Twice a day, study participants used an inhaler that contained either a drug or a placebo.

By the end of the trial, some adults in the drug (intervention) and placebo (control) groups had noticed slight respiratory improvements – this could mean they coughed less, produced less phlegm or felt less winded – which was rated through st. George’s Respiratory Questionnaire. However, the researchers found no significant differences between those receiving drugs or placebo. They reported that 56% (128 of 227) of participants who received the drug saw improvements in respiratory symptoms, compared with 59% (144 of 244) of those who received a placebo.

According to Hahn, these data highlight why we can’t keep doing what we’ve been doing, which is not doing spirometry and just treating patients with the same COPD drugs and expecting to see improvement.

Antonello Punturieri, M.D., Ph.D., program director of the NHLBI’s Chronic Obstructive Pulmonary Disease/Environment Program, said the spirometry test should be used for any patient who shows signs of COPD, airflow obstruction, or who has a history of smoking cigarettes. Although spirometry readings are used during about one-third of COPD-related medical visits, approximately half of patients who meet criteria for COPD remain undiagnosed.

Helping patients quit smoking is a major way to prevent COPD or COPD-like symptoms, the study notes. More than 30 million adults smoke, according to the Centers for Disease Control and Prevention, and many who are not diagnosed with COPD share symptoms. About one in four current or former smokers without COPD report having shortness of breath. In addition to encouraging smoking cessation, doctors can help patients who do not meet the lung function criteria for COPD by working with them to address other underlying problems, such as overweight and obesity, heart failure, or other lung problems .

“In the meantime, research should focus on finding new treatments for them,” Hahn explained. “The next question is can we develop more targeted therapies for these patients who are on the milder end of the spectrum?”

“Because cough and mucus production are prominent among these patients, we believe that therapies that target airway mucus production may be effective,” said Prescott G. Woodruff, MD, principal investigator. and senior author of the study.

Some of these therapies are already in development, and data from other studies may offer insight into the biological causes of excessive mucus in the airways. These clues could help researchers identify additional therapies.

To learn more about lung health, visit

To learn about RETHINC and the Pulmonary Trials Cooperative, visit

About the National Heart, Lung, and Blood Institute (NHLBI): NHLBI is a global leader in conducting and supporting research in heart, lung and blood diseases and sleep disorders that advances scientific knowledge, improves public health and saves lives. For more information, visit

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Han MK, Ye W, Wang D, et al. Bronchodilators in subjects with symptomatic tobacco exposure with preserved spirometry for the RETHINC Study Group. N Engl J Med. 2022; doi: 10.1056/NEJMoa2204752.


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