In a finding that could lead to better treatment of smoking-related lung diseases, a group of scientists from institutions across the country—including the University of Iowa—is reporting that about half of current or former smokers have respiratory symptoms similar to COPD and an increased risk for exacerbations or “flare-ups” of their symptoms, despite having normal lung function and not yet having received a COPD diagnosis.
Many of these individuals show COPD-like symptoms, such as shortness of breath and difficulty exercising. They also have a high rate of respiratory medication use, despite a lack of data from clinical trials about what appropriate treatment should be for this particular patient population.
In addition to raising the question about whether the definition of COPD should be adjusted, the researchers say that the study highlights a large, understudied patient population that might nevertheless benefit from early treatment intervention. Their study, published May 11 in the New England Journal of Medicine, was funded by both the National Heart, Lung, and Blood Institute (NHLBI) and the Foundation for the National Institutes of Health (FNIH).
COPD, or chronic obstructive pulmonary disease, is the third leading cause of death in the United States. It is a progressive lung disease that makes it hard to breathe. Cigarette smoking is the the most common cause of COPD. Though researchers estimate that millions of Americans have COPD, many who have the disease do not know it. The condition is currently diagnosed using spirometry, a test that measures how much air you breathe out and how fast. Researchers have long observed that some current and former smokers appear to have respiratory symptoms associated with COPD—such as coughing and shortness of breath—despite having normal spirometry test results. However, the extent and clinical implications of the problem weren’t known until now.
The current study’s research team, led by scientists at several institutions, including the University of California at San Francisco and the University of Michigan, conducted an observational study called SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study) that included patient data collected between 2010 and 2015. The scientists examined respiratory symptoms and measured lung function with spirometry among 2,736 participants—current or former smokers aged between 40 and 80 years old, as well as controls who had never smoked. They found that respiratory symptoms were present in about half of the current or former smokers, despite normal spirometry readings. These participants had an increased rate of exacerbations or “flare ups” of their symptoms. Using computed tomographic (CT) imaging scans of the lung—overseen by the SPIROMICS Radiology Center at the University of Iowa and analyzed at the VIDA Diagnostics Core Lab in the Bioventures Center of the University of Iowa—the researchers also found a high incidence of thickening of the airways, a sign of lung disease.
“These findings demonstrate that there is a large group of smokers who have COPD symptoms, including associated flare-ups, who have gone unclassified because of the reliance on pulmonary (lung) function tests. The study shows that quantitative CT scans can provide insights into underlying lung disease processes and suggests that lung function tests should not necessarily serve as the only test for diagnosing COPD and guiding treatment,” says Eric Hoffman, director of the Advanced Pulmonary Physiomic Imaging Laboratory (APPIL) within the UI Health Care Department of Radiology, home to the SPIROMICS Radiology Center.
Hoffman says the CT scans were important in this study because they were able to detect lung abnormalities even when the standard pulmonary function tests performed on each of the smokers were normal. Additionally, the scans helped differentiate between airway disease—the airway wall thickening—and emphysema. Hoffman says CT scans may provide a mechanism for following disease progression, in addition to identifying targets for treatment. CT imaging may also be useful for assessing outcomes associated with interventions.
About APPIL and VIDA
The Advanced Pulmonary Physiomic Imaging Laboratory, part of the Department of Radiology at the University of Iowa’s Carver College of Medicine, is an internationally recognized leader in the field of quantitative lung imaging. The laboratory has served as the radiology center for a growing number of national and international multi-center studies for which lung imaging was a major component of the protocol; more than 30,000 data sets have been sent to the laboratory for quality assessment and quantification. Hoffman and his research group have worked on lung imaging methods for nearly 40 years, and he has led lung imaging research at the UI for 24 of them. Standard pulmonary function testing has lumped many diseases into single entities and masked the presence of others. Imaging is allowing physicians to identify disease processes early and differentiate them from one another, thus providing hope for better, earlier treatment.
APPL was able to install a state-of-the-art CT scanner built by Siemens and known as the Somatom Force through a $2 million grant from the National Institutes of Health and support by the University of Iowa. The device enables researchers to generate CT images with up to 10 times less x-ray exposure to the patient, bringing the dose down to the equivalent of a pair of more traditional chest films while maintaining the high image quality necessary for research like the current study. With this scanner in place, the UI laboratory is in the process of establishing a new set of protocols that will be implemented in future investigations.
VIDA Diagnostics, Inc., is a company that evolved out of the University of Iowa and currently resides in the UI’s Oakdale Campus research park. VIDA provides software for the visualization and assessment of CT lung imaging and a core lab that provides the quality control and oversight. The company was founded by Eric Hoffman, along with colleagues Milan Sonka (electrical and computer engineering), Joseph Reinhardt (biomedical engineering), and Geoffrey McLennan (pulmonary medicine). McLennan passed away in 2010.
Disclosure: The founders remain shareholders within VIDA Diagnostics.