Among current and former adult smokers, symptoms like productive cough, dyspnea, and exercise intolerance may be viewed as a part of normal aging, particularly among older former smokers. Smoking cessation may reduce respiratory symptom severity and slow the rate of lung function decline, but it does not eliminate progressive lung disease risk.

Few studies have assessed the effects of smoking on patients without COPD. A group of researchers has suspected that spirometry may be insensitive to early disease or subclinical lung pathology and that current and former cigarette smokers without spirometric evidence of COPD may have impairments in physical function, quality of life, and respiratory symptoms that can go untreated. High-resolution CT scanning in this patient population may demonstrate significant lung disease, but comprehensive data has been lacking.

Finding Hidden Lung Disease

“There are no disease-modifying treatments for patients identified with smoking-related lung disease,” explains Elizabeth A. Regan, MD, PhD, “but there are many treatments that improve their symptoms, allow them to breath better, enable them to exercise, and improve quality of life.” For a study published in JAMA Internal Medicine, Dr. Regan and colleagues set out to determine whether or not patients with a heavy smoking history, but who did not meet spirometric criteria for COPD, had hidden lung disease.

Dr. Regan and colleagues completed evaluations on more than 10,000 current and former smokers aged 45 to 80 with at least a 10 pack-year smoking history and a comparison group of more than 100 never smokers of similar ages. Evaluations included high-resolution chest CT scans, spirometry, 6-minute walking tests, and multiple questionnaires about respiratory symptoms, comorbidities, and quality of life. Their analysis focused on the 4,388 smokers who did not have evidence of obstruction on their spirometry.

Among patients with a heavy smoking history but normal spirometry results, more than half had respiratory-related impairments as determined by CT scans. “These patients have real disease,” says Dr. Regan. “It’s important that abnormalities were demonstrated on the CT scans because most clinicians are not likely to order a high-resolution CT scan for this patient population. Our findings suggest that doing so is worthwhile.”

Other Key Findings

When compared with never smokers, current and former heavy smokers without COPD by spirometry had worse quality of life. The results confirm that chronic smokers even without a diagnosis of COPD have many similar symptoms and limitations as COPD patients.  Among smokers, 15.0% had a 6-minute walking test result of 1,000 feet, compared with a rate of 4.0% observed among never smokers. CT scans also found that 42.3% of smokers had evidence of emphysema or airway thickening. Whereas current smokers had more respiratory symptoms, former smoking was associated with greater emphysema and gas trapping. Significant dyspnea was found in 23.5% of smokers, compared with just 3.7% of never smokers. Current and former smokers were also more likely to have one or more impairments (54.1% vs 24.1%).

“We also found that as people age, they increasingly stop smoking,” says Dr. Regan (Figure). “However, the lung disease that was triggered by the smoking exposure does not stop; it actually progresses with time. Although less than half of those aged 60 or older are smokers, the percentage of those who have emphysema and gas trapping increases with age.” Dr. Regan and colleagues hope their findings help debunk the myth of the healthy smoker as well as stress the importance of smoking prevention and cessation in preventing lung disease.

Important Implications

The study findings suggest that clinicians should ask their patients who are current and former smokers about respiratory symptoms during evaluations, according to Dr. Regan. “It’s worthwhile to ask these patients if they have chronic bronchitis or whether or not they’re short of breath,” she says. “Current smokers with these symptoms should be advised on the importance of smoking cessation. Informing patients about research showing that shortness of breath is a sign of real lung disease caused by their smoking could be more impactful than a vague suggestion to quit smoking.”

Looking Ahead

Dr. Regan explains that she and her colleagues have been following the study cohort by touching base via phone or email every 6 months. “Patients are now coming in for a second phase of visits after 5 years to undergo repeat CT scans, spirometry, and other testing to assess their progress,” she says. “Nearly 3,500 patients have come back, and we’re at the point where we can assess whether or not those identified as having disease are progressing. If the signs of early disease in this patient population predict a long-term impact, that will further stress the importance of early disease identification.”


Regan E, Lynch D, Curran-Everett, et al. Clinical and radiologic disease in smokers with normal spirometry. JAMA Intern Med. 2015. Jun 22 [Epub ahead of print]. Available at

The 2004 United States Surgeon General’s report: the health consequences of smoking. N S W Public Health Bull. 2004;15:107.

Mohamed Hoesein  F, de Hoop  B, Zanen  P, et al. CT-quantified emphysema in male heavy smokers: association with lung function decline. Thorax. 2011;66:782-787.

Kim  S, Yagihashi  K, Stinson  D, et al. Visual assessment of CT findings in smokers with nonobstructed spirometric abnormalities in the COPDGene study. Chronic Obstr Pulm Dis (Miami). 2014;1:88-96.