Long-term smokers have respiratory symptoms not evident on spirometry

Key takeaways:

• A portion of adults who smoked/currently smoke displayed respiratory symptoms but had normal spirometry.
• These adults more frequently experienced respiratory exacerbations.

Despite normal spirometry results, some adults with more than 20 pack-years of smoking display respiratory symptoms and experience more exacerbations than asymptomatic smokers, according to results published in JAMA.

“The main impact of the findings is the recognition that a large percentage of people with tobacco exposure have a chronic lung condition associated with symptoms, activity limitations and exacerbations (‘flares’) that is currently poorly recognized,” Prescott G. Woodruff, MD, MPH, professor of medicine and division chief of pulmonology, critical care, allergy and sleep medicine at the University of California, San Francisco, told Healio. “We need to continue to emphasize avoiding or quitting smoking and lung function testing, but we also need to study this group better to develop treatment strategies.”

In the prospective SPIROMICS II cohort study, Woodruff and colleagues analyzed 1,397 adult smokers with more than 20 pack-years to evaluate how the rate of lung function decline differed between those with symptomatic tobacco exposure — such as shortness of breath, decreased exercise ability and daily cough and phlegm — and preserved spirometry (TEPS) and those without TEPS symptoms.

These adults had attended yearly visits that involved spirometry, 6-minute walk distance testing, the COPD Assessment Test and chest CT as part of the SPIROMICS I cohort study for 3 to 4 years, with follow-up testing occurring 5 to 7 years following enrollment as part of SPIROMICS II. Further, every 4 months, researchers called patients to record any respiratory symptoms and exacerbations.

Symptom prevalence, lung function decline

Within the total cohort, 226 adults (mean age, 60.1 years; 59% women; 38% Black) had symptomatic TEPS, represented by a COPD Assessment Test score of 10 or higher, whereas 269 adults (mean age, 63.1; 50% women; 15% Black) had asymptomatic TEPS, or a COPD Assessment Test score less than 10. Both groups had a normal postbronchodilator FEV₁/FVC ratio of greater than 0.7.

More adults reported current smoking in the symptomatic group vs. the asymptomatic group (58% vs. 34%).

When evaluating lung function, researchers found that adults with symptomatic TEPS had a lower yearly rate of decline in FEV₁ compared with adults with asymptomatic TEPS (–31.3 mL/year vs. –38.8 mL/year) at median follow-up of 5.76 years. Notably, compared with noncurrent smokers, current smokers in both groups had greater decreases in FEV₁.

Further, yearly FEV₁ decline was significantly greater among adults with symptomatic mild to moderate COPD (n = 459) vs. adults with symptomatic TEPS (42.3 mL/year vs. 31.3 mL/year; P = .009).

COPD incidence, exacerbations

Symptomatic TEPS adults had a comparable rate of COPD incidence to asymptomatic adults (33% vs. 31.6%; HR = 1.05; 95% CI, 0.76-1.46), which Woodruff told Healio was surprising.

“We were surprised that those with tobacco exposure, preserved spirometry and symptoms did not progress more rapidly to COPD than those without symptoms,” Woodruff said. “We expected that the condition was simply a precursor to COPD. Instead, we found that it is a persistent condition that appears to be distinct from COPD.”

Similar to lung function decline, current smokers in both groups faced a higher risk for COPD development compared with noncurrent smokers (HR = 1.95; 95% CI, 1.27-2.98). Black adults also faced a greater risk for COPD compared with white adults (HR = 2.15; 95% CI, 1.39-3.35).

Although researchers found no differences in 6-minute walk distance between those with symptomatic TEPS and those with asymptomatic TEPS, the distance achieved in this time was shorter among symptomatic adults.

Respiratory exacerbations also occurred more frequently among those with symptomatic TEPS (0.23 vs. 0.08 exacerbations per person-year; RR = 2.38; 95% CI, 1.71-3.31), which translated to more ED visits or hospitalizations for severe exacerbations (31.4% vs. 6.3%).

In terms of CT-derived measures of lung disease, researchers observed no significant differences between either group in Pi10 (marker of proximal airway disease), emphysema and parametric response mapping of functional small airway disease.

“The population we studied was older (age 40 to 80 years),” Woodruff told Healio, “We are currently doing a similar study in younger people (age 30 to 55 years) to understand the significance of symptoms of tobacco-exposed people in a younger population called the SOURCE study (the SPIROMICS study of Early COPD Progression).

“Future studies should include symptomatic TEPS in clinical trials or dedicate clinical trials specifically to symptomatic TEPS,” Woodruff added. “They are currently excluded from most clinical trials because they do not meet the definition of COPD.”

Reference:

• Millions of long-term smokers have lung disease that defies diagnosis. https://www.ucsf.edu/news/2023/08/425896/millions-long-term-smokers-have-lung-disease-defies-diagnosis. Published Aug. 1, 2023. Accessed Aug. 1, 2023.

For more information:

Prescott G. Woodruff, MD, MPH, can be reached at prescott.woodruff@ucsf.edu.