Symptomatic TEPS Not Associated With Accelerated Decline in Lung Function

Those with symptomatic TEPS experienced significantly more respiratory exacerbations over 5.8 years of follow-up vs those with asymptomatic TEPS.

Patients with symptomatic tobacco exposure and preserved spirometry (TEPS) did not have a faster decrease in lung function compared with those with asymptomatic TEPS, according to study findings published in JAMA.

Researchers reported findings from SPIROMICS II ( Identifier: NCT01969344), a longitudinal study that characterized the spirometry findings of individuals who currently or previously smoked cigarettes and have respiratory symptoms without airflow obstruction. Notably, SPIROMICS II is a longitudinal extension study of SPIROMICS I, which enrolled participants aged 40 to 80 years who had current or former tobacco use for longer than 20 pack-years as well as a control group of participants without a history of smoking or lung disease.

SPIROMICS II included participants who consented to undergo at least 3 additional years of follow-up to assess whether those with symptomatic TEPS had an accelerated rate of decline in forced expiratory volume in the first second (FEV1), developed chronic obstructive pulmonary disease (COPD) defined by spirometry, had an increased pulmonary symptom burden and respiratory exacerbations, and had progression of computed tomography-derived measures of disease associated with COPD vs those with asymptomatic TEPS.

For the current study, participants had 1 in-person visit at 5 to 10 years after their baseline visit in SPIROMICS I and were contacted by phone every 4 months.

Symptomatic TEPS was defined as currently or previously smoking cigarettes and having a history of smoking for longer than 20 pack-years, a normal postbronchodilator spirometry ratio (FEV1: forced vital capacity [FVC] >0.70) at their baseline visit in SPIROMICS I, and a COPD Assessment Test score of 10 or greater.

Participants with symptomatic TEPS did not have accelerated rates of decline in FEV1 or increased incidence of COPD vs those with asymptomatic TEPS….

A total of 1397 participants were included in SPIROMICS II; 226 had symptomatic TEPS (mean [SD] age, 60.1 [9.8] years; 59% women) and 269 had asymptomatic TEPS (mean age, 63.1 [9.1] years; 50% women). In the cohort with mild to moderate COPD, 459 participants (mean age, 65.2 years) were symptomatic, 279 (mean age, 67.8 years) were asymptomatic, and 164 (mean age, 56.8 years) never smoked.

After a median follow-up of 5.76 years, FEV1 declined by -31.3 mL/y for participants with symptomatic TEPS vs -38.8 mL/y for those with asymptomatic TEPS (between-group difference, -7.5 mL/y; 95% CI, -16.6 to 1.6 mL/y). The participants who had symptomatic mild to moderate COPD had a rate of FEV1 reduction of 42.3, which was significantly increased vs the rate of 31.3 in those with symptomatic TEPS (between-group difference, 11.1 mL/y; 95% CI, 2.8-19.3 mL/y; P =.009 in model 1).

The cumulative COPD incidence (postbronchodilator FEV1: FVC <0.70) was 33.0% in participants with symptomatic TEPS vs 31.6% in those with asymptomatic TEPS (hazard ratio [HR], 1.05; 95% CI, 0.76-1.46).

The mean COPD Assessment Test score in the symptomatic TEPS group was decreased slightly but remained 10 or greater and was increased in the asymptomatic TEPS group but remained at less than 10 during follow-up.

Acute and severe acute respiratory exacerbations were greater in number among participants with symptomatic mild to moderate COPD (0.39 per person-year) and those with symptomatic TEPS (0.23 per person-year). Participants with symptomatic TEPS had a significantly greater rate of respiratory exacerbations vs those with asymptomatic TEPS (0.23 vs 0.08 exacerbations per person-year, respectively; rate ratio [RR], 2.38; 95% CI, 1.71-3.31; P <.001) and participants in the control group (0.03 exacerbations per person-year; RR, 6.77; 95% CI, 4.04-11.34; P <.001).

Among several limitations, the population included participants aged 40 to 80 years and selection and recall bias are possible. Also, COPD Assessment Test scores may have been affected by upper respiratory tract infections.

“Participants with symptomatic TEPS did not have accelerated rates of decline in FEV1 or increased incidence of COPD vs those with asymptomatic TEPS, but participants with symptomatic TEPS did experience significantly more respiratory exacerbations over a median follow-up of 5.8 years,” the investigators concluded.

Disclosure: Support was provided by contributions made to the Foundation for the National Institutes of Health and the COPD Foundation from numerous industry sources. Some of the study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures and industry supporters.


McKleroy W, Shing T, Anderson WH, et al. Longitudinal follow-up of participants with tobacco exposure and preserved spirometry. JAMA. 2023;330(5):442-453. doi:10.1001/jama.2023.11676