Journal article
Phenotypes and Trajectories of Tobacco-exposed Persons with Preserved Spirometry: Insights from Lung Volumes
Annals of the American Thoracic Society, Vol.22(4), pp.494-505
04/2025
DOI: 10.1513/AnnalsATS.202405-527OC
PMCID: PMC12005044
PMID: 39586032
Abstract
Background-Among tobacco-exposed persons with preserved spirometry (TEPS), we previously demonstrated that different lung volume indices, specifically elevated total lung capacity (TLC) versus elevated ratio of functional residual capacity-to-TLC (FRC/TLC), identify different lung disease characteristics in the COPDGene cohort. Objective-Determine differential disease characteristics and trajectories associated with the lung volume indices among TEPS in the SPIROMICS cohort. Methods-We categorized TEPS (n=814) by tertiles (low, intermediate, high) of TLC or residual volume-to-TLC (RV/TLC) derived from baseline CT images, and then examined clinical and spirometric disease trajectories in mutually exclusive categories of participants with high TLC without high RV/TLC ([TLC]high) versus high RV/TLC without high TLC ([RV/TLC]high). We examined differences in CT-measured emphysema (HU≤-950; PRMEMPH), airway trapping (HU≤-856; PRMfSAD; DPMGasTrap), and airway geometry (Pi10), respiratory symptoms (mMRC; CAT; SGRQ; SF12), and outcomes (annualized exacerbation rate) between the two categories at baseline and over follow-up time up to 8.5 years, using regression modeling adjusted for age, sex, height, weight, and smoking status (current versus former) and burden (pack-years). Results-In TEPS participants, the pattern of spirometric disease progression differed between [TLC]high and [RV/TLC]high: increased FVC with stable FEV1 in [TLC]high versus unchanged FVC but nominally decreased FEV1 in [RV/TLC]high. Compared to [TLC]high, TEPS with [RV/TLC]high had less emphysema (by HU≤-950) but more airway disease (by HU≤-856; PRMfSAD; DPMGasTrap, and Pi10), more respiratory symptoms (by mMRC; CAT; SGRQ; SF12), and more severe exacerbations at baseline. Over an average follow-up time of 4.1±2.4 years (range: 0.5 to 8.5 years), [RV/TLC]high TEPS also had higher likelihood of developing more severe spirometric disease (PRISm or GOLD-2) and worsening of their respiratory symptoms (by CAT and SGRQ). Although the incidence rates of respiratory exacerbations, hospitalizations, and mortality were not different between the two categories over the follow-up time, [RV/TLC]high TEPS were more likely to have been placed on a respiratory inhaler at their last follow-up visit. Conclusions-In these TEPS from SPIROMICS cohort, lung volume stratification by TLC versus RV/TLC identifies two pre-COPD phenotypes with distinct respiratory symptoms, radiographic features, and clinical trajectories. The characteristics of these pre-COPD phenotypes match those previously described from COPDGene cohort using TLC versus FRC/TLC stratification.
Details
- Title: Subtitle
- Phenotypes and Trajectories of Tobacco-exposed Persons with Preserved Spirometry: Insights from Lung Volumes
- Creators
- Mehrdad Arjomandi - University of California, San FranciscoSiyang Zeng - University of California, San FranciscoIgor Barjaktarevic - University of California, Los AngelesEugene R. Bleecker - Mayo Clinic in ArizonaRussell P. Bowler - Cleveland ClinicGerard J. Criner - Temple UniversityAlejandro P. Comellas - University of IowaDavid J. Couper - University of North Carolina at Chapel HillJeffrey L. Curtis - Michigan MedicineMark T. Dransfield - University of Alabama at BirminghamM. Bradley Drummond - University of North Carolina at Chapel HillSpyridon Fortis - University of Iowa Hospitals and ClinicsMeiLan K. Han - Michigan MedicineNadia N Hansel - Johns Hopkins UniversityEric A. Hoffman - University of IowaRobert J Kaner - Cornell UniversityRichard E Kanner - University of UtahJerry A Krishnan - University of Illinois ChicagoWassim Labaki - University of MichiganVictor E. Ortega - Mayo Clinic in ArizonaStephen P. Peters - Wake Forest UniversityStephen I. Rennard - University of Nebraska at OmahaChristopher B. Cooper - Harbor–UCLA Medical CenterDonald P. Tashkin - University of California, Los AngelesRobert Paine - University of UtahPrescott G. Woodruff - University of California, San Francisco
- Resource Type
- Journal article
- Publication Details
- Annals of the American Thoracic Society, Vol.22(4), pp.494-505
- DOI
- 10.1513/AnnalsATS.202405-527OC
- PMID
- 39586032
- PMCID
- PMC12005044
- NLM abbreviation
- Ann Am Thorac Soc
- ISSN
- 2329-6933
- eISSN
- 2325-6621
- Publisher
- AMER THORACIC SOC
- Grant note
- Flight Attendant Medical Research Institute: CIA190001 California Tobacco-Related Disease Research Program: T29IR0715 U.S. National Library of Medicine training grant: T15LM007442 National Heart, Lung, and Blood Institute (NHLBI): HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, HHSN268200900020C NHLBI: U01 HL137880, U24 HL141762, R01 HL182622, R01 HL144718 AmgenAstraZeneca/MedImmuneBayerBellerophon TherapeuticsBoehringer-Ingelheim Pharmaceuticals, Inc.Nycomed GmbHChiesi Farmaceutici S.p.A.PolareanForest Research Institute, IncProterixBioGenentechRegeneron Pharmaceuticals, Inc.GlaxoSmithKlineSanofiGrifols Therapeutics, IncSunovionIkaria, IncTakeda Pharmaceutical CompanyMGC DiagnosticsTheravance Biopharma and Mylan/ViatrisNovartis Pharmaceuticals Corporation
Supported by grants from the Flight Attendant Medical Research Institute (CIA190001; to M.A.) and the California Tobacco-Related Disease Research Program (T29IR0715; to M.A.) , and by a U.S. National Library of Medicine training grant (Award No. T15LM007442; to S.Z.) . SPIROMICS was supported by National Heart, Lung, and Blood Institute (NHLBI) contracts (HHSN268200900013C, HHSN268200900014C, HHSN268200900015C, HHSN268200900016C, HHSN268200900017C, HHSN268200900018C, HHSN268200900019C, and HHSN268200900020C) and NHLBI grants (U01 HL137880, U24 HL141762, R01 HL182622, and R01 HL144718) . SPIROMICS was supplemented by contributions made through the Foundation for the NIH and the COPD Foundation from Amgen; AstraZeneca/MedImmune; Bayer; Bellerophon Therapeutics; Boehringer-Ingelheim Pharmaceuticals, Inc.; Chiesi Farmaceutici S.p.A.; Forest Research Institute, Inc.; Genentech; GlaxoSmithKline; Grifols Therapeutics, Inc.; Ikaria, Inc.; MGC Diagnostics; Novartis Pharmaceuticals Corporation; Nycomed GmbH; Polarean; ProterixBio; Regeneron Pharmaceuticals, Inc.; Sanofi; Sunovion; Takeda Pharmaceutical Company; and Theravance Biopharma and Mylan/Viatris.
- Language
- English
- Electronic publication date
- 11/25/2024
- Date published
- 04/2025
- Academic Unit
- Roy J. Carver Department of Biomedical Engineering; Radiology; Pulmonary, Critical Care, and Occupational Medicine; ICTS; Internal Medicine
- Record Identifier
- 9984750659602771
Metrics
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