Phenotypes and Trajectories of Tobacco-exposed Persons with Preserved Spirometry: Insights from Lung Volumes.

Arjomandi M, Zeng S, Barjaktarevic I, Bleecker ER, Bowler RP, Criner GJ, Comellas AP, Couper DJ, Curtis JL, Dransfield MT, Drummond MB, Fortis S, Han MK, Hansel NN, Hoffman EA, Kaner RJ, Kanner RE, Krishnan JA, Labaki W, Ortega VE, Peters SP, Rennard SI, Cooper CB, Tashkin DP, Paine R, Woodruff PG. Phenotypes and Trajectories of Tobacco-exposed Persons with Preserved Spirometry: Insights from Lung Volumes. Annals of the American Thoracic Society. 2024 Nov 25.

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Abstract:

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. Determine differential disease characteristics and trajectories associated with the lung volume indices among TEPS in the SPIROMICS cohort. 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]) versus high RV/TLC without high TLC ([RV/TLC]). We examined differences in CT-measured emphysema (HU = -950; PRM), airway trapping (HU = -856; PRM; DPM), 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). In TEPS participants, the pattern of spirometric disease progression differed between [TLC]high and [RV/TLC]: increased FVC with stable FEV in [TLC] versus unchanged FVC but nominally decreased FEV in [RV/TLC]. Compared to [TLC], TEPS with [RV/TLC] had less emphysema (by HU = -950) but more airway disease (by HU = -856; PRM; DPM, 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] 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] TEPS were more likely to have been placed on a respiratory inhaler at their last follow-up visit. 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.