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Airflow Limitation with Preserved FEV1 in People with a History of Cigarette Smoking: Associations with Clinical, Functional, and Imaging Characteristics
Journal article   Open access   Peer reviewed

Airflow Limitation with Preserved FEV1 in People with a History of Cigarette Smoking: Associations with Clinical, Functional, and Imaging Characteristics

Spyridon Fortis, Igor Z. Barjaktarevic, Ben Smith, Junfeng Guo, Eric A. Hoffman, Christopher B. Cooper, Victor E. Ortega, Prescott G. Woodruff, Fernando J. Martinez, Robert Paine III, …
CHEST pulmonary, 100289
07/2026
DOI: 10.1016/j.chpulm.2026.100289
url
https://doi.org/10.1016/j.chpulm.2026.100289View
Published (Version of record) Open Access

Abstract

Background Studies comparing individuals with FEV 1 %predicted ≥80% but FEV 1 /FVC <0.7 to those with both FEV 1 %predicted ≥80% and FEV 1 /FVC ≥0.7 have reported inconsistent results. However, these studies were limited by the use of a fixed FEV 1 /FVC threshold and the absence of adjustment for baseline FEV 1 . Given that individuals with preserved FEV 1 but airflow limitation (ALp) often have lower FEV 1 than those with normal spirometry, this imbalance may have influenced the observed outcomes. Research Question Is airflow limitation in the context of preserved FEV 1 a clinically significant spirometry pattern? Study Design and Methods We aimed to assess the association of FEV 1 /FVC< lower limit of normal (LLN) with clinical, functional, and radiographic features, and outcomes in individuals with preserved FEV1, while accounting for baseline FEV 1 . Using COPDGene data, we categorized ever-smokers with post-bronchodilator FEV1 ≥ LLN into 2 groups based on FEV 1 /FVC: Normal and ALp (airflow limitation). We applied multiple statistical models adjusting for demographics, smoking history, and baseline FEV 1 . Analyses were replicated in the SPIROMICS cohort. Results Of the 6,067 participants with normal FEV 1 , 5,192 had normal spirometry, and 875 had ALp. Compared to normal spirometry, ALp was associated with chronic bronchitis (OR=1.65; 95%CI: 1.35 to 2.01; P< 0.001), greater CT-assessed emphysema, gas trapping, and functional small airway disease. ALp was associated with an additional FEV 1 decline of 9.3 mL/year (95% CI: 6.5 to 12.0; P < 0.001), more respiratory exacerbations (incidence rate ratio=1.50; 95%CI: 1.26 to 1.81; P<0.001) but not increased mortality compared to normal spirometry. Findings were consistent in SPIROMICS. Interpretation Airflow Limitation with Preserved FEV 1 in individuals with cigarette smoking history represents a clinically meaningful obstructive phenotype, that warrants recognition in clinical practice.

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