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Updated: Aug 26, 2025

Automated Measurement of Pulmonary Emphysema and Small Airway Remodeling in Cigarette Smoke-exposed Mice
Published on: January 16, 2015
Small airway function measured using forced expiratory flow between 25% and 75% of vital capacity and its
Nowaf Y Alobaidi1,2,3, Mohammed Almeshari1,4, James Stockley5
1Birmingham Acute Care Research Group, Institute of Inflammation and Ageing, University of Birmingham, Birmingham, UK.
Background:
Chronic obstructive pulmonary disease (COPD) is diagnosed and its severity graded by traditional spirometric parameters (forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) and FEV1, respectively) but these parameters are considered insensitive for identifying early pathology. Measures of small airway function, including forced expiratory flow between 25% and 75% of vital capacity (FEF25-75), may be more valuable in the earliest phases of COPD. This study aimed to determine the prevalence of low FEF25-75 in ever-smokers with and without airflow limitation (AL) and to determine whether FEF25-75 relates to AL severity.
Method:
A retrospective analysis of lung function data of 1458 ever-smokers suspected clinically of having COPD. Low FEF25-75 was defined by z-score<-0.8345 and AL was defined by FEV1/FVC z-scores<-1.645. The severity of AL was evaluated using FEV1 z-scores. Participants were placed into three groups: normal FEF25-75/ no AL (normal FEF25-75/AL-); low FEF25-75/ no AL (low FEF25-75/AL-) and low FEF25-75/ AL (low FEF25-75/AL+).
Results:
Low FEF25-75 was present in 99.9% of patients with AL, and 50% of those without AL. Patients in the low FEF25-75/AL- group had lower spirometric measures (including FEV1 FEF25-75/FVC and FEV3/FVC) than those in the normal FEF25-75/AL- group. FEF25-75 decreased with AL severity. A logistic regression model demonstrated that in the absence of AL, the presence of low FEF25-75 was associated with lower FEV1 and FEV1/FVC even when smoking history was accounted for.
Conclusions:
Low FEF25-75 is a physiological trait in patients with conventional spirometric AL and likely reflects early evidence of impairment in the small airways when spirometry is within the 'normal range'. FEF25-75 likely identifies a group of patients with early evidence of pathological lung damage who warrant careful monitoring and reinforced early intervention to abrogate further lung injury.
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