Interpretation of Decreased FEF25-75 (PEF25-75)
A decreased FEF25-75 (forced expiratory flow at 25-75% of vital capacity) indicates small airway dysfunction, but has limited clinical utility when FEV1 and FEV1/FVC are normal; however, it may identify early airway disease in at-risk patients and warrants careful monitoring with reinforced interventions to prevent progression. 1
Clinical Significance and Limitations
Primary Interpretation Framework
FEF25-75 should not replace FEV1 and FEV1/FVC as the primary measures for diagnosing or assessing airway obstruction severity, as it has greater intrasubject and intersubject variability with a larger range of predicted values 2, 1
Low FEF25-75 (defined as <65% predicted or z-score <-0.8435) suggests small airway obstruction, but its clinical significance is limited when FEV1 and FEV1/FVC remain within normal range 1, 3
The European Respiratory Society explicitly states that FEF25-75 and similar mid-expiratory flow measures "do not provide information that is more useful in clinical practice than that provided by FEV1 and VC" 2
When FEF25-75 Has Clinical Value
In patients with normal spirometry (normal FEV1/FVC):
Low FEF25-75 identifies early pathological lung damage in ever-smokers, with 50% of symptomatic smokers without airflow limitation having reduced FEF25-75 4
Predictive value for COPD development: Patients with normal lung function but low FEF25-75 have a 3.31-fold increased risk of developing COPD over 10 years (41.8% vs 7.4% incidence) 3
In asthma patients with normal FEV1 but reduced FEF25-75, there is higher sputum eosinophil count, increased inhaled corticosteroid requirements, and correlation with airway inflammation 5
In patients with established disease:
FEF25-75 is more sensitive than FEV1 for detecting severe asthma, airflow obstruction, and severe bronchial hyperresponsiveness (area under curve: 0.84 vs 0.81,0.97 vs 0.89, and 0.74 vs 0.69 respectively) 5
Nearly 100% of patients with established airflow limitation have low FEF25-75, and it decreases progressively with airflow limitation severity 4
Management Approach
For Patients WITHOUT Airflow Limitation (Normal FEV1/FVC)
When FEF25-75 is reduced:
Implement intensive risk factor modification - particularly smoking cessation in ever-smokers, as low FEF25-75 represents early evidence of small airway pathology requiring intervention to prevent progression 4
Establish close monitoring protocol with serial spirometry including FEF25-75 measurements, as these patients warrant careful surveillance given their elevated risk of developing COPD 3
Consider bronchodilator trial in symptomatic patients, as low FEF25-75 may indicate reversible small airway dysfunction even when conventional spirometry appears normal 2, 6
Evaluate for comorbid conditions including asthma or allergic rhinitis, as low FEF25-75 is associated with bronchial hyperresponsiveness, allergic sensitization, and early asthma onset 6
For Patients WITH Airflow Limitation (Reduced FEV1/FVC)
Base severity assessment and treatment decisions on FEV1, not FEF25-75:
Use post-bronchodilator FEV1 % predicted to classify COPD severity: mild (≥70%), moderate (50-69%), severe (<50%) 2, 7
Confirm COPD diagnosis requires post-bronchodilator FEV1/FVC ≤0.70 after administering 400 mcg salbutamol or 80 mcg ipratropium 7
Implement multidimensional assessment incorporating symptom burden (mMRC ≥2), exacerbation history (≥2/year or ≥1 hospitalization), and BMI (<21 kg/m² indicates increased mortality risk) 7
Critical Pitfalls to Avoid
Common Errors in Interpretation
Do not diagnose airway obstruction based solely on low FEF25-75 - always confirm with FEV1/FVC ratio, as FEF25-75 has poor specificity 1
Do not use FEF25-75 to assess bronchodilator response - the high variability makes it unreliable for this purpose; use absolute change in FEV1 or percentage of predicted FEV1 instead 2
In advanced emphysema, do not rely on peak expiratory flow (PEF) as it may be only moderately reduced while FEV1 is severely affected 2
Special Populations
In osteogenesis imperfecta patients, FEF25-75 measurement is specifically recommended as many have normal FEV1 but abnormal FEF25-75, and it helps detect comorbid asthma or COPD 2
In cystic fibrosis, FEF25-75 (MEF 25-75%) can be more sensitive than FEV1 for detecting early airway dysfunction 1
In military medicine and primary care settings, FEF25-75 may provide useful screening information for early airway disease in at-risk populations 6