Who are volume responders in the context of Chronic Obstructive Pulmonary Disease (COPD)?

Volume Responders in COPD

Volume responders in COPD are patients who have reduced FVC due to gas trapping causing a pre-bronchodilator FEV1/FVC ratio ≥0.7, but after bronchodilator administration show a greater improvement in FVC relative to FEV1, decreasing the ratio to <0.7 and revealing previously undetected airflow obstruction. 1

Characteristics of Volume Responders

• Volume responders typically have greater degrees of airflow obstruction with lower FEV1, lower FEV1/FVC ratio, and higher residual volume at rest compared to non-responders 2
• These patients show discordant pre-bronchodilator (≥0.7) and post-bronchodilator (<0.7) FEV1/FVC ratios due to significant gas trapping that improves with bronchodilation 1
• Volume responders are characterized by greater dynamic airway collapse, assessed by the ratio of early to mid-expiratory flow 2
• They often have more severe disease characteristics, including greater hyperinflation and gas trapping 1

Physiological Mechanism

• Gas trapping in volume responders reduces FVC due to increased residual volume, which artificially elevates the FEV1/FVC ratio, potentially masking airflow obstruction 1
• Bronchodilators reduce end-expiratory lung volumes by allowing more volume to be exhaled, thereby improving inspiratory capacity 1
• These shifts in lung volumes arise from small improvements in flow enabling larger and clinically relevant improvements in volumes 1
• Reduced end-expiratory lung volumes improve the mechanical efficiency of diaphragm contraction, decreasing the work of breathing 1

Clinical Significance

• Post-bronchodilator testing is crucial to identify volume responders who would otherwise be missed using only pre-bronchodilator spirometry 1
• Volume responders are more likely to be found among patients with lower baseline FEV1 (e.g., <80% predicted) 1
• Approximately 3% of patients in large COPD cohorts are volume responders (PREN-POSTO pattern) 1
• Volume responders experience symptomatic improvement and reduced dyspnea even when there is little or no flow response measured by FEV1 1

Diagnostic Approach

• GOLD 2025 recommends using pre-BD spirometry to rule out COPD and post-BD measurements to confirm the diagnosis 1
• If pre-BD spirometry shows FEV1/FVC ≥0.7 but clinical suspicion of COPD is high, post-BD testing should be performed to identify potential volume responders 1
• Post-BD results close to the threshold (between 0.60 and 0.80) should be repeated to ensure a correct diagnosis 1
• The pre-BD FEV1 can be used as a guide to the probability that the individual may be a volume responder, as this is more likely with lower FEV1 measurements (e.g., <80% predicted) 1

Contrast with Flow Responders

• Unlike volume responders, flow responders show a greater FEV1 improvement relative to FVC which may increase FEV1/FVC from <0.7 pre-BD to ≥0.7 post-BD 1
• Flow responders (PREO-POSTN pattern) have an increased likelihood of developing post-BD obstruction during follow-up and require monitoring longitudinally 1
• Flow responses tend to decrease in more severe COPD, while volume responses become more prominent 1
• Nearly 50% of flow responders progress to persistent airflow obstruction over time, highlighting the need for close follow-up 1

Clinical Management Implications

• Volume responders benefit from bronchodilator therapy even when traditional FEV1-based reversibility criteria are not met 3, 4
• Changes in lung volumes after bronchodilator administration correlate better with exercise tolerance and symptom improvement than changes in FEV1 4
• Plethysmography can provide additional information beyond spirometry in identifying volume responders 5, 4
• The magnitude of volume responses correlates with the degree of baseline hyperinflation 4

Pitfalls and Caveats

• Relying solely on pre-bronchodilator spirometry may miss the diagnosis of COPD in volume responders 1
• Using only FEV1 to assess bronchodilator response may underestimate the clinical benefit of bronchodilators in COPD patients 2, 4
• The response pattern varies depending on COPD severity, with volume responses becoming more prominent in more advanced disease 6
• Despite GOLD recommendations, clinical practice shows that the presence of a post-bronchodilator FEV1/FVC <0.7 has only a small effect (6% increase) on the probability of a COPD diagnosis being made 7