What is the clinical significance of a positive bronchodilator response in patients with normal spirometry?

Clinical Significance of Positive Bronchodilator Response in Patients with Normal Spirometry

A positive bronchodilator response in patients with normal baseline spirometry may indicate early small airway dysfunction and increased risk of progression to COPD in smokers, despite not meeting diagnostic criteria for obstructive lung disease. 1

Definition and Prevalence

• A positive bronchodilator response is defined as an increase in FEV1 and/or FVC of ≥12% and ≥200 mL from baseline after bronchodilator administration 1
• The prevalence of positive bronchodilator response in patients with normal baseline spirometry is approximately 3.1% 2
• Frequency of positive response varies by baseline FEV1:
  • 6.9% in patients with FEV1 > lower limit of normal to 90% predicted
  • 1.9% in patients with FEV1 90-100% predicted
  • 0% in patients with FEV1 >100% predicted 2

Clinical Significance in Disease Progression

• In smokers with normal spirometry (FEV1/FVC ≥0.7), those with greater and more consistent bronchodilator response are more likely to progress to COPD 1
• The SPIROMICS study found that bronchodilator response in smokers with normal spirometry was associated with:
  • Lower pre-bronchodilator FEV1 and FEV1/FVC ratio
  • Greater gas trapping on CT scans (indicating small airway dysfunction)
  • Higher risk of progression to COPD diagnosis over time 1

Diagnostic Implications

• Historically, bronchodilator response was used to differentiate asthma from COPD, with positive response favoring asthma 1
• However, this distinction is now recognized as having poor discriminative properties, as many COPD patients also demonstrate significant flow and volume responses 1
• In patients with suspected asthma but negative bronchodilator response, methacholine challenge testing may be necessary, as negative bronchodilator testing has only a 57% negative predictive value for excluding asthma 3
• Lower FEV1/FVC ratio (even within normal range) is associated with higher frequency of bronchodilator response 2

Therapeutic Implications

• In children with asthma and normal baseline spirometry, a bronchodilator response ≥10% may help identify potential responders to inhaled corticosteroid therapy 4
• The predictive value improves when combined with other factors such as female gender and atopic status 4
• The lack of a bronchodilator response in laboratory testing does not preclude a clinical response to bronchodilator therapy 1
• Responses below significant thresholds may still be associated with symptom improvement and better patient performance 1

Practical Considerations

• Bronchodilator testing can likely be omitted in patients with normal spirometry and FEV1 above 90% predicted due to low probability of positive response (≤1.9%) 2
• For patients with normal FEV1/FVC but strong clinical suspicion of COPD, additional testing may be warranted, including assessment of FEV1/SVC ratio, which may detect more peripheral airflow obstruction 1
• In patients with normal spirometry but persistent respiratory symptoms, consider:
  • Changes in lung volumes (especially FRC or IC) which may improve after bronchodilation despite minimal changes in FEV1/FVC 1
  • Repeat testing over time, as bronchodilator response can vary temporally 3

Pitfalls and Caveats

• Bronchodilator response testing lacks standardization regarding which bronchodilator to use, appropriate dosing, and criteria for positive response 1
• Deep inhalations during spirometry may reduce airway caliber, potentially underestimating bronchodilator response compared to measurements of airway resistance or partial expiratory flow-volume maneuvers 1
• The magnitude of bronchodilator response may be more clinically relevant than simply categorizing as "positive" or "negative" 1
• In patients with preserved ratio impaired spirometry (PRISm) - low FEV1 but normal FEV1/FVC ratio - bronchodilator response may help identify those at risk for developing COPD 1