Identification of Early Predictors of Chronic Airway Obstruction

Abstract

Background: Chronic airflow obstruction (CAO) is the hallmark of chronic obstructive pulmonary disease (COPD), a progressive respiratory disorder. Early disease is confined to the small airways, yet the predictive role of isolated small airways obstruction in the general population remains unclear.

Objective: To evaluate whether isolated small airways obstruction predicts progression to CAO and to compare predictive ability between two measures: FEF25–75 and FEV3/FVC.

Methods: Data were analyzed from 3,957 participants in the multinational Burden of Obstructive Lung Disease (BOLD) study with a median follow-up of 8.3 years. Isolated small airways obstruction was defined as pre-bronchodilator FEF25–75 < LLN with FEV1/FVC > LLN; FEV3/FVC < LLN was assessed as an alternate definition. Mixed-effects regression models assessed associations, and results were replicated in 26,512 participants of the UK Biobank.

Results: Incidence of CAO was higher among participants with isolated small airways obstruction (FEF25–75: 7.1/1,000 person-years; FEV3/FVC: 6.9/1,000 person-years) compared to those without obstruction (3.2/1,000 person-years) (Table 1). Participants with FEF25–75 obstruction had a nearly threefold increased risk of CAO (OR 2.95), while those with FEV3/FVC obstruction had a twofold increased risk (OR 1.94) (Figure 1).

Conclusion: Isolated small airways obstruction is an independent predictor of CAO in the general population. FEF25–75 demonstrated superior discriminatory ability (AUC 0.764) compared to FEV3/FVC (AUC 0.692), supporting its value for early identification of at-risk individuals.

Introduction

Chronic obstructive pulmonary disease (COPD) is a leading cause of morbidity and mortality globally. Chronic airflow obstruction (CAO), its hallmark, originates in the small airways long before it becomes clinically evident. While earlier studies in smokers suggested that isolated small airways obstruction may foreshadow COPD, its predictive role in the general population remains unclear.

The Burden of Obstructive Lung Disease (BOLD) study provides an opportunity to clarify whether isolated small airways obstruction is a precursor to CAO in a diverse population sample.

Methods

Study Design and Population:

• Multinational, observational cohort study with 3,957 participants.
• Median follow-up: 3 years.
• Validation performed in 26,512 UK Biobank participants.

Definitions:

• Isolated small airways obstruction:
  • Primary measure: FEF25–75 < LLN with FEV1/FVC > LLN.
  • Alternative measure: FEV3/FVC ratio < LLN.
• Chronic airflow obstruction: Post-bronchodilator FEV1/FVC < LLN at follow-up.

Statistical Analysis:

• Mixed-effects regression models estimated the association between baseline obstruction and subsequent CAO.
• Receiver operating characteristic (ROC) curves calculated AUCs for predictive ability.

Results

Baseline Characteristics:
Participants with FEF25–75 obstruction were younger, predominantly female, and more often never-smokers compared with those with FEV3/FVC obstruction.

Incidence of Chronic Airflow Obstruction:

• FEF25–75 < LLN:1/1,000 person-years.
• FEV3/FVC < LLN:9/1,000 person-years.
• No obstruction:2/1,000 person-years.

📊 Table 1. Incidence rates for progression to chronic airflow obstruction

Risk Estimates:

• FEF25–75 obstruction: OR 95 (95% CI: 2.1–4.1).
• FEV3/FVC obstruction: OR 94 (95% CI: 1.4–2.7).

📈 Figure 1. Odds Ratios for Progression to Chronic Airflow Obstruction by Baseline Airway Status
(Insert bar chart showing OR 2.95 for FEF25–75, OR 1.94 for FEV3/FVC, and OR 1.0 for no obstruction)

Predictive Accuracy:

• FEF25–75: AUC 764.
• FEV3/FVC: AUC 692.

Results were consistent across the UK Biobank replication cohort.

Discussion

This study demonstrates that isolated small airways obstruction significantly increases the risk of chronic airflow obstruction, even among never-smokers and those without overt risk factors.

Of the two measures tested, FEF25–75 was the better discriminator of future CAO, suggesting that incorporating this parameter into routine spirometry interpretation may help clinicians identify at-risk individuals earlier.

These findings support proactive screening and monitoring strategies in primary care and respiratory clinics to slow disease progression.

Conclusion

Isolated small airways obstruction—particularly when defined by FEF25–75 < LLN—is a strong and independent predictor of chronic airflow obstruction in the general population. Early recognition and intervention strategies could alter disease trajectory and improve patient outcomes.

Reference:
BMJ Open Respir Res. 2023;10(1).