Prediction of COPD and Related Events Improves by Combining Spirometry and the Single Breath Nitrogen Test

Chronic obstructive pulmonary disease (COPD) develops in small airways. Severity of small airway pathology relates to progression and mortality. The present study evaluated the prediction of COPD of a validated test for small airway disease, i.e. a slope of the alveolar plateau of the single breath nitrogen test (N₂-slope). The N₂-slope, spirometry, age, smoking habits, and anthropometric variables at baseline were obtained in a population-based sample (n = 592). The cohort was followed for first COPD events (first hospital admission of COPD or related conditions or death from COPD) during 38 years. During follow-up, 52 subjects (8.8%) had a first COPD event, of which 18 (3.0%) died with a first COPD diagnosis. In the proportional hazard regression analysis adjusted for age and smoking habits, the cumulative COPD event incidence increased from 5% among those with high forced expired volume in one second (FEV₁) to 25% among those with low FEV₁, while increasing from 4% among those with the lowest N₂-slope to 26% among those with the highest. However, combining the N₂-slope and FEV₁ resulted in considerable synergy in the prediction of first COPD event and even more so when taking account of smoking habits. The cumulative COPD event incidence rate was 75% among heavy smokers with the highest N₂-slope and lowest FEV₁, and less than 1% among never smokers with the lowest N₂-slope and highest FEV₁. Thus, combining the results of the single breath N₂-slope and FEV₁ considerably improved the prediction of COPD events as compared to either test alone.