Longitudinal Phenotypes and Mortality in Preserved Ratio Impaired Spirometry in the COPDGene Study

Abstract

Rationale: Increasing awareness of the prevalence and significance of Preserved Ratio Impaired Spirometry (PRISm), alternatively known as restrictive or Global Initiative for Chronic Obstructive Lung Disease (GOLD)-unclassified spirometry, has expanded the body of knowledge on cross-sectional risk factors. However, longitudinal studies of PRISm remain limited.

Objectives: To examine longitudinal patterns of change in lung function, radiographic characteristics, and mortality of current and former smokers with PRISm.

Methods: Current and former smokers, aged 45 to 80 years, were enrolled in COPDGene (phase 1, 2008-2011) and returned for a 5-year follow-up (phase 2, 2012-2016). Subjects completed questionnaires, spirometry, chest computed tomography scans, and 6-minute-walk tests at both study visits. Baseline characteristics, longitudinal change in lung function, and mortality were assessed by post-bronchodilator lung function categories: PRISm (FEV₁/FVC < 0.7 and FEV₁ < 80%), GOLD0 (FEV₁/FVC > 0.7 and FEV₁ > 80%), and GOLD1-4 (FEV₁/FVC < 0.7).

Measurements and main results: Although the prevalence of PRISm was consistent (12.4-12.5%) at phases 1 and 2, subjects with PRISm exhibited substantial rates of transition to and from other lung function categories. Among subjects with PRISm at phase 1, 22.2% transitioned to GOLD0 and 25.1% progressed to GOLD1-4 at phase 2. Subjects with PRISm at both phase 1 and phase 2 had reduced rates of FEV₁ decline (-27.3 ± 42.1 vs. -33.0 ± 41.7 ml/yr) and comparable proportions of normal computed tomography scans (51% vs. 52.7%) relative to subjects with stable GOLD0 spirometry. In contrast, incident PRISm exhibited accelerated rates of lung function decline. Subjects with PRISm at phase 1 had higher mortality rates relative to GOLD0 and lower rates relative to the GOLD1-4 group.

Conclusions: PRISm is highly prevalent, is associated with increased mortality, and represents a transitional state for significant subgroups of subjects. Additional studies to characterize longitudinal progression in PRISm are warranted.

Trial registration: ClinicalTrials.gov NCT00608764.

Keywords: lung disease epidemiology; spirometry classification; spirometry mortality; spirometry statistics and numerical data.

Figure 1.

Kaplan-Meier plot of mortality by lung function category in the COPDGene cohort (n_GOLD0 = 3,783, n_PRISm = 1,058, n_GOLD1–4 = 3,959). PRISm: FEV₁/FVC ≥ 0.7 and FEV₁ < 80% predicted; GOLD0: FEV₁/FVC ≥ 0.7 and FEV₁ ≥ 80% predicted; GOLD1–4: FEV₁/FVC < 0.7. GOLD = Global Initiative for Chronic Obstructive Lung Disease; PRISm = Preserved Ratio Impaired Spirometry.

Figure 2.

Forest plot of hazard ratios for mortality from Cox proportional hazards model. PRISm: FEV₁/FVC ≥ 0.7 and FEV₁ < 80% predicted; GOLD0: FEV₁/FVC ≥ 0.7 and FEV₁ ≥ 80% predicted; GOLD1–4: FEV₁/FVC < 0.7. **P < 0.01; ***P < 0.001. AIC = Akaike information criterion; BMI = body mass index; GOLD = Global Initiative for Chronic Obstructive Lung Disease; PRISm = Preserved Ratio Impaired Spirometry.

Figure 3.

Change in lung function categories among subjects with Preserved Ratio Impaired Spirometry (PRISm) at (A) phase 1 and (B) phase 2. COPD = chronic obstructive pulmonary disease; GOLD = Global Initiative for Chronic Obstructive Lung Disease.