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

Am J Respir Crit Care Med. 2018 Dec 1;198(11):1397-1405. doi: 10.1164/rccm.201804-0663OC.


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.

Publication types

  • Observational Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Female
  • Follow-Up Studies
  • Humans
  • Longitudinal Studies
  • Lung / physiopathology*
  • Male
  • Middle Aged
  • Phenotype
  • Pulmonary Disease, Chronic Obstructive / diagnosis
  • Pulmonary Disease, Chronic Obstructive / epidemiology*
  • Pulmonary Disease, Chronic Obstructive / physiopathology*
  • Respiratory Function Tests / methods
  • Respiratory Function Tests / statistics & numerical data
  • Risk Factors
  • Smokers / statistics & numerical data
  • Spirometry / methods*
  • Surveys and Questionnaires
  • United States / epidemiology

Associated data

  • ClinicalTrials.gov/NCT00608764