ATS 2025: Evaluating Trajectories and Mortality of Preserved Ratio Impaired Spirometry: Insights from a UK Birth Cohort

Introduction:

Preserved Ratio Impaired Spirometry (PRISm) is defined by a normal FEV₁/FVC ratio (≥70%) with reduced FEV₁ (<80% predicted). It is a heterogeneous and unstable condition associated with increased symptoms and higher mortality, yet long-term outcomes are not well studied in UK populations.

Objective:

To assess the long-term trajectory of PRISm and its association with all-cause and respiratory-specific mortality using data from a UK birth cohort of ever-smokers.

Methods:

• Data Source: Medical Research Council National Survey of Health & Development (1946 UK birth cohort)
• Population: Ever-smokers undergoing pulmonary function tests (PFTs) at ages 43, 53, and 63
• Mortality information was sourced from national death registries, linked as of May 2024.
• Mortality associations were evaluated using multivariable Cox proportional hazards models, with adjustments made for sex, smoking history (in pack-years), asthma diagnosis, and airflow obstruction severity as defined by GOLD criteria.

Results:

Patient Characteristics:

1. Mortality Risk
   1. PRISm at age 43 was associated with:
      1. All-cause mortality: HR = 1.31 (95% CI: 1.04–1.6; p = 0.020)
      2. Respiratory mortality: HR = 2.5 (95% CI: 1.32–4.7; p = 0.005)
   2. PRISm at age 53: All-cause mortality: HR = 1.45 (95% CI: 1.11–1.89; p = 0.006)
2. PRISm Trajectory:
   1. From Age 43 to 53 (n = 196 with PRISm at age 43):
      1. 54% (n = 106) reverted to normal spirometry
      2. 37% (n = 72) remained with PRISm
      3. 9% (n = 18) progressed to COPD
   2. From Age 53 to 63 (among the 72 with PRISm at age 53):
      1. 78% (n = 56) continued to have PRISm
      2. 15% (n = 11) reverted to normal spirometry
      3. 7% (n = 5) progressed to COPD

Conclusion:

PRISm is a dynamic and unstable condition, with over half of cases reverting to normal lung function over time. However, it is associated with significantly increased mortality from as early as age 43, emphasizing the need for early identification and monitoring in high-risk individuals.

Am J Respir Crit Care Med 2025; 211: A2884

American Thoracic Society 2025 International Conference, May 18-21, San Francisco