Normal age-related decline in forced vital capacity: a systematic review and meta-analysis

Lung function peaks in early adulthood and declines thereafter, even without respiratory disease. Differentiating physiological ageing from pathological trajectories is critical for diagnosis, prognostication and interpretation of clinical trial end-points, particularly in interstitial lung diseases where attenuation of forced vital capacity (FVC) decline is a primary outcome in most trials. Without a benchmark for expected ageing, it is difficult to determine whether therapy preserves lung function by preventing FVC loss or mirrors natural trajectories. We conducted a systematic review and meta-analysis of longitudinal evidence on age-related FVC changes among adults without lung disease. A search of major databases and conference proceedings identified 7160 citations; 50 publications representing 35 cohorts and over 365 000 participants met eligibility criteria. Follow-up ranged from three to 35 years, with three to 12 spirometric assessments per participant. Over five decades of research, a consistent pattern of decline after early adulthood was evident, but estimates varied widely (10-80 mL·year^-1) due to heterogeneity in study design, population composition, outcome reporting and analytic approach. The strongest evidence came from an individual-level pooled analysis of over 30 000 participants, demonstrating that FVC peaks in the mid-20s, declines continuously without plateau and follows a linear trajectory in women (∼26 mL·year^-1) and a biphasic trajectory in men (∼22 mL·year^-1 before age 40, ∼36 mL·year^-1 thereafter). These normative trajectories, averaging ∼20-30 mL annually, are essential for distinguishing healthy ageing from pathological decline. Incorporating these into clinical practice and trial design will improve diagnostic precision, contextualise therapeutic effects and define clinically meaningful preservation of lung function.