The normal lung loses 20–30 mL of FVC a year, which changes how to read every ILD trial

Design

Systematic review and meta-analysis of longitudinal cohort studies

Population

50 publications from 35 cohorts, over 365,000 adults without lung disease; follow-up 3 to 35 years

Primary outcome

Annual change in forced vital capacity

Effect

Roughly 20–30 mL per year overall; in the strongest individual-level analysis (>30,000 participants), ~26 mL/year in women and ~22 mL/year before age 40 rising to ~36 mL/year after in men

Attenuation of forced vital capacity decline is the primary endpoint of almost every interstitial lung disease trial, and the field has been measuring it without a properly established benchmark for what happens to a healthy lung. This review of 35 cohorts and more than 365,000 adults without lung disease supplies one.

The headline estimate range across the literature is wide — 10 to 80 mL per year — because of heterogeneity in design, population and analysis. The authors identify the most reliable evidence as an individual-level pooled analysis of over 30,000 participants: forced vital capacity peaks in the mid-20s and then declines continuously without a plateau, linearly in women at about 26 mL per year, and biphasically in men at about 22 mL per year before age 40 and about 36 mL per year after it. The overall benchmark is roughly 20–30 mL annually.

The consequence is immediate for interpretation. A trial reporting that a drug limits annual FVC loss to, say, 80 mL is reporting a decline still well above healthy ageing; one reporting 30 mL is reporting something close to normal. Without the benchmark, both read as "slowed decline". With it, they are different claims — and the same arithmetic applies at the bedside when deciding whether an individual patient's serial spirometry represents disease or age.

• Subtract expected age-related decline before calling a fall in FVC disease progression — about 20–30 mL a year is normal.
• Use sex-specific expectations: roughly 26 mL a year in women, and in men about 22 mL before 40 and 36 mL after.
• Read antifibrotic trial results against this benchmark rather than against zero decline.
• Interpret a single year's spirometry cautiously; measurement variability can exceed a year of normal ageing.
• Plot serial values rather than comparing two points — the trajectory is what distinguishes ageing from disease.

Why it matters

"Slowed FVC decline" has been the currency of interstitial lung disease trials without anyone stating what unslowed decline looks like in a healthy lung.

Don't overread it

These are population trajectories from people without lung disease; they describe an expectation, not a threshold for any individual patient.

The statistics, in plain English

The 10–80 mL per year spread across the literature is not measurement noise but genuine methodological disagreement: cohorts differ in who they enrolled, how often they measured, and whether they modelled decline as linear. That is why the authors lean on one individual-level pooled analysis of 30,000 people rather than on a pooled average of all 35 cohorts — pooling heterogeneous study-level estimates would have produced a number with a false air of precision.

Read the rest in the app

You have read your two free briefings this month. The app carries all 27 specialties, every morning, free — and this finding is waiting in it.

Get Daily Doctor — free

Scan to keep reading on your phone. No account needed to start.