Multidimensional clinical deterioration in interstitial lung disease: longitudinal concordance of frailty, patient-reported outcomes, and lung function in a multinational European registry cohort study.

BACKGROUND

In interstitial lung disease (ILD), progression is tracked along lung physiology, patient-reported outcomes (PROMs), and frailty, and prior registries report that these dimen-sions correlate at the group level. Whether deterioration on one axis identifies the same indi-vidual patients as another has not been examined.

METHODS

In 371 adults from the multinational European ILD Registry (eurILDreg), spanning the full ILD spectrum, baseline-to-last-visit change was classified as decline at the minimal clinically important difference across eight instruments (CFS, MRC dyspnoea, K-BILD, LCQ, EQ-5D-5L, cough VAS, FVC %pred, DLCO %pred). Patient-level agreement was quantified by Cohen's κ, interpreted direction-sensitively; a pre-specified window-matched analysis was primary because instrument follow-up windows differed (analysis-specific n 127 to 178). Outcomes (death or lung transplantation) were ascertained in 312 patients (24 events).

RESULTS

At the individual-patient level, frailty, PROMs, and lung function deteriorated in largely different patients: window-matched agreement was no better than chance for every primary pair (CFS×K-BILD 0.10, CFS×FVC -0.07, K-BILD×FVC 0.28). No pair of the eight instruments reached even moderate agreement (maximum κ=0.33), and the discordance was not explained by measurement timing, diagnostic heterogeneity (persisting within IPF, κ 0.07 to 0.26), or a single domain - the two ILD PROMs themselves disagreed (K-BILD×LCQ κ=-0.19). Physiological (FVC-defined) progression independently predicted K-BILD decline (OR 5.03). A spirometry-invisible subgroup declining on K-BILD while FVC remained stable (22% of 134) carried the highest event rate (13.3%).

CONCLUSION

In interstitial lung disease, deterioration in frailty, patient-reported outcomes, and lung physiology identified largely non-overlapping populations at the level of the individual patient, with low agreement even within the patient-reported domain. Because subgroup with declining patient-reported outcomes but preserved spirometry showed the highest event rate, assessment based on any single measure, and on forced vital capacity in particular, may not capture all deteriorating patients. These findings support the integration of validated patient-reported outcomes and frailty measures into multidimensional assessment, and indicate that prospective validation of multi-axis decline against clinical outcomes should inform future ILD research and the design of progression criteria.