Abstract Background Acute exacerbations of interstitial lung disease (AEx-ILD) carry mortality rates exceeding 50%, yet reliable prognostic biomarkers remain elusive. While ground-glass opacities (GGO) characterize the acute inflammatory process, the prognostic significance of underlying chronic fibrosis burden versus acute inflammatory changes remains unknown. We hypothesized that quantitative assessment of irreversible fibrosis might provide superior prognostic information compared to reversible inflammatory parameters. Methods We performed IMBIO quantitative CT analysis in 62 consecutive ILD patients (38 with AEx-ILD, 24 without exacerbation) at acute presentation. We assessed correlations between quantitative CT parameters (GGO, reticular pattern, honeycombing, lung volumes) before, during and after the acute phase and 1-year mortality. Results Despite massive GGO increases during exacerbation (12.6%→34.1%, p 0.001) and subsequent partial recovery (→20.3%), GGO parameters showed no prognostic value. Neither acute GGO burden (r = 0.03, p = 0.81) nor GGO recovery (r = 0.066, p = 0.74) predicted mortality, challenging the traditional focus on inflammatory parameters.In stark contrast, honeycombing quantification at acute presentation emerged as the dominant prognostic determinant. Honeycombing burden independently predicted 1-year mortality (r = 0.366, p = 0.0035, AUC=0.73). An optimal threshold of ≥ 2% honeycombing identified high-risk patients with 76.9% mortality versus 29.7% in those with minimal honeycombing (p = 0.002, HR = 4.2, 95%CI 1.7-10.4).Among survivors reaching follow-up assessment, honeycombing demonstrated even stronger prognostic correlation (r = 0.606, p 0.0001), suggesting that persistent fibrosis burden dominates long-term outcomes. Reticular pattern and lung volumes showed no independent prognostic value in multivariable analyses.Strikingly, 1-year survival analysis revealed no significant difference between the AEx-ILD and non-exacerbation groups, despite initial short-term mortality differences. This finding suggests that underlying chronic fibrosis burden, rather than acute exacerbation status, determines long-term prognosis. Conclusions Quantitative honeycombing assessment at acute presentation provides objective prognostic stratification in ILD patients with respiratory deterioration, independent of exacerbation status. The reversible inflammatory component (GGO), despite its diagnostic importance, does not predict outcomes. Instead, irreversible chronic fibrosis burden (honeycombing) emerges as the critical prognostic determinant. These findings fundamentally challenge traditional approaches focusing on inflammatory parameters and suggest that quantitative fibrosis assessment should guide risk-based management strategies. The threshold of ≥ 2% honeycombing identifies a high-risk population requiring intensified monitoring and consideration for advanced therapies including transplant evaluation. IMBIO quantification offers an objective, reproducible biomarker for prognostic stratification and clinical decision-making in acute ILD deterioration. This abstract is funded by: None
Carranza et al. (Fri,) studied this question.
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