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Respir Investig. 2020 Mar 20. pii: S2212-5345(20)30032-0. doi: 10.1016/j.resinv.2020.02.004. [Epub ahead of print]

Predictors of acute exacerbation in biopsy-proven idiopathic pulmonary fibrosis.

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Department of Respiratory Medicine, Okinawa Chubu Hospital, Okinawa, Japan. Electronic address:
Second Division, Department of Internal Medicine, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Department of Rheumatology, Teikyo University Chiba Medical Center, Chiba, Japan.
Department of Radiology, National Defense Medical College, Saitama, Japan.
Department of Pathology, National Hospital Organization Tokyo National Hospital, Tokyo, Japan.



Acute exacerbation (AE) is a major cause of death in patients with idiopathic pulmonary fibrosis (IPF). Current evidence on AE-IPF has been largely based on clinical, rather than pathological, analyses.


We investigated AE incidence and its predictors using clinical, radiological, and pathological data of patients diagnosed with IPF by multi-disciplinary discussion. This study, a secondary analysis of previous research, included 155 patients with IPF who underwent surgical lung biopsy (SLB). Cumulative AE incidence was evaluated by the Kaplan-Meier method. Predictors of AE-IPF were analyzed with a Fine-Gray sub-distribution hazard model. Sub-analysis was performed using propensity score-matching analysis.


In this cohort, the median age of the patients was 66 years and the median percent-predicted forced vital capacity was 82.8%. The cumulative AE incidence rates at 30 days and one year post SLB were 1.9% and 7.6%, respectively. On multivariable analysis, a lower percent-predicted diffusing capacity of the lung for carbon monoxide (%DLCO) (hazard ratio 0.98 per 1% increase, P = 0.02) and fibroblastic foci (FF)-present (vs. absent; hazard ratio 3.01, P = 0.04) were independently associated with a higher incidence of AE. The propensity score-matching analysis with adjustment for age, gender, and %DLCO revealed that the cumulative AE incidence rate was significantly higher in the FF-present subgroup than in the FF-absent subgroup (1-year incidence rate, 10.5% vs. 0%, respectively; P = 0.04 by Gray's test).


FF and %DLCO were independent predictors of AE in patients with biopsy-proven IPF. FF may be associated with the pathogenesis of AE-IPF.


Acute exacerbation; Diffusing capacity of the lung for carbon monoxide; Fibroblastic foci; Idiopathic pulmonary fibrosis

Conflict of interest statement

Declaration of Competing Interest The authors have no conflicts of interest.

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