Combination of computed tomography imaging pattern and severity of respiratory failure as factors associated with prognosis for acute exacerbation of idiopathic chronic fibrosing interstitial pneumonia

PLOS ONE RESEARCH ARTICLE Combination of computed tomography imaging pattern and severity of respiratory failure as factors associated with prognosis for acute exacerbation of idiopathic chronic fibrosing interstitial pneumonia a1111111111 a1111111111 a1111111111 a1111111111 a1111111111 Keito Enokida1,2, Takahisa Takihara1, Yukihiro Horio1, Noriko Nakamura3, Naotaka Kutsuzawa1, Mari Takahashi1, Fuminari Takahashi1,2, Sakurako Tajiri2, Yoko Ito1, Koichiro Asano ID1* 1 Division of Pulmonary Medicine, Department of Medicine, Tokai University School of Medicine, Isehara, Japan, 2 Division of Pulmonary Medicine, Department of Medicine, Tokai University Oiso Hospital, Oiso, Japan, 3 Department of Radiology, Tokai University School of Medicine, Isehara, Kanagawa, Japan * OPEN ACCESS Citation: Enokida K, Takihara T, Horio Y, Nakamura N, Kutsuzawa N, Takahashi M, et al. (2023) Combination of computed tomography imaging pattern and severity of respiratory failure as factors associated with prognosis for acute exacerbation of idiopathic chronic fibrosing interstitial pneumonia. PLoS ONE 18(2): e0279878. https:// doi.org/10.1371/journal.pone.0279878 Editor: Robert Jeenchen Chen, Stanford University School of Medicine, UNITED STATES Received: November 4, 2021 Accepted: December 18, 2022 Published: February 24, 2023 Copyright: © 2023 Enokida et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Data Availability Statement: The approval of our protocol by the IRB is based on Ethical Guidelines for Medical and Biological Research Involving Human Subjects (https://www.mhlw.go.jp/stf/ seisakunitsuite/bunya/hokabunya/kenkyujigyou/ikenkyu/index.html, Only Japanese text available). It demands additional consent by the participants (in an opt-out format) and the approval by the IRB for the new research. The researcher can contact the IRB in Tokai University (https://irb-med-tokai.com/) Abstract Background and objectives The prognosis of idiopathic chronic fibrotic interstitial pneumonitis (CFIP) in patients with acute exacerbation (AE) is variable. We examined whether the imaging pattern on thoracic computed tomography (CT) or the severity of respiratory failure with AE-CFIP is associated with short-term prognosis. Methods Patients admitted to two university hospitals were retrospectively analyzed and divided into derivation and validation cohorts. The distribution of newly appearing parenchymal abnormalities on thoracic CT was classified into peripheral, multifocal, and diffuse patterns. Respiratory failure was defined as severe if a fraction of inspired oxygen � 0.5 was required to maintain percutaneous oxygen saturation � 90% on admission. Factors associated with 90 day-mortality were analyzed using univariate and Cox proportional hazard regression. Results In 59 patients with AE-CFIP of the derivation cohort, diffuse pattern on CT was associated with higher mortality within 90 days (43%) than peripheral/multifocal pattern (17%, p = 0.03). Additionally, compared with non-severe failure, severe respiratory failure was associated with higher mortality (47% vs. 21%, p = 0.06). Cox proportional hazard regression analysis demonstrated that a combination of diffuse pattern on CT and severe respiratory failure was associated with the poorest prognosis (hazard ratio [HR] 3.51 [interquartile range 1.26– 9.80], p = 0.016) in the derivation cohort, which was confirmed in the validation cohort (n = 31, HR 4.30 [interquartile range 1.51–12.2], p = 0.006). PLOS ONE | https://doi.org/10.1371/journal.pone.0279878 February 24, 2023 1 / 15 PLOS ONE by email () or the corresponding author directly. Then, the researcher needs to obtain approval by the IRB and to inform the study participants about the new research in an opt-out format (in Japanese language). The data without rejection by the participant will then be sent to the researcher. Funding: The authors received no specific funding for this work. Competing interests: The authors have declared that no competing interests exist. Prognostic factors for acute exacerbation of idiopathic CFIP Conclusion The combination of imaging pattern on thoracic CT and severity of respiratory failure was associated with the prognosis of idiopathic AE-CFIP. Introduction Acute exacerbation (AE) accompanied by new ground-glass opacity and consolidation in the lungs along with rapid acceleration of respiratory failure are the major causes of mortality in patients with idiopathic pulmonary fibrosis (IPF). Approximately half of the deaths of IPF patients are associated with AE, and the estimated median survival time of IPF patients who have developed AE is 3–4 months [1–5]. AE also occurs in patients with idiopathic chronic fibrotic interstitial pneumonitis (CFIP) other than IPF [6, 7]. Several studies have shown that thoracic computed tomography (CT) imaging patterns and distribution are useful for predicting the prognosis of AE in patients with IPF. Akira et al. [8] defined three distribution patterns of ground-glass opacity or consolidation newly developed during AE of IPF: peripheral, multifocal, and diffuse. They examined 58 patients with AE-CFIP and demonstrated that cases with diffuse pattern of ground-glass opacity or consolidation exhibit a significantly worse prognosis compared to those with a peripheral/multifocal pattern [8]. Another scoring system for CT imaging was proposed by Ichikado et al. [9], who semiquantitatively evaluated the extent of ground-glass opacity, consolidation, bronchiectasis, and honeycomb. An Ichikado score of � 245 has been attributed with a significantly poor prognosis in patients with AE of IPF [10]. In contrast, several other studies have shown that oxygenation status is a prognostic factor for AE in patients with IPF. Parameters for oxygenation during AE, particularly partial pressure of oxygen in arterial blood (PaO2)/ fraction of inspired oxygen (FiO2) < 200, have been reported to be associated with poor prognosis [2, 5, 6, 10–19]. The PaO2/FiO2 ratio is also a well-established parameter for classification of the severity of acute respiratory distress syndrome (ARDS) [20], which presents with the same pathological changes in the lungs as AE-IPF. ARDS with a PaO2/FiO2 ratio < 100 is considered severe and is associated with a poor prognosis regardless of the treatment [20]. Though several biomarkers, including concentration of lactate dehydrogenase, C-reactive protein, Krebs von Lungen-6 (KL-6) in serum, and neutrophil and lymphocyte counts in bronchoalveolar lavage fluid (BALF) have also been linked to poor prognosis of AE-IPF [2, 5, 11, 13, 15, 17, 21–23], the results are inconsistent. In the present study, therefore, we focused on the two parameters, imaging pattern on thoracic CT and oxygenation status, to confirm whether either o (...truncated)