Abstract
Postoperative acute exacerbation of interstitial lung disease (AE-ILD) can be fatal in patients with lung cancer concomitant with ILD. We aimed to elucidate the predictive potential of high-mobility group box 1 (HMGB1), which is associated with the development and severity of lung injury, for evaluating the risk of this complication. We included 152 patients with lung cancer and ILD who underwent radical surgery between January 2011 and August 2019. We evaluated the preoperative levels of serum HMGB1 and its predictive potential for postoperative AE-ILD. Postoperative AE-ILD developed in 17 patients. Serum levels of HMGB1 were significantly higher in patients with postoperative AE-ILD than in those without (median [interquartile range]: 5.39 [3.29–11.70] ng/mL vs. 3.55 [2.07–5.62] ng/mL). Univariate and multivariate logistic regression analyses revealed that higher HMGB1 levels were significantly associated with the development of postoperative AE-ILD in entire studied patients (n = 152). In the subgroup analysis, higher HMGB1 levels were associated with a significantly increased risk of this complication in patients who underwent lobectomy (n = 77) than in those who underwent sublobar resection (n = 75). Serum HMGB1 could be a promising marker for evaluating the risk of postoperative AE-ILD, specifically in patients who underwent lobectomy.
Highlights
Postoperative acute exacerbation of interstitial lung disease (AE-ILD) can be fatal in patients with lung cancer concomitant with ILD
We have previously reported that serum levels of high-mobility group box 1 (HMGB1) are significantly higher in patients with idiopathic pulmonary fibrosis (IPF) than in healthy subjects, and its higher levels at baseline are associated with the earlier development of acute exacerbation of IPF (AE-IPF)[5]
This study showed that higher levels of serum HMGB1 were significantly associated with a higher incidence of postoperative AE-ILD in patients with lung cancer concomitant with ILD, especially in patients who underwent lobectomy
Summary
Postoperative acute exacerbation of interstitial lung disease (AE-ILD) can be fatal in patients with lung cancer concomitant with ILD. Circulatory HMGB1 binds to pattern recognition receptors on the cell surface, such as the receptor for advanced glycation end product (RAGE) and toll-like receptor (TLR) Their interactions result in the activation of pro-inflammatory responses associated with acute lung injury[3,4]. Mechanical ventilation induces elevated expression of HMGB1 in lung tissue and bronchoalveolar lavage fluid (BALF), and anti-HMGB1 antibody can ameliorate ventilation-induced lung injury[8,9] These data led us to speculate that HMGB1 is associated with the development of postoperative AE-ILD as well as AE-IPF, and we hypothesize that baseline levels of circulatory HMGB1 can be a predictive blood marker of this severe complication
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