Radiation-induced lung injury

About: Radiation-induced lung injury is a research topic. Over the lifetime, 258 publications have been published within this topic receiving 6877 citations. The topic is also known as: Radiation Pneumonitis.

Protective effect of ulinastatin in patients with non-small cell lung cancer after radiation therapy: a randomized, placebo-controlled study

Abstract: Radiation-induced lung injury (RILI) is a frequent, sometimes life-threatening complication of radiation therapy for the treatment of lung cancer. The anti-inflammatory role of ulinastatin has been well documented, and the potential application of ulinastatin in management of acute lung injury has been suggested in multiple animal studies. In this article, we described a double-blind, randomized, placebo-controlled study in patients with non-small cell lung cancer. A total of 120 patients were randomized into two groups: the trial group was treated with ulinastatin for 3 days prior to and for the first 7 days of radiation therapy and the control group was treated with placebo for 10 days following the same schedule. The results from follow-up studies showed that the incidence and grade of RILI were significantly lower in the trial group than in the control group. Reduction in pulmonary function from baseline was significantly smaller in the trial group than that in the control group. Production of serum TGF-β1, TNF-α and IL-6 decreased significantly in the trial group promptly following radiation therapy. However, no difference in survival or tumour response rate was found between the two groups. The results indicated that ulinastatin exerted a protective effect on radiation-induced lung injury. Treatment with ulinastatin could be an effective management strategy and greatly improve the clinical efficacy of radiation therapy for patients with lung cancer.

Clinicopathologic and Transcriptomic Analysis of Radiation-Induced Lung Injury in Nonhuman Primates

Abstract: Purpose Radiation-induced lung injury (RILI) is a progressive condition with an early phase (radiation pneumonitis) and a late phase (lung fibrosis). RILI may occur after partial-body ionizing radiation exposures or internal radioisotope exposure, with wide individual variability in timing and extent of lung injury. This study aimed to provide new insights into the pathogenesis and progression of RILI in the nonhuman primate (NHP) rhesus macaque model. Methods and Materials We used an integrative approach to understand RILI and its evolution at clinical and molecular levels in 17 NHPs exposed to 10 Gy of whole-thorax irradiation in comparison with 3 sham-irradiated control NHPs. Clinically, we monitored respiratory rates, computed tomography (CT) scans, plasma cytokine levels, and bronchoalveolar lavage (BAL) over 8 months and lung samples collected at necropsy for molecular and histopathologic analyses using RNA sequencing and immunohistochemistry. Results Elevated respiratory rates, greater CT density, and more severe pneumonitis with increased macrophage content were associated with early mortality. Radiation-induced lung fibrosis included polarization of macrophages toward the M2-like phenotype, TGF-β signaling, expression of CDKN1A/p21 in epithelial cells, and expression of α-SMA in lung stroma. RNA sequencing analysis of lung tissue revealed SERPINA3, ATP12A, GJB2, CLDN10, TOX3, and LPA as top dysregulated transcripts in irradiated animals. In addition to transcriptomic data, we observed increased protein expression of SERPINA3, TGF-β1, CCL2, and CCL11 in BAL and plasma samples. Conclusions Our combined clinical, imaging, histologic, and transcriptomic analysis provides new insights into the early and late phases of RILI and highlights possible biomarkers and potential therapeutic targets of RILI. Activation of TGF-β and macrophage polarization appear to be key mechanisms involved in RILI.

Ilomastat, a synthetic inhibitor of MMPs, prevents lung injury induced by γ-ray irradiation in mice.

Abstract: Lung injury is one of the pathological features in human or animal after radiation and the main side effect for patient after lung cancer radiotherapy. The efficient protective strategy still needs to exploit and the underlying mechanisms remain to be investigated. We found that the expression and activity of matrix metalloproteinases (MMPs) significantly increased at the early stage of radiation-induced lung injury (RILI). Pretreatment with Ilomastat, a synthetic inhibitor of MMPs, decreased the expression and activity of MMPs and significantly alleviated the lung inflammation and fibrosis in the irradiated mice, as well as enhanced the survival of irradiated mice. In addition, the levels of TGF-β, IL-6, TNF-α and IL-1β in the tissues dramatically reduced in the irradiated mice pretreated with Ilomastat. Furthermore, our experiments in vitro also showed that radiation significantly increased the MMPs activity, and Ilomastat pretreatment inhibited the activity of MMPs activated by irradiation and increased the cell survival. It is the first report, to our knowledge, to demonstrate that Ilomastat is a potential effective reliever for RILI and MMPs may play important roles in the process of RILI.