Review Question - QID 217091

This patient with worsening dyspnea, nonproductive cough, history of treatment with radiation, smoking history, fine crackles on lung examination, and chest radiograph suggestive of bilateral pulmonary fibrosis most likely has radiation-induced lung injury (RILI).

RILI may be seen after thoracic irradiation in the treatment of lung, breast, or hematologic malignancies. Acutely, RILI presents as radiation pneumonitis; more chronically, RILI presents as radiation fibrosis. Immediately after radiation, direct cytotoxicity due to DNA damage leads to pulmonary edema, exudative alveolitis, and loss of type I pneumocytes. Thick secretions then accumulate with an increase in goblet cells and ciliary dysfunction. Within 3-12 weeks, loss of pneumocytes, stenosis of pulmonary capillaries and microvascular thrombosis, and leakage of fibrin-rich exudates becomes symptomatic and is clinically referred to as radiation pneumonitis. Over time, this alveolar exudate resolves but may lead to migration and hyperproliferation of fibroblasts which results in collagen deposition. This culminates in radiation fibrosis, which may manifest within 6-12 months as fibroblasts proliferate, deposit collagen, narrow alveolar space, and obliterate capillaries. Of note, bleomycin also induces sensitivity to oxygen toxicity and increases proinflammatory cytokine release, which may lead to pulmonary fibrosis.

Hanania et al. discuss the pathophysiology, risk factors, clinical assessment, and management of radiation-induced lung injury. In particular, the article describes how the management of radiation-induced lung fibrosis includes general supportive management, mobilization of airway secretions, and anti-inflammatory therapy.

Figure/Illustration A shows a chest radiograph consistent with radiation-induced pulmonary fibrosis after radiotherapy to the mediastinum. Bilateral, symmetrical, streaky, linear opacities around the mediastinum (blue arrows) are consistent with pulmonary fibrosis. Otherwise, the heart size is normal and there is no consolidation.

Incorrect Answers:
Answer 1: Chronic obstructive pulmonary disease presents with insidious, progressive dyspnea and productive cough in the setting of smoking. Although this patient has a significant smoking history, she is younger and has a nonproductive cough, recent history of radiation, and chest radiograph suggestive of pulmonary fibrosis, making RILI more likely than COPD.

Answer 2: Heart failure (HF) is a side effect of anthracyclines such as doxorubicin, which are used in the treatment of Hodgkin lymphoma. However, in this patient with normal echocardiography, no peripheral edema, and a history of radiation therapy, RILI is more likely than HF.

Answer 3: Idiopathic pulmonary fibrosis (IPF) is a chronic, progressive interstitial lung disease that usually presents in smokers over 60 years old with dyspnea on exertion and a nonproductive cough. Bibasilar fine crackles are usually heard on physical exam. However, in this younger patient with a history of malignancy treated with radiation, RILI is more likely than IPF.

Answer 4: Infection with Pneumocystis jirovecii can present with progressive fever, cough, dyspnea, and batwing edema on chest radiography. Patients with low CD4 counts (<200 cells/mm^3), a history of hematopoietic stem cell or solid organ transplant, those with malignancy, and those receiving immunosuppressive medications are at increased risk of pneumocystis pneumonia. However, in this afebrile patient without evidence of active malignancy or immunosuppression and a history of radiation therapy, RILI is more likely than infection with Pneumocystis.

Bullet Summary:
Radiation-induced lung injury is caused by a combination of direct cytotoxicity and radiation-induced cellular signal transduction and can present with dyspnea, dry cough, and pulmonary fibrosis 6-12 months after radiation.