Radiation Pneumonitis

 

Radiation Pneumonitis.

Radiant energy disrupts nucleoprotein synthesis and ultimately kills the cells. The rapidly diving cells are more severely impacted than the rest. Radiation therapy is an integral part of the treatment of malignant diseases.

Radiation of lungs for lung cancer is second only to surgery and often are combined. Localized breast cancers are treated with lumpectomy and radiation more frequently than mastectomy and chemotherapy. Metastasis of carcinoma and sarcoma in the lungs are also frequently treated with radiation along with immunotherapy. Incidence of Bone Marrow Transplantation and Stem Cell transplantation have increased in this decade and radiation of lungs is a part of the whole body radiation for the preparation for these procedures.

Adverse effects of radiation, though fewer than chemotherapy agents produce radiation pneumonitis.

In most instances about 2 months after completion of radiation therapy, the patients develop symptoms of pneumonitis, however, the onset may be delayed for 8 months or still rarely, develop at the same time the patient is undergoing radiation therapy which most instances are given over a 4 to 6 weeks period.

Risk factors for radiation pneumonitis.

Females are more prone but the precise underlying reason is not known. Elderly people, smokers, patients with chronic obstructive lung disease (COPD) and when radiation has to give on a wide area of the chest and high dose radiation is required are more prone to pneumonitis. Concomitant use and or pre and post use of many drugs are risk factors. Some of these drugs are actinomycin D, cyclophosphamide, doxorubicin methotrexate, bleomycin, vincristine, mitomycin and some the immunotherapy agents like erlotinib, sunitinib, docetaxel.

Pathophysiology of radiation pneumonitis.

The epithelium of the tracheobronchial tree, alveolar cells and endothelial cells of pulmonary capillaries are affected more severely. Inflammatory reactions are dominated by edema, inflammatory cell recruitment, the release of TNF(tissue necrosis factor) alpha, IL1 and IL6 (inter interleukin), TGF(transforming growth factor)beta, COX2 and other cytokines. The death of cells is followed by sloughing of the surface layer. The remaining epithelial cells regenerate and begin to invade the alveolar surface. Due to the absence of surfactant atelectasis begins. Loss of surface area of capillary bed follows. Decrease in lung volumes, reduced diffusion capacity of oxygen, ventilation-perfusion mismatch, intrapulmonary shunting and undersaturation of hemoglobin are the results of these changes and account for symptoms and severity of the illness. Fibrosis once begins remained unchecked unless intervention is undertaken.

Symptoms.

The patient complaints are dry cough. Soon tightness of the chest, and chest pain on coughing and deep breathing develop. Rapid breathing and shortness of breath follow. Oxygen saturation falls below the normal levels.

Diagnosis.

Chest x-ray show fine net-like shadows and some atelectasis which are new and not present prior to initiation of radiotherapy. Tests for bacterial and viral infections are negative. High resolution CT chest is necessary for a sound diagnosis, MRI and PET scans are also done in difficult cases. Functional lung volume and vital capacity along with diffusion capacity are performed as a part of PFT (pulmonary function test). Taken from all the factors, the degree of severity of pneumonitis can be categorized in separate classes and can be used as prognosis indicators.

Treatment.

Most radiation pneumonitis responds to high dose corticoid therapy. Prednisone 60 to 100 mg /day for 2 weeks followed by gradual reduction of prednisone dose stretched over 2 years is the standard treatment protocol. Oxygen is prescribed when O2 saturation is lower than 90%. Aspirin, NSAID (nonsteroidal anti inflammatory drugs), COX 2 enzyme inhibitors are also used.

Newer treatment agents.

Monoclonal antibodies, small molecules oral agents, cytokine inhibitors are new armaments and are used more and more in order to use steroids at lower doses to minimize the side effects of steroids. The rationale for the use of these agents is discussed in previous articles under Coid-19, Immunocytes & immunomodulation and Idiopathic pulmonary fibrosis.

Role of antioxidants in the treatment.

On theoretical grounds the use of antioxidants makes sense. However, in actual practice, the beneficial effects are difficult to prove. A soy product, Isoflavone, statins (inhibitors of HMG-COA reductase) and ACE1 inhibitor-captopril, and a renin-angiotensin inhibitor are said to have shown promise. These agents influence Glutathione peroxidase (RH), superoxide dismutase and prevent the formation of free oxygen radicals by converting H2O2: to H20 and ROH according to the formula RH +  H202 = H2O + ROH.                                          

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