OVERVIEW
An aseptic inflammatory disease caused by damage to lung tissue due to radiation exposure.
Symptoms include low-grade fever, cough, sputum, shortness of breath and chest pain.
Medication is the mainstay of treatment
Mild cases can be cured with medication, while severe cases have a poor prognosis and may even be life-threatening.
Definition
Radiation pneumonitis (RP), also known as radiation pneumonitis, is a sterile inflammation of the lungs caused by damage to the lung tissues as a result of exposure to large doses of radiation, including radiation accidents, radiation therapy for tumors, and nuclear accidents, at one time or many times within a few days.
Initially, exudative inflammation is the mainstay of the disease, interstitial pneumonia appears after 6 to 12 weeks, and then gradually develops into chronic inflammation, and some patients eventually form pulmonary fibrosis or even solid changes in the lungs.
The clinical manifestations of this disease are cough, sputum, chest pain, shortness of breath, low fever and other symptoms, and in severe cases, chest tightness, dyspnea, high fever, severe cough, hemoptysis.
Morbidity
Studies have shown that radiotherapy is less well tolerated by the elderly, who are more likely to develop radiation pneumonitis.
The incidence has been reported differently both at home and abroad, ranging from about 8% to 8.25% [1].
Some studies have reported that lung cancer patients in Asia are more likely to develop RP after radiotherapy than patients in Europe, America and Australia [2].
Etiology
Causes of disease
Radiation therapy for tumor
Amount of radiation
The higher the radiation dose, the higher the probability of developing radiation pneumonitis and the more serious the degree of lung damage. Radiation doses over 40 Gy lead to radiation pneumonitis, and radiation doses over 60 Gy can lead to severe lung damage.
Radiation area
For the same radiation dose, irradiating a large area results in more severe lung tissue damage than localized irradiation.
Other influencing factors
Such as the individual’s sensitivity to ionizing radiation, the higher the sensitivity, the more likely to develop radiation pneumonitis.
Nuclear accidents
Nuclear weapon explosion, nuclear power reactor out of control, nuclear fuel processing and handling accidents, in the surrounding 1,000 to 2,000 meters of personnel can cause radiation pneumonia.
Radiation accidents
If a radioactive source is lost and picked up, it can cause radiation pneumonitis in the carriers and the surrounding people.
People at risk
Patients with a history of underlying diseases such as obstructive pulmonary disease and diabetes mellitus, the elderly, and patients with a history of combined radiotherapy have an increased probability of developing radiation pneumonitis.
Symptoms
Radiation pneumonitis most often occurs 1 to 3 months after the start of radiation therapy, and may be characterized by symptoms such as low-grade fever, cough, sputum, chest pain, and shortness of breath.
Main Symptoms
Fever
Mild cases are mainly characterized by low-grade fever, while severe cases may have high fever.
Cough
Mild cases are characterized by cough, mainly dry cough, severe cases have severe cough and even hemoptysis.
Chest pain
May be pleuritic pain or sub sternal pain.
Shortness of breath
Often accompanied by shortness of breath, severe dyspnea, the disease may be left in the later stages of dyspnea after activity.
Palpitations
Some people may experience palpitations.
Cyanosis
Cyanosis may occur in severe cases.
Localized skin hardening
Localized atrophy and hardening of the skin at the site of radiation therapy.
Complications
Radiation pulmonary fibrosis
In some cases of uncontrolled radiation pneumonitis, the lung damage worsens and pulmonary fibrosis develops, which is characterized by progressive dyspnea and is evident after activity, and usually tends to occur at 2 months to 6 months after radiation therapy.
Acute respiratory distress syndrome
In severe cases, the disease may develop into acute respiratory distress syndrome, manifested by dyspnea, profuse sweating, irritability and anxiety.
Acute cardiac insufficiency
In severe cases, acute cardiac insufficiency can also occur, manifested by breathing up to 30-40 times per minute, sitting breathing, ashen face, blue lips, profuse sweating, and in severe cases, a large amount of pink foamy liquid can gush out from the mouth and nasal cavity.
Consultation
Department of Medicine
Respiratory Medicine
Patients with fever, cough, sputum, chest tightness, shortness of breath and other symptoms should seek medical treatment promptly.
Department of Oncology
Patients with tumors who need anti-tumor drug treatment should also consult the Department of Medical Oncology as prescribed by the doctor.
Preparation
Consultation: Registration, Preparation of Documents, Frequently Asked Questions
Tips for Consultation
Patients with fever should record the change of body temperature so that the doctor can understand their condition. It is recommended not to take fever-reducing drugs by oneself so as to avoid misjudging the condition.
Preparation List
Symptom list
Pay special attention to the time of onset of symptoms, special manifestations, etc.
Is there fever? What is the highest temperature? How often does the fever occur? Does the fever persist?
Is the cough paroxysmal? Is the cough paroxysmal or frequent and severe?
Is there any chest tightness, chest pain, shortness of breath, or difficulty breathing?
How soon after radiation therapy did the symptoms appear? How long have they lasted?
Medical History Checklist
Is there a history of tumor disease?
Have you received radiation therapy? How many radiation treatments? How long was the course of treatment? What was the dose of radiation therapy?
What part of the body was treated with radiation therapy? What were the chemotherapy drugs and how were they used?
Are there any underlying diseases such as COPD, diabetes, etc.?
Checklist
Test results of the last six months, which can be brought to the doctor’s office
Laboratory tests: routine blood tests, arterial blood gas analysis, blood sedimentation.
Imaging tests: Chest X-ray or Chest CT.
Other tests: Lung function.
Medication List
Medications used in the last 3 months, if available in boxes or packages, bring with you to the doctor’s office
Glucocorticoids: e.g. prednisone.
Antibiotics: e.g. ceftazidime, levofloxacin, ciprofloxacin.
Expectorants: e.g. Ambroxol.
Other drugs: e.g. reduced glutathione, amifostine, fluvastatin, selenium preparations, keratinocyte growth factor.
Chemotherapeutic agents: e.g. docetaxel, paclitaxel, cyclophosphamide, doxorubicin, gefitinib.
Diagnosis
Diagnosis is based on
medical history
There may be a history of the following.
History of tumor, radiation therapy.
Presence of risk factors such as history of underlying disease such as obstructive pulmonary disease or diabetes mellitus, elderly, history of combination chemotherapy.
Clinical manifestations
Symptoms.
Patients present with cough, sputum, fever, chest pain, shortness of breath, and palpitations; in severe cases, there is chest tightness, dyspnea, cyanosis, high fever, severe cough, and even hemoptysis.
Physical signs
Localized skin at the radiotherapy site is seen to be atrophied and hardened.
Most of the lungs do not have positive signs, and when the fibrosis in the lungs is severe, there may be telangiectasia, weakened respiratory sounds, and bursting or twisting sounds can be heard. Occasionally, there is pleural friction, and dry or wet rales may appear.
In combination with acute cardiac insufficiency, liver enlargement and tenderness, jugular venous filling may occur.
Pulmonary function tests
Purpose: To help differentiate whether symptoms are caused by an episode of COPD or interstitial lesions, and to help determine the severity of respiratory compromise.
Significance: Radiation pneumonitis is characterized by restrictive ventilation impairment due to pulmonary fibrosis, decreased lung compliance, decreased lung volumes, residual air volumes, total lung volumes, and first-second expiratory volume on exertion, impaired gas diffusion, and decreased ventilation/blood flow ratios, leading to hypoxemia.
Laboratory Tests
Blood counts and blood sedimentation
Purpose: To obtain routine blood counts of leukocytes, neutrophils and sedimentation rate.
Significance: Mild leukocytosis, elevated neutrophils, and accelerated sedimentation may be seen in combination with bacterial infection.
Arterial blood gas analysis
Purpose: To understand the arterial oxygen situation.
Meaning: Arterial oxygen partial pressure is lower than normal, suggesting the presence of hypoxemia.
Imaging
Chest CT
Purpose: To detect the presence of radiation therapy-related pneumonia.
Significance: The main manifestations are patchy hyperdense shadows, gross glassy changes in the lungs, large solid shadows, or fibrous streaks.
Early stage presents with mildly increasing homogeneous density shadows within the radiologic field with indistinct borders and lung texture seen within the shadows.
Acute stage shows a patchy uniform density blurred shadow within the lung radiation field, multiple small patchy shadows with unclear borders.
In the advanced stage, triangular or bar-shaped dense shadows distributed across the lobes of the lungs in the irradiated field with bronchial inflation signs seen within the shadows, with neat margins.
In pulmonary fibrosis, there are thin strips or thin reticular shadows in the radiological fields, which may be fused into a mass, with many fluffy spikes protruding from the margins, mainly in the hilum or mediastinum, as well as in the other radiological fields.
Chest X-ray
Purpose: To find out if there is radiation therapy related pneumonia
Significance: Chest X-ray shows patches of dense shadows and large solid shadows.
Chest CT gives a clearer picture of the lesion than chest X-ray.
Grading
According to the National Radiation Therapy Cooperative Group, RTOGRP grading criteria, radiation pneumonitis is categorized into 6 grades according to the severity of the disease.
Grading Criteria
Grade 0 No symptoms, can study, live and work normally.
Grade 0
No symptoms, can study, live and work normally.
Grade 1: Only a slight cough, symptoms can be relieved on their own without medication, but some people may have difficulty breathing if they are tired.
Grade 1
Only a slight cough, without medication, symptoms can be relieved on their own, if exertion part of the population may have difficulty breathing.
Grade 2 if the cough is persistent and dry, requiring medication to calm the cough, and dyspnea occurs after activity.
Grade 2
If the cough is persistent and dry, requires medication to suppress coughing, and has difficulty breathing after activity.
Grade 3: Pneumonia with a significant cough that is difficult to control with medication, persistent dyspnea, radiographic changes of pneumonia, and the need for hormonal therapy for symptomatic relief.
Grade 3
Pneumonia manifestations such as cough obvious, difficult to control by drugs, and persistent dyspnea, lung imaging may have radioactive pneumonia changes, need hormone therapy to relieve symptoms.
Grade 4 is the advanced stage of radiation pneumonitis, manifested by shortness of breath, severe dyspnea, severe hypoxemia, requiring continuous oxygen therapy, and some people may develop respiratory failure, requiring ventilator-assisted respiration to maintain life.
Grade 4
Advanced stage of radiation pneumonitis, characterized by shortness of breath, severe dyspnea, severe hypoxemia, requiring continuous oxygen therapy, and in some people, respiratory failure requiring ventilator-assisted ventilation to maintain life.
Grade 5 is severe and leads to death.
Grade 5
The condition is severe and leads to death.
Differential Diagnosis
Tumor progression
Similarities: Both lung tumors and radiation pneumonitis can present with symptoms of cough and dyspnea.
Differences: Imaging can see tumor enlargement compressing the airways and multiple metastases in the lungs, suggesting tumor progression. Radiation pneumonitis can be seen on imaging as a patchy uniformly dense blurred shadow, or even a fine corded strip or a slender reticular shadow.
Lung infection
Similarity: both may present with fever, cough and sputum.
Differences: patients with lung infection usually do not have a history of radiation therapy for tumors, pathogenicity testing reveals relevant pathogens, patients with tumors have an increased risk of respiratory infections during radiation/chemotherapy, and severe radiation pneumonitis can be differentiated by the imaging manifestations of pulmonary fibrosis.
Acute pulmonary embolism
Similarities: Both may present with symptoms of chest pain, chest tightness, shortness of breath, hemoptysis.
Differences: the symptoms of acute lung injury usually appear suddenly, with a sharp increase in blood D-dimer; whereas the symptoms of radiation pneumonitis are not sudden, and CT pulmonary angiography can be used for differential diagnosis.
Drug-induced lung injury
Similarities: both have symptoms of cough and dyspnea.
Differences: some chemotherapy drugs may cause lung tissue damage. In drug-related lung tissue injury, the damaged area of the lungs is more spread out, whereas in radiation pneumonitis, the damaged area of the lungs is the area that received the irradiation.
Treatment
Aims of treatment: to improve symptoms, control disease flare-ups, and improve the patient’s quality of life.
Treatment principle: Individualized treatment plan according to the condition. Those who have only imaging manifestations but no clinical symptoms do not need treatment. If there are symptoms of radiation pneumonitis, glucocorticoids, expectorants, free radical scavengers and other medications should be used under the supervision of a doctor, as well as the improvement of hypoxia treatment.
Supportive treatment
Expectorants
The commonly used drug is Ambroxol.
Drug effect: dilute mucous phlegm, so that the phlegm can be easily discharged.
Drug precautions; adverse reactions can be seen nausea, stomach pain, skin and mucous membrane allergic reactions, etc. Allergy to this product is prohibited.
Improvement of hypoxia treatment
Active oxygen inhalation can help to improve hypoxemia, etc.
Anti-infective drugs
Anti-infective drugs should be selected according to the severity of the disease and the clinical manifestations of related infections and test results.
Some studies have shown that radiation pneumonitis generally belongs to aseptic lymphocytic pneumonia, so the use of antibiotics is prophylactic [4].
Glucocorticoid therapy
Glucocorticoids are commonly used in the treatment of radiation pneumonitis, with an effective rate of up to 80%.
Commonly used drugs are prednisone, dexamethasone and so on.
After the disappearance of symptoms, the dosage is gradually reduced depending on the condition, usually not less than 6 weeks. Long-term use of hormones is prone to secondary infections, electrolyte disorders and other adverse reactions. Allergy to glucocorticoids, active peptic ulcer, systemic fungal infections, etc. are prohibited.
Other treatments
Preventive medicine
Amifostine is the most used prophylactic drug at this stage, which can reduce the toxic side effects in radiotherapy for certain tumors and attenuate the toxicity of chemotherapeutic drugs such as cisplatin [11].
Progress on the frontiers
Some new drugs such as reactive oxygen scavengers, angiotensin-converting enzyme inhibitors, cytokine inhibitors and protease inhibitors have brought hope for treatment, but most of these drugs are in the preclinical stage of animal experiments and cellular experiments, and need to be further verified in the clinic.
Recent studies have confirmed that stem cell transplantation also has a better repair effect on various lung injuries.
Some studies have shown that both azathioprine and cyclosporine can effectively treat the symptoms of radiation pneumonitis; these drugs can be considered for patients who cannot tolerate glucocorticoids or who suffer from glucocorticoid treatment-refractory diseases [3].
Prognosis
Cure
Overall prognosis
Untreated
Those with mild or asymptomatic symptoms may subside on their own, requiring prompt medical attention and treatment under medical supervision.
Untreated persons may experience worsening of the condition, serious complications, or even death.
After treatment
Most mildly ill patients can be cured with active drug treatment.
Complications such as heart failure and respiratory failure often occur in severe cases, and the prognosis is mostly poor.
Hazards
Physiological hazards
Radiation pneumonia is severe, and patients with poor response to treatment may have their daily activities affected, or even experience respiratory failure, heart failure, or even death.
Psychological hazards
Radiation pneumonia with long duration and poor prognosis may lead to depression, anxiety and fear, which may affect the recovery of the disease.
Daily
During the period at home, patients should follow the doctor’s instructions to take medication, take rest, exercise appropriately, prevent infections, and follow the doctor’s instructions to repeat the examination on time if the condition improves and stabilizes. Scientific and reasonable daily life management can ensure the normal functioning of the body and promote the recovery of the disease.
Daily management
Dietary management
Supplement sufficient calories and high quality protein;
Eat light, nutritionally balanced food, small meals and more fresh vegetables and fruits;
Strictly prohibit eating raw, cold, greasy and spicy food with irritating properties, such as wine, pepper, chili, onion, etc.; avoid pickled and greasy food.
Life management
Pay attention to rest, avoid staying up late and ensure sufficient sleep.
Regulate the indoor temperature, pay attention to indoor air circulation and keep the air fresh.
Take moderate exercise, such as walking, tai chi, yoga, etc., in order to feel that the body is not tired.
Protect yourself from cold and warmth, and pay attention to the prevention of colds and flu.
Quit smoking and avoid alcohol.
For those who cough up phlegm, pat their backs to help them expel phlegm. For those who have difficulty in breathing, take a sitting or semi-recumbent position and instruct them to take deep breaths.
Psychological support