OVERVIEW
可能有咳嗽、咳痰、胸痛、胸闷、咯血等症状
病因复杂，多种良恶性疾病都能引起多发性肺结节
根据具体原因和病情，给予个体化的治疗方案
病因不同，预后不同，可出现治愈、病情持续、死亡等结局
Definition
Lung nodules are a common clinical pathology, often detected by imaging, and appear as hyperdense shadows, essentially round or irregular lesions less than or equal to 30 millimeters in diameter in the lungs, which may be single or multiple, with clear or unclear borders.
There is no clear clinical diagnosis of “multiple pulmonary nodules”, which generally refers to two or more nodular lesions [1]. In contrast, isolated pulmonary nodules are often defined as a single roundish nodule confined to the lungs, usually less than 30 mm in diameter.
Pulmonary nodular disease can cause multiple pulmonary nodules, but the two should not be equated.
Classification
Classification according to nodule diameter
Pulmonary nodules: 10~30 mm in diameter.
Small nodules: 5~10 mm in diameter.
Micro nodules: <5 mm in diameter.
Classification according to nodule imaging density
Solid pulmonary nodules: Intrapulmonary nodules appear as hyperdense shadows on CT imaging, and the nodule shadows are sufficient to obscure the traveling blood vessels or bronchial shadows therein.
Sub-solid nodules: These include ground-glass nodules and partially solid nodules, and the nodule shadows do not obscure the traveling blood vessels or bronchial shadows on CT images.
Classification according to the benign or malignant nature of nodules
They can be divided into benign and malignant pulmonary nodules [1].
Causes
Causes
There are numerous etiologic factors and complex pathogenesis in the formation of multiple pulmonary nodules, which can be categorized into two main groups, malignant and benign, according to the benign or malignant nature of the disease causing the multiple pulmonary nodules.
Malignant lesions
原发性肺癌
Such as lung adenocarcinoma, lung squamous carcinoma, lung small cell carcinoma, and other rare primary tumors of the lung.
转移性恶性肿瘤
For example, nasopharyngeal carcinoma, melanoma, colon cancer, breast cancer, prostate cancer, thyroid cancer, etc. are easy to metastasize to the lungs, and multiple pulmonary nodules may appear, with solid nodules being relatively common.
Benign lesions
良性肿瘤
Such as lung malformation tumor, lung fibroma, lung lipoma, etc.
感染
Such as tuberculosis, lung fungal (such as Candida, Aspergillus, Trichophyton) infections.
炎性病变
Mostly seen in pulmonary nodular disease, eosinophilic granulomatous polyangiitis, rheumatoid arthritis involving the lungs can also be manifested as multiple pulmonary nodules.
肺血管异常
For example, pulmonary arteriovenous malformation (PAVM), pulmonary capillaritis [2-3].
High risk factors
The following factors are high risk factors for the development of multiple pulmonary nodules.
Smoking or a history of previous smoking.
Presence of a history of fungal, bacterial, or tuberculosis infection of the lungs.
Pre-existing malignant tumors or a family history of lung cancer.
History of environmental or high-risk occupational exposure, such as frequent exposure to asbestos.
Combined chronic obstructive pulmonary disease, diffuse pulmonary fibrosis.
Symptoms
Multiple pulmonary nodules itself is a kind of pathological changes, the imaging manifestation of the number, size, density of the shadow is not the same, some patients can be no clinical symptoms, there are also patients can appear different clinical symptoms, but most of them are manifested as the symptoms of the primary disease of multiple pulmonary nodules. The following is a description of the symptoms of several common primary diseases, but it does not mean that these are the only primary diseases and symptoms.
Symptoms of primary disease
Lung cancer
Cough is an early symptom, which is often an irritating dry cough with no or little sputum.
Lung cancer patients may also have symptoms such as blood in sputum or hemoptysis, shortness of breath or wheezing, chest pain, fever and emaciation.
Early stage lung cancer can also be asymptomatic and found through physical examination.
Lung malformation tumor
Most patients have no symptoms, and those who have symptoms often show cough, sputum, shortness of breath, chest pain, fever and other symptoms.
Lung nodular disease
Symptoms include fever, fatigue, weight loss, arthralgia, chest pain, cough, dyspnea and hemoptysis.
Tuberculosis
Coughing, coughing up sputum for more than two weeks or blood in sputum are common suspicious symptoms of tuberculosis. About 1/3 of the patients have hemoptysis, most of the patients have a small amount of hemoptysis, and a few have a large amount of hemoptysis. Chest pain may be manifested when TB lesions involve the pleura, which is aggravated by respiratory movements and coughing.
Fever is the most common symptom of systemic toxicity, which is mostly prolonged afternoon hot flashes, i.e., it starts to rise in the afternoon or evening, and then falls to normal in the next morning. Some patients have lethargy, night sweats, loss of appetite and weight loss [4-7].
Rheumatoid arthritis
When rheumatoid arthritis involves the lungs, multiple pulmonary nodules can form.
However, rheumatoid arthritis is more commonly characterized by extrapulmonary manifestations, such as joint swelling and pain, morning stiffness, and loss of joint function.
Symptoms associated with nodules
Symptoms caused by the nodules themselves damaging the lungs may not be as obvious as the symptoms of the primary disease, but they may occur.
Cough: seen when multiple pulmonary nodules invade the bronchial tubes or secondary to infection, and may be accompanied by coughing up sputum.
Chest pain: seen when the nodules involve the pleura or chest wall and may produce chest pain.
Dyspnea: This is seen when the nodules are growing and increasing in size, compressing the larger bronchi or destroying a large number of alveoli.
Hemoptysis: when the nodule invades the blood vessels in the lungs, the patient may experience hemoptysis [8].
Seek medical attention.
If multiple pulmonary nodules are detected on physical examination, or if any of the aforementioned symptoms are present, medical attention is recommended.
Department of Medicine
Respiratory medicine
Stabilized patients with symptoms such as cough, chest pain, or nodules detected by physical examination may consult the department of respiratory medicine.
Thoracic Surgery
If a physical examination reveals multiple pulmonary nodules that are large in size and very numerous, and may require surgery or surgical sampling for examination, the Department of Thoracic Surgery may be consulted.
Oncology
Long-term smokers and those with a past history of tumors may also visit the Oncology Department.
Emergency Department
For critical situations and severe symptoms, such as hemoptysis and respiratory distress, please visit the emergency department or call 120 emergency number [5].
Preparation for medical treatment
Preparation for medical consultation: registration, preparation of information, common problems
Tips for medical treatment
Most patients need imaging tests, and should wear loose clothing without metal jewelry.
Preparation checklist
症状清单
Pay special attention to the time of onset of symptoms, special manifestations, etc.
Did you experience cough, sputum, chest pain, dyspnea, hemoptysis, etc.? When did they occur?
Have the symptoms worsened recently?
Has there been any recent weight loss?
Did you have a fever before the visit? What was the highest temperature?
Any other discomfort?
病史清单
Any previous illnesses such as tuberculosis, malignant tumors, or pulmonary nodular disease?
If so, what treatment did you receive? What is the effect?
Has anyone in your family had a similar condition?
What kind of work do you do? What is the working environment?
Do you smoke? How many years have you smoked? How many cigarettes a day?
检查清单
Test results in the last six months, which can be brought to the doctor’s office.
Laboratory tests: blood sedimentation, blood routine, tuberculin test, sputum smear, culture of Mycobacterium tuberculosis, sputum culture, antinuclear antibody profile, anti-neutrophil cytoplasmic antibody, autoantibody profile of rheumatoid arthritis, tumor markers, etc.
Imaging examination: chest X-ray, chest CT, etc.
Others: bronchoscopy.
用药清单
Medication use in the last 3 months, if there is a medicine box or package, you can bring it to the doctor
Glucocorticoids: e.g. prednisone, methylprednisolone, etc.
Immunosuppressants: e.g. cyclophosphamide, mycophenolate mofetil, etc.
Antipyretic and analgesic drugs: ibuprofen, acetaminophen, etc.
Anti-tuberculosis drugs: isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin, etc.
Anti-infective drugs: e.g. levofloxacin, moxifloxacin, etc.
Diagnosis
Diagnosis basis
The doctor can make a preliminary diagnosis based on the patient’s clinical manifestations and imaging findings.
Medical history
Patients with multiple pulmonary nodules may have the following medical history.
History of occupational exposure.
History of smoking.
History of chronic lung disease.
Personal and family history of tumors.
Clinical manifestations
Symptoms: may be asymptomatic or may be characterized by cough, sputum, hemoptysis, chest pain, and dyspnea.
Signs: Multiple pulmonary nodules usually have no clear pulmonary signs. If the tumor is malignant, some patients can touch some enlarged lymph nodes in the neck and axilla.
Laboratory tests
血常规
If white blood cells and neutrophils are elevated, this often suggests bacterial infectious disease.
If the white blood cells and neutrophils are not increased, but the lymphocytes are increased, it may suggest viral infection.
炎性指标
Calcitonin, C-reactive protein, and blood sedimentation are often checked together with routine blood tests to help aid in the diagnosis of infection.
When accompanied by bacterial infection, calcitoninogen and C-reactive protein may be elevated to different degrees, and blood sedimentation is accelerated, and the more it exceeds the reference range, the more serious the infection is often indicated.
血生化检查
It is mainly to understand the liver and kidney function, which is used to assess the patient’s physical status, and is also helpful to guide the use of medication.
Elevated angiotensin-converting enzyme is also suggestive of nodal disease.
肿瘤标志物
For example, carcinoembryonic antigen (CEA), squamous carcinoma antigen (SCC), cytokeratin 19 fragment (CYFRA21-1), neurospecific enolase (NSE), alpha-fetoprotein (AFP), etc., which are suggestive of the diagnosis of malignant tumors.
病原学检查
Tests such as sputum smear and sputum culture are helpful in finding respiratory pathogens that cause infection.
Tuberculin test, T-SPOT test helps in screening for tuberculosis infection.
G test, GM test, Aspergillus IgG antibody test are useful in the diagnosis of fungi. NGS testing of alveolar lavage fluid and sputum has the potential to clarify pathogenesis more quickly.
Imaging
X线
It can be used for initial screening of multiple pulmonary nodules, but some nodules less than 1 cm in diameter do not show up clearly on chest X-ray, so X-ray chest radiography is not recommended for routine evaluation of pulmonary nodules.
CT
Chest CT scans provide more information about the location, size, morphology, density, margins, and internal features of lung nodules than chest X-rays. It is best to perform a high-resolution CT of the chest, which can clarify the nature of the hairy glass nodules.
Thin-layer scanning of the lesion at the nodule during chest CT examination can better visualize the features of the pulmonary nodule and also help to further infer the nature of the nodule [6-7].
Bronchoscopy
Bronchoscopy can visualize the airways for lesions, which is helpful for assessing the condition and making differential diagnosis.
Airway secretions and alveolar lavage fluid can be collected and sent for pathogenetic examination, which helps to clarify the diagnosis.
Samples can be taken via bronchoscopy for lung biopsy to clarify the diagnosis.
Thoracoscopy
Thoracoscopy can directly observe whether there is any involvement of the pleural (dirty layer and wall layer) surface. Samples of pleural and peripulmonary nodules can be taken for biopsy to further clarify the nature of the lesion.
Pathologic examination
Pathologic examination is the gold standard for clarifying the etiology of multiple pulmonary nodules.
The corresponding tissue specimens can be obtained through bronchoscopy, thoracoscopy, surgery, etc. for pathological examination, which can mostly clarify the diagnosis.
Diagnostic criteria
Multiple pulmonary nodules can be diagnosed by the presence of focal, rounded, hyperdense solid or subsolid lung shadows ≤30 mm in diameter and ≥2 in number on lung imaging.
Differential diagnosis
Multiple pulmonary nodules have many causes, and the differential diagnosis requires differentiation between the different etiologic factors, as well as from non-nodular diseases.
Differentiation from non-nodular diseases
The main focus is to differentiate from non-nodular diseases that can cause multiple shadows on imaging, and the following is a description of the differentiation of two common diseases.
肺大疱
Similarities: Both may present with similar symptoms or neither may show symptoms. Multiple shadows can be seen on chest X-rays and chest CTs.
Differences: lung blisters on X-ray and chest CT show a thin-walled cavity with increased translucency in the lung field, sparse lung texture in the cavity, isolated hairline-like blister walls in the periphery, and shadows of compacted lung tissue around the blisters, with occasional liquid planes visible in the blister cavities. CT can show the extent of the blisters more clearly, which is helpful for differentiation.
肺脓肿
Similarity: both can cause cough, sputum, fever and other symptoms, chest X-ray and chest CT can show multiple shadows.
Differences: X-ray shows a large, dense, fuzzy or mass-like infiltration shadow with unclear edges, distributed in one or several lung segments. After the formation of a lung abscess, the abscess cavity appears as a rounded translucent area and air-fluid plane. Chest CT can more accurately localize and identify lung abscesses.
It is important to note that lung abscesses can also be secondary to multiple lung nodules.
Identification of the cause of multiple pulmonary nodules
After the initial determination that the lesions in the lungs are indeed multiple pulmonary nodules, an etiologic differential is needed.
There are many causes of multiple pulmonary nodules, as described in the previous section, including lung cancer, lung misshapen tumor, pulmonary nodular disease, pulmonary rheumatoid arthritis, etc. Combined with the respective medical history, symptoms, laboratory tests and imaging, endoscopy, etc., the preliminary identification is possible, and pathologic examination is the gold standard for difficult identification.
Treatment
Aims of treatment: Different causes lead to different aims of treatment. For multiple pulmonary nodules caused by infectious diseases, the aim of treatment is to eradicate, prevent and reduce recurrence. For intrapulmonary tumors, the aim of treatment is to control the disease, delay the progression of the disease, prolong the patient’s life and improve the patient’s quality of life.
Treatment principle: According to the different causes of lung nodules, individualized treatment plans are given. If lung nodules are diagnosed as benign or malignant tumors, surgical resection can be considered and combined with other measures for comprehensive treatment; for those caused by Mycobacterium tuberculosis infection and fungal infection, anti-tuberculosis and anti-fungal treatments will be given respectively.
Drug treatment
Anti-tuberculosis drugs
They are mainly used for multiple pulmonary nodules caused by tuberculosis.
Commonly used drugs are isoniazid, rifampicin, pyrazinamide, ethambutol, streptomycin and so on.
Antibiotics
Mainly for patients with symptoms of infection and can prevent secondary infection.
Commonly used drugs are levofloxacin, moxifloxacin, amoxicillin, cefuroxime, cefaclor and so on.
Antifungal drugs
Mainly used for patients with fungal infections.
Commonly used drugs are fluconazole, itraconazole, voriconazole, amphotericin B and so on.
Glucocorticoids and immunosuppressants
Mainly used for rheumatoid arthritis caused by rheumatoid nodules, granulomatous polyangiitis, pulmonary nodular disease and so on.
Commonly used glucocorticosteroids are prednisone, methylprednisolone and so on.
Commonly used immunosuppressants are cyclophosphamide, mycophenolate mofetil, etc. [2-3].
Anti-tumor drugs
They are mainly used to treat lung cancer or metastatic lung tumors, and appropriate drugs are selected according to the results of pathological examinations.
Commonly used drugs include gefitinib, erlotinib, paclitaxel, cisplatin, carboplatin, pemetrexed, docetaxel, gemcitabine and so on.
Surgery
Television-assisted thoracoscopic surgery
The surgeon makes tiny incisions in the patient’s chest and inserts a tube with a camera and light source to perform the procedure. It is characterized by wide field of vision, less trauma, less pain, and quicker recovery after surgery.
Open Chest Resection
For more deeply located pulmonary nodules, open thoracotomy may be required [9-10].
Prognosis
Cure
Benign multiple pulmonary nodules
Most multiple pulmonary nodules caused by infection have a good prognosis and can be cured after prompt, rational and standardized anti-infection treatment.
For most benign tumors in the lung, most of them can be cured after timely and reasonable surgical treatment.
Multiple pulmonary nodules caused by inflammatory lesions such as eosinophilic granulomatous polyangiitis and pulmonary nodular disease can usually be controlled and have a good prognosis after reasonable treatment.
Pulmonary venous malformations usually have a good prognosis after prompt surgical or embolic treatment.
Malignant lung nodules
Malignant lung nodules (e.g. adenocarcinoma of the lung) usually have a good prognosis if diagnosed and treated early, and some patients can be clinically cured.
If not treated effectively, they may be life-threatening.
Certain specific types of tumors have a poorer prognosis, such as small cell lung cancer,[2-3].
Hazards.
Lung nodules that are not effectively controlled can cause impairment of lung function.
It can also cause damage to other parts of the body when combined with infection and metastasis of the nodule.
Lung nodules have the potential to be malignant and may be life-threatening if not treated effectively.
Daily
Daily Management
Dietary management
Light and easily digestible food is recommended.
It is advisable to eat more fresh vegetables and fruits, such as watermelon, citrus and pear.
High protein foods, such as eggs, milk, chicken, fish, shrimp, etc. can be eaten appropriately.
Avoid eating fatty and spicy stimulating food.
Life management
Quit smoking.
Semi-sitting position or high pillow position can be used when there is dyspnea to avoid causing airway compression.
Patients with sputum should cough it up in time.
Ensure sufficient sleep and regular rest.
Enhance physical fitness and exercise properly to promote recovery.
Indoor air should be kept fresh, pay attention to ventilation, but avoid direct blowing caused by cold and flu, etc. [5].
Disease monitoring
Patients can observe the changes of symptoms such as cough and sputum by themselves at home, and if the symptoms worsen, they should consult the doctor in time.
For patients who have already experienced decreased lung function and dyspnea, blood oxygen saturation can be monitored at home, and if it continues to be lower than normal, they should also seek timely medical attention. Depending on the cause of the pulmonary nodule, the monitoring program may vary.
肺部肿瘤：需根据医嘱定期监测血常规、血肿瘤标记物、胸腹盆CT等评估病情。
感染性疾病：需遵医嘱复查血常规、C反应蛋白、血沉、降钙素原及胸部CT等项目。
炎症性疾病：需遵医嘱复查血尿常规、C反应蛋白、血沉、免疫球蛋白、胸部CT等项目。
Follow-up
For multiple pulmonary nodules ≤5 mm in diameter, follow-up chest CT is recommended at 6 months, followed by annual follow-up chest CT.
For multiple pulmonary nodules, at least 1 lesion with a diameter >5 mm but <10 mm and no particularly prominent lesion, follow-up CT is recommended 3 months after the first examination; if there is no change, annual CT follow-up is recommended for at least 3 years thereafter, and long-term follow-up should also be performed thereafter, but the intervals can be appropriately relaxed.
If the diameter exceeds 10 mm, sometimes limited to 8 mm, nonsurgical biopsy and/or surgical resection is required.
If changes in the lesion are detected, the follow-up period should be adjusted; if the nodule increases, enlarges, or thickens, the follow-up period should be shortened, or selective local excision of the lesion with significant changes should be performed by evaluating the lesion’s location, size, and lung function.
If the nodules decrease, fade or absorb, the follow-up period should be extended or terminated [1,9-10].
In addition to repeat CT, repeat blood tests, C-reactive protein, blood sedimentation, calcitoninogen, and tumor markers may be required.
Prevention
Multiple pulmonary nodules cannot be completely prevented, but the following measures may reduce the risk to some extent.
Stop smoking and avoid second-hand smoke in your life.
Exercise and keep fit.
Wear protective masks when going out in smoggy weather.
Choose safe decoration materials to avoid decoration pollution.
Avoid contact with dust and other substances at work as much as possible for good protection.
Have regular medical checkups to detect lung diseases early and treat them actively.
参考文献
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