Pulmonary diseases caused by medications

　　Drug-induced lung diseases can be classified in various ways from different perspectives. According to clinical, pathological, and X-ray findings, the classification of drug-induced lung diseases is as follows (Table 1). Since the same drug can cause several different lung injuries, the drugs involved in drug-induced lung diseases are many, and only a brief discussion can be made.

　　1. Changes in pulmonary interstitium

　　1. Pulmonary interstitial fibrosis: Many drugs can cause pulmonary interstitial fibrosis, among which cytotoxic drugs are the most common. Since the first report of busulfan-induced pulmonary fibrosis in 1961, there have been increasing reports of pulmonary toxicity caused by cytotoxic drugs. The risk factors for the occurrence of pulmonary diffuse fibrosis caused by these drugs are related to the frequency of medication, total dose of medication, combined medication, combined radiotherapy, high-concentration oxygen therapy, pre-existing lung disease, pulmonary function status, liver and kidney dysfunction, and old age.

　　2. Bronchiolitis obliterans with organizing pneumonia (BOOP); common drugs that can cause BOOP are listed in Table 3.

　　3. Desquamative interstitial pneumonia and lymphocytic interstitial pneumonia: To date, the drugs reported in the literature that can cause desquamative interstitial pneumonia include busulfan, interferon alpha, sulphasalazine, furazolidone, etc. The drugs that can cause lymphocytic interstitial pneumonia include captopril, phenytoin sodium, etc.

　　4. Allergic pneumonia: Some drugs such as carbamazepine, docetaxel (DoeetaXel), gold salts, MTX, furazolidone, procarbazine, etc. can cause allergic pneumonia.

　　5. Lung infiltration with eosinophilia: Many drugs can cause lung infiltration with increased pulmonary eosinophils, including beta-lactam antibiotics, sulfonamides, penicillins, fluoroquinolones, tetracyclines, macrolides, furazolidone, methotrexate, aminosalicylic acid, procarbazine, isoniazid, chlorpropamide, aspirin, furazolidone, sodium cromoglicate, and liquid paraffin, etc.

　　6. Diffuse lung calcification: To date, there have been reports of diffuse lung calcification caused by long-term and high-dose use of calcium salts or vitamin D.

　　2. Pulmonary edema

　　There are many drugs that can cause drug-induced pulmonary edema.

　　3. Airway diseases

　　1. Bronchospasm with or without laryngeal edema: The drugs that can cause bronchospasm are listed in Table 5. The mechanism of drug-induced bronchospasm is still not fully clear and can be roughly summarized into three aspects: allergic reaction, pharmacological reaction, and direct stimulation. Penicillin, immunoglobulins, and iodo oil can cause bronchospasm through allergic reactions, while sodium cromoglycate and polymyxin B are mostly caused by direct stimulation. Most other drugs such as beta-adrenergic receptor blockers, angiotensin-converting enzyme inhibitors, non-steroidal anti-inflammatory drugs, prostaglandin E2, and aspirin cause bronchospasm by pharmacological effects within the body, leading to bronchial smooth muscle contraction. As for why some antitumor drugs and antibiotics can cause bronchospasm, it is not yet clear.

　　2. Cough: The main drugs that can cause simple cough include angiotensin-converting enzyme inhibitors, interleukin-2, methotrexate, streptokinase, and hormones. The mechanism of action is not yet clear and may be related to the metabolism of angiotensin, slow-reacting substances, substance P, and arachidonic acid, etc.

　　4. Pleural lesions

　　Furosemide, dihydromorphine, bromocriptine, clomiphene, phenytoin sodium, cyclophosphamide, procarbazine, methotrexate, propranolol, and amiodarone, which can cause lupus-like syndrome, carbamazepine, isoniazid, methyldopa, hydralazine, procainamide, and oral contraceptives can all cause varying degrees of unilateral or bilateral non-specific pleural effusion, which may sometimes be accompanied by pulmonary parenchymal infiltration. Inappropriate use of anticoagulant warfarin can cause hemorrhagic pleural effusion. In addition, some antitumor drugs such as bleomycin, BCNU, and radiotherapy can cause pulmonary interstitial fibrosis, leading to pneumothorax.

　　5. Pulmonary hemorrhage

　　Can be caused by the long-term and improper use of anticoagulants and their analogs, such as warfarin, aspirin, fibrinolytic agents, streptokinase, and urokinase, and can also be caused by other drugs such as iodo oil, mitomycin, carbamazepine, cyclosporine, furazolidone, and phenytoin sodium. In addition, penicillamine can cause bleeding in the lungs and kidneys through type III hypersensitivity reaction.

　　6. Opportunistic pulmonary infections

　　Secondary pulmonary infections can occur after the long-term use of chemotherapy drugs, corticosteroids, and antibiotics.

　　7. Changes in pulmonary blood vessels

　　Many drugs can cause changes in pulmonary blood vessels, such as oral contraceptives, cyclosporine, mitomycin, interleukin-2, and propranolol can cause pulmonary hypertension; corticosteroids, estrogen, and procainamide are prone to cause pulmonary embolism disease; bleomycin, BCNU, CCNU, oral contraceptives, and radiation can cause occlusion of pulmonary veins. Many drugs can cause pulmonary vasculitis.

　　8. Changes in the mediastinum

　　Phenytoin sodium, carbamazepine, minocycline, aspirin, and other drugs can cause unilateral or bilateral hilum and (or) mediastinal lymph node enlargement. Long-term use of corticosteroids can lead to mediastinal fat deposition, resulting in mediastinal widening. Interferon alpha and interferon beta can cause symptoms similar to sarcoidosis, while interferon gamma can cause the enlargement of the thymus.

　　Nine, neuromuscular lesions

　　Drugs that can cause hypoventilation in alveoli and respiratory failure are mainly anesthetics, sedatives, hypnotics, and muscle relaxants. There are many such drugs, and they will not be listed one by one here.

　　Ten, pulmonary granuloma-like reaction

　　Drugs can act as foreign bodies to stimulate lung tissue reaction, or as organic antigens to induce allergic reactions in the body. For example, oil inhalation into the lungs can cause lipoid pneumonia; the inhalation of liquid paraffin into the lungs can cause localized granulomas. During bronchography, iodinated oil can sometimes cause the formation of pulmonary granulomas, which may even develop into pulmonary interstitial fibrosis. In addition, amiodarone, bleomycin, carbamazepine, phenytoin sodium, vincristine, minocycline, and others can also cause multiple nodular changes in the lungs.

　　Eleven, lupus-like changes

　　So far, about 40 types of drugs can cause lupus-like changes, and pulmonary lupus-like changes are part of systemic lupus erythematosus.

　　Twelve, others

　　Some drugs can cause chest pain, such as bleomycin, bumetanide, etoposide, mesalazine, methotrexate, methyldopa, minocycline, nifedipine (Nimotop), and nitrofurantoin; salbutamol (Ventolin) can cause metabolic acidosis and respiratory distress.

　　Drug-induced lung diseases often present with asthma, respiratory failure, acute pulmonary edema, acute respiratory distress syndrome (ARDS), hemoptysis, etc. Respiratory failure is a clinical syndrome characterized by severe respiratory dysfunction due to various causes, leading to a decrease in arterial partial pressure of oxygen (PaO2), accompanied or not by an increase in arterial partial pressure of carbon dioxide (PaCO2), and a series of pathophysiological disorders. Pulmonary edema refers to a disorder of the balance of tissue fluid production and return in the lungs due to some cause, causing a large amount of tissue fluid to be unable to be absorbed by the pulmonary lymphatic and venous systems in a short period of time, leaking from the pulmonary capillaries and accumulating in the alveoli, interstitium, and small bronchi, thereby causing severe impairment of pulmonary ventilation and gas exchange.

　　Drugs can cause a variety of lung diseases, and their main clinical manifestations mainly include the following aspects:

　　1. Changes in pulmonary interstitium

　　1. Pulmonary interstitial fibrosis: Its clinical manifestations are very similar to idiopathic pulmonary interstitial fibrosis. The main symptoms of patients are cough and progressive dyspnea, and physical examination usually reveals wheezing at the end of inspiration. Clubbing fingers may sometimes be seen.

　　2. Obstructive bronchiolitis: Similar to BOOP caused by infection, connective tissue disease, and bone marrow, organ transplantation, etc., clinical symptoms include cough, difficulty breathing, low fever, and accelerated erythrocyte sedimentation rate. Physical examination usually reveals wheezing at the end of inspiration.

　　3. Desquamative interstitial pneumonia (DIP) and lymphocytic interstitial pneumonia (LIP): Clinical manifestations are similar to idiopathic pulmonary interstitial fibrosis, and diagnosis mainly relies on pathological examination.

　　4. Allergic pneumonia: Often onset acutely (days), clinical manifestations include cough, fever, difficulty breathing, accompanied by general malaise, muscle soreness, and joint pain. About 40% of patients may have varying degrees of peripheral blood eosinophilia.

　　5. Pulmonary infiltration with increased eosinophils: The clinical characteristics of this disease are subacute or gradual onset, with shortness of breath, cough, with or without fever and rash, increased eosinophils in peripheral blood, and infiltration of eosinophils and macrophages in alveoli. The clinical manifestations are similar to Loeffler syndrome.

　　2. Pulmonary edema

　　Pulmonary edema caused by drugs can occur within a few hours after taking the drug, and the main clinical manifestations are dyspnea and hypoxemia.

　　3. Pleural lesions

　　It can cause varying degrees of unilateral or bilateral non-specific pleural effusion, sometimes accompanied by pulmonary parenchymal infiltration. In some patients, antinuclear antibodies may be positive and/or the pleural fluid may have increased eosinophils, but the amount of pleural effusion is generally moderate or less, and it can gradually absorb after stopping the drug for 1 to 2 weeks. Improper use of anticoagulant drugs such as warfarin can cause bloody pleural effusion. In addition, some antitumor drugs such as bleomycin, BCNU, and radiotherapy can cause pulmonary interstitial fibrosis, leading to pneumothorax.

　　4. Pulmonary hemorrhage

　　Pulmonary hemorrhage caused by drugs is often diffuse alveolar hemorrhage. In addition, penicillamine can cause pulmonary and renal hemorrhage through type III hypersensitivity reaction, similar to the manifestations of Goodpasture syndrome.

　　5. Pulmonary vascular changes

　　The clinical manifestations can include fever, weight loss, joint pain, muscle pain, and even pulmonary hemorrhage, gastrointestinal hemorrhage, and renal failure.

　　6. Lupus-like changes

　　40% to 80% of cases have pulmonary manifestations, including pleurisy, pleural effusion, atelectasis, and bilateral diffuse interstitial pneumonia. The lupus syndrome caused by drugs is similar to systemic lupus, with polyarticular pain, fatigue, fever, skin and pulmonary lesions, but central nervous system and renal involvement is relatively rare.

　　The most important measure to prevent drug-induced pulmonary disease is to enhance the awareness of the dual nature of drugs. All drugs should be familiar with their pharmacological effects, strictly control the indications, dosage, and course of treatment. Doctors should remain vigilant about adverse drug reactions in clinical practice, frequently analyze the effects of the drugs used by patients on both sides, avoid the use of unnecessary drugs, and especially for patients with allergic constitution, try to simplify the types and dosage of medication to achieve truly rational medication.

　　The clinical examination methods for pulmonary diseases caused by drugs mainly include laboratory tests and other auxiliary examinations. During laboratory tests, in most patients with lupus-like changes, the antinuclear antibodies are positive, but the antidsDNA is negative. Serum complement determination can be normal or abnormal, and the Coombs test is approximately 1/3 positive. About 17% and 40% of patients with methotrexate can have rash and increased peripheral blood eosinophils, respectively. About 1/3 of patients with amiodarone can present with acute onset, with laboratory findings of leukocytosis and increased erythrocyte sedimentation rate, but an increase in blood eosinophils is not common. Other auxiliary examinations mainly include the following aspects:

　　1. Changes in pulmonary interstitium

　　1. Chest X-ray examination of pulmonary interstitial fibrosis: It can be found that there are reticular and nodular areas of increased density in the lower lungs, and the lesions can involve both lungs in severe cases. A few cases may show normal chest radiographs, and pulmonary function tests can show varying degrees of restrictive ventilation dysfunction and diffusion function reduction. Pathological examination of lung tissue shows atypical type II alveolar epithelial cell hyperplasia, alveolitis, or interstitial inflammation, and varying degrees of pulmonary interstitial fibrosis.

　　2. Bronchiolitis obliterans with organizing pneumonia (BOOP): Chest X-ray examination can reveal multiple patchy infiltrative shadows in both lungs. Pulmonary function tests can show either restrictive ventilation dysfunction or obstructive ventilation dysfunction, and the response to corticosteroid treatment is good.

　　3. Desquamative interstitial pneumonia (DIP) and lymphocytic interstitial pneumonia (LIP): Diagnosis mainly relies on pathological examination.

　　4. Allergic pneumonia: Chest X-ray shows acinar nodular infiltration, with lesions mostly located in the peripheral part of the lungs. Pulmonary function tests show varying degrees of restrictive ventilation dysfunction and hypoxemia. Lung biopsy shows infiltration of polymorphonuclear leukocytes or eosinophils and monocytes in the alveolar cavity, and pulmonary interstitial fibrosis is relatively rare.

　　5. Pulmonary infiltration with increased eosinophils: Chest X-ray shows patchy pulmonary infiltration, often migratory.

　　2. Chest X-ray of pulmonary edema

　　There are diffuse acinar nodular infiltrative changes, while the size and shape of the heart are normal. Lung biopsy shows pulmonary edema but rarely inflammatory response.

　　Patients with lung diseases caused by drugs should eat foods that are cool and detoxifying, rich in trace elements such as calcium and iron, and light, soft liquid foods, and avoid eating spicy, greasy, and sweet foods. Symptoms can also be significantly improved by eating the following foods and fruits and vegetables:

　　1. Foods for Detoxification

　　1. Kelp: According to traditional Chinese medicine, kelp is cold in nature and salty in taste, with the functions of softening hard masses, clearing heat and promoting diuresis, and reducing fat and blood pressure. Modern medical research has proven that the alginate in kelp can reduce the absorption of radioactive element strontium by the intestines and can be excreted out of the body, thus kelp has the effect of preventing leukemia and excreting cadmium that enters the body.

　　2. Tea: The detoxifying effect of tea has been recorded as early as in the ancient book 'Shen Nong's Materia Medica'. Modern medicine believes that tea has the effect of accelerating the excretion of toxic substances in the body, which is inseparable from the comprehensive effect of the tea polyphenols, polysaccharides, and vitamin C it contains.

　　3. Figs: Figs are rich in organic acids and various enzymes, with the effects of clearing heat, moistening the intestines, aiding digestion, and protecting the liver and detoxifying. In recent years, it has been found that figs have certain resistance to toxic substances such as sulfur dioxide, sulfur trioxide, hydrogen chloride, and benzene.

　　4. Carrot: Carrot is also an effective detoxifying food. It is not only rich in beta-carotene, which can increase the body's vitamin A after consumption, but also contains a large amount of pectin. This substance can combine with mercury and effectively reduce the concentration of mercury ions in the blood, accelerate the excretion of mercury ions in the body, and thus has a significant role in preventing mercury poisoning.

　　二、清肠利肺的果蔬食品

　　Second, intestinal cleansing and lung nourishing fruits and vegetables food

　　1, Date

　　(1) Sweet and neutral in taste. It can tonify the body, generate fluid, and nourish the lungs.

　　(2) You can add a few dates to the soup or sugar water when cooking.

　　2, Honey

　　(1) Sweet and neutral in taste, entering the spleen, lung, and large intestine meridians. It has the functions of replenishing the middle, moisturizing dryness, and detoxifying, and is often used to treat dry cough of the lung.

　　The conventional method of Western medicine for treating pulmonary diseases caused by drugs

　　The prognosis of drug-induced pulmonary edema is generally good, and the symptoms can gradually improve after stopping the drug and对症 treatment. The symptoms of pulmonary infiltration with increased eosinophils can be relieved after stopping the drug, and hormone treatment can promote absorption. The common drug that causes pulmonary interstitial fibrosis, such as busulfan (Myleran), has a poor prognosis. The overall mortality rate is between 50% and 80%. The efficacy of corticosteroid treatment varies greatly, with some patients responding well and others not.

　　The prognosis of pulmonary toxicity caused by cyclophosphamide is poor, with a mortality rate of about 50%. The mortality rate of pulmonary injury caused by methotrexate is about 10%; pulmonary edema caused by cytarabine often improves gradually after 7 to 21 days of treatment; the mortality rate of pulmonary damage caused by cytarabine is about 6% to 13%.