Ye Suyi, Beijing Institute of Respiratory Diseases, Beijing Chaoyang Hospital, Capital Medical University Ye Suyi, Department of Respiratory and Critical Care Medicine, Beijing Chaoyang Hospital What is pulmonary Langerhans cell histiocytosis? Xiao Zhang, male, 20 years old, is a college student who likes sports. He had a sudden onset of dyspnea and chest pain while playing basketball and immediately went to the emergency room of the hospital. The doctor took a chest X-ray of Xiao Zhang and found a left spontaneous pneumothorax with 60% compression;, and multiple cystic shadows in both upper lungs. The thoracic surgeon performed closed chest drainage and oxygen therapy on Xiao Zhang. A few days later, Xiao Zhang’s pneumothorax disappeared and the left lung reopened. How did the pneumothorax occur and will it recur? After repeated questioning by the doctor, Xiao Zhang admitted to smoking for 5 years and smoking 1 pack per day. The doctor gave Xiao Zhang a high-resolution CT of the chest and found multiple cystic shadows in both upper lungs. A thoracoscopic lung biopsy diagnosed Langerhans cell histiocytosis (PLCH). The rupture of these cystic cavities during exercise led to the development of pneumothorax. Pulmonary Langerhans cell histiocytosis is a relatively rare group of lung diseases characterized by proliferative infiltration of Langerhans cells, forming multiple parabronchial interstitial nodules and cystic cavities in both lungs, usually in young people, almost always smokers, and can occur repeatedly in pneumothorax, mostly with a benign and prolonged course. 2.Who are susceptible to pulmonary Langerhans cell histiocytosis? Pulmonary Langerhans cell histiocytosis can occur in any age group, and most patients who visit the hospital are between 20 and 40 years old, with more men than women. Recent reports of equal incidence in men and women may reflect an increase in female smokers. The vast majority of patients are smokers, especially heavy smokers, but those with a shorter smoking history can also develop the disease. Patients who undergo lung transplantation at the end stage may have a recurrence of disease if they continue to smoke. 3.What are the clinical manifestations of pulmonary Langerhans cell histiocytosis? The clinical manifestations of pulmonary Langerhans cell histiocytosis vary widely. Some patients have no respiratory symptoms and are therefore easily missed, or are detected when they have a more advanced disease with dry cough and dyspnea after activity. As described in the above case, about 10%; of patients have spontaneous pneumothorax due to rupture of the subpleural cystic cavity, which can be the first symptom of the disease, or recurrent pneumothorax during the course of the disease. A small number of patients have systemic symptoms such as wasting, malaise, fever, night sweats and loss of appetite, and should be examined for combined tumors. The majority of patients with pulmonary Langerhans cell histiocytosis have monosystemic involvement, and less than one fifth of patients have other organ involvement, such as skeletal involvement causing pain, limping in hip involvement, sternal involvement showing sternal pain; involvement of hypothalamus causing uremia with polyuria and irritability; skin involvement causing rash; superficial lymph node involvement causing lymph node enlargement; thyroid involvement causing goiter The abdominal discomfort is caused by the involvement of liver and spleen. Systemic examination should be emphasized, especially if important organs are involved at the same time. 4. How is pulmonary histiocytosis diagnosed? In young and middle-aged smokers, high resolution CT of the chest shows bilateral symmetrical nodules and cystic shadows, with the upper and middle lung fields as the focus, combined with CD1a positive Langerhans cells in bronchoalveolar lavage fluid greater than 5%; the clinical diagnosis of pulmonary Langerhans cell histiocytosis can be made. In cases that cannot be diagnosed clinically, surgical thoracoscopy or open lung biopsy is usually required, and the diagnosis is made by histopathology of the lung showing typical stellate interstitial nodules and cystic cavities centered in the fine bronchi with positive CD1a and S-100 staining of pulmonary Langerhans cells. Patients diagnosed with this disease should also be examined for extra-pulmonary organ involvement, such as the hip bone, skin, pituitary gland, lymph nodes, thyroid, liver and spleen. 5.How is pulmonary Langham cell histiocytosis treated? (1) Quitting smoking is the primary treatment measure. Most patients have stable or improving disease and partial or complete disappearance of imaging lesions 6 to 24 months after quitting smoking. (2) A few patients whose disease progresses even after quitting smoking can be treated with glucocorticoids. The initial dose of prednisone is 0.5 mg/kg to 1 mg/kg per day, after which the dose is gradually reduced and taken continuously for 6 to 12 months. Cytotoxic drugs such as methotrexate and cyclophosphamide can be used in patients with multi-organ involvement who do not respond to hormones. It is worth noting that the efficacy of these drugs is not certain and they have certain side effects. (3), With the increasing understanding of disease pathogenesis, recent studies have reported that verofenib, a BRAF serine-threonine kinase mutation inhibitor, which is usually used for the treatment of advanced melanoma, has some clinical efficacy in patients with pulmonary Langerhans cell histiocytosis who are positive for BRAF V600E gene mutation and whose disease still progresses after smoking cessation, and it is expected to be therapeutic drug for this disease. (4) In patients with respiratory failure or pulmonary hypertension, lung transplantation may be considered.