Pulmonary nodular disease is the most common type of sarcoidosis and affects more than 90% of the hilum, mediastinal lymph nodes and both lungs, and can involve all systems of the body. The clinical manifestations of pulmonary nodular disease are diverse and non-specific, which can lead to underdiagnosis and misdiagnosis. From January to October 2009, we used transbronchial needle aspiration (TBNA) in combination with lung biopsy. Transbronchial lung biopsy (TBLB) was used to examine 16 patients with stage I pulmonary nodulopathy, and satisfactory diagnostic results were achieved. 1. Data and methods 1.1 General data All 16 patients showed enlarged hilar and mediastinal multigroup lymph nodes by CT lung examination, and no clear infiltration was seen in the lungs. All patients had been clearly diagnosed with pulmonary nodal disease stage I by mediastinoscopy and skin nodal biopsy before performing TBNA combined with TBLB examination, including 6 cases in men and 10 cases in women. The mean age was 41.5±7.3 years old, 37-53 years old. 1.2 Examination methods All 16 patients underwent TBNA and TBLB examination simultaneously. TBNA examination method: Olympus BF P240 electronic tracheoscope was used, and Olympus NA-2C- 1 type of puncture needle was selected. The patient’s preoperative preparation was the same as that of conventional fiberoptic bronchoscopy, and the location of the TBNA puncture site was determined according to the patient’s chest CT image, referring to the WANG’s localization method [1]. The biopsy needle in the protective sleeve is first inserted into the trachea through the bronchoscopic biopsy channel, keeping the bronchoscope in the center of the trachea as much as possible to avoid damage to the tracheal mucosa caused by pushing out the puncture needle. After the puncture needle is ejected, the position is adjusted so that only the metal part of the puncture needle is exposed at the front of the tracheoscope, and the biopsy needle is fixed at the puncture site by relying on the tracheoscope, and the puncture needle is placed at a perpendicular angle to the puncture point as far as possible, and the puncture needle is punctured through the bronchial wall to the lesion by the protrusion or advancement method. Microscopically, the biopsy needle can be seen to be fully penetrated into the tracheal wall, and the penetration depth is about 1.0-1.5 cm. An empty 10 mL syringe is connected to the end of the puncture needle, and aspiration is maintained for 30-40 s to 5-7 ml, while the needle is repeatedly pumped back and forth without exiting the mucosa to obtain the best sampling effect. The negative pressure was released, the puncture needle was withdrawn and returned to the protective sleeve, then the needle was withdrawn from the tracheoscope and the puncture smear was placed in 95% alcohol for fixation, or formalin solution for fixation if there was tissue. Three groups of lymph nodes were selected for each TBNA puncture, and each site was punctured three times. The TBLB biopsy site was selected for the right lower basal lung segment, and three pieces of lung tissue were removed from each patient for examination. 1.3 Diagnostic criteria TBNA puncture smear and BALF puncture lung tissue were single-blinded (blinded to the pathologists), and the diagnosis of “non-caseous necrotizing epithelioid granuloma” was confirmed by two pathologists independently. 1.4 Statistical methods The rates were compared by x-square test, and P0.05 was considered statistically significant. 2. Results 2.1 Diagnostic compliance rate of TBNA combined with BALB Among the 16 patients, 11 cases (68.8%) of TBNA and 7 cases (43.8%) of TBLB obtained a positive diagnosis of “non-caseous necrotizing epithelioid granuloma”, and 15 cases (93.8%) obtained a positive diagnosis of the two together. The diagnostic compliance rate of TBNA combined with BALB was significantly higher than the diagnostic compliance rate of both of them alone (P0.05). 2.2 Complications of TBNA combined with BALB examination TBNA patients had only a small amount of bleeding at the puncture site, and no special treatment was required. One patient (6.2%) had a small amount of pneumothorax during TBLB, which improved after puncture and aspiration. The most important index for the diagnosis of nodular disease is the pathological findings, and the histological examination found “non-caseous necrotizing epithelioid granuloma” is the “gold standard” for the diagnosis of nodular disease. However, most pulmonary nodules are not endotracheal lesions, mainly presenting as bilateral hilar and mediastinal lymph node enlargement and intrapulmonary infiltration, and it is difficult to obtain ideal tissue for routine bronchoscopy to confirm the diagnosis. The TBNA technique was first reported by an Argentinian physician, Schieppati, in 1949, when a rigid tracheoscope was used to perform the puncture, thus opening up a new field for tracheoscopy and providing a convenient and easy diagnostic method for patients with mediastinal lesions. With the continuous improvement of soft tracheoscopy and other instruments and various operation techniques, TBNA has been widely used in clinical work, especially in the diagnosis of lung malignancies with a high compliance rate, which is important for preoperative diagnostic staging and surgical selection of lung cancer, and can largely replace mediastinoscopy and open-chest exploration [2]. In China, Wang Mengzhao [3] et al. concluded that TBNA is not very helpful for the diagnosis of benign mediastinal lesions, and Trisolini et al. and Bilaceroglu et al. reported that TBNA can clarify more than 50% of nodular disease and tuberculosis [4-5]. In our group, TBNA combined with TBLB was applied to 16 cases of confirmed pulmonary stage I nodular disease, and the diagnostic compliance rate reached more than 90%. The diagnostic compliance rate of TBNA was about 70% and that of TBLB was about 40%, and the diagnostic compliance rate of the combination of the two was significantly higher than the diagnostic compliance rate of the two alone. Nodular disease is stimulated by certain pathogenic antigens, and T lymphocytes, monocytes and macrophages infiltrate into the alveoli, forming the early stage of nodular disease – the alveolitis stage. Subsequently, the cellular component of alveolitis decreases and the number of macrophage-derived epithelioid cells gradually increases, resulting in the formation of non-caseating nodular granulomas. In later stages, macrophages release fibronectin, the number of fibroblasts increases, and surrounding inflammatory and immune cells are further reduced to the point of disappearance, eventually leading to extensive pulmonary fibrosis. The TBNA technique can directly obtain specimens from multiple points of multiple lymph nodes and immediately send them for histological examination, thus improving the positive rate of nodular disease diagnosis. Meanwhile, in stage I nodal disease without clear pulmonary imaging changes, TBLB can still obtain suitable specimens to clarify the diagnosis of nodal disease because of its possible lung infiltration, and the combined application of the two can significantly improve the positive diagnostic rate. Our results show that the TBNA technique combined with the TBLB technique can increase the positive histological diagnosis of nodular disease to more than 90% and is a recommended combination of endoscopic techniques in the diagnosis of nodular disease [6-7]. It should be noted that our experience shows that when performing TBNA, it is best to select more than three groups of lymph nodes for examination, with no less than three needle aspiration biopsy sites per group; since pulmonary nodular disease most often invades the lower lung, it is best to select the basal segment of the lower lung for TBLB, with no less than three lung tissue specimens sent for examination each time. TBNA combined with TBLB technique is minimally invasive, safe, can be operated under local anesthesia, has few complications, and has a high positive diagnostic rate, which is a safe and effective method for the diagnosis of pulmonary nodular disease.