2018年 · 第41卷第06期

This issue of "Diagnosis and Treatment Plan" column published a total of 3 important expert consensus, please pay attention to it.

Cryobiopsy is to send the tip of the frozen probe to the diseased tissue, and according to the Joule-Thomson effect, the heat of the surrounding environment is absorbed through the rapid release of refrigerant, so that the tip of the frozen probe is quickly cooled, the tissue around the probe is frozen and solidified, and the probe and the tissue around the probe are pulled out as a whole through adhesion, so as to obtain the target tissue. Because the obtained specimen tissue is large and of high quality, it does not affect the pathological analysis, and it is helpful to improve the pathological diagnosis. Therefore, it has become a new biopsy mode in medicine, especially in respiratory diseases^[1]。 transbronchial cryobiopsy is divided into endobronchial cryobiopsy (EBCB) and transbronchial cryobiopsy (TBCB). The former is for lesions visible under bronchoscopy, mainly located in the trachea and bronchial lumen; The latter refers to peripheral lung lesions that are not visible under bronchoscopy.

With the wide application of bronchoscopy and thoracoscopy, more and more problems in the diagnosis and treatment of a series of lung diseases such as tracheal and bronchial stenosis and even pleural effusion caused by malignant tumors have been solved, and the occupational exposure and damage of medical staff related to interventional respiratory diseases have also begun to attract attention. We analyze this and explore related safeguards.

The importance of pharmacokinetic/pharmacodynamic (PK/PD) theory for guiding the rational use of antimicrobial drugs in clinics has been continuously paid attention to. In 2016, the guidelines for hospital-acquired pneumonia/ventilator-associated pneumonia (HAP/VAP) jointly issued by the American Society of Infectious Diseases/American Thoracic Association (IDSA/ATS) emphasized for the first time in academia that doctors should not use drugs according to the instructions, but should use drugs according to the PK/PD of antimicrobial drugs. We do not completely agree with this statement, but it is sufficient to suggest the importance of antimicrobial drugs PK/PD to guide clinical treatment.

At present, tuberculosis is still the main infectious disease that endangers human health. According to the 2017 World Health Organization Global tuberculosis Report, the number of tuberculosis cases worldwide in 2016 was 10.4 million, including 600,000 new cases of multidrug-resistant tuberculosis (MDR-TB) and rifampicin-resistant tuberculosis (RR-TB) and 30,000 new cases of extensively drug-resistant tuberculosis (XDR-TB)^[1]。 Due to the shortage of new anti-tuberculosis drugs, the treatment of MDR-TB and RR-TB is very difficult, with poor clinical efficacy, high treatment cost, large adverse reactions, and the success rate of treatment is only about 50%. Therefore, the development and development of new anti-tuberculosis drugs is imminent. Bedaquilin is the first new anti-tuberculosis drug on the market in the past 50 years, with a unique mechanism of action and anti-Mycobacterium tuberculosis (Mycobacterium tuberculosis,MTB) has strong activity and good clinical efficacy^[2,3]。 In December 2012, the U.S. Food and Drug Administration accelerated the approval of bedaquiline for the treatment of MDR-TB in adults. In December 2016, my country's Food and Drug Administration approved the conditional listing of bedaquiline in China. In June 2013, the World Health Organization issued the "Interim Strategic Guidance for Bedaquiline in the Treatment of Multidrug-Resistant Tuberculosis"^[4]In 2017, the World Health Organization once again updated the "Bedaquiline Guidelines for the Treatment of Multidrug-Resistant Tuberculosis"^[5]。 There is very little experience in the clinical use of bedaquiline in my country, and no relevant consensus and guidelines have been formulated. To this end, the Tuberculosis Branch of Chinese Medical Association organized experts in related fields across the country to write the "Expert Consensus on Clinical Application of Bedaquiline, a new anti-tuberculosis drug" for the reference of domestic colleagues.

Example 1The patient was a 47-year-old female, a salesperson in a mall. He was admitted to hospital on January 8, 2015 due to "cough and asthma for more than 3 months". Three months ago, the patient developed dry cough with asthma after catching cold, which was aggravated after activity, and the symptoms did not improve after self-administration of "cefuroxime". X-ray chest radiograph from outside hospital showed postoperative changes of left lung and increased and thickened texture of both lungs. Pulmonary function showed severe mixed ventilatory dysfunction, which was proposed to be diagnosed as "bronchial asthma". After giving anti-infection, anti-asthma and other comprehensive treatment, the patient's asthma symptoms improved compared with before, but the cough did not improve significantly. In order to further clarify the causes of cough and asthma, he was admitted to our hospital. The patient had undergone left lower lobectomy due to car accident trauma at the age of 29. No tobacco and alcohol addiction. There is no special family history, and his parents are alive. Admission physical examination: There was no cyanosis of the lips, the breathing sound of the right upper lung was slightly low, and no dry or wet rales were heard in both lungs. No clubbed fingers (toes) were seen. Blood routine: white blood cells were 6.58×10⁹/L, 0.53 for neutrophils and 1.07×10 for eosinophils⁹/L. C-reactive protein normal. Pulmonary function test: total lung volume was 2.99 L and FVC was 1.59 L, which was significantly reduced; The residual gas volume was 1.4 L, and the residual-to-total ratio was 46.39%, which was significantly higher; FEV₁was 1.35 L, representing 49.2% of the projected value, and the FEV₁/FVC was 84.75%, suggesting severe mixed ventilatory dysfunction; Negative bronchodilation test. Exhaled nitric oxide was determined as 48.5×10^－9。 Total IgE was 403.12 kU/L, specific IgE: Alternaria spp. was 0.71 kU/L, Cladospora multiplex was 0.49 kU/L, and Aspergillus fumigatus was 1.12 kU/L, all of which were increased. High-resolution CT (HRCT) of the chest showed that the trachea and bilateral left and right bronchial lumens were significantly dilated and enlarged. Multiple patchy and nodular high-density shadows were seen in the right lung, and the left pleural hypertrophy with calcification. Consider megatracheobronchosis (Mounier-Kuhn syndrome), pulmonary infections (Figure 1，Figure 2，Figure 3，Figure 4)。 Flexible bronchoscopy showed that the tracheobronchus was significantly dilated and enlarged, showing dynamic weak collapse, slender cartilage ring, and multiple diverticula in the cavity; The protuberance is soft, and the expiratory phase collapses; More brown-yellow sputum plugs were seen in the anterior and posterior segments of the right upper lobe, and the biopsy membrane was very soft (Figure 5，Figure 6，Figure 7，Figure 8)。 Tissue biopsy was performed at the lower end of the trachea and the opening of the right upper lobe. Pathology showed acute and chronic mucosal inflammation with granulation tissue formation, inflammatory exudation, eosinophils and a small amount of scattered epithelioid cells. BALF fungal culture was negative. Based on clinical, radiographic findings and bronchoscopic findings, the final diagnosis was: Mounier-Kuhn syndrome, pulmonary infection. After treatment with flexible bronchoscope irrigation and intravenous infusion of ceftizoxime for 5 days, the symptoms were significantly relieved. Since follow-up, the patient has no obvious discomfort.

A 62-year-old female was seen on June 30, 2017 because "physical examination found that the upper lobe of the right lung occupied space for 5 days". The patient had no symptoms such as fever, cough and hemoptysis. Formerly healthy. Physical examination: body temperature 36.5 ℃, respiratory rate 21 beats/min, pulse rate 77 beats/min, blood pressure 135/85 mmHg (1 mmHg =0.133 kPa), clear consciousness, steady breathing, no bleeding spots in the skin and mucosa of the whole body, no palpable swelling of superficial lymph nodes, symmetrical breathing sounds in both lungs, no dry and wet rales, and no abnormalities in the heart and abdomen. Outpatient blood routine, electrocardiogram and hemagglutination indexes were all normal, and hepatitis B surface antigen was negative. Chest CT showed a mass of 2.3 cm ×3.3 cm in the apical segment of the upper lobe of the right lung, showing soft tissue density, and short burrs around it (Figure 1，Figure 2)。 The neck, axilla and mediastinal lymph nodes were not swollen. The preliminary diagnosis was that the nature of the shadow in the upper lobe of the right lung was to be determined. To confirm the diagnosis, it was decided to perform bronchoscopic lung tissue biopsy in the outpatient clinic.

With the increasing popularity of various needle aspiration or puncture techniques, rapid on-site evaluation (ROSE) technology has emerged as the time required to evaluate whether puncture specimens are sufficient, evaluate the quality of specimens, determine what specimens should be sent for examination after sampling, and even make preliminary diagnosis. This technique is also used in bronchoscopic biopsy. With the development of interventional respiratory technology in China, ROSE has gradually been paid attention to by everyone. Some people use its English pronunciation to call it "shredded pork". However, there are still some misunderstandings about the understanding of ROSE, especially its applicability and function, in the breathing world, and even some people use it to hype. "Shredded pork" needs to be fried before it can be eaten, but ROSE is not "shredded pork", so it should not be hyped, let alone become a tool to attract attention and fans.

rapid on-site evaluation (ROSE) refers to a clinical practice method that aims to improve the diagnostic efficiency of biopsy by performing real-time cell morphology analysis on specimens during fine needle puncture or tissue biopsy operation. ROSE examination has a strong timeliness, and its examination results can have a direct impact on the biopsy process.

rapid on-side evaluation (ROSE) refers to a method of sampling by puncture, biopsy, brushing, etc., making cytological specimens by direct cell fluid smear or tissue print, and applying rapid staining. Professionals evaluate the satisfaction of sampling and make a preliminary judgment on the diagnosis on the spot to guide the next operation and specimen diversion.

rapid On-Site evaluation (ROSE) is a service provided by pathologists and/or cytotechnologists to determine the adequacy of cell content in fine needle smears and tissue biopsy prints. Its objective is to determine whether the quality of the samples collected is sufficient for cytopathological diagnosis. ROSE can improve the success rate of puncture diagnosis and reduce the number of unnecessary punctures and the resulting complications. ROSE can also make a preliminary diagnosis of certain diseases and provide useful information for the evacuation of specimens. Bronchoscopic specimens contain a lot of information, and the evacuation examinations that can be performed include cytopathology, molecular biology, microbiology, flow cytology, genetic diagnostics and other fields. However, the specimens obtained by bronchoscopy are limited and cannot be completely covered, so ROSE is required for shunting: cytopathological examination and genetic testing are emphasized on specimens suspected of malignant neoplastic diseases; The specimens of suspected infectious diseases are subjected to microbial culture and molecular biological examination. The ROSE technique for bronchoscopic diagnostic techniques originated from traditional needle aspiration biopsies of deep tissues, such as breast and thyroid biopsies, to ensure correct sample collection, sufficient sample volume and avoid additional operations.

bronchopleural fistulas (BPF) are a kind of complication after surgical treatment (including lobectomy, segmental wedge resection, etc.), with low incidence^[1]About 1.5% to 28.0%^[2]However, the case mortality rate is high due to the difficulty of treatment when it occurs. According to the location and size of the fistula, the general condition of the patient, the benign and malignant nature of the primary disease and other factors, there are different treatment methods for BPF, and surgery is the first treatment method^[3]However, some patients cannot tolerate surgery, and can choose trans-bronchoscopic interventional treatment (such as airway stents, biofibers, coils, etc.). In 2006, cases of successful closure of tracheal fistula with atrial septal defect occluder were reported, including the treatment of tracheal-esophageal fistula and tracheal pleural fistula, and the short-term effect after treatment was obvious^[4]。 However, with the research progress of this technology, there are many controversies.

The effect of obstructive sleep apnea hypopnea syndrome (OSAHS) on the health of the population has been paid more and more attention. Intermittent hypoxia and sleep fragmentation at night can cause systemic oxidative stress, inflammatory reaction and enhanced sympathetic nerve excitability, leading to cardiovascular disease, metabolic abnormalities and cognitive dysfunction^[1]。 OSAHS is a heterogeneous disease, and apnea hypopnea index (AHI), as the main index to judge the severity, does not reflect individual differences in all aspects of OSAHS. First, AHI does not reflect the weighting of risk factors (such as age, gender and race)^[2,3]； Secondly, AHI was not correlated with daytime sleepiness scale (ESS scale), sleep quality, anxiety and depressive symptom scores^[4]； Nor can independently predict the risk of complications^[5]。 In addition, AHI did not reflect the differences in oxygen depletion characteristics and sleep fragmentation in different respiratory events^[6]。 It is worth mentioning that from the perspective of pathogenesis, the PALM model of OSAHS pathogenesis includes both structural and non-structural factors, namely, critical closure pressure (Pcrit), low arousal threshold (arousal threshold), high loop gain (loop gain) and abnormal dilator muscle function of the upper airway^[7,8,9,10]Obviously, AHI alone cannot reflect the weight of the participation of different individuals in each of the above mechanisms. In short, a single indicator of AHI can neither reflect the heterogeneity of clinical manifestations nor accurately predict the weight of PALM factors. Therefore, it is necessary to further explore the clinical subtypes of OSAHS to lay the foundation for accurate diagnosis and treatment.

Chronic obstructive pulmonary disease (COPD) is currently the fourth leading cause of death worldwide and is expected to rise to the third place in 2020^[1]。 However, up to now, the specific pathogenesis of COPD is still unclear, and the imbalance of protease/antiprotease system, oxidative stress and inflammatory response may be involved in the pathogenesis of COPD^[2]。 It is currently believed that cigarette smoke is the main environmental factor of COPD, but only a few smokers develop COPD^[3]。 It is worth noting that even if cigarette smoke exposure is stopped, lung function will still decline progressively and be accompanied by persistent lung inflammation, suggesting that there is a mechanism of self-persisting inflammatory response in COPD patients. Inflammation is a central link in the pathogenesis of COPD^[4]Permanent memory T cells, bacterial colonization, autoimmunity may mediate persistent inflammatory response in the lungs^[5]。 Houghton et al.^[6]It is believed that elastin peptide (EP) is involved in the occurrence and development of chronic lung inflammation in COPD. The literature reported that EP has many biological activities, such as chemotactic cells, promoting cell proliferation, inducing protease expression, etc^[7,8]Whether EP participates in the activation of inflammatory cells, induces cell differentiation, is recognized by antigen-presenting cells, and initiates acquired immune response, especially the role of EP in the pathogenesis of COPD, is worthy of further study. Therefore, this article reviews the inflammatory response of EP and COPD as follows.

The patient, a 62-year-old female, was seen on September 27, 2017 mainly due to "intermittent cough and expectoration for more than 2 months". The patient coughed intermittently for 2 months, coughed up sputum several times a day, and had no symptoms such as fever, hemoptysis, chest pain and dyspnea. One month ago, X-ray chest radiography in an external hospital showed multiple nodules in both lungs. First, special infection was considered, and tumor was not excluded (Figure 1)。 Then he came to our outpatient clinic for treatment. Since the onset of the disease, the patient has been able to eat and defecate as usual, and there is no obvious weight loss. Past physical health, no history of smoking or drinking. No history of exposure to radiation and toxicants. Physical examination: body temperature 36.3 ℃, pulse rate 88 beats/min, respiratory rate 24 beats/min, blood pressure 140/60 mmHg (1 mmHg =0.133 kPa). The oxygen saturation of fingertip pulse was 93%, and a few wet rales were scattered in both lungs. Heart rhythm, no murmur. The abdomen is flat and soft, without tenderness. Both lower limbs are not swollen.