2011年 · 第34卷第12期

Looking back at the author's more than 40-year medical history, I think I can say meaningful things without shame or have done two things, one is mechanical ventilation, and the other is the diagnosis and treatment of lower respiratory tract infection. The first 20 years of practicing medicine were mainly to accumulate knowledge, practice, practice and actively promote mechanical ventilation; In the next 20 years, we mainly focused on infection diagnosis and treatment, combined basic research with clinical practice, and strived to clarify the basic general situation of lower respiratory tract infections in China, such as community-acquired pneumonia (CAP), hospital-acquired pneumonia (HAP), pulmonary mycosis and mycoplasma and other special pathogenic infections, and summarized the rough guiding principles suitable for China's characteristics. Because the outcome of infectious diseases depends on the relationship between pathogens, drugs and hosts, we have also been forced to do some research work in microorganisms and anti-infectious drugs, which has been recognized by experts in relevant fields. The reason why the author chose the above two clinical research directions is of course related to interests and hobbies, but more importantly, it is to actively respond to the challenges that cannot be avoided and urgently need to be solved in clinical practice.

BACKGROUND: Although inhaled glucocorticoids (ICS) and long-acting beta-agonists (LABA) are used in patients with poorly controlled bronchial asthma (asthma for short), many patients are not effectively controlled even with these drugs. Objective: To evaluate the efficacy and safety of omalizumab in patients with severe asthma who have not been effectively controlled with high-dose ICS and LABA and other control drugs. Methods: This study was a prospective, multicenter, randomized, parallel-group, double-blind, placebo-controlled clinical study with 193 sites in the United States and 4 in Canada; Eight hundred and fifty patients aged 12 to 75 years were enrolled in the study, all of whom were asthmatic patients who were not effectively controlled with high-dose ICS plus LABA or other control drugs. The intervention method was to add omalizumab (427 cases) or placebo (423 cases) to the existing treatment regimen for 48 weeks. The primary study endpoint was acute exacerbation of asthma during the study, the secondary study endpoint included the change from the basal value in the mean number of daily salmeterol applications over 48 weeks, the mean asthma symptom score and the mean score of the standard asthma quality of life score questionnaire (AQLQ [S]), and the safety endpoint was the severity of the frequency of treatment-related acute adverse events. Results: During 48 weeks of treatment, the rate of acute exacerbation of asthma was lower in the omalizumab-treated group than in the placebo group (0.66 and 0.88, respectively,P=0.006), with a 25% reduction in the acute incidence of asthma (RR＝0.75，95%CI0.61-0.92). Compared with placebo, 48 weeks of omalizumab treatment increased the mean AQLQ (S) (0.15 to 0.43 points, mean 0.29 points), reduced daily salmeterol dosage (0.49 to 0.04 actuations/d, mean 0.27 actuations/d), and reduced asthma symptom score (0.42 to 0.10 points, mean 0.26 points). The omalizumab-treated and placebo groups had similar adverse event rates (80% and 79.5%, respectively) and serious adverse event rates (9.3% and 10.5%, respectively). Limitations: The findings may be limited by the 20.8% interruption rate at the beginning of the study, and this study has not yet detected rare safety concerns and has not shown the therapeutic effect of omalizumab in the oral glucocorticoid treatment group. Conclusion: Omalizumab can increase clinical efficacy in patients with severe asthma that cannot be effectively controlled by high-dose ICS and LABA treatment.

BACKGROUND AND OBJECTIVE: Acute exacerbation of COPD can lead to impaired lung function, decreased quality of life and increased risk of death. Even with the simultaneous application of three drugs (inhaled glucocorticoids, long-acting β₂– receptor agonists and cholinergic receptor antagonists), the mean number of acute exacerbations per COPD patient remained 1.4/year. Because macrolides have anti-infective, anti-inflammatory and immunomodulatory effects, their prospects for the treatment of COPD have attracted attention, but it is still inconclusive whether they can reduce acute exacerbation of COPD. The study conducted a randomized trial in patients with COPD at risk of acute exacerbation to determine whether azithromycin reduces acute exacerbation of COPD. Methods: A total of 1577 subjects were screened, of which 1142 (72%) were randomly divided into 2 groups on the basis of conventional treatment, 570 in the azithromycin group received azithromycin 250 mg/d for 1 year, and 572 in the placebo group as controls. Results: (1) 1-year follow-up rate: 89% (495/558) in the azithromycin group and 90% (502/550) in the placebo group. (2) Median time to first acute exacerbation: 266 d in the azithromycin group (95%CI227 to 313) and 174 d in the placebo group (95%CI143~215), the difference was statistically significant (P<0.01)。 (3) Frequency of acute exacerbation: 1.48 times/year in the azithromycin group and 1.83 times/year in the placebo group, with statistically significant differences (P<0.01)。 (4) St. George's Respiratory Questionnaire scores decreased by (2.8±12.8) points in the azithromycin group and (0.6±11.4) points in the placebo group, and the difference was statistically significant (P<0.01)。 (5) Incidence of hearing impairment: the azithromycin group (25%, 142/559) was more common than the placebo group (20%, 110/558), and the difference was statistically significant (P<0.05)。 Conclusion: Adding azithromycin (250 mg/d) to conventional treatment for 1 year in selected COPD patients can reduce the frequency of acute exacerbation of COPD and improve the quality of life of patients, but it can cause hearing impairment in some patients. While this intervention is able to alter the resistance patterns of microorganisms, its effects are unknown.

BACKGROUND AND OBJECTIVES: In women, lymphangioleiomyomatosis (LAM) is a continuously progressive cystic lesion of the lung that is associated with inappropriate activation of the rapamycin target protein (mTOR) signaling pathway in mammals, which regulates cell growth and lymphangiogenesis. Sirolimus (also known as rapamycin) inhibits mTOR and has shown therapeutic promise in phase I-II trials including patients with LAM. Methods: A randomized, double-blind, placebo-controlled 12-month trial of sirolimus (which included 89 patients with LAM with moderate lung injury) was first performed, followed by a 12-month observation period. The primary study endpoint was FEV between the two groups₁Difference in rate of change (slope). Results: During the treatment period, the placebo group (43 cases) FEV₁The slope was (– 12 ± 2) ml/month and (1 ± 2) ml/month in the sirolimus group (46 cases) (P<0.001)。 During treatment FEV₁The absolute group difference in mean change was 153 ml (approximately the mean FEV at enrollment₁11%). The sirolimus group showed improvements in FVC, functional residual gas volume, serum vascular endothelial growth factor D (VEGF-D), quality of life, and functional performance from baseline to 12 months compared with the placebo group. During this period, 6 min walking distance and D_LThere was no statistically significant difference between CO groups. After discontinuation of sirolimus, the decrease in lung function resumed in the sirolimus group and was parallel to the decrease in lung function in the placebo group. Adverse events were more common in the sirolimus group, but there was no statistically significant difference in the frequency of serious adverse events between the two groups. Conclusion: Sirolimus can stabilize lung function, reduce serum VEGF-D levels, reduce symptoms and improve quality of life in patients with LAM.

nitric oxide (NO) has been the focus of the biomedical field in recent 20 years. The research on it has developed rapidly and involves a wide range of subjects. NO is an important and unique signal transmission molecule in vivo. It plays an important role in the communication and transmission of information between nerve cells, the constant maintenance of blood pressure and the host defense response of immune system, and also participates in the occurrence and development of diseases in various systems of the body.

Non-tuberculous Mycobacterium (NTM) lung disease is more common in patients with underlying lung disease or immunodeficiency. 1997 Kahana et al.^[1]The avian-intracellular mycobacterium complex flora with allergy-like symptoms such as wheezing and hypoxemia (Mycobacterium aviumintracellulare complex, MAC) Pulmonary disease. The ATS named this particular form of MAC lung disease as hypersensitivity-like disease in its 2007 guidelines for the diagnosis and treatment of NTM^[2]。 The author makes the following review of this particular type of NTM lung disease.

Chemotherapy is the most important treatment for tuberculosis, but multiple drug resistant tuberculosis (MDR-TB) and extensively drug resistant tuberculosis (XDR-TB) make chemotherapy for tuberculosis difficult. Chemotherapy also has problems such as long course of treatment, high price of second-line anti-tuberculosis drugs and large adverse reactions, and difficulty in completely eradicating dormant or persistent bacteria. Because the occurrence, development and outcome of tuberculosis are closely related to the body's immune response, people have tried to treat tuberculosis by regulating the body's immune response.

Respiratory activity is regulated by the nervous system to adapt to the changes of various environments. Respiratory plasticity refers to the change of breathing pattern in order to adapt to the changes of internal and external environments, and gradually forms new breathing rhythm and amplitude^[1]And the duration of this change is relatively long, and the breathing pattern does not immediately return to the previous state with the elimination of internal and external factors. Intermittent hypoxia can induce two most common phenomena of respiratory plasticity, namely long-term facilitation (LTF) and progressive enhancement of respiratory activity. Respiratory LTF refers to compensatory respiratory phenomena induced by exceeding normal respiratory output, increasing and progressively enhancing ventilation for more than 1 h after transient and repetitive hypoxic or electrical stimulation interventions^[2]Including phrenic nerve activity, diaphragm motility, ventilation volume, intercostal nerve activity, etc. It is an important electrophysiological index reflecting respiratory plasticity. LTF is expressed in the upper airway muscle and hypoglossal nerve activity, so it plays an important role in the upper airway respiratory activity, which is conducive to keeping the upper airway patent and maintaining the stability of the upper airway function. OSAHS is a typical form of chronic intermittent hypoxia, and respiratory LTF may be a compensatory response to OSAHS. Induction and enhancement of LTF of hypoglossal nerve and pharyngeal dilator muscle, which is beneficial to keeping the upper airway open, has potential therapeutic significance for OSAHS, and has become a research direction at home and abroad. The research progress of LTF and OSAHS is summarized as follows.

In the review stage of "Correlation between polymorphism of tuberculosis susceptibility gene and clinical characteristics in 459 cases of Han nationality" (author Liu Jinbin et al.) published in this issue, the author and the reviewers had different opinions on academic views. After several reviews and revisions, there was still no agreement on academic views. As one of the reviewers, the author participated in the whole process of reviewing the manuscript, and now discusses the academic issues with the author of this article.

With the deepening of the research on invasive pulmonary aspergillosis (IPA) complicated by hematological diseases, the understanding of non-traditional high risk factors complicated by IPA has gradually improved. The literature reported that more than 10% of COPD patients were complicated with invasive aspergillosis, and more than 5% were complicated with IPA^[1]。 However, patients with severe COPD complicated with IPA lack clinical specificity, lagging diagnosis, difficult management, and the mortality rate is as high as 91%^[2]。 The clinical characteristics and imaging findings of 9 patients with COPD complicated with IPA admitted to our hospital are reported below.

Male, 34 years old. He was admitted to Chongqing Armed Police Corps Hospital on April 19, 2006 due to 4 months of anti-tuberculosis treatment, yellow skin staining and yellow urine for 10 days. Before admission, he was diagnosed with double pulmonary tuberculosis at the local tuberculosis hospital and was given a 2 hrZS/4 hr (H: isoniazid, R: rifampicin, Z: pyrazinamide, S: streptomycin) regimen for 4 months. Physical examination: moderate to severe yellowing of the skin and mucosa of the whole body, and unpalpable swelling of superficial lymph nodes of the whole body; It is palpable under the costal margin of the liver, percussion pain in the liver area, and Murphy's sign is negative. Laboratory test: white blood cell count 18.5×10⁹/L, 0.95 for neutrophils, 111 g/L for hemoglobin and 237×10 for platelets⁹/L. Liver function tests: total bilirubin was 129 μ mol/L, direct bilirubin was 71 μ mol/L, indirect bilirubin was 58 μ mol/L, alanine aminotransferase was 118 U/L, aspartate aminotransferase was 149 U/L, alkaline phosphatase was 361 g/L, gamma-glutamyltransferase was 440 IU/L, and total bile acids were 24 μ mol/L. All 5 items related to hepatitis B were negative. Tumor markers: 4.6 g/L for alpha-fetoprotein, 2.2 g/L for carcinoembryonic antigen, and 60 kU/L for sugar antigen CA19 – 9. Blood and urine amylase results were normal. Chest X-ray showed tuberculosis in both lungs. Abdominal B-ultrasound and magnetic resonance cholangiopancreatography showed dilatation of the upper common bile duct and main pancreas. The initial diagnosis was obstructive jaundice, space-occupying lesions of the common bile duct (suspected lymph node tuberculosis), pulmonary tuberculosis and gallbladder stones. Retrograde cholangiopancreatography (ERCP) by duodenoscopy showed progressive development of the bile duct tree, as well as the cystic duct, and symmetrical external pressure stenosis of the common bile duct between the posterior segment of the duodenum and the confluence of the cystic duct (Figure 1，Figure 2), the wall of the tube is smooth and the running is natural, the length of the stenosis is 1.5 cm, the widest part of the bile duct above the stenosis is 2.5 cm, and the left and right hepatic ducts are obviously thickened, with a diameter of 0.5~0.6 cm. On April 27, 2006, laparotomy was performed. During the operation, gallbladder swelling and effusion were observed. The diameter of the common bile duct in the upper duodenum was about 2 cm, and the common bile duct below it was wrapped by stiff fused lymph nodes, and the lumen of this common bile duct was obviously narrowed. Choledochoscopy showed congestion and edema of the mucosal surface of the common bile duct, and the lumen was slit-like stenosis. Mesenteric lymph nodes were enlarged, and grey and white hard nodules with a subserous diameter of about 1.0 cm in the upper jejunal wall were visible. Rapid frozen biopsy of mesenteric enlarged lymph nodes was taken during operation. The results showed that there were cheese-like substances, no tumor cells and no Langhans giant cells. Cystic duct-common hepatic duct surgery, cholecystojejunostomy and jejunal nodule biopsy were performed. The results of postoperative pathological examination showed that large areas of caseous necrosis in the lymph nodes, lymphocytes and histiocytes surrounded by necrosis and proliferation, and multiple Langhans giant cells (Figure 3，Figure 4)。 After anti-tuberculosis, anti-infection, liver protection, immune enhancement and symptomatic support treatment, the patient was discharged from hospital on May 5, 2006 (the 8th day after operation). After discharge, the patient continued to treat anti-tuberculosis with 2HRZS/4HR regimen for 6 months. At present, no recurrence has been seen after more than 4 years of follow-up, and the patient can engage in manual labor.

A 19-year-old female was admitted to Beijing Chest Hospital for 4 months of abdominal distension and 3 months of shortness of breath after activity. The patient developed abdominal distension without obvious trigger 4 months ago, and ascites was examined and no treatment was given. Three months ago, the patient felt that abdominal distension aggravated, accompanied by fever (body temperature 37.2~37.5 ℃) and obvious shortness of breath after activity. B-ultrasound showed bilateral pleural effusion and ascites. He was diagnosed as tuberculous purulent multi-serous effusion in another hospital. After 2 months of experimental anti-tuberculosis treatment with isoniazid, rifampicin and ethambutol, the purulent effusion in pleural and abdominal cavities still persisted, and there was obvious chest tightness and shortness of breath after activity, accompanied by lethargy, weight loss, fatigue, night sweats, loss of appetite and nausea. Physical examination at admission: body temperature 37.2℃, heart rate 100 beats/min, breathing 22 beats/min, blood pressure 100/60 mm Hg (1 mm Hg =0.133 kPa), consciousness, chronic disease, emaciation, no cyanosis of the lips, and no swelling of superficial lymph nodes throughout the body; The breathing velocity of both lower lungs was weakened, the tactile speech tremor was weakened, the percussion of both lower lungs showed void sounds, the auscultation breathing sounds were weakened, and the right middle lung could hear wet rales; The heart rhythm was uniform, and there was no murmur in the auscultation area of each valve; The abdomen is swollen, the abdominal wall is flexible, and nodules scattered in rice grains to soybean sizes can be palpable, with medium texture, mild tenderness, no rebound pain, mobile voicing (±), and attenuated intestinal sounds; Edema of both lower limbs and feet. Pathological examination of pleural effusion in other hospitals showed that there was no structural exudate necrosis, a small number of inflammatory cells, and a small number of abnormal deep stained cells in necrotic tissue. Admission diagnosis: The nature of purulent multi-serous effusion is to be investigated, and the possibility of tuberculosis is greater, and malignant tumors are not excluded.

Primary pulmonary mucinous adenocarcinoma is clinically rare and is reported to account for only 0.14% of lung adenocarcinomas. Most cases are easily misdiagnosed as pneumonia, tuberculosis and other diffuse lung lesions in the early stage, so they are not treated in time. In 2010, a patient with unexplained pleural effusion was admitted to our hospital. After internal medicine thoracoscopy, the parietal pleura and diaphragm tissue were clamped out, and it was confirmed that he was pulmonary mucinous adenocarcinoma. At the same time, the relevant literature on this disease at home and abroad in the past 10 years was reviewed and analyzed and discussed as follows.

Sparganosis mansoni is a parasitic disease caused by Sparganosis mansoni, the larva of Dierella mansoni, parasitizing the eye, subcutaneous tissue or brain, kidney and other organs of the human body. Most of the disease invades skin and brain tissue, while lung involvement is rarely reported. A case of Sparganosis mansoni admitted to the respiratory department of Shanghai Pulmonary Hospital is reported as follows.

The patient, a 28-year-old female, teacher, was admitted to the hospital on 26 October 2010 due to "cough and expectoration for 5 months and shortness of breath after activity for 1 month". In May 2010, the patient had cough and white sticky sputum after fatigue and cold, about 10~20 ml/d, occasionally low fever in the afternoon, with a maximum body temperature of 37.5℃, no fear of cold, chills, chest pain, hemoptysis, night sweats at night, palpitations, chest tightness, shortness of breath, self-medication (specifics unknown), symptoms did not improve significantly. On June 17, 2010, he visited the Respiratory Medicine Clinic of Fuxing Hospital affiliated to Capital Medical University. X-ray chest radiograph showed suspicious small nodules in the right lower lung (Figure 1), given azithromycin (0.5 g/d, intravenous drip) for 5 d, but the symptoms did not improve significantly. On June 29, 2010, the chest CT showed a 6 mm nodular shadow in the outer basal segment of the lower lobe of the right lung, and multiple enlarged lymph nodes behind the anterior vena cava of the trachea, under the carina, and next to the aortic arch. No obvious abnormalities were found in the rest (Figure 2，Figure 3)。 Later, the patient went to a traditional Chinese medicine hospital by himself and took traditional Chinese medicine for more than 1 month, but the symptoms of cough and expectoration were still not significantly relieved. On August 26, 2010, the bronchial challenge test of pulmonary function was negative in a foreign hospital, and the bronchoscopy showed significant congestion and edema of tracheal mucosa (Figure 4), clear secretion could be aspirated, secretion smear and culture results showed no obvious abnormality, BALF cytological classification and lymphocyte subset examination, showing that the lymphocyte proportion was 32%, CD₄/CD₈It was 3.68. Sarcoidosis was suspected and no special treatment was given. Regular review is recommended. The patient's cough symptoms gradually worsened, coughing white sticky sputum, about 20-30 ml/d, shortness of breath after activity, occasional fever, and the highest body temperature was 37.8 ℃. On October 20, 2010, the chest CT in the external hospital showed diffuse small nodules in both lungs (Figure 5，Figure 6), suspected miliary tuberculosis, the patient is advised to go to a tuberculosis specialist hospital for treatment. On October 25, 2010, the patient underwent tuberculosis-related examinations such as PPD, sputum smear to find acid-fast bacilli and sputum MTB culture in the tuberculosis specialist hospital. Due to the aggravation of cough and shortness of breath, the patient did not wait for the relevant examination results, so he came to our hospital for hospitalization on October 26, 2010. The patient suffered from poor appetite and sleep, fatigue and weight loss of 3 kg since the disease. Past health, denying history of infectious diseases such as tuberculosis and contact history. Penicillin allergy. Six months before the onset of illness, he moved into a newly renovated house, denied raising animals and birds, engaged in the profession of preschool teacher, and denied the history of occupational exposure to foreign bodies. Unmarried and childless, father deceased, died in a car accident, mother is healthy, no siblings. Family history of hereditary disease denied.

Probably from the beginning of this year, the new Internet word "Geli" suddenly became popular on the Internet and everyone's spoken language, even newspapers and magazines. Many people are proud to say "give force", which is used as the avant-garde capital and the basis of pride. In fact, few people delve into what "give force" really means? Where does it originate? According to research, the word "powerful" comes from a complaint by Sun Wukong in the dubbed version of the Japanese comedy anime Journey to the West: The End of the Journey: "Is this Tianzhu? It's not powerful, teacher". In fact, the original meaning of the original words is to describe that the reality (situation) is far from the expected goal, that is, it is far from that, with the meaning of disappointment and complaint. At present, people's understanding of it is that it is helpful, willing to contribute, making a difference and giving face.

Intraairway stenting has become one of the most important methods in the treatment of airway lesions^{[1,2,3,4,5,6]}。 Some scholars observed the effects of different types of capsules or bare stents on mucosa through animal experiments^[7,8,9]However, these studies are all conducted on normal animals, and it is difficult to truly reflect the specific conditions of patients' lesions. In recent years, the author observed the dynamic changes of airway in patients with airway lesions after implantation of enveloped metal stents, which are reported as follows.

More than 5,500 papers were exchanged at the 2011 ATS Annual Conference, held in Denver, USA on May 13 – 18. Thirteen doctors in China received travel funding for young Chinese researchers established by ATS for the first time, and gave speeches at a special session in China. COPD is a hot topic of discussion in the congress, and has many forms such as continuing education courses, hot topic discussions, congress speeches, poster exchanges, and pro and cons debates. The researches that left a deep impression on the participants in this conference are multi-center, interdisciplinary cooperation, large sample and high-throughput data analysis research. Some of these research contents are now introduced.

The editor-in-chief's essay column has been set up for one year, and editor-in-chief Liu Youning has worked hard and kept writing. In the essay column of the editor-in-chief of this issue, he reviewed the history of medical practice for more than 40 years, and talked freely about his insights about mechanical ventilation and the rational application of anti-infective drugs. Professor Liu believes that the rational application of anti-infective drugs is an arduous "systematic project", and the specific management methods formulated by the Ministry of Health are completely necessary. The key is that the management principles formulated should be appropriate and can be implemented. In addition to macro-management, how to delay bacterial resistance in technology is also one of the keys to the rational application of anti-infective drugs. Therefore, Professor Liu also put forward three suggestions, hoping that readers will get inspiration from them after reading them carefully.