2010年 · 第33卷第12期

idiopathic pulmonary fibrosis (IPF) is the most common type of idiopathic interstitial pneumonias (IIP), and its histopathological characteristics are usual interstitial pneumonia (UIP)^[1]。 The prognosis of IPF is poor, and the median survival time of patients after diagnosis is 2.5 to 4 years. The results of several large-scale placebo-controlled clinical studies in recent years have shown that IPF is significantly heterogeneous and the outcome is difficult to predict. Complications in the course of IPF, such as acute exacerbation, pulmonary hypertension and emphysema, which significantly affect the course and prognosis of IPF, should attract the attention of domestic clinicians and researchers.

5% ~10% of patients with bronchial asthma (asthma for short) are severe asthma. Airway remodeling is one of the characteristics of severe asthma. High-resolution CT (HRCT) evaluation of airway remodeling is repeatable and accurate. This study aims to observe whether airway remodeling exists only in certain subtypes of severe asthma through HRCT analysis. Methods: The HRCT of patients attending severe asthma clinic from 2003 to 2008 was retrospectively analyzed. The subjects included 99 cases of severe asthma and 16 healthy controls. The right upper lobe tip bronchus (RB1) was selected, and its lumen area, wall area and tracheal diameter were measured. Univariate and multivariate regression analyses were used to evaluate the correlation between RB1 measurement data and clinical and sputum inflammation indicators. Sputum examination indicators obtained at longitudinal follow-up were expressed as the area under the time curve. Patients with severe asthma were divided into four groups by cluster analysis (smoking and non-smoking groups, with or without persistent airflow obstruction), and the differences of RB1 tracheometric indexes were compared between the four groups. Results: Compared with the control group, the percentage of RB1 wall area was significantly increased and the lumen area/body surface area was significantly decreased in the severe asthma group, but there was no significant difference in the above indexes between the four groups of severe asthma; There was no significant difference in airway measurement indexes between the smoking group and the non-smoking group, and the percentage of RB1 tube wall area was significantly increased in the persistent airflow obstruction group. The percentage of RB1 wall area in severe asthma patients was positively correlated with airflow restriction and persistent airway neutrophilic inflammation (R²=0.27,P<0.01)。 Conclusion: The results of HRCT quantitative analysis showed that there was no significant difference in the degree of airway remodeling among the four groups of severe asthma patients; Proximal airway remodeling is present in patients with severe asthma, and it is well correlated with impaired lung function and neutrophil inflammation of the airway.

The increase of lactate level was significantly associated with the morbidity and mortality of patients. The study explored whether monitoring lactate levels can improve patient prognosis and its effects in the early treatment of critically ill patients. Methods: Patients with blood lactate level ≥3.0 mmol/L (3.0 mEq/L) at the time of admission to ICU were randomly divided into 2 groups. The lactate group was treated with lactate level guidance, so that the lactate level of patients decreased by more than 20% every 2 h within the first 8 h; The control group had only baseline lactate levels, and no lactate level monitoring was performed. The primary endpoint measure was mortality among hospitalized patients. Results: The lactic acid group received more fluid and vasodilators than the control group, but there was no significant difference in lactic acid levels between the two groups. In the 348 intention-to-treat population, the mortality rate was 43.5% (77/177) in the control group and 33.9% (58/171) in the lactic acid group, with no statistically significant difference (P=0.067)； However, after adjustment for risk factors, the mortality rate of hospitalized patients in the control group was lower than that in the lactic acid group (OR=0.61，95%CI0.43 to 0.87,P=0.006)。 The 9-72 h continuous organ failure assessment scores in the lactic acid group were lower than those in the control group, and the time of discontinuation of myocardial contractile drugs, offline time and transfer out of ICU were earlier than those in the control group. Conclusion: For patients with high blood lactate level when admitted to ICU, lactate level-oriented treatment can significantly reduce the mortality rate of hospitalized patients. Monitoring lactate levels is beneficial for clinical treatment.

Acute exacerbation is a critical event in the natural course of COPD. Through a large-scale cohort study, the authors sought to test the hypothesis that there is a subtype of COPD (frequent exacerbation) in which patients frequently develop acute exacerbations, the frequency of which is independent of the severity of COPD. Methods: 2138 patients with COPD were enrolled. Treatment with antibiotics, glucocorticoids or hospitalization was defined as acute exacerbation of COPD. The frequency of acute exacerbation of COPD patients and its related factors were followed up for 3 years. Results: In the first year of follow-up, the average number of acute exacerbations in COPD patients with GOLD grades 2, 3, and 4 was 0.85, 1.34, and 2.00, respectively, and more than 2 acute episodes occurred in 22%, 33%, and 47%, respectively. The frequency of acute exacerbations in these patients remained relatively stable during the 3 years of follow-up. Previous history of acute exacerbation of COPD is the only predictive factor of patients with frequent exacerbation, but there is no significant correlation with COPD severity, quality of life and gastroesophageal reflux. Conclusion: The frequency of acute exacerbation of COPD may be related to its susceptibility subtype.

Idiopathic pulmonary hypertension (IPAH) is characterized by the thickening of the pulmonary artery media caused by the proliferation of pulmonary artery smooth muscle cells (paSMC), and the inflammatory response plays a certain role in the process of vascular remodeling associated with IPAH. Interleukin (IL) -13 is a regulator during tissue remodeling, but whether IL-13 plays a role in IPAH is unclear. IL-13 receptors include IL-4R (encoded by the il4r and il4ra genes in humans and mice, respectively), IL-13R α 1 and IL-13R α 2 (encoded by the il13a1 and il13a2 genes, respectively). This study aimed to evaluate the possible role of the IL-13 system in IPAH. Methods: The expression and localization of IL-13 and IL-13 receptors (IL-4R, IL-13R α 1 and IL-13R α 2) in lung tissues, paSMC and microdissected vascular lesions were studied by real-time reverse transcription PCR, immunohistochemistry and flow cytometry. The genes regulated by IL-13 in paSMC were studied by whole genome microarray analysis. Results: In patients with IPAH and two animal models of IPAH, the expression of IL-13R α 2 in lung tissue was up-regulated than that of IL-4R and IL-13R α 1; IL-13 can transduce signals via STAT3 and STAT6, and has an important effect on G₀/G₁It plays a blocking role in paSMC, thereby inhibiting paSMC proliferation; The results of whole genome chip technology showed that IL-13 inhibited the production of endothelin-1 in paSMC cells, which suggested that IL-13 could regulate the growth of paSMC by regulating the production of endothelin. The ectopic expression of il13a2 gene led to the partial loss of IL-13 in regulating the growth of paSMC, and also attenuated the effect of IL-13 in inhibiting the production of endothelin-1 in paSMC. The opposite result could be obtained after knockout of il13a2 gene. Conclusion: IL-13 system is a new regulatory mechanism of paSMC growth; The dysregulation of IL-13 receptor expression in patients with IPAH may be one of the causes of pathological vascular remodeling smooth muscle hypertrophy in IPAH.

Patients with COPD combined with obstructive sleep apnea (OSA) are more likely to develop pulmonary hypertension than patients with one of these diseases alone. The aim of this study was to evaluate the mortality and first hospitalization due to acute exacerbation of COPD in patients with COPD complicated with OSA, and the impact of continuous positive airway pressure (CPAP) on the primary clinical outcome of patients. Methods: Among 651 subjects, 228 patients with COPD complicated with OSA were treated with CPAP, 213 patients with COPD complicated with OSA were not treated with CPAP, and 210 patients with COPD alone; The enrolled patients had no comorbidities such as heart failure, myocardial infarction and stroke. The median follow-up time was 9.4 years (3.3 to 12.7 years). The follow-up endpoints were death due to various causes and first hospitalization due to acute exacerbation of COPD. The data were corrected by age, sex, body mass index, smoking status, alcohol consumption, comorbidities and COPD severity, sleep apnea hypopnea index, daytime sleep and other indexes. Results: The relative risk of mortality was 1.79% and 95% in patients with COPD complicated with OSA without CPAPCI1.16 to 2.77; The relative risk of hospitalization due to acute exacerbation of COPD was 1.70, 95%CIThe range was 1.21 to 2.38, all of which were higher than those of COPD alone. There was no statistically significant difference in the incidence of the above two endpoints between patients with COPD combined with OSA treated with CPAP and patients with COPD alone. Conclusions: There is a significant correlation between COPD combined with OSA and increased risk of death and hospitalization due to acute exacerbation of COPD; And even if patients receive the same drug treatment and care, their mortality rate is still higher than that of COPD patients with the same severity; CPAP treatment can improve the survival rate and reduce the hospitalization rate of patients with COPD complicated with OSA.

Lymphangiomyomatosis (LAM disease) is a rare disease, but many important advances have been made in clinical and basic research of LAM disease in the past 10 years^[1]。 In January 2010, ERS published the world's first diagnosis and treatment guidelines for LAM disease, which include diagnostic criteria and assessment methods for LAM disease, as well as screening and treatment for high-risk groups^[2]This paper systematically summarizes the current academic understanding of LAM disease and the consensus reached. The author gives a brief introduction to the guide here.

Failure of mechanical ventilation withdrawal is not uncommon in ICU patients. About 25% of patients with COPD and/or left heart disease fail to withdraw despite passing the spontaneous breathing trial (SBT)^[1]。 At present, the researches on the causes of withdrawal failure mainly focus on respiratory dysfunction. In patients with normal respiratory mechanics but poor cardiac reserve function, withdrawal-induced acute cardiac dysfunction may be the main cause of withdrawal failure^[2,3]。 Correct understanding of the mechanism of acute cardiac dysfunction induced by withdrawal, monitoring the changes of cardiovascular function during withdrawal, and early intervention and treatment are the keys to successful withdrawal.

COPD is a complex chronic systemic inflammatory disease involving central airway, peripheral airway, pulmonary parenchyma and pulmonary vessels. Lung cancer is one of the common complications of COPD, both of which are related to the abnormal inflammatory reaction of the lungs to harmful gases or particles such as cigarette smoke, and the risk of lung cancer in COPD patients is increased^[1]It suggests that there is a correlation between the occurrence processes of the two. In order to investigate whether this correlation is related to smoke exposure, genetic susceptibility factors and/or abnormal immuno-inflammatory response, the biological characteristics of COPD and lung cancer in terms of epidemiology, influencing factors and pathogenesis are summarized as follows.

The pathogenesis of bronchial asthma (asthma for short) is closely related to the imbalance of immune response of helper T cell (Th) subset Th1/Th2 cells. T cells and their cytokines play a crucial role in the pathological process of asthma. Recent research results have shown that the cytokine interleukin (IL) -27 can enhance Th1 immune response, reduce Th2 immune response, inhibit excessive inflammatory response, inhibit Th17 cell differentiation and cytokine production, and act on regulatory T cells, all of which suggest that IL-27 may play an important role in the pathological process of asthma. Recent studies on the role of IL-27 in the immune network of asthma are reviewed as follows.

Tumor has become one of the killers that threaten human health, and traditional chemotherapy methods as effective measures to treat tumor have reached a plateau stage. epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) Targeted therapeutic drugs have been widely used in the treatment of lung tumors and have achieved good efficacy, but there are also limitations in clinical application: (1) There are few effective populations, and the effective populations of epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) are mainly Asian women, non-smokers and adenocarcinoma patients, while the efficacy for other patients is not significant; (2) The phenomenon of drug resistance is serious. About 50% of patients who are effective against traditional targeted therapy drugs will develop acquired drug resistance and tumor recurrence after a period of use, which may be due to the appearance of double mutation of genes^[1]； (3) Tumor metastasis. The pancreatic neuroendocrine tumor model established by RIP1-Tag2 rats was used. After using VEGFR2 specific antibody DC101, many metastases appeared in rats. At the same time, with the prolongation of treatment time, the metastasis became more serious^[2]。 Therefore, the search for new anti-tumor targets and the research and development of new targeted therapeutic drugs are particularly important. The research and application of new targeted therapeutic drugs have made significant progress in recent years, mainly including therapeutic strategies such as promoting tumor cell apoptosis, interfering with cell signaling pathways, blocking cell cycle and anti-angiogenesis.

The purpose of this study was to construct a microfluidic chip system to study the cell culture and chemotherapy resistance of lung cancer in a simulated microenvironment in a flowing medium. The microfluidic chip system consists of a polydimethylsiloxane (PDMS) chip and an MS26 portable syringe pump, which are connected by a silicone tube; Multiple microchannels are engraved on the PDMS chip for simultaneous analysis of multiple sets of cells, and the MS26 syringe pump adjusts different flow rates to control liquid flow and continuously supply nutrients to cells. Lung adenocarcinoma cells SPCA were placed in microchannels, and the flow rate was adjusted to 1 mm/24 h, 5 mm/24 h, 10 mm/24 h and 15 mm/24 h, respectively. The growth state of the cells was observed and the optimal flow rate was determined. As a result, it was found that when the flow rate was 15 mm/24 h, the cell growth state was optimal and was not easily washed away by liquid, and could grow continuously for 96 h. In order to further analyze the drug resistance, the cells were divided into an experimental group and a control group (with or without the addition of verapamil). The expression of P glycoprotein and apoptosis of cells after chemotherapy drug VP-16 were detected in the two groups, and the correlation between P glycoprotein and the resistance of SPCA cells to VP-16 was analyzed. The results of this study showed that the expression of P glycoprotein in the experimental group was significantly lower than that in the control group, but the apoptosis rate was significantly higher than that in the control group, which suggested that P glycoprotein was closely related to chemotherapy resistance of lung cancer, and inhibiting its expression could improve the sensitivity of SPCA cells to VP-16. In order to verify this result, we also used conventional cell culture and flow cytometry techniques to measure the apoptosis rate of cells. The results showed good agreement with the detection of microfluidic system, but the latter consumed a small amount of reagents and the detection time was less than the former, and the cell growth state was closer to the in vivo microenvironment.

Some scholars have suggested that when clinically diagnosing diffuse panbronchiolitis (DPB), it is sufficient to meet the six criteria for clinical diagnosis, and it does not necessarily rely on pathological diagnosis, because the risk of lung biopsy is greater than its possible benefits^[1]。 The authors agree with the above for the following reasons: (1) Independence on pathological diagnosis does not significantly increase the number of reported cases of DPB. The incidence of DPB was the highest in Japan at 11.1/100,000; From 1991 to 1996, a total of 17 cases were reported in the United States, France, Italy, Britain, Germany, Australia and Brazil, half of which were Asian patients, so DPB is relatively rare in European and American countries; In the past 30 years, less than 100 cases of DPB have been reported in China, including more than 40 cases with pathological biopsy and more than 50 cases without pathological biopsy. It is still a rare disease, and even if the diagnostic criteria are relaxed, the number of cases will not increase too much. (2) In addition to the accepted 6 diagnostic criteria for DPB, we have proposed to increase the efficacy of erythromycin treatment and the 24-h sputum volume over 100 ml, and pointed out that 14-and 15-membered cyclic macrolides are effective, while 16-membered cyclic macrolides are ineffective^[2]。 (3) Pathological data of lung biopsy should be provided when conducting scientific research. Pathologists who are unfamiliar with the morphological changes of DPB and unsure in diagnosis should take the initiative to consult experienced peers.

Recurrent nodular non-suppurative panniculitis (Weber-Christian disease, abbreviated as nodular panniculitis) is a non-suppurative inflammation originating from the fat lobules. The clinical manifestations of nodular panniculitis are complex, and the imaging findings are different. There are few cases reported with pulmonary symptoms as the first manifestation, and it is easy to miss the diagnosis. We conducted a retrospective analysis of the clinical manifestations and thoracic imaging features of 23 cases of nodular panniculitis with pulmonary damage confirmed by subcutaneous nodule biopsy and histopathology in Ruijin Hospital in the last 7 years, aiming to improve the awareness of the disease among respiratory physicians.

Emphysema and chronic airway inflammation are the main pathological changes in COPD and the main causes of incomplete reversible airflow restriction in patients with COPD. Tretinoic acid, a derivative of vitamin A, has the effect of reversing elastase-induced emphysema in rats. We confirmed that vitamin A can promote the proliferation and inhibit apoptosis of alveolar wall cells in elastase-induced emphysema in rats^[1]To further observe the preventive and therapeutic effects of vitamin A on experimental emphysema in rats, and to preliminarily explore the effects of vitamin A on MMP-2 and MMP-9 in matrix metalloproteinase (MMPs).

pulmonary surfactant associated protein (SP) -A is the most abundant protein component in pulmonary surfactants, mainly distributed on bronchial surface and alveolar gas-liquid interface, and belongs to the important member of C-type gelatin family^[1]。 Previous studies have confirmed that pulmonary surfactants play an important role in the immunoregulation of pulmonary infection and local inflammatory response. The primary mediators of immunoregulation are SP-A and SP-D^[2,3], SP-A levels are associated with susceptibility to pulmonary tuberculosis^[4,5]。 The purpose of this study was to investigate the expression of SP-A in the serum of patients with pulmonary tuberculosis.

The pathogenesis of COPD is not completely understood, and more and more research results show that apoptosis is involved in the formation of COPD. Loss of pulmonary surfactant associated protein-D (SP-D) can induce spontaneous emphysema in mice, suggesting that SP-D plays an important role in the pathogenesis of COPD^[1]。 The purpose of this study was to investigate whether alveolar septal cell apoptosis is related to the expression of SP-D.

Airway remodeling is another important pathological feature of bronchial asthma (asthma) besides chronic airway inflammation. Airway smooth muscle cells (ASMC) play an important role in the occurrence and development of airway remodeling. Some scholars believe that ASMC should be regarded as the target of asthma research^[1]。 In addition to anti-infective effects, roxithromycin also has immunomodulatory and anti-inflammatory effects. We established a rat model of chronic asthma and administered roxithromycin intervention to investigate the effect of roxithromycin on ASMC P27^kip-1Protein expression and its effect on apoptosis.

At present, it is believed that the main cause of bronchial asthma (asthma for short) lies in persistent damage and structural abnormalities of the airway, which is called airway remodeling^[1]While transforming growth factor (TGF) -β₁Is the strongest pro-airway fibrosis factor found to date for airway remodeling^[2]。 Cordyceps vigorin (Cordyceps for short) is the main active ingredient of Cordyceps sinensis, and its target may lie in adenosine receptor. The aim of this study was to observe TGF-β in the rat airway₁The expression of adenosine receptor mRNA in the airway and the transcriptional changes of adenosine receptor mRNA in the airway were preliminarily explored to investigate the intervention role and target of Cordyceps in airway remodeling of chronic asthma.

Bronchial asthma (asthma for short) is a chronic inflammatory disease of the airways, and the level of control of asthma is still not ideal despite the continuous emergence of new therapeutic measures. A 2004 global survey of asthma control levels involving 29 countries showed that^[1,2]Only 5% of asthma patients can achieve complete control, and most patients have low levels of control. This low level of control may be related to the inconsistent level of patient's perception of symptom control^[3,4]。 asthma control test (ACT) is an internationally recognized asthma control test scale, and its effectiveness and practicality have been confirmed by domestic and foreign studies^[5,6]。 In this study, we used ACT scale to analyze the differences between symptom control level and perception level of asthma patients in southern China and related influencing factors. The results are reported as follows.

inhibitor of growth 4 (ING4) gene is a newly discovered tumor suppressor in recent years, which is widely involved in the occurrence and development of tumors, and can enhance the sensitivity of chemotherapy drugs^[1]。 ING4 mainly plays a tumor suppressor role in cells. The interleukin (IL) -24 gene belongs to the IL-10 family^[2]Is a tumor suppressor gene, the expression product is secreted cytokine, which can inhibit tumor cell growth through membrane receptor mediation, induce tumor cell apoptosis, and stimulate immune response. In this study, an internal ribosome entry site (IRES) was used to construct a recombinant adenovirus expressing inhibitor of growth 4 and interleukin-24 (Ad-ING4-IL-24), which co-expressed ING4 and IL-24 genes, and observed its inhibition of tumor growth and its suppressive and synergistic effect when co-expressed.

Broncholithiasis is rare and prone to misdiagnosis and mistreatment due to atypical clinical manifestations. We retrospectively analyzed the clinical data of 27 patients with broncholithiasis admitted to Shanghai Pulmonary Hospital, and explored the classification, clinical manifestations and treatment methods of broncholithiasis, so as to provide evidence for the diagnosis and treatment of broncholithiasis.

pulmonary alveolar proteinosis (PAP) is a rare clinical disease, and at present, whole lung lavage is the standard treatment plan. With the understanding of disease, it is currently believed that granulocyte-macrophage colony-stimulating factor (GM-CSF) autoantibody is the cause of idiopathic PAP, and GM-CSF can be applied systemically or locally in the airway to treat idiopathic PAP. We report a case of idiopathic PAP with poor effect after repeated whole lung lavage treatment and good effect after subcutaneous injection of GM-CSF.

Congenital pulmonary arteriovenous fistula (PAVF) is an intrapulmonary vascular malformation that occurs between the pulmonary arteries and veins. Some patients are accompanied by cerebral infarction. Due to pulmonary arteriovenous fistula, pulmonary artery blood is not oxygenated by capillaries, resulting in SaO₂Decreased, causing a series of clinical symptoms. Such as palpitation, shortness of breath, general weakness, cyanosis, clubbing fingers (toes) and elevated hemoglobin and even impaired lung function. The neurosurgery department of Jingzhou Hospital affiliated to Huazhong University of Science and Technology used metal coil embolization to treat 2 cases of pulmonary arteriovenous fistula with cerebral infarction and achieved good results, which are reported below.

Schwannoma occurring in the trachea-bronchus is a benign tumor of the airway and is a rare disease. The data of a patient with schwannoma of the left main bronchus admitted to our hospital are reported below to improve clinicians' understanding of this disease.

tracheal adenoid cystic carcinoma (TACC) is a rare low-grade malignant tumor originating from the trachea, accounting for about 1/3 of tracheal tumors. It is easily misdiagnosed as "bronchial asthma", "asthmatic bronchitis" and other diseases in clinic, and has not been effectively diagnosed and treated for a long time. The diagnosis, treatment and follow-up of a patient with adenoid cystic carcinoma of the lower trachea admitted to the Department of Respiratory Medicine of the Second Hospital of Lanzhou University were analyzed, and retrospectively reviewed with relevant literatures.

The 5th Beijing Salon for Young and Middle-aged Respiratory Scholars in 2010 was held on July 29th, 2010. The theme of this salon was "Advances in the Diagnosis of Tuberculosis", which was presided over by Dr. Chen Xiaoyou of Beijing Chest Hospital.

Immunoglobulin E (IgE) is the lowest immunoglobulin in human serum known at present, its content only accounts for one hundredth of the total amount of human serum immunoglobulin, but it is the main antibody causing allergic reaction. The discovery of IgE led to a breakthrough in modern allergology.

Idiopathic pulmonary fibrosis (IPF) is the most common type of idiopathic interstitial pneumonia. The prognosis of IPF is poor and has obvious heterogeneity. Its complications also significantly affect the course and prognosis of the disease, so it is difficult to diagnose and treat IPF. In the special written talk column, Professor Cai Hourong, a member of the editorial board of this journal, wrote the article "Problems that need urgent attention in the clinical research of idiopathic pulmonary fibrosis", and expounded and analyzed the relationship between the comorbidities (acute exacerbation, pulmonary hypertension and emphysema) in the course of IPF and the prognosis in detail. At present, there are many basic studies related to IPF in China, but there are few clinical studies on the course, comorbidities and prognosis of IPF. The author calls for: Under the organization of relevant professional groups or leading units, we should adopt standardized terminology, exact definitions and unified diagnostic criteria, collect clinical data and biological specimens for research, conduct prospective and multi-center studies, and study the above problems from different angles and levels to find promising treatments. This suggestion is very good, and I hope to get the attention and response of domestic colleagues.