2010年 · 第33卷第08期

In recent years, through the promotion of standardized diagnosis and treatment of bronchial asthma (referred to as asthma for short), the overall control level of asthma has been improved to a certain extent, but there are still a few patients who can't achieve good control even after using high-dose control drugs (including combination therapy). At present, these patients are called refractory asthma. This issue published the "Expert Consensus on Diagnosis and Management of Refractory Asthma", hoping to further unify the understanding of the definition, disease assessment and management of refractory asthma. It is hoped that through collaborative research, efforts will be made to improve the diagnosis, treatment and research level of refractory asthma in China.

In addition to bronchial asthma (asthma for short), some clinical diseases can also be manifested as repeated asthma attacks or chronic persistent asthma attacks. Common diseases include allergic bronchopulmonary aspergillosis (ABPA), allergic granulomatous vasculitis, pulmonary eosinophil (EOS) infiltration and extrinsic allergic alveolitis (EAA). These diseases are easily misdiagnosed as refractory asthma, which in turn causes mistreatment and further worsens the primary disease. The differential diagnosis of allergic wheezing is very important. The common diseases manifesting as allergic wheezing are briefly introduced below.

Bronchial asthma (asthma for short) is a common chronic airway inflammatory disease. The 2006 revised Global Asthma Initiative (GINA) states that the goal of asthma treatment is to achieve and maintain clinical control^[1]。 However, in clinical practice, nasal-sinus diseases often affect the control of asthma, causing asthma to attack repeatedly, which brings certain difficulties to the treatment of asthma. Therefore, in recent years, the relationship between asthma and nasal-sinus diseases has become a hot topic of scholars in various countries.

The treatment goal of bronchial asthma (asthma for short) is to achieve and maintain asthma control^[1]。 Environmental factors are important risk factors for inducing asthma and acute asthma attacks. Environmental asthmatic factors persist, and asthma may persist. Therefore, to achieve and maintain asthma control goals, what are the environmental factors that induce asthma? How to induce asthma? What measures can be taken to avoid.

The results of the "Getting Optimal Control of Asthma (GOAL)" study showed that inhaled glucocorticoids (ICS) combined with long-acting beta₂Receptor agonist (LABA) treatment, more than 2/3 of moderate to severe asthma patients can achieve good clinical control, but 5% to 10% of patients are still treated by the fourth step recommended by the Global Asthma Prevention and Treatment Guidelines (GINA), that is, the acceptable level of asthma control can not be achieved with two or more control drugs, which is called refractory asthma. The treatment plan recommended by GINA for refractory asthma is to add oral glucocorticoids (referred to as hormones) and anti-IgE monoclonal antibodies to the fourth step of treatment. However, there are many long-term oral hormone adverse reactions, and anti-IgE monoclonal antibodies are expensive, have limited scope of application and curative effect, and have not yet been listed in China, which is the key to the "refractory treatment" of refractory asthma. However, new drugs and methods aimed at improving asthma treatment have been under unremitting research and development. Some research advances in recent years are introduced below.

spontaneous pneumothorax is a common clinical disease, including primary spontaneous pneumothorax (PSP) and secondary spontaneous pneumothorax (SSP), and its incidence has been reported differently, Gupta et al^[1]The reported overall incidence rate in England is 16.8/100,000, of which the incidence rate is 24/100,000 for men and 9.8/100,000 for women, and the incidence rate of male patients requiring hospitalization is 16.6/100,000 and 5.8/100,000 for women. At present, there is no data on the incidence of spontaneous pneumothorax in China.

Linezolid is a new type of antibacterial drug. Both animal experiments and in vitro tests have confirmed that linezolid has strong anti-drug-resistant MTB activity. However, it has been reported that linezolid is easy to cause anemia, thrombocytopenia and peripheral neuritis. Adverse reactions, which are poorly tolerated by patients. To further evaluate the safety, tolerability, and clinical efficacy of linezolid in the treatment of multidrug-resistant tuberculosis (MDR-TB), this study performed a retrospective analysis of 30 patients with MDR-TB in California, USA, who were treated with a linezolid-containing regimen from January 2003 to December 2007. Methods: Linezolid was administered orally once a day at a dose of 600 mg, body weight<40 kg reduced dosage and oral vitamin B at the same time₆(50-100 mg/d) to alleviate the adverse reactions caused by linezolid. Results: The average treatment time of 30 patients treated with linezolid regimen was 18.9 months (1 to 28 months), of which 29 were tuberculosis of the lung and 1 was tuberculosis of the spine; 16 cases had cavities in the lungs and 3 cases had extensively drug-resistant tuberculosis; The sputum culture of 29 patients with pulmonary tuberculosis was negative, and the median time was 7 weeks (0-50 weeks); Among the 30 cases, 22 cases completed treatment, 5 cases continued treatment, 2 cases interrupted treatment, 1 case failed treatment, and there were no deaths; 9 cases had adverse reactions, including peripheral nerve and optic neuritis, anemia, thrombocytopenia, rash and diarrhea, etc. Only 3 cases discontinued linezolid due to adverse reactions. Conclusion: Linezolid can achieve satisfactory clinical effect in the treatment of MDR-TB, and it is well tolerated by patients. Even if adverse reactions occur, it is generally not necessary to stop the drug.

Refractory asthma accounts for about 5% of patients with bronchial asthma (asthma for short). Although the proportion is not high, according to literature reports, its emergency medical treatment rate and hospitalization rate are 15 times and 20 times that of patients with mild and moderate asthma, respectively, which is one of the important reasons for the increase of asthma treatment cost. Therefore, improving the diagnosis and treatment level of refractory asthma is of great significance to improve the overall control level and prognosis of asthma and reduce the medical cost.

Vascular endothelial growth factor (VEGF) is associated with tumor growth and metastasis, possibly because it can regulate cell differentiation and promote vascular permeability, but the impact of its overexpression on prognosis in lung cancer patients is still controversial. We searched the literature on the relationship between VEGF and lung cancer prognosis in PubMed, Embase, Web of Science and CNKI databases, evaluated the literature quality by using the biological factor prognostic study method provided by the European Lung Cancer Collaborative Group, extracted the prognostic data included in this study, and quantitatively analyzed the relationship between VEGF overexpression and the prognosis of lung cancer patients such as non-small cell lung cancer (NSCLC) by meta-analysis.

Continuous positive pressure ventilation (CPAP) is the primary treatment for symptomatic OSAHS patients, however the effectiveness of its treatment is related to the patient's compliance with CPAP. During CPAP treatment, both the inspiratory and expiratory phases were positive pressures, and the positive pressure in the inspiratory phase helped to inhale, while the positive pressure in the airway in the expiratory phase became the expiratory resistance, resulting in difficulty in expiration. Some scholars speculate that some patients may give up treatment due to dyspnea caused by CPAP. Reducing expiratory phase pressure during CPAP treatment may help exhale air, help reduce end-expiratory lung volume, and in turn help inhale, reduce respiratory work, and improve treatment comfort. Since expiratory load is closely related to inspiratory load, and increased expiratory load can cause increased respiratory central drive, we hypothesized that CPAP treatment reduces positive expiratory phase pressure and may reduce inspiratory phase respiratory central drive, to explore whether expiratory phase pressure release CPAP can reduce respiratory central drive compared with conventional CPAP, and to explore the compliance of patients treated with different types of CPAP.

Glucocorticoids (hormones for short) have a good control effect on bronchial asthma (asthma for short), but 5% ~10% of asthma patients still develop partial or complete resistance to high doses of oral hormones, that is, hormone resistance. Although steroid resistant asthma (SRA) is rare, its treatment-related problems are very difficult, and it also brings a heavy social and medical burden. The research progress of the mechanism of SRA in recent years is summarized as follows.

allergic bronchopulmonary aspergillosis (ABPA) is a kind of allergic lung disease caused by hypersensitivity to Aspergillus. The clinical manifestations are chronic bronchial asthma (asthma for short), recurrent pulmonary infiltration and bronchiectasis^[1]。 1952 Hinson et al.^[2]The disease was first described in detail. ABPA is most common in patients with asthma and cystic fibrosis, and the incidence of ABPA in asthma patients is 1% to 20%^[3,4]2% to 15% of patients with cystic fibrosis. In recent 20 years, with the deepening of people's understanding of ABPA and the extensive application of serological examination technology, the number of clinical cases of ABPA has increased significantly. ABPA often becomes one of the difficult factors to control in clinical asthma. Some research results show that severe asthma is closely related to fungal infection.

Bronchial asthma (asthma for short) is a disease with recurrent wheezing, chest tightness, dyspnea and cough as the main symptoms, which can lead to death in severe cases. Acute asthma is generally characterized by airway stenosis caused by contraction of airway smooth muscle. In addition to this mechanical effect, airway smooth muscle also participates in the inflammatory response of airway through secretion of cytokines, alteration of tissue matrix composition and binding to inflammatory cells^[1]。 Chronic asthma is characterized by airway remodeling, including thickening of airway wall, increased mucous glands and goblet cells, and vascular proliferation, and most importantly, the proliferation of airway smooth muscle^[1]。 The role of smooth muscle in the pathogenesis of asthma makes targeted therapies for it possible^[2]。 Airway smooth muscle contraction is a definitive factor leading to bronchial constriction, and bronchodilation with receptor agonists is the first step in asthma treatment^[3]。 In the past 10 years or so, the combination of inhaled anti-inflammatory agents and long-acting receptor agonists has been the main method for the treatment of moderate and severe asthma. At present, despite the combination of inhaled anti-inflammatory agents and bronchodilators to control asthma, more severe asthma still occurs^[4]There are also many patients with severe asthma who are insensitive to a variety of drugs, including large doses of inhaled glucocorticoids. Transbronchoscopic radiofrequency ablation as a new method of asthma treatment when asthma symptoms cannot be alleviated by drugs^[5]Can reduce the number of airway smooth muscle and reduce the contractility of airway smooth muscle, thereby alleviating the chronic symptoms of asthma patients who are ineffective for conventional standard treatment and delaying the exacerbation of the condition. Bronchoscopic radiofrequency ablation is a technique that reduces the amount of airway smooth muscle by delivering controlled therapeutic heat to the airway wall, thereby reducing the contractility and hyperresponsiveness of airway smooth muscle. Radiofrequency therapy is widely used in the treatment of many diseases, such as lung cancer and cardiac conduction disorders^[6]。 Combined with foreign literature, this paper introduces the progress of trans-bronchoscopic radiofrequency ablation in the treatment of asthma.

pulmonary alveolar microlithiasis (PAM) is a rare disease of the lung. It is characterized by extensive deposition of calcium phosphate microstones in the alveoli. The clinical symptoms are mild. The typical X-ray chest radiograph shows "blizzard" sign, and the clinical symptoms are separated from the imaging findings. Most patients have family history and are autosomal recessive inheritance. In recent years, people's attention and awareness of it have gradually increased.

Nerve growth factor (NGF) is the key to neurogenic inflammation in bronchial asthma (asthma) and plays an important role in neuronal differentiation. Our previous research results showed that NGF can transform the phenotype and function of adrenal medullary chromaffin cells (AMCC) by initiating functional redundancy, resulting in a decrease in adrenaline levels, thus participating in the occurrence and development of asthma^[1,2,3]。 However, it is still unclear by which signaling pathway NGF regulates downstream factors to initiate AMCC redundancy. mitogen-activated protein kinase (MAPK) signal transduction pathway is an important transduction mechanism involved in cell differentiation. This study preliminarily investigated the important role of MAPK signaling pathway in the redundancy of AMCC initiated by NGF, and provided a new effective target for asthma prevention and treatment.

Bronchial asthma (asthma for short) is a common respiratory disease. The treatment of asthma is closely related to the control of airway inflammation. Glucocorticoid-based treatment has become the main treatment plan at present, but some asthma patients still can't achieve complete remission. In this study, we observed the changes of inflammatory cells and inflammatory factors in sputum of asthmatic patients before and after treatment, and understood the roles of thymus activation-regulated chemokine (TARC), interleukin-8 (IL-8) and matrix metalloproteinase-9 (MMP-9) in the pathogenesis of asthma.

Acute exacerbation of COPD (AECOPD) can be caused by a variety of causes, most of which are caused by respiratory tract infection, among which bacterial infection is the main one, and some causes are difficult to determine. Under the existing conditions, it is difficult for clinicians to make an accurate judgment on the cause of newly-onset AECOPD patients, and the course of antibiotic treatment is inconclusive. About half of AECOPD is caused by bacterial infection, but more than 85% of patients have received antibiotic treatment. Antibiotic abuse is widespread in the treatment of AECOPD, resulting in severe bacterial resistance and huge waste of medical resources. Serum procalcitonin has high clinical value in differentiating bacterial respiratory tract infections and can reduce the dosage of antibiotics in respiratory tract infectious diseases^[1]。 The purpose of this study was to investigate the guiding significance of dynamic monitoring of serum procalcitonin in the use of antibiotics in patients with AECOPD.

The possible factors causing benign tracheal stenosis include long tracheal intubation time, tracheotomy, inhalation injury, airway infection caused by tuberculosis or diphtheria, etc. In the past, endobronchial tuberculosis was the main cause of benign tracheal stenosis in China. In recent years, with the improvement of various rescue techniques and respiratory support treatment, the survival time of critically ill patients has been prolonged, and the proportion of tracheal stenosis caused by long-term tracheal intubation or tracheotomy has gradually increased. After tracheal intubation, stenosis is easy to occur at the position of the cuff. The possible pathogenesis is that the pressure of the cuff on the tracheal wall leads to a reduction in local blood flow. Ischemic injury will occur within hours after intubation, and reticular fiber repair will occur within 3 to 6 weeks. The main mechanism of stenosis after tracheotomy is the excessive proliferation of granulation tissue around the anastomosis when the incision heals. It may also occur that the cannula forms a mechanical lever at the anastomosis and compresses the tube wall, resulting in local necrosis and rupture^[1]。 Airway stent is an effective method for the treatment of tracheal stenosis, but restenosis after stent placement is a difficult problem in the treatment of benign tracheal stenosis. Therefore, it is necessary to establish a simple, reliable and repeatable tracheal stenosis model to seek the prevention and early treatment of tracheal stenosis.

At present, it is recognized that fibroblasts are the main effector cells of pulmonary fibrosis. There is high expression of β-catenin in fibroblasts of patients with idiopathic pulmonary fibrosis^[1]。 The purpose of this study was to investigate whether the high expression of β-catenin can increase the synthesis of procollagen in fibroblasts and its effect on pulmonary fibrosis.

Clemens von Pirquet is a renowned Austrian scientist and pediatrician who has made remarkable contributions to immunology. He was the first to use the term "Allergy" and is revered as the father of Allergy (Figure 1)。

The Global Initiative for Chronic Obstructive Pulmonary Disease (GOLD) project was launched in 1998, and the Global Strategy for the Diagnosis, Treatment and Prevention of COPD (GOLD Report) was first published in 2001. After the revision of the GOLD Report in 2006, the definition, classification and treatment of COPD were substantially revised, marking an important progress in the standardized diagnosis and treatment of COPD. Since then, the 2007-2009 GOLD report has been updated annually^[1]Here, the author introduces the updated part of the last three years and comments on its basis.

Recent COPD epidemiological surveys in seven regions in China show that the prevalence of COPD in men and women over 40 years old is 12.4% and 5.1%, respectively, and the overall prevalence is 8.2%^[1]。 With such a high prevalence of COPD, the burden on society and families is enormous.

The first event of Beijing Young Respiratory Scholars Salon in 2010 was held on March 25th, 2010, presided over by Bu Xiaoning, deputy chief physician of Beijing Chaoyang Hospital, with the theme of "Discussion on the Related Issues of Extracorporeal Membrane Oxygenation (ECMO) in the Treatment of New H1N1 Influenza and Severe Pneumonia".

In order to promote the standardized diagnosis and treatment of bronchial asthma (asthma for short), the asthma group of Respiratory Disease Branch of Chinese Medical Association formulated the guidelines for asthma prevention and treatment twice in 2003 and 2008 (see the columns of "Diagnosis and Treatment Plan" in Issue 3 of 2003 and Issue 3 of 2008 for details), and vigorously popularized the standardized diagnosis and treatment based on the guidelines nationwide, especially in grass-roots hospitals, which achieved good results. The overall asthma control level has been improved to a considerable extent, but there are still about 5% of patients with refractory asthma who can't reach a good control state. Therefore, the Asthma Group of the Respiratory Branch of the Chinese Medical Association organized relevant experts. After many full and serious discussions, referred to the experiences of the European Respiratory Society (ERS), the American Thoracic Society (ATS) and the Global Asthma Prevention and Treatment Initiative (GINA), and combined with the actual situation in China, several drafts were revised, and the "Expert Consensus on Diagnosis and Treatment of Refractory Asthma" was finally formed. As an important supplement to the guidelines for asthma prevention and treatment, this consensus further unifies the understanding of the definition of refractory asthma, the assessment and treatment of diseases, etc. At the same time, it puts forward guiding suggestions for future research directions, which are believed to play an important role in clinical and scientific research. As Professor Lin Jiangtao said in the review, clinicians can only fully understand the clinical characteristics of refractory asthma, understand and master the diagnosis and evaluation procedures of refractory asthma, be good at screening and dealing with the factors that make asthma difficult to control, and at the same time grasp the future research direction, so that refractory asthma may no longer be refractory to cure.