2017年 · 第40卷第10期

In the golden autumn of October, the fragrance of osmanthus is the best harvest season of the year. The 10th issue of this magazine in 2017 meets your readers.

drug-induced lung injury (drug-induced lung injury) is a general term for adverse reactions of drugs in the respiratory system, including the lungs, bronchi, pulmonary blood vessels and pleura. In recent years, with the emergence of new anti-tumor targeted drugs and biotherapeutic agents, the incidence of drug-induced lung injury is increasing year by year. Japan Drug and Medical Device Safety Information data show that the incidence of drug-induced lung injury in Japan increased by 15.9% between 2005 and 2009^[1]。 Compared with drug-induced liver injury and drug-induced kidney injury, drug-induced lung injury has attracted far less attention from the medical field, especially respiratory doctors. Due to the variety of clinical manifestations and lack of specific diagnostic methods, drug-induced lung injury is often misdiagnosed and misdiagnosed. This issue Huang Chen et al.^[2]And Chen Yuling et al.^[3]Four cases and one case of pulmonary interstitial disease caused by anti-tumor drugs were reported, respectively, hoping to attract the attention of colleagues in the respiratory field to drug-induced lung injury.

drug-induced interstitial lung disease (DILD) is a group of diffuse lung diseases caused by different kinds of drugs. The main manifestations are inflammation and fibrosis of the alveoli, pulmonary interstitial and pulmonary small vessels^[1,2]。 DILD is not uncommon and presents a diverse range of clinical features ranging from mild pulmonary infiltrates to life-threatening acute respiratory distress syndrome (ARDS). More than 350 drugs are known to cause DILD, including antimicrobial drugs, anti-inflammatory drugs, anti-tumor drugs, cardiovascular drugs, illegal drugs, etc^[1]。 In recent years, with the increase of biological agents and the expansion of application scope, it has been found that DILD caused by different biological agents, such as interferon alpha or beta, can cause acute interstitial pneumonia, diffuse alveolar injury (DAD), diffuse alveolar hemorrhage (DAH), non-specific interstitial pneumonia (NSIP), organizing pneumonia (OP), acute exacerbation of pre-existing ILD (AE-ILD), sarcoidosis-like granuloma, bronchiolitis obliterans (BO); Interferon γ can cause acute interstitial pneumonia, DAD, AE-ILD^[3,4]； Anti-tumor necrosis factor (TNF) alpha drugs, such as infliximab and adalimumab, can cause interstitial pneumonia, lupus-like acute interstitial pneumonia, BO, non-necrotic granulomatous interstitial pneumonia^[5,6,7]； Epidermal growth factor receptor tyrosine kinase inhibitors, such as gefitinib and erlotinib, can cause acute interstitial pneumonia, DAD, DAH and common interstitial pneumonia (UIP), etc.^[8,9]。

Interstitial lung disease (ILD), also known as diffuse parenchymal lung disease (DPLD), is a general term for a group of diffuse lung diseases that mainly involve the interstitial and alveolar cavities of the lung, resulting in loss of alveolar-capillary functional units. The main clinical manifestations were progressive aggravation of dyspnea, ventilatory dysfunction with reduced diffusion function, hypoxemia and diffuse lesions of both lungs on imaging^[1]。 Lung transplantation becomes the ultimate treatment when ILD reaches the terminal stage and existing medical treatments are ineffective.

lymphangioleiomyomatosis (LAM) is a rare disease that occurs in women of childbearing age and is characterized by diffuse pulmonary cystic lesions. The clinical manifestations are usually gradually aggravating dyspnea and recurrent pneumothorax and chylothorax. In 2010, the European Respiratory Society (ERS) published the world's first diagnostic and treatment guidelines for LAM, including diagnostic criteria, assessment methods, screening of high-risk groups and treatment recommendations for LAM^[1,2]。 More than 6 years have passed, and many important advances have been made in clinical diagnosis and pharmacological treatment research of LAM. In view of this, the American Thoracic Society (ATS) and the Japanese Respiratory Society (JRS) published the Clinical Guidelines for the Diagnosis and Management of LAM (abbreviated as the Guidelines) in 2016, which systematically summarized four important clinical questions about the diagnosis and treatment of LAM^[3]This paper briefly introduces this.

The human apolipoprotein M (ApoM) gene is located in the short arm of chromosome 6, p21.31. Its cDNA encodes a 188 amino acid sequence, which mainly exists in human plasma high density lipoprotein (HDL). It participates in the formation of pre-β-HDL and regulates the reverse transport of cholesterol^[1,2]。 In addition, ApoM is a physiological carrier of sphingosine-1-phosphate (S1P). After binding to S1P, ApoM can restrict the adhesion of monocytes to vascular endothelial cells and play an anti-inflammatory role^[3]。

High concentration oxygen or hyperbaric oxygen plays an important role in the treatment of patients with severe hypoxia or respiratory failure, but hyperoxia can also induce or aggravate hyperoxia-induced acute lung injury (HALI), which has become one of the hotspots of clinical research. Recent studies have shown that caveolin-1 (Cav-1) is involved in pathophysiological processes such as cell proliferation, apoptosis and inflammatory response by regulating Toll-like receptor 4, p38 mitogen-activated protein kinase and nuclear factor-κ B^[1,2,3,4], plays an important role in the occurrence and development of acute lung injury^[5,6]However, its mechanism of action has not been elucidated. In this study, the expression levels of Cav-1, caveolin-1-tyrosine residues 14 phosphorylation (P-Cav-1-Y14), tumor necrosis factor-α (TNF-α) and IL-6 in lung tissue were observed by inhibiting the phosphorylation level of Cav-1, so as to investigate the role of Cav-1 in hyperoxia-induced acute lung injury in mice and its related mechanisms.

In China, eosinophilia is more common in parasitic infection, especially in patients with Clonorchis sinensis infection. Mild cases only have digestive tract discomfort symptoms, and severe cases have multiple system involvement, which develops into hypereosinophilic syndrome (HES). HES with parasitic infection is more common clinically, but complicated with pulmonary artery thrombosis is very rare. One case admitted to our hospital is reported below.

A 49-year-old female was admitted to the hospital on November 12, 2015 due to "dry eyes and mouth for 2 years, dry cough for 6 months, and multiple cystic-like changes found on CT examination". Six months ago, the patient developed dry cough without obvious trigger, without circadian rhythm and seasonality, and was not induced by pollen, oil fume and food. He complained that the cough was aggravated after activity, accompanied by wheezing after activity, and the above symptoms were progressively aggravated. The patient had no symptoms such as morning stiffness, joint pain, muscle pain and weakness, rash and Raynaud's phenomenon. Physical examination: wasting state, small bursting sounds in both lower lungs, no deformities in the joints of the limbs, no clubbing fingers, admission imaging examination CT showed diffuse ground glass high-density shadows in both lungs with multiple cyst-like changes, and enlarged mediastinal lymph nodes (Figure 1、Figure 2、Figure 3、Figure 4、Figure 5、Figure 6), admission diagnosis: nature of interstitial lung disease to be determined.

The activity of motor neurons, nerves and muscles can be continuously enhanced after intermittent exposure to certain stimuli. This phenomenon is called long-term facilitation (LTF)^[1]This phenomenon has been demonstrated in different regimens of stimulation and in different animal species. LTF is the main form of human respiratory plasticity, and intermittent hypoxia is the most common stimulus to induce LTF, which has been widely used in the study of human respiratory plasticity^[2]。

Sarcoidosis is a multi-system granulomatous disease with unknown etiology. Its pathological characteristics are non-caseous epithelioid granuloma, more than 90% of which involve both hilar lymph nodes and lung parenchyma. Other easily affected organs are heart, liver, spleen, eyes and skin. The prognosis of sarcoidosis is relatively good, 50% of patients can heal themselves within 2 years of onset, those with a course of more than 5 years are less likely to heal themselves, and 20% of patients have persistent clinical symptoms due to irreversible fibrosis. The mortality rate of sarcoidosis was 7.6%, and the main causes of death were respiratory failure and pulmonary hypertension caused by pulmonary fibrosis. At present, the etiology of sarcoidosis is unclear, the mechanism is still unclear, and there is a lack of specific treatment. Glucocorticoid (hormone) is a classic drug for the treatment of sarcoidosis. Those with poor effect of hormone therapy can try to add immunosuppressant or biological agents. About 10% of patients with end-stage sarcoidosis continue to progress after active drug therapy, which seriously endangers the quality of life and life of patients^[1]。 Lung transplantation is the only effective treatment for end-stage sarcoidosis patients whose progression of pulmonary fibrosis cannot be controlled by drugs and conventional therapy^[2]However, because sarcoidosis is a disease with multi-system involvement and variable outcome, and there is a possibility of recurrence after lung transplantation, it has certain particularity compared with other lung diseases, so it is very important to fully grasp the timing and indications of lung transplantation. The timing and prognosis of lung transplantation for end-stage sarcoidosis are summarized as follows, so as to help clinicians make timely and reasonable decisions related to lung transplantation in the process of diagnosis and treatment.

Legionella pneumonia (legionella pneumophila, LP) is a systemic disease mainly caused by pneumonia caused by Gram-negative Legionella pneumophila. It is one of the main pathogenic bacteria of community-acquired pneumonia (CAP), which often develops into severe pneumonia^[1]。 The incidence of Legionella pneumonia among CAP patients varies globally, with approximately 14% in the United States and 6.6% in Asia^[2]； With the introduction of Legionella urine antigen test, the incidence of Legionella infection in CAP increased significantly^[3]The reason for the low incidence of Legionella pneumonia in Asia and other countries may be related to diagnostic techniques^[3]。 The 2012 Dutch CAP guidelines for adults recommend that all patients with severe CAP should be tested for Legionella urine antigen^[4]。 While Phin et al.^[5]It is recommended that any patient with symptoms of community or hospital-acquired pneumonia require a Legionella test. It can be seen that Legionella is an important pathogen of lower respiratory tract infections, especially severe pneumonia. Hyponatremia often increases morbidity, mortality and length of hospital stay^[6]。 Patients with Legionella pneumonia are often complicated with hyponatremia, the incidence rate is about 46%^[7], hyponatremia is one of the independent predictors of legionella pneumonia mortality and intensive care unit admission^[8]。 In order to strengthen the understanding of the mechanism of hyponatremia caused by Legionella, timely and effectively treat hyponatremia, and improve the prognosis of patients with Legionella pneumonia. The related studies on the mechanism of hyponatremia caused by Legionella pneumonia are summarized as follows.

At present, fluoroquinolones are still highly sensitive to common pathogenic bacteria in community acquired pneumonia (CAP) in China, and have the characteristics of high tissue concentration, good oral bioavailability and convenient administration. They are one of the ideal drugs for antibacterial treatment of CAP. However, due to many adverse drug reactions, strong anti-MTB effect and strong resistance induction ability to Enterobacteriaceae bacteria, their clinical application has been limited to some extent.

There are many kinds of airway stents, which are used in all kinds of benign and malignant airway stenosis. Airway stents can be classified according to criteria such as their indications, the anatomical site of implantation, the technique of implantation, and whether they can be removed. The commonly used classification method is to divide them into four main types according to different materials, such as metal stent, plastic or silicone stent, hybrid stent and biodegradable stent^[1]。

The clinical manifestations of chronic pulmonary aspergillosis (CPA) are diverse. In recent years, CPA has gradually received clinical attention due to its high incidence and heavy medical burden. In 2015, the European Society of Clinical Microbiology and Infectious Diseases and the European Respiratory Society jointly released the first "Guidelines for the Diagnosis and Treatment of Chronic Pulmonary Aspergillosis"^[1]CPA was classified into five types: (1) simple pulmonary aspergillus globules; (2) chronic cavitary pulmonary aspergillosis (CCPA), formerly known as complex pulmonary aspergillosis; (3) chronic fibrotic pulmonary aspergillosis (CFPA); (4) Aspergillus nodules; (5) Subacute invasive pulmonary aspergillosis (SAIA), formerly known as chronic necrotizing pulmonary aspergillosis. CPA drug therapy requires a long course of treatment and is prone to relapse. For patients with localized lesions, surgery is an important clinical choice. The progress of surgical treatment of CPA is summarized as follows.

In sleep-related breathing disorders (SRBD), patients with obstructive sleep apnea, central sleep apnea syndrome, and sleep-related hypopnea may experience CO during sleep₂Retention, most of which can be reversed in a short time after waking up, and some still occur daytime hypercapnia^[1,2], literature reports that morning waking is more than before bedtime PaCO₂The increase of difference is an independent factor in predicting the mortality of SRBD^[3]。 Some patients with chronic respiratory failure only show sleep PaCO in the early stage₂rise^[2,4]And patients with SRBD can develop acute type II respiratory failure under infection, trauma and surgical anesthesia^[4,5]。 High CO₂The resulting cell injury was independent of pH level^[6]。 Therefore, it is important to emphasize that patients with SRBD CO₂Importance of monitoring.

House dust mite is the main allergen causing allergic rhinitis and bronchial asthma (asthma) in China. Previous research results show that in the mouse model of allergen-induced upper airway inflammation, the relationship between allergic inflammation of lower airway and cytokine-mediated bone marrow progenitor cells and systemic response also confirms that the degree of house dust mite sensitization is closely related to the severity of allergic rhinitis or asthma. If we can comprehensively evaluate the pathophysiological and immunological responses of patients' airways after allergen challenge, we can provide more key information for real-world research on rhinitis and asthma. The purpose of this study was to simultaneously observe the changes of inflammation and reactivity of upper and lower airways in patients with allergic rhinitis after nasal mucosal challenge test (nasal challenge) by various non-invasive allergen detection methods. Four groups of subjects were enrolled in the study, 15 cases in allergic rhinitis group with airway hyperresponsiveness, 15 cases in simple allergic rhinitis group, 15 cases in atopic group with house dust mite sensitization and 15 cases in healthy control group. All subjects underwent allergen skin prick test, blood allergen-specific IgE test, VAS rhinitis symptom score, nasal lavage cytology classification, house dust mite nasal challenge, nasal resistance measurement, induced sputum cytology classification, lung function test and exhaled nitric oxide (FeNO) test according to the scheduled procedure at 3 clinical follow-up visits. The results showed that nasal resistance increased after nasal stimulation in all 4 groups, among which the rhinitis patients with airway hyperresponsiveness increased most obviously (P<0.05)； Post-challenge VAS rhinitis symptom scores, nasal lavage, and sputum eosinophils were significantly elevated in all rhinitis patients (P<0.001), but only rhinitis patients with airway hyperresponsiveness developed pulmonary function PD20-FEV₁Decrease in FeNO and increase in FeNO (P<0.05)； Nasal lavage eosinophils were positively correlated with sputum eosinophils and FeNO levels, respectively (r=0.737, 0.736, bothP<0.001), while with FEV, respectively₁and PD₂₀There was a negative correlation (r＝－0.287，－0.436,P<0.001)。 Results It was found that house dust mite nasal provocation can induce and aggravate inflammation and airway reactivity of upper and lower airways in patients with allergic rhinitis without asthma, which demonstrates the view of "same airway, same disease".

Chronic obstructive pulmonary disease (COPD) has become one of the major health problems in the world due to its increasing morbidity and mortality, but its pathogenesis is still unclear. Our previous study confirmed that endothelial cell apoptosis and endothelial dysfunction are involved in the development of COPD. Endothelial progenitor cells (EPC) isolated from bone marrow or peripheral blood can be transformed into mature, functional endothelial cells. The number of EPC in COPD patients decreased significantly, and it was related to hypoxia and the severity of airway destruction. Therefore, we speculated that the decrease of EPC may be related to endothelial dysfunction and pathogenesis of COPD, and EPC supplementation may play a protective role.