曲霉在自然界中广泛分布，约20种曲霉能感染人类和动物，其中最常见的有烟曲霉、黄曲霉、土曲霉和黑曲霉等。曲霉孢子在空气中传播，人吸入后曲霉可以在气道内定植、致敏、感染，当人体免疫功能低下时可产生危及生命的侵袭性肺曲霉病（IPA）。近年来IPA发病率呈上升趋势，已成为仅次于念珠菌病的主要肺部真菌感染性疾病[1]。虽然IPA已成为器官移植受者、恶性血液病和恶性肿瘤患者等高危人群的重要死因，但对其发病机制了解甚少。本文着重论述近年来IPA发病机制的研究进展。
现已认识到免疫反应、转录因子核因子κB( NF-κB) 的激活、细胞因子、中性粒细胞的激活和肺泡渗入、凝血级联反应、肾素-血管紧张素系统等多种因素构成的复杂网络参与急性肺损伤/急性呼吸窘迫综合征( ALI/ARDS) 的发病过程[ 1-5] 。虽然脓毒症、创伤、肺炎等ALI/ARDS诱发因素很常见, 但仅有部分病人发生ALI/ARDS, 并且具有相似临床特征的ALI/ARDS病人可有截然不同的结果, 这种异质性引起研究者对影响ALI/ARDS 易感性和预后的遗传因子进行鉴别的浓厚兴趣[ 6] 。由于数量庞大的表现型变异, 不完全的基因外显率、复杂的基因-环境相互作用及高度可能的基因座不均一性而使ALI 遗传学的研究受到挑战[ 7] 。近年来基因组学技术被应用于ALI/ARDS 发病机制的研究, 加深了人们对ALI/ARDS的认识并有可能发展出新的治疗策略以降低其发病率和病死率。
Cough variant asthma is a special type of asthma, of which the only or main symptom is cough, and it is the main cause of chronic cough. Early diagnosis and treatment can prevent cough variant asthma developing into typical asthma. This article summarizes the progress in pathogenesis, diagnosis and assessment, treatment, and prognosis of cough variant asthma, aiming to improve the prevention and treatment of this disease, and increase the patients’ quality of life.
Objective To investigate the effects of TiotropiumBromide on airway inflammation in a rat model of chronic obstructive pulmonary disease( COPD) . Methods Thirty Wistar rats were randomly divided into three groups. Group A received normal breeding as normal control. Group B and group C received LPS( 200 μg, intratracheally injected at the 1st and the 14th day) and tobacco exposure( from the 2nd day to the 30th day except the 14th day) to establish COPD model. And group C received a nebulized dose of Tiotropium Bromide( 0. 12 mmol / L, 10 minutes) 30 minutes before the tobacco exposure each time. Airway resistance and compliance were measured before sacrificed. Histological examination was performed with Hematoxylin-Eosin staining. The concentrations of IL-8 and LTB4 , total and differential cells counts in bronchoalveolar lavage fluid( BALF) were examined, and the concentrations of IL-8 and LTB4 in blood serum were also examined by ELISA. Results Severe lung inflammation and decreased lung function were demonstrated in the rats in the group B compared with those in the group A. The inflammatory cell counts in BALF, and the levels of IL-8 and LTB4 in BALF and serum were significantly increased in the group B compared with those in the group A. Tiotropium Bromide administration improved the parameters above. Conclusions The results suggest that Tiotropium Bromide can alleviate the lung inflammation and improve the lung function in a rat COPD model. These effects may be exerted through reducing the mediators of inflammation.
Objective To analyze the data from patients with pathologically proved granulomatous lung disease, including etiology, clinical, radiological features and laboratory results. Methods 36 patients with granulomatous lung disease confirmed by lung biopsy in Shanghai First People’s Hospital of Shanghai Jiao Tong University from January 2008 to June 2012 were retrospectively reviewed. The clinical presentation, radiological features and laboratory results were collected and statistically analyzed.Results After haematoxylin and eosin stain combined with special stain, the diagnoses were comfirmed, ie.13 cases of mycobacterial infection, 5 cases of aspergillar infection, 4 cases of cryptococcal infection, 6 cases of sarcoidosis, 4 cases of Wegener’s granulomatosis, 4 cases of unknown causes. Cough was the most common clinical symptom, followed by expectoration. Some patients also developed fever, chest tightness and weight loss. The lesions were widely distributed, of which the right upper lung was the common lesion of mycobacterial infection, inferior lobe of right lung was the common lesion of aspergillar infection. The common lesion of cryptococcal infection was uncertain. The common lesions of sarcoidosis and Wegener ’s granulomatosis were in left upper lung. Small nodule was the most common shapes of lesion, while mass and consolidation were present sometimes. Cavity, air bronchogram, pleural effusion, hilar and mediastinal lymph node enlargement could be found in the chest CT. Interferon gamma release assay, galactomannan antigen assay and latex agglutination test were helpful in the diagnosis of mycobacterial infection, aspergillar infection and cryptococcal infection induced granuloma. Conclusions The clinical presentations and radiological features of granulomatous lung disease are nonspecific. Histopathology obtained through biopsy is the key for the diagnosis. Immunological examination, test of new antigens to microorganism and clinical microorganism detection are valuble in the diagnosis and differential diagnosis of granulomatous lung disease.
Objective To investigate the blood clotting dysfunction of invasive pulmonary aspergillosis(IPA)and the therapeutic effect of low molecular hepafin in a mouse model．Methods The neutropenic IPA mouse model was constructed by being given cyclophosphamide to depress immunologic function，and then intranasally challenged with Aspergillus fumigatus conidia．(1)Blood clotting function were assessed by bleeding time，clotting time，platelet count and antithrombase-III(AT-III)activity．Seventy-two mice were randomly assigned into 4 groups．Group A received only normal saline．group B received normal saline to substitute the cycloph0sphamide，and the rest equal to group D．Group C received normal saline to substitute the AspergiUus fumigatus conidia suspension，and the rest equal to group D．Group D(model group)received cyclophosphamide(intraperitoneally，150 mg／kg，d4，d1)and Aspergillus fumigatus conidia suspension(intranasally，40 μL／mouse，1．5×10∧5／mL，d0)．Six mice were randomly sacrificed in each group for analysis of blood clotting function per 24 h after inoculation for 3 times．(2)Therapeutic effect of low molecular heparin was determined by survival time of IPA mice．One hundred and eighteen mice were randomly assigned into 4 groups after challenged with 6×10 conidia／mouse and received one of the following regimens daily from dl to d7 after challenge，vehicle(group E，n=29)，low molecular heparin(group F，n=30，subcutaneous injection，1000 IU／kg，qd×7 d)，amphotericin B(group G，n=29，intraperitoneal，1 m kg，qd×7 d)，low molecular heparin plus amphotericin B(group H，n=30)．Mice survivals were recorded once daily to d21 after innoculation．Results (1)AT-III activity of group D decreased significantly 24 h after innoculation．Bleeding time and clotting time decreased significantly and AT—III activity decreased sequentially 48 h after innoculation．The platelet decreased significantly 72 h after innoculation，and bleeding time shoaened further．Clotting time was longer than that 0f 48 h．but still shorter than norm al and AT-III activity decreased sequentially．There were significant differences when comparing group D with group A，B and C(all Plt;0.01)．And there was no significant difference between group A，B and C(all Pgt;0．05)．(2)Survival analysis indicated that the therapeutic effect of low molecular hepafin plus amphotericin B was better than that of amphotericin B or low molecular heparin alone．No therapeutic effect was found in group F(group E vs group F，Pgt;0．05，both group E and group F compared with group H，P lt;0．01．Group H vs group G，P lt;0．05．Both group E and group F compared with group G，P lt;0．05)．Conclusions The results suggest that there is blood clotting dysfunction in IPA mice and AT—III activity may be an early index to monitor the disfunction．Compared with the therapeutic effect of amphoterinein B alone，low molecular hepafin plus amphoterincin B can prolong survival of neutropenic IPA mice