Common Variable Immunodeficiency with Genetic Defects Identified by Whole Exome Sequencing.

Common variable immunodeficiency (CVID) belongs to the primary immunodeficiency disorders (PIDs), presenting a profound heterogeneity in phenotype and genotype, with monogenic or complex causes. Recurrent respiratory infections are the most common clinical manifestations. CVID patients can also develop various autoimmune and lymphoproliferative complications. Genetic testing such as whole exome sequencing (WES) can be utilized to investigate likely genetic defects, helping for better clinical management. We described the clinical phenotypes of three sporadic cases of CVID, who developed recurrent respiratory infections with different autoimmune and lymphoproliferative complications. WES was applied to screen disease-causing or disease-associated mutations. Two patients were identified to have monogenic disorders, with compound heterozygous mutations in LRBA for one patient and a frameshift insertion in NFKB1 for another. The third patient was identified to be a complex form of CVID. Two novel mutations were identified, respectively, in LRBA and NFKB1. A combination of clinical and genetic diagnosis can be more extensively utilized in the clinical practice due to the complexity and heterogeneity of CVID.

[Clinical characteristics of hospitalized cases of severe acute respiratory infection with laboratory-confirmed influenza and the risk factors analysis of influenza infection for children under 15 years old in ten provinces in China during 2009-2014].

OBJECTIVE: To identify clinical characteristics of hospitalized laboratory-confirmed influenza cases of children under 15 years old, and their risk factors of influenza infection. METHODS: Analyzing the reports of hospitalized laboratory-confirmed influenza cases of children under 15 years old who were detected by the sentinel surveillance systems in 10 provinces from December 2009 to June 2014. Such data as their demographic, medical history, clinical symptoms and signs, treatment and outcome were collected using questionnaires, with their clinical characteristics and their risk factors of influenza infection described. RESULTS: Of the 2 937 severe acute respiratory infection inpatients, 190 (6.5%) were laboratory-confirmed influenza cases. 123 (64.7%) of such confirmed cases were male, and 139 (73.2%) were children under 5 years old, with age median of 3.0 years (IQR: 1.0-5.0 years). 20 (10.5%) of them had at least one chronic medical condition, mostly chronic cardiovascular disease (3.2%), immunosuppressive disease (3.2%), and cancer/tumor (2.6%). Most common clinical symptoms of the cases were fever (92.6%) and cough (88.8%), of which abnormal pulmonary auscultation (51.1%) and abnormal chest X-ray performance (36.1%) were the most common clinical signs. 29 cases (15.8%) had complications, of which pneumonia (15.3%) was most common. 16 cases (8.6%) used antiviral drugs, and 4 cases (2.2%) were admitted into ICU. Risk factor analysis suggested that age < 6 months (OR = 0.406, 95% CI: 0.203-0.815) was a protective factor against influenza infection; and age 5-9 years old (OR = 2.535, 95% CI: 1.059-6.066) was a risk factor for influenza infection. CONCLUSION: Hospitalized laboratory-confirmed influenza cases were found mostly in children under 5 years old. Risk exposure for influenza infection varied among age groups.

[The clinical-radiologic-pathologic features of imported pulmonary histoplasmosis].

OBJECTIVE: To describe the clinical features and treatment of imported pulmonary histoplasmosis and therefore to improve the recognition and differential diagnosis of this disease. METHODS: The clinical data of 3 patients with imported pulmonary histoplasmosis in our hospital were collected and analyzed. Literatures published since 1989 were retrieved with 'pulmonary histoplasmosis' from PubMed, China National Knowledge Infrastructure (CNKI), Wanfang Data and VIP data, of which all the literatures about imported pulmonary histoplasmosis were reviewed. The clinical manifestations, diagnostic methods and treatment were summarized. RESULTS: All the 3 cases of imported pulmonary histoplasmosis were immunocompetent hosts, all were males, age were from 44-67 years, and had a history of exploring the cave or tunnel inhabited by bats in the epidemic areas. All of them developed influenza-like symptoms varying in severity after the onset of the disease. Pulmonary multiple nodules and mediastinal lymphadenopathy were found on chest images. One patient underwent percutaneous lung biopsy and the other two received video-assisted thoracoscopic lung biopsy. All the 3 patients showed consistent histopathological findings, such as granulomatous inflammation with necrosis. Pathogen culture with lung biopsy in the first case was identified as histoplasma. All the 3 cases were treated with itraconazole, and recovered with good prognosis. Thirteen literatures in English were obtained, which reported 60 cases with imported pulmonary histoplasmosis. Forty-two of them were males, 16 were females and 2 undefined. The range of their age was from 17-64 years. No imported pulmonary histoplasmosis was reported so far in Chinese literature. Common features of imported pulmonary histoplasmosis were consistent with our patients, including epidemiology, influenza-like symptoms and bilateral pulmonary nodules, recovery with or without antifungal therapy. CONCLUSION: The epidemiologic history, influenza-like symptoms and bilateral pulmonary nodules provide valuable diagnostic clues for imported histoplasmosis. Clinical features with pathologic findings and good response to antifungal therapy could make the diagnosis even without pathogen detection if other etiology is unlikely.

[Dieulafoy disease of the bronchus: 3 cases report with literature review].

OBJECTIVES: To improve the understanding of bronchial Dieulafoy disease by summarizing the clinical and literature reported cases. METHODS: The clinical data of 3 patients with bronchial Dieulafoy disease diagnosed by pathology from January 1, 2007 to May 31, 2012 in our hospital was collected and summarized. The data of 19 cases from literature case report regarding bronchial Dieulafoy disease both in Chinese and English were also reviewed through databases including Wanfang Data, National Knowledge Infrastructure, National Center for Biotechnology Information and Ovid Technologics from January 1, 2005 to May 31, 2012. The clinical characteristics, diagnosis and treatment of all the 22 cases were summarized and analyzed. RESULTS: The average age of the 22 cases with bronchial Dieulafoy disease was (47 ± 15) years, and the preponderance was in male adults (16/22). Right lung (16/22) was more commonly involved than the left lung (4/22), and rarely in both lungs (2/22). Eight cases had smoking history, and 10 cases had underlying diseases such as tuberculosis.Sudden onset of massive hemoptysis was a common manifestation. Massive or lethal hemorrhage was often caused by biopsy injury. The abnormality of bronchial Dieulafoy disease was usually demonstrated as nodular lesions within the lumen of the bronchus.However, It was unable to determine their originating of the anomalous arteries in half of the cases(11/22). Most anomalous arteries confirmed by pathology were branched from bronchial artery (9/22), and rarely from pulmonary artery (2/22). The definitive diagnosis was made by pathological examination.Selective bronchial artery embolization and pulmonary lobectomy were the major therapeutic strategies, but bleeding may relapse after bronchial artery embolization, and lobectomy of the lung was a cure approach. CONCLUSIONS: Bronchial Dieulafoy disease should be differentiated in patients with massive and unexplained hemoptysis.It takes a very high risk for biopsy, which rarely needs to be implemented. Bronchial arteriography and selective bronchial artery embolization should be promptly carried out to avoid life-threatening hemoptysis.Lobectomy could be an alternative choice for a cure.

[A study on the differential diagnosis of ciliated epithelial cells from Lophomonas blattarum in bronchoalveolar lavage fluid].

OBJECTIVE: To validate the authenticity of the cases diagnosed as pulmonary Lophomonas blattarum infection in literatures and Lophomonas blattarum as a kind of pathogen resulting in pulmonary infection. METHODS: From June 2012 to May 2013, mobile cells with cilia at the anterior end of the cells were observed in BALF from 6 patients with pulmonary disease in our hospital. Morphological feature and ultrastructure of the cells were further investigated by optical microscope and electron microscope to determine the type of the cells referring to literature-published photos of Lophomonas blattarum. Literatures about Lophomonas blattarum infection were searched with keyword Lophomonas blattarum from Wanfang Data, China National Knowledge Infrastructure (CNKI) and PubMed. Diagnostic methods and figures provided by the literature were carefully reviewed, and the accuracy of diagnosis of pulmonary Lophomonas blattarum was identified. RESULTS: Mobile cells found in BALF from the 6 patients in our hospital had the morphological features of bronchial ciliate epithelial cells. A nucleus far from the cilia was observed in the middle or at the bottom of the cytoplasm, and these cells did not display the characteristic cytological structures of Lophomonas blattarum: calyx, perinuclear tubules and axial filament. Diagnosis of pulmonary Lophomonas blattarum reported in literatures so far were all based on the morphological features of mobile cells with a cluster of flagellate at anterior end of the cell by optical microscopy. None of the authors did further exploration on the ultrastructure of such a kind of cells and compared with features of Lophomonas blattarum described in the literature. All the active cells reported in literatures had the identical morphological features to those found in our investigation. CONCLUSION: In the past 20 years, all the diagnosed cases as pulmonary Lophomonas blattarum infection reported in our country were misdiagnosed. Currently, there is no evidence to show Lophomonas blattarum as a pathogen resulting in pulmonary infection.

Chronic intermittent hypoxia from pedo-stage decreases glucose transporter 4 expression in adipose tissue and causes insulin resistance.

BACKGROUND: The persistence of sleep disordered breathing (SDB) symptoms after tonsil and/or adenoid (T&A) surgery are common in children with obstructive sleep apnea (OSA). We tested the hypothesis that disturbances of glucose transporters (GLUTs) in intraabdominal adipose tissue caused by chronic intermittent hypoxia (CIH) from the pedo-period could facilitate the appearance of periphery insulin resistance in Sprague-Dawley (SD) rats. We tested the hypothesis that the changes of GLUTs in adipose tissue may be one of the reasons for persistent SDB among clinical OSA children after T&A surgery. METHODS: Thirty 21-day-old SD rats were randomly divided into a CIH group, a chronic continuous hypoxia (CCH) group, and a normal oxygen group (control group) and exposed for 40 days. The changes of weight, fasting blood glucose and fasting blood insulin levels were measured. Hyperinsulinemic-euglycemic clamp techniques were used to measure insulin resistance in each animal. Real-time quantitative PCR and Western blotting were used to measure GLUT mRNA and proteins in intraabdominal adipose tissue. Additional intraabdomial white adipose tissue (WAT) was also processed into paraffin sections and directly observed for GLUTs1-4 expression. RESULTS: When compared with control group, CIH increased blood fasting insulin levels, (245.07 +/- 53.89) pg/ml vs. (168.63 +/- 38.70) pg/ml, P = 0.038, and decreased the mean glucose infusion rate (GIR), (7.25 +/- 1.29) mg x kg(-1) x min(-1) vs. (13.34 +/- 1.54) mg x kg(-1) x min(-1), P < 0.001. GLUT-4 mRNA and protein expression was significantly reduced after CIH compared with CCH or normal oxygen rats, 0.002 +/- 0.002 vs. 0.039 +/- 0.009, P < 0.001; 0.642 +/- 0.073 vs. 1.000 +/- 0.103, P = 0.035. CONCLUSIONS: CIH in young rats could induce insulin resistance via adverse effects on glycometabolism. These findings emphasize the importance of early detection and treatment of insulin insensitivity in obese childhood OSA.