Benralizumab efficacy and safety in severe asthma: A randomized trial in Asia.

BACKGROUND: Benralizumab is indicated as add-on therapy in patients with uncontrolled, severe eosinophilic asthma; it has not yet been evaluated in a large Asian population with asthma in a clinical trial. OBJECTIVE: To evaluate the efficacy and safety of benralizumab in patients with severe asthma in Asia. METHODS: MIRACLE (NCT03186209) was a randomized, Phase 3 study in China, South Korea, and the Philippines. Patients aged 12-75 years with severe asthma receiving medium-to-high-dose inhaled corticosteroid/long-acting ß2-agonists, stratified (2:1) by baseline blood eosinophil count (bEOS) (≥300/µL; <300/µL), were randomized (1:1) to benralizumab 30 mg or placebo. Endpoints included annual asthma exacerbation rate (AAER; primary endpoint), change from baseline at Week 48 in pre-bronchodilator (BD) forced expiratory volume in 1 second (pre-BD FEV1) and total asthma symptom score (TASS). Safety was evaluated ≤ Week 56. RESULTS: Of 695 patients randomized, 473 had baseline bEOS ≥300/µL (benralizumab n = 236; placebo n = 237). In this population, benralizumab significantly reduced AAER by 74% (rate ratio 0.26 [95% CI 0.19, 0.36], p < 0.0001) and significantly improved pre-BD FEV1 (least squares difference [LSD] 0.25 L [95% CI 0.17, 0.34], p < 0.0001) and TASS (LSD -0.25 [-0.45, -0.05], p = 0.0126) versus placebo. In patients with baseline bEOS <300/µL, there were numerical improvements in AAER, pre-BD FEV1, and TASS with benralizumab versus placebo. The frequency of adverse events was similar for benralizumab (76%) and placebo (80%) in the overall population. CONCLUSIONS: MIRACLE data reinforces the efficacy and safety of benralizumab for severe eosinophilic asthma in an Asian population, consistent with the global Phase 3 results.

Analysis of clinical characteristics of 43 patients with pulmonary mycosis diagnosed by pathology / 中华危重病急救医学

Objective:To observe the etiological distribution, clinical presentations and imaging features of pulmonary mycosis that is diagnosed by pathology.Methods:The etiological distribution, clinical presentations and imaging features of patients with pulmonary mycosis, who were collected in the Affiliated Hospital of Jining Medical University from January 2018 to July 2020, were retrospectively analyzed. The diagnosis of all the patients were confirmed by pathological examination, of lung or bronchi tissue that were obtained through operation, bronchoscope or percutaneous lung puncture biopsy.Results:There were 26 patients' (60.47%, 26/43) pathological specimens were obtained by operation, 14 cases (32.56%, 14/43) were obtained by bronchoscope, and 3 cases (6.98%, 3/43) were obtained by percutaneous lung puncture biopsy. Of the 43 patients who were diagnosed pulmonary mycosis by pathology, 27 patients (62.79%, 27/43) suffered from pulmonary aspergillosis, 11 patients (25.58%, 11/43) suffered from pulmonary cryptococcosis, 3 patients (6.98%, 3/43) suffered from pulmonary mucormycosis, and 2 patients (4.65%, 2/43) suffered from pulmonary candidiasis. There were 27 patients (62.79%, 27/43) with pulmonary fungal disease complicating risk factors of fungal infection, including diabetes mellitus (23.26%,10/43), malignant tumor (16.28%, 7/43), bronchiectasis (9.30%, 4/43), hepatitis B virus (HBV) carrier (6.98%, 3/43), taking glucocorticoids (4.65%, 2/43), pulmonary tuberculosis (4.65%, 2/43), and chemotherapy following colon carcinoma operation (2.33%, 1/43). The common clinical presentations included cough (55.81%, 24/43), expectoration (48.84%, 21/43), hemoptysis (37.21%, 16/43), fever (20.93%, 9/43), gasping (18.60%, 8/43), chest pain (16.28%, 7/43), and hoarseness (3.13%, 1/43). Imaging features of chest included lung nodes in 20 cases (46.51%, 20/43), vascular welt sign in 12 cases (27.91%, 12/43), exudative process in 10 cases (23.26%, 10/43), lung mass or consolidation in 8 cases (18.60%, 8/43), cavitary lesions in 7 cases (16.28%, 7/43), thicken bronchus wall and narrow lumina in 6 cases (13.95%, 6/43), air crescent in 5 cases (11.63%, 5/43).Conclusions:The pulmonary aspergillosis and cryptococcosis are mainly in pulmonary mycosis diagnosed by pathology. The common complications are diabetes mellitus and malignant tumor. The common clinical presentations are cough, expectoration, and hemoptysis. The main imaging features of chest are lung nodes and vascular welt sign can be found in most of pulmonary cryptococcosis.

Clinical characteristics of Streptococcus milleri infection: an analysis of 159 cases / 中华全科医师杂志

A total of 159 patients with Streptococcus milleri (S. milleri) infection were diagnosed in our hospital between January 2014 and January 2019. The demographic data, underlying diseases, infection sites, laboratory tests, and prognosis of patients were retrospectively analyzed; the clinical and microbiological data were compared among different age groups. Of the 159 patients there were 103 were males and 56 females; there were 19 patients aged<18 years [(8.1±5.3) years], 113 patients aged ≥18 and < 65 years [(45.5±13.1) years] and 27 patients aged ≥65 years[(74.7±8.6) years]. The incidence peaked in the 34-55 year age group (50 cases, 31.4%). Streptococcus anginosus was identified in 97 cases (61.0%), Streptococcus constellatus in 55 patients (34.6%) and Streptococcus intermedius in 7 cases (4.4%). The abdomen (44 cases, 27.7%) and the chest (19 cases, 11.9%) were the main involving sites. For patients younger than 18 years and those aged ≥18 and<65 years, suppurative appendicitis was the most common condition[12 cases(12/19) and 21 cases(18.6%), respectively]; while in patients aged ≥65 years, chest infection ranked the first (9 cases, 33.3%). All 159 patients were treated with anti-infection therapy alone or anti-infection and invasive procedures with a favorable prognosis, 2 patients died with a overall fatality rate of 1.3%.

Exogenous lipid pneumonia: a clinical analysis of 9 cases / 中华全科医师杂志

The clinical data of 9 patients with exogenous lipid pneumonia confirmed by pathology were retrospectively analyzed. There were 4 males and 5 females, aged 57-79 years, with a history of intestinal obstruction and oral administration of liquid paraffin. The main clinical symptoms were cough, expectoration and fever (8 cases), and combined with wheezing (5 case); and crackles and rhonchi were revealed on chest auscultation in all patients. The right lung lower lobe was involved in all 9 cases, the left lower lobe, right middle and lower lobe were also involved in 6 case. The CT scan showed that infiltration (7 case) and consolidation (6 case) were the most common imaging features, followed by the septal thickening (5 case) and pleural effusion (4 case); the low density fat-like changes within the consolidative opacities was a specific feature of lipid pneumonia (3 case). The lung biopsy was performed in the target site through bronchoscope, and pathology showed the interstitial fibrous tissue hyperplasia with chronic inflammatory cell infiltration and adipocyte-like cells. Six patients were treated with glucocorticoid and repeated bronchoalveolar lavage with good response, one cases died and two cases discharged automatically. The clinical manifestation and imaging features of exogenous lipid pneumonia are lack of specificity; transbronchial lung biopsy is an effective method for the diagnosis. The repeated bronchoalveolar lavage with saline combined with medication of glucocorticoids are effective for the treatment of exogenous lipid pneumonia.

Diagnostic value of the combinations of bronchoalveolar lavage fluid galactomannan test and serum galactomannan test in invasive pulmonary aspergillosis / 中华危重病急救医学

Objective To evaluate the accuracy and diagnostic value of bronchoalveolar lavage fluid galactomannan test (BALF-GM) combined with serum GM test on invasive pulmonary aspergillosis (IPA). Methods 190 cases of BALF-GM and 4 787 cases of serum GM specimens suspected of fungal infection in patients admitted to Affiliated Hospital of Jining Medical University from January 2016 to June 2018 were enrolled and analyzed. All patients were classified into clinically confirmed IPA, clinically diagnosed IPA, suspected IPA and excluded IPA according to the classification standard of Expert consensus on diagnosis and treatment of pulmonary mycosis. The coincidence rate of BALF and serum GM test results with clinical diagnosis was analyzed. Receiver operating characteristic (ROC) curve was performed, and the diagnostic value of BALF and serum GM test alone or in combination for IPA was evaluated. Subgroup analysis was performed in patients with normal or abnormal immune function, and the sensitivity and specificity of BALF and serum GM test were compared separately or jointly. Results The positive rate of BALF-GM was 46.8% (89/190), and 10.4% (497/4 787) on serum GM. Among them, 156 patients were both tested on BALF and serum GM. There were 44 cases with both positive in BALF and serum GM, the coincidence rate of clinical definite was 93.2% (41/44). There were 34 cases with positive BALF-GM and negative GM test in serum, and the coincidence rate of clinical definite was 64.7% (22/34). There were 56 cases positive in serum GM and negative in BALF-GM, and the coincidence rate of clinical definite was 48.2% (27/56). BALF and serum GM tests were both negative in 22 cases, and the coincidence rate of exclusion diagnosis was 90.9% (20/22). ROC curve analysis showed that the diagnostic value of BALF-GM test combined with serum GM test for IPA was better than that of BALF-GM test or serum GM test alone [area under ROC curve (AUC): 0.992 vs. 0.983, 0.976]. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 95.3%, 87.0%, 93.2% and 90.9%, respectively. Subgroup analysis showed that among 89 patients with positive BALF-GM test, 85 cases (95.5%) had normal immune function and 4 cases (4.5%) had unknown condition. Among 497 patients with positive serum GM test, 12 cases (2.4%) had normal immune function, 372 cases (74.9%) had abnormal immune function and 113 cases (22.7%) were uncertain. It was shown by ROC curve analysis that the sensitivity of positive BALF-GM test in diagnosis of IPA in patients with normal immune function was higher than that of positive serum GM test (95.6% vs. 88.9%), while the sensitivity of positive serum GM test in patients with abnormal immune function was higher than that of positive BALF-GM test (91.8% vs. 89.9%). Conclusion The results of BALF and serum GM tests are in good agreement with clinical diagnosis, and the combined detection of BALF and serum GM is more valuable for IPA diagnosis than single detection, especially for patients with unknown immune function.

Clinical characteristics of 72 patients with brucellosis / 中华地方病学杂志

Objective To analyze and review clinical characteristics of brucellosis and improve awareness of brucellosis and level of diagnosis.Methods Totally 72 in-patients treated for brucellosis from March 2012 to June 2015 in Affiliated Hospital of Jining Medical University were retrospectively analyzed for epidemiology,clinical feature,laboratory data,treatment and prognosis.Results A total of 72 cases were confirmed and included.Thirty seven patients (51.39％) had definitely contact history with raw meat or progeny and 3 (4.17％) with brucellosis patients.The common clinical presentations included persistent fever (100.00 ％,72/72),followed by headache (87.50％,63/72),chills (48.61％,35/72),muscle-joint pain (47.22％,34/72) and cough (43.06％,31/72).The laboratory test showed there were 14 patients (19.44％,14/72) with decreased leukopenia,49 patients (68.06％,49/72) with elevated C-reactive protein and 46 patients (63.89％,46/72) with elevated procalcitonin.Abnormal liver function showed elevated alanine aminotransferase (69.44％,50/72),aspartate aminotransferase (66.67％,48/72) and alkaline phosphatase (61.11％,44/72) with proportions.The mainly abnormal imaging features showed hepatomegaly,splenomegaly,lymphadenopathy,pulmonary infiltrating and nodules.Sixty-five patients (90.28％) had positive blood culture and 13 cases (18.06％) had positive marrow culture.Seventy-two patients were cured after active medical treatment and no recurrence after 1 year of follow-up.Conclusions Brucellosis is a invasive infectious disease with many systemic involvements,whose clinical symptoms are not typical.For those patients with long-term fever of unknown origin and poor effect anti-infection treatment,especially complicated with multi-system damage hepatomegaly,splenomegaly,lymphadenopathy,brucellosis should be suspected and be treated early.

Clinical analysis of endobronchial aspergilloma / 中国内镜杂志

Objective To discuss the clinical feature of endobronchial aspergilloma approach strategy for diagnosis and therapy. Methods 2 cases of endobronchial aspergilloma were diagnosed and literature review were made in this study. The clinical manifestation, bronchoscopic characters, imaging performances were retrospectively studied. Results The most common complaint was bloody sputum or mild hemoptysis, and chest CT usually revealed a soft tissue mass shadow with the increasing popularity of flexible bronchoscopy, it is being recognized as a necrotic mass causing bronchial obstruction, with or without a parenchymal lesion in cavity. Conclusions Bronchoscopy maybe is the key approach to detect endobronchial aspergilloma. It should be alert to lung cancer when antifungal therapy is not effective and the lesions have no reduction or even increasing.

Diagnostic significance of dendritic cells for chronic obstructive pulmonary dis-ease / 中国免疫学杂志

Objective:To detect the levels of dendritic cells(DCs)in peripheral blood of patients with acute exacerbations of chronic obstructive pulmonary disease(AECOPD)and explore the relationship between the content of DCs with AECOPD.Methods:The levels of DCs subsets( mDCs and pDCs) in peripheral blood with thirty-four cases of AECOPD and fifteen cases of healthy persons were measured by flow cytometry with four-color fluorescent analysis;and the pulmonary function tests in every subjects were evaluated by spirometry.Results:Compared with the control group,the levels of mDCs and pDCs inAE COPD groups with GOLDⅠ,GOLDⅡ, GOLDⅢand ClassⅣwere significantly higher( P<0.05) ,and with the severity of lung function in AECOPD patients,the levels were also increased( P<0.05).Conclusion:The levels of mDCs and pDCs inAE COPD patients were higher and significantly correlated with the severity of the disease,suggesting that DCs may be involved in the inflammation reaction process of COPD.