Impact of inhaled corticosteroid use on elderly chronic pulmonary disease patients with community acquired pneumonia

To the Editor:With an aging global population,the incidences of community-acquired pneumonia(CAP)and chronic obstructive pulmonary disease(COPD)have signicantly increased.[1]Previous studies have conrmed that COPD and asthma are independently associated with the prevalence of CAP.The use of inhaled corticosteroid(ICS),the cornerstone of treatment for asthma,COPD with frequent acute exacerbations,and asthma-COPD overlap(ACO)may induce changes in the local lung microbiome and abnormal lung immunity,ultimately,causing a signicantly increased risk of pneumonia.However,in cases of pneumonia,the effect of the use of ICS on CAP mortality remains controversial.While data from one study favored the prior use of ICS,which was associated with a signicantly lower short-term mortality rate,[2]other studies have identied no impact on mortality.To date,data on the impact of the use of ICS on mortality,prehospitalization or during hospitalization,are scarce,particularly in the older population.Therefore,this multicenter,retrospective study explored the association between the use of ICS during hospitalization and short-term mortality in older patients with CAP and those with chronic pulmonary disease(CPD).

Effect of Comprehensive Therapy based on Chinese Medicine Patterns on Self-Efficacy and Effectiveness Satisfaction in Chronic Obstructive Pulmonary Disease Patients

Objective: To evaluate the effect of comprehensive therapy based on Chinese medicine(CM) patterns on self-efficacy and satisfaction with its effectiveness in patients with chronic obstructive pulmonary disease(COPD). Methods: A total of 216 patients were randomly divided into the trial group(n=108) and the control group(n=108) based on the stratified and block randomization design. Patients in the trial group were treated with conventional Western medicine combined with Bufei Jianpi Granules(补肺健脾颗粒), Bufei Yishen Granules(补肺益肾颗粒), and Yiqi Zishen Granules(益气滋肾颗粒) according to the CM patterns respectively, and patients in the control group were treated with conventional Western medicine. The COPD Self-Efficacy Scale(CSES) and the Effectiveness Satisfaction Questionnaire for COPD(ESQ-COPD) were employed in a 6-month treatment and in further 6 month follow-up visit. Results: Among the 216 patients, 191 patients(97 in the trial group and 94 in the control group) fully completed the study. After 12-month treatment and follow-up, the mean scores of the trial group all continued to increase over time, which were significantly higher than those of the control group(P<0.05), and the improvement in the following trial group domain: negative affect domain(12.13%), intense emotional arousal domain(12.21%), physical exertion domain(11.72%), weather/environmental domain(13.77%), behavioral risk domain(7.67%) and total score(10.65%). The trial group also exhibited significantly higher mean scores in the ESQ-COPD(P<0.05) and the improvement in the following domain: capacity for life and work domain(30.59%), clinical symptoms domain(53.52%), effect of therapy domain(35.95%), convenience of therapy domain(35.54%), and whole effect domain(52.47%). Conclusions: Bufei Jianpi Granules, Bufei Yishen Granules and Yiqi Zishen Granules can improve the self-efficacy and satisfaction of COPD patients.

Drug-resistant genes carried by Acinetobacter baumanii isolated from patients with lower respiratory tract infection

Background Acinetobacter baumanii （A. baumanii ） remains an important microbial pathogen resulting in nosocomialacquired infections with significant morbidity and mortality. The mechanism by which nosocomial bacteria, like A. baumanii, attain multidrug resistance to antibiotics is of considerable interest. The aim in this study was to investigate the spread status of antibiotic resistance genes, such as multiple 13-1actamase genes and aminoglycoside-modifying enzyme genes, from A. baumanii strains isolated from patients with lower respiratory tract infections （LRTIs）. Methods Two thousand six hundred and ninety-eight sputum or the bronchoalveolar lavage samples from inpatients with LRTIs were collected in 21 hospitals in the mainland of China from November 2007 to February 2009. All samples were routinely inoculated. The isolated bacterial strains and their susceptibility were analyzed via VITEK-2 expert system. Several kinds of antibiotic resistant genes were further differentiated via polymerase chain reaction and sequencing methods. Results Totally, 39 A. baumanii strains were isolated from 2698 sputum or bronchoalveolar lavage samples. There was not only a high resistant rate of the isolated A. baumanfi strains to ampicillin and first- and second-generation cephalosporins （94.87%, 100% and 97.44%, respectively）, but also to the third-generation cephalosporins （ceftriaxone at 92.31%, ceftazidine at 51.28%） and imipenem （43.59%） as well. The lowest antibiotic resistance rate of 20.51% was found to amikacin. The OXA-23 gene was identified in 17 strains of A. baumanii, and the AmpC gene in 23 strains. The TEM-1 gene was carried in 15 strains. PER-1 and SHV-2 genes were detected in two different strains. Aminoglycoside-modifying enzyme gene aac-3-1a was found in 23 strains, and the aac-6＂lb gene in 19 strains, aac-3-1a and aac-6＂lb genes hibernated in three A. baumanfi strains that showed no drug-resistant phenotype. Conclusions A. baumanii can carry multiple drug-resistant genes at the same time and result in multi-drug resistance. Aminoglycoside-modifying enzyme genes could be hibernating in aminoglycoside sensitive strains without expressing their phenotype.

Eligibility of C-BIOPRED severe asthma cohort for type-2 biologic therapies

To the Editor:Patients with severe persistent asthma experience greater morbidity with more impairment in quality of life despite higher use of health care resources and being treated with existing asthma treatments such as inhaled corticosteroids and b-agonists,and sometimes oral corticosteroid(OCS)therapy.Type-2(T2)high asthma has been identified as a phenotype that responds to targeted T2 biologic therapies such as anti-IgE,anti-interleukin(IL)5,or anti-IL5Ra and anti-IL4Ra monoclonal antibodies,which are currently available in Europe and North America,and are currently introduced in the rest of the world.[1]

Overexpression of transcription factor EB regulates mitochondrial autophagy to protect lipopolysaccharide-induced acute lung injury

Background:Acute lung injury (ALI) is characterized by an acute inflammatory process, and oxidative stress in the lung tissue leads to a lack of effective therapeutics. This study aimed to identify whether the overexpression of transcription factor EB (TFEB) regulates mitophagy to protect against lipopolysaccharide (LPS)-induced ALI. Methods: We detected the expression of inflammatory factors, cytochrome c (Cyt.c) and nicotinamide adenine dinucleotide phosphate (NADPH), and autophagy-related proteins and observed the changes in lung histopathology induced by ALI in rats and the changes in the cell ultrastructure of primary alveolar type II epithelial cells induced by changing the expression of TFEB in the context of ALI. Results: The overexpression of TFEB could reduce the expression of proinflammatory factors, such as IL-1 and IL-6, and increase the expression of anti-inflammatory factors, such as IL-10, both in vitro and in vivo. In addition, the overexpression of TFEB could reduce the Cyt.c and NADPH levels both in vivo and in vitro. The overexpression of TFEB could upregulate the expression of autophagy-related proteins, such as lysosomal-associated membrane protein 1 (LAMP1), microtubule-associated protein light chain 3B (LC3B), and Beclin both in vivo and in vitro^ and promote mitochondrial autophagy. The overexpression of TFEB significantly improved the histopathologic changes induced by LPS-induced ALI in rats. However, low TFEB expression produced the opposite results. Conclusion: TFEB overexpression can decrease inflammation and mitochondrial damage in the lung tissue and alveolar epithelial cells through regulating mitochondrial autophagy to protect against LPS-induced ALI. Therefore, TFEB is likely a potential therapeutic target in LPS-induced ALI.

Clinical characteristics and outcomes of hypersensitivity pneumonitis: a population-based study in China

Backgrounds:Hypersensitivity pneumonitis (HP) is an immune-mediated interstitial lung disease (ILD) that develops in response to the inhalation of various antigens. The clinical pathologies are very complex and undetermined. The clinical features and outcomes of HP have not been fully elucidated. The aim of this study was to analyze the incidence, clinical features, and outcomes of HP patients and construct a simple clinical model for diagnosing chronic HP (CHP). Methods: The cohort study included 101 patients with HP admitted to the Nanjing Drum Tower Hospital from January 2009 to December 2017. The patients were categorized into acute HP (AHP, n = 72) and CHP (n = 29) groups according to the updated international criteria. The clinical, imaging, treatment, and follow-up data were retrospectively reviewed. All patients were followed up until December 31,2017. Statistical analysis was performed, and a clinical scoring system for CHP was constructed by SPSS 20.0 software. Results: The incidence of HP was 2.4% in ILD inpatients in our center. Patients in the CHP group were older =-2.212, P = 0.029), had more smokers (x^2 = 8.428, P = 0.004), and longer duration of symptoms (t =-4.852, P < 0.001) than those in the AHP group. Weight loss, crackles, digital clubbing, and cyanosis were more common in the CHP group than those in the AHP group (x^2 = 5.862, P < 0.001;x^2 = 8.997, P = 0.003;x^2 = 11-939, P = 0.001;and x^2 = 4.025, P = 0.045, respectively). On chest high-resolution computed tomography (HRCT), reticular patterns, traction bronchiectasis, and accompanying honeycombing were more common in CHP cases than those in AHP cases (x^2 = 101.000, P < 0.001;x^2 = 32.048, P < 0.001;a n d /2 = 36.568,P < 0.001, respectively). The clinical scoring system for CHP was established based on the clinical variables (age [A], duration of symptoms [D], smoking history [S], unidentified exposure [U], and chest HRCT [C];ADSUC)(area under the curve 0.935, 95% confidence interval: 0.883-0.987, P < 0.001). Eleven patients (15.3%) in the AHP group developed CHP, and unidentified exposure was an independent risk factor for the progression of disease (P = 0.038). The survival of patients with CHP, smoking history, unidentified antigens and fibrosis on Chest HRCT were significantly worse (P = 0.011, P = 0.001, F = 0.005, and P = 0.011, respectively) by Kaplan-Meier analysis. Cox multivariate regression analysis revealed that unidentified exposure and total lung volume (TLC pred%) were independent prognostic predictors for HP patients (P = 0.017 and P = 0.017, respectively). Conclusions: The clinical features and outcomes of the CHP patients differ from those of the AHP patients. ADSUC is a simple and feasible clinical model for CHP. Unidentified exposure is an independent risk factor for the progression of AHP to CHP. Unidentified exposure and a low baseline TLC pred% are independent predictors for survival in HP patients.

Performance of the bronchoalveolar lavage fluid later-flow device test in the rapid diagnosis of non-neutropenic invasive pulmonary aspergillosis

To the Editor:A multicenter retrospective survey in China shows that the most common pulmonary fungal disease is pulmonary aspergillosis.[1]The diagnosis of invasive pulmonary aspergillosis(IPA)remains challenging because of the high false-negative and false-positive rate of galactomannan(GM)test.Domestic research reports that the IPA misdiagnosis rate can be as high as 73%.Besides,GM is time consuming,making the diagnosis delayed.

Cerebral infarction after drug-eluting bead bronchial arterial chemoembolization due to the mechanical force-mediated opening of an errant passage

To the Editor:Drug-eluting bead bronchial arterial chemoembolization(DEB-BACE)has been proven to be a feasible and well-tolerated treatment option for patients with non-small cell lung cancer(NSCLC)who are ineligible for or refuse to receive standard chemotherapy.[1]Here,we report a rare complication of multiple cerebral embolic infarcts,mainly in the posterior cerebral circulation,in a patient with squamous cell lung cancer who was performed with DEB-BACE.To our knowledge,this complication has rarely been reported in patients with NSCLC undergoing DEB-BACE.Approval was obtained from our Institutional Review Board and patient for the publication of this case report.

Sintilimab versus docetaxel as second-line treatment in advanced or metastatic squamous non-small-cell lung cancer:an open-label,randomized controlled phase 3 trial(ORIENT-3)

Background:Treatment options for Chinese patients with locally advanced or metastatic squamous-cell non-small-cell lung cancer(sqNSCLC)after failure of first-line chemotherapy are limited.This study(ORIENT-3)aimed to evaluate the efficacy and safety of sintilimab versus docetaxel as second-line treatment in patients with locally advanced or metastatic sqNSCLC.Methods:ORIENT-3 was an open-label,multicenter,randomized controlled phase 3 trial that recruited patients with stage IIIB/IIIC/IV sqNSCLC after failure with first-line platinum-based chemotherapy.Patients were randomized in a 1:1 ratio to receive either 200 mg of sintilimab or 75 mg/m^(2) of docetaxel intravenously every 3 weeks,stratified by the Eastern Cooperative Oncology Group performance status.The primary endpoint was overall survival(OS)in the full analysis set(FAS).Secondary endpoints included progression-free survival(PFS),objective response rate(ORR),disease control rate(DCR),duration of response(DoR)and safety.Results:Between August 25,2017,and November 7,2018,290 patients were randomized.For FAS,10 patients fromthe docetaxel armwere excluded.Themedian OS was 11.79(n=145;95%confidence interval[CI],10.28-15.57)months with sintilimab versus 8.25(n=135;95%CI,6.47-9.82)months with docetaxel(hazard ratio[HR]:0.74;95%CI,0.56-0.96;P=0.025).Sintilimab treatment significantly prolonged PFS(median 4.30 vs.2.79 months;HR:0.52;95%CI,0.39-0.68;P<0.001)and showed higher ORR(25.50%vs.2.20%,P<0.001)and DCR(65.50%vs.37.80%,P<0.001)than the docetaxel arm.The median DoRwas 12.45(95%CI,4.86-25.33)months in the sintilimab arm and 4.14(95%CI,1.41-7.23)months in the docetaxel arm(P=0.045).Treatment-related adverse events of grade≥3were reported in 26(18.1%)patients in the sintilimab arm and 47(36.2%)patients in the docetaxel arm.Exploratory biomarker analysis showed potential predictive values of expression levels of two transcription factors,including OVOL2(HR:0.35;P<0.001)and CTCF(HR:3.50;P<0.001),for sintilimab treatment.Conclusions:Compared with docetaxel,sintilimab significantly improved the OS,PFS,and ORR of Chinese patients with previously treated locally advanced or metastatic sqNSCLC.