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He R, Feng J, Xun Q, Qin Q, Hu C. High-intensity training induces EIB in rats through neuron transdifferentiation of adrenal medulla chromaffin cells. Am J Physiol Lung Cell Mol Physiol 304: L602-L612, 2013. First published February 15, 2013 doi:10.1152/ajplung.00406.2012.-A high prevalence of exercise-induced bronchoconstriction (EIB) can be found in elite athletes, but the underlying mechanisms remain elusive. Airway responsiveness, NGF and epinephrine (EPI) levels, and chromaffin cell structure in high-(HiTr) and moderate-intensity training (MoTr) rats with or without ovalbumin (OVA) sensitization were measured in a total of 120 male Sprague-Dawley rats. The expression of NGF-associated genes in rat adrenal medulla was tested. Both HiTr and OVA intervention significantly increased airway resistance to aerosolized methacholine measured by whole body plethysmography. HiTr significantly increased inflammatory reaction in the lung with a major increase in peribronchial lymphocyte infiltration, whereas OVA significantly increased the infiltration of various inflammatory cells with an over 10-fold increase in eosinophil level in bronchoalveolar lavage. Both HiTr and OVA intervention upregulated circulating NGF level and peripherin level in adrenal medulla, but downregulated phenylethanolamine N-methyl transferase level in adrenal medulla and circulating EPI level. HiTr ϩ OVA and HiTr ϩ ExhEx (exhaustive exercise) interventions significantly enhanced most of the HiTr effects. The elevated NGF level was significantly associated with neuronal conversion of adrenal medulla chromaffin cells (AMCC). The levels of p-Erk1/2, JMJD3, and Mash1 were significantly increased, but the levels of p-p38 and p-JNK were significantly decreased in adrenal medulla in HiTr and OVA rats. Injection of NGF antiserum and moderate-intensity training reversed these changes observed in HiTr and/or OVA rats. Our study suggests that NGF may play a vital role in the pathogenesis of EIB by inducing neuron transdifferentiation of AMCC via MAPK pathways and subsequently decreasing circulating EPI. exercise; asthma; lung; inflammation; NGF; neuron conversion; adrenal medulla EXERCISE-INDUCED BRONCHOCONSTRICTION (EIB) is the increase in airway obstruction with symptoms of coughing, wheezing, or dyspnea as a result of exercise (23). EIB occurs in ϳ11% of the general population without asthma (13). Inhalation of cold air and sudden changes in humidity or temperature have been associated with EIB (20). High prevalence of EIB is usually observed among endurance athletes (7), implicating that intensity of exercise may be associated with EIB.Although thermal and osmotic consequences of water loss play prominent roles in the emergence of EIB (2), more studies are needed to elucidate the underlying mechanism. Circulating epinephrine (EPI), produced by adrenal medulla chromaffin cells (AMCC), is believed to bind the adrenergic receptors of airway smooth muscles to achieve adrenergic bronchodilation, and a loss of this function could directly influence the sev...

BackgroundTimely identification of causative pathogens is important for the diagnosis and treatment of pulmonary infections. Metagenomic next-generation sequencing (mNGS), a novel approach to pathogen detection, can directly sequence nucleic acids of specimens, providing a wide range of microbial profile. The purpose of this study was to evaluate the diagnostic performance of mNGS in the bronchoalveolar lavage fluid (BALF) of patients with suspected pulmonary infection.MethodsFrom April 2019 to September 2021, 502 patients with suspected pneumonia, who underwent both mNGS of BALF and conventional microbiological tests (CMTs), were classified into different groups based on comorbidities. The diagnostic performances of mNGS and CMTs were compared. Comprehensive clinical analysis was used as the reference standard.ResultsThe diagnostic accuracy and sensitivity of mNGS were 74.9% (95% confidence interval [CI], 71.7-78.7%) and 72.5% (95% CI, 68.2-76.8%) respectively, outperformed those of CMTs (36.9% diagnostic accuracy, 25.4% sensitivity). For most pathogens, the detection rate of mNGS was higher than that of CMTs. Polymicrobial infections most often occurred in immunocompromised patients (22.1%). Only 2.3% patients without underlying diseases developed polymicrobial infections. Additionally, the spectrums of pathogens also varied among the different groups. We found the positive predictive values (PPV) to be dependent upon both the pathogen of interest as well as the immunologic status of the patient (e.g., the PPV of Mycobacterium tuberculosis was 94.9% while the PPV of Pneumocystis jirovecii in immunocompetent individuals was 12.8%). This information can help physicians interpret mNGS results.ConclusionmNGS of BALF can greatly enhance the accuracy and detection rate of pathogens in patients with pulmonary infections. Moreover, the comorbidities and types of pathogens should be taken consideration when interpreting the results of mNGS.

Background: Timely identification of causative pathogens is always an important link for the diagnosis and treat for pulmonary infection. As a novel approach to detect the pathogens, metagenomic next-generation sequencing (mNGS) can directly sequence the nucleic acid of specimens, providing a wide range of microbial profiles. The purpose of this study is to evaluate the diagnostic performance of mNGS of bronchoalveolar lavage fluid (BALF) in patients suspected with pulmonary infection.Methods: From April 2019 to July 2021, 502 patients with suspected pneumonia undergoing both mNGS of BALF and conventional microbiological tests (CMTs) were classified into different groups based on the comorbidities. The diagnostic performance was compared between mNGS and CMTs. Clinical comprehensive analysis was regarded as reference standard. Result: The diagnostic accuracy and sensitivity of mNGS were 74.9% (95% confidence interval [CI], 71.7-78.7%) and 72.5% (95% CI, 68.2-76.8%) respectively, outperformed those of CMTs (36.2% for diagnostic accuracy, 25.4% for sensitivity). In most of the pathogens, the detection rate of mNGS was higher than CMTs. Polymicrobial infections most often occurred in immunocompromised group (22.1%), followed by other comorbidities group (22.1% vs 13.3%, p= 0.13) and bronchiectasis group (22.1% vs 9.7%, p= 0.018). Only 2.3% (95%CI, 0.3%-4.4%) patients developed polymicrobial infection in simple pulmonary infection group. Besides, the spectrums of pathogens also varied in different groups. Importantly, the positive predictive values (PPVs) of mNGS were observed discrepant in different pathogens: 94.9% (95%CI 89.1-100%) for Mycobacterium tuberculosis, 86.2% (95%CI,72.9-99.6%) for Chlamydia psittaci, 86.0% (95%CI, 76.0-96.0%) for Aspergillus, and 67.6% (95%CI, 51.1-84.2%) for Non-mycobacterium tuberculosis, 67.3% (95%,54.1-80.5%) for Pneumocystis jeroveci; as for bacteria, the PPVs also show differences in different types of bacteria. Conclusion: mNGS of BALF can highly enhance the accuracy and detection rate of pathogens in patients with pulmonary infection. Besides, the comorbidities and the types of pathogens should be taken into consideration when interpreting the report of mNGS.

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Asthma is a serious public health problem globally, and the major types of it include allergic asthma, non-allergic asthma, late-onset asthma, fixed airflow-related asthma and obesity-related asthma. In accordance with the data from the World Health Organization, about 235 million people are affected by asthma worldwide. 1 Asthma is a heterogeneous disorder caused by various factors, such as allergies and air pollution, and is closely associated with inflammation and airway constriction. 2,3 Currently, although many drugs were applied for asthma treatment, the outcome of asthma treatment still is unsatisfactory. 4 Glucocorticoid-induced transcript 1 gene (GLCCI1) was first described as a thymocyte-specific transcript; the polymorphism of it was proved to be involved in the response to inhaled corticosteroids in asthmatic patients. 5,6 Some previous evidence has indicated that the polymorphisms of GLCCI1 are associated with the airway

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Objective. To investigate the patients with stable chronic obstructive pulmonary disease (COPD) to understand the use of double bronchodilator therapy and influencing factors. Methods. The patients with stable COPD who used double bronchodilators were continuously enrolled in our hospital. The information of demographic characteristics, medical history, physical examination, drug use, and correct treatment methods after using inhaled drugs were collected by standardized questionnaire. Measurement data between groups were compared by using the independent sample t-test, and counting data between groups were compared by using the chi-square test. Results. A total of 102 patients were included in the analysis. The proportion of patients with stable COPD who correctly used dual bronchodilators was 59.8% (61 patients). In the GOLD classification, the correct use rate of C-level patients was 69.8%, which was significantly higher than the used correct rate of D-level patients (49.0%) ( P = 0.032 ). In the age group, the correct use rate of patients <65 years old was 72.1%, which was significantly higher than that of patients ≥65 years old (50.8%) ( P = 0.031 ). In addition, education level, duration of drug use, and drug type may also affect the correct use of drugs, but no significant statistical significance was found between the groups of these three factors ( P > 0.05 ). Conclusion. There is still a gap between the treatment of dual bronchodilators in patients with stable COPD and the guidelines, so the management of COPD should be strengthened. Besides, the correct use rate could be affected by the GOLD classification and age.