ABSTRACT
Systematic characterizations of adipose regulatory T (Treg) cell subsets and their phenotypes remain uncommon. Using single-cell ATAC-sequencing and paired single-cell RNA and T cell receptor (TCR) sequencing to map mouse adipose Treg cells, we identified CD73hiST2lo and CD73loST2hi subsets with distinct clonal expansion patterns. Analysis of TCR-sharing data implied a state transition between CD73hiST2lo and CD73loST2hi subsets. Mechanistically, we revealed that insulin signaling occurs through a HIF-1α-Med23-PPAR-γ axis to drive the transition of CD73hiST2lo into a CD73loST2hi adipose Treg cell subset. Treg cells deficient in insulin receptor, HIF-1α or Med23 have decreased PPAR-γ expression that in turn promotes accumulation of CD73hiST2lo adipose Treg cells and physiological adenosine production to activate beige fat biogenesis. We therefore unveiled a developmental trajectory of adipose Treg cells and its dependence on insulin signaling. Our findings have implications for understanding the dynamics of adipose Treg cell subsets in aged and obese contexts.
Subject(s)
Adipose Tissue/immunology , Insulin Resistance/immunology , Insulin/metabolism , Receptor, Insulin/metabolism , T-Lymphocytes, Regulatory/immunology , 5'-Nucleotidase/genetics , 5'-Nucleotidase/metabolism , Adipose Tissue/cytology , Aging/immunology , Animals , Cells, Cultured , High-Throughput Nucleotide Sequencing , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Interleukin-1 Receptor-Like 1 Protein/genetics , Interleukin-1 Receptor-Like 1 Protein/metabolism , Male , Mediator Complex/metabolism , Mice , Mice, Inbred C57BL , Obesity/genetics , Obesity/immunology , PPAR gamma/metabolism , Receptors, Antigen, T-Cell/genetics , Signal Transduction/genetics , Signal Transduction/immunology , T-Lymphocytes, Regulatory/cytologyABSTRACT
BACKGROUND: Cough-variant asthma (CVA) may respond differently to antiasthmatic treatment. There are limited data on the heterogeneity of CVA. OBJECTIVE: We aimed to classify patients with CVA using cluster analysis based on clinicophysiologic parameters and to unveil the underlying molecular pathways of these phenotypes with transcriptomic data of sputum cells. METHODS: We applied k-mean clustering to 342 newly physician-diagnosed patients with CVA from a prospective multicenter observational cohort using 10 prespecified baseline clinical and pathophysiologic variables. The clusters were compared according to clinical features, treatment response, and sputum transcriptomic data. RESULTS: Three stable CVA clusters were identified. Cluster 1 (n = 176) was characterized by female predominance, late onset, normal lung function, and a low proportion of complete resolution of cough (60.8%) after antiasthmatic treatment. Patients in cluster 2 (n = 105) presented with young, nocturnal cough, atopy, high type 2 inflammation, and a high proportion of complete resolution of cough (73.3%) with a highly upregulated coexpression gene network that related to type 2 immunity. Patients in cluster 3 (n = 61) had high body mass index, long disease duration, family history of asthma, low lung function, and low proportion of complete resolution of cough (54.1%). TH17 immunity and type 2 immunity coexpression gene networks were both upregulated in clusters 1 and 3. CONCLUSION: Three clusters of CVA were identified with different clinical, pathophysiologic, and transcriptomic features and responses to antiasthmatics treatment, which may improve our understanding of pathogenesis and help clinicians develop individualized cough treatment in asthma.
Subject(s)
Anti-Asthmatic Agents , Asthma , Female , Male , Humans , Cough , Prospective Studies , Phenotype , Anti-Asthmatic Agents/therapeutic useABSTRACT
BACKGROUNDS: The respiratory microbiota and radiomics correlate with the disease severity and prognosis of chronic obstructive pulmonary disease (COPD). We aim to characterize the respiratory microbiota and radiomics features of COPD patients and explore the relationship between them. METHODS: Sputa from stable COPD patients were collected for bacterial 16 S rRNA gene sequencing and fungal Internal Transcribed Spacer (ITS) sequencing. Chest computed tomography (CT) and 3D-CT analysis were conducted for radiomics information, including the percentages of low attenuation area below - 950 Hounsfield Units (LAA%), wall thickness (WT), and intraluminal area (Ai). WT and Ai were adjusted by body surface area (BSA) to WT/[Formula: see text] and Ai/BSA, respectively. Some key pulmonary function indicators were collected, which included forced expiratory volume in one second (FEV1), forced vital capacity (FVC), diffusion lung carbon monoxide (DLco). Differences and correlations of microbiomics with radiomics and clinical indicators between different patient subgroups were assessed. RESULTS: Two bacterial clusters dominated by Streptococcus and Rothia were identified. Chao and Shannon indices were higher in the Streptococcus cluster than that in the Rothia cluster. Principal Co-ordinates Analysis (PCoA) indicated significant differences between their community structures. Higher relative abundance of Actinobacteria was detected in the Rothia cluster. Some genera were more common in the Streptococcus cluster, mainly including Leptotrichia, Oribacterium, Peptostreptococcus. Peptostreptococcus was positively correlated with DLco per unit of alveolar volume as a percentage of predicted value (DLco/VA%pred). The patients with past-year exacerbations were more in the Streptococcus cluster. Fungal analysis revealed two clusters dominated by Aspergillus and Candida. Chao and Shannon indices of the Aspergillus cluster were higher than that in the Candida cluster. PCoA showed distinct community compositions between the two clusters. Greater abundance of Cladosporium and Penicillium was found in the Aspergillus cluster. The patients of the Candida cluster had upper FEV1 and FEV1/FVC levels. In radiomics, the patients of the Rothia cluster had higher LAA% and WT/[Formula: see text] than those of the Streptococcus cluster. Haemophilus, Neisseria and Cutaneotrichosporon positively correlated with Ai/BSA, but Cladosporium negatively correlated with Ai/BSA. CONCLUSIONS: Among respiratory microbiota in stable COPD patients, Streptococcus dominance was associated with an increased risk of exacerbation, and Rothia dominance was relevant to worse emphysema and airway lesions. Peptostreptococcus, Haemophilus, Neisseria and Cutaneotrichosporon probably affected COPD progression and potentially could be disease prediction biomarkers.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Pulmonary Emphysema , Humans , Pulmonary Disease, Chronic Obstructive/diagnostic imaging , Lung , Forced Expiratory Volume , Vital CapacityABSTRACT
Alternatively activated macrophages (M2 polarization) play an important role in asthma. Short-chain fatty acids (SCFAs) possessed immune-regulatory functions, but their effects on M2 polarization of alveolar macrophages and its underlying mechanisms are still unclear. In our study, murine alveolar macrophage MH-S cell line and human monocyte-derived macrophages were used to polarize to M2 subset with interleukin-4 (IL-4) treatment. The underlying mechanisms involved were investigated using molecule inhibitors/agonists. In vivo, female C57BL/6 mice were divided into five groups: CON group, ovalbumin (OVA) asthma group, OVA+Acetate group, OVA+Butyrate group, and OVA+Propionate group. Mice were fed with or without SCFAs (Acetate, Butyrate, Propionate) in drinking water for 20 days before developing OVA-induced asthma model. In MH-S, SCFAs inhibited IL-4-incuced protein or mRNA expressions of M2-associated genes in a dose-dependent manner. G-protein-coupled receptor 43 (GPR43) agonist 4-CMTB and histone deacetylase (HDAC) inhibitor (trichostatin A, TSA), but not GPR41 agonist AR420626 could inhibit the protein or mRNA expressions M2-associated genes. 4-CMTB, but not TSA, had no synergistic role in the inhibitory effect of SCFAs on M2 polarization. In vivo study indicated Butyrate and Propionate, but not Acetate, attenuated OVA-induced M2 polarization in the lung and airway inflammation. We also found the inhibitory effect of SCFAs on M2 polarization in human-derived macrophages. Therefore, SCFAs inhibited M2 polarization in MH-S likely through GPR43 activation and/or HDAC inhibition. Butyrate and Propionate but not Acetate could inhibit M2 polarization and airway inflammation in asthma model. SCFAs also abrogated M2 polarization in human-derived macrophages.
Subject(s)
Fatty Acids, Volatile , Macrophage Activation , Animals , Butyrates/pharmacology , Fatty Acids, Volatile/metabolism , Fatty Acids, Volatile/pharmacology , Female , Macrophages/metabolism , Mice , Mice, Inbred C57BLABSTRACT
The combination of new noble metal nanomaterials and surface enhanced Raman scattering (SERS) technology has become a new strategy to solve the problem of low sensitivity in the detection of traditional Chinese medicine. In this work, taking natural cicada wing (C.w.) as a template, by optimizing the magnetron sputtering experimental parameters for the growth of Ag nanoparticles (NPs) on vanadium-titanium (V-Ti) nanorods, the nanogaps between the nanorods were effectively regulated and the Raman signal intensity of the Ag15/V-Ti20/C.w. substrate was improved. The proposed homogeneous nanostructure exhibited high SERS activity through the synergistic effect of the electromagnetic enhancement mechanism at the nanogaps between the Ag NPs modified V-Ti nanorods. The analytical enhancement factor (AEF) value was as high as 1.819 × 108, and the limit of detection (LOD) was 1 × 10-11 M for R6G. The large-scale distribution of regular electromagnetic enhancement "hot spots" ensured the good reproducibility with the relative standard deviation (RSD) value less than 7.31%. More importantly, the active compound of Artemisinin corresponded the pharmacological effect of Artemisia annua was screened out by SERS technology, and achieved a LOD of 0.01â mg/l. This reliable preparation technology was practically applicable to produce SERS-active substrates in detection of pharmacodynamic substance in traditional Chinese medicine.
Subject(s)
Artemisinins , Metal Nanoparticles , Nanotubes , Animals , Spectrum Analysis, Raman , Titanium/chemistry , Metal Nanoparticles/chemistry , Silver/chemistry , Vanadium , Reproducibility of Results , Nanotubes/chemistryABSTRACT
Sirtuins are nicotinamide adenine dinucleotide (NAD+)-dependent lysine deacylases and deacetylases that participate in a variety of cellular processes, including transcriptional activity, energy metabolism, DNA damage response, inflammation, apoptosis, autophagy, and oxidative stress. As a result, sirtuins are linked to multiple pathophysiological processes, such as cardiovascular diseases, metabolic diseases, autoimmune diseases, infectious diseases, and respiratory diseases. Asthma is the most common respiratory disease, which is characterized by airway inflammation and airway remodeling. Accumulating evidence has indicated that sirtuins are involved in the pathogenesis of asthma. Furthermore, some studies have suggested that sirtuin modulators are potential agents for the treatment of asthma via alteration of the expression or activity of sirtuins. In this review, we illustrate the role of sirtuins in asthma, discuss related molecular mechanisms, and evaluate the sirtuins-targeted therapy for asthma.
Subject(s)
Asthma , Sirtuins , Asthma/drug therapy , Humans , Inflammation , Lysine , NAD/metabolism , Sirtuins/genetics , Sirtuins/metabolismABSTRACT
BACKGROUND: Asthma is a heterogeneous disease with variable symptoms, which presents with cough either as the sole or predominant symptom with or without wheezing. We compared the clinical and pathophysiological characteristics of cough predominant asthma (CPA), cough variant asthma (CVA) and classic asthma (CA) in order to determine any differential phenotypic traits. METHODS: In 20 clinics across China, a total of 2088 patients were finally recruited, including 327 CVA, 1041 CPA and 720 CA patients. We recorded cough and wheezing visual analogue scale, Leicester cough questionnaire (LCQ) and asthma control test scores. Fractional exhaled nitric oxide (FeNO), induced sputum cell counts, and capsaicin cough challenge were also measured and compared. RESULTS: CPA patients more frequently presented with cough as the initial symptom, and laryngeal symptoms (p < 0.001), had less symptoms related with rhinitis/sinusitis and gastroesophageal reflux (p < 0.05) than CA patients. Comorbidities including rhinitis and gastroesophageal reflux were similar, while the proportion of COPD and bronchiectasis was higher in CA patients. There were no differences in FeNO levels, sputum eosinophil and neutrophil counts, FEV1 (%pred) decreased from CVA to CPA to CA patients (p < 0.001). Cough sensitivity was higher in CVA and CPA compared to CA (p < 0.001), and was positively correlated with LCQ scores. CONCLUSIONS: CVA, CPA and CA can be distinguished by the presence of laryngeal symptoms, cough sensitivity and airflow obstruction. Asthma-associated chronic cough was not associated with airway inflammation or comorbidities in our cohort. Trial registration The Chinese Clinical Trial Registration Center, ChiCTR-POC-17011646, 13 June 2017.
Subject(s)
Asthma , Gastroesophageal Reflux , Rhinitis , Asthma/complications , Asthma/diagnosis , Asthma/epidemiology , Cough/diagnosis , Cough/epidemiology , Humans , Nitric Oxide , Phenotype , Prospective Studies , Respiratory Sounds , Rhinitis/complications , Surveys and QuestionnairesABSTRACT
BACKGROUND: Organisms have orchestrated coagulation and immune systems. Although a link between inflammation and haemostasis has been reported in asthma, the interaction mechanism has not been completely elucidated. Here, we investigated the direct link between the mammalian immune and coagulation systems. METHODS: Mice were administered protease or antigens intranasally to induce airway inflammation with or without thrombin inhibitors treatment. The effects of thrombin and its inhibitors on interleukin (IL)-33 were investigated both in vivo and in vitro. Peripheral blood mononuclear cells (PBMCs) and plasma from asthma patients are collected to verify the correlation between thrombin and group 2 innate lymphocytes (ILC2s). RESULTS: Low-molecular-weight heparin (LMWH, an indirect inhibitor of thrombin) restrained both papain- and fungus-induced type 2 immune responses in mice by inhibiting IL-33 cleavage. Upon examining the potential thrombin protease consensus sites, we found that IL-33 was directly cleaved by thrombin at specific amino acids (R48 and R106) to generate a mature form of IL-33 with potent biological activity. In addition, we found that bivalirudin TFA (a direct inhibitor of thrombin) inhibited a variety of type 2 inflammatory responses, such as those in house dust mite (HDM)- and ovalbumin (OVA)-mediated pulmonary inflammation models. We found that plasma thrombin-antithrombin complex (TATc) levels in asthma patients were positively associated with the number and function of IL-33-responder group 2 innate lymphocytes (ILC2s) among peripheral blood mononuclear cells (PBMCs) from asthma patients. CONCLUSION: The data suggested that thrombin inhibitors administration could be effective in treating lung inflammation by regulating ILC2s via IL-33 maturation, indicating that targeting thrombin is a potential way to treat allergic diseases.
Subject(s)
Alveolitis, Extrinsic Allergic , Asthma , Pulmonary Eosinophilia , Animals , Cytokines/metabolism , Heparin, Low-Molecular-Weight/metabolism , Heparin, Low-Molecular-Weight/pharmacology , Immunity, Innate , Inflammation/metabolism , Interleukin-33/metabolism , Leukocytes, Mononuclear/metabolism , Lung , Lymphocytes , Mice , Thrombin/metabolism , Thrombin/pharmacologyABSTRACT
The transcription factor forkhead box P3 (FOXP3) is essential for the development of regulatory T cells (Tregs) and their function in immune homeostasis. Previous studies have shown that in natural Tregs (nTregs), FOXP3 can be regulated by polyubiquitination and deubiquitination. However, the molecular players active in this pathway, especially those modulating FOXP3 by deubiquitination in the distinct induced Treg (iTreg) lineage, remain unclear. Here, we identify the ubiquitin-specific peptidase 44 (USP44) as a novel deubiquitinase for FOXP3. USP44 interacts with and stabilizes FOXP3 by removing K48-linked ubiquitin modifications. Notably, TGF-ß induces USP44 expression during iTreg differentiation. USP44 co-operates with USP7 to stabilize and deubiquitinate FOXP3. Tregs genetically lacking USP44 are less effective than their wild-type counterparts, both in vitro and in multiple in vivo models of inflammatory disease and cancer. These findings suggest that USP44 plays an important role in the post-translational regulation of Treg function and is thus a potential therapeutic target for tolerance-breaking anti-cancer immunotherapy.
Subject(s)
Forkhead Transcription Factors , T-Lymphocytes, Regulatory , Forkhead Transcription Factors/genetics , Humans , Inflammation/genetics , Transforming Growth Factor beta , Ubiquitin Thiolesterase , Ubiquitin-Specific Peptidase 7ABSTRACT
BACKGROUND: Inhaled corticosteroids (ICSs) have been widely used in chronic airway diseases, such as asthma, chronic obstructive pulmonary disease (COPD), and bronchiectasis. However, whether ICS use causes mycobacterial infection is uncertain. Some conclusions of published studies were inconsistent. OBJECTIVE: We aimed to investigate the association between the use of ICSs and mycobacterial infections in patients with chronic airway diseases. METHODS: This review was registered on PROSPERO (CRD42021284607). We focused on examining the association between ICS use and mycobacterial infection (nontuberculous mycobacterial [NTM] infection as well as tuberculosis [TB]). We searched PubMed (MEDLINE), Sciencenet, Cochrane, and EMBASE databases for studies up to 2021 to retrieve articles. The enrollment conditions included gender, enrollment diagnosis and ICS use in chronic airway disease patients, and so on. Preclinical studies, review articles, editorials, reviews, conference abstracts, and book chapters were excluded. Methodologically, the study was assessed using the Newcastle Ottawa Scale, and Rev-man5 was used for statistical analysis. RESULTS: Ten studies (including 4 NTM and 6 TB articles) with 517,556 patients met the inclusion criteria and were included in this meta-analysis. From the NTM pooled analyses, ICS use was associated with increased odds of NTM infection in patients with chronic airway diseases (odds ratio [OR] = 3.93, 95% confidence interval [CI] 2.12-7.27), subgroup analysis showed that high-dose ICS use (OR = 2.27, 95% CI 2.08-2.48) and fluticasone use (OR = 2.42, 95% CI 2.23-2.63) were associated with increased odds of NTM infection risk in patients with chronic respiratory diseases. The TB pooled analyses showed a significant association between ICS use and risk of TB infection in patients with chronic respiratory diseases (OR = 2.01, 95% CI 1.23-3.29). Subgroup analysis showed that in chronic respiratory diseases, ICS use increased odds of TB infection in high-dose ICS use (OR = 1.70, 95% CI 1.56-1.86) and in COPD patients (OR = 1.45, 95% CI 1.29-1.63). CONCLUSION: Our meta-analysis indicated that ICS use may increase the odds of mycobacterial infection in chronic respiratory disease patients, and this conclusion is more applicable to patients with high dose of ICS or fluticasone in NTM infection subgroups. In addition, high-dose ICS use may have higher risk of TB infection in patients with chronic respiratory diseases, especially COPD. Therefore, we should be vigilant about the application of ICS use in chronic respiratory diseases to avoid infection.
Subject(s)
Asthma , Mycobacterium Infections, Nontuberculous , Pulmonary Disease, Chronic Obstructive , Tuberculosis , Administration, Inhalation , Adrenal Cortex Hormones/adverse effects , Asthma/drug therapy , Fluticasone/adverse effects , Humans , Mycobacterium Infections, Nontuberculous/drug therapy , Mycobacterium Infections, Nontuberculous/epidemiology , Pulmonary Disease, Chronic Obstructive/complications , Pulmonary Disease, Chronic Obstructive/drug therapy , Tuberculosis/drug therapyABSTRACT
BACKGROUND: Exosomes have emerged as a vital player in cell-cell communication; however, whether airway epithelial cell (AEC)-generated exosomes participate in asthma development remains unknown. OBJECTIVE: Our aims were to characterize the AEC-secreted exosomes and the potentially functional protein(s) that may contribute to the proinflammatory effects of AEC exosomes in the dendritic cell (DC)-dominant airway allergic models and to confirm their clinical significance in patients with asthma. METHODS: Mice were treated with exosomes derived from house dust mite (HDM)-stimulated AECs (HDM-AEC-EXOs) or monocyte-derived DCs primed by HDM and/or contactin-1 (CNTN1). The numbers of DCs in the lung were determined by flow cytometry. Proteomic analysis of purified HDM-AEC-EXOs was performed. CNTN1 small interfering RNA was designed to probe its role in airway allergy, and γ-secretase inhibitor was used to determine involvement of the Notch pathway. RESULTS: HDM-AEC-EXOs facilitate the recruitment, proliferation, migration, and activation of monocyte-derived DCs in cell culture and in mice. CNTN1 in exosomes is a critical player in asthma pathology. RNA interference-mediated silencing and pharmaceutical inhibitors characterize Notch2 receptor as necessary for relaying the CNTN1 signal to activate TH2 cell/TH17 cell immune response. Studies of patients with asthma also support existence of the CNTN1-Notch2 axis that has been observed in cell and mouse models. CONCLUSION: This study's findings reveal a novel role for CNTN1 in asthma pathogenesis mediated through exosome secretion, indicating a potential strategy for the treatment of allergic airway inflammation.
Subject(s)
Asthma/immunology , Contactin 1/metabolism , Dendritic Cells/immunology , Exosomes/metabolism , Hypersensitivity/immunology , Respiratory Mucosa/metabolism , Th2 Cells/immunology , Animals , Antigens, Dermatophagoides/immunology , Cell Movement , Cell Proliferation , Cells, Cultured , Contactin 1/genetics , Humans , Mice , Mice, Inbred C57BL , Monocytes/cytology , RNA, Small Interfering/genetics , Receptor, Notch2/genetics , Receptor, Notch2/metabolismABSTRACT
TiO2 films exhibiting structural colors were successfully prepared using one-step electrochemical oxidation. Results of theoretical analyses and digital simulations revealed that the structural color of a TiO2 thin film could be regulated by adjusting oxidation voltage and oxidation time with different oxidation voltages leading to changes in structural color annulus number. At a low oxidation voltage, each thin film exhibited a single structural color, while thin films with different structural colors were obtained by varying the oxidation time. By contrast, at a higher oxidation voltage, each film exhibited iridescent and circular structural color patterns associated with symmetrical decreases in surface oxidation current density along radial lines emanating from the film center to its outer edges. TiO2 films exhibiting iridescent structural colorations have broad application prospects in industrial fields related to photocatalysis and photovoltaic cells.
Subject(s)
Titanium , Color , Oxidation-Reduction , Titanium/chemistryABSTRACT
BACKGROUND: This study was to describe the clinical characteristics, chest CT image findings, and potential role of T cells immunity in adenovirus positive pneumonia. METHODS: In this retrospective study, medical records of 53 adult Adv+ patients who were admitted to the Ruijin Hospital, Shanghai Jiao Tong University School of Medicine, from May 2015 to August 2019 were included. The presence of adenovirus and other respiratory viruses was detected using polymerase chain reaction of throat swabs samples. Clinical features and chest computed tomography (CT) findings were compared between patients with Adv+ pneumonia and Adv+ non-pneumonia. RESULTS: The top 3 most commonly occurring symptoms in Adv+ pneumonia patients were fever (66.7%), cough (63.3%), and tachypnea (16.7%). Patients with Adv+ pneumonia showed significantly higher rates of cough and fever and longer duration of hospitalization than patients with Adv+ non-pneumonia. In the Adv+ pneumonia group, consolidation (73.3%) was the most common imaging finding on chest CT scan, and the likelihood of involvement of bilateral lobes (60%) was high. Classical conspicuous consolidation with surrounding ground-glass opacity was observed in 5 (16.6%) patients with Adv+ pneumonia. Patients with Adv+ pneumonia showed a higher inhibition of T-cell immunity than did patients with Adv+ non-pneumonia, and counts of CD3+, CD4+, and CD8+ T-cells may predict the presence of pneumonia in Adv+ patients. DISCUSSION: With regard to Adv+ pneumonia, the most frequent symptoms were cough and fever, and the most common CT pattern was consolidation; classical CT findings such as consolidation with surrounding ground-glass opacity could also be observed. Furthermore, our data indicated the incidence of abrogated cellular immunity in patients with Adv+ pneumonia.
Subject(s)
Pneumonia, Viral , Adenoviridae , Adult , China/epidemiology , Cough/etiology , Fever/etiology , Humans , Lung/diagnostic imaging , Pneumonia, Viral/diagnostic imaging , Pneumonia, Viral/epidemiology , Retrospective StudiesABSTRACT
OBJECTIVE: Asthma and bronchiectasis are known to be two distinct diseases with different etiology, pathophysiology, management, and prognosis. However, a high prevalence of bronchiectasis has been reported in patients with severe asthma. Thus, it is of great importance to identify the impact of bronchiectasis on asthmatic patients. DATA SOURCES: Databases including PubMed, Embase, Cochrane, Web of Science were searched comprehensively to identify relevant human clinical studies published until February 2020. STUDY SELECTIONS: Two investigators (Gelei Lan and Guochao Shi) independently obtained the potentially eligible articles based on their titles and abstracts. When opinions differed between the investigators, discussions were made to reach an agreement. The authors of the included studies were contacted for inquiry when necessary. RESULTS: Six observational studies with 1004 patients were included in the meta-analysis. The mean prevalence of bronchiectasis in patients with asthma was 35.2% (ranging from 2.2% to 47%). Asthmatic patients with bronchiectasis were older, had a longer disease duration, exhibited greater severity, and showed more frequent exacerbations and hospitalization, and poorer lung function, compared with the patients without bronchiectasis. CONCLUSION: Despite of the heterogeneity between included studies and detectable publication bias, this meta-analysis demonstrated the impact of comorbid bronchiectasis on asthmatic patients. Thus, coexistence of bronchiectasis should be considered a clinical phenotype of asthma, which may have associations with exacerbation and hospitalization.
Subject(s)
Asthma/epidemiology , Asthma/physiopathology , Bronchiectasis/epidemiology , Age Factors , Hospitalization/statistics & numerical data , Humans , Observational Studies as Topic , Respiratory Function Tests , Severity of Illness Index , Time FactorsABSTRACT
To achieve a multidimensional evaluation of chronic obstructive pulmonary disease (COPD) patients, the spirometry measures are supplemented by assessment of symptoms, risk of exacerbations, and CT imaging. However, the measurement of diffusing capacity of the lung for carbon monoxide (DLCO) is not included in most common used models of COPD assessment. Here, we conducted a meta-analysis to evaluate the role of DLCO in COPD assessment.The studies were identified by searching the terms "diffusing capacity" OR "diffusing capacity for carbon monoxide" or "DLCO" AND "COPD" AND "assessment" in Pubmed, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase, Scopus, and Web of Science databases. The mean difference of DLCO % predict was assessed in COPD patient with different severity (according to GOLD stage and GOLD group), between COPD patients with or without with frequent exacerbation, between survivors and non-survivors, between emphysema dominant and non-emphysema dominant COPD patients, and between COPD patients with or without pulmonary hypertension.43 studies were included in the meta-analysis. DLCO % predicted was significantly lower in COPD patients with more severe airflow limitation (stage II/IV), more symptoms (group B/D), and high exacerbation risk (group C/D). Lower DLCO % predicted was also found in exacerbation patients and non-survivors. Low DLCO % predicted was related to emphysema dominant phenotype, and COPD patients with PH.The current meta-analysis suggested that DLCO % predicted might be an important measurement for COPD patients in terms of severity, exacerbation risk, mortality, emphysema domination, and presence of pulmonary hypertension. As diffusion capacity reflects pulmonary ventilation and perfusion at the same time, the predictive value of DLCO or DLCO combined with other criteria worth further exploration.
Subject(s)
Pulmonary Disease, Chronic Obstructive , Pulmonary Emphysema , Forced Expiratory Volume , Humans , Pulmonary Diffusing Capacity , Pulmonary Disease, Chronic Obstructive/complications , SpirometryABSTRACT
The lung is one of the most important organs exposed to environmental agents. People spend approximately 90% of their time indoors, and risks to health may thus be greater from exposure to poor air quality indoors than outdoors. Multiple indoor pollutants have been linked to chronic respiratory diseases. Environmental tobacco smoke (ETS) is known as an important source of multiple pollutants, especially in indoor environments. Indoor PM2.5 (particulate matter with aerodynamic diameterâ¯<â¯2.5⯵m) was reported to be the most reliable marker of the presence of tobacco smoke. Recent studies have demonstrated that PM2.5 is closely correlated with chronic lung diseases. In this paper, we reviewed the relationship of tobacco smoking and indoor PM2.5 and the mechanism that underpin the link of tobacco smoke, indoor PM2.5 and chronic lung diseases.
Subject(s)
Air Pollutants , Air Pollution, Indoor , Lung Diseases , Tobacco Smoke Pollution , Environmental Monitoring , Humans , Particulate Matter , Tobacco SmokingABSTRACT
BACKGROUND: Gastroesophageal reflux disease (GERD) was suggested to be associated with exacerbations of chronic obstructive pulmonary disease (COPD) in recent years. The aim of this study was to examine the association between GERD and COPD exacerbation through a meta-analysis. METHODS: Databases including EMBASE, MEDLINE, and the Cochrane Central Register of Controlled Trials were searched with a systematic searching strategy for original articles, published until Jan 2019, without language restriction. RESULTS: A total of 13,245 patients from 10 observational articles were included in the meta-analysis. The meta-analysis indicated that GERD is associated with increased risk of COPD exacerbation (OR: 5.37; 95% CI 2.71-10.64). Patients with COPD and GERD had increased number of exacerbation (WMD: 0.48; 95% CI: 0.31 to 0.65). CONCLUSIONS: The meta-analysis showed that there was a significant correlation between GERD and COPD exacerbation.
Subject(s)
Gastroesophageal Reflux/complications , Pulmonary Disease, Chronic Obstructive/complications , Disease Progression , Gastroesophageal Reflux/physiopathology , Humans , Observational Studies as Topic , Risk FactorsABSTRACT
The human microbiome harbors a diverse array of microbes which establishes a mutually beneficial relation with the host in healthy conditions, however, the dynamic homeostasis is influenced by both host and environmental factors. Smoking contributes to modifications of the oral, lung and gut microbiome, leading to various diseases, such as periodontitis, asthma, chronic obstructive pulmonary disease, Crohn's disease, ulcerative colitis and cancers. However, the exact causal relationship between smoking and microbiome alteration remains to be further explored.
Subject(s)
Gastrointestinal Microbiome , Lung/microbiology , Microbiota , Mouth/microbiology , Smoking/adverse effects , Disease , HumansABSTRACT
Considering the complexity and high-consumption of the existing approaches to fabricate three-dimensional (3D) regular substrate templates, the scales of the moth wings with evenly-distributed nanoarrays were discovered to provide an ideal bioscaffold for metal silver (Ag) to decorate on to fabricate a flexible, highly-ordered, low-cost and large-scale Ag nanoislands/moth wing (Ag/MW) SERS-active substrate. The grating-like substrate with the optimal morphology of rough and hierarchical Ag nanoislands exhibited high enhancement factor (EF, ~4.16 × 105), low detection limit (10-10 M) to 4-aminothiophenol (4-ATP), outstanding signal uniformity (the relative standard deviations were less than 15%) and superior identification performance in the quantitative detection of pesticide cypermethrin. The three-dimensional finite-difference time-domain (3D-FDTD) method simulated the spatial distribution of the electric field intensity in the substrates with different morphologies, showing a potential strong enhancement of Raman signals in sub-10 nm gaps between two adjacent Ag nanoislands of different layers. These prominent SERS properties of novel Ag/MW SERS-active substrates suggest their potential value in rapid on-side biological and chemical sensing. Meanwhile, the highly-ordered nanoarrays of moth wings provide a new idea for the preparation of regular biomimetic nanomaterials.
ABSTRACT
BACKGROUND: Adipose-derived mesenchymal stem cell (ASCs) exerts immunomodulatory roles in asthma. However, the underlying mechanism remains unclear. The present study aimed to explore the effects and mechanisms of ASCs on chronic asthma using an ovalbumin (OVA)-sensitized asthmatic mouse model. METHODS: Murine ASCs (mASCs) were isolated from male Balb/c mice and identified by the expression of surface markers using flow cytometry. The OVA-sensitized asthmatic mouse model was established and then animals were treated with the mASCs through intratracheal delivery. The therapy effects were assessed by measuring airway responsiveness, performing immuohistochemical analysis, and examining bronchoalveolar lavage fluid (BALF). Additionally, the expression of inflammatory cytokines and lgE was detected by CHIP and ELISA, respectively. The mRNA levels of serum indices were detected using qRT-PCR. RESULTS: The mASCs grew by adherence with fibroblast-like morphology, and showed the positive expression of CD90, CD44, and CD29 as well as the negative expression of CD45 and CD34, indicating that the mASCs were successfully isolated. Administering mASCs to asthmatic model animals through intratracheal delivery reduced airway responsiveness, the number of lymphocytes (P < 0.01) and the expression of lgE (P < 0.01), IL-1ß (P < 0.05), IL-4 (P < 0.001), and IL-17F (P < 0.001), as well as increased the serum levels of IL-10 and Foxp3, and the percentage of CD4 + CD25 + Foxp3+ Tregs in the spleen, and reduced the expression of IL-17 (P < 0.05) and RORγ. CONCLUSIONS: Intratracheal administration of mASCs alleviated airway inflammation, improved airway remodeling, and relieved airway hyperresponsiveness in an OVA-sensitized asthma model, which might be associated with the restoration of Th1/Th2 cell balance by mASCs.