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BACKGROUND: The gut-lung axis, pivotal for respiratory health, is inadequately explored in pulmonary and critical care medicine (PCCM) inpatients. METHODS: Examining PCCM inpatients from three medical university-affiliated hospitals, we conducted 16S ribosomal RNA sequencing on stool samples (inpatients, n = 374; healthy controls, n = 105). We conducted statistical analyses to examine the gut microbiota composition in PCCM inpatients, comparing it to that of healthy controls. Additionally, we explored the associations between gut microbiota composition and various clinical factors, including age, white blood cell count, neutrophil count, platelet count, albumin level, hemoglobin level, length of hospital stay, and medical costs. RESULTS: PCCM inpatients exhibited lower gut microbiota diversity than healthy controls. Principal Coordinates Analysis revealed marked overall microbiota structure differences. Four enterotypes, including the exclusive Enterococcaceae enterotype in inpatients, were identified. Although no distinctions were found at the phylum level, 15 bacterial families exhibited varying abundances. Specifically, the inpatient population from PCCM showed a significantly higher abundance of Enterococcaceae, Lactobacillaceae, Erysipelatoclostridiaceae, Clostridiaceae, and Tannerellaceae. Using random forest analyses, we calculated the areas under the receiver operating characteristic curves (AUCs) to be 0.75 (95% CIs 0.69-0.80) for distinguishing healthy individuals from inpatients. The four most abundant genera retained in the classifier were Blautia, Subdoligranulum, Enterococcus, and Klebsiella. CONCLUSIONS: Evidence of gut microbiota dysbiosis in PCCM inpatients underscores the gut-lung axis's significance, promising further avenues in respiratory health research.
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Disbiose , Microbioma Gastrointestinal , Humanos , Microbioma Gastrointestinal/fisiologia , Masculino , Disbiose/diagnóstico , Feminino , Pessoa de Meia-Idade , Idoso , Cuidados Críticos , Pacientes Internados , Adulto , Fezes/microbiologiaRESUMO
BACKGROUND: Non-cystic fibrosis bronchiectasis is a chronic respiratory disease characterized by bronchial dilation. However, the significance of elevated eosinophil counts in acute exacerbations of bronchiectasis remains unclear. METHODS: This retrospective case-control study included 169 hospitalized patients with acute exacerbations of non-cystic fibrosis bronchiectasis. Based on blood eosinophil levels, patients were categorized into eosinophilic and non-eosinophilic bronchiectasis groups. Various clinical variables, including lung function, comorbidities and clinical features were collected for analysis. The study aimed to examine the differences between these groups and their clinical phenotypes. RESULTS: Eosinophilic bronchiectasis (EB) was present in approximately 22% of all hospitalized patients with bronchiectasis, and it was more prevalent among male smokers (P < 0.01). EB exhibited greater severity of bronchiectasis, including worse airway obstruction, higher scores in the E-FACED (FACED combined with exacerbations) and bronchiectasis severity index (BSI), a high glucocorticoids medication possession ratio, and increased hospitalization cost (P < 0.05 or P < 0.01). Furthermore, we observed a significant positive correlation between blood eosinophil count and both sputum eosinophils (r = 0.49, P < 0.01) and serum total immunoglobulin E levels (r = 0.21, P < 0.05). Additional analysis revealed that patients with EB had a higher frequency of shortness of breath (P < 0.05), were more likely to have comorbid sinusitis (P < 0.01), and exhibited a greater number of lung segments affected by bronchiectasis (P < 0.01). CONCLUSIONS: These findings suggest that EB presents a distinct pattern of bronchiectasis features, confirming the notion that it is a specific phenotype.
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Bronquiectasia , Eosinófilos , Humanos , Masculino , Estudos Retrospectivos , Estudos de Casos e Controles , Fenótipo , FibroseRESUMO
BACKGROUND: Dysbiosis of the gut microbiome is involved in the pathogenesis of various diseases, but the contribution of gut microbes to the progression of chronic obstructive pulmonary disease (COPD) is still poorly understood. METHODS: We carried out 16S rRNA gene sequencing and short-chain fatty acid analyses in stool samples from a cohort of 73 healthy controls, 67 patients with COPD of GOLD stages I and II severity, and 32 patients with COPD of GOLD stages III and IV severity. Fecal microbiota from the three groups were then inoculated into recipient mice for a total of 14 times in 28 days to induce pulmonary changes. Furthermore, fecal microbiota from the three groups were inoculated into mice exposed to smoke from biomass fuel to induce COPD-like changes. RESULTS: We observed that the gut microbiome of COPD patients varied from that of healthy controls and was characterized by a distinct overall microbial diversity and composition, a Prevotella-dominated gut enterotype and lower levels of short-chain fatty acids. After 28 days of fecal transplantation from COPD patients, recipient mice exhibited elevated lung inflammation. Moreover, when mice were under both fecal transplantation and biomass fuel smoke exposure for a total of 20 weeks, accelerated declines in lung function, severe emphysematous changes, airway remodeling and mucus hypersecretion were observed. CONCLUSION: These data demonstrate that altered gut microbiota in COPD patients is associated with disease progression in mice model.
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Bactérias/crescimento & desenvolvimento , Microbioma Gastrointestinal , Intestinos/microbiologia , Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/microbiologia , Idoso , Remodelação das Vias Aéreas , Animais , Bactérias/genética , Bactérias/metabolismo , Estudos de Casos e Controles , China , Estudos Transversais , Modelos Animais de Doenças , Progressão da Doença , Disbiose , Ácidos Graxos Voláteis/metabolismo , Transplante de Microbiota Fecal , Fezes/química , Fezes/microbiologia , Feminino , Humanos , Pulmão/patologia , Masculino , Camundongos Endogâmicos C57BL , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/patologia , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , RibotipagemRESUMO
BACKGROUND: The role of the microbiota in the pathogenesis of chronic obstructive pulmonary disease (COPD) following exposure to ambient particulate matter (PM) is largely unknown. METHODS: Fifty-four male Sprague-Dawley rats were exposed to clean air, biomass fuel (BMF), or motor vehicle exhaust (MVE) for 4, 12, and 24 weeks. We performed pulmonary inflammation evaluation, morphometric measurements, and lung function analysis in rat lung at three different times points during exposure. Lung and gut microbial composition was assessed by 16S rRNA pyrosequencing. Serum lipopolysaccharide levels were measured and short-chain fatty acids in colon contents were quantified. RESULTS: After a 24-week PM exposure, rats exhibited pulmonary inflammation and pathological changes characteristic of COPD. The control and PM exposure (BMF and MVE) groups showed similar microbial diversity and composition in rat lung. However, the gut microbiota after 24 weeks PM exposure was characterized by decreased microbial richness and diversity, distinct overall microbial composition, lower levels of short-chain fatty acids, and higher serum lipopolysaccharide. CONCLUSION: Chronic exposure to ambient particulate matter induces gut microbial dysbiosis and metabolite shifts in a rat model of chronic obstructive pulmonary disease.
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Disbiose/induzido quimicamente , Microbioma Gastrointestinal/efeitos dos fármacos , Exposição por Inalação/efeitos adversos , Pulmão/efeitos dos fármacos , Material Particulado/toxicidade , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , Animais , Líquido da Lavagem Broncoalveolar , Modelos Animais de Doenças , Disbiose/sangue , Disbiose/fisiopatologia , Microbioma Gastrointestinal/fisiologia , Pulmão/fisiopatologia , Masculino , Material Particulado/administração & dosagem , Doença Pulmonar Obstrutiva Crônica/sangue , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Ambient particulate matter exposure has been shown to increase the risks of respiratory diseases. However, the role of the lung microbiome and the immune response to inhaled particulate matter are largely unexplored. We studied the influence of biomass fuel and motor vehicle exhaust particles on the lung microbiome and pulmonary immunologic homeostasis in rats. METHODS: Fifty-seven Sprague-Dawley rats were randomly divided into clean air (CON), biomass fuel (BMF), and motor vehicle exhaust (MVE) groups. After a 4-week exposure, the microbial composition of the lung was assessed by 16S rRNA pyrosequencing, the structure of the lung tissue was assessed with histological analysis, the phagocytic response of alveolar macrophages to bacteria was determined by flow cytometry, and immunoglobulin concentrations were measured with commercial ELISA kits. RESULTS: There was no significant difference in lung morphology between the groups. However, the BMF and MVE groups displayed greater bacterial abundance and diversity. Proteobacteria were present in higher proportions in the MVE group, and 12 bacterial families differed in their relative abundances between the three groups. In addition, particulate matter exposure significantly increased the capacity of alveolar macrophages to phagocytose bacteria and induced changes in immunoglobulin levels. CONCLUSION: We demonstrated that particulate matter exposure can alter the microbial composition and change the pulmonary immunologic homeostasis in the rat lung.
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Bactérias/efeitos dos fármacos , Biomassa , Fontes Geradoras de Energia , Pulmão/efeitos dos fármacos , Macrófagos Alveolares/efeitos dos fármacos , Material Particulado/toxicidade , Emissões de Veículos/toxicidade , Animais , Bactérias/classificação , Bactérias/imunologia , Ensaio de Imunoadsorção Enzimática , Citometria de Fluxo , Interações Hospedeiro-Patógeno , Imunoglobulinas/imunologia , Exposição por Inalação , Pulmão/imunologia , Pulmão/microbiologia , Macrófagos Alveolares/imunologia , Macrófagos Alveolares/microbiologia , Masculino , Fagocitose/efeitos dos fármacos , Ratos Sprague-Dawley , Ribotipagem , Fatores de TempoRESUMO
Constrictive pericarditis is a rare disease. Localized constrictive pericarditis leading to bilateral pleural effusion is more difficult to recognize, and the diagnostic procedure can be ambiguous. Here, we report two patients diagnosed with localized constrictive pericarditis who presented with bilateral pleural effusion. A thorough work-up showed that the pleural effusion was nonspecific, as was the pathology of the pleura. One patient had a history of pericardial effusion 2 years ago, and the other had undergone surgery for an anterior mediastinum teratoma. Pericardial scarring was found on their chest CT scans. The patients underwent pericardiectomy, and localized pericardial thickening was excised. The bilateral pleural effusion was effectively cured, and the patients showed satisfactory recovery on follow-up. Physicians should be aware of localized pericarditis leading to bilateral pleural effusion, and pericardiectomy is an effective diagnostic and therapeutic procedure.
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Pericardiectomia , Pericardite Constritiva , Derrame Pleural , Tomografia Computadorizada por Raios X , Humanos , Pericardite Constritiva/diagnóstico , Pericardite Constritiva/cirurgia , Pericardite Constritiva/complicações , Masculino , Pericardiectomia/métodos , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Pessoa de Meia-Idade , Feminino , Ecocardiografia , Adulto , Diagnóstico DiferencialRESUMO
Cough is one of the most common symptoms observed in patients presenting with COVID-19, persisting for an extended duration following SARS-CoV-2 infection. We aim to describe the distribution of airway microbiota and explore its role in patients with post-COVID-19 chronic cough. A total of 57 patients experiencing persistent cough after infection were recruited during the Omicron wave of SARS-CoV-2 in China. Airway microbiota profiling is assessed in nasopharyngeal swab, nasal lavage, and induced sputum samples at 4 and 8 weeks after SARS-CoV-2 infection. Our findings reveal that bacterial families Staphylococcaceae, Corynebacteriaceae, and Enterobacteriaceae are the most prevalent in the upper airway, while Streptococcaceae, Lachnospiraceae, and Prevotellaceae emerge as the most prevalent bacterial families in the lower airway. An increase in the abundance of Staphylococcus in nasopharyngeal swab samples and of Streptococcus in induced sputum samples is observed after one month. Furthermore, the abundance of Staphylococcus identified in nasopharyngeal swab samples at the baseline period emerges as an insightful predictor for improvement in cough severity. In conclusion, dynamic alterations in the airway microbial composition may contribute to the post-COVID-19 chronic cough progression, while the compositional signatures of nasopharyngeal microbiota could reflect the improvement of this disease.
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Background: Minute pulmonary meningothelial-like nodules (MPMNs) and diffuse pulmonary meningotheliomatosis (DPM) are both rare lung diseases that involve the proliferation of cells of meningothelial origin in the lungs. However, few studies have focused on the clinical, pathological, and radiological features of MPMNs and DPMs. Methods: The clinicopathological data of 167 cases diagnosed as MPMNs and 13 cases diagnosed as DPM in the China National Center for Respiratory Medicine were examined. Based on clinical data, CT images, and morphological features, this study analyzed the similarities and differences between MPMNs and DPM. Results: The detection rates of MPMNs and DPM were 1.9 and 0.15%, respectively. Compared to MPMNs, DPM patients were all women (100% vs. 79.4%, P = 0.066), had a younger age (51.4 ± 7.7 vs. 57.9 ± 8.5, P < 0.01), and had higher pulmonary function (P < 0.01 or P < 0.05). The chest CT of DPM patients showed diffuse ground-glass opacity nodules measuring 2.0-8.0 mm in diameter, with the number of nodules ranging from 40 to >600 per lung. There were no significant differences in nodule volume [28.0 (12.1, 65.1) mm3 vs. 28.7 (17.1, 48.9) mm3, P = 0.451] and CT values [-646.8 (-732.5, -514.5) Hu vs. -588 (-674, -480) Hu, P = 0.215] between MPMNs and DPM. MPMNs are characterized by reactive hyperplasia pulmonary nodules, which can be solitary or multiple. Conclusion: This study suggests that there are many different characteristics between patients with MPMNs and DPM. The limited findings challenge the notion that DPM is a rare subtype of MPMNS.
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Background: The link between gut microbial dysbiosis and the development of chronic obstructive pulmonary disease (COPD) is of considerable interest. However, little is known regarding the potential for the use of the fecal metagenome for the diagnosis of COPD. Methods: A total of 80 healthy controls, 31 patients with COPD severity stages I or II, and 49 patients with COPD severity stages III or IV fecal samples were subjected to metagenomic analysis. We characterized the gut microbiome, identified microbial taxonomic and functional markers, and constructed a COPD disease classifier using samples. Results: The fecal microbial diversity of patients with COPD stages I or II was higher than that of healthy controls, but lower in patients with COPD stages III or IV. Twenty-one, twenty-four, and eleven microbial species, including potential pathogens and pro-inflammatory bacteria, were significantly enriched or depleted in healthy controls, patients with COPD stages I or II, and patients with COPD stages III & IV. The KEGG orthology (KO) gene profiles derived demonstrated notable differences in gut microbial function among the three groups. Moreover, gut microbial taxonomic and functional markers could be used to differentiate patients with COPD from healthy controls, on the basis of areas under receiver operating characteristic curves (AUCs) of 0.8814 and 0.8479, respectively. Notably, the gut microbial taxonomic features differed between healthy individuals and patients in stages I-II COPD, which suggests the utility of fecal metagenomic biomarkers for the diagnosis of COPD (AUC = 0.9207). Conclusion: Gut microbiota-targeted biomarkers represent potential non-invasive tools for the diagnosis of COPD.
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Background: Sanfeng Tongqiao Diwan has shown the potential to alleviate acute, recurrent, and chronic rhinitis in adults based on available studies. However, the evidence for its application in upper airway cough syndrome (UACS) is unclear. The purpose of this study was thus to investigate the efficacy and safety of Sanfeng Tongqiao Diwan in the treatment of UACS. Methods: This was a single-center, randomized, double-blind, placebo-controlled clinical trial. A total of 60 patients who satisfied the inclusion criteria were randomly divided into experimental and placebo groups in a 1:1 ratio. The experimental group was given Sanfeng Tongqiao Diwan, and the placebo group was given a simulant for 14 consecutive days. The follow-up period was 15 days. The primary outcome was the total effective rate. The secondary outcomes included clinical efficacy, Visual Analogue Scale (VAS) of related symptoms, and Leicester Cough Questionnaire in Mandarin-Chinese (LCQ-MC) scores before and after the treatment. Additionally, the safety was also evaluated. Results: The total effective rate in the experimental group was 86.6% (26/30), which was significantly higher than the 7.1% (2/28) in the placebo group (difference 79.6; 95% CI: 57.0 to 89.1; P<0.001). Nasal congestion, runny nose, cough, postnasal drip, and overall symptoms in the experimental group were significantly lower than those in the placebo group after treatment (3.7±1.5 vs. 5.0±1.1, 3.6±1.3 vs. 5.9±1.1, 3.8±1.2 vs. 6.8±1.3, 3.5±1.4 vs. 6.1±1.5, 3.8±2.0 vs. 7.3±1.4, respectively; all P values <0.001). After treatment, the LCQ-MC score in the experimental group was significantly higher than that in the placebo group (all P values <0.001). The blood eosinophil count in the placebo group was significantly higher after treatment than before treatment (P=0.037). No abnormalities were found in liver or renal indicators during the treatment period in the 2 groups, and no adverse reactions occurred. Conclusions: Sanfeng Tongqiao Diwan improved the symptoms and living quality of patients with UACS and showed acceptable safety. The results of this trial represent rigorous clinical evidence for the application of Sanfeng Tongqiao Diwan and further support a new option in UACS treatment. Trial Registration: Chinese Clinical Trial Registry ChiCTR2300069302.
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Chronic obstructive pulmonary disease (COPD) is a heterogeneous illness associated with aberrant inflammatory immune reaction in the lung in response to noxious particles and gases. Our previous epidemiological studies discovered that long-term exposure to air pollution PM was associated with an increase in the incidence of COPD and lung function decline, but the impact of air pollution on the onset of COPD and its pathogenesis remains obscure. In recent years, long noncoding RNAs (lncRNAs) have been documented to have a crucial role in COPD. Our preliminary study found that the expression of lncRNA MHC-R in the lung tissues of rats exposed to air pollution PM was dramatically elevated, and the specific expression was mainly focused on the immune-related MHC I, antigen-presenting, and adaptive immune response. After transcription factor prediction, it was found that GATA3 could be combined with the specific sequence of the lncRNA MHC-R promoter region. Dendritic cells (DCs) are necessary antigen-presenting cells (APCs) with the most potent antigen-presenting function. We proved that GATA3/lncRNA MHC-R might regulate the immune activities of DCs to participate in the pathogenic mechanism of COPD induced by air pollution PM, which opens up a new way for early COPD diagnosis and treatment.
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Poluentes Atmosféricos , Células Dendríticas , Fator de Transcrição GATA3 , Material Particulado , Doença Pulmonar Obstrutiva Crônica , RNA Longo não Codificante , Poluentes Atmosféricos/toxicidade , Animais , Células Dendríticas/imunologia , Fator de Transcrição GATA3/genética , Inflamação , Material Particulado/toxicidade , Doença Pulmonar Obstrutiva Crônica/induzido quimicamente , RNA Longo não Codificante/genética , RatosRESUMO
Background: Outdoor traffic-related air pollution has negative effects on respiratory health. In this study, we aimed to explore the effect of outdoor traffic-related air pollution on chronic obstructive pulmonary disease (COPD) in Guangzhou. Methods: We enrolled 1,460 residents aged 40 years or older between 21 January 2014 and 31 January 2018. We administered questionnaires and spirometry tests. The distance of participants' residences or locations of outdoor activities from busy roads (as indicators of outdoor traffic-related air pollution), indoor air pollution, and smoking history were queried in the questionnaires. Results: Of the 1,460 residents with valid survey and test results, 292 were diagnosed with COPD, with a detection rate of 20%. Participants who lived and did their outdoor activities near busy roads had a higher detection rate of COPD. Among residents living at distances of <50 meters, 50-199 meters, and more than 200 meters from busy roads, the detection rates were 20.6, 21.2, and 14.8%, respectively; the rates for outdoor activities at these distances were 23.8, 24.5, and 13.7%, respectively (p < 0.05). After adjusting for sex, age, smoking status, family history, and smoking index, the distance of outdoor activities from busy roads was an independent risk factor for COPD. Participants whose outdoor activities were conducted <50 meters and 50-199 meters of main roads had odds ratios of 1.54 (95% confidence interval 1.01-2.36) and 1.84 (95% interval 1.23-2.76) for the risk of COPD in comparison with a distance of more than 200 meters from busy roads. Conclusions: Residents of Guangzhou whose outdoor activities were close to busy roads had a high risk of COPD. Traffic-related air pollution presents a risk to human health and a risk of COPD.
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Poluição do Ar , Doença Pulmonar Obstrutiva Crônica , Humanos , Exposição Ambiental/efeitos adversos , Emissões de Veículos , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/etiologia , Fatores de Risco , Poluição do Ar/efeitos adversosRESUMO
Rural environments and microbiota are linked to a reduction in the prevalence of allergies. However, the mechanism underlying the reduced allergies modulated by rural residency is unclear. Here, we assessed gut bacterial composition and metagenomics in urban and rural children in the EuroPrevall-INCO cohort. Airborne dusts, including mattress and rural henhouse dusts, were profiled for bacterial and fungal composition by amplicon sequencing. Mice were repeatedly exposed to intranasal dust extracts and evaluated for their effects on ovalbumin (OVA)-induced allergic airway inflammation, and gut microbiota restoration was validated by fecal microbiota transplant (FMT) from dust-exposed donor mice. We found that rural children had fewer allergies and unique gut microbiota with fewer Bacteroides and more Prevotella. Indoor dusts in rural environments harbored higher endotoxin level and diversity of bacteria and fungi, whereas indoor urban dusts were enriched with Aspergillus and contained elevated pathogenic bacteria. Intranasal administration of rural dusts before OVA sensitization reduced respiratory eosinophils and blood IgE level in mice and also led to a recovery of gut bacterial diversity and Ruminiclostridium in the mouse model. FMT restored the protective effect by reducing OVA-induced lung eosinophils in recipient mice. Together, these results support a cause-effect relationship between exposure to dust microbiota and allergy susceptibility in children and mice. Specifically, rural environmental exposure modulated the gut microbiota, which was essential in reducing allergy in children from Southern China. Our findings support the notion that the modulation of gut microbiota by exposure to rural indoor dust may improve allergy prevention.
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Microbioma Gastrointestinal , Hipersensibilidade , Animais , Bactérias/genética , Poeira , Endotoxinas , Hipersensibilidade/microbiologia , Hipersensibilidade/prevenção & controle , Imunoglobulina E , Inflamação , Camundongos , OvalbuminaRESUMO
BACKGROUND: Severe asthma is difficult to control. Therapeutic patient education enables patients to better understand their disease and cope with treatment, but the effect of therapeutic patient education in severe uncontrolled asthma is unclear. We evaluated whether therapeutic patient education is effective in improving asthma control and decreasing the frequency of exacerbations in severe uncontrolled asthma. METHODS: This was a prospective, observational, and self-controlled study that enrolled 40 subjects with severe uncontrolled asthma. Patients were seen at a clinic four times (on day 1 and after 3, 6, and 12 months). After baseline data collection, the subjects completed a therapeutic patient education program and were also followed-up via telephone after 1, 2, 4, 5, 7, 8, 9, 10, and 11 months to monitor asthma medication adherence and collect asthma-related information. RESULTS: Within the 1-year study period, a total of 23 exacerbations were recorded in 14 patients, seven of whom required emergency treatment and two of whom were hospitalized. Twelve months after the standardized therapeutic patient education program, pulmonary function and fractional exhaled nitric oxide levels improved significantly in all 40 patients. Moreover, the scores from three standardized asthma questionnaires and indices suggested improved quality of life in these patients with severe uncontrolled asthma. Serum levels of biomarkers reflecting asthma immune responses did not change between baseline and the 1-year follow-up time point. CONCLUSIONS: Therapeutic patient education is effective in improving asthma control and decreasing exacerbations in patients with severe uncontrolled asthma.
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Objective: Peroxisome proliferator-activated receptor gamma (PPARγ) has an anti-proliferation effect on pulmonary arterial smooth muscle cells (PASMCs) via the transient receptor potential channel (TRPC) and protects against pulmonary artery hypertension (PAH), whereas nuclear factor-kappa B (NF-κB) has pro-proliferation and pro-inflammation effects, which contributes to PAH. However, the association between them in PAH pathology remains unclear. Therefore, this study aimed to investigate this association and the mechanisms underlying TRPC1/6 signaling-mediated PAH. Methods: Human pulmonary arterial smooth muscle cells (hPASMCs) were transfected with p65 overexpressing (pcDNA-p65) and interfering plasmids (shp65) and incubated in normal and hypoxic conditions (4% O2 and 72 h). The effects of hypoxia and p65 expression on cell proliferation, invasion, apoptosis, [Ca2+]i, PPARγ, and TRPC1/6 expression were determined using Cell Counting Kit-8 (CCK-8), Transwell, Annexin V/PI, Fura-2/AM, and western blotting, respectively. In addition, the binding of p65 or PPARγ proteins to the TRPC6 promoter was validated using a dual-luciferase report assay, chromatin-immunoprecipitation-polymerase chain reaction (ChIP-PCR), and electrophoretic mobility shift assay (EMSA). Results: Hypoxia inhibited hPASMC apoptosis and promoted cell proliferation and invasion. Furthermore, it increased [Ca2+]i and the expression of TRPC1/6, p65, and Bcl-2 proteins. Moreover, pcDNA-p65 had similar effects on hypoxia treatment by increasing TRPC1/6 expression, [Ca2+]i, hPASMC proliferation, and invasion. The dual-luciferase report and ChIP-PCR assays revealed three p65 binding sites and two PPARγ binding sites on the promoter region of TRPC6. In addition, hypoxia treatment and shPPARγ promoted the binding of p65 to the TRPC6 promoter, whereas shp65 promoted the binding of PPARγ to the TRPC6 promoter. Conclusion: Competitive binding of NF-κB p65 and PPARγ to TRPC6 produced an anti-PAH effect.
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Almost three billion people in developing countries are exposed to biomass smoke (BS), which predisposes them to developing chronic obstructive pulmonary disease (COPD). COPD is associated with abnormal innate and adaptive immune responses in the lungs and systemic circulation, but the mechanisms underlying BS-COPD development are uncertain. We investigated the role of dendritic cells (DCs) and interleukin (IL)-17A in BS-COPD. We investigated T helper cell responses in the BS-exposed COPD rat model by flow cytometry, quantitative PCR, and enzyme-linked immunosorbent assays. We conducted ex vivo experiments to determine which antigen-presenting cells induce Th17 cell responses. We evaluated the in vitro effects of BS-related particulate matter (BRPM) (2.5 µm) on the function of bone marrow-derived dendritic cells (BMDCs). We found that BS exposure enhanced Th17 responses in the lungs of the COPD-modelled rats, and the stimulated DCs (but not the macrophages) were sufficient to induce naïve CD4 + T cells to produce IL-17A in ex vivo experiments. BRPM significantly enhanced the maturation and activation of DCs through Toll-like receptor 2 (TLR2), but not TLR4, and induced Th17 responses. Therefore, BS activated lung DCs through TLR2, which led to Th17 responses and emphysema in the rats. This process is possibly therapeutically targetable.
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Células Dendríticas/imunologia , Pulmão/imunologia , Doença Pulmonar Obstrutiva Crônica/imunologia , Fumaça/efeitos adversos , Células Th17/citologia , Receptor 2 Toll-Like/fisiologia , Animais , Diferenciação Celular , Modelos Animais de Doenças , Interleucina-17/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Material Particulado/toxicidade , Enfisema Pulmonar/etiologia , Enfisema Pulmonar/imunologia , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Little is known about the quality and potential impacts of the guidelines for coronavirus disease 2019 (COVID-19) management. METHODS: We systematically searched PubMed, Web of Science, Cochrane Library, guideline databases, and specialty society websites to evaluate the quality of the retrieved guidelines using the Appraisal of Guidelines for Research and Evaluation II. RESULTS: A total of 66 guidelines were identified. Only 24% were categorized as "recommended" for clinical practice. The 211 identified recommendations for COVID-19 management were classified into 4 topics: respiratory support (27), acute respiratory distress syndrome management (31), antiviral or immunomodulatory therapy (95), or other medicines (58). Only 63% and 56% of recommendations were supported by, respectively, assessment of the strength of the recommendations or level of evidence. There were notable discrepancies between the different guidelines regarding the recommendations on COVID-19 management. CONCLUSIONS: The quality of the guidelines for COVID-19 management is heterogeneous, and the recommendations are rarely supported by evidence.
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OBJECTIVE: Guidelines from different regions on the use of non-invasive ventilation in COVID-19 have generally been inconsistent. The aim of this systematic review was to appraise the quality and availability of guidelines, and whether non-invasive ventilation in the early stages of the pandemic is of importance. DESIGN AND METHOD: Databases, including PubMed, Web of Science, and Cochrane Library, as well as websites of international organizations and gray literature, were searched up to June 23, 2020. The reference lists of eligible papers were also hand-searched. RESULTS: A total of 26 guidelines met the inclusion criteria. According to the Appraisal of Guidelines for Research and Evaluation (AGREE) II instrument, the guidelines' methodological quality was low. Among six domains, Rigour of Development and Editorial Independence were of the lowest quality. Given the lack of evidence from randomized clinical trials and the great variation between different regions, recommendations for non-invasive ventilation have generated considerable debate regarding the early stages of COVID-19. CONCLUSIONS: Improving the methodological quality of the guidelines should be a goal with regard to future pandemics. Additionally, better-designed randomized clinical trials are needed to resolve contradictions regarding the impact of non-invasive ventilation. PROSPERO REGISTRATION NUMBER: CRD42020198410.
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COVID-19/terapia , Guias como Assunto/normas , Ventilação não Invasiva , Humanos , SARS-CoV-2RESUMO
BACKGROUND: Asthma is a heterogeneous disease with diverse clinical manifestations and inflammatory pathologies that is punctuated by exacerbations. OBJECTIVE: To describe the clinical and inflammatory characteristics of patients with asthma treated in hospital for an acute exacerbation. METHODS: Data from 320 adult patients receiving treatment for an acute exacerbation of asthma were obtained. In 218 patients with complete data, we used the Ward hierarchical clustering to obtain clusters. Pulmonary function, blood cell counts, sputum cell counts, serum IgE levels, and fractional exhaled nitric oxide were measured on hospital admission. We selected 13 variables with which we performed the Ward minimum-variance hierarchical clustering. RESULTS: Four clusters were defined. Clusters 1 (24.5%) and 3 (36.7%) were characterized by predominantly female patients with asthma with sputum neutrophilia, with cluster 1 associated with a small degree of airflow obstruction and early-onset asthma and cluster 3 with a moderate degree of reduction in FEV1. Clusters 2 (22.0%) and 4 (16.5%) were associated with high sputum eosinophilia and severe airflow obstruction. Cluster 4 was made exclusively of male smoking subjects, whereas cluster 2 was made up of predominantly female nonsmoking subjects with the worst FEV1, forced expiratory flow at 25% to 75% of forced vital capacity (% predicted), and partial pressure of oxygen in arterial blood on admission. There were no differences between clusters in terms of atopy, serum IgE, prevalence of nasal disease, dose of maintenance inhaled corticosteroids, or oral/systemic corticosteroid use and asthma exacerbations. CONCLUSIONS: The clusters during recovery from an exacerbation of asthma were distinguished by airflow obstruction and a neutrophilic, eosinophilic, or mixed inflammation. Eosinophilic inflammation was found in smoking and nonsmoking patients with asthma during an exacerbation.