Small RNA Sequencing Reveals Exosomal miRNAs as Unique Feature Markers in Unprovoked Venous Thromboembolism.

INTRODUCTION: Venous thromboembolism (VTE) is a common cardiovascular disease. MicroRNAs (miRNAs) play a key role in VTE; however, the role of exosomal miRNAs in VTE remains unknown. Therefore, we aimed to identify key exosomal miRNAs and their potential mechanisms in VTE. METHODS: We collected 31 samples from unprovoked VTE patients and 25 samples from healthy individuals. Exosomal miRNA sequencing was performed on 11 unprovoked VTE samples and 9 normal samples, and the remaining samples were used to verify the expression level of candidate 9 miRNAs in VTE and normal samples. The sequencing data were used to analyze exosomal miRNA expression. Meanwhile, gene ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed to determine the potential biological functions of differentially expressed miRNA target genes. RESULTS: A total of 32 differentially expressed miRNAs were identified by sequencing. Among the 32 miRNAs, 23 miRNAs were upregulated (72%), and 9 miRNAs were downregulated (28%). In addition, we found that the biological functions and metabolic pathways of the target genes were related to hemostatic factors involved in VTE, indicating the regulation of differentially expressed miRNAs. We identified key miRNAs by constructing a miRNA-messenger RNA regulatory network and found that the target genes were related to VTE. We finally determined that the abnormal expression of 9 miRNAs is closely related to VTE, and the expression level between VTE and normal was verified through other samples. CONCLUSION: Our study identified a set of key miRNAs for future research on the molecular mechanisms of VTE.

Altered gut microbiome compositions are associated with the severity of asthma.

BACKGROUND: Despite substantial evidence on the contribution of the diversity of the gut microbiome to the pathogenesis of asthma and allergic diseases, little is known about their relationship with asthma severity and/or clinical phenotypes. We analyzed the difference in composition of the gut microbiome between subjects with asthma and healthy subjects and explored its role in the development of asthma. METHODS: Fecal samples from 15 subjects with severe asthma (SA), 14 with non-severe asthma (NSA), and 15 healthy subjects were assessed by 16S ribosomal RNA gene sequencing methods to identify the gut bacterial composition. RESULTS: Compared with those in the NSA group, patients in the SA group had a higher dose of inhaled corticosteroids, and there were more atopic subjects (60% vs. 35.7%, respectively). No significant differences were found at the phylum level either in operational taxonomic unit numbers or in diversity scores among the SA, NSA, and healthy groups. However, at the family level, the relative abundance of Acidaminococcaceae in the SA group was remarkedly lower than that in the group with healthy subjects (P<0.05). Furthermore, Veillonellaceae and Prevotellaceae were significantly more common in samples from the SA group than in those from the NSA group (P<0.05). In the SA group, positive correlations were observed between the relative abundance of Veillonellaceae and mid-expiratory flow 25% (MEF25%) predicted (r=0.538, P=0.047), as well as between the relative abundance of Acidaminococcaceae and body mass index (r=0642, P=0.010). Principal component analysis suggested that the relative abundances of Acidaminococcaceae and Prevotellaceae were associated with severe asthma. Moreover, we found that class Betaproteobacteria, order Burkholderiales, and family Alcaligenaceae were significantly different among the groups defined by serum immunoglobulin E (IgE) levels. CONCLUSIONS: Our findings suggest that altered gut microbiome compositions are involved in the severity of asthma and that there are specific bacteria related to different asthma phenotypes in terms of serum IgE levels.

Positive change in asthma control using therapeutic patient education in severe uncontrolled asthma: a one-year prospective study.

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.

Retrospective comparison of high-resolution computed tomography of eosinophilic granulomatosis with polyangiitis with severe asthma.

BACKGROUND: Eosinophilic granulomatosis with polyangiitis (EGPA) is often misdiagnosed as severe asthma due to their similar clinical presentations. We compared the pulmonary radiologic features of EGPA to those of severe asthma by high-resolution computed tomography (HRCT) in order to early diagnose EGPA. METHODS: We retrospectively reviewed clinical records and HRCT findings of 96 patients with EGPA and 82 patients with severe asthma who were seen at our hospital from 2011 to 2017. We used a semi-quantitative grading system to evaluate radiological findings. A radiological only and a clinical-radiological model were used to differentiate EGPA from severe asthma. RESULTS: Bronchial wall thickening, air trapping, tree-in-bud opacities, bronchial mucus plugging, bronchiectasis, diffuse ground-glass opacities (GGOs), consolidation, and increased small vascular markings were more common in EGPA patients than in severe asthmatics (P<0.05). The gradings of GGO (grade 2 vs. grade 1) and tree-in-bud opacities (grade 2 vs. grade 0) were higher in EGPA patients than in severe asthmatics. The total image score of EGPA patients was significantly higher than that of severe asthmatics (P<0.05). In the radiological only and the clinical-radiological model, the area under the receiver operating characteristic (ROC) curves (AUCs) for the identification of EGPA and severe asthma were 0.904 [95% confidence interval (CI): 0.860 to 0.948] and 0.974 (95% CI: 0.955 to 0.993), respectively. CONCLUSIONS: Lung HRCT scan is useful in differentiating EGPA from severe asthma. In patients with difficult-to-treat asthma, an HRCT scan of the thorax should be performed should there be features that raise the suspicion of EGPA.

Early radiologic and bronchoscopic changes after bronchial thermoplasty in patients with severe asthma.

Bronchial thermoplasty (BT) is a treatment to reduce the airway smooth muscle mass by delivering radiofrequency thermal energy to the airways. BT is used in patients with severe asthma. The present study reported on cases of pneumothorax directly after BT and retrospectively analyzed early radiologic and bronchoscopic modifications after BT. The clinical data and radiologic and bronchoscopic findings of 12 patients with severe asthma who were subjected to BT between July 2014 and October 2017 were analyzed. A total of 33 chest radiographs were collected within 18-24 h after BT. Radiological abnormalities were observed in 32 radiographs as atelectasis (53.1%), peribronchial consolidations (84.4%), pleural effusion (18.8%), effusion in oblique fissures (3.1%), pleural thickening (6.3%) and pneumothorax (3.1%). Of note, one patient suffered pneumothorax after the third BT session and underwent chest drain insertion, followed by mechanical ventilation at the intensive care unit and multiple bronchoscopic interventions, which revealed extensive phlegm plugs. A total of six patients with worsened symptoms and lobar atelectasis also required bronchoscopic intervention, which revealed that phlegm plugs occluded the bronchus in the treated lobe. No bronchoscopic intervention was required in the remaining five patients. During 16-30 days of follow-up, 95.7% of the findings on chest radiography were resolved. To the best of our knowledge, the present study reported the first case of pneumothorax following BT. Early radiologic modifications such as atelectasis and peribronchial consolidations appear common after BT. However, whether bronchoscopic intervention is required for atelectasis following BT warrants further investigation. Of note, BT should be audited and recorded in detail to ideally contribute to a framework of clinical trials to improve risk-benefit evaluations and the selection of patients likely to benefit from treatment.

Uncontrolled asthma phenotypes defined from parameters using quantitative CT analysis.

OBJECTIVE: Asthma is a heterogeneous disease with diverse clinical phenotypes that have been identified via cluster analyses. However, the classification of phenotypes based on quantitative CT (qCT) is poorly understood. The study was conducted to investigate CT determination of uncontrolled asthma phenotypes. METHODS: Sixty-five patients with uncontrolled asthma (37 with severe asthma, 28 with non-severe asthma) underwent detailed clinical, laboratory, and pulmonary function tests, as well as qCT analysis. Twenty-five healthy subjects were also included in this study and underwent clinical physical examinations, pulmonary function tests, and low-dose CT scans. RESULTS: The mean lumen area/body surface area ratio was smaller in patients with severe uncontrolled asthma compared with that in healthy subjects (9.84 mm2 [SD, 2.57 mm2], 11.96 mm2 [SD, 3.09 mm2]; p = 0.026). However, the percentage of mean wall area (WA) was greater (64.39% [SD, 2.55%], 62.09% [SD, 3.81%], p = 0.011). Air trapping (measured based on mean lung density and VI-856 [%] on expiratory scan) was greater in patients with severe uncontrolled asthma than in those with non-severe uncontrolled asthma and was higher in all patients with uncontrolled asthma than that in healthy subjects (all p < 0.001). Three CT-determined uncontrolled asthma phenotypes were identified. Cluster 1 had mild air trapping with or without proximal airway remodeling. Cluster 2 had moderate air trapping with or without proximal airway remodeling. Cluster 3 had severe air trapping with proximal airway remodeling. CONCLUSIONS: There was obvious air trapping and proximal airway remodeling in patients with severe uncontrolled asthma. The three CT-determined uncontrolled asthma phenotypes might reflect underlying mechanisms of disease in patient stratification and in the different stages of disease development. KEY POINTS: • Obvious air trapping and proximal airway remodeling were present in patients with severe uncontrolled asthma. • CT air trapping indices showed a good correlation with disease duration, total IgE, atopy, and OCS and ICS doses, and were even more strongly correlated with clinical lung function. • Three CT-determined uncontrolled asthma phenotypes were identified, which might reflect underlying mechanisms of disease in patient stratification and in the different stages of disease development.

Bronchiectasis after bronchial thermoplasty.

Bronchial thermoplasty (BT) is used in the treatment of severe refractory asthma. It has been found to be beneficial to long-term improvements in the rate of asthma exacerbation, quality of life questionnaire answers (AQLQ), hospitalization, and emergency room visits. Atelectasis and lung abscess as direct complication of BT, but not bronchiectasis, have been reported previously. In this study, we report bronchiectasis after BT in what we believe may be the first case, combined with optical coherence tomography (OCT) and a 3-year follow-up of chest computed tomography (CT), to evaluate a patient with severe persistent asthma. We describe a 49-year-old Chinese male who complained of recurrent wheezing lasting over 5 years. His chest CT scan was normal before BT, but one month thereafter, he presented with mild central bronchiectasis on high-resolution CT, which persisted for more than 4 years. It remains unclear why this patient developed bronchiectasis so early post-BT treatment. This case highlights the need for short-term and long-term safety data on BT.