[Effectiveness and safety of bronchial thermoplasty in patients with severe asthma].

OBJECTIVE: To assess the effectiveness and safety of bronchial thermoplasty (BT) in patients with severe asthma. METHOD: The China-Japan Friendship Hospital recruited 12 patients with severe asthma who were voluntary to take BT treatment from March 2014 to November 2014. The levels of airway inflammation and biological markers (percentage of blood eosinophils, percentage of sputum eosinophils, serum IgE, fractional exhaled nitric oxide) of the patients were examined before the treatment in order to identify the types of airway inflammation. The numbers of severe exacerbations and related hospitalizations within 1 year before and after BT were obtained for each patient. The occurrence of adverse events within 3 weeks after the treatment was collected. And the patient status within 1 year after the BT treatment was compared with that before the treatment, in terms of the number of severe exacerbations, exacerbation rate, the number of related hospitalizations, hospitalization rate and oral corticosteroid dose. RESULTS: For before and 1 year after the treatment, the numbers of subjects suffering severe exacerbations were 11 and 6, the numbers of total severe exacerbation were 76 and 16, the numbers of patients hospitalized due to acute attacks were 10 and 3, and the numbers of total hospitalizations were 56 and 6, respectively. The severe exacerbation rate, hospitalization rate and oral corticosteroid dose were significantly reduced 1 year after the treatment [(1.3±0.48 vs. 6.3±1.9) events/subject/year, (0.50±0.26 vs. 4.67±1.90) events/subject/year, (8.5±4.6 vs. 22.0±2.6) mg/d, P<0.05]. The most common adverse events within 3 weeks after BT treatment were cough (8 events), expectoration (20 events), temporary PEF reduction (7 events), wheezing (4 events), but most of these symptoms were relieved in 1 week. One subject suffered pneumonia after each of the 3 procedures but also recovered soon after an antibiotic therapy. No adverse events occurred because of BT treatment within 3 weeks after the treatment. Computed tomographic scans from baseline to 1 year after the BT treatment showed no structural abnormalities related to BT. CONCLUSIONS: These data demonstrate the benefits of BT with regard to both asthma control (based on reduction in severe exacerbations and hospitalizations due to acute exacerbations) and safety. BT might offer a new approach to treating severe asthma.

[Airway inflammatory phenotypes of asthmatic patients].

OBJECTIVE: To analyze the airway inflammatory phenotypes and clinical features of severe asthma compared to mild-moderate ("common") asthma. METHODS: A total of 946 cases of asthma were retrospectively analyzed in our hospital from January 2013 to December 2014. Sixty-one patients were classified to the severe asthma group, and 885 patients to the common asthma group. Severe asthma was diagnosed based on the protocol from ATS/ERS guidelines. All patients received induced sputum cell counts and pulmonary function tests, and 543 of them received fractional exhaled nitric oxide (FeNO) tests. The airway inflammatory phenotypes were defined and the clinical features of patients of severe asthma were studied. RESULTS: The distribution of airway inflammatory phenotypes of asthma was as follows: eosinophilic subtype (46.6%, 441/946), mixed granulocytic subtype (27.5%, 260/946), neutrophilic subtype (21.5%, 203/946), and paucigranulocytic subtype (4.4%, 42/946). There were no differences between the severe asthma group and the common asthma group in the distributions. Compared with common asthma patients, severe asthma patients had higher sputum eosinophil percentages (29.1 % ± 28.5% vs 22.2% ± 25.2%, t = 1.98, P < 0.05), higher FeNO values [(66.4 ± 64.1) ppb vs (48.0 ± 43.7) ppb, P < 0.01], lower percentages of FEV1% pred [(63.7 ± 24.1) % vs (84.7 ± 23.7)%, P < 0.01], and lower ratios of FEV1/FVC [(56.4 ± 15.1) % vs (69.1 ± 14.5)% P < 0.01]. In severe asthma patients, FeNO values were higher in the eosinophilic subtype and mixed granulocytic subtype (P < 0.05). Neutrophilic subtype patients had the lowest sputum eosinophil percentage [(1.8 ± 0.8)%, P < 0.01], the lowest percentage of FEV1% pred [(46.6 ± 16.1)%, P < 0.01], and the lowest ratios of FEV1/FVC [(45.2 ± 16.1)%, P < 0.01]. CONCLUSIONS: The common airway inflammatory phenotypes included eosinophilic subtype, mixed granulocytic subtype and neutrophilic subtype, in both severe and common asthma patients. Severe asthma patients had more severe eosinophilic airway inflammation and poorer lung function. Neutrophilic subtype might be the most intractable subtype with severely damaged pulmonary function in severe asthma.

Predictive effect of exhaled NO and VEGF expression levels on the severity of bronchial asthma and airway inflammation.

OBJECTIVE: To investigate the relationship between exhaled NO and vascular endothelial growth factor (VEGF) expression in bronchial asthma patients with asthma severity and airway inflammation. METHODS: From January 2015 to December 2017, 260 patients with bronchial asthma diagnosed in our hospital were enrolled. The expression of VEGF in the induced sputum was measured by enzyme-linked immunosorbent assay (ELISA) in the control (n=260) and asthma groups (n=260) in the same period. The NO concentration was measured on the same day. RESULTS: Intercellular adhesion molecule-1 (ICAM-1), VEGF, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels were significantly elevated in sputum of patients with acute asthma, and the concentration in exhaled NO of all patients was also significantly higher than the control group and the stable phase of asthma. The expression of ICAM-1, VEGF, TNF-α and IL-6 was significantly elevated in patients with severe asthma. There were significant differences in patients with mild to moderate asthma (P<0.05). Correlation analysis showed that VEGF, IL-6 and TNF-α were positively correlated with the degree of asthma (P<0.05), but negatively correlated with FEV1.0, FEV1.0/FVC% and PEF (P<0.05). CONCLUSION: The expression of VEGF in sputum in patients with bronchial asthma is closely related to the severity of asthma and airway inflammation.

Oxidative damage and DNA damage in lungs of an ovalbumin-induced asthmatic murine model.

BACKGROUND: Asthma is characterized to chronic airway inflammation. However, the role of oxidative damage and DNA damage in the pathophysiology of asthma have rarely been studied. On the other hand, there are evidences that DNA-dependent protein kinase (DNA-PK) participates in DNA damage repair and regulates innate immune responses and proinflammatory signaling pathways. METHODS: After ovalbumin (OVA)-induced asthmatic murine model was established, airway hyper-responsiveness (AHR), total and differential bronchoalveolar lavage fluid (BALF) cell counts. IL-4, IL-8, IL-13 and TNF-α were chosen to evaluate the airway inflammation, and oxidative damage indicators levels (8-isoprostane and 8-OhdG) in BALF were measured. Alkaline comet assay was conducted to detected DNA damage. Histological analysis was conducted after hematoxylin and eosin (HE) straining, and proteins were extracted for 3-nitrotyrosine (3-NT) detection and immunoblotting. RESULTS: AHR, infiltration of inflammatory cells and pro-inflammatory cytokine levels in lungs were significantly higher in asthmatic mice. OVA challenge resulted in robust increase in 3-NT, 8-isoprostane and 8OHdG in lungs, which represented oxidative damage level. DNA damage and repair proteins levels in asthma were also increased. NU7441 aggravated the DNA damage level. However, it suppressed infiltration of lung inflammatory cells and inflammatory cytokine levels, suggesting that DNA-PK may be a potential target for treatment of allergic asthma. CONCLUSIONS: Our study showed that oxidative damage and DNA damage existed in the airway of asthmatic mice. NU7441 augmented DNA damage level, and moreover, it also attenuated infiltration of inflammatory cells and pro-inflammatory cytokine levels in asthmatic lungs.