OBJECTIVEAsthma and chronic obstructive pulmonary disease (COPD) are representative chronic inflammatory airway diseases responsible for a considerable burden of disease. In this article, we reviewed the relationship between neutrophil extracellular traps (NETs) and chronic inflammatory airway diseases.

DATA SOURCESArticles published up to January 1, 2017, were selected from the PubMed, Ovid Medline, Embase databases, with the keywords of "asthma" or "pulmonary disease, chronic obstructive", "neutrophils" and "extracellular traps."

STUDY SELECTIONArticles were obtained and reviewed to analyze the role of NETs in asthma and COPD.

RESULTSNETs are composed of extracellular DNA, histones, and granular proteins, which are released from activated neutrophils. Multiple studies have indicated that there are a large amount of NETs in the airways of asthmatics and COPD patients. NETs can engulf and kill invading pathogens in the host. However, disordered regulation of NET formation has shown to be involved in the development of asthma and COPD. An overabundance of NETs in the airways or lung tissue could cause varying degrees of damage to lung tissues by inducing the death of human epithelial and endothelial cells, and thus resulting in impairing pulmonary function and accelerating the progress of the disease.

CONCLUSIONSExcessive NETs accumulate in the airways of asthmatics and COPD patients. Although NETs play an essential role in the innate immune system against infection, excessive components of NETs can cause lung tissue damage and accelerate disease progression in asthmatics and COPD patients. These findings suggest that administration of NETs could be a novel approach to treat asthma and COPD. Mechanism studies, clinical practice, and strategies to regulate neutrophil activation or directly interrupt NET function in asthmatics and COPD patients are desperately needed.

Animals ; Asthma ; metabolism ; pathology ; Extracellular Traps ; metabolism ; physiology ; Humans ; Neutrophils ; metabolism ; pathology ; Pulmonary Disease, Chronic Obstructive ; metabolism ; pathology

OBJECTIVETo investigate the role and mechanism of matrix metalloproteinase 9 (MMP-9) and tumor necrosis factor α (TNF-α) in the pathogenesis of allergic rhinitis (AR) and asthma(AS).

METHODSThe rat models of AR and AS were made by injecting ovalbumin. The infiltration of eosinophils and mast cells were detected by hematoxylin-eosin (HE) staining and toluidine blue staining respectively, and the expression of MMP-9 and TNF-α in nasal mucosa and lung tissue were examined by immunohistochemical staining (SP method). The relationship of their expression with upper and lower respiratory tract inflammation was analyzed. SPSS 13.0 software was used to analyze the data.

RESULTSThe numbers of MMP-9 positive inflammatory cells in nasal mucosa and lung tissue of AR were (154.8 ± 12.0) and (124.0 ± 8.2), (43.2 ± 7.6) and (34.5 ± 5.0) in the control groups, the difference was significant (t value were 24.260, 29.525 respectively, all P < 0.05). The numbers of MMP-9 positive inflammatory cells in nasal mucosa and lung tissue of AS were (149.9 ± 11.7) and (120.1 ± 7.3), (48.6 ± 7.6) and (39.1 ± 5.2) in control groups, the difference was significant (t value were 22.929 and 28.530 respectively, all P < 0.05). The numbers of TNF-α positive inflammatory cells in nasal mucosa and lung tissue of AR were (188.8 ± 17.0), and (134.8 ± 7.9), (57.6 ± 23.3) and (40.3 ± 8.2) in control groups, the difference was significant (t value were 13.836 and 26.220, all P < 0.05). The numbers of TNF-α positive inflammatory cells in nasal mucosa and lung tissue of AS were (179.2 ± 15.4) and (153.5 ± 10.1), (70.5 ± 33.1) and (33.8 ± 14.0) in control groups, the difference was significant (t value were 9.412 and 21.858, all P < 0.05). There was a correlation between the expression of MMP-9 and TNF-α in nasal mucosa and lung tissue of AR (r values were 0.893 and 0.700 respectively, P values were 0.001 and 0.024, respectively) and AS (r values were 0.692 and 0.644 respectively, P values were 0.027 and 0.044 respectively) groups.

CONCLUSIONSThe inflammation is similar between AR and AS. The MMP-9 and TNF-α may play an important role in the pathogenesis of upper and lower respiratory tract inflammation.

Animals ; Asthma ; metabolism ; pathology ; Eosinophils ; metabolism ; Inflammation ; Male ; Matrix Metalloproteinase 9 ; metabolism ; Rats ; Rats, Sprague-Dawley ; Rhinitis, Allergic, Perennial ; metabolism ; pathology ; Tumor Necrosis Factor-alpha ; metabolism

OBJECTIVETo investigate the changes of neutrophils in airway inflammation in children with severe asthma.

METHODChildren with mild to moderate asthma (n=23), severe asthma (n=16) and healthy control subjects (n=16) underwent lung function tests and sputum induction. The sputum specimens were assayed for cellular differential count, the supernatant and peripheral blood were assayed for the concentrations of IL-8 by "sandwich" enzyme linked immunosorbent assay (ELISA). Sputum supernatant, IL-8 and mifepristone were assessed for their abilities to prolong the in vitro survival of blood-derived neutrophils.

RESULTThe percentage of sputum neutrophils was significantly higher in severe asthmatics [59.54 (41.99-74.65)%] than mild-moderate asthmatics [30.03 (15.94-47.71)%] and healthy control subjects [29.72(16.53-45.74)%] (P < 0. 01); the level of IL-8 in sputum was significantly higher in severe asthmatics [2907.78 (331.67 - 3457.93) ng/L] than mild-moderate asthmatics [287.58 (130.75-656.84) ng/L] and healthy control subjects [179.2 (58.55-346.59) ng/L] (P < 0.01); the percentages of neutrophilic apoptosis respectively cultured with LPS [(10.57 +/- 1.97)%], severe asthmatics supernatant [(11.82 +/- 2.96)%], IL-8 [(10.47 +/- 1.93)%], dexamethasone [(9.93 +/- 1.95)%], severe asthma supernatant + mifepristone [(12.15 +/- 2.86)%] in vitro were lower than that cultured with PBS [(17.98 +/- 2.27)%], healthy control supernatant [(17.37 +/- 2.50)%], mild-moderate asthmatics supernatant [(16.35 +/- 3.26)%], mifepristone [(17.89 +/- 2.38)%], and dexamethasone + mifepristone [(17.06 +/- 2.59)%] (P < 0.01).

CONCLUSIONSuppression of neutrophilic apoptosis seems to play a potential role in airway neutrophilic inflammation in severe asthmatics, and the level of IL-8 in sputum was significantly higher in patients with severe asthmatics.

Adolescent ; Apoptosis ; Asthma ; metabolism ; pathology ; physiopathology ; Case-Control Studies ; Child ; Female ; Humans ; Inflammation ; Interleukin-8 ; metabolism ; Leukocyte Count ; Male ; Neutrophils ; cytology ; Respiratory System ; metabolism ; pathology ; Sputum ; metabolism

OBJECTIVETo observe the effect of Wenyang Yiqi Pingchuan Recipe (WYPR) on the pathomorphology of lung and its regulation on lung tissue contents of nitric oxide (NO) and endothelin-1 (ET-1) in rats with bronchial asthma.

METHODSSixty SD rats were randomly divided into 6 groups: the normal group, the model group, and the four treated groups treated with high dose WYPR, low dose WYPR, Guilong Kechuanning Capsule and aminophylline, respectively, 10 in each group. Except those in the normal group, all rats of bronchial asthma model were established by egg protein sensitization and provocated by inhalation. The treatments were given via gastrogavage every day starting from the first provocation (the 3rd week of modeling) to the execution. Rats were sacrificed after 4-week treatment, their lung was taken for determining the contents of NO and ET-1, and histopathological changes in lung were observed as well.

RESULTSCompared with the normal group, the contents of NO and ET-1 in the lung tissue, the thickness of bronchus wall and bronchus smooth muscle, the number of eosinophil granulocytes increased in the model group and the low dose WYPR group, showing statistical significance (P < 0. 01). As compared with the model group, all the above-mentioned indices were lower in all the 4 treated groups (P < 0.05 or P < 0.01), but the lowering in the WYPR treated groups (either high or low dose) was more significant than in the Guilong Kechuanning treated group (P < 0.05 or P < 0.01); while compared with the aminophylline treated group, the high dose WYPR group was superior in reducing eosinophile granulocytes (P < 0.01), but no significance between them was shown in NO and ET-1 levels (P > 0.05).

CONCLUSIONSWYPR could reduce the eosinophilic infiltration, decrease the contents of NO and ET-1 in the lung tissue, restrain the air passage inflammation and inhibit the pathological process as airway remodeling.

Animals ; Asthma ; drug therapy ; Drugs, Chinese Herbal ; pharmacology ; Endothelin-1 ; metabolism ; Inflammation ; pathology ; Lung ; metabolism ; pathology ; Nitric Oxide ; metabolism ; Rats ; Rats, Sprague-Dawley

OBJECTIVETo explore the effect of different doses of 1,25-(OH)(2)VitD(3) early supplementation on airway inflammation and lung inflammatory factors in baby rats with asthma.

METHODSForty male weaned Wistar rats were divided into normal group, model group, low 1,25-(OH)(2)VitD(3) group, middle 1,25-(OH)(2)VitD(3) group, high 1,25-(OH)(2)VitD(3) group using random number table (8 rats each group). The rats in low, middle and high 1,25-(OH)(2)VitD(3) groups were given 1, 4, 10 µg/kg of 1,25-(OH)(2)VitD(3) every other day by intraperitoneal injection respectively for 25 days. Except normal group, the rats in other groups were challenged with ovalbumin to establish the asthma model. The pathologic changes of lung tissue, the total white blood cell and classified cell counts in bronchoalveolar lavage fluid (BALF) were measured. The concentrations of IL-4, IL-5 and IFN-γ in serum and BALF were measured by ELISA method.

RESULTSThe level of total white blood cell counts in BALF were (5.98 ± 1.67)×10(5)/ml, (25.34 ± 4.28)×10(5)/ml, (17.24 ± 3.3)×10(5)/ml, (9.31 ± 3.37)×10(5)/ml, (45.1 ± 15.75)×10(5)/ml, respectively (F = 33.453, P < 0.01). The percent ratio of EOS in BALF were (1.44 ± 0.78)%, (17.81 ± 6.88)%, (15.00 ± 5.70)%, (8.89 ± 3.66)%, (25.88 ± 5.57)%, respectively (F = 27.299, P < 0.01). The level of IL-4 in serum of normal, model, low, middle and high-1,25-(OH)(2)VitD(3) groups were (0.62 ± 0.54), (7.57 ± 1.04), (3.58 ± 0.56), (2.70 ± 0.78) and (5.27 ± 0.30) pg/ml, respectively (F = 116.287, P < 0.01); IL-5 in resume were (32.20 ± 4.23), (67.14 ± 18.14), (37.51 ± 0.47), (40.69 ± 2.47) and (124.60 ± 36.19) pg/ml, respectively (F = 23.902, P < 0.01); IFN-γ in serum were (79.71 ± 10.08), (49.06 ± 4.46), (59.15 ± 2.51), (59.27 ± 2.33) and (53.85 ± 1.97) pg/ml, respectively (F = 39.954, P < 0.01). Also in BLAF, the IL-4 of all groups were (0.51 ± 0.30), (102.92 ± 54.61), (8.64 ± 4.07), (3.10 ± 1.28) and (33.67 ± 8.1) pg/ml, respectively (F = 24.062, P < 0.01); the IFN-γ were (247.37 ± 189.18), (43.82 ± 13.76), (81.32 ± 17.07), (86.50 ± 14.26) and (59.89 ± 34.17) pg/ml, respectively (F = 7.157, P < 0.01); the IL-5 in BALF were (38.81 ± 0.60), (80.48 ± 17.90), (45.11 ± 1.33), (43.39 ± 1.11) and (149.60 ± 45.87) pg/ml, respectively (F = 35.978, P < 0.01). Pathologic changes in lung of asthma rat groups were obvious. The lung pathologic changes in low and middle dose groups showed a significant improvement compared to the asthma group and high dosage group showed more serious pathologic changes compared to the low and middle dose groups.

CONCLUSIONIntervention with appropriate dose of 1,25-(OH)(2)VitD(3) in the early life could improve lung pathologic changes and reduce the effect of inflammatory factors in air way of baby rat asthma model. However, overdose might play detrimental effect.

Animals ; Asthma ; metabolism ; pathology ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Interferon-gamma ; metabolism ; Interleukin-4 ; metabolism ; Interleukin-5 ; metabolism ; Lung ; metabolism ; pathology ; Male ; Pneumonia ; metabolism ; pathology ; Rats ; Rats, Wistar ; Vitamin D ; administration & dosage ; pharmacology

OBJECTIVE: To explore the regulatory role of COX-2 and aggregation of EOS in the pathogenesis of Aspirin triad syndrome. METHOD: There were 34 patients with ST (group 1), 30 patients with chronic sinusitis and nasal polyps and asthma (group 2), 30 patients with sinusitis (control group). Nasal polyps of 94 patients were obtained in endoscopic sinus surgery,HE staining and immunohistochemical SP staining were performed to detect the distribution of eosinophils(EOS) and the expression of COX-2. Statistical analysis was performed using the SPSS software and then the relationship between their expression and distribution with clinical pathology and pathogenesis was analyzed. RESULT: EOS infiltrated extensively in nasal polyps, and EOS counts in these groups were 80.02 +/- 6.11, 76.62 +/- 5.22, 65.97 +/- 4.78,respectively. The difference between ST group, ATA group and control group are significant (P < 0.05), no significant difference between ST group and ATA group. COX-2 in the nasal polyps was mainly expressed in submucosal glands, glandular epithelial cells, epithelial cells, endothelial cells and EOS in interstitium. The positive cell count were 88.13 +/- 6.26, 89.46 +/- 5.97, 91.22 +/- 4.11, respectively. There was significant difference (P < 0.05) between ST group and control group. No significant difference (P > 0.05) was found between ATA group and control group,ST group and ATA group. CONCLUSION The difference of EOS infiltration in patients with ST may be associated with an inflammatory response underlying specific clinical manifestations after exposure to non-steroidal anti-inflammatory drugs, and the difference of COX-2 expression in patients with ST may be related to the conversion of metabolic pathway of arachidonic acid and the formation of nasal polyps.
Adult ; Anti-Inflammatory Agents, Non-Steroidal ; adverse effects ; Aspirin ; adverse effects ; Asthma ; metabolism ; pathology ; Cyclooxygenase 2 ; metabolism ; Endoscopy ; Eosinophils ; pathology ; Female ; Humans ; Leukocyte Count ; Male ; Middle Aged ; Nasal Polyps ; metabolism ; pathology ; Paranasal Sinuses ; Sinusitis ; metabolism ; pathology

OBJECTIVETo study the role of urotension-II in serum and bronchoalveolar lavage fluid (BALF) in the process of airway remodelling in asthmatic rats.

METHODSThirty-two male Sprague-Dawley (SD) rats were randomly divided into normal control and 2-week, 4-week and 8-week asthmatic groups (OVA inhalation of 2, 4 and 8 weeks respectively). Rats were sensitized and challenged by OVA to establish a model of asthma. The bronchial wall thickness and the airway smooth muscle thickness were measured by image analysis system. The urotension-II contents in serum and BALF were determined using ELISA.

RESULTSThe bronchial wall thickness and the airway smooth muscle thickness in the three asthmatic groups significantly increased compared with those in the normal control group (P<0.01). The urotension-II contents in serum and BALF in the three asthmatic groups also increased significantly compared with those in the normal control group (P<0.01). The urotension-II contents in serum and BALF in the 8-week asthmatic group were the highest, followed by the 4-week and the 2-week asthmatic groups (P<0.01). BALF urotension-II contents were positively correlated with the bronchial wall thickness and the airway smooth muscle thickness as well as serum U-II contents in the four groups.

CONCLUSIONSThe urotension-II contents in serum and BALF in the process of airway remodeling increase in asthmatic rats. The changes in serum and BALF urotension-II contents may be associated with airway remodeling in asthmatic rats.

Airway Remodeling ; Animals ; Asthma ; metabolism ; pathology ; Bronchi ; pathology ; Bronchoalveolar Lavage Fluid ; chemistry ; Male ; Muscle, Smooth ; pathology ; Rats ; Rats, Sprague-Dawley ; Urotensins ; analysis ; blood

OBJECTIVEThymic stromal lymphopoietin (TSLP) plays an important role in initiating dendritic cell mediated allergic inflammation. This study was designed to examine the effects of inhaled budesonide on TSLP expression in the lung tissues and on the bronchial-pulmonary pathology in asthmatic rats.

METHODSThirty-two female Sprague-Dawley rats were sensitized and challenged with inhaled ovalbumin (OVA) to induce asthma. The asthmatic rats were randomly divided into 2 groups on the 22nd day of OVA challenge: a budesonide treatment group that received inhaled budesonide at 0.32 mg/kg daily for 7 days and an asthma control group that received inhaled 0.9% normal saline for 7 days. TSLP expression in the lung tissues was measured by Western blot and fluorescent-immunohistochemistry 29 and 36 days after OVA challenge. Bronchial-pulmonary pathological changes were evaluated by hematoxylin & eosin and periodic acid-schiff staining.

RESULTSBudesonide treatment alleviated airway inflammation when compared with the asthma control group 29 days after OVA challenge. However, the airway inflammatory reactions were aggravated in the budesonide treatment group 36 days after OVA challenge (7 days after budesonide discontinuance). TSLP expression in the lung tissues was significantly lower in the budesonide treatment group than that in the asthma control group both 29 and 36 days after OVA challenge (P<0.05).

CONCLUSIONSInhaled budesonide can inhibit the TSLP expression in the lung tissues and alleviate lung inflammatory reactions in asthmatic rats, but there is end-of-dose failure.

Administration, Inhalation ; Animals ; Asthma ; drug therapy ; metabolism ; pathology ; Blotting, Western ; Bronchi ; pathology ; Budesonide ; administration & dosage ; Cytokines ; analysis ; Female ; Immunohistochemistry ; Lung ; pathology ; Rats ; Rats, Sprague-Dawley

AIMTo explore the expression of heme oxygenase-1 (HO-1) in the peripheral blood mononuclear cell (PBMC) and relationship to ventilatory function in asthmatic patients.

METHODSEighteen asthmatic patients and eighteen healthy subjects were selected. HO-1 protein levels in PBMC were measured by immunohistochemical staining and PBMC HO-1 mRNA were determined by reverse transcription-polymerase chain reaction (RT-PCR), blood carbon monoxide Hb (COHb) percent value, serum total IgE concentration and pulmonary ventilatory function were observed in asthmatic patients and healthy subjects.

RESULTSThe percentage of cells in immunohistochemical staining positive staining of HO-1 were significantly higher in asthmatic patients (41.7 +/- 7.44%) compared with that of healthy subjects (10.5 +/- 4.36%, P < 0.01), the optical densities of PBMC HO-1 mRNA were higher in asthmatic patients (26.05 +/- 4.14) compared with that of healthy subjects (10.82 +/- 4.26, P < 0.01). The relation analysis showed PBMC HO-1 protein levels had significantly negative relation with FEV1, PEFR, MEFR50%, respectively (r = -0.89, -0.56, -0.51, P < 0.01, respectively) and positive relation with COHb percent value, serum total I gE concentration (r = 0.80, 0.48, P < 0.05, respectively), and PBMC HO-1 mRNA levels had significantly negative relation with FEV1, PEFR, MEFR50%, respectively (r = -0.89, -0.65, -0.67, P < 0.05, respectively) and positive relation with COHb percent value, serum total IgE concentration (r = 0.85, 0.62, P < 0.01, respectively).

CONCLUSIONThe expression of PBMC HO-1 protein and mRNA are increased significantly in asthmatic patients, HO-1 may play a significant role in the pathogenesis of asthma. The expression of HO-1 has relation with severity of asthma.

Adult ; Asthma ; blood ; pathology ; Case-Control Studies ; Female ; Heme Oxygenase-1 ; blood ; Humans ; Leukocytes, Mononuclear ; metabolism ; Male ; Middle Aged

OBJECTIVETo investigate the activation of Toll like receptor 4 (TLR4) on passively sensitized human airway smooth muscle cells (HASMCs) proliferation and the synthesis and secretion function.

METHODSThrough the cultivation of primary HASMCs, we studied TLR4 expression on cell surface, cell proliferation and transformation of parturient factor-beta1 (TGF-beta1) in asthma under the condition of synthesis and secretion level by passively sensitized HASMCs with asthma serum.

RESULTSCompared with the control group, in passive sensitized group and TNF-alpha group TLR4 expression were significantly increased (P < 0.01), significantly enhanced proliferation (P < 0.01), total protein concentration, IgE secretion and TGF-beta1 were significantly higher (P < 0.01); and all the above parameters were increased more significantly in TNF group compared with those in the target effect of passively group; and those parameters were significantly reduced in anti-TLR4 antibody group compared with those in the target effect both of passively sensitized group and TNF-alpha group.

CONCLUSIONTLR4 on passively sensitized HASMCs activated can induce the excessive proliferation of HASMCs and a large number of synthesis and secretion of TGF-beta1, resulting in changing airway micro-environment, which involved in airway remodeling in asthma.

Airway Remodeling ; Asthma ; metabolism ; pathology ; Bronchi ; cytology ; Cell Proliferation ; Cells, Cultured ; Humans ; Myocytes, Smooth Muscle ; cytology ; metabolism ; Toll-Like Receptor 4 ; immunology ; Transforming Growth Factor beta1 ; metabolism