Mucociliary clearance system is the primary innate defense mechanism of the lung. It plays a vital role in protecting airways from microbes and irritants infection. Mucociliary clearance system, which is mediated by the actions of airway and submucosal gland epithelial cells, plays a critical role in a multilayered defense system via secreting fluids, electrolytes, antimicrobial and anti-inflammatory proteins, and mucus onto airway surfaces. Changes in environment, drugs or diseases can lead to mucus overproduction and cilia dysfunction, which in turn decrease the rate of mucociliary clearance and enhance mucus gathering. The dysfunction of mucociliary clearance system often occurs in several respiratory diseases, such as primary ciliary dysfunction, cystic fibrosis, asthma and chronic obstructive pulmonary disease, which are characterized by goblet cell metaplasia, submucosal gland cell hypertrophy, mucus hypersecretion, cilia adhesion, lodging and loss, and airway obstruction.
Humans ; Mucociliary Clearance ; Respiratory Tract Diseases ; Pulmonary Disease, Chronic Obstructive/metabolism* ; Mucus/metabolism* ; Lung ; Respiratory System

OBJECTIVETo investigate the effect of noninvasive positive pressure ventilation( NIPPy) on the gene and protein expression of biquitin-proteasome of skeletal muscle in patients with acute exacerbation of chronic obstructive pulmonary disease(AECOPD).

METHODSSeven patients with AECOPD by NIPPV were used as the study group, meanwhile, 6 patients with AECOPD who refused NIPPV was the control group. The blood gas analysis, heart rate (HR) and mean arterial pressure (MBp) were monitored before and 14 days after treatment. A skeletal muscle biopsy was performed after 14 days of therapy. The mRNA expression of ribosomal protein S21 (RPS21), Ubiquitin, Ubiquitin combined with enzyme E2 (E2), Ubiquitin ligase E3 (E3) in skeletal muscle cell were measured by RT-PCR. The protein expression of mitochondrial aconitase (AC02), protease C3 (C3), ribosomal protein SLC16 (SLC16) were detected by Western blot.

RESULTSForteen days after treatment, the patients in NIPPV group got much better improvement in PaCO2, PaO2 and HR than that of the patients.in the control group (P < 0.05). The gene expression of RPS21,Ubiquitin, E2 and E3 in skeletal muscle cell on patients with NIPPV were obviously lower than that of the control group (P < 0.05, P < 0.01). Compared with that of the control group, the protein expression of C3 and AC2 increased significantly in the NIPPV group (P < 0.01). The protein expression of SLC16 was significantly lowered in the treated group (P < 0.01).

CONCLUSIONNIPPV can ameliorate the proteasome pathway and energy metabolic disorders in patients with AECOPD.

Humans ; Muscle, Skeletal ; metabolism ; Positive-Pressure Respiration ; Proteasome Endopeptidase Complex ; metabolism ; Pulmonary Disease, Chronic Obstructive ; metabolism ; therapy ; Ubiquitin ; metabolism

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

BACKGROUNDThe relationship between chronic obstructive pulmonary disease (COPD) and coronary artery disease (CAD) remains largely unknown. This study aimed to explore the association of COPD with CAD, especially with multi-vessel disease (VD).

METHODSThe data of 354 patients who underwent multi-detector computed tomography (MDCT) for suspected CAD were analyzed. Luminal narrowing was defined as at least one lesion 50% or greater stenosis. The analysis of serum biochemistry profile and spirometry were performed on all eligible patients, and the diagnosis of COPD was defined as the criteria of Global Initiative for Chronic Obstructive Lung Disease.

RESULTSPatients with CAD had a significantly higher complication of COPD than those without CAD (11.8% vs. 3.7%, P < 0.001). Comparing with patients without COPD, those with COPD were more likely to have multi-VD, proportion of smoking and high C-reactive protein (CRP) (P < 0.001). Multivariate Logistic regression analysis revealed that the multi-VD was significantly correlated with COPD (P=0.012) and CRP (P=0.015).

CONCLUSIONSThere was a high complication of COPD in patients with CAD, and COPD may be a critical risk factor for CAD, especially for multi-VD. CAD and COPD were closely associated and the interplay of systemic inflammation might in part explain the relationship between them.

Coronary Artery Disease ; complications ; diagnostic imaging ; metabolism ; Humans ; Pulmonary Disease, Chronic Obstructive ; complications ; diagnostic imaging ; metabolism ; Radiography ; Risk Factors

OBJECTIVETo investigate the protective and therapeutic effects of pulmonary surfactant in the pathogenesis of chronic obstructive pulmonary disease (COPD) in hamsters.

METHODSCOPD animal model was established by smoke inhalations and intratracheal instillations of pancreatic elastase in hamsters. Ninty hamsters were divided into 9 groups as follows: normal group (N), two groups received smoke inhalations for 1 and 3 months (S1 and S3), one group received intratracheal instillation of surfactant (10 mg/100 g BW) for once after 1 month smoking (SP1), one group was treated with surfactant after 1.5, 2 and 2.5 months of smoking (SP3), and two groups received intratracheal administration of elastase (40 U/100 g BW) and were killed after 1 month and 3 months, respectively (E1 and E3). The surfactant was injected intratracheally after 1 week, 0.5, 1.0, 1.5, 2.0, and 2.5 months, followed by administration with elastase (EP1 and EP3). EP1 group were killed at the first month, and EP3 at the third month. Light microscopy and electromicroscopy observations were performed in each group. Pulmonary mean linear intercept (MLI), mean alveolar numbers (MAN), and pulmonary alveolar area (PAA) was measured by image analysis. The expression of surfactant protein A (SP-A) were observed by immunohistochemistry.

RESULTSSmoking for 3 months and instillations of elastase resulted in chronic bronchitis and emphysema. MLI and PAA increased and MAN decreased in all the experimental groups compared with in the normal group (P < 0.05 or P < 0.01). Administration of surfactant for 3 months resulted in statistically significant inhibition of pulmonary injury. MLI and PAA decreased and MAN increased in SP3 compared with in S3. Only MLI decreased in EP3 compared with E3. The expressions of SP-A in the type II alveolar epithelia decreased in S3 and E3 (compared with the normal group P < 0.01). After pulmonary surfactant intervention, the expression of SP-A increased significantly.

CONCLUSIONPulmonary surfactant may have a long-term protective effect on chronic smoking and elastase-induced COPD.

Animals ; Cricetinae ; Male ; Mesocricetus ; Pancreatic Elastase ; Pulmonary Alveoli ; ultrastructure ; Pulmonary Disease, Chronic Obstructive ; metabolism ; prevention & control ; Pulmonary Surfactant-Associated Protein A ; metabolism ; Pulmonary Surfactants ; therapeutic use ; Smoking

AIMTo elucidate the location and effects of transcription factor-nuclear factor-kappaB (NF-kappaB) in lung tissues of rats with chronic obstructive pulmonary disease (COPD).

METHODSFourteen male Wistar rats were randomly divided into COPD model and control groups equally. The COPD model was established by intratracheal instillation of lipopolysaccharide twice and exposure to cigarette smoke daily. We detected the NF-kappaB p65 protein in lung by immunohistochemical method, and the expression of NF-kappaB p65 mRNA in lung by in situ hybridization.

RESULTSImmunohistochemistry, the expression of NF-kappaB p65 protein in alveolar, bronchiolar epithelium and arteriolar endothelium was significantly higher in the COPD group (0.426 +/- 0.007, 0.434 +/- 0.012 and 0.313 +/- 0.007, respectively) than those of the control group (0.115 +/- 0.006, 0.116 +/- 0.005 and 0.095 +/- 0.007, respectively, all P < 0.01). In situ hybridization showed that the expressions of NF-kappaB p65 mRNA in alveolar epithelium (0.203 +/- 0.008), bronchiolar and arteriolar smooth muscle cell (0.208 + 0. 010 and 0.206 + 0.007) of rats in the COPD group were stronger than those in the control group (0.100 +/- 0.006, 0.102 +/- 0.002 and 0.103 +/- 0.003 respectively) by semiquantitative analysis (all P < 0.01).

CONCLUSIONThe expression and nuclear translocation of NF-kappaB may be the basis event of gene expression of many cytokines and inflammatory mediators, which may positively regulate gene expression of many cytokines and inflammatory mediators in various cell lines.

Animals ; Lung ; metabolism ; pathology ; Male ; Pulmonary Disease, Chronic Obstructive ; metabolism ; pathology ; Rats ; Rats, Wistar ; Transcription Factor RelA ; metabolism

OBJECTIVETo explore the expressions of glucocorticoid receptor (GCR) and nuclear factor-kappaB (NF-kappaB) in patients with stable chronic obstructive pulmonary disease (COPD).

METHODSBronchial biopsies and blood specimens were obtained from 8 smokers with stable COPD (COPD group) and 8 nonsmokers with normal lung function (control group). The expressions of NF-kappaB and GCR in nucleus protein of bronchial biopsies and peripheral blood lymphocyte from these two groups were examined by Western blot.

RESULTSThe expressions of GCR in nuclear protein of peripheral blood lymphocyte and the bronchial biopsies, especially in bronchi, were significantly lower in COPD group than in control group (P<0.05, P <0.01). Also, the expressions of NF-kappaB in nuclear proteins of the bronchial biopsies and peripheral blood lymphocyte were significantly higher in COPD group than in control group (P<0.05). The expressions of NF-kappaB and GCR were significantly higher in bronchial biopsies than in peripheral blood lymphocyte in both groups (P<0.05, P<0.01).

CONCLUSIONChronic inflammation, especially airway inflammation, still exists in patients with stable COPD, as suggested by the different expressions of GCR and NF-kappaB between COPD patients and normal controls.

Aged ; Female ; Humans ; Male ; Middle Aged ; NF-kappa B ; metabolism ; Pulmonary Disease, Chronic Obstructive ; metabolism ; Receptors, Glucocorticoid ; metabolism

Numerous randomised controlled trials have suggested the positive effects of acupuncture on chronic obstructive pulmonary disease (COPD). However, the underlying therapeutic mechanisms of acupuncture for COPD have not been clearly summarized yet. Inflammation is central to the development of COPD. In this review, we elucidate the effects and underlying mechanisms of acupuncture from an anti-inflammatory perspective based on animal studies. Cigarette smoke combined with lipopolysaccharide is often used to establish animal models of COPD. Electroacupuncture can be an effective intervention to improve inflammation in COPD, and Feishu (BL13) and Zusanli (ST36) can be used as basic acupoints in COPD animal models. Different acupuncture types can regulate different types of inflammatory cytokines; meanwhile, different acupuncture types and acupoint options have similar effects on modulating the level of inflammatory cytokines. In particular, acupuncture exerts anti-inflammatory effects by inhibiting the release of inflammatory cells, inflammasomes and inflammatory cytokines. The main underlying mechanism through which acupuncture improves inflammation in COPD is the modulation of relevant signalling pathways: nuclear factor-κB (NF-κB) (e.g., myeloid differentiation primary response 88/NF-κB, toll-like receptor-4/NF-κB, silent information regulator transcript-1/NF-κB), mitogen-activated protein kinase signalling pathways (extracellular signal-regulated kinase 1/2, p38 and c-Jun NH2-terminal kinase), cholinergic anti-inflammatory pathway, and dopamine D2 receptor pathway. The current synthesis will be beneficial for further research on the effect of acupuncture on COPD inflammation. Please cite this article as: Jiang LH, Li PJ, Wang YQ, Jiang ML, Han XY, Bao YD, Deng XL, Wu WB, Liu XD. Anti-inflammatory effects of acupuncture in the treatment of chronic obstructive pulmonary disease. J Integr Med. 2023; 21(6): 518-527.
Animals ; NF-kappa B/metabolism* ; Pulmonary Disease, Chronic Obstructive/drug therapy* ; Acupuncture Therapy ; Cytokines ; Disease Models, Animal ; Inflammation/therapy*

Adiponectin ; blood ; metabolism ; Cytokines ; blood ; Female ; Humans ; Male ; Oxidation-Reduction ; Protein Isoforms ; blood ; metabolism ; Pulmonary Disease, Chronic Obstructive ; blood

BACKGROUNDPulmonary hypertension (PH) is a common complication of chronic obstructive pulmonary disease (COPD). Although alveolar hypoxia is considered as a main cause of PH in COPD, structural and functional changes of pulmonary circulation are apparent at the initial stage of COPD. We hypothesized that an inflammatory response and oxidative stress might contribute to the formation of PH in COPD.

METHODSWe measured the levels of interleukin-6 (IL-6) and 8-iso-prostaglandin (8-iso-PSG) in exhaled breath condensate (EBC) and serum in 40 patients with COPD only or in 45 patients with COPD combined with PH. Pulmonary arterial systolic pressure (PASP) was assessed by Doppler echocardiography and defined as PH when the value of systolic pressure was greater than 40 mmHg.

RESULTSCompared with the COPD only group, the level of IL-6 in EBC was significantly increased in all 45 patients with COPD combined with PH ((8.27±2.14) ng/L vs. (4.95±1.19) ng/L, P < 0.01). The level of IL-6 in serum was also elevated in patients with COPD combined with PH compared with the COPD only group ((72.8±21.6) ng/L vs. (43.58±13.38) ng/L, P < 0.01). Similarly, we also observed a significant increase in the level of 8-iso-PSG in both EBC and serum in the COPD with PH group, compared with the COPD only group (EBC: (9.00±2.49) ng/L vs. (5.96±2.31) ng/L, P < 0.01 and serum: (41.87±9.75) ng/L vs. (27.79±11.09) ng/L, P < 0.01). Additionally, the value of PASP in the PH group was confirmed to be positively correlated with the increase in the levels of IL-6 and 8-iso-PSG in both EBC and serum (r = 0.477-0.589, P < 0.05).

CONCLUSIONThe increase in the levels of IL-6 and 8-iso-PSG in EBC and serum correlates with the pathogenesis of PH in COPD.

Aged ; Breath Tests ; Female ; Humans ; Hypertension, Pulmonary ; blood ; metabolism ; Interleukin-6 ; blood ; metabolism ; Male ; Middle Aged ; Prostaglandins A ; blood ; metabolism ; Pulmonary Disease, Chronic Obstructive ; blood ; metabolism