Objective To investigate the relationship between intestinal inflammatory group 2 innate lymphoid cells (iILC2s) and lung ILC2s and its inflammatory response in chronic obstructive pulmonary disease (COPD). Methods Mouse COPD model was established by smoking method. The mice were randomly divided into normal group and COPD group. HE staining was used to detect the pathological changes in lung and intestine tissues of mice in normal group and COPD group, and the contents of natural ILC2s(nILC2s) and iILC2s cells were measured by flow cytometry. Wright-Giemsa staining was used to measure the number of immune cells in the bronchoalveolar lavage fluid (BALF) of mice in normal group and COPD group, and the concentration of IL-13 and IL-4 was detected by ELISA. Results In COPD mice, epithelial cells of the lung and intestinal tissues exhibited pathological hyperplasia, partial atrophy or deletion, inflammatory cell infiltration, increased pathological score and significantly increased neutrophils, monocytes, and lymphocytes in BALF. Lung iILC2s, intestinal nILC2s and iILC2s were increased significantly in the COPD group. The contents of IL-13 and IL-4 in BALF were significantly increased. Conclusion The increase of iILC2s and their related cytokines in COPD lung may be related to intestinal inflammatory ILC2s.
Mice ; Animals ; Cytokines ; Immunity, Innate ; Interleukin-13 ; Interleukin-4 ; Lymphocytes ; Lung/pathology* ; Pulmonary Disease, Chronic Obstructive ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal ; Intestines

Objective: To compare the incidence of radiation-related toxicities between conventional and hypofractionated intensity-modulated radiation therapy (IMRT) for limited-stage small cell lung cancer (SCLC), and to explore the risk factors of hypofractionated radiotherapy-induced toxicities. Methods: Data were retrospectively collected from consecutive limited-stage SCLC patients treated with definitive concurrent chemoradiotherapy in Cancer Hospital of Chinese Academy of Medical Sciences from March 2016 to April 2022. The enrolled patients were divided into two groups according to radiation fractionated regimens. Common Terminology Criteria for Adverse Events (CTCAE, version 5.0) was used to evaluate the grade of radiation esophagus injuries and lung injuries. Logistic regression analyses were used to identify factors associated with radiation-related toxicities in the hypofractionated radiotherapy group. Results: Among 211 enrolled patients, 108 cases underwent conventional IMRT and 103 patients received hypofractionated IMRT. The cumulative incidences of acute esophagitis grade ≥2 [38.9% (42/108) vs 35.0% (36/103), P=0.895] and grade ≥ 3 [1.9% (2/108) vs 5.8% (6/103), P=0.132] were similar between conventional and hypofractionated IMRT group. Late esophagus injuries grade ≥2 occurred in one patient in either group. No differences in the cumulative incidence of acute pneumonitis grade ≥2[12.0% (13/108) vs 5.8% (6/103), P=0.172] and late lung injuries grade ≥2[5.6% (6/108) vs 10.7% (11/103), P=0.277] were observed. There was no grade ≥3 lung injuries occurred in either group. Using multiple regression analysis, mean esophageal dose ≥13 Gy (OR=3.33, 95% CI: 1.23-9.01, P=0.018) and the overlapping volume between planning target volume (PTV) and esophageal ≥8 cm(3)(OR=3.99, 95% CI: 1.24-12.79, P=0.020) were identified as the independent risk factors associated with acute esophagitis grade ≥2 in the hypofractionated radiotherapy group. Acute pneumonitis grade ≥2 was correlated with presence of chronic obstructive pulmonary disease (COPD, P=0.025). Late lung injuries grade ≥2 was correlated with tumor location(P=0.036). Conclusions: Hypofractionated IMRT are tolerated with manageable toxicities for limited-stage SCLC patients treated with IMRT. Mean esophageal dose and the overlapping volume between PTV and esophageal are independently predictive factors of acute esophagitis grade ≥2, and COPD and tumor location are valuable factors of lung injuries for limited-stage SCLC patients receiving hyofractionated radiotherapy. Prospective studies are needed to confirm these results.
Humans ; Small Cell Lung Carcinoma/pathology* ; Lung Neoplasms/pathology* ; Radiotherapy, Intensity-Modulated/methods* ; Retrospective Studies ; Lung Injury ; Radiotherapy Dosage ; Radiation Injuries/epidemiology* ; Esophagitis/epidemiology* ; Risk Factors ; Pulmonary Disease, Chronic Obstructive/complications*

Macrophages are highly plastic and can be polarized into classical activated macrophages (M1) and alternative activated macrophages (M2) under the induction of inflammatory factors and regulation of a variety of information molecules. Chronic pulmonary inflammation and pulmonary parenchyma injury are the main pathological manifestations of chronic obstructive pulmonary disease (COPD). M1 promotes pulmonary inflammation, whereas M2 inhibits inflammatory response, participates in lung tissue injury and repair, and swallows and removes pathogenic microorganisms and apoptotic cells. Target intervention in the polarization direction of macrophages may be a new strategy for COPD treatment.
Humans ; Lung ; Macrophages ; cytology ; Pulmonary Disease, Chronic Obstructive ; pathology

We investigated the anti-inflammatory effect of Pyunkang-tang extract (PGT), a complex herbal extract based on traditional Chinese medicine that is used in Korea for controlling diverse pulmonary diseases, on cigarette smoke-induced pulmonary pathology in a rat model of chronic obstructive pulmonary disease (COPD). The constituents of PGT were Lonicerae japonica, Liriope platyphylla, Adenophora triphilla, Xantium strumarinum, Selaginella tamariscina and Rehmannia glutinosa. Rats were exposed by inhalation to a mixture of cigarette smoke extract (CSE) and sulfur dioxide for three weeks to induce COPD-like pulmonary inflammation. PGT was administered orally to rats and pathological changes to the pulmonary system were examined in each group of animals through measurement of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) levels in bronchoalveolar lavage fluid (BALF) at 21 days post-CSE treatment. The effect of PGT on the hypersecretion of pulmonary mucin in rats was assessed by quantification of the amount of mucus secreted and by examining histopathologic changes in tracheal epithelium. Confluent NCI-H292 cells were pretreated with PGT for 30 min and then stimulated with CSE plus PMA (phorbol 12-myristate 13-acetate), for 24 h. The MUC5AC mucin gene expression was measured by RT-PCR. Production of MUC5AC mucin protein was measured by ELISA. The results were as follows: (1) PGT inhibited CSE-induced pulmonary inflammation as shown by decreased TNF-α and IL-6 levels in BALF; (2) PGT inhibited the hypersecretion of pulmonary mucin and normalized the increased amount of mucosubstances in goblet cells of the CSE-induced COPD rat model; (3) PGT inhibited CSE-induced MUC5AC mucin production and gene expression in vitro in NCI-H292 cells, a human airway epithelial cell line. These results suggest that PGT might regulate the inflammatory aspects of COPD in a rat model.
Animals ; Bronchoalveolar Lavage Fluid ; Campanulaceae ; Enzyme-Linked Immunosorbent Assay ; Epithelial Cells ; Epithelium ; Gene Expression ; Goblet Cells ; Humans ; In Vitro Techniques ; Inflammation ; Inhalation ; Interleukin-6 ; Korea ; Lonicera ; Lung Diseases ; Medicine, Chinese Traditional ; Models, Animal ; Mucins ; Mucus ; Necrosis ; Pathology ; Pneumonia ; Pulmonary Disease, Chronic Obstructive ; Rats ; Rehmannia ; Selaginellaceae ; Smoke ; Sulfur Dioxide ; Tobacco Products

Chronic obstructive pulmonary disease (COPD) is a type of progressive lung disease, featured by airflow obstruction. Recently, a comprehensive analysis of the transcriptome in lung tissue of COPD patients was performed, but the heterogeneity of the sample was not seriously considered in characterizing the mechanistic dysregulation of COPD. Here, we established a new transcriptome analysis pipeline using a deconvolution process to reduce the heterogeneity and clearly identified that these transcriptome data originated from the mild or moderate stage of COPD patients. Differentially expressed or co-expressed genes in the protein interaction subnetworks were linked with mitochondrial dysfunction and the immune response, as expected. Computational protein localization prediction revealed that 19 proteins showing changes in subcellular localization were mostly related to mitochondria, suggesting that mislocalization of mitochondria-targeting proteins plays an important role in COPD pathology. Our extensive evaluation of COPD transcriptome data could provide guidelines for analyzing heterogeneous gene expression profiles and classifying potential candidate genes that are responsible for the pathogenesis of COPD.
Gene Expression Profiling ; Humans ; Lung ; Lung Diseases ; Mitochondria ; Pathology ; Population Characteristics ; Pulmonary Disease, Chronic Obstructive ; Transcriptome

Adult ; Aged ; Antifungal Agents ; administration & dosage ; adverse effects ; classification ; Candida ; drug effects ; isolation & purification ; Carcinoma ; pathology ; therapy ; Cross Infection ; microbiology ; therapy ; Drug Resistance, Multiple, Fungal ; Female ; Fractures, Bone ; surgery ; Humans ; Male ; Middle Aged ; Mycoses ; microbiology ; therapy ; Patient Care Management ; methods ; Pulmonary Disease, Chronic Obstructive ; complications ; therapy ; Surgical Wound Infection ; microbiology ; therapy ; Symptom Flare Up ; Treatment Outcome

Adrenal Cortex Hormones ; metabolism ; Adrenergic beta-2 Receptor Agonists ; metabolism ; Humans ; Multiple Pulmonary Nodules ; diagnosis ; metabolism ; pathology ; Pulmonary Disease, Chronic Obstructive ; diagnosis ; metabolism ; pathology ; World Health Organization

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

PURPOSE: Recent experimental evidence shows that extracellular vesicles (EVs) in indoor dust induce neurtrophilic pulmonary inflammation, which is a characteristic pathology in patients with severe asthma and chronic obstructive pulmonary disease (COPD). In addition, COPD is known to be an important risk factor for lung cancer, irrespective of cigarette smoking. Here, we evaluated whether sensitization to indoor dust EVs is a risk for the development of asthma, COPD, or lung cancer. METHODS: Serum IgG antibodies against dust EVs were measured in 90 healthy control subjects, 294 asthmatics, 242 COPD patients, and 325 lung cancer patients. Serum anti-dust EV IgG titers were considered high if they exceeded a 95 percentile value of the control subjects. Age-, gender-, and cigarette smoke-adjusted multiple logistic regression analyses were performed to determine odds ratios (ORs) for asthma, COPD, and lung cancer patients vs the control subjects. RESULTS: In total, 4.4%, 13.6%, 29.3%, and 54.9% of the control, asthma, COPD, and lung cancer groups, respectively, had high serum anti-dust EV IgG titers. Adjusted multiple logistic regression revealed that sensitization to dust EVs (high serum anti-dust EV IgG titer) was an independent risk factor for asthma (adjusted OR, 3.3; 95% confidence interval [CI], 1.1-10.0), COPD (adjusted OR, 8.0; 95% CI, 2.0-32.5) and lung cancer (adjusted OR, 38.7; 95% CI, 10.4-144.3). CONCLUSIONS: IgG sensitization to indoor dust EVs appears to be a major risk for the development of asthma, COPD, and lung cancer.
Antibodies ; Asthma* ; Dust* ; Humans ; Immunoglobulin G* ; Logistic Models ; Lung Neoplasms* ; Lung* ; Odds Ratio ; Pathology ; Pneumonia ; Prevalence* ; Pulmonary Disease, Chronic Obstructive* ; Risk Factors ; Smoking ; Tobacco Products

BACKGROUNDOsteoporosis is a common complication of chronic obstructive pulmonary disease (COPD). Recent clinical and biological researches have increasingly delineated the biomolecular pathways of bone metabolism regulation in COPD. We extended this work by examining the specific association and potential contribution of the osteoprotegerin (OPG)/receptor activator of nuclear factor-κB ligand (RANKL) axis to the pathogenesis of osteoporosis in advanced COPD. The aim of this study was to assess the relationships of serum OPG, RANKL, and tumor necrosis factor-alpha (TNF-μ) with bone turnover in men with very severe COPD.

METHODSPulmonary function, T-score at the lumbar spine (LS) and femoral neck (FN), serum OPG, RANKL, soluble receptor of tumor necrosis factor-alpha-I and II (sTNFR-I, sTNFR-II), osteocalcin (OC), and β-CrossLaps (βCL) levels were measured in 45 men with very severe stage COPD and 36 male non-COPD volunteers. COPD patients and healthy controls were compared using an independent t-test and Mann-Whitney U-test. The Pearson coefficient was used to assess the relationships between variables.

RESULTSOPG and OC were lower in male COPD patients than in control subjects whereas RANKL, serum βCL, TNF-μ, and its receptors were higher. OPG directly correlated with forced expiratory volume in 1 s (FEV1) % predicted (r = 0.46, P < 0.005), OC (r = 0.34, P < 0.05), LS (r = 0.56, P < 0.001), and FN T-score (r = 0.47, P < 0.01). In contrast, serum RANKL inversely associated with LS and FN T-score (r = -0.62, P < 0.001 and r = -0.48, P < 0.001) but directly correlated with βCL (r = 0.48, P < 0.001). In addition, OPG was inversely correlated with RANKL (r = -0.39, P < 0.01), TNF-μ (r = -0.56, P < 0.001), and sTNFR-I (r = -0.40, P < 0.01).

CONCLUSIONOur results suggest that serum OPG and RANKL levels are inversely associated with bone loss in men with advanced stage COPD.

Bone Density ; physiology ; Cross-Sectional Studies ; Humans ; Male ; Middle Aged ; Osteoporosis ; metabolism ; pathology ; Osteoprotegerin ; metabolism ; Pulmonary Disease, Chronic Obstructive ; metabolism ; pathology ; RANK Ligand ; metabolism ; Respiratory Function Tests ; Tumor Necrosis Factor-alpha ; metabolism