Pathogenesis of respiratory inflammation (original) (raw)
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Airways Inflammation and COPD *
CHEST Journal, 2002
Neutrophils are recognized as major cellular mediators of inflammation. They contain specific and highly regulated mechanisms for controlling the expression of adhesion molecules that allow for their tethering and migration into inflammatory sites. These adhesion molecules not only are activated by exogenous pollutants but are regulated by endothelial and epithelial cell signals. Lipid mediators, such as platelet-activating factor, reactive oxygen and nitrogen species, and cytokines from airway epithelial cells, further control neutrophil functions such as infiltration and activation resulting in an increase in respiratory burst activity and release of granule enzymes, such as elastase. Furthermore, virus and bacteria products affect inflammation by increasing secondary epithelial mediators. However, once the endogenous or exogenous agents are expelled, neutrophil populations are programmed to die and are cleared by macrophage phagocytosis.
Lung inflammation in COPD: why does it matter?
F1000 Medicine Reports, 2012
COPD is characterized by lung inflammation, which intensifies with disease progression. Recent studies suggest that COPD has multiple phenotypes, each with a distinct molecular pathway. Proteolytic enzymes may have a prominent role in the emphysematous phenotype, while nitric oxide pathways may be more relevant for pulmonary vessel remodelling in COPD. This article provides a synopsis of the possible role that lung inflammation plays in the pathogenesis of COPD.
Sarcoidosis, vasculitis, and diffuse lung diseases : official journal of WASOG / World Association of Sarcoidosis and Other Granulomatous Disorders, 2003
The presence of a heterogeneous infiltrate of macrophages, neutrophils and CD8+ Tc1 cells is a characteristic feature in the lung of patients with chronic obstructive pulmonary disease (COPD). This paper points out the contribution of different inflammatory cells and mediators to the pathogenesis and natural history of COPD. We will comment on data suggesting that CD8 cytotoxic T cells with an activated Tc1 phenotype migrate from the secondary lymphoid tissue to pulmonary tissue damaged by smoke or infective agents. On the basis of the knowledge of the pathophysiology of immunologic events, drugs that can potentially block the inflammation leading to the disability of COPD are being investigated. Long-term study in a large number of patients with COPD will be needed to verify the impact of a number of anti-inflammatory compounds in this increasingly common disease.
Airway epithelial inflammatory responses and clinical parameters in COPD
European Respiratory Journal, 2003
This study examined inflammatory responses from primary cultured human bronchial epithelial cells in chronic obstructive pulmonary disease (COPD) and the clinical factors modulating them. Epithelial cells from bronchoscopic biopsies from 14 patients with COPD ((mean ¡ SD) age 74.6 ¡ 5.7 yrs, forced expiratory volume in one second (FEV1) 1.21¡0.36 L, FEV1 % predicted 51.1¡15.8%, 51.5¡24.0 pack-yrs of smoking, inhaled steroid dosage 1237.5¡671.0 mg?day-1 , Medical Research Council (MRC) dyspnoea score 3.18¡1.33) and eight current/exsmokers with normal pulmonary function (age 60.4¡13.5 yrs, FEV1 2.66¡1.27 L, FEV1 % pred 89.6¡17.7%, 49¡44 pack-yrs of smoking, MRC dyspnoea score 1¡0) were grown in primary culture and exposed to 50 ng?mL-1 tumour necrosis factor-a. Stimulated COPD cells produced significantly more interleukin (IL)-6 at 24 and 48 h, and IL-8 at 6 and 24 h than unstimulated COPD cells. This response was not seen in cells from current/exsmokers. IL-6 and IL-8 production was lower in COPD patients taking inhaled steroids. Following an inflammatory stimulus, bronchial epithelial cells in chronic obstructive pulmonary disease show a significant cytokine response not seen in smokers with normal pulmonary function and this may be modified by inhaled steroid therapy.
Profiling cellular and inflammatory changes in the airway wall of mild to moderate COPD
Respirology (Carlton, Vic.), 2017
The objective of this study was to enumerate total cells and the number of inflammatory cell differentials in large airways (LAs) versus small airways (SAs) of mild-moderate COPD, and against appropriate controls. For LA, we used endobronchial biopsies and for SA resected lung tissues. Immunostaining was enumerated (cells per mm(2) ) for macrophages, neutrophils, CD4 and CD8 T cells in the lamina propria (LP) up to 150 µM deep for LA and full wall thickness for SA. We confirmed hypocellularity in the LA and in the SA wall in smokers and COPD (P < 0.001). LA cellularity was least in current smokers with COPD (COPD-CS) (P < 0.01), while SA cellularity was similar across smoker/COPD groups. LA neutrophils were decreased in COPD-CS (P < 0.01), while SA neutrophil counts were unchanged. Compared with controls, LA macrophage numbers in COPD were significantly lower (P < 0.05), with SA macrophage numbers unchanged. A significant increase was observed in SA CD8+ cells in both no...
The clinical respiratory journal, 2008
Chronic obstructive pulmonary disease (COPD) is identified as an inflammatory disorder characterised by airway and lung inflammation and destruction with systemic involvement of multiple organ systems. The inflammatory reaction could be monitored not only in the airways by the use of bronchoalveolar lavage (BAL), sputum, exhaled air, and exhaled breath condensate but also in blood and urine as well as in tissue obtained at surgery or autopsy. There is a large number of cytokines, chemoattractants and other mediators that are of importance for the interplay of inflammatory mechanisms in COPD. Neutrophilic granulocytes are key players in the inflammatory reaction and the most important chemoattractants for these cells seem to be IL-8 (CXCL8) and leukotriene B(4) (LTB(4)). Also, the macrophages and chemoattractants for mononuclear cells (CCL2, CCL3) are of importance as are T-lymphocytes, predominantly of the cytotoxic subtype (CD8+). Analyses in exhaled breath condensates and exhaled ...
In vivoassessment of lung inflammatory cell activity in patients with COPD and asthma
European Respiratory Journal, 2003
The involvement of inflammatory cells in the pathogenesis of chronic obstructive pulmonary disease (COPD) and asthma is well established. This study aimed to quantify differences in inflammatory cell function in situ in these patients as compared to normal subjects. Positron emission tomography was used to assess neutrophil activity (18 F-fluorodeoxyglucose (18 FDG)) and macrophage accumulation (11 C-PK11195) in six patients with COPD, six chronic asthmatics and five age-matched normal control subjects. 18 FDG uptake was greater in COPD than in normal subjects, with no increase in asthmatics. The mean slope of 18 FDG uptake, corrected for volume of distribution, was 4.0 min-1 in COPD patients compared with 1.5 min-1 in control subjects and 1.7 min-1 in asthmatics. Mean 11 C-PK11195 uptake (plateau tissue:plasma) was higher in four of six COPD patients (10.8) and three of five asthmatics (11.8) than the maximum value in control subjects (6.2). From this preliminary study the authors conclude that positron emission tomography may be useful to assess polymorphonuclear neutrophil and macrophage activity in vivo in chronic obstructive pulmonary disease and asthma, and may reveal differences in cell behaviour between the study groups. In addition, positron emission tomography may provide indices of disease activity for future therapeutic studies.
Airway Inflammation in Severe Chronic Obstructive Pulmonary Disease
American Journal of Respiratory and Critical Care Medicine, 2002
The lung pathology of severe chronic obstructive pulmonary disease (COPD) has been poorly investigated. We examined surgical specimens obtained from patients with severe (forced expiratory volume in 1 second [FEV 1 ] ϭ 29 Ϯ 3% predicted, n ϭ 9) or mild/no airflow limitation (FEV 1 ϭ 86 Ϯ 5% predicted, n ϭ 9) and similar smoking history. With histochemical and immunohistochemical methods we quantified the structural changes and the inflammatory cells in small airways and in muscular pulmonary arteries. As compared with smokers with mild/no COPD, smokers with severe COPD had an increased number of leukocytes in the small airways, which showed a positive correlation with the radiologic score of emphysema and with the value of residual volume, and a negative correlation with the values of FEV 1 and carbon monoxide diffusing capacity. The inflammatory process was characterized by an increase in CD8 ϩ and CD4 ϩ T-lymphocytes in the airway wall and by an increase in macrophages in the airway epithelium. When all smokers were considered together, the smoking history was correlated with both the airway wall and smooth muscle thickness, suggesting that smoking itself may play a role in the development of structural changes. No structural and cellular differences were observed in pulmonary arteries between smokers with severe COPD and smokers with mild/no COPD. In conclusion, in the small airways of smokers with severe COPD, there is an increased number of leukocytes, which is correlated with reduced expiratory flow, lung hyperinflation, carbon monoxide diffusion impairment, and radiologic emphysema, suggesting a role for this inflammatory response in the clinical progression of the disease.
Cellular and molecular mechanisms in chronic obstructive pulmonary disease: an overview
Clinical <html_ent glyph="@amp;" ascii="&"/> Experimental Allergy, 2004
In the last decade, the analysis of bronchial biopsies and lung parenchyma obtained from chronic obstructive pulmonary disease (COPD) patients compared with those from smokers with normal lung function and non-smokers has provided new insights on the role of the different inflammatory and structural cells, their signalling pathways and mediators, contributing to a better knowledge of the pathogenesis of COPD. This review summarizes and discusses the lung pathology of COPD patients with emphasis on inflammatory cell phenotypes that predominate in different clinical conditions. In bronchial biopsies, a cascade of events takes place during progression from mild-to-severe disease. T lymphocytes, particularly CD8+ cells and macrophages are the prevalent inflammatory cells in the lung of healthy smokers and patients with mild COPD, while total and activated neutrophils predominate in severe COPD. The number of CD4+, CD8+ cells and macrophages expressing nuclear factor-kappa B (NF-kappaB), STAT-4 and IFN-gamma proteins as well as endothelial adhesion molecule-1 in endothelium is increased in mild/moderate disease. In contrast, activated neutrophils (MPO+ cells) and increased nitrotyrosine immunoreactivity develops in severe COPD. In bronchial biopsies obtained during COPD exacerbations, some studies have shown an increased T cell and granulocyte infiltration. Regular treatment with high doses of inhaled glucocorticoids does not significantly change the number of inflammatory cells in bronchial biopsies from patients with moderate COPD. The profile in lung parenchyma is similar to bronchial biopsies. 'Healthy' smokers and mild/moderate diseased patients show increased T lymphocyte infiltration in the peripheral airways. Pulmonary emphysema is associated with a general increase of inflammatory cells in the alveolar septa. The molecular mechanisms driving the lymphocyte and neutrophilic prevalence in mild and severe disease, respectively, needs to be extensively studied. Up-regulation of pro-inflammatory transcription factors NF-kappaB and STAT-4 in mild, activated epithelial and endothelial cells in the more severe disease may contribute to this differential prevalence of infiltrating cells.