Pathophysiology of Exacerbations of Chronic Obstructive Pulmonary Disease

Papi, Alberto; Luppi, Fabrizio; Franco, Francesca; Fabbri, Leonardo M.

doi:10.1513/pats.200512-125sf

Cited by 150 publications

(110 citation statements)

References 97 publications

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“…Moreover, these findings provide a biological hypothesis for the epidemiological relationship between ozone and increased pulmonary morbidity and mortality. Loss of lung function in chronic obstructive pulmonary disease is related to exposure to environmental air pollutants (34,35) and frequency of exacerbations (36). Our observations support that exposure to ozone can significantly enhance both lung injury and macrophage apoptosis after exposure to inhaled endotoxin.…”

Section: Discussionsupporting

confidence: 70%

Ambient Ozone Primes Pulmonary Innate Immunity in Mice

Hollingsworth

Maruoka

et al. 2007

The Journal of Immunology

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Exposure to ozone in air pollution in urban environments is associated with increases in pulmonary-related hospitalizations and mortality. Because ozone also alters clearance of pulmonary bacterial pathogens, we hypothesized that inhalation of ozone modifies innate immunity in the lung. To address our hypothesis, we exposed C57BL/6J mice to either free air or ozone, and then subsequently challenged with an aerosol of Escherichia coli LPS. Pre-exposure to ozone resulted in enhanced airway hyperreactivity, higher concentrations of both total protein and proinflammatory cytokines in lung lavage fluid, enhanced LPS-mediated signaling in lung tissue, and higher concentrations of serum IL-6 following inhalation of LPS. However, pre-exposure to ozone dramatically reduced inflammatory cell accumulation to the lower airways in response to inhaled LPS. The reduced concentration of cells in the lower airways was associated with enhanced apoptosis of both lung macrophages and systemic circulating monocytes. Moreover, both flow cytometry and confocal microscopy indicate that inhaled ozone causes altered distribution of TLR4 on alveolar macrophages and enhanced functional response to endotoxin by macrophages. These observations indicate that ozone exposure increases both the pulmonary and the systemic biologic response to inhaled LPS by priming the innate immune system.

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Section: Discussionsupporting

confidence: 70%

Ambient Ozone Primes Pulmonary Innate Immunity in Mice

Hollingsworth

Maruoka

et al. 2007

The Journal of Immunology

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“…The 'triad' of mucus gland hyperplasia, mucus retention and surfactant dysfunction produces dire consequences on the pulmonary gas-exchange. The inflammatory response has prompted some researchers to propose the 'inflammatory/anti-inflammatory' hypothesis for COPD, that also provides a sound basis for the use of anti-inflammatory drugs in the disease [50].…”

Section: The Pathobiology Of Copdmentioning

confidence: 99%

Oxidative/Nitrosative Stress and the Pathobiology of Chronic Obstructive Pulmonary Disease

Pandey

Singh²,

Singhal³

et al. 2013

JCDR

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The understanding of the pathobiology of Chronic Obstructive Pulmonary Disease (COPD) has undergone a major change in the past three decades. The classical 'protease-antiprotease' hypothesis still holds true, nevertheless, the sequence of the biochemical events which lead to the protease/antiprotease imbalance have been unraveled. For instance, tobacco smoke, a primary risk factor for COPD, contains a plethora of reactive Oxygen/ Nitrogen Species (ROS/RNS) that serve to initiate the oxidant/ antioxidant imbalance in the respiratory tract of chronic smokers, a phenomenon that is amplified if certain other risk factors co-exist (e.g. a genetic deficiency of the major antiproteases, a suboptimal antioxidant defense system, airway hyper responsiveness etc.). The inflammatory response that ensues as a result of the initial occult exogenous oxidative/ nitrosative stress becomes a secondary endogenous source of ROS/RNS. This perpetuates the ongoing lung damage, even though the primary insult may no longer be present (abstinence). Depletion of the pulmonary antioxidants, damage to the local antiprotease protective screen, a decreased immune response, hypersecretion of mucus, superadded infections, oxygen therapy-induced oxidant production, etc. are some of the critical factors which account for the oxidative/ nitrosative stressmediated pulmonary as well as extrapulmonary features of COPD. In the light of the recent developments, remarkable efforts are being made, either to develop novel therapeutic strategies or to improve the existing ones, which are aimed at treating different aspects of the disease. Thus, it is reasonable to recommend antioxidants as a useful adjunct to the more conventional treatment options, keeping in view the 'oxidant/antioxidant' hypothesis as a unifying theme for the 'protease/antiprotease' theory of COPD. INTRODUCTIONChronic Obstructive Pulmonary Disease (COPD) is characterized by a poorly reversible airflow limitation that is usually progressive and associated with the abnormal inflammatory response of the lung to noxious particles and/ or gases which are present in cigarette smoke [1,2]. The characteristic features of the disease are chronic inflammation of the peripheral airways, chronic bronchitis and destruction of the lung parenchyma (emphysema), which include systemic extra-pulmonary manifestations [3]. The patients can suffer from one, some or all of these conditions. The peripheral airways inflammation or small-airway disease involves various morphological abnormalities such as airway narrowing with goblet cell hyperplasia, smooth muscle hypertrophy, excess mucous, oedema and inflammatory cellular infiltration. Airway remodeling with sub-epithelial and peribronchial fibrosis has been postulated as the critical factor in the small-airway narrowing and the fixed airway obstruction in the small-airways of the patients with COPD [4].Anatomically, the disease can be viewed as a part of a spectrum, with chronic bronchitis at one end and emphysema at the other. Chronic bronchitis is ...

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“…It was reported that the airway epithelium is an abundant source of chemokines/ cytokines which attract both macrophages and neutrophils [51]. Activated neutrophils can result in wide spread inflammation of the lung tissue, destruction of basement membrane of alveolar capillary membrane and increase of its permeability.…”

Section: Discussionmentioning

confidence: 99%