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Reactive Oxygen Species and Obstructive Lung Disease

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Systems Biology of Free Radicals and Antioxidants

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Abstract

The respiratory system is constantly exposed to both endogenous and exogenous oxidants. Oxidative stress plays a critical role in the development, progression, monitoring, and, perhaps in the future, the treatment of both asthma and chronic obstructive pulmonary disease. It is estimated that asthma currently affects 300 million people globally, with its prevalence increasing by 50 % every decade. COPD is projected to become the third leading cause of death by 2020. The fundamental pathology in asthma is the interplay between the defective epithelial barrier, the inappropriate immune response to common allergens with the development of chronic inflammation, leading to airway remodeling and asthmatic symptoms. Reactive Oxygen species (ROS) induce airway epithelial dysfunction, resulting in oxidative damage of the underlying tissue, and can skew the immune system to a TH2 type response. The development of COPD has been strongly linked to the chronic inhalation of noxious gases, inducing inflammatory responses and oxidative damage to the lung parenchyma. Oxidative stress alters gene transcription, induces mucous gland hyper-secretion/hyperplasia, and accelerates cellular apoptosis; all these relate closely to the clinical manifestations of COPD. A lack of ability to both detect ROS and develop agents that cure or reverse these diseases means that the global burden of both conditions continues to be a major health issue. However, recent studies demonstrate the potential of exhaled breath condensate in the diagnosis and monitoring of respiratory diseases and may provide a method of measuring airway oxidative stress. Future breakthroughs in antioxidant therapy may provide an alternative pathway in the treatment of both asthma and COPD.

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Abbreviations

AP-1:

Activating protein-1

APC:

Antigen-presenting cell

COPD:

Chronic obstructive pulmonary disease

DC:

Dendritic cell

DEP:

Diesel exhaust particulate

EBC:

Exhaled breath condensate

EGFR:

Epidermal growth factor receptors

ETS:

Environmental tobacco smoking

FEV1 :

Forced expiratory volume in 1 s

GM-CSF:

Granulocyte macrophage colony-stimulating factor

GOLD:

Global initiative for Chronic Obstructive Lung Disease

GPx:

Glutathione peroxide

GRX:

Glutaredoxins

GSH:

Glutathione

GSSG:

Glutathione disulfide

GST:

Glutathione-S-transferase

H2O2 :

Hydrogen peroxide

HAT:

Histone acetyl transferase

HDAC:

Histone deacetyl transferase

IFN:

Interferon

IL:

Interleukin

iNOS:

Inducible nitric oxide synthase

MDA:

Malondialdehyde

MIP:

Macrophage inflammatory protein

NAC:

N-acetyl cysteine

NADPH:

Nicotinamide adenine dinucleotide phosphate-oxidase

NF-κB:

Nuclear factor kappa-light-chain-enhancer of activated B cells

NO:

Nitric oxide

NO2 :

Nitrite

NO3 − :

Nitrate

Nrf2:

NF-E2-related factor-2

O2 •− :

Superoxide anion

OH•− :

Hydroxyl radical

PM:

Particulate matter

QoL:

Quality of life

RNA:

Ribonucleic acid

RNS:

Reactive nitrogen species

ROS:

Reactive oxygen species

SOD:

Superoxide dismutase

TGF:

Transforming growth factor

TH:

T helper

TSLP:

Thymic stromal lymphopoietin

VEGF:

Vascular endothelial growth factor

WHO:

World Health Organization

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  1. Inflammation and Infection Research Centre (IIRC), Faculty of Medicine, University of New South Wales, Sydney, NSW, 2052, Australia

    Qi Zhang, Jiun-Lih Lin & Paul S. Thomas

  2. Department of Respiratory Medicine, Prince of Wales Hospital, Randwick, NSW, 2031, Australia

    Qi Zhang, Jiun-Lih Lin & Paul S. Thomas

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  1. Department of Pharmacology and Therapeutics, University of British Colombia, Vancouver, British Columbia, Canada

    Ismail Laher

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Zhang, Q., Lin, JL., Thomas, P.S. (2014). Reactive Oxygen Species and Obstructive Lung Disease. In: Laher, I. (eds) Systems Biology of Free Radicals and Antioxidants. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-30018-9_121

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