Molecular Biology of Chronic Obstructive Pulmonary Disease: Basic Research and Clinical Application | Chapter 12 | Current Trends in Medicine and Medical Research Vol. 2
Chronic
obstructive pulmonary disease (COPD) is a global public health problem. It is
projected that by 2020 it will be the third leading cause of dead worldwide,
and the fifth leading cause of years of life lost due to disability coupled
with years of life lost due to premature dead. The definition provides that,
besides being preventable, treatable and characterized by a chronic and
persistent airflow limitation (usually progressive), COPD is due to an
increased chronic inflammatory response. It has an overwhelming prevalence, yet
accepted therapies are ineffective in reducing disease progression.
Bronchodilators, the mainstay of COPD treatment, only provide symptomatic
relief. Therefore, in order to provide a superior approach, it is important to
better understand the rationale behind therapy and the underlying mechanisms by
which the inflammatory process, through various pathogenic pathways, leads to
deterioration. Cigarette smoke and other pollutants/biomass fuels affect the
lungs ability to counterbalance proteases and neutralize different types of
stress. Even if the initial noxa is discontinued, inflammation, infection and
autoimmunity promote a chronic lung inflammatory response; leading to the
development of emphysema and small airway disease. This is due to continuous
endogenous production of reactive oxygen species, nitrative and carbonyl
stress. The process then continues into a harmful spiral and systemic disease.
The objective of this paper is to offer an updated review of COPD, simplifying
the integration of basic science research and introducing the concepts and
evidence of therapeutic alternatives. This review discusses why some drugs have
failed and which alternatives are emerging. Probably there is no unique
effective therapy, but several combinations of drugs might be required to impact
the different subcellular compartments and obtain a more effective therapy in
COPD. High level of ROS initiates the inflammatory process in COPD, with a
highly specific cellular and molecular profile. Through protease/anti-protease
imbalance and diverse kinds of stress, the pathological phenomena involving the
bronchopulmonary, vascular and systemic compartment is generated. Autoimmunity
and repeated infections potentially perpetuate and amplify the inflammatory
process, even if the initial stimulus is suspended. Failure of current
bronchodilator and steroid therapies to attenuate natural evolution of the
disease and progressive deterioration indicates the need to develop powerful
new drugs with innovative effects. It is likely than drug combinations are
required, instead of monotherapy, in order to improve the effectiveness and
impact the progressive course and mortality of COPD.
Biography of author(s)
Alcibey Alvarado-González
Internal
Medicine and Neumology, Clínica de Diagnóstico Médico, San José, Costa Rica.
View Volume: https://doi.org/10.9734/bpi/ctmmr/v2
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