Molecular Biology of Chronic Obstructive Pulmonary Disease from the Bases to the Therapeutic Decision: A Review

Abstract

Chronic obstructive pulmonary disease (COPD) is a global public health problem. 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.