ABSTRACT: Chronic Obstructive Pulmonary Disease (COPD) is a progressive and irreversible respiratory condition characterized by airflow obstruction, which worsens over time. COPD is one of the leading causes of morbidity and mortality worldwide, responsible for a significant burden of hospitalizations, disability, and premature death. Its pathophysiology is multifactorial, involving a complex interplay between genetic and environmental factors, such as smoking, which promotes chronic airway inflammation and pulmonary emphysema. Although COPD shares similar clinical symptoms with asthma, such as dyspnea and cough, the two conditions have distinct pathological mechanisms. Asthma is a reversible disease, characterized by bronchial hyperresponsiveness and predominantly eosinophilic inflammation, while COPD is an irreversible disease, associated with the destruction of airways and alveoli and dysfunction of the epithelial barrier. Currently, the diagnosis of COPD is based on clinical criteria and spirometric functional tests; however, these methods do not provide sufficient information regarding the molecular mechanisms that differentiate COPD from asthma or other respiratory conditions. While clinical characterization is an important step, conventional tests are not sensitive enough to detect the disease at early stages or in patients with comorbidities, such as asthma. Therefore, there is a growing need to develop molecular biomarkers that can complement traditional diagnostic methods and provide a more effective and accurate means of diagnosing COPD, especially in complex clinical situations. The use of advanced proteomic techniques, such as liquid chromatography coupled with mass spectrometry (LC-MS/MS), enables the identification of differentially expressed proteins that may serve as potential biomarkers for the early diagnosis of complex diseases like COPD. Shotgun proteomics, an approach that allows global and untargeted analysis of proteins in serum, can reveal protein expression patterns characteristic of specific pathological states, such as COPD. Previous studies have shown that proteomic analysis has successfully identified promising biomarkers for various respiratory diseases, including COPD. However, most studies have focused solely on comparing COPD with healthy controls, without considering the complex interactions with comorbid diseases, such as asthma. Additionally, many of these biomarkers still need to be validated in larger populations with more stringent diagnostic criteria. The lack of an approach combining proteomic analyses with advanced bioinformatics tools, such as PANTHER and Reactome, limits the understanding of the molecular pathways involved in COPD and hinders the translation of these biomarkers into clinical practice. In this context, the present research is justified by the need to identify a set of differentially expressed protein biomarkers in serum samples from patients with COPD, asthma, and control groups. The objective is not only to improve the differential diagnosis between COPD and asthma but also to provide a solid molecular foundation for the development of more targeted therapies, aligned with the principles of precision medicine. The identification of robust biomarkers could facilitate the implementation of more effective therapeutic strategies, improving the clinical management of COPD, particularly in the early stages of the disease, where early intervention can significantly impact disease progression.
Tatiane Bastos