A Proteomics-Based Analysis of Blood Biomarkers

Chronic obstructive pulmonary disease (COPD) is characterized by irreversible airflow restrictions, which occur as a result of chronic airway inflammation and parenchymal destruction.1 With an estimated prevalence of 11.7% in the adult population,2 COPD is a heterogeneous and complex disease that has a high mortality rate and represents a significant burden on the healthcare system. Indeed, it has been estimated that COPD will be the third leading cause of death worldwide by 2030.3 Additionally, COPD is a risk factor for lung cancer, which is the leading cause of cancer-related death in the world. worldwide with a 5-year survival rate of 15%.4–6 It is also known to worsen the prognosis of lung cancer due to higher morbidity and mortality.4

Acute exacerbation of COPD (AECOPD) is characterized by an acute worsening of respiratory symptoms, leading to the need for additional treatment. triggered by a number of factors, including bacterial or viral infection, environmental pollutants, cold weather and interruption of regular treatment, and can have a high economic and social burden.9,10 For example, the AECOPD is associated with temporary or permanent loss of lung function and a rapid decline in exercise capacity and quality of life, leading to hospitalization or sometimes death.11 Although diagnostic follow-up for AECOPD is the one of the main objectives of COPD management, there is still no clear and objective diagnostic tool. Currently, the diagnosis of AECOPD relies solely on the patient's clinical presentation, which is hampered by the complexity and heterogeneity of the disease.

Several studies have assessed the characteristics of AECOPD. The traditional approach has been to use the clinical phenotype to classify individuals into groups based on similar clinical symptoms, prognosis, and response to treatment. For example, the Spanish guidelines on COPD (GesPOC) define the different clinical phenotypes as follows: non-exacerbating phenotype with chronic bronchitis or emphysema; asthma-COPD overlap syndrome; frequent exacerbating phenotype with emphysema; and exacerbating phenotype common with chronic bronchitis.12 However, this method of classifying COPD is limited by overlapping phenotypes and the possibility that different biological mechanisms may exist within the same group of phenotypes.

Additionally, molecular diagnostic assays using multi-omics approaches have also been used to characterize and diagnose COPD.13 Multi-omics is a tool for analyzing complex datasets including genomics, transcriptomics, proteomics and metabolomics.14 In particular, some studies have attempted to identify blood biomarkers of COPD and AECOPD.

15,16 One study reported that the serum level of IGFBP7 is up-regulated in the EAMPOC.17),18 a type of data-independent acquisition (DIA), has been used to discover clinical biomarkers.19–21 With this next-generation proteomics method that takes into account both methods for monitoring the Selected Reaction (SRM) and Data Dependent Acquisition (DDA). , it is possible to obtain stable quantitative information with high reproducibility for as many proteins as possible. produced in the recovery phase.

Patients and methods

This single-center prospective pilot study recruited 12 patients who came to Asan Medical Center (South Korea) via the outpatient clinic or emergency department with symptoms of AECOPD and then underwent follow-up treatment in the outpatient clinic between 2015 and 2017. Blood samples were collected from each patient during the treatment-naïve and stable COPD (recovery) phases. All patients visited Asan Medical Center within 14 days of onset of AECOPD symptoms.

A follow-up visit with sampling was carried out at least 6 weeks after discharge. This study was approved by the Institutional Review Board (IRB) of Asan Medical Center (IRB number: 2019-0581) and was based on a previous cohort of patients with COPD (IRB number: 2015-0088). All patients provided written informed consent. This study was conducted in accordance with the principles of the Declaration of Helsinki.

Diagnosis of COPD was based on Global Initiative for Chronic Obstructive Lung Disease (GOLD) criteria (a compatible history [example: age ≥ 40 years, history of smoking] and spirometry results [a forced expiratory volume post bronchodilator in one second (FEV1 )/capac