Study Finds Novel Proteins Associated with COPD Lung Function Decline


Little is understood about the systemic markers of worsening COPD. Investigators have observed at least 3 novel pathways.


Investigators believe they have identified novel molecular targets and pathways that could help clinicians modify the course of chronic obstructive pulmonary disease (COPD) in afflicted patients.

In new findings planned for presentation at the American Thoracic Society (ATS) 2020 International Conference this year, a team of US-based investigators led by Debby Ngo, MD, of Beth Israel Deaconess Medical Center, shared the identification of nearly 200 proteins associated with pulmonary function as per forced expiratory volume at 1 second (FEV1).

Of those, a dozen-odd proteins were associated with pulmonary function decline.

The team noted that COPD, characterized by airway obstruction and accelerated lung function decline in patients, is comprised of systemic markers that are still not fully understood by clinicians.

“We tested whether aptamer-based protein profiling could identify markers and pathways associated with impaired pulmonary function and lung function decline in multiple studies,” Ngo and colleagues wrote.

Their assessment included 3827 non-Hispanic and European White participants from 4 population-based cohorts and 2 longitudinal COPD case-control studies—in which aptamer-based plasma proteomic data was available on 1305 proteins, as well as patient spirometry measurements.

Investigators used linear regression models to examine the associations of these 1300-plus proteins with baseline FEV1 and FEV1/FVC ratio measurements. They adjusted FEV1 measurements for patient age, height, sex, body mass index (BMI), smoking status, and pack-years smoking.

FEV1/FVC ratio measurements were adjusted for age, sex, BMI, smoking status, pack-years, and COPD case status in COPDGene and SPIROMICS.

Lung function decline, as per FEV1 ml/year, was gauged for its association with baseline protein levels in 2636 participants from the 4 cohorts. Ngo and colleagues used a model including a random intercept and fixed effects for time, protein and its interaction with time, baseline age, sex, height, smoking status, and pack-years.

The team identified 198 proteins associated with baseline FEV1. Of those, 12 were also significantly associated with FEV1/FVC—novel associations included retinal binding protein 4 and bactericidal permeability increasing protein.

Another 15 proteins were observed to have association with the rate of FEV1 decline in patients—the novel ones being coagulation cascade initiator tissue factor, extracellular matrix protein nidogen, and potent angiogenic factor angiogenin.

As such, the team noted, pathways which are now believed to be associated with lung function include extracellular matrix remodeling, dysregulation of coagulation, and angiogenesis.

“In this study, we have identified many novel circulating protein associations with baseline lung function and FEV1 decline,” investigators concluded. “These associations could represent novel molecular targets and pathways to modify the clinical course of COPD or be used for preventive and therapeutic strategies.”

The study, “Systemic Biomarkers of Lung Function and FEV1 Decline Across Multiple Cohorts,” was published online by ATS.

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