Not All COPD Created Equal

Why do people with COPD sometimes exhibit such different symptoms, disease trajectories, and treatment responses? Respiratory therapists have long wondered, and researchers at the Yale School of Medicine have now provided an answer.

In a study published in Nature Genetics, researchers examined lung tissue from people with COPD in unprecedented detail using single-cell sequencing technology, complemented by spatial transcriptomic and proteomic analyses. The results provided a much better understanding of what is occurring in COPD than prior research has revealed.

The tissue samples were obtained from 141 individuals with COPD who were enrolled in the Lung Tissue Resource Consortium, funded by the National Heart, Lung, and Blood Institute. Overall, 1.5 million cells were analyzed, with results suggesting COPD is not a single disease with variable severity but instead an evolving cellular ecosystem shaped by coordinated interactions among distinct cell states.

The microenvironments identified in the study varied in abundance across individuals, which the authors believe helps explain why COPD can appear so different from person to person.

“What sets this study apart is the use of a large, well-phenotyped human cohort across disease stages combined with integrated multi-omic analyses,” said study author Yuening Zhang, PhD. “Collectively, this provides us with an unprecedented resolution of the diseased lung, enabling us to discover new disease microenvironments and therapeutic targets.”

Senior study author Maor Sauler, MD, an adjunct associate professor in the Section of Pulmonary, Critical Care, and Sleep Medicine at Yale, shares Dr. Zhang’s hope that this laboratory study can be translated into more targeted treatments for people with COPD.

“Right now, our understanding of COPD subtypes is largely based on imaging or symptoms,” he said. “Here, we’re seeing clear evidence of distinct underlying biologies. Stratifying patients based on these differences could allow for more precise treatment, where one patient responds to one therapy and another to something else.”

He also believes the work may help remove the negative connotation that COPD has long had for many patients and the general public alike.

“COPD is often unfairly framed as a disease people brought on themselves,” said Dr. Sauler. “In reality, there’s a substantial genetic component, and many environmental exposures, not just smoking, contribute to risk. Even as smoking rates decline, COPD continues to rise, underscoring the need to treat it as the complex, biologically driven disease it is.” 

Highlighted in RC Buzz February 9, 2026