Researchers find that lung recovery differs across lung cell types, and that quitting may leave its own distinct biological signature on the lungs

A new study by a team of McGill researchers could help explain why people who have quit smoking remain at elevated risk of lung disease long after their last cigarette.

Their paper, published in Translational Research, provides one of the most detailed pictures to date of how quitting smoking affects the human lung at the cellular level.

“Current smokers have the highest risk of deadly diseases such as lung cancer, but former smokers still face a higher risk than people who never smoked. Despite more than a century of research on smoking, we don’t fully understand why,” said senior author Carolyn Baglole, Professor in McGill’s Department of Pharmacology and Therapeutics and researcher at the Research Institute of the McGill University Health Centre.

“Our findings show that while some damage appears reversible, other changes persist long after people stop smoking,” she said.

Mapping recovery after smoking

Using publicly available data, the researchers analyzed more than 100,000 lung cells from 21 people: nine who had never smoked, five current smokers and seven former smokers. The data captured molecular activity across more than 40 lung cell types, offering a highly detailed picture of how the lungs respond to smoking and of recovery after quitting.

Some lung cells recovered after smoking ended, while others showed lasting changes in genes linked to tissue structure, immune function and blood vessel health. In some cases, former smokers displayed molecular patterns not seen in either current smokers or people who had never smoked, suggesting quitting leaves its own biological signature on the lung.

Impacts of active smoking and cessation on the pulmonary transcriptome

Smoking dysregulated genes involved in immune response and tissue structure across cell types. Cessation mitigated some effects of active smoking, such as dysregulation of antigen presentation genes in naLMs, cMono, and ncMono; it also resolved gene set dysregulation in AT1s, which had dysregulation of extracellular matrix genes in active smoker cells but no gene set dysregulation in former smoker cells. However, extracellular matrix genes were downregulated in active smoker MFAP5^hi fibroblasts and similarly downregulated after cessation, demonstrating that some pathways did not recover from the effects of smoking after cessation. Additionally, there were pathways that were differentially dysregulated by active smoking and cesssation, with antigen presentation genes downregulated in active smoker AMs and moAMs but instead upregulated in former smoker cells. Together, these findings show that the transcriptomic signature of cessation is unique from that of active smoking. 

Could inform treatment

“These findings are an important step toward understanding what damage caused by smoking can heal and what may be permanent,” said first author Nicole Heimbach, a doctoral student at McGill. “By knowing what damage remains after quitting, we can better understand how smoking-related diseases develop and how to treat them.”

Although smoking rates have declined over the past several decades, about one in eight Canadian adults still uses tobacco, which remains one of the leading causes of preventable death.

Source – McGill University