Research Spotlight: All People with High Cigarette Use May Not Face the Same Health Risks

Yohannes Tesfaigzi, PhD, of the Division of Pulmonary and Critical Care Medicine at Mass General Brigham, and Bartolome Celli, MD, are the lead and senior authors of a paper published in Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation, “Low Lung Function in Middle-Aged Smokers Impacts Health Status, Morbidities, and Mortality: An Observational Analysis of the Lovelace Smokers Cohort.”

Q: How would you summarize your study for a lay audience?

The human lungs grow until young adulthood and typically reach peak function around ages 20–25. However, peak lung function looks different for everyone. Whether people reach a “low” peak lung function or a “high” peak lung function is influenced by a combination of genetic and environmental factors.

Our study examined whether baseline lung function influenced the long-term health outcomes of people with high cigarette use. Our analysis showed that a significantly higher proportion of participants with low lung function at the start of the study had died after 17 years of follow up compared to participants with high lung function. Further, those with low lung function were more likely to have developed wheezing, cardiovascular disease, diabetes and chronic lung diseases, and were in generally worse health.

Q: What knowledge gap does your study help to fill?

Few studies have investigated whether people who smoke cigarettes and have low lung function, as opposed to people who smoke cigarettes and have high lung function, are at a greater risk for developing chronic diseases over a long period of time. Our study helps close this knowledge gap, showing that those with low lung function may indeed be at higher risk for developing diseases or dying. This suggests it could be beneficial to closely monitor the lung function of people who smoke cigarettes at younger ages to achieve earlier intervention of disease.

Q: What methods or approach did you use?

The Lovelace Smokers Cohort (LSC) is a community-based cohort of current or “ever” cigarette users between the ages of 40–75. Participants were recruited between 2001 and 2011 and had a smoking history equal to or more than 10 pack years (a unit calculated by multiplying the number of packs smoked per day by the number of years smoked).

For this study, we leveraged a subpopulation of these LSC participants—specifically those who were between 40–60 years old and without airway obstruction—to comprise our overall cohort. We then grouped this subset based on lung function, and focused our analysis on those with the lowest and highest levels. Additionally, we selected an even smaller group to attend a single clinical visit at the approximate 17-year follow-up mark for more in-depth testing.

Using a variety of methods, we were able to compare survival rates between the low and high lung function groups after adjusting for many variables.

Q: What did you find?

Those with the lowest and highest lung functions that were chosen for analysis from our overall cohort were broadly similar in age, sex, body mass index and smoking history at baseline. However, in our matched comparison over the duration of the study, we found that those with low lung function had more than double the mortality risk compared to those with high lung function.

For the participants who returned for a dedicated clinical visit, their original lung function statuses remained unchanged. In addition, those with low lung function had increased prevalence of wheezing, cardiovascular diseases, diabetes and chronic lung diseases, and reported overall worse health status.

Q: What are the implications?

These findings show that all people with high cigarette use—even those without overt lung disease—could benefit from the use of a simple spirometry test of their lung health in early adulthood. These tests can detect lower than normal lung function and help identify which individuals need to have their health more closely monitored.

Q: What are the next steps?

We are in the process of analyzing blood biomarkers in participants from each of these lung function groups. These biomarkers could help identify those with the highest risk of developing severe disease and be a foundation for understanding the molecular causes for health problems and mortality over time in people who smoke cigarettes frequently. Further, these biomarkers could be useful for selecting patients for clinical trials who may show benefit from new drug treatments.

Authorship: In addition to Tesfaigzi and Celli, other Mass General Brigham authors include Congjian Liu.

Paper cited: Tesfaigzi Y., et al. “Low Lung Function in Middle Aged Smokers Impacts Health Status, Morbidities and Mortality: An Observational Analysis of the Lovelace Smokers Cohort.” Chronic Obstructive Pulmonary Diseases: Journal of the COPD Foundation. DOI: 10.15326/jcopdf.2025.0605

Funding: This work was supported by grants from AstraZeneca.

Disclosures: YT reports consulting fees for Verra Therapeutics. FXB, KO, and MP are employees of AstraZeneca and hold stock/stock options in the company. VAH (currently employed by Amgen) and MNB (currently employed by Sanofi) are former employees of AstraZeneca and hold stock options in AstraZeneca. PD is a current contractor for and former employee of AstraZeneca and has previously held stock and/or stock options in the company. BRC is a consultant for AstraZeneca, Boehringer Ingelheim, Chiesi, Gala Therapeutics, GlaxoSmithKline, Menarini, Novartis, Pulmonx, and Sanofi-Aventis; is a data and safety monitoring board member for AstraZeneca, Sanofi-Aventis, and Vertex; is an advisory committee member for AstraZeneca, Chiesi, Gala Therapeutics, Menarini, Novartis, Pulmonx, Sanofi-Aventis, and Vertex; is a speaker for AstraZeneca, GlaxoSmithKline, and Menarini; and has received payment or honoraria for lectures, presentations, speakers bureaus, manuscript writing, or educational events for AstraZeneca, Chiesi, GlaxoSmithKline, Menarini, and Regeneron. CL, DH, SAB, and MAP have no disclosures to report.