Low-Dose Computed Tomography: A Window Into Early Lung Disease?

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Ravi Kalhan, MD, MS

Ravi Kalhan, MD, MS

Lung health in adults has traditionally been defined as the absence of disease, but it may be time to rethink this paradigm, according to Ravi Kalhan, MD, MS, Director of the Northwestern Asthma and Chronic Obstructive Pulmonary Disease (COPD) Program at Northwestern University Feinberg School of Medicine.

New research involving low-dose computed tomography (CT) has shown that impaired lung health is associated with adverse consequences, including respiratory symptoms, decreased cognition, and a high risk of cardiovascular events. During the Quantitative Imaging Workshop XVIII, Dr. Kalhan discussed how redefining respiratory health coupled with earlier intervention strategies may improve quality of life, morbidity, and mortality.1

Changing Perspective on Lung Health

“Ideal lung health is more than the absence of lung disease,” said Dr. Kalhan. “Disease-focused studies, even when inclusive of early disease, do not inform lung health or prevention strategies, nor do they typically enable interception strategies. Thinking about how to preserve and promote ideal lung health is critical for disease interception,” he added.

As Dr. Kalhan explained, perspectives on lung health have changed significantly in recent years with the discovery of multiple pathways to COPD. Although there are people with normal lung function at baseline who experience accelerated decline in lung function, there are also those with abnormal lung function at baseline who experience less of a decline, and both groups can have COPD defined by the ratio of forced expiratory volume to forced vital capacity.

Results of the CARDIA study, which looked at how longitudinal patterns of smoking exposure are associated with loss of lung function, obstructive lung physiology, and CT-measured emphysema, showed that the prevalence of abnormal lung function was greatest among those with consistently poor lung health.2

An analysis of abnormal CT scans also showed that people who had both persistently poor lung health and accelerated decline in lung function had similar prevalence of emphysema. An intermediate phenotype of preserved impaired lung health was again found to have more emphysema than groups who had preserved good lung health or ideal respiratory health, said Dr. Kalhan.

Having respiratory symptoms such as cough, phlegm, wheeze, or chest illness between the ages of 25 and 27 was also associated with greater odds of future obstructive impairment. In contrast, reporting shortness of breath between the ages of 25 and 27 was associated with a development later in life (25–30 years later) of restrictive physiologic impairment.

“We don’t really know what’s going on in the lungs of people with these symptoms,” said Dr. Kalhan. “In my view, an opportunity to utilize novel imaging techniques could really emerge.”

Novel Imaging Techniques to Assess Risk of Disease

One imaging technique that has shown promise is the local histogram, which has been used to create a lung health map that characterizes areas of lung across a variety of features. One of these features, high attenuation, has now been termed lung injury and is associated with an increase in ICAM-1 and C-reactive protein in people with COPD. In the CARDIA study, both biomarkers were associated with the odds of developing interstitial lung disease and emphysema several years later.

“It’s been said that we’ll never find biomarkers in the blood of future lung disease, but we may be able to integrate blood biomarkers with a CT-based risk factor that depicted early lung injury to define the risk of future disease,” said Dr. Kalhan. “In people with intermediate phenotypes who are susceptible to future lung disease, we could then test therapies that intercept impaired respiratory health and prevent progression to chronic lung disease.”

According to Dr. Kalhan, major gains in cardiovascular disease prevention are attributable to health promotion, but absence of disease-agnostic respiratory health studies has hindered efforts at prevention. “We do not have a cholesterol of the lungs, but integrating imaging biomarkers with traditional blood biomarkers presents a clear opportunity,” he said.

Dr. Kalhan and colleagues are currently recruiting a cohort of individuals between 25 and 35 across the country and collecting respiratory health data for a longitudinal study of biomarkers in conjunction with lung injury. 

DISCLOSURE: Dr. Kalhan reported industry relationships with AstraZeneca, CVS Caremark, GlaxoSmithKline, and HealthSTAR Communications; and has an investment interest in Moda Spira.


1. Kalhan R: Is annual thoracic screening a venue to deliver preventive interventions? Quantitative Imaging Workshop XVIII. Presented November 5, 2021.

2. Mathew AR, Bhatt SP, Colangelo LA, et al: Life-course smoking trajectories and risk for emphysema in middle age: The CARDIA Lung Study. Am J Respir Crit Care Med 199:237-240, 2019.

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