SPECT smokes out cigarette-related changes in the lung leading to COPD

Ventilation and perfusion (V/Q) SPECT could one day be used to track the early warning signs of cigarette smoke-induced chronic obstructive pulmonary disease (COPD) by documenting telltale airflow dysfunction, according to a study published in the April issue of The Journal of Nuclear Medicine.

Brian N. Jobse, PhD, from the department of medicine and division of respirology at McMaster University in Hamilton, Ontario, Canada, and colleagues, leveraged V/Q SPECT to provide quantitative analysis of the progression of airflow impairment associated with COPD in mice exposed to daily cigarette smoke before CT could pick up any structural changes in the lungs.

COPD is a progressive lung disease associated with emphysema and chronic inflammation, production of mucus, lung fibrosis and airspace enlargement. Sustained exposure to cigarette smoke is a major risk factor for developing emphysema and COPD. The condition first develops in small airways in the lungs and a typical evaluation for COPD uses spirometric airflow measures to assess forced vital capacity and forced expiratory volume. Although this method has been shown to be simple and effective, it does not have the capacity to detect the subtle changes in small airways in the beginning stages of disease and diagnosis is often made after irreparable lung damage has occurred.

“Better diagnostic tools are needed to detect early changes in smokers to prevent further lung dysfunction and provide patients with individualized treatment regimens,” said co-author N. Renee Labiris, PhD, also from the department of medicine and division of respirology at McMaster University in Hamilton, Ontario, Canada, in a release. “Our preclinical study suggests that not only can V/Q imaging detect early and small changes in lung pathology, the type of V/Q mismatching could provide insight into the underlying pathologies, which current measures of lung function are unable to do.”

Mice were exposed to whole-body cigarette smoke for either eight or 24 weeks five days a week for a total of 50 minutes twice a day. Control groups of healthy mice were age-matched to provide a comparison study of the effects of cigarette smoke on lung function. After exposure, mice underwent V/Q SPECT imaging to quantify ventilation of alveolar units and perfusion of the pulmonary capillary beds, the two major components of respiratory gas exchange. Histological analysis of airspace enlargement was completed from dissected lung sections. Results of the study confirmed mismatching in lung function in smoke-exposed mice compared to healthy controls. Those exposed to cigarette smoke showed signs of inflammation, pronounced airspace enlargement, particularly in the acinar complex of the lungs, at eight weeks and worsening at 24 weeks, and increased presence of neutrophil and mononuclear cells. These changes were ascertained by SPECT but not by structural imaging using CT, despite respiratory gating and fine resolution.

“This study demonstrated that, before CT detection of structural changes, V/Q imaging detected changes in gas-exchange potential,” wrote Jobse et al. “This functional impairment corresponded to increased lung inflammation and increased airspace enlargement. In vivo V/Q imaging can detect early changes to the lung caused by [cigarette smoke] exposure and thus provides a noninvasive method of longitudinally studying lung dysfunction in preclinical models. In the future, these measures could be applied clinically to study and diagnose the early stages of chronic obstructive pulmonary disease.”

Further preclinical research is required before this technique could be translated to human studies for early diagnosis and treatment monitoring for cigarette-smoke related emphysema and COPD.