Emphysema Severity Proves Strong Predictor of Mortality

Jenni Laidman

January 20, 2013

Emphysema severity, as measured by computed tomography (CT), accurately predicted mortality among current and former smokers regardless of whether they had chronic obstructive pulmonary disease (COPD), according to results from a study published online January 17 in the American Journal of Respiratory and Critical Care Medicine.

In addition, the researchers show that airway wall thickness is associated with respiratory mortality, but only in those with severe emphysema.

Ane Johannessen, PhD, postdoctoral researcher, Centre for Clinical Research, Haukeland University Hospital, Bergen, Norway, and colleagues followed up 947 ever-smokers, 462 of whom had COPD, for 8 years, from 2003 to 2011. At baseline, all patients underwent spirometry for COPD diagnosis and CT scanning. Emphysema severity was categorized as low, medium, or high according to the percentage of low attenuation areas (%LAA). Study participants were aged 40 to 85 years at baseline with 2.5 or more pack years of smoking history.

During the study, 4% of the 568 participants with %LAA lower than 3% died compared with 18% of the 190 participants with %LAA between 3% and 10% and 44% of the 189 patients with %LAA higher than 10% (all P < .01). When adjusted for sex, case/control status, postbronchodilator forced expiratory volume in 1 second, COPD status, age, body mass index, smoking status, age of smoking onset, pack years, and inflation level, the comparable percentile participants with medium and high emphysema severity lived 19 fewer months than those with mild disease. Those in the highest LAA category lost 33 months for respiratory mortality and 37 months for cardiovascular mortality compared with those with mild emphysema. Emphysema severity had no association with lung cancer mortality or mortality from other cancers.

Better Assessment Needed

The findings point to a growing need for the anatomic assessment of lung function.

"Our main metric for quite a while has been the degree of lung function impairment. Although that is good, it really doesn't capture everything," David M. Mannino, MD, professor and chair, Department of Preventive Medicine and Environmental Health, University of Kentucky College of Public Health, Lexington, told Medscape Medical News. Dr. Mannino, who has investigated the relationship between lung function and mortality, was not involved with the current study.

"I think we're still a ways from incorporating this into practice. That may change," Dr. Mannino said. "Over the next year or so there's going to be a growing conversation about the need for CT-based lung cancer screening for people who have a smoking history. There's good evidence now that CT scans can detect early lung cancer that actually leads to a survival advantage. If that becomes more common, it becomes relatively easy to implement, when screening for lung cancer, to run an algorithm that would give you the proportion of low-attenuation area."

However, readily available technology has to catch up before such an advance is possible. "The current CT scanners, the equipment that takes the image and processes it, do not have the software embedded in the scanner to measure the amount of emphysema," Barry J. Make, MD, codirector of the COPD Program at National Jewish Health and Professor at the University of Colorado School of Medicine, Denver, told Medscape Medical News. Dr. Make was not associated with the current study.

"Studies like this indicate that we need to have those scores available on real-time basis," Dr. Make said. He is an investigator in the National Institutes of Health–funded COPDGene Study, which is looking for the underlying genetic causes of COPD.

Emphysema as Predictor of Death

In the current study, those who died in the lowest %LAA category died within 79 months. The first 4% to die in the medium category died in 23 months, and the first 4% to die in the high category died within a year.

This tendency for increasing mortality with increasing emphysema was most pronounced for respiratory mortality. The research showed that emphysema predicted respiratory mortality with excellent discrimination and predicted respiratory and cardiovascular mortality more accurately than the Global Initiative for Obstructive Lung Disease severity classification did.

Of the 144 deaths from baseline through June 2011, 28% of the patients died of respiratory causes, 10% of cardiovascular causes, 11% of cancer other than lung cancer, and 17% died of lung cancer.

Increased airway wall thickness led to reduced survival time in patients with more severe emphysema, although it had no effect on respiratory mortality overall. The authors write that "[w]e need studies with more statistical power and more robust airway wall thickness measurements to examine this association further."

One coauthor reports GlaxoSmithKline funded data sampling and reports receiving money for lectures from GlaxoSmithKline, AstraZeneca, and Pfizer. The other authors, Dr. Mannino, and Dr. Make have disclosed no relevant financial relationships.

Am J Resp Crit Care Med. Published online January 17, 2013. Abstract