Meta-analysis Finds Link Between Emphysema Severity, Lung Cancer Risk

A new meta-analysis found that more severe emphysema is associated with an increased risk of lung cancer.

Findings from a meta-analysis published in Radiology revealed that an individual’s emphysema severity—measured via CT scan—is associated with a higher lung cancer risk.

Several well-known risk factors for lung cancer exist, including chronic lung inflammation, smoking, genetics, diet, and occupational exposure, the researchers explained.

Although both lung cancer and emphysema are linked by common predisposing risk factors and molecular inflammatory processes, past studies exploring the association between chest CT assessment of emphysema and lung cancer have yielded inconsistent results.

Due to its high sensitivity, chest CT is considered the reference standard for noninvasive assessment of emphysema, but radiography and pulmonary function tests can also be used. As such, the researchers hypothesized that different methods used to assess the condition may have affected previous outcomes.

In an effort to update and synthesize data from existing new studies, the investigators performed a systematic review and meta-analysis on any potential association between the 2 conditions.

“Visual emphysema was defined as disrupted lung vasculature and parenchyma with low attenuation occupying any lung zone (at least trace) at chest CT, as evaluated by radiologists using the National Emphysema Treatment Trial or Fleischner Society guidelines or comparable,” they wrote, adding that the main emphysema subtypes were paraseptal and centrilobular.

A total of 21 studies were included in the meta-analysis, which included data on 3907 patients with lung cancer and 103,175 controls. There were 26 subsets of patients identified. Fifty-two percent of studies included were cohort studies and 48% were case-control studies. The majority (74%) of included participants came from North America.

Analyzes revealed:

  • The overall pooled odds ratios (ORs) for lung cancer given the presence of emphysema were 2.3 (95% CI, 2.0 to 2.6; I2 = 35%; 19 subsets) and 1.02 (95% CI, 1.01 to 1.02; 6 subsets) per 1% increase in low attenuation area
  • Studies with visual (pooled OR, 2.3; 95% CI, 1.9 to 2.6; I2 = 48%; 12 subsets) and quantitative (pooled OR, 2.2; 95% CI, 1.8 to 2.8; I2 = 3.7%; 8 subsets) assessments yielded comparable results for the dichotomous assessment
  • Based on 6 studies (1716 patients), the pooled ORs for lung cancer increased with emphysema severity and were higher for visual assessment (2.5, 3.7, and 4.5 for trace, mild, and moderate to severe, respectively) than for quantitative assessment (1.9 , 2.2, and 2.5) based on point estimates
  • Compared with no emphysema, only centrilobular emphysema (3 studies) was associated with lung cancer (pooled OR, 2.2; 95% CI, 1.5-3.2; P < .001)

Researchers found no evidence indicating the source of population or study design influenced the overall association seen. However, each method of emphysema assessment has limitations, they cautioned.

Based on the findings “it is recommended that a thin section thickness (≤1.5 mm) and 2950-HU [Hounsfield unit] cutoff value are used for quantitative emphysema assessment,” the authors wrote.

Lack of adjustment for airflow obstruction, an independent risk factor for lung cancer, in some studies included in the analyzes marks a limitation. Furthermore, only 6 included studies reported on the effect of emphysema severity on lung cancer and 2 on the association of trace emphysema. Cutoff values ​​for emphysema presence and severity also varied between studies.

“Our meta-analysis showed that not only visually assessed but also quantitatively assessed emphysema on CT is associated with lung cancer and that this risk increases for more severe emphysema,” said coauthor Marleen Vonder, PhD, of the Department of Epidemiology at University Medical Center Groningen in Groningen, the Netherlands.

But, she continued, “it is too early to conclude whether the presence of CT-defined emphysema leads to incremental and independent prognostic value over that of already known shared risk factors of emphysema and lung cancer.”

With more research, it may be possible in the future to detect emphysema on a baseline CT scan and use these data to identify high-risk patients who need more frequent follow-up lung cancer screening, she said.


Yang X, Wisselink HJ, Vliegenthart R, et al. Association between chest CT-defined emphasyma and lung cancer: a systematic review and meta-analysis. Radiology. Published online May 3, 2022. doi:10.1148/212904


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