Quantitative CT as a New Tool for Evaluating COPD in Alpha-1 Antitrypsin Deficiency
For such a rare hereditary disorder as alpha-1 antitrypsin deficiency (AATD), we have so far used functional tests as the main tool for monitoring the progression of lung disease. Now we are moving further. Quantitative CT examination is even more advantageous in terms of assessing clinical development.
Etiopathogenesis of AATD
Alpha-1 antitrypsin deficiency is associated with a low serum level or dysfunctional molecule of alpha-1-proteinase inhibitor. In the lung parenchyma, this disorder leads to a loss of protection against certain serine proteases, especially neutrophil elastase. The resulting imbalance of protease and antiprotease activity leads to an increased risk of early emphysema and chronic obstructive pulmonary disease (COPD).
More Precise Assessment of Disease Severity
As with traditional smoking-related COPD, the severity of AATD is conventionally assessed by evaluating lung functions. However, functional tests cannot distinguish between emphysema and chronic bronchitis, which are the two main components of COPD. Recent developments in quantitative computed tomography (CT) methods have significantly improved our ability to assess lung architecture, providing more detailed information regarding the extent and severity of COPD in patients with AATD.
The distribution of emphysema can be assessed either qualitatively (visually) or quantitatively. While visual assessment has been shown to correlate well with pathological findings and remains sufficient for diagnosis, it can be subject to considerable variability not only between different physicians but also with different readings by the same physician. The severity of pathological changes can thus be underestimated or overestimated.
Quantitative CT is independent of the interpreting physician. The assessment is performed by special software that can automatically recognize the lungs and their contours and determine attenuation histograms, distinguishing emphysematous from structurally normal areas of the lung. Healthy lungs typically have attenuation values ranging from -750 to -850 HU, with an average value of -789 HU. In contrast, emphysematous lungs, which accumulate an abnormal amount of air, have lower density and therefore lower attenuation. Objectively determined attenuation correlates well with visual and pathological lung assessments.
What Reduces the Value of the Examination?
An important confounding factor in consistent lung density measurement is variability caused by the current lung volume, which depends on the degree of inspiration during the CT examination and the current state of the disease. The lung expands with breathing, significantly and naturally changing its density. Progressive hyperinflation is one of the factors characterizing the disease and reducing lung density, along with pathological changes in tissue.
Volume correction of the lungs is thus essential for the usefulness of the examination. There are two solutions: one is physiological adjustment, and the other is statistical. This is currently a computational issue, but in the near future, this part of the software will be more widely available, and this limit will not need to be considered.
Other confounding factors include interstitial lung disease, pulmonary edema, and the current level of smoking.
The Importance of Lung Densitometry
In both mentioned types of COPD, smoking-related and AATD, quantitative CT correlates with the severity of symptoms, the degree of airway obstruction, lung volumes, gas transfer coefficient, and the number of leukocytes. Worse CT results are also associated with a decline in health status and physical condition and even with an increased risk of death, especially if there is a noticeable decrease in density in the lower lung fields. The association with mortality is even stronger than with one-second vital capacity (FEV1).
According to available data, quantitative CT is highly sensitive (more so than other tests) and easily reproducible. COPD progresses long-term and slowly, with considerable variability in FEV1 decline. Given the high sensitivity and excellent correlation, lung densitometry should be used not only for examining and clinically evaluating patients but also for setting clinical study objectives, which can then be shorter and involve smaller patient cohorts, a practice that has already proven effective.
Conclusion
With quantitative computed tomography, we have a new diagnostic tool that has the potential to radically change our procedures and provide us with more accurate data on the effectiveness of treatment for patients with alpha-1 antitrypsin deficiency.
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Source: Campos M. A., Diaz A. A. The role of computed tomography for the evaluation of lung disease in alpha-1 antitrypsin deficiency. Chest 2018; 153 (5): 1240−1248, doi: 10.1016/j.chest.2017.11.017.
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