Emphysema Progression and Lung Function Decline Among Angiotensin Converting Enzyme Inhibitors and Angiotensin-Receptor Blockade Users in the COPDGene Cohort

Abstract

Background: Attenuation of transforming growth factor β by blocking angiotensin II has been shown to reduce emphysema in a murine model. General population studies have demonstrated that the use of angiotensin converting enzyme inhibitors (ACEis) and angiotensin-receptor blockers (ARBs) is associated with reduction of emphysema progression in former smokers and that the use of ACEis is associated with reduction of FEV₁ progression in current smokers.

Research question: Is use of ACEi and ARB associated with less progression of emphysema and FEV₁ decline among individuals with COPD or baseline emphysema?

Methods: Former and current smokers from the Genetic Epidemiology of COPD Study who attended baseline and 5-year follow-up visits, did not change smoking status, and underwent chest CT imaging were included. Adjusted linear mixed models were used to evaluate progression of adjusted lung density (ALD), percent emphysema (%total lung volume <-950 Hounsfield units [HU]), 15th percentile of the attenuation histogram (attenuation [in HU] below which 15% of voxels are situated plus 1,000 HU), and lung function decline over 5 years between ACEi and ARB users and nonusers in those with spirometry-confirmed COPD, as well as all participants and those with baseline emphysema. Effect modification by smoking status also was investigated.

Results: Over 5 years of follow-up, compared with nonusers, ACEi and ARB users with COPD showed slower ALD progression (adjusted mean difference [aMD], 1.6; 95% CI, 0.34-2.9). Slowed lung function decline was not observed based on phase 1 medication (aMD of FEV₁ % predicted, 0.83; 95% CI, -0.62 to 2.3), but was when analysis was limited to consistent ACEi and ARB users (aMD of FEV₁ % predicted, 1.9; 95% CI, 0.14-3.6). No effect modification by smoking status was found for radiographic outcomes, and the lung function effect was more pronounced in former smokers. Results were similar among participants with baseline emphysema.

Interpretation: Among participants with spirometry-confirmed COPD or baseline emphysema, ACEi and ARB use was associated with slower progression of emphysema and lung function decline.

Trial registry: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.

Keywords: COPD; angiotensin II; emphysema progression.

Figure 1

Flowchart showing inclusion and exclusion criteria. COPDGene = Genetic Epidemiology of COPD; TLV = total lung volume; LVRS = lung volume reduction surgery.

Figure 2

Forest plot showing change in radiographic features and FEV₁ in ACEi and ARB users vs nonusers among participants with COPD. ACEi = angiotensin converting enzyme inhibitor; ARB = angiotensin-receptor blocker; HU = Hounsfield unit; Perc15 = 15th percentile of the attenuation histogram.