title: Angiotensin-Converting Inhibitors and Angiotensin II Receptor Blockers and Longitudinal Change in Percent Emphysema on Computed Tomography. The Multi-Ethnic Study of Atherosclerosis Lung Study.
abstract: BACKGROUND
  Although emphysema on computed tomography (CT) is associated with increased morbidity and mortality in patients with and without spirometrically defined chronic obstructive pulmonary disease, no available medications target emphysema outside of alpha-1 antitrypsin deficiency. Transforming growth factor-β and endothelial dysfunction are implicated in emphysema pathogenesis, and angiotensin II receptor blockers (ARBs) inhibit transforming growth factor-β, improve endothelial function, and restore airspace architecture in murine models. Evidence in humans is, however, lacking.
  
  
  OBJECTIVE
  To determine whether angiotensin-converting enzyme (ACE) inhibitor and ARB dose is associated with slowed progression of percent emphysema by CT.
  
  
  METHODS
  The Multi-Ethnic Study of Atherosclerosis researchers recruited participants ages 45-84 years from the general population from 2000 to 2002. Medication use was assessed by medication inventory. Percent emphysema was defined as the percentage of lung regions less than -950 Hounsfield units on CTs. Mixed-effects regression models were used to adjust for confounders.
  
  
  RESULTS
  Among 4,472 participants, 12% used an ACE inhibitor and 6% used an ARB at baseline. The median percent emphysema was 3.0% at baseline, and the rate of progression was 0.64 percentage points over a median of 9.3 years. Higher doses of ACE or ARB were independently associated with a slower change in percent emphysema (P = 0.03). Over 10 years, in contrast to a predicted mean increase in percent emphysema of 0.66 percentage points in those who did not take ARBs or ACE inhibitors, the predicted mean increase in participants who used maximum doses of ARBs or ACE inhibitors was 0.06 percentage points (P = 0.01). The findings were of greatest magnitude among former smokers (P < 0.001). Indications for ACE inhibitor or ARB drugs (hypertension and diabetes) and other medications for hypertension and diabetes were not associated independently with change in percent emphysema. There was no evidence that ACE inhibitor or ARB dose was associated with decline in lung function.
  
  
  CONCLUSIONS
  In a large population-based study, ACE inhibitors and ARBs were associated with slowed progression of percent emphysema by chest CT, particularly among former smokers. Randomized clinical trials of ACE and ARB agents are warranted for the prevention and treatment of emphysema.
authors.affiliation: 1 Department of Medicine, College of Physicians and Surgeons.
authors.forename: Megha A
authors.initials: MA
authors.lastname: Parikh
authors.affiliation: 1 Department of Medicine, College of Physicians and Surgeons.
authors.forename: Carrie P
authors.initials: CP
authors.lastname: Aaron
authors.affiliation: 2 Department of Radiology, University of Iowa, Iowa City, Iowa.
authors.forename: Eric A
authors.initials: EA
authors.lastname: Hoffman
authors.affiliation: 1 Department of Medicine, College of Physicians and Surgeons.|3 Department of Psychiatry, Stony Brook University, Stony Brook, New York.
authors.forename: Joseph E
authors.initials: JE
authors.lastname: Schwartz
authors.affiliation: 4 Department of Environmental Health Sciences, Mailman School of Public Health.
authors.forename: Jaime
authors.initials: J
authors.lastname: Madrigano
authors.affiliation: 5 Department of Radiology, College of Physicians and Surgeons, and.
authors.forename: John H M
authors.initials: JHM
authors.lastname: Austin
authors.affiliation: 6 Division of Pulmonary and Critical Care Medicine, Feinberg School of Medicine, Northwestern University, Chicago, Illinois.
authors.forename: Ravi
authors.identifier: http://orcid.org/0000-0003-2443-0876
authors.initials: R
authors.lastname: Kalhan
authors.affiliation: 7 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: Gina
authors.initials: G
authors.lastname: Lovasi
authors.affiliation: 8 Division of Cardiology, School of Medicine, University of California, Los Angeles, Los Angeles, California; and.
authors.forename: Karol
authors.initials: K
authors.lastname: Watson
authors.affiliation: 9 Department of Biostatistics, University of Washington, Seattle, Washington.
authors.forename: Karen Hinckley
authors.initials: KH
authors.lastname: Stukovsky
authors.affiliation: 1 Department of Medicine, College of Physicians and Surgeons.|7 Department of Epidemiology, Mailman School of Public Health, Columbia University, New York, New York.
authors.forename: R Graham
authors.initials: RG
authors.lastname: Barr
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D057911:Angiotensin Receptor Antagonists / Q000008:administration & dosage*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage*; D005260:Female; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D008875:Middle Aged; D029424:Pulmonary Disease, Chronic Obstructive / Q000150:complications* / Q000503:physiopathology; D011656:Pulmonary Emphysema / Q000000981:diagnostic imaging* / Q000188:drug therapy*; D012044:Regression Analysis; D012129:Respiratory Function Tests; D012907:Smoking / Q000009:adverse effects; D013147:Spirometry; D014057:Tomography, X-Ray Computed; D014481:United States
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors
keywords: emphysema; lung; pharmacoepidemiology