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Air pollution and percent emphysema identified by computed tomography in the Multi-Ethnic study of Atherosclerosis.

ABSTRACT: BACKGROUND:Air pollution is linked to low lung function and to respiratory events, yet little is known of associations with lung structure. OBJECTIVES:We examined associations of particulate matter (PM2.5, PM10) and nitrogen oxides (NOx) with percent emphysema-like lung on computed tomography (CT). METHODS:The Multi-Ethnic Study of Atherosclerosis (MESA) recruited participants (45-84 years of age) in six U.S. states. Percent emphysema was defined as lung regions < -910 Hounsfield Units on cardiac CT scans acquired following a highly standardized protocol. Spirometry was also conducted on a subset. Individual-level 1- and 20-year average air pollution exposures were estimated using spatiotemporal models that included cohort-specific measurements. Multivariable regression was conducted to adjust for traditional risk factors and study location. RESULTS:Among 6,515 participants, we found evidence of an association between percent emphysema and long-term pollution concentrations in an analysis leveraging between-city exposure contrasts. Higher concentrations of PM2.5 (5 ?g/m3) and NOx (25 ppb) over the previous year were associated with 0.6 (95% CI: 0.1, 1.2%) and 0.5 (95% CI: 0.1, 0.9%) higher average percent emphysema, respectively. However, after adjustment for study site the associations were -0.6% (95% CI: -1.5, 0.3%) for PM2.5 and -0.5% (95% CI: -1.1, 0.02%) for NOx. Lower lung function measures (FEV1 and FVC) were associated with higher PM2.5 and NOx levels in 3,791 participants before and after adjustment for study site, though most associations were not statistically significant. CONCLUSIONS:Associations between ambient air pollution and percentage of emphysema-like lung were inconclusive in this cross-sectional study, thus longitudinal analyses may better clarify these associations with percent emphysema.

SUBMITTER: Adar SD

PROVIDER: S-EPMC4314244 | biostudies-literature | 2015 Feb

REPOSITORIES: biostudies-literature

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Air pollution and percent emphysema identified by computed tomography in the Multi-Ethnic study of Atherosclerosis.

Adar Sara D SD Kaufman Joel D JD Diez-Roux Ana V AV Hoffman Eric A EA D'Souza Jennifer J Stukovsky Karen H KH Rich Stephen S SS Rotter Jerome I JI Guo Xiuqing X Raffel Leslie J LJ Sampson Paul D PD Oron Assaf P AP Raghunathan Trivellore T Barr R Graham RG

Environmental health perspectives 20141010 2

<h4>Background</h4>Air pollution is linked to low lung function and to respiratory events, yet little is known of associations with lung structure.<h4>Objectives</h4>We examined associations of particulate matter (PM2.5, PM10) and nitrogen oxides (NOx) with percent emphysema-like lung on computed tomography (CT).<h4>Methods</h4>The Multi-Ethnic Study of Atherosclerosis (MESA) recruited participants (45-84 years of age) in six U.S. states. Percent emphysema was defined as lung regions < -910 Houn ...[more]

PMID: 25302408

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Project description:RationalePulmonary emphysema overlaps partially with spirometrically defined chronic obstructive pulmonary disease and is heritable, with moderately high familial clustering.ObjectivesTo complete a genome-wide association study (GWAS) for the percentage of emphysema-like lung on computed tomography in the Multi-Ethnic Study of Atherosclerosis (MESA) Lung/SNP Health Association Resource (SHARe) Study, a large, population-based cohort in the United States.MethodsWe determined percent emphysema and upper-lower lobe ratio in emphysema defined by lung regions less than -950 HU on cardiac scans. Genetic analyses were reported combined across four race/ethnic groups: non-Hispanic white (n = 2,587), African American (n = 2,510), Hispanic (n = 2,113), and Chinese (n = 704) and stratified by race and ethnicity.Measurements and main resultsAmong 7,914 participants, we identified regions at genome-wide significance for percent emphysema in or near SNRPF (rs7957346; P = 2.2 × 10(-8)) and PPT2 (rs10947233; P = 3.2 × 10(-8)), both of which replicated in an additional 6,023 individuals of European ancestry. Both single-nucleotide polymorphisms were previously implicated as genes influencing lung function, and analyses including lung function revealed independent associations for percent emphysema. Among Hispanics, we identified a genetic locus for upper-lower lobe ratio near the α-mannosidase-related gene MAN2B1 (rs10411619; P = 1.1 × 10(-9); minor allele frequency [MAF], 4.4%). Among Chinese, we identified single-nucleotide polymorphisms associated with upper-lower lobe ratio near DHX15 (rs7698250; P = 1.8 × 10(-10); MAF, 2.7%) and MGAT5B (rs7221059; P = 2.7 × 10(-8); MAF, 2.6%), which acts on α-linked mannose. Among African Americans, a locus near a third α-mannosidase-related gene, MAN1C1 (rs12130495; P = 9.9 × 10(-6); MAF, 13.3%) was associated with percent emphysema.ConclusionsOur results suggest that some genes previously identified as influencing lung function are independently associated with emphysema rather than lung function, and that genes related to α-mannosidase may influence risk of emphysema.

Project description:RationaleAlthough 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.ObjectivesTo determine whether angiotensin-converting enzyme (ACE) inhibitor and ARB dose is associated with slowed progression of percent emphysema by CT.MethodsThe 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.ResultsAmong 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.ConclusionsIn 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.

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Air pollution and percent emphysema identified by computed tomography in the Multi-Ethnic study of Atherosclerosis.

Publications

Air pollution and percent emphysema identified by computed tomography in the Multi-Ethnic study of Atherosclerosis.

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