Indices of Childhood Socioeconomic Status and Dysanapsis among Older Adults: The Multi-Ethnic Study of Atherosclerosis Lung Study

To the Editor:Dysanapsis refers to a developmental mismatch between airway tree caliber and lung size (1).The concept was first proposed by Green and colleagues as a potential mechanism to explain interindividual differences in maximal expiratory airflow among healthy adults (1).Dysanapsis assessed by computed tomography (CT) is strongly associated with chronic obstructive pulmonary disease (COPD) risk (2) and all-cause mortality, but the origins of dysanapsis remain poorly understood.CT-assessed dysanapsis is evident by early adulthood (3), suggesting that factors that arise in childhood may contribute to the phenotypic differences in airway caliber relative to lung size.Socioeconomic status (SES), a marker of relative social and economic position and opportunities, can be measured across the life-course and operationalized as a composite of education, income, and occupation.SES is a known predictor of early-life anthropometric growth and lung function, as well as COPD risk and premature mortality (4-17).However, the association between early-life SES and dysanapsis in adulthood has yet to be investigated.We hypothesized that lower childhood SES, assessed by lower parental educational attainment, would be associated with smaller adult airway tree caliber relative to lung volume.Furthermore, we hypothesized that associations between SES and dysanapsis would be consistent across sex and racial and ethnic groups, given that dysanapsis is a risk predictor, and risk related to low lung function is fairly consistent across racial and ethnic groups in this and other cohorts (16, 18). Methods MESA (the Multi-Ethnic Study of Atherosclerosis) recruited a multiethnic sample of adults (45-84 yr), who self-reported Asian, Black, Hispanic, or White race and/or ethnicity, free of clinical cardiovascular disease, from six U.S. sites.Institutional review board approval was obtained from each site, and written informed consent was obtained.Childhood SES was quantified by participant-reported educational attainment of each parent.Response options were grouped into three categories: both parents with at least a college degree, both parents with at least a high school degree, at least one parent without a college or high school degree.Secondary indices included the sum of both parents' educational attainment, with 1 = no schooling; 2 = some schooling, no degree; 3 = high school degree; 4 = some college; 5 = college degree; 6 = graduate degree; and each parent's individual educational attainment.The MESA Lung Study quantified dysanapsis using airway measurements from cardiac CT at full inspiration on cardiac-gated multidetector-row and electron-beam scanners and analyzed using a modified version of Pulmonary Analysis Software Suite with semiautomated airway and lung analysis, as previously described (19-22).The primary outcome was dysanapsis quantified as the mean of airway lumen diameters in centimeters divided by the cube-root of cardiac-CT estimated total lung volume in centimeters cubed (airway-to-lung ratio CardiacCT ) (2, 23, 24).To evaluate whether variation in airway tree caliber specifically (rather than lung volume) was associated with childhood SES (25), a secondary outcome was mean CT-measured airway lumen diameter in millimeters.Multivariable linear regression models adjusted for: model 1 (base model): participant age, height (at time of CT), sex, selfidentified race and/or ethnicity, principal components of genetic ancestry (26); model 2 (base model plus confounders): self-reported cigarette, pipe, or cigar smoking status and years (19); self-reported secondhand smoke exposure and duration; self-reported parent smoking status during childhood; asthma diagnosis; dysanapsis genetic risk score (27); residential air pollutant concentrations (fine particulate matter [particulate matter <2.5 μm in aerodynamic diameter], nitrogen oxides [NO x ], and ozone [O 3 ]) from spatiotemporal MESA Air models (28); model 3 (base model plus confounders and precision variables): study site, number and spatial distribution of airways measured on CT, and voxel size; model 4 (base model plus confounders, precision variables, and participant's adult SES): participant's educational attainment, household income, employment status, and wealth index.Secondary analyses were: 1) modeled mean airway lumen diameter instead of airway-to-lung ratio; 2) adjusted for percentage of emphysema-like lung (29) and for forced expiratory volume in 1 second/forced vital capacity (FEV 1 / FVC; measured at a follow-up visit); 3) replaced the highest joint parent educational attainment with each parent's individual educational attainment; and 4) assessed for interactions by sex, race, and ethnicity using cross-product terms. ResultsDemographic characteristics for the 6,069 participants in this analysis are summarized in Table 1.Mean (standard deviation) airway-to-lung ratio CardiacCT was 0.218 (0.059).There were 391 (6.4%) participants who reported both parents with a college degree or higher; 1,704 (28.1%) reported both parents with a high school degree (no college) and 3,977 (65.5%) reported at least one parent A full list of participating MESA investigators and institutions can be found at http://www.mesa-nhlbi.org.

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