RESUMEN
RATIONALE: Computed tomography (CT)-based lung density is used to quantitate the percentage of emphysema-like lung (hereafter referred to as percent emphysema), but information on its distribution among healthy nonsmokers is limited. OBJECTIVES: We evaluated percent emphysema and total lung volume on CT scans of healthy never-smokers in a multiethnic, population-based study. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study investigators acquired full-lung CT scans of 3,137 participants (ages 54-93 yr) between 2010-12. The CT scans were taken at full inspiration following the Subpopulations and Intermediate Outcome Measures in COPD Study (SPIROMICS) protocol. "Healthy never-smokers" were defined as participants without a history of tobacco smoking or respiratory symptoms and disease. "Percent emphysema" was defined as the percentage of lung voxels below -950 Hounsfield units. "Total lung volume" was defined by the volume of lung voxels. MEASUREMENTS AND MAIN RESULTS: Among 854 healthy never-smokers, the median percent emphysema visualized on full-lung scans was 1.1% (interquartile range, 0.5-2.5%). The percent emphysema values were 1.2 percentage points higher among men compared with women and 0.7, 1.2, and 1.2 percentage points lower among African Americans, Hispanics, and Asians compared with whites, respectively (P < 0.001). Percent emphysema was positively related to age and height and inversely related to body mass index. The findings were similar for total lung volume on CT scans and for percent emphysema defined at -910 Hounsfield units and measured on cardiac scans. Reference equations to account for these differences are presented for never, former and current smokers. CONCLUSIONS: Similar to lung function, percent emphysema varies substantially by demographic factors and body size among healthy never-smokers. The presented reference equations will assist in defining abnormal values for percent emphysema and total lung volume on CT scans, although validation is pending.
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Etnicidad , Vigilancia de la Población , Enfisema Pulmonar/etnología , Distribución por Edad , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Humanos , Mediciones del Volumen Pulmonar , Masculino , Persona de Mediana Edad , Prevalencia , Estudios Prospectivos , Enfisema Pulmonar/diagnóstico , Valores de Referencia , Distribución por Sexo , Tomografía Computarizada por Rayos X , Estados Unidos/epidemiologíaRESUMEN
RATIONALE: Pulmonary emphysema overlaps partially with spirometrically defined chronic obstructive pulmonary disease and is heritable, with moderately high familial clustering. OBJECTIVES: To 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. METHODS: We 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 RESULTS: Among 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. CONCLUSIONS: Our 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.
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Estudio de Asociación del Genoma Completo , Polimorfismo de Nucleótido Simple , Enfisema Pulmonar/genética , Tomografía Computarizada por Rayos X , Anciano , Anciano de 80 o más Años , Femenino , Estudios de Seguimiento , Marcadores Genéticos , Técnicas de Genotipaje , Humanos , Masculino , Manosidasas/genética , Persona de Mediana Edad , N-Acetilglucosaminiltransferasas/genética , Proteínas del Tejido Nervioso/genética , Enfisema Pulmonar/diagnóstico por imagen , Enfisema Pulmonar/etnología , ARN Helicasas/genética , Tioléster Hidrolasas/genética , Estados Unidos/epidemiología , alfa-Manosidasa/genética , Proteínas Nucleares snRNP/genéticaRESUMEN
BACKGROUND: The potential consequences of asthma in childhood and young adulthood on lung structure in older adults have not been studied in a large, population-based cohort. OBJECTIVE: The authors hypothesized that a history of asthma onset in childhood (age 18 years or before) or young adulthood (age 19-45 years) was associated with altered lung structure on computed tomography in later life. METHODS: The Multi-Ethnic Study of Atherosclerosis Lung Study recruited 3965 participants and assessed asthma history by using standardized questionnaires, guideline-based spirometry, and segmental airway dimensions and percentage of low attenuation area (%LAA) on computed tomographic scans. RESULTS: Asthma with onset in childhood and young adulthood was associated with large decrements in FEV(1) among participants with a mean age of 66 years (-365 mL and -343 mL, respectively; P < .001). Asthma with onset in childhood and young adulthood was associated with increased mean airway wall thickness standardized to an internal perimeter of 10 mm (0.1 mm, P < .001 for both), predominantly from narrower segmental airway lumens (-0.39 mm and -0.34 mm, respectively; P < .001). Asthma with onset in childhood and young adulthood also was associated with a greater %LAA (1.69% and 4.30%, respectively; P < .001). Findings were similar among never smokers, except that differential %LAA in childhood-onset asthma were not seen in them. CONCLUSION: Asthma with onset in childhood or young adulthood was associated with reduced lung function, narrower airways, and among asthmatic patients who smoked, greater %LAA in later life.
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Asma/diagnóstico por imagen , Asma/patología , Aterosclerosis/diagnóstico por imagen , Aterosclerosis/patología , Pulmón/diagnóstico por imagen , Pulmón/patología , Factores de Edad , Anciano , Asma/etnología , Aterosclerosis/etnología , Estudios de Cohortes , Etnicidad , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas de Función Respiratoria/métodos , Fumar/patología , Encuestas y Cuestionarios , Tomografía Computarizada por Rayos X/métodosRESUMEN
BACKGROUND: Autopsy studies show that smoking contributes to airway wall hyperplasia and narrowing of the airway lumen. Studies of smoking and airway measures on computed tomography (CT) scan are limited to case-control studies of measures that combine airway lumen and wall thickness. OBJECTIVES: We hypothesized that cumulative cigarette smoking would be associated with increased airway wall thickness in a large, population-based cohort. METHODS: The Multi-Ethnic Study of Atherosclerosis enrolled participants age 45-84 years from the general population. Smoking history was assessed via standardized questionnaire items; current smoking was confirmed in half the cohort with cotinine. Airway lumen and wall thickness were measured in two dimensions in posterior basal segmental bronchi on cardiac-gated CT scans. Analyses were adjusted for age, gender, genetic ancestry, education, height, weight, asthma history, particulate matter, scanner type, and scanner current. RESULTS: Half of the 7898 participants had smoked and 14% were current smokers. Pack-years of smoking were associated with thicker airway walls (mean increase 0.002 mm per ten pack-years [95% CI: 0.00002, 0.004] p = 0.03). Current smoking was associated with narrower airway lumens (mean decrease -0.11 mm [95% CI: -0.2, -0.02] p = 0.02). There was no evidence that either association was modified by genetic ancestry, and findings persisted among participants without clinical disease. CONCLUSIONS: Long-term cigarette smoking was associated with subclinical increases in wall thickness of sub-segmental airways whereas current smoking was associated with narrower airway lumen diameters. Smoking may contribute to airway wall thickening prior to the development of overt chronic obstructive pulmonary disease.
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Bronquios/patología , Fumar/patología , Anciano , Anciano de 80 o más Años , Estudios de Cohortes , Estudios Transversales , Femenino , Humanos , Hiperplasia/etnología , Hiperplasia/patología , Masculino , Persona de Mediana Edad , Fumar/etnología , Tomografía Computarizada por Rayos X , Estados Unidos/epidemiologíaRESUMEN
RATIONALE AND OBJECTIVES: Cardiac computed tomographic (CT) scans for the assessment of coronary calcium scores include approximately 70% of the lung volume and may be useful for the quantitative assessment of emphysema. The reproducibility of lung density measures from cardiac computed tomography and their validity compared to lung density measures from full-lung scans is unknown. MATERIALS AND METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) performed paired cardiac CT scans for 6814 participants at baseline and at follow-up. The MESA-Lung Study assessed lung density measures in the lung fields of these cardiac scans, counting voxels below -910 HU as moderate-to-severe emphysema-like lung regions. We evaluated: 1) the reproducibility of lung density measures among 120 randomly selected participants; 2) the comparability of measures acquired on electron beam CT (EBCT) and multidetector CT (MDCT) scanners among 10 participants; and 3) the validity of these measures compared to full-lung scans among 42 participants. Limits of agreement were determined using Bland-Altman approaches. RESULTS: Percent emphysema measures from paired cardiac scans were highly correlated (r = 0.92-0.95) with mean difference of -0.05% (95% limits of agreement: -8.3, 8.4%). Measures from EBCT and MDCT scanners were comparable (mean difference -0.9%; 95% limits of agreement: -5.1, 3.3%). Percent emphysema measures from MDCT cardiac and MDCT full-lung scans were highly correlated (r = 0.93) and demonstrated reasonable agreement (mean difference 2.2%; 95% limits of agreement: -9.2, 13.8%). CONCLUSIONS: Although full-lung imaging is preferred for the quantification of emphysema, the lung imaging from paired cardiac computed tomography provided a reproducible and valid quantitative assessment of emphysema in a population-based sample.