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1.
Artigo em Inglês | MEDLINE | ID: mdl-35063614

RESUMO

BACKGROUND: Pericardial fat has been associated with adverse cardiovascular outcomes through adiposity-associated inflammation and insulin resistance, which in turn are linked to cardiac dysfunction. We sought to evaluate the association between pericardial fat volume with cardiac structure and function in adults without baseline cardiovascular disease. METHODS: We analyzed data from the Multi-Ethnic Study of Atherosclerosis (MESA). Linear regression was used to examine the association between pericardial fat volume (by cardiac CT during Exam 1; 2000-2002) with cardiac function by echocardiography, six-minute walk distance (6MWD), and symptom severity as assessed using the Kansas City Cardiomyopathy Questionnaire (KCCQ)-12 (Exam 6; 2016-2018). RESULTS: Among 3,032 participants, each standard-deviation (39.3 cm3) increase in pericardial fat volume was associated with lower (worse) absolute left atrial reservoir strain (ß -0.98%; 95%CI -1.29, -0.68; p<0.001), right ventricular free wall strain (ß -0.75%; 95%CI -1.00, -0.51; p<0.001) and right atrial reservoir strain (ß -0.59%; 95%CI -1.00, -0.19; p<0.01) after adjustment for potential confounders. Greater pericardial fat volume was associated with lower six-minute walk distances (ß -5.70 m; 95%CI -10.34, -1.06; p=0.02), but not with KCCQ-12 scores or NT-proBNP after multivariable adjustment. CONCLUSIONS: In a population-based cohort of adults, pericardial fat volume was independently associated with subclinical atrial and right ventricular dysfunction and reduced six-minute walk distance. These distinct changes in cardiac structure and function suggests a potential mechanistic role for pericardial fat in early heart failure.

2.
Blood ; 2021 Sep 10.
Artigo em Inglês | MEDLINE | ID: mdl-34855941

RESUMO

Chronic obstructive pulmonary disease (COPD) is associated with age and smoking, but other determinants of the disease are incompletely understood. Clonal hematopoiesis of indeterminate potential (CHIP) is a common, age-related state in which somatic mutations in clonal blood populations induce aberrant inflammatory responses. Patients with CHIP have an elevated risk for cardiovascular disease, but the association with COPD remains unclear. We analyzed whole-genome and exome sequencing data to detect CHIP in 48,835 subjects, of whom 8,444 had moderate-to-very-severe COPD, from four separate cohorts with COPD phenotyping and smoking history. We measured emphysema in murine models in which Tet2 was deleted in hematopoietic cells. In COPDGene, individuals with CHIP had a risk of moderate-to-severe and severe or very severe COPD 1.6 and 2.2 times greater than non-carriers, respectively (adjusted 95% confidence intervals [CI], 1.1 to 2.2 and 1.5 to 3.2). These findings were consistent observed in three additional cohorts and meta-analyses of all subjects. CHIP was also associated with decreased FEV1% predicted in COPDGene (mean between group difference -5.7%; adjusted 95% CI, -8.8 to -2.6), a finding replicated in additional cohorts. Smoke exposure was associated with a small but significant increased risk of having CHIP (OR 1.03 per ten pack-years, 95% CI 1.01-1.05) in the meta-analysis of all subjects. Inactivation of Tet2 in mouse hematopoietic cells exacerbated emphysema development and inflammation in cigarette smoke exposure models. Somatic mutations in blood cells are associated with the development and severity of COPD, independent of age and cumulative smoke exposure.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34913855

RESUMO

RATIONALE: African Americans have worse outcomes in chronic obstructive pulmonary disease (COPD). OBJECTIVE: Assess whether race-specific approaches for estimating lung function contribute to racial inequities by failing to recognize pathological decrements and considering them normal. METHODS: In a cohort with and at-risk-for COPD, we assessed whether lung function prediction equations applied in a race-specific versus universal manner better modeled the relationship between forced expiratory volume in one second (FEV1), forced vital capacity (FVC), and other COPD outcomes, including COPD Assessment Test (CAT), St George's Respiratory Questionnaire (SGRQ), CT percent emphysema, airway wall thickness (Pi10) and six-minute walk test (6MWT). We related these outcomes to differences in FEV1 using multiple linear regression, and compared predictive performance between fitted models using root mean squared error and Alpaydin's paired F test. MEASUREMENTS AND MAIN RESULTS: Using race-specific equations, African Americans were calculated to have better lung function than Non-Hispanic Whites ([FEV1] 76.2% vs. 71.3% predicted, P=0.02). Using universally-applied equations, African Americans were calculated to have worse lung function. Using NHW-H, FEV1 was 61.4%% versus 71.3%; (P<0.001). Using GLI-O, FEV1 was 69.4% versus 77.4% (P<0.001). Prediction errors from linear regression were less for universally-applied equations compared with race-specific equations when comparing FEV1 %predicted with CAT (P<0.01), SGRQ (P<0.01) and Pi10 (P<0.01). While African Americans had greater adversity (P<0.001), less adversity was only associated with better FEV1 in Non-Hispanic White participants (P-for-interaction=0.041). CONCLUSIONS: Race-specific equations may under-estimate COPD severity in African Americans.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34929108

RESUMO

RATIONALE: Higher blood monocyte counts are associated with worse survival in adults with clinically diagnosed pulmonary fibrosis. Their association with the development and progression of interstitial lung abnormalities (ILA) in humans is unknown. OBJECTIVES: We evaluated the associations of blood monocyte count, and other immune cell types, with ILA, high attenuation areas (HAA), and forced vital capacity (FVC) in four independent cohorts. METHODS: We included participants with measured monocyte counts and CT imaging enrolled in the Multi-Ethnic Study of Atherosclerosis (MESA, n=484), Age/Gene Environment Susceptibility Study (AGES-Reykjavik, n=3,547), Genetic Epidemiology of COPD (COPDGene, n=2,719), and the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE, n=646). MEASUREMENTS AND MAIN RESULTS: After adjustment for covariates, a 1-SD increment in blood monocyte count was associated with ILA in MESA (odds ratio (OR) 1.3, 95% CI 1.0-1.8), AGES-Reykjavik (OR 1.2, 95% CI 1.1-1.3), COPDGene (OR 1.3, 95% CI 1.2-1.4), and ECLIPSE (OR 1.2, 95% CI 1.0-1.4). A higher monocyte count was associated with ILA progression over 5 years in AGES-Reykjavik (OR 1.2, 95% CI 1.0-1.3). Compared with participants without ILA, there was a higher percentage of activated monocytes among those with ILA in MESA. Higher monocyte count was associated with greater HAA in MESA and lower FVC in MESA and COPDGene. Associations of other immune cell types were less consistent. CONCLUSIONS: Higher blood monocyte counts were associated with the presence and progression of interstitial lung abnormalities and lower FVC.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34913853

RESUMO

RATIONALE: Normal values for forced expiratory volume in one second (FEV1) and forced vital capacity (FVC) are currently calculated using cross-sectional reference equations that include terms for race/ethnicity, an approach that may reinforce disparities and is of unclear clinical benefit. OBJECTIVES: To determine whether race/ethnic-based spirometry reference equations improve the prediction of incident chronic lower respiratory disease (CLRD) events and mortality compared to race/ethnic-neutral equations. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) Lung Study, a population-based, prospective cohort study of White, Black, Hispanic, and Asian adults, performed standardized spirometry in 2004-06. Predicted values for spirometry were calculated using race/ethnic-based equations following guidelines and, alternatively, race/ethnic-neutral equations without terms for race/ethnicity. Participants were followed for events through 2019. MEASUREMENTS AND MAIN RESULTS: The mean age of 3,344 participants was 65 years and self-reported race/ethnicity was 36% White, 25% Black, 23% Hispanic, and 17% Asian. There were 181 incident CLRD-related events and 547 deaths over a median of 11.6 years. There was no evidence that percent-predicted FEV1 or FVC calculated by race/ethnic-based equations improved the prediction of CLRD-related events compared to that calculated by race/ethnic-neutral equations (difference in C-statistics -0.005, 95% CI -0.013, 0.003, and -0.008, 95% CI -0.016, -0.0006, respectively). Findings were similar for mortality (difference in C-statistics -0.002, 95% CI -0.008, 0.003, and -0.004, 95% CI -0.009, 0.001, respectively). CONCLUSIONS: There was no evidence that race/ethnic-based spirometry reference equations improved the prediction of clinical events compared to race/ethnic-neutral equations. The inclusion of race/ethnicity in spirometry reference equations should be reconsidered.

6.
Chest ; 2021 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-34801592

RESUMO

BACKGROUND: Improved understanding of the pathways associated with airway pathophysiology in chronic obstructive pulmonary disease (COPD) will identify new predictive biomarkers and novel therapeutic targets. RESEARCH QUESTION: Which physiologic pathways are altered in the airways of subjects with COPD and predict exacerbations? STUDY DESIGN AND METHODS: We applied a mass spectrometric panel of metabolomic biomarkers related to mucus hydration and inflammation to sputa from the SPIROMICS multi-center COPD study. Biomarkers elevated in sputa from subjects with COPD were evaluated for relationships to measures of COPD disease severity and their ability to predict future exacerbations. RESULTS: Sputum supernatants from 980 subjects (77 healthy non-smokers [NS], 341 smokers with preserved spirometry [SPS], and 562 COPD subjects [178 GOLD 1, 303 GOLD 2, and 81 GOLD 3]) were analyzed. Biomarkers from multiple pathways were elevated in COPD and correlated with sputum neutrophil counts. Among the most significant analytes (at FDR 0.1) were sialic acid, hypoxanthine, xanthine, methylthioadenosine, adenine, and glutathione. Sialic acid and hypoxanthine were strongly associated with measures of disease severity, and elevation of these biomarkers was associated with shorter time to exacerbation and improved prediction models of future exacerbations. INTERPRETATION: Biomarker evaluation implicated pathways involved in mucus hydration, adenosine metabolism, methionine salvage, and oxidative stress in COPD airway pathophysiology. Therapies that target these pathways may be of benefit in COPD, and a simple model adding sputum soluble phase biomarkers improves prediction of pulmonary exacerbations.

7.
Chest ; 2021 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-34767825

RESUMO

BACKGROUND: Small airways are known to be affected early in the course of chronic obstructive pulmonary disease (COPD); however, traditional spirometric indices may not accurately identify small airways disease. RESEARCH QUESTION: Can FEV3/FEV6 identify early airflow abnormalities and predict future clinically important respiratory-related outcomes, including development of COPD? STUDY DESIGN AND METHODS: We included eight hundred thirty-two current and former smokers with post-bronchodilator FEV1/FVC ≥0.7 from the SPIROMICS cohort. Participants were classified as having a reduced pre-bronchodilator FEV3/FEV6 based on lower limit of normal (LLN) values. Repeatability analysis was performed for FEV3 and FEV6. Regression modeling was used to evaluate the relationship between baseline FEV3/FEV6 and outcome measures including functional small airways disease on thoracic imaging and respiratory exacerbations. Interval censored analysis was used to assess progression to COPD. RESULTS: FEV3/FEV6

8.
J Sleep Res ; : e13475, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34498326

RESUMO

Impairment of the circadian rhythm promotes lung inflammation and fibrosis in pre-clinical models. We aimed to examine whether short and/or long sleep duration and other markers of sleep-wake patterns are associated with a greater burden of lung parenchymal abnormalities on computed tomography among adults. We cross-sectionally examined associations of sleep duration captured by actigraphy with interstitial lung abnormalities (n = 1111) and high attenuation areas (n = 1416) on computed tomography scan in the Multi-Ethnic Study of Atherosclerosis at Exam 5 (2010-2013). We adjusted for potential confounders in logistic and linear regression models for interstitial lung abnormalities and high attenuation area, respectively. High attenuation area models were also adjusted for study site, lung volume imaged, radiation dose and stratified by body mass index. Secondary exposures were self-reported sleep duration, sleep fragmentation index, sleep midpoint and chronotype. The mean age of those with longer sleep duration (≥ 8 hr) was 70 years and the prevalence of interstitial lung abnormalities was 14%. Increasing actigraphy-based sleep duration among participants with ≥ 8 hr of sleep was associated with a higher adjusted odds of interstitial lung abnormalities (odds ratio of 2.66 per 1-hr increment, 95% confidence interval 1.42-4.99). Longer sleep duration and higher sleep fragmentation index were associated with greater high attenuation area on computed tomography among participants with a body mass index < 25 kg m-2 (p-value for interaction < 0.02). Self-reported sleep duration, later sleep midpoint and evening chronotype were not associated with outcomes. Actigraphy-based longer sleep duration and sleep fragmentation were associated with a greater burden of lung abnormalities on computed tomography scan.

9.
Ann Am Thorac Soc ; 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34499590

RESUMO

RATIONALE: The effect of insulin resistance on left ventricular function is well documented, however less is known regarding its effect on the right ventricle (RV). OBJECTIVES: To evaluate the association between insulin resistance and RV function by echocardiography in a cohort of adults without baseline cardiovascular disease. METHODS: We performed a retrospective cohort study in the Multi-Ethnic Study of Atherosclerosis (MESA). Linear regression was used to examine the association between overall insulin resistance measured by the mean triglyceride to HDL cholesterol ratio (TG:HDL), and change in TG:HDL over time for each participant with echocardiographic RV function. Logistic regression was used to calculate the odds ratios of RV systolic and diastolic dysfunction. RESULTS: Among 3,032 participants, higher mean TG:HDL was associated with lower (worse) absolute RV longitudinal strain (ß -0.38; 95%CI -0.64, -0.13; p<0.01), tricuspid annular plane systolic excursion (TAPSE; ß -0.05; 95%CI -0.07, -0.04; p<0.001) and higher odds of abnormal RV strain (OR 1.26; 95%CI 1.08, 1.47; p<0.01) and abnormal TAPSE (OR 1.31; 95%CI 1.14, 1.51; p<0.001). TG:HDL was also associated with lower tricuspid E/A ratio (ß -0.03; 95%CI -0.04, -0.01; p<0.01), higher E/e' ratio (ß 0.15; 95%CI 0.07, 0.23; p<0.001), and higher odds of graded RV diastolic dysfunction (OR 1.19; 95%CI 1.03, 1.39; p<0.05). These associations remained following multivariable adjustment. CONCLUSIONS: Insulin resistance was associated with decreased RV systolic and diastolic function after adjusting for alternative causes of RV dysfunction, suggesting that insulin resistant individuals are at risk for early RV dysfunction, even in the absence of cardiovascular disease.

10.
Circ Cardiovasc Imaging ; 14(8): e012943, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34387095

RESUMO

Imaging genomics is a rapidly evolving field that combines state-of-the-art bioimaging with genomic information to resolve phenotypic heterogeneity associated with genomic variation, improve risk prediction, discover prevention approaches, and enable precision diagnosis and treatment. Contemporary bioimaging methods provide exceptional resolution generating discrete and quantitative high-dimensional phenotypes for genomics investigation. Despite substantial progress in combining high-dimensional bioimaging and genomic data, methods for imaging genomics are evolving. Recognizing the potential impact of imaging genomics on the study of heart and lung disease, the National Heart, Lung, and Blood Institute convened a workshop to review cutting-edge approaches and methodologies in imaging genomics studies, and to establish research priorities for future investigation. This report summarizes the presentations and discussions at the workshop. In particular, we highlight the need for increased availability of imaging genomics data in diverse populations, dedicated focus on less common conditions, and centralization of efforts around specific disease areas.


Assuntos
Pesquisa Biomédica , Cardiopatias/diagnóstico por imagem , Genômica por Imageamento , Pneumopatias/diagnóstico por imagem , Animais , Inteligência Artificial , Difusão de Inovações , Predisposição Genética para Doença , Variação Genética , Cardiopatias/genética , Cardiopatias/terapia , Humanos , Pneumopatias/genética , Pneumopatias/terapia , National Heart, Lung, and Blood Institute (U.S.) , Fenótipo , Valor Preditivo dos Testes , Prognóstico , Estados Unidos
12.
Ann Am Thorac Soc ; 2021 Aug 19.
Artigo em Inglês | MEDLINE | ID: mdl-34410883

RESUMO

RATIONALE: Individuals with Chronic Obstructive Pulmonary Disease (COPD) have a high prevalence of depression, which is associated with increased COPD hospitalizations and readmissions. OBJECTIVES: Examine the impact of depressive symptoms compared to FEV1% on COPD morbidity. METHODS: Using longitudinal data from individuals with COPD in the Subpopulations and Intermediate Outcome Measures in COPD Study, longitudinal growth analysis was performed to assess COPD morbidity by assessing differences in baseline 6 minute walk distance (6MWD) and patient reported outcomes (PROs) and their rate of change over time explained by depressive symptoms or lung function, as measured by Hospital Anxiety and Depression Scale (HADS) or FEV1% respectively. PROs consisted of in person completion of St. George's Respiratory Questionnaire (SGRQ), COPD Assessment Test (CAT), Functional Assessment of Chronic Illness Therapy Fatigue (FACIT-F), and Modified Medical Research Council Dyspnea Scale (mMRC) measures. RESULTS: Of individuals analyzed (n=1830), 43% were females, 81% Caucasian with mean ±SD age of 65.1±8.1, and 52.7±27.5 pack-years smoking. Mean ±SD FEV1% was 60.9±23.0% and 20% had clinically significant depressive symptoms. Adjusted models showed higher HADS scores and lower FEV1% each were associated with worse PROs at baseline (p≤0.001). Depression accounted for more baseline variance in SGRQ, CAT, and FACT-F than FEV1%, explaining 30-67% of heterogeneity. While FEV1% accounted for more baseline variance in mMRC and 6MWD than depression, explaining 16-32% of heterogeneity. Depressive symptoms accounted for 3-17% variance in change over time in PROs. In contrast, FEV1% accounted for 1-4% variance over time in PROs. CONCLUSIONS: Depression is more strongly associated with many PROs at baseline and their change over time compared to FEV1%. Recognizing and incorporating the impact of depressive symptoms into individualized care may improve COPD outcomes.

13.
IEEE Trans Med Imaging ; 40(12): 3652-3662, 2021 12.
Artigo em Inglês | MEDLINE | ID: mdl-34224349

RESUMO

Pulmonary emphysema overlaps considerably with chronic obstructive pulmonary disease (COPD), and is traditionally subcategorized into three subtypes previously identified on autopsy. Unsupervised learning of emphysema subtypes on computed tomography (CT) opens the way to new definitions of emphysema subtypes and eliminates the need of thorough manual labeling. However, CT-based emphysema subtypes have been limited to texture-based patterns without considering spatial location. In this work, we introduce a standardized spatial mapping of the lung for quantitative study of lung texture location and propose a novel framework for combining spatial and texture information to discover spatially-informed lung texture patterns (sLTPs) that represent novel emphysema subtype candidates. Exploiting two cohorts of full-lung CT scans from the MESA COPD (n = 317) and EMCAP (n = 22) studies, we first show that our spatial mapping enables population-wide study of emphysema spatial location. We then evaluate the characteristics of the sLTPs discovered on MESA COPD, and show that they are reproducible, able to encode standard emphysema subtypes, and associated with physiological symptoms.

14.
Chronic Obstr Pulm Dis ; 8(3): 326-335, 2021 Jul 28.
Artigo em Inglês | MEDLINE | ID: mdl-34197703

RESUMO

Secondary polycythemia has long been recognized as a consequence of chronic pulmonary disease and hypoxemia and is associated with lower mortality and fewer hospitalizations among individuals with chronic obstructive pulmonary disease (COPD)-prescribed long-term oxygen therapy. This study investigates the association of polycythemia with COPD severity, phenotypic features, and respiratory exacerbations in a contemporary and representative sample of individuals with COPD. Current and former smokers with COPD (forced expiratory volume in 1 second [FEV1] to forced vital capacity [FVC] ratio <70%) without a history of hematologic/oncologic disorders were selected from the SubPopulations and InteRmediate Outcomes Measures In COPD Study (SPIROMICS), a multi-center observational cohort. Participants with polycythemia (hemoglobin ≥15g/dL [females] or ≥17g/dL [males]), were compared to individuals without anemia (hemoglobin ≥12g/dL [females] or ≥13g/dL [males]). Cross-sectional outcomes including percent predicted FEV1, respiratory symptoms, quality of life, exercise tolerance, and percentage and distribution of emphysema (voxels<-950 Hounsfield units [HU] at total lung capacity) were evaluated using linear or logistic regression. Longitudinal acute exacerbation of COPD (AECOPD) and severe AECOPD (requiring an emergency department visit or hospitalization) were assessed using zero-inflated negative binomial models. Among 1261 participants, 148 (11.7%) had polycythemia. Average follow-up was 4.2±1.7 years and did not differ by presence of polycythemia. In multivariate analysis, compared to participants with normal hemoglobin, polycythemia was associated with a reduced rate of severe AECOPD (adjusted incidence rate ratio 0.57, 95% CI: 0.33-0.98), lower percent predicted FEV1, lower resting oxygen saturation, increased upper to lower lobe ratio of emphysema, and a greater degree of emphysema, though the latter was attenuated after adjusting for lung function. There were no significant differences in total AECOPD, patient-reported outcomes, or exercise tolerance. These findings suggest that polycythemia, while associated with less favorable physiologic parameters, is not independently associated with symptoms, and is associated with fewer severe exacerbations. Future studies should explore the potentially protective role of increased hemoglobin beyond the correction of anemia.

15.
PLoS Med ; 18(7): e1003700, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34242221

RESUMO

BACKGROUND: Given the central role of skeletal muscles in glucose homeostasis, deposition of adipose depots beneath the fascia of muscles (versus subcutaneous adipose tissue [SAT]) may precede insulin resistance and type 2 diabetes (T2D) incidence. This study was aimed to investigate the associations between computed tomography (CT)-derived biomarkers for adipose tissue and T2D incidence in normoglycemic adults. METHODS AND FINDINGS: This study was a population-based multiethnic retrospective cohort of 1,744 participants in the Multi-Ethnic Study of Atherosclerosis (MESA) with normoglycemia (baseline fasting plasma glucose [FPG] less than 100 mg/dL) from 6 United States of America communities. Participants were followed from April 2010 and January 2012 to December 2017, for a median of 7 years. The intermuscular adipose tissue (IMAT) and SAT areas were measured in baseline chest CT exams and were corrected by height squared (SAT and IMAT indices) using a predefined measurement protocol. T2D incidence, as the main outcome, was based on follow-up FPG, review of hospital records, or self-reported physician diagnoses. Participants' mean age was 69 ± 9 years at baseline, and 977 (56.0%) were women. Over a median of 7 years, 103 (5.9%) participants were diagnosed with T2D, and 147 (8.4%) participants died. The IMAT index (hazard ratio [HR]: 1.27 [95% confidence interval [CI]: 1.15-1.41] per 1-standard deviation [SD] increment) and the SAT index (HR: 1.43 [95% CI: 1.16-1.77] per 1-SD increment) at baseline were associated with T2D incidence over the follow-up. The associations of the IMAT and SAT indices with T2D incidence were attenuated after adjustment for body mass index (BMI) and waist circumference, with HRs of 1.23 (95% CI: 1.09-1.38) and 1.29 (95% CI: 0.96-1.74) per 1-SD increment, respectively. The limitations of this study include unmeasured residual confounders and one-time measurement of adipose tissue biomarkers. CONCLUSIONS: In this study, we observed an association between IMAT at baseline and T2D incidence over the follow-up. This study suggests the potential role of intermuscular adipose depots in the pathophysiology of T2D. TRIAL REGISTRATION: ClinicalTrials.gov NCT00005487.


Assuntos
Tecido Adiposo/diagnóstico por imagem , Diabetes Mellitus Tipo 2/epidemiologia , Gordura Subcutânea/diagnóstico por imagem , Idoso , Estudos de Coortes , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Tomografia Computadorizada por Raios X
16.
Int J Chron Obstruct Pulmon Dis ; 16: 1477-1496, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34103907

RESUMO

Purpose: Quantitative computed tomography (qCT) imaging-based cluster analysis identified clinically meaningful COPD former-smoker subgroups (clusters) based on cross-sectional data. We aimed to identify progression clusters for former smokers using longitudinal data. Patients and Methods: We selected 472 former smokers from SPIROMICS with a baseline visit and a one-year follow-up visit. A total of 150 qCT imaging-based variables, comprising 75 variables at baseline and their corresponding progression rates, were derived from the respective inspiration and expiration scans of the two visits. The COPD progression clusters identified were then associated with subject demography, clinical variables and biomarkers. Results: COPD severities at baseline increased with increasing cluster number. Cluster 1 patients were an obese subgroup with rapid progression of functional small airway disease percentage (fSAD%) and emphysema percentage (Emph%). Cluster 2 exhibited a decrease of fSAD% and Emph%, an increase of tissue fraction at total lung capacity and airway narrowing over one year. Cluster 3 showed rapid expansion of Emph% and an attenuation of fSAD%. Cluster 4 demonstrated severe emphysema and fSAD and significant structural alterations at baseline with rapid progression of fSAD% over one year. Subjects with different progression patterns in the same cross-sectional cluster were identified by longitudinal clustering. Conclusion: qCT imaging-based metrics at two visits for former smokers allow for the derivation of four statistically stable clusters associated with unique progression patterns and clinical characteristics. Use of baseline variables and their progression rates enables identification of longitudinal clusters, resulting in a refinement of cross-sectional clusters.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Enfisema Pulmonar , Estudos Transversais , Humanos , Avaliação de Resultados em Cuidados de Saúde , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Enfisema Pulmonar/diagnóstico por imagem , Fumantes
17.
JBMR Plus ; 5(5): e10484, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33977202

RESUMO

Osteoporosis causes fragile bone, and bone microstructural quality is a critical determinant of bone strength and fracture risk. This study pursues technical validation of novel CT-based methods for assessment of peripheral bone microstructure together with a human pilot study examining relationships between bone microstructure and vertebral fractures in smokers. To examine the accuracy and reproducibility of the methods, repeat ultra-high-resolution (UHR) CT and micro-CT scans of cadaveric ankle specimens were acquired. Thirty smokers from the University of Iowa COPDGene cohort were recruited at their 5-year follow-up visits. Chest CT scans, collected under the parent study, were used to assess vertebral fractures. UHR CT scans of distal tibia were acquired for this pilot study to obtain peripheral cortical and trabecular bone (Cb and Tb) measures. UHR CT-derived Tb measures, including volumetric bone mineral density (BMD), network area, transverse trabecular density, and mean plate width, showed high correlation (r > 0.901) with their micro-CT-derived values over small regions of interest (ROIs). Both Cb and Tb measures showed high reproducibility-intra-class correlation (ICC) was greater than 0.99 for all Tb measures except erosion index and greater than 0.97 for all Cb measures. Female sex was associated with lower transverse Tb density (p < 0.1), higher Tb spacing (p < 0.05), and lower cortical thickness (p < 0.001). Participants with vertebral fractures had significantly degenerated values (p < 0.05) for all Tb measures except thickness. There were no statistically significant differences for Cb measures between non-fracture and fracture groups. Vertebral fracture-group differences of Tb measures remained significant after adjustment with chronic obstructive pulmonary disease (COPD) status. Although current smokers at baseline had more fractures-81.8% versus 63.2% for former smokers-the difference was not statistically significant. This pilot cross-sectional human study demonstrates CT-based peripheral bone microstructural differences among smokers with and without vertebral fractures. © 2021 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research. © 2021 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.

19.
Lancet Respir Med ; 9(11): 1241-1254, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34058148

RESUMO

BACKGROUND: We previously described the contributions of increased total airway mucin concentrations to the pathogenesis and diagnosis of the chronic bronchitic component of chronic obstructive pulmonary disease (COPD). Here, we investigated the relative contribution of each of the major airway gel-forming mucins, MUC5AC and MUC5B, to the initiation, progression, and early diagnosis of airways disease in COPD. METHODS: SPIROMICS was a multicentre, observational study in patients aged 40-80 years recruited from six clinical sites and additional subsites in the USA. In this analysis, MUC5AC and MUC5B were quantitated by stable isotope-labelled mass spectrometry in induced sputum samples from healthy never-smokers, ever-smokers at risk for COPD, and ever-smokers with COPD. Participants were extensively characterised using results from questionnaires, such as the COPD assessment test (CAT) and St George's Respiratory Questionnaire; quantitative CT, such as residual volume/total lung capacity ratio (RV/TLC) and parametric response mapping-functional small airway disease (PRM-fSAD); and pulmonary function tests, such as FEV1, forced vital capacity (FVC), and forced expiratory flow, midexpiratory phase (FEF25-75%). Absolute concentrations of both MUC5AC and MUC5B were related to cross-sectional (baseline, initial visit) and 3-year follow-up longitudinal data, including lung function, small airways obstruction, prospective acute exacerbations, and smoking status as primary outcomes. This study is registered with ClinicalTrials.gov (NCT01969344). FINDINGS: This analysis included 331 participants (mean age 63 years [SEM 9·40]), of whom 40 were healthy never-smokers, 90 were at-risk ever-smokers, and 201 were ever-smokers with COPD. Increased MUC5AC concentrations were more reliably associated with manifestations of COPD than were MUC5B concentrations, including decreased FEV1 and FEF25-75%, and increased prospective exacerbation frequency, RV/TLC, PRM-fSAD, and COPD assessment scores. MUC5AC concentrations were more reactive to cigarette smoke exposure than were MUC5B concentrations. Longitudinal data from 3-year follow-up visits generated a multivariate-adjusted odds ratio for two or more exacerbations of 1·24 (95% CI 1·04-1·47, p=0·015) for individuals with high baseline MUC5AC concentration. Increased MUC5AC, but not MUC5B, concentration at baseline was a significant predictor of FEV1, FEV1/FVC, FEF25-75%, and CAT score decline during the 3-year follow-up. Moreover, current smokers in the at-risk group showed raised MUC5AC concentrations at initial visits and decreased lung function over 3 years. By contrast, former smokers in the at-risk group showed normal MUC5AC concentrations at the initial visit and preserved lung function over 3 years. INTERPRETATION: These data indicate that increased MUC5AC concentration in the airways might contribute to COPD initiation, progression, exacerbation risk, and overall pathogenesis. Compared with MUC5B, greater relative changes in MUC5AC concentrations were observed as a function of COPD severity, and MUC5AC concentration seems to be an objective biomarker to detect disease in at-risk and pre-COPD individuals. These data suggest that MUC5AC-producing pathways could be potential targets for future therapeutic strategies. Thus, MUC5AC could be a novel biomarker for COPD prognosis and for testing the efficacy of therapeutic agents. FUNDING: National Institutes of Health; National Heart, Lung, and Blood Institute.

20.
Am J Respir Crit Care Med ; 204(5): 536-545, 2021 09 01.
Artigo em Inglês | MEDLINE | ID: mdl-33971109

RESUMO

Rationale: Racial residential segregation has been associated with worse health outcomes, but the link with chronic obstructive pulmonary disease (COPD) morbidity has not been established.Objectives: To investigate whether racial residential segregation is associated with COPD morbidity among urban Black adults with or at risk of COPD.Methods: Racial residential segregation was assessed using isolation index, based on 2010 decennial census and baseline address, for Black former and current smokers in the multicenter SPIROMICS (Subpopulations and Intermediate Outcome Measures in COPD Study), a study of adults with or at risk for COPD. We tested the association between isolation index and respiratory symptoms, physiologic outcomes, imaging parameters, and exacerbation risk among urban Black residents, adjusting for established COPD risk factors, including smoking. Additional mediation analyses were conducted for factors that could lie on the pathway between segregation and COPD outcomes, including individual and neighborhood socioeconomic status, comorbidity burden, depression/anxiety, and ambient pollution.Measurements and Main Results: Among 515 Black participants, those residing in segregated neighborhoods (i.e., isolation index ⩾0.6) had worse COPD Assessment Test score (ß = 2.4; 95% confidence interval [CI], 0.7 to 4.0), dyspnea (modified Medical Research Council scale; ß = 0.29; 95% CI, 0.10 to 0.47), quality of life (St. George's Respiratory Questionnaire; ß = 6.1; 95% CI, 2.3 to 9.9), and cough and sputum (ß = 0.8; 95% CI, 0.1 to 1.5); lower FEV1% predicted (ß = -7.3; 95% CI, -10.9 to -3.6); higher rate of any and severe exacerbations; and higher percentage emphysema (ß = 2.3; 95% CI, 0.7 to 3.9) and air trapping (ß = 3.8; 95% CI, 0.6 to 7.1). Adverse associations attenuated with adjustment for potential mediators but remained robust for several outcomes, including dyspnea, FEV1% predicted, percentage emphysema, and air trapping.Conclusions: Racial residential segregation was adversely associated with COPD morbidity among urban Black participants and supports the hypothesis that racial segregation plays a role in explaining health inequities affecting Black communities.


Assuntos
Afro-Americanos/estatística & dados numéricos , Disparidades nos Níveis de Saúde , Doença Pulmonar Obstrutiva Crônica/etnologia , Doença Pulmonar Obstrutiva Crônica/mortalidade , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Segregação Social , População Urbana/estatística & dados numéricos , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Características de Residência , Classe Social , Inquéritos e Questionários , Estados Unidos/etnologia
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