Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 233
Filtrar
1.
Artigo em Inglês | MEDLINE | ID: mdl-33290645

RESUMO

Background: Little is known about factors associated with emphysema progression in cigarette smokers. We evaluated factors associated with change in emphysema and FEV1 in subjects with and without chronic obstructive pulmonary disease (COPD). Methods: This retrospective study included subjects participating in the COPDGene study and who completed the 5-year follow-up, including inspiratory and expiratory computed tomography (CT) and spirometry. All paired CT scans were analyzed using micro-mapping, which classifies individual voxels as emphysema or functional small airway disease (fSAD). Presence and progression of emphysema and FEV1 were determined based on comparison to nonsmoker values. Logistic regression analyses were used to identify clinical parameters associated with disease progression. Results: 3088 subjects were included with a mean ± SD age of 60.7±8.9 years, including 72 nonsmokers. In all GOLD stages, the presence of emphysema at baseline was associated with emphysema progression (Odds ratio (OR): GOLD 0: 4.32; PRISm; 5.73; GOLD 1: 5.16; GOLD 2: 5.69; GOLD 3/4: 5.55; all p≤0.01). If there was no emphysema at baseline, the amount of fSAD at baseline was associated with emphysema progression (OR for 1% increase: GOLD 0: 1.06; PRISm: 1.20; GOLD 1: 1.7; GOLD 3/4: 1.08 all p ≤ 0.03). In 1735 subjects without spirometric COPD, progression in emphysema occurred in 105 (6.1%) subjects and only 21 (1.2%) had progression in both emphysema and FEV1. Conclusions: The presence of emphysema is an important predictor of emphysema progression. In patients without emphysema, fSAD is associated with the development of emphysema. In subjects without spirometric COPD, emphysema progression occurred independently of FEV1 decline.

2.
J Orthop Res ; 2020 Dec 21.
Artigo em Inglês | MEDLINE | ID: mdl-33347639

RESUMO

Biofilm-associated infections in orthopedic surgery lead to worse clinical outcomes and greater morbidity and mortality. The scope of the problem encompasses infected total joints, internally fixed fractures, and implanted devices. Diagnosis is difficult. Cultures are often negative, and antibiotic treatments are ineffective. The infections resist killing by the immune system and antibiotics. The organized matrix structure of extracellular polymeric substances within the biofilm shields and protects the bacteria from identification and immune cell action. Bacteria in biofilms actively modulate their redox environment and can enhance the matrix structure by creating an oxidizing environment. We postulated that a potent redox-active metalloporphyrin MnTE-2-PyP (chemical name: manganese (II) meso-tetrakis-(N-methylpyridinium-2-yl) porphyrin) that scavenges reactive species and modulates the redox state to a reduced state, would improve the effect of antibiotic treatment for a biofilm-associated infection. An infected fracture model with a midshaft femoral osteotomy was created in C57B6 mice, internally fixed with an intramedullary 23-gauge needle and seeded with a biofilm-forming variant of Staphylococcus aureus. Animals were divided into three treatment groups: control, antibiotic alone, and combined antibioticplus MnTE-2-PyP. The combined treatment group had significantly decreased bacterial counts in harvested bone, compared with antibiotic alone. In vitro crystal violet assay of biofilm structure and corresponding nitroblue tetrazolium assay for reactive oxygen species (ROS) demonstrated that MnTE-2-PyP decreased the biofilm structure and reduced ROS in a correlated and dose-dependent manner. The biofilm structure is redox-sensitive in S. aureus and an ROS scavenger improved the effect of antibiotic therapy in model of biofilm-associated infections.

3.
Artigo em Inglês | MEDLINE | ID: mdl-33103191

RESUMO

OBJECTIVE: Chronic obstructive pulmonary disease (COPD) is characterized by airflow limitation; however, pulmonary function does not fully account for patients' functional difficulties. The primary aim of the study was to determine the association between several domains of cognition and daily activity among those with COPD. METHOD: Eighty-nine former smokers completed a neuropsychological battery including measures across multiple domains of cognition, pulmonary function measures, and daily activity questionnaires. Using a cross-sectional design, we compared daily activity between former smokers with and without COPD using two measures (St. George's Respiratory Questionnaire [SGRQ] Activity Subscale and Lawton Instrumental Activities of Daily Living [IADL] Scale) and examined the association between cognition and daily activity among those with COPD. RESULTS: As expected, former smokers with COPD reported more difficulty than those without COPD on both activity measures (SGRQ Activity Subscale p < .001; Lawton IADL Scale p = .040). Among former smokers with COPD, poorer delayed recall was associated with more difficulty with daily activities (SGRQ Activity Subscale) (p = .038) while adjusting for severity of airflow limitation, exercise tolerance, oxygen use, dyspnea, and symptoms of anxiety and depression. CONCLUSION: The findings suggest that cognition is associated with daily activity in patients with COPD. Future research should examine whether cognitive interventions may help to maximize patients' engagement in daily activities.

4.
Chronic Obstr Pulm Dis ; 7(4): 346-361, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32877963

RESUMO

Background: Risk factor identification is a proven strategy in advancing treatments and preventive therapy for many chronic conditions. Quantifying the impact of those risk factors on health outcomes can consolidate and focus efforts on individuals with specific high-risk profiles. Using multiple risk factors and longitudinal outcomes in 2 independent cohorts, we developed and validated a risk score model to predict mortality in current and former cigarette smokers. Methods: We obtained extensive data on current and former smokers from the COPD Genetic Epidemiology (COPDGene®) study at enrollment. Based on physician input and model goodness-of-fit measures, a subset of variables was selected to fit final Weibull survival models separately for men and women. Coefficients and predictors were translated into a point system, allowing for easy computation of mortality risk scores and probabilities. We then used the SubPopulations and InteRmediate Outcome Measures In COPD Study (SPIROMICS) cohort for external validation of our model. Results: Of 9867 COPDGene participants with standard baseline data, 17.6% died over 10 years of follow-up, and 9074 of these participants had the full set of baseline predictors (standard plus 6-minute walk distance and computed tomography variables) available for full model fits. The average age of participants in the cohort was 60 for both men and women, and the average predicted 10-year mortality risk was 18% for women and 25% for men. Model time-integrated area under the receiver operating characteristic curve statistics demonstrated good predictive model accuracy (0.797 average), validated in the external cohort (0.756 average). Risk of mortality was impacted most by 6-minute walk distance, forced expiratory volume in 1 second and age, for both men and women. Conclusions: Current and former smokers exhibited a wide range of mortality risk over a 10- year period. Our models can identify higher risk individuals who can be targeted for interventions to reduce risk of mortality, for participants with or without chronic obstructive pulmonary disease (COPD) using current Global initiative for obstructive Lung Disease (GOLD) criteria.

5.
Radiology ; 296(3): 641-649, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32633676

RESUMO

Background The clinical significance of visually evident emphysema on CT images in individuals without spirometric evidence of chronic obstructive pulmonary disease (COPD) by current diagnostic criteria is, to the knowledge of the authors, unknown. Purpose To evaluate whether participants with visually evident emphysema at CT were more likely to have progressive disease and increased mortality at 5 years compared with those without visual emphysema. Materials and Methods This secondary analysis of the prospective Genetic Epidemiology of COPD study evaluated current or former smokers enrolled between 2008 and 2011 who did not meet current criteria for COPD (defined as Global Initiative for Obstructive Lung Disease stage 0). Statistical analysis was performed by using linear mixed models to estimate mean physiologic, imaging, and clinical outcomes for those with and without visual emphysema. Hazard ratios for mortality were calculated by using Cox regression models with emphysema as the main predictor. Results Of the 4095 participants, 48.3% (1979 participants; 1096 men and 883 women; mean age, 57 years ± 8 [standard deviation]) had trace or greater visual emphysema at CT and 51.7% (2116 participants; 1068 men and 1048 women; mean age, 56 years ± 8) had no emphysema at CT. At 5 years, participants with visual emphysema at CT demonstrated progressive airflow obstruction with lower values of ratio of forced expiratory volume in 1 second (FEV1)-to-functional vital capacity (FVC) ratio (-1.7 vs -0.7) and greater progression in quantitative emphysema measured by 15th percentile lung density (-3.3 vs -0.3 HU), adjusted lung density (-3.1 vs -0.2 g/L), and percentage of lung voxels with CT attenuation less than -950 HU (0.17 vs -0.20) than participants without emphysema (P < .001 for each). The rate of quantitative emphysema progression increased with greater grades of emphysema severity within the emphysema group. Conclusion The presence of visual emphysema at CT in current and former Global Initiative for Obstructive Lung Disease stage 0 smokers predicted structural and physiologic disease progression. © RSNA, 2020 Online supplemental material is available for this article. See also the editorial by Grenier in this issue.

6.
Lancet Respir Med ; 8(7): 696-708, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32649918

RESUMO

BACKGROUND: Genetic factors influence chronic obstructive pulmonary disease (COPD) risk, but the individual variants that have been identified have small effects. We hypothesised that a polygenic risk score using additional variants would predict COPD and associated phenotypes. METHODS: We constructed a polygenic risk score using a genome-wide association study of lung function (FEV1 and FEV1/forced vital capacity [FVC]) from the UK Biobank and SpiroMeta. We tested this polygenic risk score in nine cohorts of multiple ethnicities for an association with moderate-to-severe COPD (defined as FEV1/FVC <0·7 and FEV1 <80% of predicted). Associations were tested using logistic regression models, adjusting for age, sex, height, smoking pack-years, and principal components of genetic ancestry. We assessed predictive performance of models by area under the curve. In a subset of studies, we also studied quantitative and qualitative CT imaging phenotypes that reflect parenchymal and airway pathology, and patterns of reduced lung growth. FINDINGS: The polygenic risk score was associated with COPD in European (odds ratio [OR] per SD 1·81 [95% CI 1·74-1·88] and non-European (1·42 [1·34-1·51]) populations. Compared with the first decile, the tenth decile of the polygenic risk score was associated with COPD, with an OR of 7·99 (6·56-9·72) in European ancestry and 4·83 (3·45-6·77) in non-European ancestry cohorts. The polygenic risk score was superior to previously described genetic risk scores and, when combined with clinical risk factors (ie, age, sex, and smoking pack-years), showed improved prediction for COPD compared with a model comprising clinical risk factors alone (AUC 0·80 [0·79-0·81] vs 0·76 [0·75-0·76]). The polygenic risk score was associated with CT imaging phenotypes, including wall area percent, quantitative and qualitative measures of emphysema, local histogram emphysema patterns, and destructive emphysema subtypes. The polygenic risk score was associated with a reduced lung growth pattern. INTERPRETATION: A risk score comprised of genetic variants can identify a small subset of individuals at markedly increased risk for moderate-to-severe COPD, emphysema subtypes associated with cigarette smoking, and patterns of reduced lung growth. FUNDING: US National Institutes of Health, Wellcome Trust.


Assuntos
Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/genética , Adulto , Estudos de Casos e Controles , Estudos de Coortes , Feminino , Volume Expiratório Forçado , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Fenótipo , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Fatores de Risco , Capacidade Vital
7.
Respir Res ; 21(1): 103, 2020 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-32357885

RESUMO

BACKGROUND: Standard spirometry cannot identify the predominant mechanism underlying airflow obstruction in COPD, namely emphysema or airway disease. We aimed at validating a previously developed methodology to detect emphysema by mathematical analysis of the maximal expiratory flow-volume (MEFV) curve in standard spirometry. METHODS: From the COPDGene population we selected those 5930 subjects with MEFV curve and inspiratory-expiratory CT obtained on the same day. The MEFV curve descending limb was fit real-time using forced vital capacity (FVC), peak expiratory flow, and forced expiratory flows at 25, 50 and 75% of FVC to derive an emphysema severity index (ESI), expressed as a continuous positive numeric parameter ranging from 0 to 10. According to inspiratory CT percent lung attenuation area below - 950 HU we defined three emphysema severity subgroups (%LAA-950insp < 6, 6-14, ≥14). By co-registration of inspiratory-expiratory CT we quantified persistent (%pLDA) and functional (%fLDA) low-density areas as CT metrics of emphysema and airway disease, respectively. RESULTS: ESI differentiated CT emphysema severity subgroups increasing in parallel with GOLD stages (p < .001), but with high variability within each stage. ESI had significantly higher correlations (p < .001) with emphysema than with airway disease CT metrics, explaining 67% of %pLDA variability. Conversely, standard spirometric variables (FEV1, FEV1/FVC) had significantly lower correlations than ESI with emphysema CT metrics and did not differentiate between emphysema and airways CT metrics. CONCLUSIONS: ESI adds to standard spirometry the power to discriminate whether emphysema is the predominant mechanism of airway obstruction. ESI methodology has been validated in the large multiethnic population of smokers of the COPDGene study and therefore it could be applied for clinical and research purposes in the general population of smokers, using a readily available online website.

8.
10.
Chronic Obstr Pulm Dis ; 7(2): 86-98, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32324980

RESUMO

Background: Apparent increased female susceptibility to chronic obstructive pulmonary disease (COPD) suggests sex hormones modulate disease pathogenesis. Little is known about associations between multiparity and lung function in smokers. Research Question: We hypothesized that multiparity is associated with lung function and measures of emphysema and airway disease. Study Design and Methods: Utilizing female participants from the 5-year follow up of the COPD Genetic Epidemiology (COPDGene®) study we performed multivariable linear regressions to assess the effect of multiparity and number of pregnancies on forced expiratory volume in 1 second (FEV1) percentage of predicted (% predicted), FEV1/forced vital capacity (FVC), percent emphysema on computed tomography (CT) scans, and Pi10, a measure of airway thickening. We sampled never smokers and those with lower smoking exposure from the National Health and Nutrition Examination Survey (NHANES) 2011-2012 dataset. Results: We included 1820 participants from COPDGene® and 418 participants from NHANES (321 never smokers, 97 ever smokers). In COPDGene®, multiparity (beta coefficient [ß] = -3.8, 95% confidence interval [CI]: [-6.5, -1.1], p = 0.005) and higher number of pregnancies were associated with lower FEV1 % predicted. Multiparity was not associated with percent emphysema or Pi10. In individuals with no or mild obstruction, multiparity was associated with lower FEV1 % predicted. There was an interaction with multiparity and age on FEV1 % predicted (p = 0.025). In NHANES, there was no association between multiparity and FEV1 % predicted in never smokers or the lower smoking exposure group. Interpretation: Multiparity was associated with lower FEV1 % predicted in current and former smokers in COPDGene® study participants. These preliminary results emphasize the importance of smoking abstinence in women of child-bearing age.

11.
J Am Heart Assoc ; 9(9): e014862, 2020 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32338117

RESUMO

Background Heavy smokers perform worse on neuropsychological assessment than age-matched peers. However, traditional pulmonary measures of airflow limitation and hypoxemia explain only a modest amount of variance in cognition. The current objective was to determine whether carotid artery stiffness is associated with cognition in former smokers beyond the effects of amount of smoking and pulmonary function. Methods and Results Eighty-four former smokers including individuals across a spectrum of airflow limitation severity were included: 30 without chronic obstructive pulmonary disease (Global Initiative for Chronic Obstructive Lung Disease [GOLD] 0 with normal spirometry and lung computed tomography), 31 with mild-moderate chronic obstructive pulmonary disease (GOLD 1-2), and 23 with severe-very severe chronic obstructive pulmonary disease (GOLD 3-4). Participants completed questionnaires, spirometry, carotid ultrasonography, and neuropsychological testing. Multiple linear regression was used to determine whether carotid artery stiffness is associated with neuropsychological performance in 4 cognitive domains after adjusting for age, sex, pack-years of smoking, estimated premorbid intellectual functioning, and airflow limitation. Higher carotid artery ß-stiffness index was associated with reduced executive functioning-processing speed in the fully adjusted model (ß=-0.49, SE=0.14; P=0.001). Lower premorbid intellectual function, male sex, and presence of airflow limitation (GOLD 1 or 2 and GOLD 3 or 4) were also associated with worse executive functioning-processing speed. ß-Stiffness index was not significantly associated with performance in other cognitive domains. Conclusions Carotid artery stiffness is associated with worse performance on executive functioning-processing speed in former smokers beyond the effects of aging, amount of past smoking, severity of airflow limitation, and hypoxemia. Future research should examine whether carotid stiffness can be used to identify former smokers at risk for subsequent cognitive impairment.

12.
Crit Care Med ; 48(5): 623-633, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32141923

RESUMO

Prediction models aim to use available data to predict a health state or outcome that has not yet been observed. Prediction is primarily relevant to clinical practice, but is also used in research, and administration. While prediction modeling involves estimating the relationship between patient factors and outcomes, it is distinct from casual inference. Prediction modeling thus requires unique considerations for development, validation, and updating. This document represents an effort from editors at 31 respiratory, sleep, and critical care medicine journals to consolidate contemporary best practices and recommendations related to prediction study design, conduct, and reporting. Herein, we address issues commonly encountered in submissions to our various journals. Key topics include considerations for selecting predictor variables, operationalizing variables, dealing with missing data, the importance of appropriate validation, model performance measures and their interpretation, and good reporting practices. Supplemental discussion covers emerging topics such as model fairness, competing risks, pitfalls of "modifiable risk factors", measurement error, and risk for bias. This guidance is not meant to be overly prescriptive; we acknowledge that every study is different, and no set of rules will fit all cases. Additional best practices can be found in the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis (TRIPOD) guidelines, to which we refer readers for further details.

13.
Sci Rep ; 10(1): 5169, 2020 03 20.
Artigo em Inglês | MEDLINE | ID: mdl-32198360

RESUMO

One quarter of individuals with Preserved Ratio Impaired Spirometry (PRISm) will develop airflow obstruction, but there are no established methods to identify these individuals. We examined the utility of FVC/TLC in identifying features of obstructive lung disease. The ratio of post-bronchodilator FVC and TLCCT from chest CT (FVC/TLCCT) among current and former smokers with PRISm (FEV1/FVC ≥ 0.7 and FEV1 < 80%) in COPDGene was used to stratify subjects into quartiles: very high, high, low, and very low. We examined the associations between FVC/TLCCT quartiles and (1) baseline characteristics, (2) respiratory exacerbations, (3) progression to COPD at 5 years, and (4) all-cause mortality. Among participants with PRISm at baseline (n = 1,131), the very low FVC/TLCCT quartile was associated with increased gas trapping and emphysema, and higher rates of progression to COPD at 5 years (36% versus 17%; p < 0.001) relative to the very high quartile. The very low FVC/TLCCT quartile was associated with increased total (IRR = 1.65; 95% CI [1.07-2.54]) and severe (IRR = 2.24; 95% CI [1.29-3.89]) respiratory exacerbations. Mortality was lower in the very high FVC/TLCCT quartile relative to the other quartiles combined. Reduced FVC/TLCCT ratio in PRISm is associated with increased symptoms, radiographic emphysema and gas trapping, exacerbations, and progression to COPD.

14.
Radiology ; 295(1): 218-226, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32013794

RESUMO

Background CT is used to quantify abnormal changes in the lung parenchyma of smokers that might overlap chronic obstructive pulmonary disease (COPD), but studies on the progression of expiratory air trapping in smokers are scarce. Purpose To evaluate the relationship between longitudinal changes in forced expiratory volume in 1 second (FEV1) and CT-quantified emphysema and air trapping in smokers. Materials and Methods Cigarette smokers with and those without COPD participating in the multicenter observational COPDGene study were evaluated. Subjects underwent inspiratory and expiratory chest CT and spirometry at baseline and 5-year follow-up. Emphysema was quantified by using adjusted lung density (ALD). Air trapping was quantified by using mean lung density at expiratory CT and CT-measured functional residual capacity-to-total lung volume ratio. Linear models were used to regress quantitative CT measurements taken 5 years apart, and models were fit with and without adding FEV1 as a predictor. Analyses were stratified by Global Initiative for Chronic Obstructive Lung Disease (GOLD) stage (GOLD 0, no COPD; GOLD 1, mild COPD; GOLD 2, moderate COPD; GOLD 3, severe COPD; GOLD 4, very severe COPD). Subjects with preserved FEV1-to-forced vital capacity ratio and reduced FEV1 percentage predicted were categorized as having preserved ratio impaired spirometry (PRISm). Results A total of 4211 subjects (503 with PRISm; 2034 with GOLD 0, 388 with GOLD 1, 816 with GOLD 2, 381 with GOLD 3, 89 with GOLD 4) were evaluated. ALD decreased by 1.7 g/L (95% confidence interval [CI]: -2.5, -0.9) in subjects with GOLD 0 at baseline and by 5.3 g/L (95% CI: -6.2, -4.4) in those with GOLD 1-4 (P < .001 for both). When adjusted for changes in FEV1, corresponding numbers were -2.2 (95% CI: -3.0, -1.3) and -4.6 g/L (95% CI: -5.6, -3.4) (P < .001 for both). Progression in air trapping was identified only in GOLD stage 2-4. Approximately 33%-50% of changes in air trapping in GOLD stages 2-4 were accounted for by changes in FEV1. Conclusion CT measures of emphysema and air trapping increased over 5 years in smokers. Forced expiratory volume in one second accounted for less than 10% of emphysema progression and less than 50% of air trapping progression detected at CT. © RSNA, 2020 Online supplemental material is available for this article.


Assuntos
Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/fisiopatologia , Fumar/efeitos adversos , Tomografia Computadorizada por Raios X , Idoso , Ar , Progressão da Doença , Feminino , Volume Expiratório Forçado , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Índice de Gravidade de Doença , Fatores de Tempo
15.
Chest ; 157(1): 47-60, 2020 01.
Artigo em Inglês | MEDLINE | ID: mdl-31283919

RESUMO

BACKGROUND: Multiple studies have identified COPD subtypes by using visual or quantitative evaluation of CT images. However, there has been no systematic assessment of a combined visual and quantitative CT imaging classification. We integrated visually defined patterns of emphysema with quantitative imaging features and spirometry data to produce a set of 10 nonoverlapping CT imaging subtypes, and we assessed differences between subtypes in demographic features, physiological characteristics, longitudinal disease progression, and mortality. METHODS: We evaluated 9,080 current and former smokers in the COPDGene study who had available volumetric inspiratory and expiratory CT images obtained using a standardized imaging protocol. We defined 10 discrete, nonoverlapping CT imaging subtypes: no CT imaging abnormality, paraseptal emphysema (PSE), bronchial disease, small airway disease, mild emphysema, upper lobe predominant centrilobular emphysema (CLE), lower lobe predominant CLE, diffuse CLE, visual without quantitative emphysema, and quantitative without visual emphysema. Baseline and 5-year longitudinal characteristics and mortality were compared across these CT imaging subtypes. RESULTS: The overall mortality differed significantly between groups (P < .01) and was highest in the 3 moderate to severe CLE groups. Subjects having quantitative but not visual emphysema and subjects with visual but not quantitative emphysema were unique groups with mild COPD, at risk for progression, and with likely different underlying mechanisms. Subjects with PSE and/or moderate to severe CLE had substantial progression of emphysema over 5 years compared with findings in subjects with no CT imaging abnormality (P < .01). CONCLUSIONS: The combination of visual and quantitative CT imaging features reflects different underlying pathological processes in the heterogeneous COPD syndrome and provides a useful approach to reclassify types of COPD. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT00608764; URL: www.clinicaltrials.gov.


Assuntos
Doença Pulmonar Obstrutiva Crônica/classificação , Doença Pulmonar Obstrutiva Crônica/diagnóstico por imagem , Fumantes , Tomografia Computadorizada por Raios X , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fenótipo , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/mortalidade , Testes de Função Respiratória
16.
J Rheumatol ; 47(4): 531-538, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31043539

RESUMO

OBJECTIVE: Diffuse idiopathic skeletal hyperostosis (DISH) is a condition characterized by bony proliferation at sites of tendinous and ligamentous insertions in the spine. Spinal mobility is reduced in DISH and may affect movement in the thorax, potentially leading to restrictive pulmonary function. This study investigated whether DISH is associated with restrictive spirometric pattern (RSP) in former and current smokers. METHODS: Participants (n = 1784) with complete postbronchodilator spirometry who did not meet spirometric criteria for chronic obstructive pulmonary disease (COPD) at time of enrollment in the COPDGene study were included in this study. Subjects were classified as RSP if they had forced expiratory volume in 1 s(FEV1) to forced vital capacity (FVC) ratio > 0.7 with an FVC < 80%. Computed tomography (CT) scans were scored for the presence of DISH in accordance with the Resnick criteria. Chest CT measures of interstitial and alveolar lung disease, clinical symptoms, health surveys, and 6-min walking distance were recorded. Uni- and multivariable analyses were performed to test the association of DISH with RSP. RESULTS: DISH was present in 236 subjects (13.2%). RSP was twice as common in participants with DISH (n = 90/236, 38.1%) compared to those without DISH (n = 301/1548, 19.4%; p < 0.001). In multivariable analysis, DISH was significantly associated with RSP (OR 1.78; 95% CI 1.22-2.60; p = 0.003) after adjusting for potential confounders. The RSP group with and without DISH had significantly worse spirometry, dyspnea, St. George's Respiratory Questionnaire score, BODE index (Body mass index, airflow Obstruction, Dyspnea and Exercise capacity), and Medical Outcomes Study Short Form-36 questionnaire score. CONCLUSION: In heavy smokers with an FEV1/FVC ratio > 0.70, DISH is associated with RSP after adjustment for intrinsic and extrinsic causes of restrictive lung function. (Clinical trial registration number: NCT00608764.).

18.
Radiology ; 294(2): 434-444, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31793851

RESUMO

BackgroundPattern of emphysema at chest CT, scored visually by using the Fleischner Society system, is associated with physiologic impairment and mortality risk.PurposeTo determine whether participant-level emphysema pattern could predict impairment and mortality when classified by using a deep learning method.Materials and MethodsThis retrospective analysis of Genetic Epidemiology of COPD (COPDGene) study participants enrolled between 2007 and 2011 included those with baseline CT, visual emphysema scores, and survival data through 2018. Participants were partitioned into nonoverlapping sets of 2407 for algorithm training, 100 for validation and parameter tuning, and 7143 for testing. A deep learning algorithm using convolutional neural network and long short-term memory architectures was trained to classify pattern of emphysema according to Fleischner criteria. Deep learning scores were compared with visual scores and clinical parameters including pulmonary function tests. Cox proportional hazard models were used to evaluate relationships between emphysema scores and survival. The algorithm was also tested by using CT and clinical data in 1962 participants enrolled in the Evaluation of COPD Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE) study.ResultsA total of 7143 COPDGene participants (mean age ± standard deviation, 59.8 years ± 8.9; 3734 men and 3409 women) were evaluated. Deep learning emphysema classifications were associated with impaired pulmonary function tests, 6-minute walk distance, and St George's Respiratory Questionnaire at univariate analysis (P < .001 for each). Testing in the ECLIPSE cohort showed similar associations (P < .001). In the COPDGene test cohort, deep learning emphysema classification improved the fit of linear mixed models in the prediction of these clinical parameters compared with visual scoring (P < .001). Compared with participants without emphysema, mortality was greater in participants classified by the deep learning algorithm as having any grade of emphysema (adjusted hazard ratios were 1.5, 1.7, 2.9, 5.3, and 9.7, respectively, for trace, mild, moderate, confluent, and advanced destructive emphysema; P < .05).ConclusionDeep learning automation of the Fleischner grade of emphysema at chest CT is associated with clinical measures of pulmonary insufficiency and the risk of mortality.© RSNA, 2019Online supplemental material is available for this article.


Assuntos
Interpretação de Imagem Assistida por Computador/métodos , Enfisema Pulmonar/diagnóstico por imagem , Tomografia Computadorizada por Raios X/métodos , Idoso , Idoso de 80 Anos ou mais , Aprendizado Profundo , Feminino , Humanos , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Índice de Gravidade de Doença
19.
Chronic Obstr Pulm Dis ; 6(5): 400-413, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31710795

RESUMO

Background: Previous attempts to explore the heterogeneity of chronic obstructive pulmonary disease (COPD) clustered individual patients using clinical, demographic, and disease features. We developed continuous multidimensional disease axes based on radiographic and spirometric variables that split into an airway-predominant axis and an emphysema-predominant axis. Methods: The COPD Genetic Epidemiology study (COPDGene®) is a cohort of current and former smokers, > 45 years, with at least 10 pack years of smoking history. Spirometry measures, blood pressure and body mass were directly measured. Mortality was assessed through continuing longitudinal follow-up and cause of death was adjudicated. Among 8157 COPDGene® participants with complete spirometry and computed tomography (CT) measures, the top 2 deciles of the airway-predominant and emphysema-predominant axes previously identified were used to categorize individuals into 3 groups having the highest risk for mortality using Cox proportional hazard ratios. These groups were also assessed for causal mortality. Biomarkers of COPD (fibrinogen, soluble receptor for advanced glycation end products [sRAGE], C-reactive protein [CRP], clara cell secretory protein [CC16], surfactant-D [SP-D]) were compared by group. Findings: High-risk subtype classification was defined for 2638 COPDGene® participants who were in the highest 2 deciles of either the airway-predominant and/or emphysema-predominant axis (32% of the cohort). These high-risk participants fell into 3 groups: airway-predominant disease only (APD-only), emphysema-predominant disease only (EPD-only) and combined APD-EPD. There was 26% mortality for the APD-only group, 21% mortality for the EPD-only group, and 54% mortality for the combined APD-EPD group. The APD-only group (n=1007) was younger, had a lower forced expiratory volume in 1 second (FEV1) percent (%) predicted and a strong association with the preserved ratio-impaired spirometry (PRISm) quadrant. The EPD-only group (n=1006) showed a relatively higher FEV1 % predicted and included largely GOLD stage 0, 1 and 2 partipants. Individuals in each of the 3 high-risk groups were at greater risk for respiratory mortality, while those in the APD-only group were additionally at greater risk for cardiovascular mortality. Biomarker analysis demonstrated a significant association of the APD-only group with CRP, and sRAGE demonstrated greatest significance with both the EPD-only and the combined APD-EPD groups. Interpretation: Among current and former smokers, individuals in the highest 2 deciles for mortality risk on the airway-predominant axis and the emphysema-predominant axis have unique associations to spirometric patterns, different imaging characteristics, biomarkers and causal mortality.

20.
Chronic Obstr Pulm Dis ; 6(5): 414-429, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31710796

RESUMO

Rationale: We classified individuals into pulmonary disease subtypes based on 2 underlying pathophysiologic disease axes (airway-predominant and emphysema-predominant) and their increased mortality risk. Our next objective was to determine whether some subcomponents of these subtypes are additionally associated with unique patterns of Global initiative for chronic Obstructive Lung Disease (GOLD) spirometry stage progression. Methods: After accounting for intra-individual measurement variability in spirometry measures between baseline (Phase 1) and the 5-year follow up (Phase 2) of the COPD Genetic Epidemiology (COPDGene®) study, 4615 individuals had complete data that would characterize patterns of disease progression over 5 years (2033 non-Hispanic whites; 827 African Americans; 48% female). Individuals could express increased risk for mortality on one or both of the primary subtype axes (airway-predominant or emphysema-predominant) and thus they were further classified into 6 groups: high-risk airway-predominant disease only (APD-only), moderate-risk airway-predominant disease only (MR-APD-only), high-risk emphysema-predominant disease only (EPD-only), combined high-risk airway- and emphysema-predominant disease (combined APD-EPD), combined moderate-risk airway- and emphysema-predominant disease (combined MR-APD-EPD), and no high-risk pulmonary subtype. Outcomes were dichotomized for GOLD spirometry stage progression from Phase 1 to Phase 2. Logistic regression of the progression outcomes on the pulmonary subtypes were adjusted for age, sex, race, and change in smoking status. Results: The MR-APD-only group was associated with conversion from GOLD 0 to preserved ratio-impaired spirometry (PRISm) status (odds ratio [OR] 11.3, 95% confidence interval [CI] 5.7-22.1) and GOLD 0 to GOLD 2-4 (OR 6.0, 95% CI 2.0-18.0). The EPD-only group was associated with conversion from GOLD 0 to GOLD 1 (OR 2.4, 95% CI 1.2-4.6), and GOLD 1 to GOLD 2-4 (OR 2.6, 95% CI 1.0-6.9). Conversion between PRISm and GOLD 2-4 (31%-38%) occurred in both the APD-only and the MR-APD-only groups. Conclusion: Differential conversion occurs from GOLD 0 to PRISm and GOLD 0 to GOLD 1 based on groups expressing airway-predominant disease or emphysema-predominant disease independently or in combination. Airway-predominant and emphysema-predominant subtypes are highly important in determining patterns of early disease progression.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA