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1.
Artigo em Inglês | MEDLINE | ID: mdl-34739356

RESUMO

RATIONALE: The ability of peripheral blood biomarkers to assess COPD risk and progression is unknown. Genetics and gene expression may capture important aspects of COPD-related biology that predict disease activity. OBJECTIVES: Develop a transcriptional risk score (TRS) for COPD and assess the contribution of the TRS and a polygenic risk score (PRS) for disease susceptibility and progression. METHODS: We randomly split 2,569 COPDGene participants with whole blood RNA sequencing into training (n=1,945) and testing (n=624) samples, and utilized 468 ECLIPSE COPD cases with microarray data for replication. We developed a TRS using penalized regression (LASSO) to model FEV1/FVC, and studied the predictive value of TRS for COPD (GOLD 2-4), prospective FEV1 change (mL/year), and additional COPD-related traits. We adjusted for potential confounders, including age and smoking. We evaluated the predictive performance of the TRS in the context of a previously-derived PRS and clinical factors. MEASUREMENTS AND MAIN RESULTS: The TRS included 147 transcripts and was associated with COPD (OR = 3.3 [95% CI: 2.4-4.5], p < 0.001), FEV1 change (ß=-17 ml/year [95% CI: -28,-6.6, p=0.002]), and other COPD-related traits. In ECLIPSE cases, we replicated the association with FEV1 change (ß=-8.2 [95% CI: -15,-1, p=0.025]) and the majority of other COPD-related traits. Models including PRS, TRS, and clinical factors were more predictive of COPD (AUC=0.84) and annualized FEV1 change compared to models with one risk score or clinical factors alone. CONCLUSIONS: Blood transcriptomics can improve prediction of COPD and lung function decline when added to a PRS and clinical risk factors.

2.
ERJ Open Res ; 7(4)2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34616836

RESUMO

Background: Breath analysis is a burgeoning field, with interest in volatile organic compounds (VOCs) as a noninvasive diagnostic tool or an outcome measure, but no randomised controlled trials (RCTs) have yet evaluated this technology in a clinical trial longitudinally. In a pilot RCT, our exploratory objectives were feasibility of measuring VOCs via multiple techniques, assessing relationships between VOCs and Haemophilus colonisation and whether CXCR2 antagonism with danirixin altered lung microbiome composition in individuals with COPD. Method: 43 participants had VOCs and sputum biomarkers evaluated. VOCs and induced sputum were collected after 6 h of fasting at screening and at days 1, 7 and 14. VOCs were analysed via gas chromatography mass spectrometry (GC-MS), field asymmetric ion mobility spectrometry (FAIMS) and eNose. The primary outcome for these analyses was the relationship between VOCs and Haemophilus abundance determined by 16S rRNA sequencing. Results: A joint-effects model demonstrated a modest relationship between four exhaled VOCs and Haemophilus relative abundance (R2=0.55) measured only by GC-MS, but not as measured using gas chromtaography FAIMS or eNose. There was considerable variability in absolute quantities of individual VOCs longitudinally. Conclusions: VOC measurement in clinical trials to identify subsets of COPD is feasible, but assessment of new VOC technologies must include concurrent GC-MS validation. Further work to standardise collection of VOCs and measuring a background or "housekeeper" VOC is required to understand and normalise individual VOC quantities.

3.
Artigo em Inglês | MEDLINE | ID: mdl-34672872

RESUMO

Chronic Obstructive Pulmonary Disease is the end-result of a series of dynamic and cumulative gene-environment interactions over a lifetime. The evolving understanding of COPD biology provides novel opportunities for prevention, early diagnosis, and intervention. To advance these concepts we propose therapeutic trials in two major groups of subjects: those "young" individuals with COPD and those with pre-COPD. Given that lungs grow to about 20 years of age and begin to age at approximately 50 years, we consider "young" COPD those patients in the age range of 20-50 years. Pre-COPD relates to individuals of any age who have respiratory symptoms with or without structural and/or functional abnormalities, in the absence of airflow limitation, and who may develop persistent airflow limitation over time. We exclude from the current discussion infants and adolescents because of their unique physiological context and COPD in older adults given their representation in prior randomized clinical trials (RCTs). We highlight the need of RCTs focused on young COPD or Pre-COPD patients to reduce disease progression, providing innovative approaches to identifying and engaging potential study subjects. We detail approaches to RCTs design including potential outcomes such as lung function, patient reported outcomes, exacerbations, lung imaging, mortality, and composite endpoints. We critically review study design components such as statistical powering and analysis, duration of study treatment, and formats to trial structure including platform, basket, and umbrella trials. We provide a call to action for treatment RCTs in (1) young adults with COPD and (2) those with pre-COPD at any age.

4.
Am J Physiol Lung Cell Mol Physiol ; 321(5): L983-L987, 2021 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-34612086

RESUMO

World COPD Day raises awareness about chronic obstructive pulmonary disease (COPD). COPD accounts for over 150,000 US deaths per year. A major challenge is that COPD receives only a fraction of the research funding provided to other major diseases. Control of COPD is dependent on developing new approaches to diagnose the disease earlier with a recognition of either pre-COPD or established COPD based on symptoms, lung structural change and/or loss of lung function that occurs before meeting long established criteria for a population-based definition of obstruction. Optimization of current therapies improves lung function, exercise capacity, quality of life, and survival. New pathways of disease progression are being identified creating new opportunities for development of therapies that could stop or cure this disease.


Assuntos
Pneumonia , Nascimento Prematuro , Doença Pulmonar Obstrutiva Crônica , Adulto , Criança , Feminino , Saúde Global , Humanos , Recém-Nascido , Gravidez , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia , Qualidade de Vida
5.
ERJ Open Res ; 7(3)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34476245

RESUMO

Rationale: COPD and smoking are characterised by pulmonary inflammation. 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) imaging may improve knowledge of pulmonary inflammation in COPD patients and aid early development of novel therapies as an imaging biomarker. Objectives: To evaluate pulmonary inflammation, assessed by FDG uptake, in whole and regional lung in "usual" (smoking-related) COPD patients, alpha-1 antitrypsin deficiency (α1ATD) COPD patients, smokers without COPD and never-smokers using FDG PET/CT. Secondly, to explore cross-sectional associations between FDG PET/CT and systemic inflammatory markers in COPD patients and repeatability of the technique in COPD patients. Methods: Data from two imaging studies were evaluated. Pulmonary FDG uptake (normalised Ki; nKi) was measured by Patlak graphical analysis in four subject groups: 84 COPD patients, 11 α1ATD-COPD patients, 12 smokers and 10 never-smokers. Within the COPD group, associations between nKi and systemic markers of inflammation were assessed. Repeatability was evaluated in 32 COPD patients comparing nKi values at baseline and at 4-month follow-up. Results: COPD patients, α1ATD-COPD patients and smokers had increased whole lung FDG uptake (nKi) compared with never-smokers (0.0037±0.001, 0.0040±0.001, 0.0040±0.001 versus 0.0028±0.001 mL·cm-3·min-1, respectively, p<0.05 for all). Similar results were observed in upper and middle lung regions. In COPD participants, plasma fibrinogen was associated with whole lung nKi (ß=0.30, p=0.02) in multivariate analysis adjusted for current smoking, forced expiratory volume in 1 s % predicted, systemic neutrophils and C-reactive protein levels. Mean percentage difference in nKi between the baseline and follow-up was 3.2%, and the within subject coefficient of variability was 7.7%. Conclusions: FDG PET/CT has potential as a noninvasive tool to enable whole lung and regional quantification of FDG uptake to assess smoking- and COPD-related pulmonary inflammation.

6.
Artigo em Inglês | MEDLINE | ID: mdl-34523824

RESUMO

BACKGROUND: Chronic obstructive pulmonary disease (COPD) is the third leading cause of death globally. COPD patients with cachexia or weight loss have increased risk of death independent of body mass index (BMI) and lung function. We tested the hypothesis genetic variation is associated with weight loss in COPD using a genome-wide association study approach. METHODS: Participants with COPD (N = 4308) from three studies (COPDGene, ECLIPSE, and SPIROMICS) were analysed. Discovery analyses were performed in COPDGene with replication in SPIROMICS and ECLIPSE. In COPDGene, weight loss was defined as self-reported unintentional weight loss > 5% in the past year or low BMI (BMI < 20 kg/m2 ). In ECLIPSE and SPIROMICS, weight loss was calculated using available longitudinal visits. Stratified analyses were performed among African American (AA) and Non-Hispanic White (NHW) participants with COPD. Single variant and gene-based analyses were performed adjusting for confounders. Fine mapping was performed using a Bayesian approach integrating genetic association results with linkage disequilibrium and functional annotation. Significant gene networks were identified by integrating genetic regions associated with weight loss with skeletal muscle protein-protein interaction (PPI) data. RESULTS: At the single variant level, only the rs35368512 variant, intergenic to GRXCR1 and LINC02383, was associated with weight loss (odds ratio = 3.6, 95% confidence interval = 2.3-5.6, P = 3.2 × 10-8 ) among AA COPD participants in COPDGene. At the gene level in COPDGene, EFNA2 and BAIAP2 were significantly associated with weight loss in AA and NHW COPD participants, respectively. The EFNA2 association replicated among AA from SPIROMICS (P = 0.0014), whereas the BAIAP2 association replicated in NHW from ECLIPSE (P = 0.025). The EFNA2 gene encodes the membrane-bound protein ephrin-A2 involved in the regulation of developmental processes and adult tissue homeostasis such as skeletal muscle. The BAIAP2 gene encodes the insulin-responsive protein of mass 53 kD (IRSp53), a negative regulator of myogenic differentiation. Integration of the gene-based findings participants with PPI data revealed networks of genes involved in pathways such as Rho and synapse signalling. CONCLUSIONS: The EFNA2 and BAIAP2 genes were significantly associated with weight loss in COPD participants. Collectively, the integrative network analyses indicated genetic variation associated with weight loss in COPD may influence skeletal muscle regeneration and tissue remodelling.

7.
ERJ Open Res ; 7(3)2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34527722

RESUMO

COPD is heterogeneous, and its presentation varies between countries. The major COPD cohort studies have only been performed in Western populations; the disease is not well characterised in other regions. The COMPASS (Investigation of the Clinical, Radiological and Biological Factors, Humanistic and Healthcare Utilisation Burden Associated with Disease Progression, Phenotypes and Endotypes of COPD in China; NCT04853225) is a prospective, 2.5-year-long, multi-centre, longitudinal, observational study with three aims: 1) to characterise stable and exacerbation phenotypes/endotypes in terms of clinical characteristics, blood and sputum biomarkers, lung microbiome and lung imaging; 2) to understand the relevance of markers of COPD disease progression identified in Western cohorts to Chinese patients; and 3) to characterise treatment pathways and healthcare resource utilisation. COMPASS will recruit 2000 participants, of which 1700 will be in Global Initiative for Chronic Obstructive Lung Disease (GOLD) Grades I-IV (n=700, 700, 200 and 100, respectively), 180 participants with chronic bronchitis without airflow limitation and 120 never-smoker healthy controls. Study visits will be at baseline, 6, 18 and 30 months and at exacerbation. Assessments include lung function, exacerbation frequency, health status, blood biomarkers and, in a sub-cohort of 400 patients, chest high-resolution computed tomography, additional blood and sputum biomarkers, airway micro-, viral- and myco-biome, and physical activity. COMPASS will establish a unique clinical and biological dataset in a well-characterised cohort of individuals with COPD in China, with a particular focus on milder patients. As the first study of its kind attempting to understand the disease in an Asian setting, it will provide valuable insights into regional and ethnic differences in COPD.

8.
Int J Chron Obstruct Pulmon Dis ; 16: 2665-2675, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34588775

RESUMO

Purpose: Many individuals with obstructive airway disease (OAD), including chronic obstructive pulmonary disease (COPD) and asthma, remain undiagnosed, despite the potential for reducing disease burden through early detection and treatment. OCEAN aimed to determine the prevalence of, and characteristics associated with, impaired lung function in a Japanese population, with the goal of improving strategies for early OAD detection. Methods: OCEAN was an observational, cross-sectional study in sequentially recruited Japanese individuals ≥40 years of age undergoing routine health examinations. Participants completed screening questionnaires and spirometry testing. Airflow limitation was defined as forced expiratory volume in 1 second/forced vital capacity (FEV1/FVC) <0.7 by pre-bronchodilator spirometry. Preserved ratio impaired spirometry (PRISm) was defined as FEV1/FVC ≥0.7 and FEV1 <80% predicted. The primary endpoint was prevalence of spirometry-based airflow limitation and PRISm. The characteristics of study participants were reported as secondary endpoints. Results: Overall, 2518 individuals were included; 79% were <60 years of age (mean 52.0 years). Airflow limitation and PRISm were observed in 52 (2.1%) and 420 (16.7%) participants, respectively. FEV1 in the PRISm group was between that in the no airflow limitation/PRISm and airflow limitation groups, FVC was similar in the PRISm and airflow limitation groups. The PRISm group had higher mean body mass index and a higher proportion of comorbid metabolic disease compared with the airflow limitation group. The prevalence of airflow limitation and PRISm was highest among current smokers (3.9% and 21.3%, respectively) versus former or never smokers. Conclusion: A significant proportion of Japanese individuals <60 years of age attending their annual health examination had impaired lung function (airflow limitation and PRISm); prevalence was highest among current smokers. These findings support screening of current or former smokers ≥40 years of age using patient-reported questionnaires to inform the need for spirometry to confirm an OAD diagnosis.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Estudos Transversais , Volume Expiratório Forçado , Humanos , Japão/epidemiologia , Pulmão , Pessoa de Meia-Idade , Prevalência , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Espirometria , Capacidade Vital
9.
Chronic Obstr Pulm Dis ; 8(4): 528-550, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34433239

RESUMO

Physical activity (PA) is of key importance for health among healthy persons and individuals with chronic obstructive pulmonary disease (COPD). PA has multiple dimensions that can be assessed and quantified objectively using activity monitors. Moreover, as shown in the published literature, variable methodologies have been used to date to quantify PA among individuals with COPD, precluding clear comparisons of outcomes across studies. The present paper aims to provide a summary of the available literature for the rationale behind using objectively measured PA and proposes a standardized methodology for assessment, including standard operating procedures for future research. The present paper, therefore, describes the concept of PA, reports on the importance of PA, summarizes the dimensions of PA, provides a standard operating procedure on how to monitor PA using objective assessments, and describes the psychometric properties of objectively measured PA. The present international task force recommends implementation of the standard operating procedure for PA data collection and reporting in the future. This should further clarify the relationship between PA and clinical outcomes, test the impact of treatment interventions on PA in individuals with COPD, and successfully propose a PA endpoint for regulatory qualification in the future.

10.
Chest ; 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34217679

RESUMO

BACKGROUND: Reduced physical activity is common in COPD and is associated with poor outcomes. Physical activity is therefore a worthy target for intervention in clinical trials; however, trials evaluating physical activity have used heterogeneous methods. RESEARCH QUESTION: What is the available evidence on the efficacy and/or effectiveness of various interventions to enhance objectively measured physical activity in patients with COPD, taking into account the minimal preferred methodologic quality of physical activity assessment? STUDY DESIGN AND METHODS: In this narrative review, the COPD Biomarker Qualification Consortium (CBQC) task force searched three scientific databases for articles that reported the effect of an intervention on objectively measured physical activity in COPD. Based on scientific literature and expert consensus, only studies with ≥ 7 measurement days and ≥ 4 valid days of ≥ 8 h of monitoring were included in the primary analysis. RESULTS: Thirty-seven of 110 (34%) identified studies fulfilled the criteria, investigating the efficacy and/or effectiveness of physical activity behavior change programs (n = 7), mobile or electronic-health interventions (n = 9), rehabilitative exercise (n = 9), bronchodilation (n = 6), lung volume reduction procedures (n = 3), and other interventions (n = 3). Results are generally variable, reflecting the large differences in study characteristics and outcomes. Few studies show an increase beyond the proposed minimal important change of 600 to 1100 daily steps, indicating that enhancing physical activity levels is a challenge. INTERPRETATION: Only one-third of clinical trials measuring objective physical activity in people with COPD fulfilled the preset criteria regarding physical activity assessment. Studies showed variable effects on physical activity even when investigating similar interventions.

11.
Int J Chron Obstruct Pulmon Dis ; 16: 1813-1822, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34168442

RESUMO

Background: Asthma, chronic obstructive pulmonary disease (COPD), and asthma-COPD overlap (ACO) are complex and heterogeneous diseases that share clinical characteristics (phenotypes) and molecular mechanisms (endotypes). Whilst physicians make clinical decisions on diagnostic groups, for some such as ACO there is no commonly accepted criteria. An alternative approach is to evaluate phenotypes and endotypes that are considered to respond well to a specific type of treatment ("treatable traits") rather than diagnostic labels. Purpose: The prospective, longitudinal, and observational TRAIT study will evaluate disease characteristics, including both phenotypes and endotypes, in relation to the presentation of obstructive respiratory disease characteristics in patients diagnosed with asthma, COPD, or ACO in Japan, with the aim of further understanding the clinical benefit of a treatable traits-based approach. Patients and Methods: A total of 1500 participants will be enrolled into three cohorts according to their treating physician's diagnosis of asthma, COPD, or ACO at screening. Part 1 of the study will involve cross-sectional phenotyping and endotyping at study enrollment. Part 2 of the study will evaluate the progression of clinical characteristics, biomarker profiles, and treatment over a 3-year follow-up period. The follow-up will involve three annual study visits and three telephone calls scheduled at 6-month intervals. A substudy involving 50 participants from the asthma cohort (in which the ratio will be approximately 1:1 including 25 participants with a smoking history of ≥10 pack-years and 25 participants with no smoking history), 100 participants from the ACO cohort, and 100 participants from the COPD cohort will evaluate disease phenotypes using inspiratory and expiratory computed tomography scans. Conclusion: TRAIT will describe clinical characteristics of patients with obstructive respiratory diseases to better understand potential differences and similarities between clinical diagnoses, which will support the improvement of personalized treatment strategies.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Estudos de Coortes , Estudos Transversais , Humanos , Japão/epidemiologia , Fenótipo , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Doença Pulmonar Obstrutiva Crônica/terapia
12.
Int J Chron Obstruct Pulmon Dis ; 16: 1771-1782, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34168439

RESUMO

Purpose: A considerable proportion of patients with chronic obstructive pulmonary disease (COPD) remain undiagnosed and untreated even though they may have a burden of respiratory symptoms that impact quality of life. The OCEAN study assessed the ability of screening questionnaires to identify individuals with, or at risk of, COPD by comparing questionnaire outcomes with spirometric measures of lung function. Methods: This observational study included participants ≥40 years of age presenting for their annual health examination at a single medical center in Okinawa, Japan. Participants completed COPD screening questionnaires (CAPTURE and COPD-Q), the Chronic Airways Assessment Test (CAAT), and general demographic and health-related questionnaires. The performance characteristics of CAPTURE and COPD-Q were compared with spirometry-based airflow limitation by calculating the area under the receiver operating characteristic (ROC-AUC) curve. Results: A total of 2518 participants were included in the study; 79% of whom were <60 years of age (mean 52.0 years). A total of 52 (2.1%) participants had airflow limitation defined as forced expiratory volume in 1 second (FEV1)/forced vital capacity (FVC) <0.7, and 420 (16.7%) participants were classified as Preserved Ratio Impaired Spirometry (PRISm). Among participants with PRISm, 75 (17.9%) had a CAAT total score ≥10. Airflow limitation and PRISm were more prevalent in current smokers versus past smokers. For the CAPTURE questionnaire, ROC-AUC for screening airflow limitation, PRISm, and PRISm with a CAAT total score ≥10 were 0.59, 0.55, and 0.69, respectively; for COPD-Q, these three clinical features were 0.67, 0.58 and 0.68, respectively. Conclusion: This study demonstrated that CAPTURE and COPD-Q appear to be effective screening tools for identifying symptomatic individuals with undiagnosed, or at risk of developing COPD in adults ≥40 years of age in Okinawa. Furthermore, early diagnosis and management of PRISm is important to improve future outcomes and the societal burden of disease.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Qualidade de Vida , Adulto , Volume Expiratório Forçado , Humanos , Japão/epidemiologia , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Espirometria , Inquéritos e Questionários , Capacidade Vital
13.
Respir Res ; 22(1): 127, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33906653

RESUMO

BACKGROUND: Soluble receptor for advanced glycation end products (sRAGE) is a proposed emphysema and airflow obstruction biomarker; however, previous publications have shown inconsistent associations and only one study has investigate the association between sRAGE and emphysema. No cohorts have examined the association between sRAGE and progressive decline of lung function. There have also been no evaluation of assay compatibility, receiver operating characteristics, and little examination of the effect of genetic variability in non-white population. This manuscript addresses these deficiencies and introduces novel data from Pittsburgh COPD SCCOR and as well as novel work on airflow obstruction. A meta-analysis is used to quantify sRAGE associations with clinical phenotypes. METHODS: sRAGE was measured in four independent longitudinal cohorts on different analytic assays: COPDGene (n = 1443); SPIROMICS (n = 1623); ECLIPSE (n = 2349); Pittsburgh COPD SCCOR (n = 399). We constructed adjusted linear mixed models to determine associations of sRAGE with baseline and follow up forced expiratory volume at one second (FEV1) and emphysema by quantitative high-resolution CT lung density at the 15th percentile (adjusted for total lung capacity). RESULTS: Lower plasma or serum sRAGE values were associated with a COPD diagnosis (P < 0.001), reduced FEV1 (P < 0.001), and emphysema severity (P < 0.001). In an inverse-variance weighted meta-analysis, one SD lower log10-transformed sRAGE was associated with 105 ± 22 mL lower FEV1 and 4.14 ± 0.55 g/L lower adjusted lung density. After adjusting for covariates, lower sRAGE at baseline was associated with greater FEV1 decline and emphysema progression only in the ECLIPSE cohort. Non-Hispanic white subjects carrying the rs2070600 minor allele (A) and non-Hispanic African Americans carrying the rs2071288 minor allele (A) had lower sRAGE measurements compare to those with the major allele, but their emphysema-sRAGE regression slopes were similar. CONCLUSIONS: Lower blood sRAGE is associated with more severe airflow obstruction and emphysema, but associations with progression are inconsistent in the cohorts analyzed. In these cohorts, genotype influenced sRAGE measurements and strengthened variance modelling. Thus, genotype should be included in sRAGE evaluations.


Assuntos
Pulmão/fisiopatologia , Doença Pulmonar Obstrutiva Crônica/sangue , Enfisema Pulmonar/sangue , Receptor para Produtos Finais de Glicação Avançada/sangue , Idoso , Biomarcadores/sangue , Feminino , Volume Expiratório Forçado , Humanos , Estudos Longitudinais , Pulmão/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Fenótipo , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Enfisema Pulmonar/diagnóstico , Enfisema Pulmonar/fisiopatologia , Índice de Gravidade de Doença , Espirometria , Tomografia Computadorizada por Raios X , Capacidade Vital
14.
Comput Biol Med ; 132: 104322, 2021 05.
Artigo em Inglês | MEDLINE | ID: mdl-33780868

RESUMO

Nighttime symptoms are important indicators of impairment for many diseases and particularly for respiratory diseases such as chronic obstructive pulmonary disease (COPD). The use of wearable sensors to assess sleep in COPD has mainly been limited to the monitoring of limb motions or the duration and continuity of sleep. In this paper we present an approach to concisely describe sleep patterns in subjects with and without COPD. The methodology converts multimodal sleep data into a text representation and uses topic modeling to identify patterns across the dataset composed of more than 6000 assessed nights. This approach enables the discovery of higher level features resembling unique sleep characteristics that are then used to discriminate between healthy subjects and those with COPD and to evaluate patients' disease severity and dyspnea level. Compared to standard features, the discovered latent structures in nighttime data seem to capture important aspects of subjects sleeping behavior related to the effects of COPD and dyspnea.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Humanos , Índice de Gravidade de Doença , Sono
15.
Chronic Obstr Pulm Dis ; 8(2): 269-276, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33780603

RESUMO

Background: Pulmonary rehabilitation (PR) is an important therapy for patients with chronic obstructive pulmonary disease (COPD), yet uptake remains low. Intervention strategies which recapitulate the benefits of PR are, therefore, needed and digital, home-based therapies present opportunity in this space. Digital therapies also potentially offer an opportunity to standardize PR in clinical trials for new COPD therapies. Aims and Methods: We aimed to create a digital application (app), Respercise®, consisting of up to 4 strengthening exercises in conjunction with Therbands™ and a daily physical activity program with individualized step goals, and to test its feasibility in a clinical trial. App usability was surveyed qualitatively before development iterations and deployment in a 13-week interventional clinical trial. All participants who completed the study were invited for an exit interview and performed the 5-repetition sit-to-stand test amongst other measures. Results: Feedback from clinical trial participants was positive; 97% of respondents liked the app. A total of 88% of participants reported that it was easy to fit the exercises into their daily routine, and there was over 90% adherence for entering daily step counts. Notably, on day 90 both females and males using Respercise alone demonstrated a 2.22- and 2.27-seconds improvement in time for 5-repetition sit-to-stand tests respectively, above the 1.7 second threshold that is considered clinically meaningful in COPD. Conclusions: Respercise can be successfully deployed in clinical trials, offering the opportunity for standardization of exercise in clinical trials and, with further development, could have wider reach as a home-based intervention for individuals with COPD.

16.
Radiology ; 299(1): 222-231, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33591891

RESUMO

Background The relationship between emphysema progression and long-term outcomes is unclear. Purpose To determine the relationship between emphysema progression at CT and mortality among participants with emphysema. Materials and Methods In a secondary analysis of two prospective observational studies, COPDGene (clinicaltrials.gov, NCT00608764) and Evaluation of Chronic Obstructive Pulmonary Disease Longitudinally to Identify Predictive Surrogate End-points (ECLIPSE; clinicaltrials.gov, NCT00292552), emphysema was measured at CT at two points by using the volume-adjusted lung density at the 15th percentile of the lung density histogram (hereafter, lung density perc15) method. The association between emphysema progression rate and all-cause mortality was analyzed by using Cox regression adjusted for ethnicity, sex, baseline age, pack-years, and lung density, baseline and change in smoking status, forced expiratory volume in 1 second, and 6-minute walk distance. In COPDGene, respiratory mortality was analyzed by using the Fine and Gray method. Results A total of 5143 participants (2613 men [51%]; mean age, 60 years ± 9 [standard deviation]) in COPDGene and 1549 participants (973 men [63%]; mean age, 62 years ± 8) in ECLIPSE were evaluated, of which 2097 (40.8%) and 1179 (76.1%) had emphysema, respectively. Baseline imaging was performed between January 2008 and December 2010 for COPDGene and January 2006 and August 2007 for ECLIPSE. Follow-up imaging was performed after 5.5 years ± 0.6 in COPDGene and 3.0 years ± 0.2 in ECLIPSE, and mortality was assessed over the ensuing 5 years in both. For every 1 g/L per year faster rate of decline in lung density perc15, all-cause mortality increased by 8% in COPDGene (hazard ratio [HR], 1.08; 95% CI: 1.01, 1.16; P = .03) and 6% in ECLIPSE (HR, 1.06; 95% CI: 1.00, 1.13; P = .045). In COPDGene, respiratory mortality increased by 22% (HR, 1.22; 95% CI: 1.13, 1.31; P < .001) for the same increase in the rate of change in lung density perc15. Conclusion In ever-smokers with emphysema, emphysema progression at CT was associated with increased all-cause and respiratory mortality. © RSNA, 2021 Online supplemental material is available for this article. See also the editorial by Lee and Park in this issue.


Assuntos
Enfisema Pulmonar/diagnóstico por imagem , Enfisema Pulmonar/mortalidade , Fumantes , Tomografia Computadorizada por Raios X/métodos , Idoso , Ensaios Clínicos como Assunto , Progressão da Doença , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estados Unidos/epidemiologia
17.
Age Ageing ; 50(3): 795-801, 2021 05 05.
Artigo em Inglês | MEDLINE | ID: mdl-32894757

RESUMO

RATIONALE: chronic obstructive pulmonary disease (COPD) is a leading cause of mortality and common in older adults. The BODE Index is the most recognised mortality risk score in COPD but includes a 6-minute walk test (6MWT) that is seldom available in practise; the BODE Index may be better adopted if the 6MWT was replaced. OBJECTIVES: we investigated whether a modified BODE Index in which 6MWT was replaced by an alternative measure of physical capacity, specifically the short physical performance battery (SPPB) or components, retained its predictive ability for mortality in individuals with COPD. METHODS: we analysed 630 COPD patients from the ERICA cohort study for whom UK Office for National Statistics verified mortality data were available. Variables tested at baseline included spirometry, 6MWT, SPPB and its components (4-m gait speed test [4MGS], chair stand and balance). Predictive models were developed using stratified multivariable Cox regression, and assessed by C-indices and calibration plots with 10-fold cross-validation and replication. RESULTS: during median 2 years of follow-up, 60 (10%) individuals died. There was no significant difference between the discriminative ability of BODE6MWT (C-index 0.709, 95% confidence interval [CI], 0.680-0.737), BODESPPB (C-index 0.683, 95% CI, 0.647-0.712), BODE4MGS (C-index 0.676, 95% CI, 0.643-0.700) and BODEBALANCE (C-index 0.686, 95% CI, 0.651-0.713) for predicting mortality. CONCLUSIONS: the SPPB, and its 4MGS and balance components, can potentially be used as an alternative to the 6MWT in the BODE Index without significant loss of predictive ability in all-cause mortality.


Assuntos
Doença Pulmonar Obstrutiva Crônica , Idoso , Estudos de Coortes , Tolerância ao Exercício , Marcha , Humanos , Desempenho Físico Funcional , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Índice de Gravidade de Doença , Teste de Caminhada
18.
Eur Respir J ; 57(3)2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-32972986

RESUMO

INTRODUCTION: The chronic obstructive pulmonary disease (COPD) bacteriome associates with disease severity, exacerbations and mortality. While COPD patients are susceptible to fungal sensitisation, the role of the fungal mycobiome remains uncertain. METHODS: We report the largest multicentre evaluation of the COPD airway mycobiome to date, including participants from Asia (Singapore and Malaysia) and the UK (Scotland) when stable (n=337) and during exacerbations (n=66) as well as nondiseased (healthy) controls (n=47). Longitudinal mycobiome analysis was performed during and following COPD exacerbations (n=34), and examined in terms of exacerbation frequency, 2-year mortality and occurrence of serum specific IgE (sIgE) against selected fungi. RESULTS: A distinct mycobiome profile is observed in COPD compared with controls as evidenced by increased α-diversity (Shannon index; p<0.001). Significant airway mycobiome differences, including greater interfungal interaction (by co-occurrence), characterise very frequent COPD exacerbators (three or more exacerbations per year) (permutational multivariate ANOVA; adjusted p<0.001). Longitudinal analyses during exacerbations and following treatment with antibiotics and corticosteroids did not reveal any significant change in airway mycobiome profile. Unsupervised clustering resulted in two clinically distinct COPD groups: one with increased symptoms (COPD Assessment Test score) and Saccharomyces dominance, and another with very frequent exacerbations and higher mortality characterised by Aspergillus, Curvularia and Penicillium with a concomitant increase in serum sIgE levels against the same fungi. During acute exacerbations of COPD, lower fungal diversity associates with higher 2-year mortality. CONCLUSION: The airway mycobiome in COPD is characterised by specific fungal genera associated with exacerbations and increased mortality.


Assuntos
Micobioma , Doença Pulmonar Obstrutiva Crônica , Ásia , Progressão da Doença , Humanos , Malásia , Escócia , Singapura
19.
J Allergy Clin Immunol ; 147(1): 158-167, 2021 01.
Artigo em Inglês | MEDLINE | ID: mdl-32353489

RESUMO

BACKGROUND: The sputum microbiome has a potential role in disease phenotyping and risk stratification in chronic obstructive pulmonary disease (COPD), but few large longitudinal cohort studies exist. OBJECTIVE: Our aim was to investigate the COPD sputum microbiome and its association with inflammatory phenotypes and mortality. METHODS: 16S ribosomal RNA gene sequencing was performed on sputum from 253 clinically stable COPD patients (4-year median follow-up). Samples were classified as Proteobacteria or Firmicutes (phylum level) and Haemophilus or Streptococcus (genus level) dominant. Alpha diversity was measured by using Shannon-Wiener diversity and Berger-Parker dominance indices. Survival was modeled by using Cox proportional hazards regression. A subset of 78 patients had label-free liquid chromatography with tandem mass spectrometry performed, with partial least square discriminant analysis integrating clinical, microbiome, and proteomics data. RESULTS: Proteobacteria dominance and lower diversity was associated with more severe COPD according to the Global Initiative for Chronic Obstructive Lung Disease classification system (P = .0015), more frequent exacerbations (P = .0042), blood eosinophil level less than or equal to 100 cells/µL (P < .0001), and lower FEV1 (P = .026). Blood eosinophil counts showed a positive relationship with percent of Firmicutes and Streptococcus and a negative association with percent Proteobacteria and Haemophilus. Proteobacteria dominance was associated with increased mortality compared with Firmicutes-dominated or balanced microbiome profiles (hazard ratio = 2.58; 95% CI = 1.43-4.66; P = .0017 and hazard ratio = 7.47; 95% CI = 1.02-54.86; P = .048, respectively). Integrated omics analysis showed significant associations between Proteobacteria dominance and the neutrophil activation pathway in sputum. CONCLUSION: The sputum microbiome is associated with clinical and inflammatory phenotypes in COPD. Reduced microbiome diversity, associated with Proteobacteria (predominantly Haemophilus) dominance, is associated with neutrophil-associated protein profiles and an increased risk of mortality.


Assuntos
Microbiota , Proteobactérias/classificação , Doença Pulmonar Obstrutiva Crônica , Escarro/microbiologia , Idoso , Intervalo Livre de Doença , Feminino , Humanos , Inflamação , Estudos Longitudinais , Masculino , Doença Pulmonar Obstrutiva Crônica/microbiologia , Doença Pulmonar Obstrutiva Crônica/mortalidade , Taxa de Sobrevida
20.
Chronic Obstr Pulm Dis ; 8(2): 213-218, 2021 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-33291190

RESUMO

Objectives: To investigate telemedicine adoption, emergency department avoidance, and related characteristics of patients with chronic obstructive pulmonary disease (COPD) with and without exacerbations since the coronavirus 2019 (COVID-19) pandemic began. Methods: We conducted the second of a series of online surveys via SurveyMonkey.com of people with COPD between May 1, 2020 and May 31, 2020. Frequency, percentage, and Fisher's exact test (2-sided) were calculated using SPSS version 26. Results: More than half of respondents (157, 64%), indicated that they started using telemedicine in 2020. A total of 47% of respondents reported having had at least 1 exacerbation since January 1, 2020. Respondents who had at least 1 exacerbation in 2020 were more likely to start using telemedicine in 2020 than respondents who did not report any exacerbation in 2020 (75.7% versus 54.3%, p < 0.001). Respondents reporting a 2020 exacerbation indicated having a significantly higher avoidance of emergency health care since the pandemic began (27.8%) as compared to those who did not have an exacerbation in 2020 (10.1%), p < 0.001. Conclusions: In response to social distancing and other COVID-19 precautions, people with COPD are avoiding traditional, in-person health care environments and turning to telemedicine to prevent and manage exacerbations. Further investigation is needed to identify best practices in and barriers to telemedicine in this population.

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