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1.
Sci Rep ; 11(1): 2909, 2021 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-33536488

RESUMO

The identification of factors predisposing to severe COVID-19 in young adults remains partially characterized. Low birth weight (LBW) alters cardiovascular and lung development and predisposes to adult disease. We hypothesized that LBW is a risk factor for severe COVID-19 in non-elderly subjects. We analyzed a prospective cohort of 397 patients (18-70 years) with laboratory-confirmed SARS-CoV-2 infection attended in a tertiary hospital, where 15% required admission to Intensive Care Unit (ICU). Perinatal and current potentially predictive variables were obtained from all patients and LBW was defined as birth weight ≤ 2.500 g. Age (adjusted OR (aOR) 1.04 [1-1.07], P = 0.012), male sex (aOR 3.39 [1.72-6.67], P < 0.001), hypertension (aOR 3.37 [1.69-6.72], P = 0.001), and LBW (aOR 3.61 [1.55-8.43], P = 0.003) independently predicted admission to ICU. The area under the receiver-operating characteristics curve (AUC) of this model was 0.79 [95% CI, 0.74-0.85], with positive and negative predictive values of 29.1% and 97.6% respectively. Results were reproduced in an independent cohort, from a web-based survey in 1822 subjects who self-reported laboratory-positive SARS-CoV-2 infection, where 46 patients (2.5%) needed ICU admission (AUC 0.74 [95% CI 0.68-0.81]). LBW seems to be an independent risk factor for severe COVID-19 in non-elderly adults and might improve the performance of risk stratification algorithms.


Assuntos
/patologia , Recém-Nascido de Baixo Peso , Adolescente , Adulto , Idoso , Área Sob a Curva , Feminino , Humanos , Unidades de Terapia Intensiva/estatística & dados numéricos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Curva ROC , Fatores de Risco , Autorrelato , Índice de Gravidade de Doença , Inquéritos e Questionários , Centros de Atenção Terciária , Adulto Jovem
2.
PLoS One ; 16(2): e0245046, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33630849

RESUMO

The hepatopulmonary syndrome (HPS) is defined by the presence of pulmonary gas exchange abnormalities due to intrapulmonary vascular dilatations in patients with chronic liver disease. Changes in DNA methylation reflect the genomic variation. Since liver transplant (LT) reverts HPS we hypothesized that it may be associated with specific liver epigenetic changes. Thus, the aim of this study was to investigate the role of the liver epigenome in patients with HPS. We extracted DNA from paraffin embedded liver tissue samples from 10 patients with HPS and 10 age-, sex- and MELD (Model for End-stage Liver Disease)-matched controls. DNA methylation was determined using the 850K array (Illumina). Weighted Gene Co-expression Network Analysis (WGCNA) was used to identify modules related to defining physiologic characteristics of HPS. Only 12 out of the 20 liver biopsies (7 HPS and 5 controls) had sufficient quality to be analyzed. None of the 802,688 DNA probes analyzed in the case control comparison achieved a significant False Discovery Rate (FDR). WGCNA identified 5 co-methylated gene-modules associated to HPS markers, mainly related to nervous and neuroendocrine system, apoptotic processes, gut bacterial translocation, angiogenesis and vascular remodeling ontologies. To conclude, HPS is associated with nervous/neuroendocrine system and vascular remodeling related liver epigenetic changes.

3.
Lancet ; 2021 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-33631128

RESUMO

Low-income and middle-income countries (LMICs) bear a disproportionately high burden of the global morbidity and mortality caused by chronic respiratory diseases (CRDs), including asthma, chronic obstructive pulmonary disease, bronchiectasis, and post-tuberculosis lung disease. CRDs are strongly associated with poverty, infectious diseases, and other non-communicable diseases (NCDs), and contribute to complex multi-morbidity, with major consequences for the lives and livelihoods of those affected. The relevance of CRDs to health and socioeconomic wellbeing is expected to increase in the decades ahead, as life expectancies rise and the competing risks of early childhood mortality and infectious diseases plateau. As such, the World Health Organization has identified the prevention and control of NCDs as an urgent development issue and essential to the achievement of the Sustainable Development Goals by 2030. In this Review, we focus on CRDs in LMICs. We discuss the early life origins of CRDs; challenges in their prevention, diagnosis, and management in LMICs; and pathways to solutions to achieve true universal health coverage.

4.
Eur Respir J ; 2021 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-33632799

RESUMO

BACKGROUND: Studies of asthma and chronic obstructive pulmonary disease (COPD) typically focus on these diagnoses separately, limiting understanding of disease mechanisms and treatment options. NOVELTY is a global, 3-year, prospective observational study of patients with asthma and/or COPD from real-world clinical practice. We investigated heterogeneity and overlap by diagnosis and severity in this cohort. METHODS: Patients with physician-assigned asthma, COPD or both (asthma+COPD) were enrolled, stratified by diagnosis and severity. Baseline characteristics were reported descriptively by physician-assigned diagnosis and/or severity. Factors associated with physician-assessed severity were evaluated using ordinal logistic regression analysis. RESULTS: Of 11 243 patients, 5940 (52.8%) had physician-assigned asthma, 1396 (12.4%) had asthma+COPD and 3907 (34.8%) had COPD; almost half were from primary care. Symptoms, health-related quality of life and spirometry showed substantial heterogeneity and overlap between asthma, asthma+COPD and COPD, with 23%, 62% and 64% of patients, respectively, having post-bronchodilator FEV1/FVC

5.
Arch Bronconeumol ; 2021 Jan 20.
Artigo em Inglês, Espanhol | MEDLINE | ID: mdl-33551276
7.
Eur Respir J ; 2020 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-33303557

RESUMO

RATIONALE: There are no validated measures of disease activity in chronic obstructive pulmonary disease (COPD). Since "active" disease is expected to have worse outcomes (e.g. mortality), we explored potential markers of disease activity in patients enrolled in the ECLIPSE cohort in relation to 8-year all-cause mortality. METHODS: We investigated: (1) how changes in relevant clinical variables over time (1 or 3 years) relate to 8-year mortality; (2) whether these variables inter-relate; and (3) if any clinical, imaging, and/or biological marker measured cross-sectionally at baseline relates to any activity component. RESULTS: Results showed that: (1) After 1 year, hospitalisation for COPD, exacerbation frequency, worsening of body mass index, airflow obstruction, dyspnoea, and exercise (BODE) index or health status (St. George's Respiratory Questionnaire [SGRQ]), and persistence of systemic inflammation were significantly associated with 8-year mortality; (2) At 3 years, the same markers, plus forced expiratory volume in 1 s (FEV1) decline and to a lesser degree computed tomography (CT) emphysema, showed association, thus qualifying as markers of disease activity; (3) Changes in FEV1, inflammatory cytokines and CT emphysema were not inter-related, while the multidimensional indices (BODE and SGRQ) showed modest correlations; and, (4) Changes in these markers could not be predicted by any baseline cross-sectional measure. CONCLUSIONS: In COPD, 1- and 3-year changes in exacerbation frequency, systemic inflammation, BODE and SGRQ scores, and FEV1 decline are independent markers of disease activity associated with 8-year all-cause mortality. These disease activity markers are generally independent and not predictable from baseline measurements.

9.
Artigo em Inglês | MEDLINE | ID: mdl-33146552

RESUMO

The SARS-CoV-2 pandemic has raised many questions about the management of COPD patients and whether modifications of their therapy are required. It has raised questions about recognising and differentiating COVID-19 from COPD given the similarity of the symptoms. It is unclear whether COPD patients are at increased risk of becoming infected with SARS-CoV-2. During periods of high prevalence of COVID-19, spirometry should be used when essential for COPD diagnosis and/or to assess lung function status for interventional procedures or surgery. COPD patients should follow basic infection control measures including social distancing, hand washing and wearing a mask or face covering. Although data are limited, inhaled corticosteroids, long-acting bronchodilators, roflumilast, or chronic macrolides should continue to be used as indicated for stable COPD management. Systemic steroids and antibiotics should be used in COPD exacerbations according to the usual indications. Differentiating symptoms of COVID-19 infection from chronic underlying symptoms or those of an COPD exacerbation may be challenging. If there is suspicion for COVID-19, testing for SARS-CoV-2 should be considered. Patients who developed moderate to severe COVID-19, including hospitalization and pneumonia, should be treated with evolving pharmacotherapeutic approaches, as appropriate, including remdesivir, dexamethasone, and anticoagulation. Managing acute respiratory failure should include appropriate oxygen supplementation, prone positioning, noninvasive ventilation, and protective lung ventilation in patients with ARDS. Patients who develop mild COVID-19 should be followed as normal. Patients who developed moderate or worse COVID-19 should be monitored more frequently than normally with particular attention to the need for oxygen therapy. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

10.
Artigo em Inglês | MEDLINE | ID: mdl-33211970

RESUMO

Currently the diagnosis of chronic obstructive pulmonary disease (COPD) requires the demonstration of airflow limitation, defined as a post-bronchodilator FEV1/FVC <0.7, a measurement that remains methodologically robust and widely available. FEV1 is one of the most powerful predictors of clinically relevant outcomes including symptoms, exacerbations and mortality. However, reliable data suggest that respiratory symptoms, in particular chronic bronchitis, airway abnormality and emphysema detected using modern imaging techniques such as computed tomography (CT), and certain physiologic measures including rapid decline in FEV1 and DLCO are present among individuals who do not meet spirometric criteria for COPD. These abnormalities may help to identify individuals at increased risk for developing airflow limitation in the future. Here, we review the evidence that support the use of the term "pre-COPD" in individuals with symptoms (e.g., "Non-Obstructive Chronic Bronchitis" (NOCB)), physiologic (e.g., low DLCO) and/or imaging abnormalities (e.g. CT emphysema) but spirometry in the normal range, who are at risk of developing COPD defined by a reduced FEV1/FVC ratio. We acknowledge, however, that further research on early disease in young individuals will be critical to develop a clinically operable definition of "pre-COPD" that demonstrates good sensitivity and specificity. This article is open access and distributed under the terms of the Creative Commons Attribution Non-Commercial No Derivatives License 4.0 (http://creativecommons.org/licenses/by-nc-nd/4.0/).

12.
Artigo em Inglês | MEDLINE | ID: mdl-33039647

RESUMO

BACKGROUND: A strategy based on the assessment and management of treatable traits (TTs) has been proposed as a new paradigm in airway disease. There is a potentially long list of TTs with likely different clinical impact. OBJECTIVE: To identify TTs most strongly associated with poorer health-related quality of life (HRQOL) and treatments that most substantially improved HRQOL. METHODS: We pooled data from 2 parallel-group clinical trials of multidimensional assessment and individualized management targeted to TTs versus usual care in patients with chronic obstructive pulmonary disease or severe asthma (intervention N = 45; control N = 46). Following multidimensional assessment, 22 TTs were identified and the intervention group received treatments tailored to their identified TT. We used Bayesian Model Averaging to examine associations between TTs and HRQOL (St George's Respiratory Questionnaire) at baseline, as well as between each TT treatment and the observed change in HRQOL postintervention. RESULTS: TTs most substantially associated with poorer baseline HRQOL were frequent chest infections, breathing pattern disorder, inadequate inhaler technique, systemic inflammation (C-reactive protein >3 mg/L), and depression. In both trials, TT treatment led to a large, significant improvement in HRQOL compared with usual care (Cohen's d = 1.19; P < .001). Receiving a statin for systemic inflammation and oral corticosteroid for eosinophilic airway inflammation was associated with the largest HRQOL improvements. Treatments for exercise intolerance, anxiety, and obesity were associated with smaller improvements in HRQOL. CONCLUSIONS: This study contributes to identifying clinically impactful TTs by showing that TTs across pulmonary, extrapulmonary, and behavioral domains were associated with HRQOL impairment and treatment response.

13.
ERJ Open Res ; 6(4)2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33043045

RESUMO

The phenotypic characteristics of chronic obstructive pulmonary disease (COPD) in individuals younger than 50 years of age (early COPD) are not well defined. This prospective, multicentre, case-control study sought to describe these characteristics and compare them with those of smokers (≥10 pack-years) of similar age with normal spirometry (controls). We studied 92 cases (post-bronchodilator forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) <0.7) and 197 controls. Results were contrasted with participants with similar inclusion criteria recruited into the ECLIPSE and COPDGene cohorts. Cases had moderate airflow limitation (FEV1 71.3±20.8%) but were often symptomatic, used healthcare resources frequently, had air trapping (residual volume 150.6±55.5% ref.), had reduced diffusing capacity (84.2±20.7% ref.) and had frequent evidence of computed tomography (CT) emphysema (61%). Of note, less than half of cases (46%) had been previously diagnosed with COPD. Interestingly, they also often reported a family history of respiratory diseases and had been hospitalised because of respiratory problems before the age of 5 years more frequently than controls (12% versus 3%, p=0.009). By and large, these observations were reproduced when available in the ECLIPSE and COPDGene cohorts. These results show that early COPD is associated with substantial health impact and significant structural and functional abnormalities, albeit it is often not diagnosed (hence, treated). The fact that a sizeable proportion of patients with early COPD report a family history of respiratory diseases and/or early-life events (including hospitalisations before the age of 5 years) renders further support to the possibility of early-life origin of COPD.

14.
ERJ Open Res ; 6(3)2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32964006

RESUMO

Randomised controlled trials (RCTs) on the management of COPD exacerbations evaluate heterogeneous outcomes, often omitting those that are clinically important and patient relevant. This limits their usability and comparability. A core outcome set (COS) is a consensus-based minimum set of clinically important outcomes that should be evaluated in all RCTs in specific areas of health care. We present the study protocol of the COS-AECOPD ERS Task Force, aiming to develop a COS for COPD exacerbation management, that could remedy these limitations. For the development of this COS we follow standard methodology recommended by the COMET initiative. A comprehensive list of outcomes is assembled through a methodological systematic review of the outcomes reported in relevant RCTs. Qualitative research with patients with COPD will also be conducted, aiming to identify additional outcomes that may be important to patients, but are not currently addressed in clinical research studies. Prioritisation of the core outcomes will be facilitated through an extensive, multi-stakeholder Delphi survey with a global reach. Selection will be finalised in an international, multi-stakeholder meeting. For every core outcome, we will recommend a specific measurement instrument and standardised time points for evaluation. Selection of instruments will be based on evidence-informed consensus. Our work will improve the quality, usability and comparability of future RCTs on the management of COPD exacerbations and, ultimately, the care of patients with COPD. Multi-stakeholder engagement and societal support by the European Respiratory Society will raise awareness and promote implementation of the COS.

15.
Am J Physiol Lung Cell Mol Physiol ; 319(5): L879-L883, 2020 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-32964724
17.
J Pers Med ; 10(3)2020 Aug 18.
Artigo em Inglês | MEDLINE | ID: mdl-32824824

RESUMO

The contribution of genetic ancestry on chronic obstructive pulmonary disease (COPD) predisposition remains unclear. To explore this relationship, we analyzed the associations between 754,159 single nucleotide polymorphisms (SNPs) and risk of COPD (n = 214 cases, 193 healthy controls) in Talca, Chile, considering the genetic ancestry and established risk factors. The proportion of Mapuche ancestry (PMA) was based on a panel of 45 Mapuche reference individuals. Five PRDM15 SNPs and two PPP1R12B SNPs were associate with COPD risk (p = 0.05 to 5×10-4) in those individuals with lower PMA. Based on linkage disequilibrium and sliding window analyses, an adjacent PRDM15 SNPs were associated with COPD risk in the lower PMA group (p = 10-3 to 3.77×10-8). Our study is the first to report an association between PPP1R12B and COPD risk, as well as effect modification between ethnicity and PRDM15 SNPs in determining COPD risk. Our results are biologically plausible given that PPP1R12B and PRDM15 are involved in immune dysfunction and autoimmunity, providing mechanistic evidence for COPD pathogenesis and highlighting the importance to conduct more genome wide association studies (GWAS) in admixed populations with Amerindian descent.

19.
Clin Chest Med ; 41(3): 307-314, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32800186

RESUMO

Chronic obstructive pulmonary disease (COPD) has been traditionally considered a self-inflicted disease caused by tobacco smoking. Current available evidence, however, indicates that the pathogenesis of COPD needs to consider the dynamic and cumulative nature of a series of environment (including smoking plus other exposures)-host interactions that eventually determine lung development, maintenance, repair, and aging. By doing so, these factors modulate the trajectory of lung function of the individual through life and the odds of developing COPD through different routes, which likely represent different forms of the disease that require different preventive and therapeutic strategies.


Assuntos
Doença Pulmonar Obstrutiva Crônica/patologia , Feminino , Humanos , Masculino
20.
Eur Respir J ; 56(1)2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32646894
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