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1.
Maturitas ; 184: 107951, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38471294

RESUMO

In the face of rising global urbanisation, understanding how the associated environment and lifestyle impact public health is a cornerstone for prevention, research, and clinical practice. Cardiovascular disease is the leading cause of morbidity and mortality worldwide, with urban risk factors contributing greatly to its burden. The current narrative review adopts an exposome approach to explore the effect of urban-associated physical-chemical factors (such as air pollution) and lifestyle on cardiovascular health and ageing. In addition, we provide new insights into how these urban-related factors alter the gut microbiome, which has been associated with an increased risk of cardiovascular disease. We focus on vascular ageing, before disease onset, to promote preventative research and practice. We also discuss how urban ecosystems and social factors may interact with these pathways and provide suggestions for future research, precision prevention and management of vascular ageing. Most importantly, future research and decision-making would benefit from adopting an exposome approach and acknowledging the diverse and boundless universe of the microbiome.


Assuntos
Envelhecimento , Doenças Cardiovasculares , Microbioma Gastrointestinal , Humanos , Envelhecimento/fisiologia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/microbiologia , Doenças Cardiovasculares/etiologia , Fatores de Risco , Estilo de Vida , Poluição do Ar/efeitos adversos , Expossoma
2.
J Cyst Fibros ; 23(1): 50-57, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37666709

RESUMO

BACKGROUND: Nontuberculous mycobacteria (NTM) are an important cause of airway infections in people with cystic fibrosis (pwCF). Isolation of NTM from respiratory specimens of pwCF do not mandate treatment in the absence of clinical and radiologic features of NTM pulmonary disease (NTM-PD), as some pwCF clear the infection without treatment and others do not appear to progress to NTM-PD despite persistent infection. An evidence-based protocol to standardize diagnosis of NTM-PD is needed to systematically identify pwCF who may benefit from treatment. METHODS: In this multicenter observational study, eligible pwCF who are 6 years of age and older and who have had a recent positive NTM culture are systematically evaluated for NTM-PD. Participants are identified based on positive NTM culture results obtained during routine clinical care and following enrollment are evaluated for NTM-PD and CF-related comorbidities. Participants are followed in PREDICT until they meet NTM-PD diagnostic criteria and are ready to initiate NTM treatment, or until study termination. Active participants who have not met these criteria are re-consented every 5 years to enable long-term participation. RESULTS: The primary endpoint will summarize the proportion of participants who meet the NTM-PD diagnosis definition. The time from enrollment to NTM-PD diagnosis will be derived from Kaplan-Meier estimates. CONCLUSION: A prospective protocol to identify NTM-PD in pwCF will test if this standardized approach defines a cohort with signs and symptoms associated with NTM-PD, to assist with clinical decision making and to build a framework for future therapeutic trials. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT02073409.


Assuntos
Fibrose Cística , Infecções por Mycobacterium não Tuberculosas , Humanos , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Fibrose Cística/microbiologia , Infecções por Mycobacterium não Tuberculosas/tratamento farmacológico , Micobactérias não Tuberculosas
5.
PLoS One ; 18(12): e0291910, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38117792

RESUMO

BACKGROUND: Healthcare-associated acquisition and transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been described, and remains a concern for both patients and providers. This report describes the design of a prospective observational study utilizing the standardized epidemiologic investigation toolkit for healthcare-associated links in transmission of NTM among pwCF. METHODS: This is a parallel multi-site study of pwCF who have infections with respiratory NTM isolates and receive healthcare within a common CF Care Center. Participants have a history of one or more NTM positive airway cultures and have been identified as having NTM infections suggestive of a possible outbreak within a single Center, based on NTM isolate genomic analysis. Participants are enrolled in the study over a 3-year period. Primary endpoints are identification of shared healthcare-associated source(s) among pwCF in a Center, identification of healthcare environmental dust and water biofilm NTM isolates that are genetically highly-related to respiratory isolates, and identification of common home of residence watersheds among pwCF infected with clustered isolates. Secondary endpoints include characterization of healthcare-associated transmission and/or acquisition modes and settings as well as description of incidence and prevalence of healthcare-associated environmental NTM species/subspecies by geographical region. DISCUSSION: We hypothesize that genetically highly-related isolates of NTM among pwCF cared for at the same Center may arise from healthcare sources including patient-to-patient transmission and/or acquisition from health-care environmental dust and/or water biofilms. This study design utilizes a published, standardized, evidence-based epidemiologic toolkit to facilitate confidential, independent healthcare-associated NTM outbreak investigations within CF Care Centers. This study will facilitate real-time, rapid detection and mitigation of healthcare-associated NTM outbreaks to reduce NTM risk, inform infection prevention and control guidelines, and characterize the prevalence and origin of NTM outbreaks from healthcare-associated patient-to-patient transmission and/or environmental acquisition. This study will systematically characterize human disease causing NTM isolates from serial collection of healthcare environmental dust and water biofilms and define the most common healthcare environmental sources harboring NTM biofilms. TRIAL REGISTRATION: ClinicalTrials.gov NCT05686837.


Assuntos
Fibrose Cística , Infecções por Mycobacterium não Tuberculosas , Humanos , Fibrose Cística/microbiologia , Atenção à Saúde , Poeira , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas/genética , Estudos Prospectivos , Água
6.
Int J Cardiol Cardiovasc Risk Prev ; 18: 200205, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37664166

RESUMO

Background: People living with HIV (PLWHIV) are at a higher risk of developing coronary artery disease (CAD). We aimed to assess the factors associated with CAD among PLWHIV in Colombia. Methods: We conducted a retrospective cohort study based on adults newly diagnosed with HIV, reported to the Colombian HIV/AIDS registry from 2018 to 2021. Baseline demographic and clinical characteristics were compared by age (<50 and ≥ 50 years). Our main outcome was the presence of CAD. Logistic regression models were used to assess the association between traditional and HIV-related factors with CAD. These associations were also evaluated in stratified models by age. Effect measures were odds ratios (OR) and their 95% confidence intervals. Results: Among 36,483 PLWHIV, the frequency of CAD was 0.53% (n = 196). There was a high prevalence of impaired fasting glucose/diabetes mellitus (12.62%), overweight/obesity (27.79%), elevated LDL-c (86.69%), and hypertriglyceridemia (72.76%). Factors associated with CAD included male gender (OR: 2.01, 95% CI: 1.12-3.58), age ≥50 years (OR: 4.96, 95% CI: 3.29-7.45), lipoatrophy or lipodystrophy (OR 5.12, 95% CI: 1.12-23.33), AIDS-defining conditions (OR: 1.83, 95% CI: 1.07-3.12), obesity (OR: 2.95, 95% CI: 1.69-5.10), diabetes mellitus (OR: 2.50, 95% CI: 1.25-4.97), and renal impairment (OR: 3.15, 95% CI: 1.83-5.42). Conclusions: Traditional CAD risk factors are common in PLWHIV. There were traditional and disease-specific factors associated with increased odds of CAD. These findings may aid clinicians and decision-makers in reducing the impact of CAD in PLWHIV.

8.
bioRxiv ; 2023 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-37293112

RESUMO

Mycobacterium abscessus is a nontuberculous mycobacterium emerging as a significant pathogen for individuals with chronic lung disease, including cystic fibrosis and chronic obstructive pulmonary disease. Current therapeutics have poor efficacy. New strategies of bacterial control based on host defenses are appealing, but anti-mycobacterial immune mechanisms are poorly understood and are complicated by the appearance of smooth and rough morphotypes with distinct host responses. We explored the role of the complement system in the clearance of M. abscessus morphotypes by neutrophils, an abundant cell in these infections. M. abscessus opsonized with plasma from healthy individuals promoted greater killing by neutrophils compared to opsonization in heat-inactivated plasma. Rough clinical isolates were more resistant to complement but were still efficiently killed. Complement C3 associated strongly with the smooth morphotype while mannose-binding lectin 2 was associated with the rough morphotype. M. abscessus killing was dependent on C3, but not on C1q or Factor B; furthermore, competition of mannose-binding lectin 2 binding with mannan or N-acetyl-glucosamine during opsonization did not inhibit killing. These data suggest that M. abscessus does not canonically activate complement through the classical, alternative, or lectin pathways. Complement-mediated killing was dependent on IgG and IgM for smooth and on IgG for rough M. abscessus. Both morphotypes were recognized by Complement Receptor 3 (CD11b), but not CR1 (CD35), and in a carbohydrate- and calcium-dependent manner. These data suggest the smooth-to-rough adaptation changes complement recognition of M. abscessus and that complement is an important factor for M. abscessus infection.

9.
Microbiol Spectr ; 11(1): e0327922, 2023 02 14.
Artigo em Inglês | MEDLINE | ID: mdl-36651756

RESUMO

Nontuberculous mycobacteria (NTM), including Mycobacterium avium, are clinically important pathogens in cystic fibrosis (CF). The innate immune response to M. avium remains incompletely understood. We evaluated the role of complement opsonization in neutrophil-mediated killing of M. avium. Killing assays were performed using neutrophils from healthy donors (HDs) and persons with CF (pwCF). Clinical isolates of M. avium were opsonized with plasma from HDs or pwCF, which was intact or heat-treated to inactivate complement. HD neutrophils had killing activity against M. avium opsonized with intact HD plasma and killing was significantly reduced when M. avium was opsonized with heat-inactivated HD plasma. When opsonized with HD plasma, CF neutrophils had killing activity against M. avium that was not different than HD neutrophils. When opsonized with intact plasma from pwCF, HD neutrophil killing of M. avium was significantly reduced. Opsonization of M. avium with C3-depleted serum or IgM-depleted plasma resulted in significantly reduced killing. Plasma C3 levels were elevated in pwCF with NTM infection compared to pwCF without NTM infection. These studies demonstrate that human neutrophils efficiently kill M. avium when opsonized in the presence of plasma factors from HD that include C3 and IgM. Killing efficiency is significantly lower when the bacteria are opsonized with plasma from pwCF. This indicates a novel role for opsonization in neutrophil killing of M. avium and a deficiency in complement opsonization as a mechanism of impaired M. avium killing in CF. IMPORTANCE Mycobacterium avium is a member of a group of bacterial species termed nontuberculous mycobacteria (NTM) that cause lung disease in certain populations, including persons with cystic fibrosis (CF). NTM infections are challenging to diagnose and can be even more difficult to treat. This study investigated how the immune system responds to M. avium infection in CF. We found that neutrophils, the most abundant immune cell in the lungs in CF, can effectively kill M. avium in individuals both with and without CF. Another component of the immune response called the complement system is also required for this process. Levels of complement proteins are altered in persons with CF who have a history of NTM compared to those without a history of NTM infection. These results add to our understanding of how the immune system responds to M. avium, which can help pave the way toward better diagnostic and treatment strategies.


Assuntos
Fibrose Cística , Infecções por Mycobacterium não Tuberculosas , Humanos , Fibrose Cística/microbiologia , Neutrófilos , Mycobacterium avium , Opsonização , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas , Proteínas do Sistema Complemento , Imunoglobulina M
10.
Ann Am Thorac Soc ; 20(5): 677-686, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-36656594

RESUMO

Rationale: Outbreaks of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) have been reported at CF centers with conflicting conclusions. The occurrence of NTM at the UVMC (University of Vermont Medical Center) adult CF program was investigated. Objectives: Use the HALT NTM (Healthcare-associated Links in Transmission of NTM) toolkit to investigate the healthcare-associated transmission and/or acquisition of NTM among pwCF having genetically similar NTM isolates. Methods: Whole genome sequencing of NTM isolates from 23 pwCF was conducted to identify genetically similar NTM isolate clusters (30 or fewer single-nucleotide polymorphism differences). The epidemiological investigation, comparison of respiratory and healthcare environmental isolates, and home residence watershed mapping were analyzed. Results: Whole genome sequencing analysis revealed two clusters of NTM isolates (Mycobacterium avium and M. intracellulare ssp. chimaera) among pwCF. The epidemiologic investigation demonstrated opportunities for healthcare-associated transmission within both clusters. Healthcare environmental M. avium isolates revealed no genetic similarity to respiratory isolates. However, M. intracellulare ssp. chimaera respiratory isolates revealed greater genetic similarity to a hospital water biofilm isolate than to each other. Neither cluster had all subjects residing in the same watershed. Conclusions: This study suggests the healthcare-associated transmission of M. avium among pwCF is unlikely at UVMC but supports the healthcare-associated environmental acquisition of M. intracellulare ssp. chimaera. The presence of genetically similar isolates alone is insufficient to confirm healthcare-associated transmission and/or acquisition. The HALT NTM toolkit standardizes outbreak investigation with genetic analysis, epidemiologic investigation, healthcare environmental sampling, and home of residence watershed identification to test the frequency and nature of healthcare-associated NTM transmission among pwCF.


Assuntos
Fibrose Cística , Infecções por Mycobacterium não Tuberculosas , Mycobacterium , Pneumonia , Humanos , Adulto , Complexo Mycobacterium avium , Micobactérias não Tuberculosas , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Pulmão
11.
Tuberculosis (Edinb) ; 138: 102276, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36417800

RESUMO

Nontuberculous mycobacteria (NTM) are opportunistic pathogens that affect a relatively small but significant portion of the people with cystic fibrosis (CF), and may cause increased morbidity and mortality in this population. Cultures from the airway are the only test currently in clinical use for detecting NTM. Culture techniques used in clinical laboratories are insensitive and poorly suited for population screening or to follow progression of disease or treatment response. The lack of sensitive and quantitative markers of NTM in the airway impedes patient care and clinical trial design, and has limited our understanding of patterns of acquisition, latency and pathogenesis of disease. Culture-independent markers of NTM infection have the potential to overcome many of the limitations of standard NTM cultures, especially the very slow growth, inability to quantitate bacterial burden, and low sensitivity due to required decontamination procedures. A range of markers have been identified in sputum, saliva, breath, blood, urine, as well as radiographic studies. Proposed markers to detect presence of NTM or transition to NTM disease include bacterial cell wall products and DNA, as well as markers of host immune response such as immunoglobulins and the gene expression of circulating leukocytes. In all cases the sensitivity of culture-independent markers is greater than standard cultures; however, most do not discriminate between various NTM species. Thus, each marker may be best suited for a specific clinical application, or combined with other markers and traditional cultures to improve diagnosis and monitoring of treatment response.


Assuntos
Fibrose Cística , Infecções por Mycobacterium não Tuberculosas , Mycobacterium tuberculosis , Humanos , Fibrose Cística/complicações , Fibrose Cística/diagnóstico , Fibrose Cística/epidemiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas , Pulmão
13.
Lancet Microbe ; 3(12): e956-e968, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36370748

RESUMO

BACKGROUND: Antimicrobial resistance of bacterial pathogens is an increasing clinical problem and alternative approaches to antibiotic chemotherapy are needed. One of these approaches is the use of lytic bacterial viruses known as phage therapy. We aimed to assess the efficacy of phage therapy in preclinical animal models of bacterial infection. METHODS: In this systematic review and meta-analysis, MEDLINE/Ovid, Embase/Ovid, CINAHL/EbscoHOST, Web of Science/Wiley, Cochrane Central Register of Controlled Trials, Cochrane Database of Systematic Reviews, and Google Scholar were searched from inception to Sept 30, 2021. Studies assessing phage efficacy in animal models were included. Only studies that assessed the efficacy of phage therapy in treating established bacterial infections in terms of survival and bacterial abundance or density were included. Studies reporting only in-vitro or ex-vivo results and those with incomplete information were excluded. Risk-of-bias assessment was performed using the Systematic Review Centre for Laboratory Animal Experimentation tool. The main endpoints were animal survival and tissue bacterial burden, which were reported using pooled odds ratios (ORs) and mean differences with random-effects models. The I2 measure and its 95% CI were also calculated. This study is registered with PROSPERO, CRD42022311309. FINDINGS: Of the 5084 references screened, 124 studies fulfilled the selection criteria. Risk of bias was high for 70 (56%) of the 124 included studies; therefore, only studies classified as having a low-to-moderate risk of bias were considered for quantitative data synthesis (n=32). Phage therapy was associated with significantly improved survival at 24 h in systemic infection models (OR 0·08 [95% CI 0·03 to 0·20]; I2=55% [95% CI 8 to 77]), skin infection (OR 0·08 [0·04 to 0·19]; I2 = 0% [0 to 79]), and pneumonia models (OR 0·13 [0·06 to 0·31]; I2=0% [0 to 68]) when compared with placebo. Animals with skin infections (mean difference -2·66 [95% CI -3·17 to -2·16]; I2 = 95% [90 to 96]) and those with pneumonia (mean difference -3·35 [-6·00 to -0·69]; I2 = 99% [98 to 99]) treated with phage therapy had significantly lower tissue bacterial loads at 5 ±â€ˆ2 days of follow-up compared with placebo. INTERPRETATION: Phage therapy significantly improved animal survival and reduced organ bacterial loads compared with placebo in preclinical animal models. However, high heterogeneity was observed in some comparisons. More evidence is needed to identify the factors influencing phage therapy performance to improve future clinical application. FUNDING: Swiss National Foundation and Swiss Heart Foundation.


Assuntos
Infecções Bacterianas , Terapia por Fagos , Humanos , Infecções Bacterianas/terapia , Antibacterianos/uso terapêutico
14.
Microbiol Spectr ; 10(4): e0187422, 2022 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-35863022

RESUMO

Nontuberculous mycobacteria (NTM) infections are increasingly prevalent in chronic lung diseases, including cystic fibrosis (CF). Mycobacterium abscessus is of particular concern due to relatively greater virulence and intrinsic antimicrobial resistance. Airway culture identification, the standard method for detecting pulmonary infection, is hindered by low sensitivity, long culture times, and reliance on sputum production or lavage. A culture-independent test for detecting NTM infection could complement, or replace, sputum culture, which is becoming more difficult to obtain with reduced sputum production by people with CF (pwCF) on highly effective modulator therapy. We describe an assay for the detection of plasma anti-M. abscessus antibodies of pwCF to antigens from M. abscessus lysates. Anti-M. abscessus IgG and IgA, but not IgM, discriminated with high specificity subjects infected with M. abscessus from those infected by M. avium complex, and from those with distant or no NTM infections. The IgG3 subclass predominated with minor contributions by other subclasses. Both aqueous and organic soluble antigens were recognized by plasma IgG. A validation cohort measuring IgG and IgG3 identified M. abscessus positive subjects, and elevated IgG was sustained over several years. These studies show the benefit of M. abscessus cell lysates to detect plasma IgG of subjects with CF and M. abscessus infections. Subclass analysis suggests that IgG3 is the predominant subtype in these subjects with chronic bacterial infections suggesting a defect in class maturation. Serodiagnosis could be useful to monitor M. abscessus group infections in chronic lung disease as an adjunct or alternative to culture. IMPORTANCE Lung infections with nontuberculous mycobacteria (NTM), and particularly Mycobacterium abscessus, a pathogen with high antibiotic resistance, are of great concern due to poor clinical outcomes and challenging detection in people with cystic fibrosis and other diseases. Standard detection methods are insensitive and increasingly difficult. We describe the measurement of NTM-specific antibodies from plasma to identify subjects infected with M. abscessus. The assay is sensitive and provides information on the immune response to NTM infections. This assay could be used to help identify subjects with NTM pulmonary infections and track disease progression, either alone or in conjunction with other tests.


Assuntos
Fibrose Cística , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Fibrose Cística/complicações , Fibrose Cística/microbiologia , Humanos , Imunoglobulina G , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas
15.
Infectio ; 26(2): 113-120, Jan.-June 2022. tab, graf
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1356256

RESUMO

Abstract HIV/AIDS information systems are a critical tool for keeping track of the HIV pandemic in any country, leading to the AIDS elimination to 2030 and achievement of the 95-95-95 goals set by 2025. In this article, we describe the data management process of the Colombian National HIV/AIDS registry, its epidemiological results and contributions to research and health risk management. This registry is a longitudinal database. Variables and periodicity are defined by The Ministry of Health and Social Protection. Reporting is done by health insurers and their healthcare providers on annual bases. The information is uploaded through a web platform run by the High-Cost Diseases Fund, in charge of the validation, auditing process, consolidation, analysis and publication of the data. Security and confidentiality of the information is also taken care of by the High-Cost Disease Fund. Main results include epidemiological follow up of the epidemic, periodic evaluation of 25 risk management indicators, publication of research studies and the calculation of an economic incentive for insurers to improve health risk management. The registry has shown to be useful not only for the management of clinical information but also for administrative purposes.


Resumen Los sistemas de información sobre el VIH/SIDA son una herramienta fundamental para realizar el seguimiento de la pandemia del VIH en cualquier país, con miras a la eliminación del SIDA hasta el 2030 y al logro de las metas 95-95-95 establecidas para el 2025. En este artículo se describe el proceso de gestión de datos del Registro Nacional de VIH/SIDA de Colombia, sus resultados epidemiológicos, sus aportes a la investigación y a la gestión del riesgo en salud. Este registro es una base de datos longitudinal. Las variables y la periodicidad son definidas por el Ministerio de Salud y Protección Social. Los reportes son realizados por las aseguradoras de salud y sus prestadores de servicios de salud sobre bases anuales. La información se carga a través de una plataforma web gestionada por el Fondo de Enfermedades de Alto Costo, encargado del proceso de validación, auditoría, consolidación, análisis y publicación de los datos. El Fondo de Enfermedades de Alto Coste también se encarga de la seguridad y la confidencialidad de la información. Los principales resultados son el seguimiento epidemiológico de la epidemia, la evaluación periódica de 25 indicadores de gestión del riesgo, la publicación de estudios de investigación y el cálculo de un incentivo económico para que las aseguradoras mejoren la gestión del riesgo sanitario. El registro ha demostrado ser útil no sólo para la gestión de la información clínica, sino también para fines administrativos.

16.
Cell ; 185(11): 1860-1874.e12, 2022 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-35568033

RESUMO

Two mycobacteriophages were administered intravenously to a male with treatment-refractory Mycobacterium abscessus pulmonary infection and severe cystic fibrosis lung disease. The phages were engineered to enhance their capacity to lyse M. abscessus and were selected specifically as the most effective against the subject's bacterial isolate. In the setting of compassionate use, the evidence of phage-induced lysis was observed using molecular and metabolic assays combined with clinical assessments. M. abscessus isolates pre and post-phage treatment demonstrated genetic stability, with a general decline in diversity and no increased resistance to phage or antibiotics. The anti-phage neutralizing antibody titers to one phage increased with time but did not prevent clinical improvement throughout the course of treatment. The subject received lung transplantation on day 379, and systematic culturing of the explanted lung did not detect M. abscessus. This study describes the course and associated markers of a successful phage treatment of M. abscessus in advanced lung disease.


Assuntos
Bacteriófagos , Fibrose Cística , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Bacteriófagos/genética , Fibrose Cística/tratamento farmacológico , Humanos , Pulmão , Masculino , Infecções por Mycobacterium não Tuberculosas/terapia , Mycobacterium abscessus/fisiologia
17.
PLoS One ; 17(5): e0267592, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35511761

RESUMO

Inhaled antibiotics control chronic airway infection and maintain respiratory health in cystic fibrosis (CF). Given variation in patient responses to inhaled antibiotics, the ability to identify distinct responder phenotypes would facilitate the delivery of personalized care. Previously, a 10-gene panel was identified, measured directly from blood leukocytes, which predicted host response to intravenous antibiotic treatment during pulmonary exacerbations. In the current study, we tested whether the same panel predicted clinical response in subjects receiving a month of inhaled antibiotic therapy with aztreonam lysine (AZLI; Cayston®). A small cohort of CF subjects infected with Pseudomonas aeruginosa were enrolled at baseline health, prior to initiating one month's treatment with AZLI using the Altera® nebulizer system. Eighteen CF subjects underwent blood leukocyte gene panel measurements, sputum quantitative microbiology, spirometry, and C-reactive protein (CRP) measurement prior to onset and at completion of 4 weeks of AZLI therapy. Mean absolute improvement in percent predicted Forced Expiratory Volume in one second (ppFEV1) was 3%. Significant reductions in sputum bacterial colony counts were detected with treatment. CRP increased following treatment. While single genes within the panel did not change significantly following treatment, the analysis of multigene panel data demonstrated that HCA112 gene predicted ppFEV1 improvement. Hierarchical clustering based on gene expression yielded two distinctive molecular clusters before and after AZLI therapy. In conclusion, peripheral blood leukocyte genes quantifying inflammation are associated with responses to inhaled antibiotic therapy. Molecular quantification of systemic inflammation may indicate subgroups of CF subjects with variations in underlying inflammation and with variable clinical responses to inhaled antibiotics. Given the size limitation of the study, larger studies are needed in order to evaluate whether molecular measures may add precision to the determination of infectious and inflammatory outcomes following courses of inhaled antimicrobial therapies. Clinical Trials.gov Identifier: NCT01736839.


Assuntos
Fibrose Cística , Infecções por Pseudomonas , Administração por Inalação , Antibacterianos/uso terapêutico , Biomarcadores , Fibrose Cística/complicações , Fibrose Cística/tratamento farmacológico , Fibrose Cística/genética , Humanos , Inflamação/tratamento farmacológico , Estudos Prospectivos , Infecções por Pseudomonas/complicações , Infecções por Pseudomonas/tratamento farmacológico , Pseudomonas aeruginosa/genética , RNA Mensageiro , Escarro/microbiologia
18.
rev.cuid. (Bucaramanga. 2010) ; 13(2): 1-18, 20220504.
Artigo em Inglês | LILACS, BDENF - Enfermagem, COLNAL | ID: biblio-1402300

RESUMO

Introduction: The 2019 coronavirus disease (COVID-19) pandemic, should be an opportunity to ensure greater visibility of nursing in health systems and society worldwide. Objective: Review and synthesize the patterns on COVID-19 and nursing research, identifying the main journals, country of origin, language, topics, designs, and area of applicability of the results. Materials and Methods: Systematic review. Searches in PubMed, CINAHL, LILACS, and EMBASE databases (from the inception of the pandemic to May 15, 2020) were performed. Articles of any language related were related to SARS-CoV-2 infection or COVID-19 disease and nursing in any of its roles (care, management, education, among others) and using any epidemiological design or a scientific report were included. Two reviewers independently selected the studies and extracted the data. The main findings from the included studies were summarized through narrative synthesis and descriptive tables. The characteristics of the studies were presented as absolute values and proportions. Results: Three hundred and sixty-five articles were assessed for eligibility. Thirty-eight were included, published in 28 journals. Of those, 53.57% (n=15) were nursing specific. Most articles were "narrative reviews", accounting for 23.68% (n=9). Most studies were conducted in China (n=18, 47.37%), followed by the United Kingdom and the United States. Thirty-four (89.47%) articles were published in English, followed by Portuguese and Chinese. We identified five areas of application of the results, and the most frequent was the "clinical" setting with 47.00% (n=18). Discussion: These findings are crucial to give visibility to nursing work during the emergency of the COVID-19 pandemic. Mental health was the main research topic, while the clinical setting concentrates the major number of articles. This pattern was aligned with the challenges of the initial phase of the pandemic. Conclusion: Future research should explore the current state of evidence in the main topics identified in this review and continue to give visibility to work carried out by nursing in the emergency of the COVID-19 pandemic.


Introducción: La pandemia de la enfermedad de coronavirus 2019 (COVID-19), debería ser una oportunidad para asegurar una mayor visibilidad de la enfermería en los sistemas de salud y la sociedad en todo el mundo. Objetivo: Revisar y sintetizar los patrones de investigación en enfermería y COVID-19, identificando las principales revistas, país de origen, idioma, temas, diseños y área de aplicabilidad de los resultados. Materiales y Metodos: Una revisión sistemática. Se realizaron búsquedas en las bases de datos PubMed, CINAHL, LILACS y EMBASE (desde el inicio de la pandemia hasta el 15 de mayo de 2020). Se incluyeron artículos de cualquier idioma relacionados con la infección por SARS-CoV-2 o COVID-19 y enfermería en cualquiera de sus roles (cuidado, administración, educación, entre otros) que utilizaron cualquier diseño epidemiológico o informe científico. Dos revisores seleccionaron de forma independiente los estudios y extrajeron los datos. Los principales hallazgos de los estudios incluidos se resumieron mediante una síntesis narrativa y tablas descriptivas. Las características de los estudios se presentaron como valores absolutos y proporciones. Resultados: En 325 artículos se evaluaron los criterios de elegibilidad y se incluyeron 38 publicados en 28 revistas. De ellos, el 53,57% (n=15) eran específicos de enfermería. La mayoría de los artículos fueron "revisiones narrativas", que representan el 23,68% (n=9). La mayoría de los estudios se realizaron en China (n=18, 47,37%), seguido de Reino Unido y Estados Unidos. Treinta y cuatro (89,47%) artículos se publicaron en inglés, seguidos de portugués y chino. Identificamos cinco áreas de aplicación de los resultados y la más frecuente fue el ámbito "clínico" con un 47,00% (n=18). Discusión: Estos hallazgos son cruciales para dar visibilidad al trabajo de enfermería en la emergencia de la pandemia COVID-19. Se destaca que la salud mental fue el principal tópico de investigación mientras que el escenario clínico concentró el mayor número de artículo. Este patrón estuvo alineado con los desafíos impuestos por la fase inicial de la pandemia. Conclusión: Las investigaciones futuras deberán explorar el estado actual de la evidencia en los principales temas identificados en esta revisión y continuar dando visibilidad al trabajo realizado por enfermería en la emergencia de la pandemia por COVID-19.


Introdução: A pandemia da doença coronavírus (COVID-19) de 2019 deve ser uma oportu-nidade para garantir maior visibilidade da enfermagem nos sistemas de saúde e na sociedade em todo o mundo. Objetivo: Revisar e sintetizar os padrões de pesquisa em enfermagem e COVID-19, identificando as principais revistas, país de origem, língua, tópicos, desenhos e área de aplicabilidade dos resultados. Materiais e Métodos: Uma revisão sistemática. As ba-ses de dados PubMed, CINAHL, LILACS e EMBASE foram pesquisadas (Do início da pan-demia até 15 de maio de 2020). Artigos de qualquer língua relacionados à infecção por SARS-CoV-2 ou COVID-19 e enfermagem foram incluídos em qualquer das suas funções (assistên-cia, administração, educação, entre outras) que utilizassem qualquer desenho epidemiológico ou relatório científico. Dois revisores selecionaram independentemente estudos e extraíram os dados. As principais conclusões dos estudos incluídos foram resumidas através de uma síntese narrativa e tabelas descritivas. As características dos estudos foram apresentadas em valores absolutos e proporções. Resultados: Em 325 artigos foram avaliados os critérios de elegibili-dade e incluídos 38 publicados em 28 revistas. Destes, 53,57% (n=15) eram específicos da enfermagem. A maioria dos artigos eram "revisões narrativas", representando 23,68% (n=9). A maioria dos estudos foi realizada na China (n=18, 47,37%), seguida do Reino Unido e dos Estados Unidos. Trinta e quatro (89,47%) artigos foram publicados em inglês, seguidos de português e chinês. Identificamos cinco áreas de aplicação dos resultados e a mais frequente foi a área "clínica" com 47,00% (n=18). Discussão: Estas conclusões são cruciais para dar vi-sibilidade ao trabalho de enfermagem durante a emergência da pandemia da COVID-19. A saúde mental foi o principal tema de investigação, enquanto que o cenário clínico concentra o maior número de artigos. Este padrão foi alinhado com os desafios da fase inicial da pande-mia. Conclusão: A investigação futura deve explorar o estado atual das provas nos principais tópicos identificados nesta revisão e continuar a dar visibilidade ao trabalho realizado pela enfermagem na emergência da pandemia da COVID-19.


Assuntos
Infecções por Coronavirus , Pandemias , Betacoronavirus , Revisão Sistemática , Cuidados de Enfermagem
19.
J Breath Res ; 16(3)2022 05 13.
Artigo em Inglês | MEDLINE | ID: mdl-35487186

RESUMO

Pulmonary infections caused by mycobacteria cause significant mortality and morbidity in the human population. Diagnosing mycobacterial infections is challenging. An infection can lead to active disease or remain indolent with little clinical consequence. In patients with pulmonarynontuberculosis mycobacteria(PNTM) identification of infection and diagnosis of disease can take months to years. Our previous studies showed the potential diagnostic power of volatile molecules in the exhaled breath samples to detect active pulmonaryM. tuberculosisinfection. Herein, we demonstrate the ability to detect the disease status of PNTM in the breath of persons with cystic fibrosis (PwCF). We putatively identified 17 volatile molecules that could discriminate between active-NTM disease (n= 6), indolent patients (n= 3), and those patients who have never cultured an NTM (n= 2). The results suggest that further confirmation of the breath biomarkers as a non-invasive and culture-independent tool for diagnosis of NTM disease in a larger cohort of PwCF is warranted.


Assuntos
Fibrose Cística , Infecções por Mycobacterium , Biomarcadores , Testes Respiratórios/métodos , Fibrose Cística/diagnóstico , Expiração , Humanos , Projetos Piloto
20.
Am J Respir Crit Care Med ; 205(9): 1064-1074, 2022 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-35085056

RESUMO

Rationale: Healthcare-associated transmission of nontuberculous mycobacteria (NTM) among people with cystic fibrosis (pwCF) has been investigated at CF centers worldwide, with conflicting conclusions. We investigated transmission at the Colorado Adult CF Program. Objectives: To systematically investigate healthcare-associated transmission and/or acquisition of NTM to determine similarity among respiratory and environmental isolates, and to compare home residence watershed mapping among pwCF having genetically similar NTM isolates. Methods: Whole-genome sequencing of NTM isolates from 80 pwCF was conducted to identify genetically similar isolate clusters (⩽30 SNP differences). Epidemiology, comparison of respiratory and environmental isolates, and home residence watershed mapping were analyzed. Measurements and Main Results: Whole-genome sequencing analysis revealed 11 clusters of NTM [6 Mycobacterium abscessus subspecies (ssp.) abscessus, 1 M. abscessus ssp. massiliense, 2 Mycobacterium avium, and 2 Mycobacterium intracellulare] among pwCF. Epidemiologic investigation demonstrated opportunities for healthcare-associated transmission in two M. abscessus and two M. avium clusters. Respiratory and healthcare environmental isolate comparisons revealed no genetic similarity. Individuals comprising one M. abscessus cluster, with no plausible healthcare-associated transmission, resided in the same watershed. Conclusions: This study suggests healthcare-associated transmission of M. abscessus is rare and includes a report of potential healthcare-associated transmission of M. avium among pwCF. One M. abscessus cluster possibly had common acquisition arising from residing in the same watershed. The presence of genetically similar isolates is insufficient to demonstrate healthcare-associated NTM transmission. Standardizing epidemiologic investigation, combined with environmental sampling and watershed analysis, will improve understanding of the frequency and nature of healthcare-associated NTM transmission among pwCF.


Assuntos
Fibrose Cística , Infecções por Mycobacterium não Tuberculosas , Mycobacterium abscessus , Adulto , Colorado/epidemiologia , Fibrose Cística/complicações , Humanos , Infecções por Mycobacterium não Tuberculosas/epidemiologia , Infecções por Mycobacterium não Tuberculosas/microbiologia , Micobactérias não Tuberculosas/genética
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