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1.
Chest ; 154(4): 990-991, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30290939
2.
Artigo em Inglês | MEDLINE | ID: mdl-30261735

RESUMO

RATIONALE: Chronic lower respiratory diseases (CLRD), including COPD and asthma, are the fourth leading cause-of-death. Prior studies suggest that albuminuria, a biomarker of endothelial injury, is increased in COPD patients. OBJECTIVES: To test if albuminuria was associated with lung function decline and incident CLRD. METHODS: Six US population-based cohorts were harmonized and pooled. Participants with prevalent clinical lung disease were excluded. Albuminuria (urine albumin-to-creatinine ratio) was measured in spot samples. Lung function was assessed by spirometry. Incident CLRD-related hospitalizations and deaths were classified via adjudication and/or administrative criteria. Mixed and proportional-hazards models were used to test individual-level associations adjusted for age, height, weight, sex, race/ethnicity, education, birth-year, cohort, smoking status, pack-years, renal function, hypertension, diabetes, and medications. MEASUREMENTS AND MAIN RESULTS: Among 10,961 participants with preserved lung function, mean age at albuminuria measurement was 60 years, 51% were never-smokers, median albuminuria was 5.6mg/g, and mean FEV1 decline was 31.5mL/year. For each standard deviation increase in ln-albuminuria, there was 2.81% greater FEV1 decline (95% confidence interval [CI], 0.86-4.76%; P=0.0047), 11.02% greater FEV1/FVC decline (95% CI, 4.43-17.62%; P=0.0011), and 15% increased hazard of incident spirometry-defined moderate-to-severe COPD (95% CI, 2-31%, P=0.0021). Each standard deviation ln-albuminuria increased hazards of incident COPD-related hospitalization/mortality by 26% (95% CI, 18-34%, P<0.0001) among 14,213 participants followed for events. Asthma events were not significantly associated. Associations persisted in participants without current smoking, diabetes, hypertension, or cardiovascular disease. CONCLUSIONS: Albuminuria was associated with greater lung function decline, incident spirometry-defined COPD, and incident COPD-related events in a US population-based sample.

3.
Wellcome Open Res ; 3: 4, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30175238

RESUMO

Background: Over 90 regions of the genome have been associated with lung function to date, many of which have also been implicated in chronic obstructive pulmonary disease. Methods: We carried out meta-analyses of exome array data and three lung function measures: forced expiratory volume in one second (FEV 1), forced vital capacity (FVC) and the ratio of FEV 1 to FVC (FEV 1/FVC). These analyses by the SpiroMeta and CHARGE consortia included 60,749 individuals of European ancestry from 23 studies, and 7,721 individuals of African Ancestry from 5 studies in the discovery stage, with follow-up in up to 111,556 independent individuals. Results: We identified significant (P<2·8x10 -7) associations with six SNPs: a nonsynonymous variant in RPAP1, which is predicted to be damaging, three intronic SNPs ( SEC24C, CASC17 and UQCC1) and two intergenic SNPs near to LY86 and FGF10. Expression quantitative trait loci analyses found evidence for regulation of gene expression at three signals and implicated several genes, including TYRO3 and PLAU. Conclusions: Further interrogation of these loci could provide greater understanding of the determinants of lung function and pulmonary disease.

4.
Nat Commun ; 9(1): 2976, 2018 07 30.
Artigo em Inglês | MEDLINE | ID: mdl-30061609

RESUMO

Nearly 100 loci have been identified for pulmonary function, almost exclusively in studies of European ancestry populations. We extend previous research by meta-analyzing genome-wide association studies of 1000 Genomes imputed variants in relation to pulmonary function in a multiethnic population of 90,715 individuals of European (N = 60,552), African (N = 8429), Asian (N = 9959), and Hispanic/Latino (N = 11,775) ethnicities. We identify over 50 additional loci at genome-wide significance in ancestry-specific or multiethnic meta-analyses. Using recent fine-mapping methods incorporating functional annotation, gene expression, and differences in linkage disequilibrium between ethnicities, we further shed light on potential causal variants and genes at known and newly identified loci. Several of the novel genes encode proteins with predicted or established drug targets, including KCNK2 and CDK12. Our study highlights the utility of multiethnic and integrative genomics approaches to extend existing knowledge of the genetics of lung function and clinical relevance of implicated loci.

5.
Chest ; 153(4): 1082-1083, 2018 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-29626963
6.
Am J Respir Crit Care Med ; 198(2): 208-219, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29394082

RESUMO

RATIONALE: Lung function and chronic obstructive pulmonary disease (COPD) are heritable traits. Genome-wide association studies (GWAS) have identified numerous pulmonary function and COPD loci, primarily in cohorts of European ancestry. OBJECTIVES: Perform a GWAS of COPD phenotypes in Hispanic/Latino populations to identify loci not previously detected in European populations. METHODS: GWAS of lung function and COPD in Hispanic/Latino participants from a population-based cohort. We performed replication studies of novel loci in independent studies. MEASUREMENTS AND MAIN RESULTS: Among 11,822 Hispanic/Latino participants, we identified eight novel signals; three replicated in independent populations of European Ancestry. A novel locus for FEV1 in ZSWIM7 (rs4791658; P = 4.99 × 10-9) replicated. A rare variant (minor allele frequency = 0.002) in HAL (rs145174011) was associated with FEV1/FVC (P = 9.59 × 10-9) in a region previously identified for COPD-related phenotypes; it remained significant in conditional analyses but did not replicate. Admixture mapping identified a novel region, with a variant in AGMO (rs41331850), associated with Amerindian ancestry and FEV1, which replicated. A novel locus for FEV1 identified among ever smokers (rs291231; P = 1.92 × 10-8) approached statistical significance for replication in admixed populations of African ancestry, and a novel SNP for COPD in PDZD2 (rs7709630; P = 1.56 × 10-8) regionally replicated. In addition, loci previously identified for lung function in European samples were associated in Hispanic/Latino participants in the Hispanic Community Health Study/Study of Latinos at the genome-wide significance level. CONCLUSIONS: We identified novel signals for lung function and COPD in a Hispanic/Latino cohort. Including admixed populations when performing genetic studies may identify variants contributing to genetic etiologies of COPD.

7.
8.
Nat Genet ; 50(1): 42-53, 2018 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-29273806

RESUMO

We examined common variation in asthma risk by conducting a meta-analysis of worldwide asthma genome-wide association studies (23,948 asthma cases, 118,538 controls) of individuals from ethnically diverse populations. We identified five new asthma loci, found two new associations at two known asthma loci, established asthma associations at two loci previously implicated in the comorbidity of asthma plus hay fever, and confirmed nine known loci. Investigation of pleiotropy showed large overlaps in genetic variants with autoimmune and inflammatory diseases. The enrichment in enhancer marks at asthma risk loci, especially in immune cells, suggested a major role of these loci in the regulation of immunologically related mechanisms.

9.
Ann Am Thorac Soc ; 14(4): 505-512, 2017 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-28165295

RESUMO

Wellness is critical to physicians in training and the general physician workforce. At present, physicians in general and especially intensive care unit physicians are experiencing high rates of depression and burnout. The prevalence of burnout is greatest in resident and fellow trainees. The Accreditation Council for Graduate Medical Education has recognized the importance of physician wellness by proposing Common Program Requirements that pertain to trainee and faculty well-being. Several individual-focused, organizational, and structural strategies have been described in the literature as helpful in decreasing burnout. Successful implementation of a trainee wellness program requires institutional resources and collaborative efforts between the institution, leadership, faculty, and trainees. To ensure the greatest effect in reducing burnout, training programs and institutions should create programs that intervene at both the organizational and individual levels. Additional steps to implement a trainee wellness program include the following: (1) establish support from institutional and divisional leadership; (2) create a wellness committee; (3) perform a needs assessment; (4) assess trainee wellness and burnout; (5) perform targeted interventions; and (6) routinely reassess trainee wellness and burnout. More research is needed to identify and refine strategies that improve wellness and decrease burnout among physicians and trainees. As a community, we must take on the challenge of improving wellness among physicians for the benefit of our trainees, ourselves, and our patients.


Assuntos
Esgotamento Profissional/prevenção & controle , Educação de Pós-Graduação em Medicina , Promoção da Saúde , Internato e Residência , Saúde Mental , Humanos , Liderança , Tutoria , Grupo Associado , Qualidade de Vida
10.
Chest ; 151(5): 1114-1121, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-28132754

RESUMO

Interventional pulmonology (IP) is a rapidly evolving subspecialty of pulmonary medicine. In the last 10 years, formal IP fellowships have increased substantially in number from five to now > 30. The vast majority of IP fellowship trainees are selected through the National Resident Matching Program, and validated in-service and certification examinations for IP exist. Practice standards and training guidelines for IP fellowship programs have been published; however, considerable variability in the environment, curriculum, and experience offered by the various fellowship programs remains, and there is currently no formal accreditation process in place to standardize IP fellowship training. Recognizing the need for more uniform training across the various fellowship programs, a multisociety accreditation committee was formed with the intent to establish common accreditation standards for all IP fellowship programs in the United States. This article provides a summary of those standards and can serve as an accreditation template for training programs and their offices of graduate medical education as they move through the accreditation process.


Assuntos
Acreditação , Broncoscopia/educação , Currículo/normas , Educação de Pós-Graduação em Medicina/normas , Bolsas de Estudo/normas , Pneumologia/educação , Toracoscopia/educação , Competência Clínica/normas , Docentes de Medicina , Humanos , Sociedades Médicas , Fatores de Tempo
11.
Intensive Care Med ; 41(4): 686-94, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25763756

RESUMO

PURPOSE: Investigate the prevalence, risk factors and impact of continuous EEG (cEEG) abnormalities on mortality through the 1-year follow-up period in patients with severe sepsis. METHODS: Prospective, single-center, observational study of consecutive patients admitted with severe sepsis to the Medical ICU at an academic medical center. RESULTS: A total of 98 patients with 100 episodes of severe sepsis were included; 49 patients (50%) were female, median age was 60 (IQR 52-74), the median non-neuro APACHE II score was 23.5 (IQR 18-28) and median non-neuro SOFA score was 8 (IQR 6-11). Twenty-five episodes had periodic discharges (PD), of which 11 had nonconvulsive seizures (NCS). No patient had NCS without PD. Prior neurological history was associated with a higher risk of PD or NCS (45 vs. 17%; CI 1.53-10.43), while the non-neuro APACHE II, non-neuro SOFA, severity of cardiovascular shock and presence of sedation during cEEG were associated with a lower risk of PD or NCS. Clinical seizures before cEEG were associated with a higher risk of nonconvulsive status epilepticus (24 vs. 6%; CI 1.42-19.94) while the non-neuro APACHE II and non-neuro SOFA scores were associated with a lower risk. Lack of EEG reactivity was present in 28% of episodes. In the survival analysis, a lack of EEG reactivity was associated with higher 1-year mortality [mean survival time 3.3 (95% CI 1.8-4.9) vs. 7.5 (6.4-8.7) months; p = 0.002] but the presence of PD or NCS was not [mean survival time 3.3 (95% CI 1.8-4.9) vs. 7.5 (6.4-8.7) months; p = 0.592]. Lack of reactivity was more frequent in patients on continuous sedation during cEEG. In patients with available 1-year data (34% of the episodes), 82% had good functional outcome (mRS ≤ 3, n = 27). There were no significant predictors of functional outcome, late cognition, and no patient with complete follow-up data developed late seizure or new epilepsy. CONCLUSIONS: NCS and PD are common in patients with severe sepsis and altered mental status. They were less frequent among the most severely sick patients and were not associated with outcome in this study. Lack of EEG reactivity was more frequent in patients on continuous sedation and was associated with mortality up to 1 year after discharge. Larger studies are needed to confirm these findings in a broader population and to further evaluate long-term cognitive outcome, risk of late seizure and epilepsy.


Assuntos
Eletroencefalografia/métodos , Unidades de Terapia Intensiva , Convulsões/diagnóstico , Sepse/fisiopatologia , APACHE , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Estudos Prospectivos , Convulsões/etiologia , Sepse/complicações , Sepse/mortalidade , Estado Epiléptico/complicações
12.
Ann Am Thorac Soc ; 12(4): 567-73, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25742296

RESUMO

This paper outlines specific tips for those applying to pulmonary and/or critical care medicine fellowship training in the United States using the PAIR-Match steps: preparation, application, interview, ranking, and match. Preparation for fellowship begins long before the application process with an assessment of one's long-term goals (to the extent that these are known). The cornerstone of the application is the curriculum vitae, which should highlight applicants' pulmonary and critical care-related experiences and scholarly work. Applicants should obtain letters of recommendation from faculty members who know them well and can write a letter that speaks to their strengths in clinical, scholarly, or leadership areas. The personal statement is an opportunity to share experiences not otherwise shared in the application and is an opportunity to explain any breaks in training or performance lapses. When selecting programs to which they will apply, applicants should pay close attention to the areas of education and curriculum, clinical experience, scholarly opportunity, and personal factors. Preparing for interviews should include a review of the program at which one is interviewing and development of relevant questions regarding details of the program. The interview day is the applicant's opportunity to see the "personality" of the program by meeting with the program director, faculty, and current fellows and to assess whether the program is a good fit for their goals. Applicants should only rank those programs they are willing to attend, in order of preference; they should be aware that the match process is binding.


Assuntos
Cuidados Críticos , Bolsas de Estudo , Medicina Interna , Internato e Residência , Pneumologia/educação , Humanos , Candidatura a Emprego , Estados Unidos
13.
Ann Am Thorac Soc ; 12(3): 340-8, 2015 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-25584925

RESUMO

RATIONALE: Genome-wide association studies (GWAS) of chronic obstructive pulmonary disease (COPD) have identified disease-susceptibility loci, mostly in subjects of European descent. OBJECTIVES: We hypothesized that by studying Hispanic populations we would be able to identify unique loci that contribute to COPD pathogenesis in Hispanics but remain undetected in GWAS of non-Hispanic populations. METHODS: We conducted a metaanalysis of two GWAS of COPD in independent cohorts of Hispanics in Costa Rica and the United States (Multi-Ethnic Study of Atherosclerosis [MESA]). We performed a replication study of the top single-nucleotide polymorphisms in an independent Hispanic cohort in New Mexico (the Lovelace Smokers Cohort). We also attempted to replicate prior findings from genome-wide studies in non-Hispanic populations in Hispanic cohorts. MEASUREMENTS AND MAIN RESULTS: We found no genome-wide significant association with COPD in our metaanalysis of Costa Rica and MESA. After combining the top results from this metaanalysis with those from our replication study in the Lovelace Smokers Cohort, we identified two single-nucleotide polymorphisms approaching genome-wide significance for an association with COPD. The first (rs858249, combined P value = 6.1 × 10(-8)) is near the genes KLHL7 and NUPL2 on chromosome 7. The second (rs286499, combined P value = 8.4 × 10(-8)) is located in an intron of DLG2. The two most significant single-nucleotide polymorphisms in FAM13A from a previous genome-wide study in non-Hispanics were associated with COPD in Hispanics. CONCLUSIONS: We have identified two novel loci (in or near the genes KLHL7/NUPL2 and DLG2) that may play a role in COPD pathogenesis in Hispanic populations.


Assuntos
Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Hispano-Americanos , Polimorfismo de Nucleotídeo Único , Doença Pulmonar Obstrutiva Crônica/etnologia , Adolescente , Adulto , Idoso , Criança , Feminino , Volume Expiratório Forçado/fisiologia , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Doença Pulmonar Obstrutiva Crônica/genética , Doença Pulmonar Obstrutiva Crônica/fisiopatologia , Estudos Retrospectivos , Estados Unidos/epidemiologia , Adulto Jovem
14.
ASAIO J ; 61(2): 216-8, 2015 Mar-Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25485559

RESUMO

Extracorporeal membrane oxygenation (ECMO) may be used to support patients with severe hypoxemic respiratory failure refractory to conventional mechanical ventilation. However, because systemic anticoagulation is generally required to maintain circuit patency, severe bleeding is often seen as a contraindication to ECMO. We describe our center's experience with four patients who received ECMO for refractory hypoxemic respiratory failure due to diffuse alveolar hemorrhage (DAH), a condition for which anticoagulation is typically contraindicated, and provide a review of the literature. The mean age was 35.8 ± 16.4 years. The mean pre-ECMO PaO2 to FIO2 ratio was 52.3 ± 9.4 mm Hg. All patients were treated with continuous infusions of heparin with a goal-activated partial thromboplastin time between 40 and 60 seconds (mean, 47.4 ± 11.6 seconds). All four subjects (100%) survived to decannulation, and three subjects (75%) survived to discharge. The results from this case series, along with previously published data, suggest that ECMO is a reasonable management option for patients with DAH-associated severe, refractory hypoxemic respiratory failure. This is especially true in the era of modern ECMO technology where lower levels of anticoagulation are able to maintain circuit patency while minimizing bleeding risk.


Assuntos
Oxigenação por Membrana Extracorpórea , Hemorragia/terapia , Pneumopatias/terapia , Adulto , Anticoagulantes/administração & dosagem , Humanos , Pessoa de Meia-Idade , Alvéolos Pulmonares , Insuficiência Respiratória/terapia , Estudos Retrospectivos , Resultado do Tratamento , Adulto Jovem
15.
Ann Thorac Surg ; 99(2): 590-5, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25499483

RESUMO

BACKGROUND: Extracorporeal membrane oxygenation support (ECMO) typically requires multiple blood transfusions and is associated with frequent bleeding complications. Blood transfusions are known to increase morbidity and mortality in critically ill patients, which may extend to patients receiving ECMO. Aiming to reduce transfusion requirements, we implemented a blood conservation protocol in adults with severe acute respiratory distress syndrome (ARDS) receiving ECMO. METHODS: This was a retrospective study of adults receiving ECMO for ARDS after initiation of a blood conservation protocol that included a transfusion trigger of hemoglobin of less than 7.0 g/dL, use of low-dose anticoagulation targeting an activated partial thromboplastin time of 40 to 60 seconds, and autotransfusion of circuit blood during decannulation. The primary objective was to evaluate transfusion requirements during ECMO support. Clinical outcomes included survival, neurologic function, renal function, bleeding, and thrombotic complications. RESULTS: The analysis included 38 patients; of these, 24 (63.2%) received a transfusion while receiving ECMO. Median hemoglobin was 8.29 g/dL. A median of 1.0 units (range, 250 to 300 mL) was transfused during ECMO support over a median duration of 9.0 days, equivalent to 0.11 U/d (range, 27.5 to 33.3 mL/d). The median activated partial thromboplastin time was 46.5 seconds. Bleeding occurred in 10 patients (26.3%); severe bleeding occurred in 2 patients (5.3%). Twenty-eight patients (73.7%) survived to hospital discharge. CONCLUSIONS: Implementation of a blood conservation protocol in adults receiving ECMO for ARDS resulted in lower transfusion requirements and bleeding complications than previously reported in the literature and was associated with comparable survival and organ recovery.


Assuntos
Procedimentos Médicos e Cirúrgicos de Sangue , Oxigenação por Membrana Extracorpórea , Síndrome do Desconforto Respiratório do Adulto/terapia , Adulto , Transfusão de Sangue/estatística & dados numéricos , Feminino , Hemoglobinas/análise , Humanos , Masculino , Pessoa de Meia-Idade , Síndrome do Desconforto Respiratório do Adulto/sangue , Estudos Retrospectivos , Adulto Jovem
16.
Am J Med ; 128(2): 171-180.e5, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25447621

RESUMO

BACKGROUND: Dyspnea on exertion is a common and debilitating symptom, yet evidence for the relative value of cardiac and pulmonary tests for the evaluation of chronic dyspnea among adults without known cardiac or pulmonary disease is limited. METHODS: The Multi-Ethnic Study of Atherosclerosis (MESA) enrolled participants aged 45 to 84 years who were free of clinical cardiovascular disease from 6 communities; participants with clinical pulmonary disease were excluded from this report. Dyspnea on exertion was assessed via structured interview. Tests included electrocardiograms, cardiac computed tomography (CT) for coronary artery calcium, cardiac magnetic resonance imaging, spirometry, percent emphysema (percent of lung regions <-950 HU) on CT, inflammatory biomarkers, and N-terminal pro-brain natriuretic peptide (NT-proBNP). Logistic regression was used to identify independent correlates of dyspnea after adjustment for age, sex, body mass index, physical activity, anxiety, and leg pain. RESULTS: Among 1969 participants without known cardiopulmonary disease, 9% had dyspnea. The forced expiratory volume in 1 second (FEV1) (P < .001), NT-proBNP (P = .004), and percent emphysema on CT (P = .004) provided independent information on the probability of self-reported dyspnea. Associations with the FEV1 were stronger among smokers and participants with other recent respiratory symptoms or seasonal allergies; associations with NT-proBNP were present only among participants with coexisting symptoms of lower-extremity edema. Only the FEV1 provided a significant improvement in the receiver operating curve. CONCLUSIONS: Among adults without known cardiac or pulmonary disease reporting dyspnea on exertion, spirometry, NT-proBNP, and CT imaging for pulmonary parenchymal disease were the most informative tests.


Assuntos
Dispneia/diagnóstico , Idoso , Idoso de 80 Anos ou mais , Aterosclerose/diagnóstico , Biomarcadores/sangue , Doença da Artéria Coronariana/diagnóstico , Dispneia/diagnóstico por imagem , Dispneia/etiologia , Dispneia/patologia , Dispneia/fisiopatologia , Eletrocardiografia , Feminino , Volume Expiratório Forçado , Coração/diagnóstico por imagem , Humanos , Pulmão/patologia , Pulmão/fisiopatologia , Imagem por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Peptídeo Natriurético Encefálico/sangue , Pacientes Ambulatoriais/estatística & dados numéricos , Fragmentos de Peptídeos/sangue , Espirometria , Tomografia Computadorizada por Raios X
17.
Chest ; 145(4): 876-882, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24687709

RESUMO

Extracorporeal membrane oxygenation (ECMO) can serve as a bridge to recovery in cases of acute reversible illness, a bridge to transplantation in circumstances of irreversible cardiac or respiratory failure, a bridge to ventricular assist device therapy in select cases of cardiac failure, or a bridge to decision when the prognosis remains uncertain. Recent advances in ECMO technology that allow for prolonged support with decreased complications, the development of mobile ECMO teams, the rapidity of initiation, and the growing body of evidence, much of which remains controversial, have led to a significant increase in the use of ECMO worldwide. This increasing use of a technology that is not a destination device in itself introduces many ethical dilemmas specific to this technology. In this article, we explore some of the ethical issues inherent in the decisions surrounding the initiation and withdrawal of ECMO by raising key questions and providing a framework for clinicians. We will address extracorporeal cardiopulmonary resuscitation, the inability to bridge a patient to transplant or recovery--the so-called "bridge to nowhere"--and the significance of resuscitation preferences in the setting of continual extracorporeal circulatory support.


Assuntos
Oxigenação por Membrana Extracorpórea/ética , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade
18.
Eur Respir J ; 43(4): 1003-17, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-23900982

RESUMO

Chronic obstructive pulmonary disease (COPD) is linked to cardiovascular disease; however, there are few studies on the associations of cardiovascular genes with COPD. We assessed the association of lung function with 2100 genes selected for cardiovascular diseases among 20 077 European-Americans and 6900 African-Americans. We performed replication of significant loci in the other racial group and an independent consortium of Europeans, tested the associations of significant loci with per cent emphysema and examined gene expression in an independent sample. We then tested the association of a related lipid biomarker with forced expiratory volume in 1 s (FEV1)/forced vital capacity (FVC) ratio and per cent emphysema. We identified one new polymorphism for FEV1/FVC (rs805301) in European-Americans (p=1.3×10(-6)) and a second (rs707974) in the combined European-American and African-American analysis (p=1.38×10(-7)). Both single-nucleotide polymorphisms (SNPs) flank the gene for apolipoprotein M (APOM), a component of high-density lipoprotein (HDL) cholesterol. Both were replicated in an independent cohort. SNPs in a second gene related to apolipoprotein M and HDL, PCSK9, were associated with FEV1/FVC ratio among African-Americans. rs707974 was associated with per cent emphysema among European-Americans and African-Americans and APOM expression was related to FEV1/FVC ratio and per cent emphysema. Higher HDL levels were associated with lower FEV1/FVC ratio and greater per cent emphysema. These findings suggest a novel role for the apolipoprotein M/HDL pathway in the pathogenesis of COPD and emphysema.


Assuntos
Apolipoproteínas/genética , HDL-Colesterol/sangue , Enfisema/sangue , Lipocalinas/genética , Pulmão/fisiologia , Doença Pulmonar Obstrutiva Crônica/sangue , Adulto , Afro-Americanos , Idoso , Apolipoproteínas M , Estudos de Coortes , Grupo com Ancestrais do Continente Europeu , Feminino , Volume Expiratório Forçado , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Espirometria , Estados Unidos , Capacidade Vital
20.
Pulm Circ ; 3(2): 432-5, 2013 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24015346

RESUMO

Pulmonary arterial hypertension (PAH) is a disease with significant morbidity and mortality, particularly during an acute decompensation. We describe a single-center experience of three patients with severe Group 1 PAH, refractory to targeted medical therapy, in which an extubated, nonsedated, extracorporeal membrane oxygenation (ECMO) strategy with an upper-body configuration was used as a bridge to recovery or lung transplantation. All three patients were extubated within 24 hours of ECMO initiation. Two patients were successfully bridged to lung transplantation, and the other patient was optimized on targeted PAH therapy with subsequent recovery from an acute decompensation. The upper-body ECMO configuration allowed for daily physical therapy, including one patient, who would otherwise have been unsuitable for transplantation, ambulating over 850 meters daily. This series demonstrates the feasibility of using ECMO to bridge PAH patients to recovery or transplantation while avoiding the complications of immobility and invasive mechanical ventilation.

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