RESUMO
BACKGROUND: The impact of the new "borderline" hemodynamic class for pulmonary hypertension (PH) (mean pulmonary artery pressure [mPAP], 21-24 mm Hg and pulmonary vascular resistance, [PVR], ≥3 wood units, [WU]) in chronic obstructive pulmonary disease (COPD) and interstitial lung disease (ILD) is unclear. OBJECTIVES: The aim of this study was to assess the effect of borderline PH (BLPH) on survival in COPD and ILD patients. METHOD: Survival was analyzed from retrospective data from 317 patients in 12 centers (Italy, Spain, UK) comparing four hemodynamic groups: the absence of PH (NoPH; mPAP <21 mm Hg or 21-24 mm Hg and PVR <3 WU), BLPH (mPAP 21-24 mm Hg and PVR ≥3 WU), mild-moderate PH (MPH; mPAP 25-35 mm Hg and cardiac index [CI] ≥2 L/min/m2), and severe PH (SPH; mPAP ≥35 mm Hg or mPAP ≥25 mm Hg and CI <2 L/min/m2). RESULTS: BLPH affected 14% of patients; hemodynamic severity did not predict survival when COPD and ILD patients were analyzed together. However, survival in the ILD cohort for any PH level was worse than in NoPH (3-year survival: NoPH 58%, BLPH 32%, MPH 28%, SPH 33%, p = 0.002). In the COPD cohort, only SPH had reduced survival compared to the other groups (3-year survival: NoPH 82%, BLPH 86%, MPH 87%, SPH 57%, p = 0.005). The mortality risk correlated significantly with mPAP in ILD (hazard ratio [HR]: 2.776, 95% CI: 2.057-3.748, p < 0.001) and notably less in COPD patients (HR: 1.015, 95% CI: 1.003-1.027, p = 0.0146). CONCLUSIONS: In ILD, any level of PH portends worse survival, while in COPD, only SPH presents a worse outcome.
Assuntos
Hipertensão Pulmonar , Doenças Pulmonares Intersticiais , Doença Pulmonar Obstrutiva Crônica , Humanos , Pulmão , Doenças Pulmonares Intersticiais/complicações , Doença Pulmonar Obstrutiva Crônica/complicações , Estudos RetrospectivosAssuntos
Doenças Assintomáticas , Forame Oval Patente/cirurgia , Linfadenopatia/diagnóstico por imagem , Sarcoidose Pulmonar/diagnóstico por imagem , Adulto , Biópsia , Humanos , Achados Incidentais , Linfadenopatia/patologia , Masculino , Mediastino , Cuidados Pré-Operatórios , Remissão Espontânea , Sarcoidose Pulmonar/patologia , Tomografia Computadorizada por Raios XAssuntos
Parto Obstétrico/métodos , Oxigenação por Membrana Extracorpórea/métodos , Hipertensão Pulmonar/terapia , Complicações Cardiovasculares na Gravidez/terapia , Adulto , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico por imagem , Recém-Nascido , Gravidez , Complicações Cardiovasculares na Gravidez/diagnóstico por imagemRESUMO
Emerging fungal infections are a major challenge in solid organ transplantation (SOT) and are associated with high morbidity and mortality. We report two cases of Malassezia restricta pneumonia in SOT recipients. Infections were diagnosed with molecular analysis and histology. Patients were treated with antifungal therapy and have fully recovered.
RESUMO
Bronchiolitis Obliterans Syndrome is the major determinant of the graft function loss after lung transplantation, but its pathogenesis is still incompletely understood and currently available therapeutic strategies are poorly effective. A deeper understanding of its pathogenic mechanisms is crucial for the development of new strategies to prevent and treat this devastating complication. In this study, we focused on the mesenchymal stromal cells, recently recognized as BOS key effectors, and our primary aim was to identify their epigenetic determinants, such as histone modifications and non-coding RNA regulation, which could contribute to their differentiation in myofibroblasts. Interestingly, we identified a deregulated expression of histone deacetylases and methyltransferases, and a microRNA-epigenetic regulatory network, which could represent novel targets for anti-fibrotic therapy. We validated our results in vitro, in a cell model of fibrogenesis, confirming the epigenetic involvement in this process and paving the way for a new application for epigenetic drugs.
Assuntos
Bronquiolite Obliterante/patologia , Epigênese Genética/genética , Pulmão/patologia , Células-Tronco Mesenquimais/patologia , Transcriptoma , Adulto , Idoso , Bronquiolite Obliterante/etiologia , Líquido da Lavagem Broncoalveolar , Diferenciação Celular , Linhagem Celular , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Progressão da Doença , Feminino , Fibrose/metabolismo , Rejeição de Enxerto/patologia , Código das Histonas , Inibidores de Histona Desacetilases/metabolismo , Histona Desacetilases/metabolismo , Histona Metiltransferases/metabolismo , Humanos , Transplante de Pulmão/efeitos adversos , Masculino , MicroRNAs/genética , MicroRNAs/metabolismo , Pessoa de Meia-Idade , Miofibroblastos/metabolismo , Fator de Crescimento Transformador beta1/metabolismo , Vorinostat/metabolismoRESUMO
BACKGROUND: Conventional hemodynamic parameters are considered to be the gold standard indices of outcome in pulmonary arterial hypertension (PAH); on the contrary, few data support the hypothesis that the pulsatile component of right ventricular afterload provides important prognostic information. The aim of the study was to investigate the prognostic significance of pulmonary arterial compliance (PCa) after therapy initiation or escalation in PAH patients. METHODS: A cohort of 419 consecutive PAH patients (308 naive and 111 prevalent) underwent right heart catheterisation (RHC) prior to initiating or escalating PAH-targeted therapy. RHC was repeated in 255 patients (61%) after 4 to 12months of therapy as 62 patients (15%) died and 102 (24%) did not undergo a follow-up RHC within the first year. RESULTS: After the follow-up RHC, 63 patients died over a median follow-up period of 39months. At multivariate analysis, age>50years old, male gender, etiology associated with systemic sclerosis, persistence of WHO class III/IV, and reduced PCa at follow-up RHC were the independent parameters significantly associated with poor prognosis. At ROC analysis, the optimal cut-off point of PCa to predict survival was 1.4mL/mmHg (AUC 0.73, sensitivity 81.8%, specificity 58.8%). CONCLUSIONS: In PAH patients hospitalized to initiate or to escalate PAH-specific therapy, failure to improve PCa after therapy is a strong hemodynamic predictor of poor prognosis.
Assuntos
Hipertensão Pulmonar/fisiopatologia , Hipertensão Pulmonar/terapia , Artéria Pulmonar/fisiopatologia , Idoso , Cateterismo Cardíaco , Estudos de Coortes , Feminino , Humanos , Hipertensão Pulmonar/diagnóstico , Masculino , Pessoa de Meia-Idade , Prognóstico , Curva ROC , Resistência Vascular/fisiologiaRESUMO
BACKGROUND: Pulmonary hypertension (PH) is a well-known independent prognostic factor in chronic obstructive pulmonary disease (COPD) and a sufficient criterion for lung transplant candidacy. Limited data are currently available on the hemodynamic and clinical effect of phosphodiesterase 5 inhibitors in patients with severe PH associated with COPD. This study assessed the effect of sildenafil on pulmonary hemodynamics and gas exchange in severe PH associated with COPD. METHODS: After screening, this multicenter, randomized, placebo-controlled double-blind trial randomized patients to receive 20 mg sildenafil or placebo 3 times a day (ratio 2:1) for 16 weeks. The primary end point was the reduction in pulmonary vascular resistance. Secondary end points included BODE (body mass index, airflow obstruction, dyspnea, and exercise capacity) index, 6-minute walk test, and quality of life questionnaire. Changes in the partial pressure of arterial oxygen were evaluated as a safety parameter. RESULTS: The final population included 28 patients, 18 in the sildenafil group and 10 in the placebo group. At 16 week, patients treated with sildenafil had a decrease in pulmonary vascular resistance (mean difference with placebo -1.4 WU; 95% confidence interval, ≤ -0.05; p = 0.04). Sildenafil also improved the BODE index, diffusion capacity of the lung for carbon monoxide percentage, and quality of life. Change from baseline in the partial pressure of arterial oxygen was not significantly different between the sildenafil and placebo groups. CONCLUSIONS: This pilot study found that treatment with sildenafil reduced pulmonary vascular resistance and improved the BODE index and quality of life, without a significant effect on gas exchange.
Assuntos
Hipertensão Pulmonar/tratamento farmacológico , Doença Pulmonar Obstrutiva Crônica/tratamento farmacológico , Troca Gasosa Pulmonar/efeitos dos fármacos , Citrato de Sildenafila/administração & dosagem , Resistência Vascular/efeitos dos fármacos , Adulto , Idoso , Idoso de 80 Anos ou mais , Intervalos de Confiança , Relação Dose-Resposta a Droga , Método Duplo-Cego , Esquema de Medicação , Feminino , Seguimentos , Hemodinâmica/efeitos dos fármacos , Humanos , Hipertensão Pulmonar/complicações , Hipertensão Pulmonar/diagnóstico , Masculino , Pessoa de Meia-Idade , Seleção de Pacientes , Projetos Piloto , Doença Pulmonar Obstrutiva Crônica/complicações , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Valores de Referência , Medição de Risco , Índice de Gravidade de Doença , Resultado do TratamentoAssuntos
Dispneia/epidemiologia , Avaliação Nutricional , Distúrbios Nutricionais/epidemiologia , Doença Pulmonar Obstrutiva Crônica/epidemiologia , Distribuição por Idade , Idoso , Antropometria , Metabolismo Basal , Estudos de Coortes , Comorbidade , Dispneia/diagnóstico , Feminino , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Distúrbios Nutricionais/diagnóstico , Percepção , Probabilidade , Prognóstico , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Medição de Risco , Índice de Gravidade de Doença , Distribuição por Sexo , Estatísticas não Paramétricas , Inquéritos e Questionários , Análise de SobrevidaRESUMO
BACKGROUND: Physical activity (PA) has been reported to be reduced in severe chronic obstructive pulmonary disease (COPD). Studies in moderate COPD are currently scarce. The aim of the present study was to investigate physical activity in daily life in patients with COPD (n=70) and controls (n=30). METHODS: A multi-center controlled study was conducted. PA was assessed using a multisensor armband device (SenseWear, BodyMedia, Pittsburgh, PA) and is reported as the average number of steps per day, and the time spent in mild and moderate physical activity. RESULTS: Patients suffered from mild (n=9), moderate (n=28), severe (n=23) and very severe (n=10) COPD. The time spent in activities with mild (80 + or - 69 min vs 160 + or - 89 min, p<0.0001) and moderate intensity (24 + or - 29 min vs 65 + or - 70 min; p<0.0036) was reduced in patients compared to controls. The number of steps reached 87 + or - 34%, 71 + or - 32%, 49 + or - 34% and 29 + or - 20% of control values in GOLD-stages I to IV respectively. The time spent in activities at moderate intensity was 53 + or - 47%, 41 + or - 45%, 31 + or - 47% and 22 + or - 34% of the values obtained in controls respectively with increasing GOLD-stage. These differences reached statistical significance as of GOLD stage II (p<0.05). No differences were observed among centers. CONCLUSIONS: Physical activity is reduced early in the disease progression (as of GOLD-stage II). Reductions in physical activities at moderate intensity seem to precede the reduction in the amount of physical activities at lower intensity.