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1.
J Clin Immunol ; 2018 Jun 07.
Artigo em Inglês | MEDLINE | ID: mdl-29882021

RESUMO

The pathogenesis of life-threatening influenza A virus (IAV) disease remains elusive, as infection is benign in most individuals. We studied two relatives who died from influenza. We Sanger sequenced GATA2 and evaluated the mutation by gene transfer, measured serum cytokine levels, and analyzed circulating T- and B-cells. Both patients (father and son, P1 and P2) died in 2011 of H1N1pdm IAV infection at the ages of 54 and 31 years, respectively. They had not suffered from severe or moderately severe infections in the last 17 (P1) and 15 years (P2). A daughter of P1 had died at 20 years from infectious complications. Low B-cell, NK- cell, and monocyte numbers and myelodysplastic syndrome led to sequence GATA2. Patients were heterozygous for a novel, hypomorphic, R396L mutation leading to haplo-insufficiency. B- and T-cell rearrangement in peripheral blood from P1 during the influenza episode showed expansion of one major clone. No T-cell receptor excision circles were detected in P1 and P3 since they were 35 and 18 years, respectively. Both patients presented an exuberant, interferon (IFN)-γ-mediated hypercytokinemia during H1N1pdm infection. No data about patients with viremia was available. Two previously reported adult GATA2-deficient patients died from severe H1N1 IAV infection; GATA2 deficiency may predispose to life-threatening influenza in adulthood. However, a role of other genetic variants involved in immune responses cannot be ruled out. Patients with GATA2 deficiency can reach young adulthood without severe infections, including influenza, despite long-lasting complete B-cell and natural killer (NK) cell deficiency, as well as profoundly diminished T-cell thymic output.

2.
Chest ; 128(6): 3916-24, 2005 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-16354864

RESUMO

STUDY OBJECTIVE: Noninvasive mechanical ventilation (NIMV) is beneficial for patients with acute respiratory failure (ARF) when added to medical treatment. However, its role as an alternative to conventional mechanical ventilation (CMV) remains controversial. Our aim was to compare the efficacy and resource consumption of NIMV against CMV in patients with ARF. DESIGN: A randomized, multicenter, controlled trial. SETTING: Seven multipurpose ICUs. PATIENTS: Sixty-four patients with ARF from various causes who fulfilled criteria for mechanical ventilation. INTERVENTION: The noninvasive group received ventilation through a face mask in pressure-support mode plus positive end-expiratory pressure; the conventional group received ventilation through a tracheal tube. MEASUREMENTS AND RESULTS: Avoidance of intubation, mortality, and consumption of resources were the outcome variables. Thirty-one patients were assigned to the noninvasive group, and 33 were assigned to the conventional group. In the noninvasive group, 58% patients were intubated, vs 100% in the conventional group (relative risk reduction, 43%; p < 0.001). Stratification by type of ARF gave similar results. In the ICU, death occurred in 23% and 39% (p = 0.09) and complications occurred in 52% and 70% (p = 0.07) in the noninvasive and conventional groups, respectively. There were no differences in length of stay. The Therapeutic Intervention Score System-28, but not the direct nursing activity time, was lower in the noninvasive group during the first 3 days. CONCLUSIONS: NIMV reduces the need for intubation and therapeutic intervention in patients with ARF from different causes. There is a nonsignificant trend of reduction in ICUs and hospital mortality together with fewer complications during ICU stay.


Assuntos
Intubação Intratraqueal/métodos , Oxigenoterapia/métodos , Respiração Artificial/métodos , Insuficiência Respiratória/mortalidade , Insuficiência Respiratória/terapia , APACHE , Doença Aguda , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Cuidados Críticos/métodos , Estado Terminal , Feminino , Humanos , Unidades de Terapia Intensiva , Intubação Intratraqueal/efeitos adversos , Máscaras Laríngeas , Masculino , Pessoa de Meia-Idade , Oxigenoterapia/efeitos adversos , Respiração com Pressão Positiva/efeitos adversos , Respiração com Pressão Positiva/métodos , Probabilidade , Prognóstico , Respiração Artificial/efeitos adversos , Insuficiência Respiratória/diagnóstico , Medição de Risco , Estatísticas não Paramétricas , Taxa de Sobrevida , Resultado do Tratamento
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