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1.
Ann Biol Clin (Paris) ; 81(4): 403-409, 2023 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-37864446

RESUMO

OBJECTIVES: SARS-CoV-2 has impacted the detection of seasonal respiratory viruses. We retrospectively assessed the trend in the detection of 10 viruses in the COVID-19 area in 2 hospitals located in the Paris area. METHODS: All patients positive for a respiratory virus in two hospitals from September 2016 to August 2021 were retrospectively included. The rate of RT-PCR positive for each virus was calculated for the 2020-2021 season and the 2019-2020 season in comparison to a baseline of 3 seasons, i.e. 2016-2017, 2017-2018, and 2018-2019. RESULTS: Overall, 7,835 patients were tested positive from September 2016 to August 2021. The detection of respiratory virus dramatically falls on week-11 of 2020, as the number of RT-PCR performed. Then, 3 trends were identified: a) almost a disappearance for influenza; b) a 10-weeks delay in the seasonal outbreak for RSV; c) a persistence of circulation with variable activity for other viruses. In comparison to a baseline of three seasons (2016-2019), the rate of positive patients was lower during the 2020-2021 season for coronavirus (4.51% vs. 1.26%, P < 0.0001), adenovirus (1.93% vs. 1.34%, P = 0.14), bocavirus (0.58% vs. 0.11%, P = 0.08), and enterovirus (0.28% vs. 0.0%, P = 0.12). In contrast, the rate of hMPV-positive (1.92% vs. 2.83%, P = 0.03) and hPIV-positive (2.17% vs. 2.99%, P = 0.06) patients increased. CONCLUSIONS: The fall in the number of respiratory viruses detected might be related to the lower number of tests performed and the implementation of non pharmaceutical intervention (NPI). Then, all viruses except influenza are detected, probably as a consequence of high adherence to influenza vaccines. Despite, a lower number of tests being performed, the rate of hMPV-positive and hPIV-positive patients increased suggesting an active circulation of these viruses. Altogether, these findings suggest a persistent circulation of common respiratory viruses all over the COVID-19 era.


Assuntos
COVID-19 , Influenza Humana , Infecções Respiratórias , Vírus , Humanos , Lactente , Influenza Humana/epidemiologia , Estudos Retrospectivos , COVID-19/diagnóstico , COVID-19/epidemiologia , SARS-CoV-2 , Infecções Respiratórias/diagnóstico , Infecções Respiratórias/epidemiologia
2.
Lancet Rheumatol ; 5(12): e707-e715, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38251561

RESUMO

BACKGROUND: Interleukin-5 (IL-5) inhibitors represent novel therapies for eosinophilic granulomatosis with polyangiitis (EGPA). This study assessed the effectiveness and safety of the IL-5 receptor inhibitor benralizumab in a European cohort of patients with EGPA. METHODS: This retrospective cohort study included patients with EGPA from 28 European referral centres of the European EGPA Study Group across six countries (Italy, France, UK, Russia, Spain, and Switzerland) who received benralizumab as any line of treatment between Jan 1, 2019, and Sep 30, 2022. We assessed the rates of complete response, defined as no disease activity (Birmingham Vasculitis Activity Score [BVAS] of 0) and a prednisone dose of up to 4 mg/day, in contrast to partial response, defined as a BVAS of 0 and a prednisone dose greater than 4 mg/day. Active disease manifestations, pulmonary function, variation in glucocorticoid dose, and safety outcomes were also assessed over a 12-month follow-up. FINDINGS: 121 patients with relapsing-refractory EGPA treated with benralizumab at the dose approved for eosinophilic asthma were included (64 [53%] women and 57 [47%] men; median age at the time of beginning benralizumab treatment 54·1 years [IQR 44·2-62·2]). Complete response was reported in 15 (12·4%, 95% CI 7·1-19·6) of 121 patients at month 3, 25 (28·7%, 19·5-39·4) of 87 patients at month 6, and 32 (46·4%, 34·3-58·8) of 69 patients at month 12; partial response was observed in an additional 43 (35·5%, 27·0-44·8) patients at month 3, 23 (26·4%, 17·6-37·0) at month 6, and 13 (18·8%, 10·4-30·1) at month 12. BVAS dropped from 3·0 (IQR 2·0-8·0) at baseline to 0·0 (0·0-2·0) at months 3 and 6, and to 0·0 (0·0-1·0) at month 12. The proportion of patients with systemic manifestations, active peripheral neurological disease, ear, nose, and throat involvement, and pulmonary involvement decreased, with an improvement in lung function tests. Six patients relapsed after having a complete response. The oral prednisone (or equivalent) dose decreased from 10·0 mg/day (5·0-12·5) at baseline to 5·0 mg/day (3·6-8·5) at month 3 (p<0·01), to 5·0 mg/day (2·5-6·3) at month 6, and to 2·5 mg/day (0·0-5·0) at month 12 (p<0·0001). 19 (16%) of 121 patients had adverse events and 16 (13%) discontinued benralizumab. INTERPRETATION: These data suggest that benralizumab could be an effective treatment for EGPA in real-life clinical practice. Further clinical trials are required to confirm the efficacy of benralizumab in patients with a higher baseline disease activity. FUNDING: None.


Assuntos
Anticorpos Monoclonais Humanizados , Síndrome de Churg-Strauss , Granulomatose com Poliangiite , Transtornos Leucocíticos , Masculino , Humanos , Feminino , Adulto , Pessoa de Meia-Idade , Estudos Retrospectivos , Estudos de Coortes , Síndrome de Churg-Strauss/diagnóstico , Prednisona , Granulomatose com Poliangiite/tratamento farmacológico , Inibidores de Interleucina , 60410
4.
Chest ; 160(5): 1783-1788, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34102143
6.
Sci Rep ; 11(1): 6388, 2021 03 18.
Artigo em Inglês | MEDLINE | ID: mdl-33737704

RESUMO

Eosinophils have widespread procoagulant effects. Eosinophilic cardiovascular toxicity mostly consists of endomyocardial damage or eosinophilic vasculitis, while reported cases of venous thrombosis (VT) are scarce. We aimed to report on the clinical features and treatment outcomes of patients with unexplained VT and eosinophilia, and to identify predictors of relapse. This retrospective, multicenter, observational study included patients aged over 15 years with VT, concomitant blood eosinophilia ≥ 1G/L and without any other moderate-to-strong contributing factors for VT. Fifty-four patients were included. VT was the initial manifestation of eosinophil-related disease in 29 (54%) patients and included pulmonary embolism (52%), deep venous thrombosis (37%), hepatic (11%) and portal vein (9%) thromboses. The median [IQR] absolute eosinophil count at VT onset was 3.3G/L [1.6-7.4]. Underlying eosinophil-related diseases included FIP1L1-PDGFRA-associated chronic myeloid neoplasm (n = 4), Eosinophilic Granulomatosis with Polyangiitis (n = 9), lymphocytic (n = 1) and idiopathic (n = 29) variants of hypereosinophilic syndrome. After a median [IQR] follow-up of 24 [10-62] months, 7 (13%) patients had a recurrence of VT. In multivariate analysis, persistent eosinophilia was the sole variable associated with a shorter time to VT relapse (HR 7.48; CI95% [1.94-29.47]; p = 0.015). Long-term normalization of eosinophil count could prevent the recurrence of VT in a subset of patients with unexplained VT and eosinophilia ≥ 1G/L.


Assuntos
Síndrome de Churg-Strauss/terapia , Eosinofilia/terapia , Síndrome Hipereosinofílica/terapia , Leucemia/terapia , Trombose Venosa/terapia , Adulto , Idoso , Síndrome de Churg-Strauss/epidemiologia , Síndrome de Churg-Strauss/patologia , Eosinofilia/complicações , Eosinofilia/epidemiologia , Eosinofilia/patologia , Eosinófilos/patologia , Feminino , Humanos , Síndrome Hipereosinofílica/epidemiologia , Síndrome Hipereosinofílica/genética , Síndrome Hipereosinofílica/patologia , Leucemia/epidemiologia , Leucemia/genética , Leucemia/patologia , Masculino , Pessoa de Meia-Idade , Veia Porta/patologia , Embolia Pulmonar/epidemiologia , Embolia Pulmonar/patologia , Embolia Pulmonar/terapia , Recidiva , Estudos Retrospectivos , Resultado do Tratamento , Trombose Venosa/epidemiologia , Trombose Venosa/genética , Trombose Venosa/patologia , Fatores de Poliadenilação e Clivagem de mRNA/genética
7.
PLoS Pathog ; 16(11): e1009025, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-33253297

RESUMO

The development of HIV-1 vaccines is challenged by the lack of relevant models to accurately induce human B- and T-cell responses in lymphoid organs. In humanized mice reconstituted with human hematopoietic stem cells (hu-mice), human B cell-development and function are impaired and cells fail to efficiently transition from IgM B cells to IgG B cells. Here, we found that CD40-targeted vaccination combined with CpG-B adjuvant overcomes the usual defect of human B-cell switch and maturation in hu-mice. We further dissected hu-B cell responses directed against the HIV-1 Env protein elicited by targeting Env gp140 clade C to the CD40 receptor of antigen-presenting cells. The anti-CD40.Env gp140 vaccine was injected with CpG-B in a homologous prime/boost regimen or as a boost of a NYVAC-KC pox vector encoding Env gp140 clade C. Both regimens elicited Env-specific IgG-switched memory hu-B cells at a greater magnitude in hu-mice primed with NYVAC-KC. Single-cell RNA-seq analysis showed gp140-specific hu-B cells to express polyclonal IgG1 and IgG3 isotypes and a broad Ig VH/VL repertoire, with predominant VH3 family gene usage. These cells exhibited a higher rate of somatic hypermutation than the non-specific IgG+ hu-B-cell counterpart. Both vaccine regimens induced splenic GC-like structures containing hu-B and hu-Tfh-like cells expressing PD-1 and BCL-6. We confirmed in this model that circulating ICOS+ memory hu-Tfh cells correlated with the magnitude of gp140-specific B-cell responses. Finally, the NYVAC-KC heterologous prime led to a more diverse clonal expansion of specific hu-B cells. Thus, this study shows that CD40-targeted vaccination induces human IgG production in hu-mice and provides insights for the development of a CD40-targeting vaccine to prevent HIV-1 infection in humans.


Assuntos
Vacinas contra a AIDS/imunologia , Antígenos CD40/imunologia , Anticorpos Anti-HIV/imunologia , Infecções por HIV/prevenção & controle , HIV-1/imunologia , Receptor Toll-Like 9/agonistas , Animais , Anticorpos Neutralizantes/imunologia , Linfócitos B/imunologia , Infecções por HIV/imunologia , Infecções por HIV/virologia , Células-Tronco Hematopoéticas , Humanos , Imunoglobulina G/imunologia , Camundongos , Linfócitos T/imunologia , Vacinação , Produtos do Gene env do Vírus da Imunodeficiência Humana/imunologia
8.
J Rheumatol ; 47(10): 1522-1531, 2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-31787599

RESUMO

OBJECTIVE: To report on a large series of patients with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and bronchiectasis, with a specific focus on the timeline of occurrence of both features. METHODS: Retrospective nationwide multicenter study of patients diagnosed with both AAV and bronchiectasis. RESULTS: Sixty-one patients were included, among whom 27 (44.25%) had microscopic polyangiitis (MPA), 27 (44.25%) had granulomatosis with polyangiitis (GPA), and 7 (11.5%) had eosinophilic GPA. Thirty-nine (64%) had myeloperoxidase (MPO)-ANCA and 13 (21%) had proteinase 3-ANCA. The diagnosis of bronchiectasis either preceded (n = 25; median time between both diagnoses: 16 yrs, IQR 4-54 yrs), was concomitant to (n = 12), or followed (n = 24; median time between both diagnoses: 1, IQR 0-6 yrs) that of AAV. Patients in whom bronchiectasis precedes the onset of AAV (B-AAV group) have more frequent mononeuritis multiplex, MPA, MPO-ANCA, and a 5-fold increase of death. The occurrence of an AAV relapse tended to be protective against bronchiectasis worsening (HR 0.6, 95% CI 0.4-0.99, P = 0.049), while a diagnosis of bronchiectasis before AAV (HR 5.8, 95% CI 1.2-28.7, P = 0.03) or MPA (HR 18.1, 95% CI 2.2-146.3, P = 0.01) were associated with shorter survival during AAV follow-up. CONCLUSION: The association of bronchiectasis with AAV is likely not accidental and is mostly associated with MPO-ANCA. Patients in whom bronchiectasis precedes the onset of AAV tend to have distinct clinical and biological features and could carry a worse prognosis.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos , Bronquiectasia , Granulomatose com Poliangiite , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/complicações , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/diagnóstico , Anticorpos Anticitoplasma de Neutrófilos , Bronquiectasia/etiologia , Humanos , Peroxidase , Prognóstico , Estudos Retrospectivos
9.
Eur J Immunol ; 50(4): 589-602, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-31840802

RESUMO

Studies support the beneficial effects of glucocorticoids (GCs) during septic shock, steering research toward the potential role of GC-induced proteins in controlling excessive inflammatory responses. GILZ is a glucocorticoid-induced protein involved in the anti-inflammatory effects of GCs. We investigated whether the overexpression of GILZ specifically limited to monocytes and macrophages (M/M) alone could control inflammation, thus improving the outcome of septic shock in animal models. We also monitored the expression of GILZ in M/M from septic mice and septic-shock patients. M/M from patients and septic mice displayed significantly lower expression of GILZ than those isolated from controls. Furthermore, transgenic mice (Tg-mice) experiencing sepsis, with increased expression of GILZ restricted to M/M, showed lower frequencies of inflammatory monocytes than their littermates and lower plasma levels of inflammatory cytokines. Tg-mice also had lower blood bacterial counts. We further established that the upregulation of GILZ in M/M enhanced their phagocytic capacity in in vivo assays. The increase of GILZ in M/M was also sufficient to improve the survival rates of septic mice. These results provide evidence for a central role of both GILZ and M/M in the pathophysiology of septic shock and a possible clue for the modulation of inflammation in this disease.


Assuntos
Inflamação/metabolismo , Macrófagos/imunologia , Monócitos/imunologia , Sepse/metabolismo , Fatores de Transcrição/metabolismo , Animais , Anti-Inflamatórios/metabolismo , Carga Bacteriana , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Regulação da Expressão Gênica , Glucocorticoides/metabolismo , Humanos , Imunidade Inata , Imunomodulação , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Transgênicos , Fatores de Transcrição/genética
10.
Respir Res ; 20(1): 275, 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31801528

RESUMO

BACKGROUND: Bronchiectasis is a heterogeneous disease depending on etiology. It represents the most frequent non-infectious pulmonary complication of primary immunodeficiencies (PID). We investigated whether bronchiectasis associated with PID had a distinct course in comparison to bronchiectasis of other causes. METHODS: Retrospective single-center study of adult patients diagnosed with non-cystic fibrosis bronchiectasis with more than 5 years of follow-up and at least 4 pulmonary functional tests available at one year apart. They were divided into three groups: PID- related bronchiectasis, idiopathic/post infectious-related bronchiectasis and other causes of bronchiectasis. Respiratory functional data and clinical outcomes were compared. RESULTS: Of 329 patients with bronchiectasis diagnosed in Foch Hospital (Suresnes, France), 98 patients fulfilled the selected criteria (20 PID-related cases, 39 idiopathic or post-infectious cases, and 39 cases with other causes). Median time of follow-up was 9.5 years. Groups were similar concerning initial characteristics (female 70.4%, never smokers 59.2%, mild severity bronchiectasis according to the FACED score and median FEV1 at diagnosis 73.5% predicted values [Q1-Q3: 53.75-90.5]), except PID patients who were younger (median age of 51.5 vs 62 years, p = 0.02). Eighty-five percent of PID patients received immunoglobulin substitution (median trough level was measured at 10.5 g/dl [10;10.92]). Global median FEV1 annual decline was 25.03 ml/year [8.16;43.9] and 19.82 ml/year [16.08;48.02] in the PID patients group. Forty-five percent of patients had bacterial colonization, pneumoniae occurred in 56% of patients and median exacerbation annual rate was 0.8 [0.3-1.4]. Hemoptysis occurred in 31.6% of patients. Global mortality rate was 11.2%. We did not record any significant difference for all clinical and functional outcomes between patients with PID and other etiologies. The median decline in FEV1 was similar in the three groups. CONCLUSIONS: The course of PID-related bronchiectasis was similar to bronchiectasis of other causes. Provided that patients receive immunoglobulin replacement, the course of PID-related bronchiectasis seems to be independent of the underlying immune disorder.


Assuntos
Bronquiectasia/diagnóstico , Bronquiectasia/epidemiologia , Causas de Morte , Doenças da Imunodeficiência Primária/diagnóstico , Doenças da Imunodeficiência Primária/epidemiologia , Adulto , Fatores Etários , Estudos de Coortes , Comorbidade , Fibrose Cística , Feminino , França/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Testes de Função Respiratória , Estudos Retrospectivos , Medição de Risco , Índice de Gravidade de Doença , Fatores Sexuais , Análise de Sobrevida , Centros de Atenção Terciária
11.
J Allergy Clin Immunol Pract ; 7(6): 1986-1995.e3, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30878710

RESUMO

BACKGROUND: Autosomal-dominant signal transducer and activator of transcription 3 (STAT3) deficiency predisposes to recurrent bacterial pneumonia, complicated by bronchiectasis and cavitations. Aspergillosis is a major cause of morbidity in these patients. However, its diagnosis, classification, and treatment are challenging. OBJECTIVE: We aimed to assess the prevalence and describe the clinical, mycological, and radiological presentation and related therapy and outcome of Aspergillus infections of the respiratory tract in the STAT3-deficient patients of the National French cohort. METHODS: We performed a retrospective study of all pulmonary aspergillosis cases in STAT3-deficient patients (n = 74). Clinical and mycological data were collected up to October 2015 and imaging was centralized. RESULTS: Twenty-one episodes of pulmonary aspergillosis in 13 (17.5%) STAT3-deficient patients were identified. The median age at first episode was 13 years (interquartile range, 10-26 years). Ninety percent of patients had previous bronchiectasis or cavitations. Infections were classified as follows: 5 single aspergilloma, 9 chronic cavity pulmonary aspergillosis, 5 allergic bronchopulmonary aspergillosis-like disease, and 2 mixed forms of concomitant allergic bronchopulmonary aspergillosis-like disease and chronic cavity pulmonary aspergillosis. No invasive aspergillosis cases were identified. Aspergillus species were isolated in 71% of episodes and anti-Aspergillus antibodies in 93%. Eleven episodes were breakthrough infections. Antifungal treatment was prolonged, with a median of 13 months, and 6 patients (7 episodes) required surgery, with a high rate of postsurgical complications. One patient died and 6 had a relapse. CONCLUSIONS: Chronic and allergic forms of aspergillosis occurred in 17.5% of STAT3-deficient patients, mostly in lung cavities. Almost half had recurrences, despite prolonged antifungal treatment and/or surgery.


Assuntos
Síndrome de Job , Aspergilose Pulmonar , Fator de Transcrição STAT3/deficiência , Adolescente , Adulto , Antifúngicos/uso terapêutico , Criança , Feminino , França/epidemiologia , Humanos , Síndrome de Job/diagnóstico por imagem , Síndrome de Job/tratamento farmacológico , Síndrome de Job/epidemiologia , Masculino , Aspergilose Pulmonar/diagnóstico por imagem , Aspergilose Pulmonar/tratamento farmacológico , Aspergilose Pulmonar/epidemiologia , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Adulto Jovem
16.
Eur Respir J ; 45(6): 1613-23, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25614174

RESUMO

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by failure of superoxide production in phagocytic cells. The disease is characterised by recurrent infections and inflammatory events, frequently affecting the lungs. Improvement of life expectancy now allows most patients to reach adulthood. We aimed to describe the pattern of pulmonary manifestations occurring during adulthood in CGD patients. This was a retrospective study of the French national cohort of adult patients (≥16 years old) with CGD. Medical data were obtained for 67 adult patients. Pulmonary manifestations affected two-thirds of adult patients. Their incidence was significantly higher than in childhood (mean annual rate 0.22 versus 0.07, p=0.01). Infectious risk persisted despite anti-infectious prophylaxis. Invasive fungal infections were frequent (0.11 per year per patient) and asymptomatic in 37% of the cases. They often required lung biopsy for diagnosis (10 out of 30). Noninfectious respiratory events concerned 28% of adult patients, frequently associated with a concomitant fungal infection (40%). They were more frequent in patients with the X-linked form of CGD. Immune-modulator therapies were required in most cases (70%). Respiratory manifestations are major complications of CGD in adulthood. Noninfectious pulmonary manifestations are as deleterious as infectious pneumonia. A specific respiratory monitoring is necessary.


Assuntos
Doença Granulomatosa Crônica/complicações , Pneumopatias Fúngicas/etiologia , Pulmão/patologia , Pneumonia Bacteriana/etiologia , Adolescente , Adulto , Anti-Infecciosos/uso terapêutico , Doenças Assintomáticas , Biópsia , Estudos de Coortes , Feminino , Doença Granulomatosa Crônica/tratamento farmacológico , Doença Granulomatosa Crônica/genética , Humanos , Fatores Imunológicos/uso terapêutico , Pneumopatias/etiologia , Pneumopatias Fúngicas/diagnóstico , Pneumopatias Fúngicas/tratamento farmacológico , Masculino , Glicoproteínas de Membrana/genética , Pessoa de Meia-Idade , NADPH Oxidase 2 , NADPH Oxidases/genética , Pneumonia Bacteriana/diagnóstico , Pneumonia Bacteriana/tratamento farmacológico , Estudos Retrospectivos , Adulto Jovem
18.
Rheumatology (Oxford) ; 53(3): 532-9, 2014 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-24282319

RESUMO

OBJECTIVES: Rituximab has been shown to induce remission of ANCA-associated vasculitides (AAVs). Our study was undertaken to describe AAV clinical responses to rituximab used for remission-induction and/or maintenance therapy, assess rituximab's safety profile and evaluate French clinical practices. METHODS: This retrospective study concerned AAV patients who had received one or more rituximab infusion between 2002 and January 2011 and had follow-up lasting ≥12 months. RESULTS: Eighty patients were included, most with refractory or relapsing AAV: 70 (88%) with granulomatosis with polyangiitis (GPA), 9 (11%) with microscopic polyangiitis and 1 (1%) with eosinophilic GPA. Rituximab was the first agent used to induce remission in 73 patients. The two most commonly administered regimens were an infusion of 375 mg/m(2)/week for 4 weeks (54 patients) and an infusion of 1 g every 2 weeks for a month (16 patients). Rituximab was first prescribed to maintain remission in seven patients. Respective 1-, 2-, and 3-year relapse-free survival rates after the first infusion were 80% (95% CI 72, 89), 63% (51, 77) and 52% (39, 70). Relapse-free survival was longer for patients receiving rituximab maintenance therapy (P = 0.002). Among 22 (28%) rituximab-treated patients experiencing severe adverse events, 12 (15%) had infectious complications leading to 4 (5%) deaths. Only 15 (19%) patients had received anti-pneumococcal vaccine before rituximab. CONCLUSION: Rituximab was able to induce AAV remission and seemed to maintain remission better than other agents, but caution is needed concerning its safety, especially regarding bacterial infections, in this population.


Assuntos
Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/tratamento farmacológico , Anticorpos Monoclonais Murinos/uso terapêutico , Antirreumáticos/uso terapêutico , Gerenciamento Clínico , Adulto , Idoso , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/epidemiologia , Vasculite Associada a Anticorpo Anticitoplasma de Neutrófilos/mortalidade , Anticorpos Monoclonais Murinos/efeitos adversos , Antirreumáticos/efeitos adversos , Infecções Bacterianas/epidemiologia , Feminino , França/epidemiologia , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Indução de Remissão , Estudos Retrospectivos , Fatores de Risco , Rituximab , Taxa de Sobrevida , Resultado do Tratamento
19.
Semin Respir Crit Care Med ; 34(5): 645-53, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-24037631

RESUMO

Pulmonary arterial hypertension (PAH) is a severe complication of human immunodeficiency virus (HIV) infection and a leading major cause of death when present. HIV-PAH could be the consequence of multiple hits including the direct effects of HIV proteins, use of illicit drugs, and chronic inflammation. Indeed, HIV infection has long been identified as an immunosuppressive disease but, since the advent of highly active antiretroviral treatments (HAART), HIV infection is considered as an inflammatory disease in which vascular complications have become a major cause of morbidity and death. Conversely to immunosuppression, which correlates with blood CD4 + T cell level, inflammation in HIV infection is due to the lack of gut CD4 + T cell restoration. Such gut T cell depletion favors lipopolysaccharide translocation and, in turn, chronic systemic interleukin-6 overproduction. Conversely to blood CD4 + T cells, gut CD4 + T cells are only partially restored with HAART, usually slowly after several months or years, with a large heterogeneity from one patient to another. These characteristics may cause chronic inflammation, and we hypothesize that PAH may occur because of this inflammatory component despite HAART, even with apparently good response to therapy (i.e., blood CD4 + T cell normalization and undetectable HIV load). Inflammation theory in HIV-PAH (as in other forms of PAH) could open new treatment options.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Infecções por HIV/imunologia , Proteínas do Vírus da Imunodeficiência Humana/imunologia , Hipertensão Pulmonar/imunologia , Terapia Antirretroviral de Alta Atividade , Hipertensão Pulmonar Primária Familiar , Infecções por HIV/complicações , Infecções por HIV/tratamento farmacológico , Humanos , Hipertensão Pulmonar/etiologia , Inflamação/imunologia , Interleucina-6/imunologia , Lipopolissacarídeos/imunologia
20.
Chest ; 142(5): 1150-1157, 2012 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-22459770

RESUMO

BACKGROUND: Precapillary pulmonary hypertension (PH) is a complication of pulmonary Langerhans cell histiocytosis (PLCH) associated with increased mortality. However, outcomes and efficacy of pulmonary arterial hypertension (PAH) therapies in patients with PH complicating PLCH(PLCH-PH) remain unknown. METHODS: Consecutive patients with PLCH with PH confirmed by right-sided heart catheterization were included in the study. Characteristics at baseline and during follow-up as well as survival were analyzed. RESULTS: Twenty-nine patients were studied. Baseline characteristics of patients with PLCH-PH wereas follows: 83% of patients in World Health Organization (WHO) functional class III to IV, mean 6-min walk distance of 355 ±95 m, mean pulmonary arterial pressure (mPAP) of 45 ±14 mm Hg,cardiac index of 3.2± 0.9 L/min/m 2 , and pulmonary vascular resistance (PVR) of 555 ±253 dyne/s/cm 5. Use of PAH therapy in 12 patients was followed by an improvement in mPAP (56±14 mm Hg and 45±12 mm Hg, P 5 .03) and PVR (701±239 dyne/s/cm 5 and 469±210 dyne/s/cm 5 , P = .01) between baseline and follow-up evaluations. No significant oxygen worsening was observed in the treated group. The 1-, 3-, and 5-year survival estimates of the 29 patients were 96%, 92%, and 73%,respectively. Except a trend toward a better survival rate associated with the use of PAH therapy,WHO functional class was the only variable significantly associated with death. CONCLUSIONS: In this group of patients, PAH therapies improved hemodynamics without oxygen worsening or pulmonary edema. WHO functional class was the only prognostic factor identified.Prospective clinical trials focusing on this population of patients are warranted


Assuntos
Histiocitose de Células de Langerhans/complicações , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/terapia , Adulto , Cateterismo Cardíaco , Distribuição de Qui-Quadrado , Feminino , Hemodinâmica , Humanos , Hipertensão Pulmonar/fisiopatologia , Masculino , Pessoa de Meia-Idade , Prognóstico , Modelos de Riscos Proporcionais , Sistema de Registros , Testes de Função Respiratória , Estudos Retrospectivos , Estatísticas não Paramétricas , Taxa de Sobrevida , Resultado do Tratamento
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