Respiratory functional characteristics of human leptospirosis

Introdução: O comprometimento respiratório da leptospirose humana pode ser sua principal manifestação clínica e comumente está associado a maior morbimortalidade. Métodos: Objetivando descrever aspectos funcionais respiratórios nessa doença, foram analisados 21 pacientes com oximetrias de pulso e espirometrias em dois momentos: em avaliação inicial e após cerca de 28 dias. Resultados: Dois (9,5%) doentes tinham saturação periférica de oxigênio menor que 95%. Padrões espirométricos normais foram observados em 8 (38,1%) casos; distúrbios ventilatórios restritivos foram inferidos em 7 (33,3%), obstrutivos com capacidade vital forçada reduzida em 4 (19%), e inespecíficos em 2 (9,5%). Espirometrias anormais se associaram a pior escore APACHE II (p=0,02) e anormalidades na radiografia de tórax (p=0,05). Após resolução clínica, verificou-se ganho funcional significativo (p<0,05) no grupo de pacientes com espirometria alterada. Conclusões: Alterações espirométricas foram detectadas no curso da enfermidade e estiveram associadas a pior gravidade clínica e maior freqüência de anormalidades radiológicas torácicas. _________________________________________________________________________________________ ABSTRACT: Introduction: Respiratory impairment may be the main clinical manifestation of human leptospirosis. Methods: With the aim of describing the respiratory functional characteristics of this disease, 21 patients were evaluated using pulse oximetry and spirometry at two times: an initial evaluation and after around 28 days. Results: Two (9.5%) patients presented peripheral oxygen saturation of less than 95%. Normal spirometric patterns were observed in eight (38.1%); cases restrictive ventilatory disorders were inferred in seven (33.3%), obstructive disorders with reduced forced vital capacity in four (19%), and nonspecific disorders in two (9.5%). Abnormal spirometry findings were associated with worse APACHE II scores (p = 0.02) and abnormalities on chest x-ray (p = 0.05). After clinical resolution, significant functional gain was observed (p < 0.05) in the group of patients with abnormal spirometry findings. Conclusions: It was concluded that respiratory functional abnormalities were detected during the course of the disease and were associated with greater clinical severity and higher frequency of chest radiographic abnormalities

Antiinflammatory Therapy with Canakinumab for Atherosclerotic Disease

Background: Experimental and clinical data suggest that reducing inflammation without affecting lipid levels may reduce the risk of cardiovascular disease. Yet, the inflammatory hypothesis of atherothrombosis has remained unproved. Methods: We conducted a randomized, double-blind trial of canakinumab, a therapeutic monoclonal antibody targeting interleukin-1β, involving 10,061 patients with previous myocardial infarction and a high-sensitivity C-reactive protein level of 2 mg or more per liter. The trial compared three doses of canakinumab (50 mg, 150 mg, and 300 mg, administered subcutaneously every 3 months) with placebo. The primary efficacy end point was nonfatal myocardial infarction, nonfatal stroke, or cardiovascular death. RESULTS: At 48 months, the median reduction from baseline in the high-sensitivity C-reactive protein level was 26 percentage points greater in the group that received the 50-mg dose of canakinumab, 37 percentage points greater in the 150-mg group, and 41 percentage points greater in the 300-mg group than in the placebo group. Canakinumab did not reduce lipid levels from baseline. At a median follow-up of 3.7 years, the incidence rate for the primary end point was 4.50 events per 100 person-years in the placebo group, 4.11 events per 100 person-years in the 50-mg group, 3.86 events per 100 person-years in the 150-mg group, and 3.90 events per 100 person-years in the 300-mg group. The hazard ratios as compared with placebo were as follows: in the 50-mg group, 0.93 (95% confidence interval [CI], 0.80 to 1.07; P = 0.30); in the 150-mg group, 0.85 (95% CI, 0.74 to 0.98; P = 0.021); and in the 300-mg group, 0.86 (95% CI, 0.75 to 0.99; P = 0.031). The 150-mg dose, but not the other doses, met the prespecified multiplicity-adjusted threshold for statistical significance for the primary end point and the secondary end point that additionally included hospitalization for unstable angina that led to urgent revascularization (hazard ratio vs. placebo, 0.83; 95% CI, 0.73 to 0.95; P = 0.005). Canakinumab was associated with a higher incidence of fatal infection than was placebo. There was no significant difference in all-cause mortality (hazard ratio for all canakinumab doses vs. placebo, 0.94; 95% CI, 0.83 to 1.06; P = 0.31). Conclusions: Antiinflammatory therapy targeting the interleukin-1β innate immunity pathway with canakinumab at a dose of 150 mg every 3 months led to a significantly lower rate of recurrent cardiovascular events than placebo, independent of lipid-level lowering. (Funded by Novartis; CANTOS ClinicalTrials.gov number, NCT01327846.

Estudo do lavado broncoalveolar em pacientes com comprometimento pulmonar na leptospirose Study of bronchoalveolar lavage in leptospirosis patients with pulmonary involvement

INTRODUÇÃO: O comprometimento pulmonar é freqüente na leptospirose e caracteriza-se por hemoptise, dispnéia e infiltrados pulmonares bilaterais no radiograma de tórax. Esses achados podem ser compatíveis com hemorragia alveolar, previamente descrita por alguns autores em autópsias e em lavado broncoalveolar. OBJETIVO: Avaliar a presença de hemorragia alveolar, diagnosticada por meio do lavado broncoalveolar, em pacientes portadores de leptospirose com alterações pulmonares, enfatizando-se a importância do método para o diagnóstico precoce da complicação. MÉTODO: Sete pacientes com leptospirose foram submetidos à broncoscopia com lavado broncoalveolar. Todos apresentavam sinais e/ou sintomas respiratórios, e/ou infiltrados no radiograma de tórax, e/ou hipoxemia. A hemorragia alveolar foi definida pelos seguintes achados no lavado: porcentagem de siderófagos e"20%, escore de Golde > 100, e/ou presença de líquido hemorrágico. Foram realizados exame direto e cultura para Leptospiras, com o uso de meios específicos. O diagnóstico da doença foi confirmado por soroaglutinação microscópica para leptospirose. RESULTADOS: O aspecto da broncoscopia foi normal em 5 pacientes, mostrou sangramento na árvore brônquica em 1 caso e sinais inflamatórios em outro. O aspecto do lavado foi hemorrágico em todos os pacientes, configurando o quadro de hemorragia alveolar. A pesquisa direta e a cultura para Leptospiras foram negativas. CONCLUSÃO: A leptospirose deve ser considerada no diagnóstico diferencial das hemorragias alveolares.O lavado broncoalveolar mostrou-se um método eficaz para a detecção de hemorragia alveolar na leptospirose, servindo para orientar a terapêutica imediata, com a finalidade de prevenir sua evolução, caracterizada pela presença de hemoptises maciças e insuficiência respiratória.<br>BACKGROUND: Pulmonary involvement is common in leptospirosis and usually characterized by hemoptysis, dyspnea and diffuse bilateral infiltrates in chest X-rays. Such findings may be compatible with alveolar hemorrhage, already described by some authors both in autopsies and bronchoalveolar lavage (BAL). OBJECTIVE: To evaluate the presence of alveolar hemorrhage, diagnosed through BAL, in bearers of leptospirosis patients with pulmonary involvement emphasizing the methodís importance for early detection of this complication. METHOD: Seven patients with leptospirosis were submitted to BAL. All presented respiratory symptoms and/or infiltrates in the chest X-rays and/or hypoxemia.Alveolar hemorrhage was defined by the following findings in BAL: percentage of siderophages eî20% and/ or Golde score >100 and/or hemorrhagic fluid. Culture and direct tests for leptospirosis were performed in BAL. Diagnosis of disease was confirmed by microscopy serum agglutination. RESULTS: The aspect of the bronchoscopy was normal in five patients, showed blood in the bronchial tree in one case and inflammatory manifestations in another. The BAL aspect was hemorrhagic for all patients portraying alveolar hemorrhage. Culture and direct tests were negative for Leptospiras in the BAL. CONCLUSIONS: Leptospirosis must be taken into account in the differential diagnosis of alveolar hemorrhage. The BAL was confirmed as an efficient method for detection of alveolar hemorrhage in leptospirosis, to recommend immediate therapy for the purpose of preventing its evolution to massive hemoptysis and respiratory failure