Low expression of antigen-presenting and costimulatory molecules by lung cells from tuberculosis patients

Costimulatory and antigen-presenting molecules are essential to the initiation of T cell immunity to mycobacteria. The present study analyzed by immunocytochemistry, using monoclonal antibodies and alkaline phosphatase-anti-alkaline phosphatase method, the frequency of costimulatory (CD86, CD40, CD40L, CD28, and CD152) and antigen-presenting (MHC class II and CD1) molecules expression on human lung cells recovered by sputum induction from tuberculosis (TB) patients (N = 22) and non-TB controls (N = 17). TB cases showed a statistically significant lower percentage of HLA-DR+ cells than control subjects (21.9 ± 4.2 vs 50.0 ± 7.2 percent, P < 0.001), even though similar proportions of TB cases (18/22) and control subjects (16/17, P = 0.36) had HLA-DR-positive-stained cells. In addition, fewer TB cases (10/22) compared to control subjects (16/17) possessed CD86-expressing cells (P = 0.04; OR: 0.05; 95 percentCI = 0.00-0.51), and TB cases expressed a lower percentage of CD86+ cells (P = 0.04). Moreover, TB patients with clinically limited disease (£1 lobe) on chest X-ray exhibited a lower percentage of CD86-bearing cells compared to patients with more extensive lung disease (>1 lobe) (P = 0.02). The lower expression by lung cells from TB patients of HLA-DR and CD86, molecules involved in antigen presentation and activation of T cells, may minimize T cell recognition of Mycobacterium tuberculosis, fostering an immune dysfunctional state and active TB.

Protective effects of phosphodiesterase inhibitors on lung function and remodeling in a murine model of chronic asthma

The aim of the present study was to compare the efficacy of a novel phosphodiesterase 4 and 5 inhibitor, LASSBio596, with that of dexamethasone in a murine model of chronic asthma. Lung mechanics (airway resistance, viscoelastic pressure, and static elastance), histology, and airway and lung parenchyma remodeling (quantitative analysis of collagen and elastic fiber) were analyzed. Thirty-three BALB/c mice were randomly assigned to four groups. In the asthma group (N = 9), mice were immunized with 10 æg ovalbumin (OVA, ip) on 7 alternate days, and after day 40 they were challenged with three intratracheal instillations of 20 æg OVA at 3-day intervals. Control mice (N = 8) received saline under the same protocol. In the dexamethasone (N = 8) and LASSBio596 (N = 8) groups, the animals of the asthma group were treated with 1 mg/kg dexamethasone disodium phosphate (0.1 mL, ip) or 10 mg/kg LASSBio596 dissolved in dimethyl sulfoxide (0.2 mL, ip) 24 h before the first intratracheal instillation of OVA, for 8 days. Airway resistance, viscoelastic pressure and static elastance increased significantly in the asthma group (77, 56, and 76 percent, respectively) compared to the control group. The asthma group presented more intense alveolar collapse, bronchoconstriction, and eosinophil and neutrophil infiltration than the control group. Both LASSBio596 and dexamethasone inhibited the changes in lung mechanics, tissue cellularity, bronchoconstriction, as well as airway and lung parenchyma remodeling. In conclusion, LASSBio596 at a dose of 10 mg/kg effectively prevented lung mechanical and morphometrical changes and had the potential to block fibroproliferation in a BALB/c mouse model of asthma.

Bronchial hyperresponsiveness and analysis of induced sputum cells in Crohn's disease

With the aim of investigating the presence of latent inflammatory process in the lungs of patients with Crohn's disease, 15 patients with Crohn's disease were evaluated by spirometry, the methacholine challenge test, induced sputum, and skin tests for inhaled antigens. Serum IgE, erythrocyte sedimentation rate and hematocrit were also determined. The patients were compared with 20 healthy controls by the Mann-Whitney and Fisher exact tests. Their respiratory physical examination was normal. None had a personal or family history of clinical atopy. None had a previous history of pulmonary disease, smoking or toxic bronchopulmonary exposure. None had sinusitis, migraine, diabetes mellitus, or cardiac failure. Four (26.6 percent) of the patients with Crohn's disease had a positive methacholine challenge test whereas none of the 20 controls had a positive methacholine test (P = 0.026, Fisher exact test). Patients with Crohn's disease had a higher level of lymphocytes in induced sputum than controls (mean 14.59 percent, range 3.2-50 vs 5.46 percent, 0-26.92 percent, respectively; P = 0.011, Mann-Whitney test). Patients with Crohn's disease and a positive methacholine challenge test had an even higher percentage of lymphocytes in induced sputum compared with patients with Crohn's disease and a negative methacholine test (mean 24.88 percent, range 12.87-50 vs 10.48 percent, 3.2-21.69 percent; P = 0.047, Mann-Whitney test). The simultaneous findings of bronchopulmonary lymphocytosis and bronchial hyperresponsiveness in patients with Crohn's disease were not reported up to now. These results suggest that patients with Crohn's disease present a subclinical inflammatory process despite the absence of pulmonary symptoms.

Tuberculose ganglionar em pacientes co-infectados pelo HIV-1: estudo clínico e laboratorial / Ganglionic tuberculosis in patients co-infected by HIV-1: clinical and laboratorial study

Estudos clínicos e laboratoriais apontam diferenças marcantes entre pacientes soropositivos para HIV-1 e imunocompetentes. A tuberculose ganglionar é uma forma freqüente de apresentaçäo extrapulmonar nestes pacientes. A apresentaçäo histopatológica é muito diferente dos pacientes imunocompetentes, com mais de 70 por cento dos casos de várias séries näo apresentando granulomas ou, quando presentes, malformados, com extensa necrose caseosa, raras células gigantes e presença de muitos bacilos álcool-ácido resistentes, denotando uma resposta imune incompleta. Estudamos os diversos aspectos clínicos e laboratoriais, incluídos exames microbiológicos e histopatológicos de 27 pacientes encaminhados para tratamento e diagnóstico no Hospital Evandro Chagas/FIOCRUZ. De acordo com o diagnóstico histopatológico, os casos foram subdivididos em três grupos: Grupo I (n = 7): tuberculose ganglionar sem infecçäo pelo HIV - 1; Grupo II (n = 9): tuberculose ganglionar em pacientes co-infectados por HIV - 1; Grupo III (n = 11): linfadenite reativa associada à AIDS. No grupo de pacientes co-infectados em relaçäo aos imunocompetentes, verificou-se grannulomas malformados, verificou-se granulomas malformados, extensa necrose e grande riqueza bacilar, além de queda acentuada de hemácias e linfócitos e grande freqüência de infecçöes oportunísticas denotando grave defeito na resposta imune, explicando a apresentaçäo de formas bem mais severas e nao usuais de tuberculose nos pacientes com AIDS.

Emergence of T-lymphocytes, eosinophils and dendritic cells in the bronchi of actively sensitized guinea pigs after antigenic challenge

Bronchi from guinea pigs actively sensitized to ovalbumin and boosted two weeks later display increased numbers of CD4+ T-lymphocytes and eosinophils. We have further investigated immunopathological changes in sensitized guinea pigs 2 or 24 h after antigenic challenge with ovalbumin. Lungs were resected, frozen and cryostat sections stained with monoclonal antibodies that recognize relevant guinea pig epitopes. Cyanide-resistant peroxidase activity was used to stain eosinophils. No further increase in T-lymphocytes or eosinophils was observed 2 h after challenge. At 24 h, a marked increase in EPO+ eosinophils was found, and this was accompanied by severe mucosal damage characterized by epithelial shedding and ulceration. The numbers of T-lymphocytes remained stable but a novel population of cells with the appearance of dendritic cells was seen in the bronchial wall. They were negative for macrophage markers but were strongly Class II positive. These findings suggest that antigenic challenge results in further recruitment of eosinophils, their activation and release of toxic substances to the epithelium. Furthermore, other cell types, possibly dendritic cells, are attracted to the bronchi and could play a role in maintaining allergic inflammation via antigen presentation.

Sintomas respiratórios e testes espirográficos dos funcionários de uma pedreira do Rio de Janeiro / Respiratory symptoms and spirometric tests of the quarry workers Rio de Janeiro

Foram investigados os sintomas e antecedentes respiratórios, bem como os resultados das provas espirográficas, de 72 dos 86 (83,7 por cento) funcionários de uma pedreira de porte médio do Rio de Janeiro. Setenta e um (98,6 por cento) eram homens, e a média das idades foi de 36,2 + ou - 9,3 anos (20 a 65 anos). Quarenta e dois (58,3 por cento) tinham ocupaçöes consideradas muito expostas ao pó de pedra e 30 (44,7 por cento) pouco expostas. Quarenta (55,6 por cento) eram fumantes, 20 (27,8 por cento) näo fumantes e 12 (16,7 por cento) ex-fumantes. Foi utilizado um questionário padronizado baseado em modelos internacionais e adaptados a condiçöes brasileiras. Houve elevada freqüência de sintomas, com exceçäo da dispnéia: 47 (65,3 por cento) referiram um ou mais sintomas, dos quais 31,9 por cento referiram tosse, 41,7 por cento expectoraçäo, 9,7 por cento dispnéia e 33,3 por cento chiado torácico. Os sintomas se associaram principalmente à presença de antecedentes de doenças respiratórias, havendo também associaçäo com o tabagismo. Um ou outro desses fatores explicaram os sintomas. Näo houve associaçäo com a maior exposiçäo ao pó de pedra, qua näo explicou os sintomas. As provas espirográficas foram realizadas com o espirógrafo de campânula de 6 litros, observando-se discreta reduçäo das médias da capacidade vital forçada (CVF) (89,9 + ou - 11,2 por cento do teórico), do volume de expiraçäo forçada do 1§ segundo (VEF1) (90,1 + ou - 12,9 por cento) e do fluxo expiratório forçado entre 25 por cento e 75 por cento da CVF (FEF 25-75) (92,9 + ou - 32,7 por cento) em relaçäo às médias esperadas numa amostra populacional näo selecionada. Contudo, as proporçöes de valores subnormais foram comparáveis às de amostras näo selecionadas da literatura nacional e internacional. Näo houve influência estatisticamente significativa da maior exposiçäo ao pó de pedra, antecedentes respiratórios e tabagismo sobre as médias dos resultados espirográficos. Concluímos que, neste grupo de funcionários de uma pedreira, näo se demonstrou associaçäo entre a maior exposiçäo ao pó de pedra e os sintomas respiratórios, ou influência dessa exposiçäo sobre as médias dos resultados espirográficos. Com relaçäo aos antecedentes respiratórios e tabagismo, houve associaçäo com os sintomas mas näo influência sobre as médias dos resultados espirográficos.

Carcinoide bronquico - relato de dois casos em criancas. / Bronchial carcinoid - report of 2 cases in children

Os autores descrevem dois casos de adenoma bronquico carcinoide em menores de 16 anos: o primeiro paciente era do sexo feminino, de 11 anos, teve diagnostico clinico-radiologico de tuberculose, e o segundo do sexo masculino, de 15 anos, cursou com pneumonia de repeticao e igualmente chegou a receber tratamento especifico.Em ambos os doentes o exame endoscopico evidenciou tumor endobronquico. Os pacientes foram submetidos a cirurgia, visando a diagnostico e terapeutica. A evolucao foi favoravel nos dois casos