The TORCH (towards a revolution in COPD health) survival study protocol

Only long-term home oxygen therapy has been shown in randomised controlled trials to increase survival in chronic obstructive pulmonary disease (COPD). There have been no trials assessing the effect of inhaled corticosteroids and long-acting bronchodilators, alone or in combination, on mortality in patients with COPD, despite their known benefit in reducing symptoms and exacerbations. The "TOwards a Revolution in COPD Health" (TORCH) survival study is aiming to determine the impact of salmeterol/fluticasone propionate (SFC) combination and the individual components on the survival of COPD patients. TORCH is a multicentre, randomised, double-blind, parallel-group, placebo-controlled study. Approximately 6,200 patients with moderate-to-severe COPD were randomly assigned to b.i.d. treatment with either SFC (50/500 microg), fluticasone propionate (500 microg), salmeterol (50 microg) or placebo for 3 yrs. The primary end-point is all-cause mortality; secondary end-points are COPD morbidity relating to rate of exacerbations and health status, using the St George's Respiratory Questionnaire. Other end-points include other mortality and exacerbation end-points, requirement for long-term oxygen therapy, and clinic lung function. Safety end-points include adverse events, with additional information on bone fractures. The first patient was recruited in September 2000 and results should be available in 2006. This paper describes the "TOwards a Revolution in COPD Health" study and explains the rationale behind it.

Viability of Pseudomonas aeruginosa in cough aerosols generated by persons with cystic fibrosis

Background Person-to-person transmission of respiratory pathogens, including Pseudomonas aeruginosa, is a challenge facing many cystic fibrosis (CF) centres. Viable P aeruginosa are contained in aerosols produced during coughing, raising the possibility of airborne transmission.

Methods Using purpose-built equipment, we measured viable P aeruginosa in cough aerosols at 1, 2 and 4 m from the subject (distance) and after allowing aerosols to age for 5, 15 and 45 min in a slowly rotating drum to minimise gravitational settling and inertial impaction (duration). Aerosol particles were captured and sized employing an Anderson Impactor and cultured using conventional microbiology. Sputum was also cultured and lung function and respiratory muscle strength measured.

Results Nineteen patients with CF, mean age 25.8 (SD 9.2) years, chronically infected with P aeruginosa, and 10 healthy controls, 26.5 (8.7) years, participated. Viable P aeruginosa were detected in cough aerosols from all patients with CF, but not from controls; travelling 4 m in 17/18 (94%) and persisting for 45 min in 14/18 (78%) of the CF group. Marked inter-subject heterogeneity of P aeruginosa aerosol colony counts was seen and correlated strongly (r=0.73-0.90) with sputum bacterial loads. Modelling decay of viable P aeruginosa in a clinic room suggested that at the recommended ventilation rate of two air changes per hour almost 50 min were required for 90% to be removed after an infected patient left the room.

Conclusions: Viable P aeruginosa in cough aerosols travel further and last longer than recognised previously, providing additional evidence of airborne transmission between patients with CF.

Avaliação do débito máximo da tosse (peak cough flow) na doença pulmonar obstrutiva crónica

Resumo Objectivos: Avaliação da Tosse em doentes com Doença Pulmonar Obstrutiva Crónica (DPOC). Identificar e determinar a relação dos factores preditivos que contribuem para a deterioração da capacidade de tosse nestes indivíduos. Tipo de estudo: Estudo observacional descritivo de natureza transversal. Definição dos casos: Os critérios de diagnóstico da DPOC são o quadro clínico e o Gold standard para diagnóstico da DPOC – a espirometria. População-alvo: Todos os utentes com patologia primária de DPOC diagnosticada que se desloquem ao serviço de função respiratória do Hospital de Viseu, para realizar provas. Método de Amostragem: Foi utilizada uma amostra aleatória constituída por todos os indivíduos, que cumpriram os critérios de inclusão, conscientes e colaborantes, que aceitaram participar neste estudo. Dimensão da amostra: Uma amostra de 55 indivíduos que se deslocaram ao serviço de função respiratória, entre Janeiro e Junho de 2009, para realizar provas de função respiratória. Condução do estudo: Os utentes que aceitaram participar neste estudo foram sujeitos a um questionário de dados clínicos e realizaram 5 testes: índice de massa corporal (IMC), estudo funcional respiratório e gasometria arterial, avaliação da força dos músculos respiratórios (PImax e PEmax) e avaliação do débito máximo da tosse (Peak Cough Flow). Análise estatística: Foram obtidos dados caracterizadores da amostra em estudo, sendo posteriormente correlacionado o valor de débito máximo da tosse (Peak Cough Flow) com os resultados obtidos para as avaliações do IMC, estudo funcional respiratório, PImax e PEmax, gasometria, avaliação da capacidade de Tosse e número de internamentos no último ano por agudização da DPOC. Tendo sido encontrados os valores de correlação entre o Peak Cough Flow e os restantes parâmetros. Resultados: Após análise dos resultados, foram obtidos os valores de Peak Cough Flow para a população com DPOC e verificou-se valores diminuídos em comparação com os valores normais da população, tendo-se verificado maiores valores de PCF em indivíduos do sexo masculino, em comparação aos valores do sexo feminino. Foi analisada a relação entre o PCF e a idade, peso, altura e IMC, não tendo sido encontrada relação, dado que a tosse não apresenta uma variação segundo os valores antropométricos, tal como a relação com os valores espirométricos. Quanto aos parâmetros funcionais respiratórios foram analisadas as relações com o PCF. Verificou-se relações significativas entre o PCF e o FEV1, a FVC, o PEF, apresentando uma relação positiva, onde maiores valores destes parâmetros estão correlacionados com maiores picos de tosse. Quanto a RAW e RV, o PCF apresenta uma relação negativa, onde uma maior resistência da via aérea ou doentes mais hiperinsuflados leva a menores valores de PCF. Por outro lado não foi encontrada relação entre o PCF e a FRC e o TLC. Quanto à força dos músculos respiratórios, verificou-se relação significativa com o PImax e a PEmax em que a fraqueza ao nível dos músculos respiratórios contribuem para um menor valor de PCF. Relativamente aos valores da gasometria arterial, verificou-se relação entre o PCF e a PaO2 de forma positiva, em que doentes hipoxémicos apresentam menores valores de tosse, e a PaCO2, de forma negativa, em que os doentes hipercápnicos apresentam menores valores de PCF tendo sido verificada relação entre o PCF e o pH e sO2. Quanto à relação entre o número de internamentos por agudização da DPOC no último ano e o PCF verificou-se uma relação significativa, onde um menor valor de PCF contribui para uma maior taxa de internamento por agudização da DPOC. Conclusão: Este conjunto de conclusões corrobora a hipótese inicialmente formulada, de que o Peak Cough Flow se encontra diminuído nos indivíduos com Doença Pulmonar Obstrutiva Crónica onde a variação do PCF se encontra directamente relacionada com os parâmetros funcionais respiratórios, com a força dos músculos respiratórios e com os valores de gasometria arterial. ABSTRACT: Aims: Cough evaluation in Chronic Obstructive Pulmonary Disease (COPD) patients. Identify and determine the relation of the predictive factors that contribute to the cough capacity degradation in this type of patients. Type of study: Descriptive observational study of transversal nature. Case definition: The COPD diagnosis criteria are the clinical presentation and the gold standard to the COPD diagnosis- the Spirometry. Target Population: Every patients, with primary pathology of COPD diagnosed, who went to the respiratory function service of Viseu hospital to perform tests. Sampling Method: It was used a random sample constituted by all the, conscious and cooperating individuals, who complied with the inclusion criteria and who accepted to make part of this study. Sample size: A sample of 55 individuals that went to the respiratory function service between January and June 2009 to perform respiratory function tests. Study: The patients who accepted to make part of this study were submitted to a clinical data questionary and performed 5 tests: body mass index (BMI), respiratory functional study, arterial blood gas level, evaluation of respiratory muscles strength (maximal inspiratory pressure (MIP) and maximum expiratory pressure (MEP)), and Peak Cough Flow evaluation. Statistic Analysis: Were obtained characterizing data of the sample in study, and later correlated the value of the Peak Cough Flow with the results from the evaluation of the body mass index (BMI), the respiratory functional study the MIP and MEP, the arterial blood gas level and also with the ability to cough evaluation and the number of hospitalizations in the last year for COPD exacerbations. The values of correlation between the Peak Cough Flow and the other parameters were found. Results: After analyzing the results, were obtained the values of Peak Cough Flow for the population with COPD. There were decreased values compared with the population normal values, having been found higher values of PCF in males compared to female values. It was analyzed the relation between the PCF and the age, weight, height and BMI but no relation was found on account of the fact that the cough does not show a variation according to anthropometric parameters, such as the relation with spirometric values. As for the respiratory functional parameters were analyzed relations with the PCF. There were significant relations between the PCF and FEV1, the FVC, the PEF, presenting a positive relation, where higher values of these parameters are correlated with higher incidence of cough. Concerning the RAW and RV, the PCF has a negative relation, in which a higher airway resistance or in more hyperinflated patients, leads to lower values of PCF. On the other hand no correlation was found between the PCF and the FRC and TLC. Regarding the respiratory muscle strength, there was a significant relation with the MIP and MEP, in which the weakness at the level of respiratory muscles contribute to a lower value of PCF. For values of arterial blood gas level, there was no relation between the PCF and PaO2, in a positive way, in which patients with hypoxemia present lower values of cough, and PaCO2, in a negative way in which hypercapnic patients had lower values of PCF, having being founded a relation between the PCF and the pH and sO2. As for the relation between the number of hospitalizations for COPD exacerbation in the last year and the PCF was found a significant relation, in which a smaller value of PCF contributes to a higher rate of hospitalization for COPD exacerbation. Conclusion: This set of findings supports the hypothesis first formulated that Peak Cough Flow is decreased in individuals with Chronic Obstructive Pulmonary Disease, in which the variation of the PCF is directly related to the respiratory function parameters, the strength of respiratory muscles and the values of arterial blood gases.

Transfer factor for carbon monoxide: a glance behind the scene.

The transfer factor for carbon monoxide (TLCO) is widely used in pulmonary function laboratories because it represents a unique non-invasive window on pulmonary microcirculation. The TLCO is the product of two primary measurements, the alveolar volume (VA) and the CO transfer coefficient (KCO). This test is most informative when VA and KCO are examined, together with their product TLCO. In a normal lung, a low VA due to incomplete expansion is associated with an elevated KCO, resulting in a mildly reduced TLCO. Thus, in case of low VA, a seemingly "normal KCO" must be interpreted as an abnormal gas transfer. The most common clinical conditions associated with an abnormal TLCO are characterised by a limited number of patterns for VA and KCO: incomplete lung expansion, discrete loss of alveolar units, diffuse loss of alveolar units, emphysema, pulmonary vascular disorders, high pulmonary blood volume, alveolar haemorrhage.

Avaliação da cinemática do complexo tóracoabdominal durante repouso e endurance muscular respiratória em obesos

Background: Obesity may affect the respiratory system, causing changes in respiratory function and in the pulmonary volumes and flows. Objectives: To evaluate the influence of obesity in the movement of thoracoabdominal complex at rest and during maximal voluntary ventilation (MVV), and the contribution between the different compartments of this complex and the volume changes of chest wall between obese and non-obese patients. Materials and Methods: We studied 16 patients divided into two groups: the obese group (n = 8) and group non-obese (n = 8). The two groups were homogeneous in terms of spirometric characteristics (FVC mean: 4.97 ± 0.6 L - 92.91 ± 10.17% predicted, and 4.52 ± 0.6 L - 93.59 ± 8.05%), age 25.6 ± 5.0 and 26.8 ± 4.9 years, in non-obese and obese respectively. BMI was 24.93 ± 3.0 and 39.18 ± 4.3 kg/m2 in the groups investigated. All subjects performed breathing calm and slow and maneuver MVV, during registration for optoelectronic plethysmography. Statistical analysis: we used the unpaired t test and Mann-Whitney. Results: Obese individuals had a lower percentage contribution of the rib cage abdominal (RCa) during breathing at rest and VVM. The variation of end expiratory (EELV) and end inspiratory (EILV) lung volumes were lower in obese subjects. It has been found asynchrony and higher distortion between compartments of thoracoabdominal complex in obese subjects when compared to non-obese. Conclusions: Central obesity impairs the ventilation lung, reducing to adaptation efforts and increasing the ventilatory work

Efeitos do estímulo verbal sobre o desempenho no teste de escada e ajustes cardiorrespiratórios em sujeitos saudáveis

Esta pesquisa teve o objetivo de avaliar os efeitos do estímulo verbal (EV) no tempo do teste de escada (TEsc) e nas variáveis cardiorrespiratórias de adultos saudáveis. Trinta e um adultos saudáveis realizaram dois TEsc (com EV e sem EV). Antes e depois de cada teste, foram avaliados os sinais vitais e a Escala de Borg. Os tempos nos TEsc foram comparados por meio do Teste t de Student para amostras pareadas e as diferenças, de acordo com a ordem de realização dos testes utilizando o Teste de Mann-Whitney. Os sinais vitais e a Escala de Borg foram comparados por meio do Teste de Friedman ou ANOVA com post hoc do Teste de Tukey. As variações foram comparadas utilizando o Teste t Student para amostras independentes ou Teste de Mann-Whitney (p<0,05). O tempo no TEsc sem EV foi de 23,48±8,28 segundos, significativamente maior que o teste com EV, que foi de 21,60±7,18 segundos (p<0,05). Todas as variáveis aumentaram após os testes, e a Escala de Borg foi a única que teve maior variação no TEsc com EV, variando 2,5±1,4 no teste sem estímulo e 3,0±1,8 pontos no com estímulo (p<0,05). O estímulo verbal melhora o desempenho no TEsc e leva à maior sensação de esforço.

Comparison between actual and predicted postoperative stair-climbing test, walk test and spirometric values in patients undergoing lung resection

OBJETIVO: Verificar se os testes: Volume Expiratório Forçado no 1º segundo (VEF1), Teste de Caminhada de 6 minutos (TC6) e Teste de Escada (TE) se alteram proporcionalmente ao pulmão funcionante ressecado. MÉTODOS: Foram incluídos pacientes candidatos a toracotomia para ressecção pulmonar. No pré-operatório (pré) e no mínimo três meses após a cirurgia (pós), realizaram espirometria, TC6 e TE. O TE foi realizado em escada com 12,16m de altura. O tempo para subir todos os degraus o mais rápido possível foi chamado tempo de escada (tTE). Os cálculos dos valores dos testes preditos para o pós-operatório (ppo) foram realizados conforme o número de segmentos funcionantes perdidos. Os valores pré, ppo e pós foram comparados entre si para cada teste. Estatística: foi utilizada a análise de variância para medidas repetidas (ANOVA), com significância de 5%. RESULTADOS: Foram estudados 40 pacientes. A ressecção pulmonar variou desde o ganho de dois segmentos funcionantes até a perda de 9. Os valores pré, ppo e pós foram respectivamente: VEF1 -pré = 2,6±0,8L, ppo = 2,3±0,8L, pós = 2,3±0,8L (VEF1pré > VEF1ppo = VEF1pós), TC6-pré = 604±63m, ppo = 529±103m, pós = 599±74m (TC6pré = TC6pós > TC6ppo), tTE-pré = 32,9±7,6s, ppo = 37,8±12,1s, pós = 33,7±8,5s (tTEpré = tTEpós < tTEppo). CONCLUSÃO: Nas ressecções pulmonares, este grupo de pacientes perdeu função pulmonar medida através da espirometria, mas não perdeu a capacidade de exercício, medida através dos testes de escada e caminhada.

Paracoccidioidomicose: estudo radiológico e pulmonar de 58 casos

Spirometric and haemogasimetric tests were performed in 52 patients with unifocal and multifocal progressive Paracoccidioidomycosis pulmonary diseases, in 5 patients with juvenile and 1 female internal genital forms. The age ranged from 20 to 74 years old and the duration of disease from 3 to 25 years. Dyspnea, cough, tegumentary and lymphatic manifestations were the most predominant signs observed. Fourteen of them was developed Cor pulmonale. Impaired renal function was recorded in 19 patients, cardiac symptoms were described in 7 and hyporeactor adrenal activity was showed in 13 patients. Radiological studies demonstrated mild in 16, moderate in 24 and severe pulmonary lesions types in 18 patients. The pulmonary function revealed: normal spyrographic findings in 17, pure obstructive type in 32 and mixed form in 9 of them. Hyperventilation was described in 54 individuals and all of them showed an increasing of the alveolo-arterial difference. PaO2 less than 80 mm/Hg observed in 36 of them. Statistical analysis demonstrated significative association between clinical evolution and radiological interpretation. Similar data were obtained in radiology evaluations, clinical evolutive studies and pulmonary functions described in these patients. The granulomatous reaction due to Paracoccidioidomycosis, in heavy smokers patients, gave origin to the alterations in small airways predisposing the interalveolar dissemination an impaired alveolo-arterial diffusion.

Assessment of vitamin A status in chronic obstructive pulmonary disease patients and healthy smokers

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

Acurácia do teste de escada utilizando o consumo máximo de oxigênio como padrão-ouro

Objective: To determine the accuracy of the variables related to the fixed-height stair-climbing test (SCT) using maximal oxygen uptake (V̇O 2 max) as the gold standard. Methods: The SCT was performed on a staircase consisting of 6 flights (72 steps; 12.16 m total height), with verbal encouragement, in 51 patients. Stair-climbing time was measured, the variables 'work' and 'power' also being calculated. The V̇O2 max was measured using ergospirometry according to the Balke protocol. We calculated the Pearson linear correlation (r), as well as the values of p, between the SCT variables and V̇O2 max. To determine accuracy, the V̇O 2 max cut-off point was set at 25 mL/kg/min, and individuals were classified as normal or altered. The cut-off points for the SCT variables were determined using the receiver operating characteristic curve. The Kappa statistic (k) was used in order to assess concordance. Results: The following values were obtained for the variable 'time': cut-off point = 40 s; mean = 41 ± 15.5 s; r = -0.707; p < 0.005; specificity = 89%; sensibility = 83%; accuracy = 86%; and k = 0.724. For 'power', the values obtained were as follows: cut-off point = 200 w; mean = 222.3 ± 95.2 w; r = 0.515; p < 0.005; specificity = 67%; sensibility= 75%; accuracy = 71%; and k = 0.414. Since the correlation between the variable 'work' and V̇O2 max was not significant, that variable was discarded. Conclusion: Of the SCT variables tested, using V̇O2 max as the gold standard, the variable 'time' was the most accurate.

Effects of active smoking on airway and systemic inflammation profiles in patients with chronic obstructive pulmonary disease

Background: The markers that characterize local and systemic inflammation in chronic obstructive pulmonary disease (COPD) remain unclear, as do their correlations with smoking status and presence of disease. The aim of this study was to assess markers of inflammation in the peripheral blood and airways of current smokers without COPD, of current smokers with COPD and of ex-smokers with COPD. METHODS: In this study, 17 current smokers with COPD (mean age: 58.2 ± 9.6 years; mean forced expiratory volume in 1 second [FEV1]: 56.1 ± 15.9%), 35 ex-smokers with COPD (mean age: 66.3 ± 7.3 years; mean FEV1: 47.9 ± 17.2%) and 20 current smokers without COPD (mean age: 49.1 ± 6.2 years; mean FEV1: 106.5 ± 15.8%) were evaluated. Spirometry findings, body composition and serum/induced sputum concentrations of tumor necrosis factor α (TNF-α), interleukin (IL)-6, IL-8 and IL-10, together with serum C-reactive protein (CRP) levels, were assessed. RESULTS: Serum TNF-α concentration was higher in all current smokers than in ex-smokers with COPD. In current smokers without COPD, serum CRP level was lower than in ex-smokers with COPD and significantly lower than in current smokers with COPD. Sputum TNF-α concentration was higher in current and ex-smokers with COPD than in current smokers without COPD. Multiple regression analyses showed that serum TNF-α was associated with active smoking, and serum CRP and sputum TNF-α were associated with COPD diagnosis. CONCLUSIONS: Smoking is associated with higher systemic inflammation in patients with COPD. Current findings also support the hypothesis that smoking and COPD have different effects on the regulation of airway and systemic inflammatory processes. © 2013 Lippincott Williams and Wilkins.

Correlação entre os resultados pré-operatórios de testes cardiopulmonares e a evolução pós-operatória em cirurgia bariátrica

Pós-graduação em Bases Gerais da Cirurgia - FMB

Immunophenotyping and extracellular matrix remodeling in pulmonary and extrapulmonary sarcoidosis

Objective: To investigate the significance of cellular immune markers, as well as that of collagen and elastic components of the extracellular matrix, within granulomatous structures in biopsies of patients with pulmonary or extrapulmonary sarcoidosis. Methods: We carried out qualitative and quantitative evaluations of inflammatory cells, collagen fibers, and elastic fibers in granulomatous structures in surgical biopsies of 40 patients with pulmonary and extrapulmonary sarcoidosis using histomorphometry, immunohistochemistry, picrosirius red staining, and Weigert's resorcin-fuchsin staining. Results: The extrapulmonary tissue biopsies presented significantly higher densities of lymphocytes, macrophages, and neutrophils than did the lung tissue biopsies. Pulmonary granulomas showed a significantly higher number of collagen fibers and a lower density of elastic fibers than did extrapulmonary granulomas. The amount of macrophages in the lung samples correlated with FVC (p < 0.05), whereas the amount of CD3+, CD4+, and CD8+ lymphocytes correlated with the FEV1/FVC ratio and VC. There were inverse correlations between TLC and the CD1a+ cell count (p < 0.05), as well as between DLCO and collagen/elastic fiber density (r = -0.90; p = 0.04). Conclusions: Immunophenotyping and remodeling both showed differences between pulmonary and extrapulmonary sarcoidosis in terms of the characteristics of the biopsy samples. These differences correlated with the clinical and spirometric data obtained for the patients, suggesting that two different pathways are involved in the mechanism of antigen clearance, which was more effective in the lungs and lymph nodes.

Extracellular matrix composition in COPD

Extracellular matrix (ECM) composition has an important role in determining airway structure. We postulated that ECM lung composition of chronic obstructive pulmonary disease (COPD) patients differs from that observed in smoking and nonsmoking subjects without airflow obstruction. We determined the fractional areas of elastic fibres, type-I, -III and -IV collagen, versican, decorin, biglycan, lumican, fibronectin and tenascin in different compartments of the large and small airways and lung parenchyma in 26 COPD patients, 26 smokers without COPD and 16 nonsmoking control subjects. The fractional area of elastic fibres was higher in non-obstructed smokers than in COPD and nonsmoking controls, in all lung compartments. Type-I collagen fractional area was lower in the large and small airways of COPD patients and in the small airways of non-obstructed smokers than in nonsmokers. Compared with nonsmokers, COPD patients had lower versican fractional area in the parenchyma, higher fibronectin fractional area in small airways and higher tenascin fractional area in large and small airways compartments. In COPD patients, significant correlations were found between elastic fibres and fibronectin and lung function parameters. Alterations of the major ECM components are widespread in all lung compartments of patients with COPD and may contribute to persistent airflow obstruction.

Imunofenotipagem e remodelamento da matriz extracelular na sarcoidose pulmonar e extrapulmonar

OBJETIVO: Investigar o significado de marcadores de imunidade celular e de componentes elásticos/colágeno da matriz extracelular em estruturas granulomatosas em biópsias de pacientes com sarcoidose pulmonar ou extrapulmonar. MÉTODOS: Determinações qualitativas e quantitativas de células inflamatórias, de fibras de colágeno e de fibras elásticas em estruturas granulomatosas em biópsias cirúrgicas de 40 pacientes com sarcoidose pulmonar e extrapulmonar foram realizadas por histomorfometria, imuno-histoquímica, e técnicas de coloração com picrosirius e resorcina-fucsina de Weigert. RESULTADOS: A densidade de linfócitos, macrófagos e neutrófilos nas biópsias extrapulmonares foi significativamente maior do que nas biópsias pulmonares. Os granulomas pulmonares apresentaram uma quantidade significativamente maior de fibras de colágeno e menor densidade de fibras elásticas que os granulomas extrapulmonares. A quantidade de macrófagos nos granulomas pulmonares correlacionou-se com CVF (p < 0,05), ao passo que as quantidades de linfócitos CD3+, CD4+ e CD8+ correlacionaram-se com a relação VEF1/CVF e com CV. Houve correlações negativas entre CPT e contagem de células CD1a+ (p < 0,05) e entre DLCO e densidade de fibras colágenas/elásticas (r = -0,90; p = 0,04). CONCLUSÕES: A imunofenotipagem e o remodelamento apresentaram características diferentes nas biópsias dos pacientes com sarcoidose pulmonar e extrapulmonar. Essas diferenças correlacionaram-se com os dados clínicos e espirométricos dos pacientes, sugerindo que há duas vias envolvidas no mecanismo de depuração de antígenos, que foi mais eficaz nos pulmões e linfonodos.