Panbronquiolite difusa: uma doença subdiagnosticada? Estudo de quatro casos no Brasil

BACKGROUND: Diffuse panbronchiolitis is a clinical pathologic condition characterized by chronic inflammation of respiratory bronchioles, with clinical features that position it as a differential diagnosis among the sinopulmonary syndromes. METHODS AND RESULTS: We present 4 cases (1 Black, 2 Japanese descendants, and 1 Japanese), living in Brazil, in which the diagnosis was made by the clinical and radiological features and confirmed by transbronchial biopsy. The clinical findings included chronic sinusitis, productive cough, rhonchi, and wheezes. The pulmonary function tests showed an obstructive pattern. High resolution computerized tomography showed a diffuse nodular pattern, airway ectasia, and airway wall thickening. The biopsy showed interstitial accumulation of foam cells and lymphoid cells in the walls of respiratory bronchioles: 2 of our cases had bronchus-associated lymphoid tissue hyperplasia. We searched for the HLA Bw54 in all of our patients, but only 1 was positive. A low dose macrolide treatment was introduced, resulting in with clinical and functional improvement. A score that rated the extent of nodules, airway ectasia, mucus plugging, and airway wall thickening was applied on pre- and post-treatment High resolution computerized tomography results, revealing an improvement in tomographic pattern related to that observed in the pulmonary function tests. CONCLUSION: We conclude that diffuse panbronchiolitis is a systemic disease that is not exclusive to the Asian population, whose clinical and radiological features should be better known by occidental pulmonary physicians.INTRODUÇÃO: A Panbronquiolite Difusa é uma entidade clínico-patológica caracterizada pela inflamação crônica dos bronquíolos respiratórios e que, clinicamente, apresenta-se como diagnóstico diferencial das síndromes sino-pulmonares. MÉTODOS E RESULTADOS: Apresentamos 4 casos (um negro, dois descendentes de japoneses e um japonês), que moram no Brasil, nos quais a suspeita diagnóstica se baseou nos aspectos clínicos e radiológicos e foi confirmada através da biópsia transbrônquica. As principais características clínicas eram sinusite crônica, tosse produtiva, além da presença de roncos e sibilos. Os testes de função pulmonar evidenciaram um padrão obstrutivo. A tomografia de tórax de alta resolução demonstrou um padrão nodular difuso, além de ectasia e espessamento das paredes das vias aéreas. O exame histológico evidenciou acúmulo intersticial de macrófagos xantomatosos e infiltração de linfócitos na região dos bronquíolos respiratórios, sendo que 2 de nossos casos ainda apresentaram hiperplasia de tecido linfocitário associado aos brônquios. Investigamos a presença do HLA Bw54 nos quatro casos, sendo apenas um positivo. Após o diagnóstico, instituiu-se o tratamento com macrolídeos em dose baixa, tendo como resultado melhora clínica e funcional. Um escore que avalia a extensão do padrão nodular, a ectasia e o espessamento das vias aéreas e ainda o grau de impactação mucóide visíveis à tomografia foi utilizado pré e pós tratamento evidenciando uma melhora compatível com a observada à função pulmonar. CONCLUSÃO: Concluímos que a Panbronquiolite Difusa é uma doença sistêmica, não exclusiva da população oriental, cujas características clínicas e radiológicas devem ser melhor conhecidas pelos médicos ocidentais

Desaturation – distance ratio: a new concept for a functional assessment of interstitial lung diseases

INTRODUCTION: The functional evaluation has become increasingly important in the understanding and management of patients with interstitial lung diseases. The cardiopulmonary exercise test and the six-minute walk test (6MWT), through their isolated variables, have been used to do this evaluation, with some limitations. OBJECTIVES: We proposed a new composite index (desaturation distance ratio using continuous peripheral oxygen saturation (SpO2) and the distance walked as a more reliable tool for doing a functional evaluation of these patients. METHODS: 6MWT was performed by interstitial lung diseases patients and controls. Analyzed parameters were walked distance and desaturation area (DAO2), obtained by taking the difference between maximal SpO2 possible (100%) and patient's SpO2 every 2 seconds. desaturation distance ratio was calculated using the ratio between DAO2 and distance walked. RESULTS: Forty-nine interstitial lung diseases patients and 11 control subjects completed the protocol. The mean (SD) age was 60 (12) years and 65 (9) years, respectively (p:NS). Data obtained from 6MWT showed a significant statistical difference between interstitial lung diseases patients and controls: mean walked distance (430 and 602 meters, respectively); SpO2 minimal maintained at least 10 seconds - SpO2 min (85% and 94%, respectively), and median desaturation distance ratio (10 and 2.5, respectively). A correlation analysis, considering interstitial lung diseases patients, revealed the best correlation between desaturation distance ratio and DLco (r= - 0.72; p<0.001), being the correlation between SpO2 min and DLco of 0.61 (p<0.001) and among walked distance and DLco of 0.58 (p<0.05). CONCLUSION: Desaturation distance ratio is a promising concept and a more reliable physiologic tool to assess pulmonary diseases characterized by involvement of the alveolar-capillary membrane, such as interstitial lung diseases

Lymphatic fluctuation in the parenchymal remodeling stage of acute interstitial pneumonia, organizing pneumonia, nonspecific interstitial pneumonia and idiopathic pulmonary fibrosis

Because the superficial lymphatics in the lungs are distributed in the subpleural, interlobular and peribroncovascular interstitium, lymphatic impairment may occur in the lungs of patients with idiopathic interstitial pneumonias (IIPs) and increase their severity. We investigated the distribution of lymphatics in different remodeling stages of IIPs by immunohistochemistry using the D2-40 antibody. Pulmonary tissue was obtained from 69 patients with acute interstitial pneumonia/diffuse alveolar damage (AIP/DAD, N = 24), cryptogenic organizing pneumonia/organizing pneumonia (COP/OP, N = 6), nonspecific interstitial pneumonia (NSIP/NSIP, N = 20), and idiopathic pulmonary fibrosis/usual interstitial pneumonia (IPF/UIP, N = 19). D2-40+ lymphatic in the lesions was quantitatively determined and associated with remodeling stage score. We observed an increase in the D2-40+ percent from DAD (6.66 +/- 1.11) to UIP (23.45 +/- 5.24, P = 0.008) with the advanced process of remodeling stage of the lesions. Kaplan-Meier survival curves showed a better survival for patients with higher lymphatic D2-40+ expression than 9.3%. Lymphatic impairment occurs in the lungs of IIPs and its severity increases according to remodeling stage. The results suggest that disruption of the superficial lymphatics may impair alveolar clearance, delay organ repair and cause severe disease progress mainly in patients with AIP/DAD. Therefore, lymphatic distribution may serve as a surrogate marker for the identification of patients at greatest risk for death due to IIPs.CNPqCNPqFAPESP [07/52785-0, 08/53022-3, 08/57130-5]FAPESPLaboratorio Diagnostika, Hospital das Clinicas and Faculdade de Medicina, Universidade de Sao PauloLaboratorio Diagnostika, Hospital das Clinicas and Faculdade de Medicina, Universidade de Sao Paul