Evaluation of the histological parameters in usual interstitial pneumonia (idiopathic pulmonary fibrosis)

Idiopathic pulmonary fibrosis (cryptogenic fibrosing alveolitis) is a progressive interstitial pulmonary disease of unknown etiology. Since Hamman's and Rich's (1944) reports, many studies have tried to find a histological marker for the correlation between prognosis and response to therapy. However, there are many doubts regarding pathogenesis. In addition, it is generally accepted that response to therapy is related to the relative degree of cellularity and fibrosis. The purpose of this study is to describe the results of inflammatory/exudative changes, fibrotic/reparative changes, and airway alterations, using a semi-quantitative method by independent evaluation of two pathologists, in 24 open lung biopsies with the diagnosis of idiopathic pulmonary fibrosis. Fourteen histological features were analyzed using the 0 to 5 scale for interstitial alterations and the 0 to 2 scale for the airway changes. There was significant interobserver agreement for all histological features with Kw (Kappa) variations between 0.47 and 0.92. There was significant disagreement only for septal inflammatory intensity analysis, suggesting that these features must be discussed by the pathologists. The semi-quantitative method assessment was effective.A fibrose pulmonar idiopática (alveolite fibrosante criptogênica) é uma doença pulmonar intersticial progressiva de etiologia desconhecida, morfologicamente reconhecida como pneumonia intersticial usual. Desde a publicação de Hamman e Rich (1944) até os dias atuais, uma das grandes preocupações foi a tentativa de encontrar um marcador histológico para correlacionar com prognóstico e resposta terapêutica. A busca desta situação não tem sido muito alentadora, pois existem vários pontos duvidosos na patogênese desta doença. Admite-se que a resposta terapêutica desta entidade se relaciona com a celularidade e fibrose presentes no tecido. A proposta deste estudo é descrever os resultados de método semiquantitativo segundo a avaliação independente de dois patologistas, das alterações exsudativo-inflamatórias, reparativo-fibróticas e de vias aéreas, em 24 pacientes com diagnóstico de fibrose pulmonar idiopática, submetidos à biópsia a céu aberto. Foram analisados 14 parâmetros histológicos segundo escala de 0 a 5 para as alterações intersticiais e de 0 a 2 para o comprometimento de vias aéreas e de espaços aéreos. Da análise independente realizada pelos dois observadores constatou-se concordância significante em todas as variáveis histológicas com Kw (teste de Kappa) indo de 0,47 a 0,92. Apenas na análise da intensidade da inflamação septal as discordâncias também foram significantes, sugerindo que para este parâmetro a percentagem de comprometimento tecidual deve ser previamente discutida entre os observadores. O método utilizado demonstrou ser rápido e eficiente.Universidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PatologiaUNIFESP, EPM, Depto. de PatologiaSciEL

Diagnóstico tardio da sarcoidose é comum no Brasil

OBJECTIVE:To determine the frequency of and the factors related to delayed diagnosis of sarcoidosis in Brazil.METHODS:We evaluated patients with a biopsy-proven diagnosis of sarcoidosis, using a questionnaire that addressed the following: time since symptom onset and since the first medical visit; and the number and specialty of the physicians visited. We divided the patients by the timeliness of the diagnosis-timely (< 6 months) and delayed (≥ 6 months)-comparing the two groups in terms of systemic and pulmonary symptoms; extrathoracic involvement; spirometric data; radiological staging; level of education; income; and tuberculosis (diagnosis and treatment).RESULTS:We evaluated 100 patients. The median number of physicians consulted was 3 (range, 1-14). In 11 cases, sarcoidosis was diagnosed at the first visit. In 54, the first physician seen was a general practitioner. The diagnosis of sarcoidosis was timely in 41 patients and delayed in 59. The groups did not differ in terms of gender; race; type of health insurance; level of education; income; respiratory/systemic symptoms; extrathoracic involvement; and radiological staging. In the delayed diagnosis group, FVC was lower (80.3 ± 20.4% vs. 90.5 ± 17.1%; p = 0.010), as was FEV1 (77.3 ± 19.9% vs. 86.4 ± 19.5%; p = 0.024), misdiagnosis with and treatment for tuberculosis (≥ 3 months) also being more common (24% vs. 7%, p = 0.032, and 20% vs. 0%; p = 0.002, respectively).CONCLUSIONS:The diagnosis of sarcoidosis is often delayed, even when the imaging is suggestive of sarcoidosis. Delayed diagnosis is associated with impaired lung function at the time of diagnosis. Many sarcoidosis patients are misdiagnosed with and treated for tuberculosis.OBJETIVO:Avaliar a frequência do diagnóstico tardio de sarcoidose no Brasil e os fatores relacionados a esse atraso.MÉTODOS:Avaliamos pacientes com diagnóstico de sarcoidose confirmado por biópsia utilizando um questionário que abordava o tempo entre o início dos sintomas e a data da primeira consulta médica; e o número e especialidades dos médicos consultados. Sintomas sistêmicos e pulmonares, envolvimento extratorácico, dados espirométricos, estadiamento radiológico, escolaridade, renda individual e diagnóstico/tratamento de tuberculose foram comparados entre os pacientes com diagnóstico precoce (< 6 meses até o diagnóstico) e tardio (≥ 6 meses).RESULTADOS:Foram incluídos 100 pacientes. A mediana do número de médicos consultados foi 3 (variação: 1-14). O diagnóstico de sarcoidose foi feito na primeira consulta em 11 casos. Um clínico geral foi inicialmente consultado em 54 casos. O diagnóstico de sarcoidose foi precoce em 41 casos e tardio em 59. Não houve diferença entre os grupos no tocante ao gênero, raça, tipo de seguro saúde, escolaridade, renda, sintomas sistêmicos e respiratórios, envolvimento extratorácico e estadiamento radiológico. Os pacientes com diagnóstico tardio apresentavam menor CVF (80,3 ± 20,4% vs. 90,5 ± 17,1%; p = 0,010) e VEF1 (77,3 ± 19,9% vs. 86,4 ± 19,5%; p = 0,024), além de mais frequentemente receberem diagnóstico de tuberculose (24% vs. 7%; p = 0,032) e tratamento para tuberculose (≥ 3 meses; 20% vs. 0%; p = 0,002).CONCLUSÕES:O diagnóstico de sarcoidose é tardio em muitos casos, mesmo quando há achados de imagem sugestivos. O diagnóstico tardio está associado a menor função pulmonar na época do diagnóstico. Vários pacientes com sarcoidose recebem diagnóstico e tratamento de tuberculose.São Paulo Hospital for State Civil Servants Department of Respiratory DiseasesFederal University of São Paulo Department of PathologyFederal University of São PauloUNIFESP, Department of PathologyUNIFESPSciEL

Airway-centered interstitial fibrosis: etiology, clinical findings and prognosis

Background: Airway-centered Interstitial Fibrosis (ACIF) is a common pathologic pattern observed in our practice.Objectives: the objectives of this study are to describe the causes associated with ACIF in a large sample of patients and its effect on survival.Methods: A retrospective study in three centers of interstitial lung disease in São Paulo, between January of 1995 and December of 2012. the surgical lung biopsy specimens were reviewed by three pathologists. the clinical, functional and tomographic findings were analyzed by a standardized protocol.Results: There were 68 cases of ACIF, most of them women. the mean age was 57 +/- 12 yr. Dyspnea, cough, restrictive pattern at spirometry and oxygen desaturation at exercise were common. A reticular pattern with peribronchovascular infiltrates was found in 79% of the cases. the etiologies of ACIF were hypersensitivity pneumonitis in 29 (42.6%), gastroesophageal reflux disease in 17 (25.0%), collagen vascular disease in 4 (5.9%), a combination of them in 15 cases and idiopathic in 3 (4.4%). the median survival was 116 months (95% CI = 58.5 - 173.5). Lower values of oxygen saturation at rest, presence of cough and some histological findings - organizing tissue in the airways, fibroblastic foci and microscopic honeycombing - were predictors of worse survival.Conclusions: ACIF is an interstitial lung disease with a better survival when compared with IPF. the main etiologies are HP and GERD. the oxygen saturation at rest, the presence of cough and some histological findings are predictors of survival.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)Universidade Federal de São Paulo, Dept Pulm, São Paulo, BrazilMayo Clin, Dept Pathol, Scottsdale, AZ USAUniversidade Federal de São Paulo, Dept Pathol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pulm, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pathol, São Paulo, BrazilWeb of Scienc

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia accompanied by airflow obstruction

Diffuse idiopathic pulmonary neuroendocrine cell hyperplasia with airflow obstruction is a rare form of lung injury. All of the reported cases have been diagnosed by surgical lung biopsy. Only three of the reported cases presented with diffuse interstitial lung opacities on HRCT scans. We report three additional cases of this entity. All of the patients were female and presented with mild-to-moderate airflow obstruction. In the first case, transbronchial biopsy and imaging data were sufficient to make the diagnosis. Although the HRCT scans of all three cases revealed a mosaic pattern, that of the third patient also revealed diffuse interstitial infiltrate. In extremely rare cases, HRCT findings can simulate those seen in other interstitial lung diseases.A hiperplasia de células neuroendócrinas pulmonares difusas com obstrução ao fluxo aéreo é uma lesão pulmonar rara. Todos os casos publicados foram diagnosticados por biópsia pulmonar cirúrgica. Apenas três casos relatados apresentavam opacidades intersticiais difusas na TCAR. Nós relatamos três casos adicionais desta entidade. Todos eram mulheres, com obstrução leve ou moderada ao fluxo aéreo. No primeiro caso, uma biópsia transbrônquica, associada com dados de imagem foram considerados suficientes para o diagnóstico. Um padrão em mosaico foi observado nos três casos, mas no terceiro um infiltrado pulmonar difuso foi também observado. Em casos muito raros, o aspecto na TCAR pode simular aquele encontrado em outras doenças pulmonares intersticiais.Universidade Federal de São Paulo (UNIFESP) Departamento de PatologiaHospital do Servidor Público EstadualHospital do Servidor Publico Estadual Serviço de PneumologiaUniversidade Federal de São Paulo (UNIFESP)Hospital de MessejanaHospital Beneficiência Portuguesa Centro Integrado de PatologiaUNIFESP, Depto. de PatologiaUNIFESPSciEL

Survival in idiopathic pulmonary fibrosis - cytotoxic agents compared to corticosteroids

Study objective: To compare the survival of patients with IPF treated retrospectively with corticosteroids atone, to survival of patients treated with immunosuppressive and corticosteroids combined. Design: Non-randomized retrospective cohort study.Setting: Three tertiary centers in Brazil.Patients: Eighty-two IPF patients were included. the diagnosis was confirmed by open lung biopsy in 48. Patients received either corticosteroids alone (group 1) or cytotoxic agents in addition to corticosteroids (group 11).Measurements and results: the primary end-point was mortality. Secondary outcome included longitudinal changes in FVC. Mean age was 66+8 years. FVC was 71 +/- 17% of predicted. There were 48 deaths during the study period (59%), 44 secondary to respiratory causes. From preliminary univariate analysis, for the group as a whole, worse survival was found to be associated with FVC% = 70% and = 70% (Log Rank = 6.84, P = 0.009).Conclusions: the combination of immunosuppressive agents and prednisone results in better survival when compared to prednisone alone in patients with IPF the benefit seems to occur only in patients with less severe disease, as reflected by FVC >= 70%. (c) 2005 Elsevier B.V. All rights reserved.Universidade Federal de São Paulo, Dept Pulmonol, Paulista Sch Med, BR-04082001 São Paulo, BrazilUniversidade Federal de São Paulo, Dept Pulmonol, Paulista Sch Med, BR-04082001 São Paulo, BrazilWeb of Scienc

Subacute and chronic hypersensitivity pneumonitis: Histopathological patterns and survival

Background: in hypersensitivity pneumonitis (HP), survival can be predicted on the basis of the severity of fibrosis in surgical lung biopsy, but few data are available on the influence of clinical, functional, tomographic and histologic findings on prognosis. Objectives: To describe the impact on survival. of clinical data, histological patterns, and HRCT findings in subacute/chronic HP.Methods: A retrospective analysis of 103 patients diagnosed with HP submitted to surgical lung biopsy. Chronic HP was characterized by HRCT findings indicative of fibrosis (n = 76).Results: the most relevant exposures were to molds and birds. Lung biopsies revealed typical HP with granulomas in 46 patients, bronchiolocentric interstitial pneumonia in 27, and nonspecific interstitial pneumonia (NSIP) in 16. By univariate analysis, several findings were predictors of mortality: older age, mate sex, velcro crackles, higher FEV(1)/FVC ratio, lower oxygen saturation during exercise, and absence of mosaic pattern/air trapping and presence of fibrosis on HRCT. By multivariate analysis, remained significant: age (p = 0.007), oxygen saturation during exercise (p = 0.003), and mosaic pattern/air trapping on HRCT (p = 0.004). Patients with NSIP had a greater survival than did those with typical histology and those with bronchiolocentric pneumonia (p = 0.033).Conclusions: A wide range of histological features are found in FIR Typical findings are seen in 45% of cases, Other common patterns are NSIP and centriacinar lesions. Survival is better in patients with NSIP and worse in those with older age, desaturation during exercise, and absence of mosaic pattern/air trapping on HRCT. (c) 2009 Etsevier Ltd. All rights reserved.Universidade Federal de São Paulo, Div Resp Dis, Dept Med, Escola Paulista Med, BR-04023062 São Paulo, BrazilHosp Servidor Publ Estadual, Div Resp Dis, Dept Med, BR-04023062 São Paulo, BrazilUniversidade Federal de São Paulo, Div Resp Dis, Dept Med, Escola Paulista Med, BR-04023062 São Paulo, BrazilWeb of Scienc

Highlights of the Brazilian Thoracic Association guidelines for interstitial lung diseases

Interstitial lung diseases (ILDs) are heterogeneous disorders, involving a large number of conditions, the approach to which continues to pose an enormous challenge for pulmonologists. The 2012 Brazilian Thoracic Association ILD Guidelines were established in order to provide Brazilian pulmonologists with an instrument that can facilitate the management of patients with ILDs, standardizing the criteria used for the diagnosis of different conditions and offering guidance on the best treatment in various situations. The objective of this article was to briefly describe the highlights of those guidelines.As doenças pulmonares intersticiais (DPIs) são afecções heterogêneas, envolvendo um elevado número de condições, cuja abordagem ainda é um grande desafio para o pneumologista. As Diretrizes de DPIs da Sociedade Brasileira de Pneumologia e Tisiologia, publicadas em 2012, foram estabelecidas com o intuito de fornecer aos pneumologistas brasileiros um instrumento que possa facilitar a abordagem dos pacientes com DPIs, padronizando-se os critérios utilizados para a definição diagnóstica das diferentes condições, além de orientar sobre o melhor tratamento nas diferentes situações. Esse artigo teve como objetivo descrever resumidamente os principais destaques dessas diretrizes.Universidade de São Paulo Faculdade de Medicina Hospital das ClínicasUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Curso de Pós-Graduação de Doenças Pulmonares IntersticiaisUniversidade Federal de Ciências da Saúde de Porto AlegreSanta Casa de Porto Alegre Ambulatório de Doenças IntersticiaisSES Hospital Regional da Asa Norte Serviço de Doenças TorácicasFundação Jorge Duprat Figueiredo de Segurança e Medicina do Trabalho Serviço de MedicinaUniversidade Estadual de Campinas Faculdade de Ciências Médicas Departamento de Clínica MédicaUniversidade Federal do Estado do Rio de JaneiroUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de Medicina Departamento de PatologiaHospital do Servidor Público Estadual de São Paulo Serviço de Anatomia PatológicaUniversidade Federal de São Paulo (UNIFESP) Escola Paulista de MedicinaUniversidade de São Paulo Faculdade de Medicina de Ribeirão Preto Divisão de PneumologiaUniversidade Federal de Santa Catarina Departamento de Clínica MédicaUniversidade Federal de Santa Catarina Hospital UniversitárioHospital de Messejana Ambulatório de Doenças IntersticiaisHospital do Servidor Público Estadual de São Paulo Ambulatório de Doenças IntersticiaisUniversidade de São Paulo Faculdade de Medicina Instituto do CoraçãoUniversidade Federal FluminenseUniversidade de São Paulo Faculdade de MedicinaHospital Sírio Libanês Núcleo Avançado de TóraxUniversidade Federal da BahiaHospital do Servidor Público Estadual de São PauloHospital do Câncer Antônio Cândido CamargoUNIFESP, EPM, Curso de Pós-Graduação de Doenças Pulmonares IntersticiaisUNIFESP, EPM, Depto. de PatologiaUNIFESP, EPMSciEL