Imunomarcação não homogênea das membranas hialinas na sindrome da angustia respiratório do adulto pulmonar, extrapulmonar e idiopática

PURPOSE: To determine the nature of hyaline membranes in different manifestations of diffuse alveolar damage, [pulmonary and extrapulmonary acute respiratory distress syndrome], and idiopathic [acute interstitial pneumonia]. MATERIALS AND METHODS: Pulmonary specimens were obtained from 17 patients with acute respiratory distress syndrome and 9 patients with acute interstitial pneumonia. They were separated into 3 different groups: (a) pulmonary diffuse alveolar damage (pDAD) (n = 8), consisting only of pneumonia cases; (b) extrapulmonary diffuse alveolar damage (expDAI) (n = 9), consisting of sepsis and septic shock cases; and (c) idiopathic diffuse alveolar damage (iDAD) (n = 9), consisting of idiopathic cases (acute interstitial pneumonia). Hyaline membranes, the hallmark of the diffuse alveolar damage histological pattern, were examined using various kinds of antibodies. The antibodies used were against surfactant apoprotein-A (SP-A), cytokeratin 7 (CK7), cytokeratin 8 (CK8), alpha smooth muscle actin (a-SMA), cytokeratin AE1/AE3 (AE1/AE3), and factor VIII-related antigen (factor VIII). RESULTS: Pulmonary diffuse alveolar damage showed the largest quantity of hyaline membranes (12.65% ± 3.24%), while extrapulmonary diffuse alveolar damage (9.52% ± 3.64%) and idiopathic diffuse alveolar damage (7.34% ± 2.11%) showed intermediate and lower amounts, respectively, with the difference being statistically significant between pulmonary and idiopathic diffuse alveolar damage (P < 0.05). No significant difference was found for hyaline membranes Sp-A immunostaining among pulmonary (15.36% ± 3.12%), extrapulmonary (16.12% ± 4.58%), and idiopathic (13.74 ± 4.20%) diffuse alveolar damage groups. Regarding factor VIII, we found that idiopathic diffuse alveolar damage presented larger amounts of immunostained hyaline membranes (14.12% ± 6.25%) than extrapulmonary diffuse alveolar damage (3.93% ± 2.86%), with this difference being statistically significant (P < 0.001). Equally significant was the difference for progressive decrease of cytokeratin AE1/AE3 immunostaining in hyaline membranes present in the extrapulmonary diffuse alveolar damage (5.42% ± 2.80%) and idiopathic diffuse alveolar damage (0.47% ± 0.81%) groups (P < 0.001). None of the groups stained for cytokeratin CK-7, CK-8, vimentin, or a anti-smooth muscle actin. CONCLUSIONS: This study showed that only the epithelial/endothelial components (SP-A, factor VIII, and AE1/AE3) of the alveolar/capillary barrier are present in hyaline membranes formation in the 3 groups of patients with diffuse alveolar damage. The significant difference in the expression of factor VIII-related antigen and cytokeratin AE1/AE3 in the expDA versus iDAD groups as well as the significant difference in the amount of hyaline membranes present in the pDAD versus iDAD groups are suggestive of a local and specific lesion with different pathways (direct, indirect, or idiopathic), depending on the type of diffuse alveolar damage.OBJETIVO: Determinar a natureza da membrana hialina nas diferentes manifestações do dano alveolar difuso [pulmonar e extrapulmonar síndrome do desconforto respiratório] e idiopático [pneumonia intersticial aguda]. MATERIAIS E MÉTODOS: Espécimes pulmonares foram obtidos de 17 pacientes com SDRA e 9 pacientes com pneumonia intersticial aguda e separados em três diferentes grupos: (a) dano alveolar difuso pulmonar (DADp) (n=8) constituído por casos de pneumonia, (b) dano alveolar difuso extrapulmonar (DADexp) (n=9) constituído por casos de sepse e choque séptico e (c) dano alveolar difuso idiopático (DADi) (n=9) constituído por casos idopáticos (ou pneumonia intersticial aguda). As características das membranas hialinas do padrão histológico de dano alveolar difuso foram examinadas usando vários tipos de anticorpos. Os anticorpos usados foram surfactante apoproteina A (SP-A), anti-citokeratina 7 (CK7), citokeratina 8 (CK8), alfa actina de músculo liso (a-SMA), citokeratina AE1/AE3 (AE1/AE3) e antígeno relacionado ao fator VIII (Fator VIII). RESULTADOS: Observaram-se aumentos maiores da quantidade de membrana hialina no dano alveolar difuso pulmonar (12.65 ± 3.24%), intermediários no dano alveolar difuso extrapulmonar (9.52 ± 3.64%) e baixos no dano alveolar difuso idiopático (7.34 ± 2.11%) respectivamente, esta diferencia foi estatística significante entre o dano alveolar difuso pulmonar e o dano alveolar difuso idiopático (

Causas de óbito por pneumonia intersticial secundária em autópsias pulmonares de pacientes imunocomprometidos

PURPOSE: To present the more frequent associations found in autopsies of immunocompromised patients who developed secondary interstitial pneumonia as well as the risk of death (odds ratio) in having specific secondary interstitial pneumonia according to the cause of immunocompromise. METHOD: From January 1994 to March 2004, 17,000 autopsies were performed at Hospital das Clínicas, São Paulo University Medical School. After examining the pathology report review, we selected 558 of these autopsies (3.28%) from patients aged 15 years or more with primary underlying diseases who developed radiologically diffuse infiltrates of the lung during their hospital course and died after secondary interstitial pneumonia (bronchopneumonia, lobar pneumonia, interstitial pneumonia, diffuse alveolar damage, pulmonary recurrence of underlying disease, drug-induced lung disease, cardiogenic pulmonary edema, or pulmonary embolism). Histology slides were reviewed by experienced pathologists to confirm or not the presence of secondary interstitial pneumonia. Statistical analysis included the Fisher exact test to verify any association between histopathology and the cause of immunocompromise; a logistic regression was used to predict the risk of death for specific histological findings for each of the independent variables in the model. RESULTS: Secondary interstitial pneumonia was histologically represented by diffuse interstitial pneumonitis ranging from mild nonspecific findings (n = 213) to a pattern of diffuse alveolar damage (n = 273). The principal causes of immunocompromise in patients with diffuse alveolar damage were sepsis (136 cases), neoplasia (113 cases), diabetes mellitus (37 cases), and transplantation (48 cases). A high risk of death by pulmonary edema was found for patients with carcinoma of colon. Similarly, in patients with lung cancer or cachexia, A high risk of death by bronchopneumonia (OR = 3.6; OR = 2.6, respectively) was found. Pulmonary thromboembolism was associated with an appreciable risk of death (OR = 2.4) in patients with arterial hypertension. The risk of death was also high in patients presenting hepatic cancer (OR = 2.5) or steroid therapy (OR = 2.4) who developed pulmonary hemorrhage as the histological pattern of secondary interstitial pneumonia . The risk of death by lung metastasis was also elevated (OR = 1.6) for patients that were immunosuppressed after radiotherapy. CONCLUSION: Patients with secondary immunosuppression who developed secondary interstitial pneumonia during treatment in hospital should be evaluated to avoid death by diffuse alveolar damage, pulmonary edema, bronchopneumonia, lung hemorrhage, pulmonary thromboembolism, or lung metastasis. The high-risk patients are those immunosuppressed by hematologic disease; those under steroid treatment; or those with colon or hepatic carcinoma, cachexia, or arterial hypertension.OBJETIVO: Apresentar as associações mais freqüentes encontradas em autópsias de pacientes imunossuprimidos que desenvolveram pneumonia intersticial secundária bem como o risco de óbito (Odds Ratio) de desenvolver PIS associada à causa da imunossupressão. MÉTODO: De janeiro de 1994 a março de 2004, 17000 autópsias foram realizadas no Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo. A partir da revisão dos laudos patológicos foram selecionados 558 destas autópsias (3,28%) de pacientes com 15 anos de idade ou mais, com alguma doença de base que desenvolveu um infiltrado pulmonar radiologicamente difuso durante o curso da hospitalização e que depois foi para óbito com pneumonia intersticial secundária (broncopneumonia, pneumonia lobar, pneumonia intersticial, dano alveolar difuso, doença pulmonar recorrente, doença pulmonar induzida por drogas, edema pulmonar cardiogênico e embolismo pulmonar). As lâminas histológicas foram revisadas por patologistas experientes para confirmar ou não a presença de pneumonia intersticial secundária. A análise estatística incluiu o "Teste exato de Fisher" para verificar associação entre a histolopatologia e causa de imunocomprometimento; e regressão logística para predizer o risco de óbito por achados histológicos específicos para cada variável independente do modelo. RESULTADOS: A pneumonia intersticial secundária foi representada histológicamente por pneumonite intersticial difusa variando de características não especificas leves (n=213) ao padrão histológico de dano alveolar difuso (n=273). A principal causa de imunossupressão nos pacientes com dano alveolar difuso foi sepse (136 casos), neoplasia (113 casos), diabetes melito (37 casos) e transplantados (37 casos). O maior risco de morte por edema pulmonar foi encontrado nos pacientes com carcinoma de cólon. Da mesma forma, nos pacientes com câncer pulmonar ou cachexia ocorreu um alto risco de morte (OR=3.6; OR=2.6, respectivamente) por broncopneumonia. O tromboembolismo pulmonar ofereceu um importante risco de morte (OR=2.4) nos pacientes com hipertensão arterial. Observou-se também risco de morte por câncer hepático (OR=2.5) ou terapia esteroidea (OR=2.4) nos pacientes que desenvolveram hemorragia pulmonar com padrão histológico de pneumonia intersticial secundária. Da mesma forma houve alto risco de morte por metástase pulmonar (OR= 1.6) nos pacientes imunossuprimidos após radioterapia. CONCLUSÃO: Pacientes com imunossupressão secundária que desenvolveram pneumonia intersticial secundária durante o tratamento dentro do hospital podem ser avaliados para evitar como evento final o dano alveolar difuso, o edema pulmonar, a broncopneumonia, a hemorragia pulmonar, o tromboembolismo pulmonar e a metástase pulmonar. Os pacientes com aumento de risco são aqueles imunossuprimidos por doença hematológica, sob tratamento com esteroides, carcimona hepático, cachexia e hipertensão

Post-Mortem Histological Pulmonary Analysis in Patients with HIV/AIDS

OBJECTIVES: Certain aspects of pulmonary pathology observed in autopsies of HIV/AIDS patients are still unknown. This study considers 250 autopsies of HIV/AIDS patients who died of acute respiratory failure and describes the demographic data, etiology, and histological pulmonary findings of the various pathologies. METHODS: The following data were obtained: age, sex, and major associated diseases (found at the autopsy). Pulmonary histopathology was categorized as: diffuse alveolar damage; pulmonary edema; alveolar hemorrhage; and acute interstitial pneumonia. Odds ratio of the HIV/AIDS-associated diseases developing a specific histopathological pattern was determined by logistic regression. RESULTS: A total of 197 men and 53 women were studied. The mean age was 36 years. Bacterial bronchopneumonia was present in 36% (91 cases) and Pneumocystis jiroveci pneumonia in 27% (68) of patients. Pulmonary histopathology showed acute interstitial pneumonia in 40% (99), diffuse alveolar damage in 36% (89), pulmonary edema in 13% (33), and alveolar hemorrhage in 12% (29) of patients. Multivariate analysis showed a significant and positive association between Pneumocystis jiroveci pneumonia and acute interstitial pneumonia (Odds ratio, 4.51; 95% CI, 2.46 - 8.24; p < 0.001), severe sepsis and/or septic shock and diffuse alveolar damage (Odds ratio, 3.60; 95% CI, 1.78 -7.27; p < 0.001), and cytomegalovirus and acute interstitial pneumonia (Odds ratio, 2.22; 95% CI, 1.01 - 4.93; p = 0.05). CONCLUSIONS: This report is the first autopsy study to include demographic data, etiologic diagnosis, and respective histopathological findings in patients with HIV/AIDS and acute respiratory failure. Further studies are necessary to elucidate the complete pulmonary physiopathological mechanism involved with each HIV/AIDS-associated disease

Efeito protetor do pré-tratamento com ácido ascóbico em modelo experimental de isquemia-reperfusão intestinal: um estudo histomorfométrico

BACKGROUND: Ascorbic acid has shown promise in attenuation of intestinal ischemia-reperfusion (I/R) injury. The aim of this study was to determine the protective effects of ascorbic acid on intestinal morphology during IR injury in rats. MATERIALS AND METHODS: We examined morphological changes in the small intestine of Wistar rats after (i) 40 minutes of ischemia (I), (ii) ischemia followed by 30 min of reperfusion (IR), (iii) ischemia with ascorbic acid (IA), (iv) ischemia followed by reperfusion and ascorbic acid (IRA) and (v) in a sham group (S). We used morphometry to evaluate the amount of villous architecture, crypts, necrosis, hemorrhagic infarcts and inflammatory cells at the mesenteric and antimesenteric borders of the small intestine. RESULTS: Ascorbic acid caused a significant reduction of antimesenteric villous hemorrhagic infarction (pINTRODUÇÃO: O ácido ascórbico tem se mostrado como um agente promissor na atenuação da lesão causada pela isquemia/reperfusão (IR). O objetivo deste estudo foi determinar os efeitos protetores do ácido ascórbico na morfologia intestinal durante a IR em ratos. MATERIAL E MÉTODOS: Examinamos alterações morfológicas no intestino delgado de ratos do tipo Wistar. Após 40 minutos de isquemia (I), isquemia seguida de reperfusão (IR), isquemia com tratamento com ácido ascórbico (IA), isquemia seguida por 30 minutos de reperfusão e tratamento com ácido ascórbico (IRA) e do grupo sham (S). Utilizamos a morfometria para avaliar quantitativamente a arquitetura dos vilos da mucosa intestinal, criptas intestinais, necrose, hemorragia, células inflamatórias nas bordas mesentéricas e antimesentéricas do intestino delgado. RESULTADOS: O ácido ascórbico causou uma redução significativa (

Increased fibroblast telomerase expression precedes myofibroblast &#945;-smooth muscle actin expression in idiopathic pulmonary fibrosis

OBJECTIVE: This study sought to identify the relationship between fibroblast telomerase expression, myofibroblasts, and telomerase-mediated regulatory signals in idiopathic pulmonary fibrosis. METHODS: Thirty-four surgical lung biopsies, which had been obtained from patients with idiopathic pulmonary fibrosis and histologically classified as usual interstitial pneumonia, were examined. Immunohistochemistry was used to evaluate fibroblast telomerase expression, myofibroblast &#945;-smooth muscle actin expression and the tissue expression of inter leu kin-4, transforming growth factor-&#946;, and basic fibroblast growth factor. The point-counting technique was used to quantify the expression of these markers in unaffected, collapsed, mural fibrosis, and honeycombing areas. The results were correlated to patient survival. RESULTS: Fibroblast telomerase expression and basic fibroblast growth factor tissue expression were higher in collapsed areas, whereas myofibroblast expression and interleukine-4 tissue expression were higher in areas of mural fibrosis. Transforming growth factor-&#946; expression was higher in collapsed, mural fibrosis and honeycombing areas in comparison to unaffected areas. Positive correlations were found between basic fibroblast growth factor tissue expression and fibroblast telomerase expression and between interleukin-4 tissue expression and myofibroblast &#945;-smooth muscle actin expression. Negative correlations were observed between interleukin-4 expression and basic fibroblast growth factor tissue expression in areas of mural fibrosis. Myofibroblast &#945;-smooth muscle actin expression and interleukin-4 tissue expression in areas of mural fibrosis were negatively associated with patient survival. CONCLUSION: Fibroblast telomerase expression is higher in areas of early remodeling in lung tissues demonstrating typical interstitial pneumonia, whereas myofibroblast &#945;-smooth muscle actin expression predominates in areas of late remodeling. These events seem to be regulated by basic fibroblast growth factor and interleukin-4 tissue expression, respectively

Pathological and ultrastructural analysis of surgical lung biopsies in patients with swine-origin influenza type A/H1N1 and acute respiratory failure

BACKGROUND: Cases of H1N1 and other pulmonary infections evolve to acute respiratory failure and death when co-infections or lung injury predominate over the immune response, thus requiring early diagnosis to improve treatment. OBJECTIVE: To perform a detailed histopathological analysis of the open lung biopsy specimens from five patients with ARDS with confirmed H1N1. METHODS: Lung specimens underwent microbiologic analysis, and examination by optical and electron microscopy. Immunophenotyping was used to characterize macrophages, natural killer, T and B cells, and expression of cytokines and iNOS. RESULTS: The pathological features observed were necrotizing bronchiolitis, diffuse alveolar damage, alveolar hemorrhage and abnormal immune response. Ultrastructural analysis showed viral-like particles in all cases. CONCLUSIONS: Viral-like particles can be successfully demonstrated in lung tissue by ultrastructural examination, without confirmation of the virus by RT-PCR on nasopharyngeal aspirates. Bronchioles and epithelium, rather than endothelium, are probably the primary target of infection, and diffuse alveolar damage the consequence of the effect of airways obliteration and dysfunction on innate immunity, suggesting that treatment should be focused on epithelial repair.(CNPq) National Council for Scientific and Technological Development(FAPESP) São Paulo Research Foundatio

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

Histomorphometric analysis of cutaneous remodeling in the early stage of the scleroderma model

INTRODUCTION/OBJECTIVES: Systemic sclerosis, or scleroderma, is a rheumatic disease characterized by autoimmunity, vasculopathy, and fibrosis of the skin and several internal organs. In the present study, our aim was to assess the skin alterations in animals with scleroderma during the first stages of disease induction. METHODS: To induce scleroderma, female New Zealand rabbits (n = 12) were subcutaneously immunized with 1 mg/ml of collagen V (Col V) in complete Freund's adjuvant, twice with a thirty-day interval. Fifteen days later, the animals received an intramuscular booster with type V collagen in incomplete Freund's adjuvant, twice with a fifteen-day interval. The control group was inoculated with 1 ml of 10 mM acetic acid solution diluted with an equal amount of Freund's adjuvant. Serial dorsal skin biopsies were performed at 7, 15, and 30 days and stained with H&E, Masson's trichrome and Picrosírius for morphological and morphometric analyses. RESULTS: Immunized rabbits presented a significant increase in collagen in skin collected seven days after the first immunization (p=0.05). CONCLUSION: The results from this experimental model may be very important to a better understanding of the pathogenic mechanisms involved in the beginning of human SSc. Therapeutic protocols to avoid early remodeling of the skin may lead to promising treatments for SSc in the future

Pre-operative sera levels of CEA and CA19-9 and tissular distribution of tumor marker CA19-9 in colorectal carcinoma: correlation with morphological features of neoplasia

OBJETIVO: Comparar os níveis séricos de CA19-9 e CEA e a expressão tecidual do CA19-9 e relacioná-los com os aspectos morfológicos do carcinoma colorretal. MÉTODOS: Quarenta e cinco pacientes com carcinoma colorretal foram operados com coleta de CEA e CA19-9 séricos pré-operatórios. Valores séricos de CEA = 5,0ng/mL e de CA19-9 = 37UI/mL foram considerados aumentados. A avaliação da imunoexpressão do CA19-9 no tecido neoplásico foi realizada por meio de estudo imunoistoquímico com anticorpo monoclonal anti-CA19-9. A intensidade de expressão do CA19-9 no tecido neoplásico foi semiquantificada em leve(+/+++), moderada(++/+++), intensa(+++/+++) e ausente. RESULTADOS: Os valores do CA19-9 sérico foram progressivamente maiores conforme o aumento da expressão do CA19-9 no tecido neoplásico, porém sem significância (p=0,06). O aumento do nível sérico do CA19-9 foi acompanhado de elevação significante (p<0,001) do nível sérico do CEA. O nível sérico do CA19-9, a imunoexpressão tecidual do CA19-9 e o nível sérico do CEA não apresentaram associação significante com características morfológicas do carcinoma colorretal. CONCLUSÃO: As expressões sérica e tissular do CA19-9 demonstraram relação diretamente proporcional entre si, enquanto que os aspectos morfológicos da neoplasia não tiveram influência no CEA e CA19-9 séricos ou na imunoexpressão do CA19-9 tissular.OBJECTIVE: To compare sera levels of CEA and CA19-9 and tissular expression of the CA19-9 and to correlate these with morphological features of the colorectal carcinoma. METHODS: Forty five patients with colorectal carcinoma underwent surgical treatment following measurement of pre-operative levels of CA19-9 and CEA. Sera levels of CEA = 5.0ng/ml and CA19-9 = 37UI were deemed high values. Evaluation of CA19-9 immunoexpression in neoplastic tissue was carried through by means of immunohistochemical study with monoclonal antibody anti-CA19-9. The intensity of expression of CA19-9 in neoplastic areas was semi-quantified in each area of tumor differentiation into mild(+/+++), moderate(++/+++), intense(+++/+++) or absent. RESULTS: Sera CA19-9 values were progressively higher in the presence of elevated CA19-9 immunoexpression in colorectal carcinoma tissue, although not significant (p=0.06). Increased sera CA19-9 levels were found to be associated with significantly elevated (p<0.001) sera CEA levels. Levels of sera CA19-9, tissular immunoexpression of CA19-9 and sera levels of CEA presented no significant association with morphological features of the colorectal carcinoma. CONCLUSION: Sera and tissular levels of the CA19-9 marker exhibited, each other, a directly proportional relationship. The morphological features of the neoplasia had no influence on sera CEA or CA19-9 levels or tissular immunoexpression of CA19-9

Avaliação semiquantitativa da biópsia pulmonar cirúrgica: valor preditivo e impacto na sobrevida de pacientes com infiltrado pulmonar difuso

PURPOSE: Surgical lung biopsy has been studied in distinct populations, mostly going beyond clinical issues to impinge upon routine histopathological diagnostic information in diffuse infiltrates; however, detailed tissue analyses have rarely been performed. The present study was designed to investigate the prognostic contribution provided by detailed tissue analysis in diffuse infiltrates. METHODS: Medical records and surgical lung biopsies from the period of 1982 to 2003 of 63 patients older than 18 years with diffuse infiltrates were retrospectively examined. Lung parenchyma was histologically divided into 4 anatomical compartments: interstitium, airways, vessels, and alveolar spaces. Histological changes throughout these anatomical compartments were then evaluated according to their acute or chronic evolutional character. A semiquantitative scoring system was applied to histologic findings to evaluate the intensity and extent of the pathological process. We applied logistic regression to predict the risk of death associated with acute and chronic histological changes and to estimate the odds ratios for each of the independent variables in the model. RESULTS: Impact on survival was found for male gender (P = 0.03), presence of diffuse alveolar damage (P = 0.001), and chronic histological changes (P = 0.0004) on biopsy. Thus, being male was associated with a slightly lower risk (O.R. = 0.18; P=0.03) of dying than being female. Death risk was increased 17 times in the presence of acute histological changes such as diffuse alveolar damage and 2.5 times in the presence of chronic histological changes. CONCLUSION: Detailed analysis of histological specimens can provide more than a nosological diagnosis: this approach can provide valuable information concerning prognosis.PROPOSIÇÃO: A biópsia pulmonar cirúrgica tem sido estudada em populações distintas, geralmente abordando aspectos histopatológicos puramente diagnósticos em infiltrados pulmonares difusos, além de dados clínicos. Contudo, análises teciduais detalhadas em tais casos têm sido pouco exploradas. O presente estudo foi delineado com o intuito de se investigar a contribuição prognóstica fornecida pela análise histológica detalhada em infiltrados difusos. MÉTODOS: Foram examinados retrospectivamente os prontuários e biópsias pulmonares cirúrgicas de 63 pacientes maiores de 18 anos, com infiltrados difusos, de 1982 a 2003. O parênquima pulmonar foi dividido em 4 compartimentos histológicos: interstício, vias aéreas, vasos e espaços alveolares. Alterações histológicas de cada compartimento histológico foram então avaliadas de acordo com seu caráter evolutivo agudo ou crônico. Um escore semiquantitativo foi aplicado a achados histopatológicos com o intuito de se avaliar a intensidade e a extensão do processo patológico. Aplicamos regressão logística para predizer o risco de morte para alterações histológicas agudas e crônicas e para estimar a razão de probabilidades para cada uma das variáveis independentes do modelo. RESULTADOS: O impacto sobre a sobrevida foi observado para o gênero masculino (p=0.03), para a presença de dano alveolar difuso (p=0.001) e para alterações histológicas crônicas (p=0.0004) em biópsias. Assim, homens apresentariam menor chance (O.R. = 0.18; P=0.03) de morrer do que mulheres. O risco de morte foi 17 vezes maior na presença de alterações histológicas agudas como dano alveolar difuso e 2,5 vezes na presença de alterações histológicas crônicas. CONCLUSÃO: A análise detalhada de espécimes histológicos pode proporcionar maiores e mais valiosas informações de valor prognóstico do que o simples diagnóstico nosológico