Relative incidence of interstitial lung diseases in Brazil / Incidência relativa de doenças pulmonares intersticiais no Brasil

ABSTRACT Objective: To assess the relative frequency of incident cases of interstitial lung diseases (ILDs) in Brazil. Methods: This was a retrospective survey of new cases of ILD in six referral centers between January of 2013 and January of 2020. The diagnosis of ILD followed the criteria suggested by international bodies or was made through multidisciplinary discussion (MDD). The condition was characterized as unclassifiable ILD when there was no specific final diagnosis following MDD or when there was disagreement between clinical, radiological, or histological data. Results: The sample comprised 1,406 patients (mean age = 61 ± 14 years), and 764 (54%) were female. Of the 747 cases exposed to hypersensitivity pneumonitis (HP)-related antigens, 327 (44%) had a final diagnosis of HP. A family history of ILD was reported in 8% of cases. HRCT findings were indicative of fibrosis in 74% of cases, including honeycombing, in 21%. Relevant autoantibodies were detected in 33% of cases. Transbronchial biopsy was performed in 23% of patients, and surgical lung biopsy, in 17%. The final diagnoses were: connective tissue disease-associated ILD (in 27%), HP (in 23%), idiopathic pulmonary fibrosis (in 14%), unclassifiable ILD (in 10%), and sarcoidosis (in 6%). Diagnoses varied significantly among centers (c2 = 312.4; p < 0.001). Conclusions: Our findings show that connective tissue disease-associated ILD is the most common ILD in Brazil, followed by HP. These results highlight the need for close collaboration between pulmonologists and rheumatologists, the importance of detailed questioning of patients in regard with potential exposure to antigens, and the need for public health campaigns to stress the importance of avoiding such exposure.

RESUMO Objetivo: Avaliar a frequência relativa de casos incidentes de doenças pulmonares intersticiais (DPI) no Brasil. Métodos: Levantamento retrospectivo de casos novos de DPI em seis centros de referência entre janeiro de 2013 e janeiro de 2020. O diagnóstico de DPI seguiu os critérios sugeridos por órgãos internacionais ou foi feito por meio de discussão multidisciplinar (DMD). A condição foi caracterizada como DPI não classificável quando não houve um diagnóstico final específico após a DMD ou houve discordância entre dados clínicos, radiológicos ou histológicos. Resultados: A amostra foi composta por 1.406 pacientes (média de idade = 61 ± 14 anos), sendo 764 (54%) do sexo feminino. Dos 747 casos expostos a antígenos para pneumonite de hipersensibilidade (PH), 327 (44%) tiveram diagnóstico final de PH. Houve relato de história familiar de DPI em 8% dos casos. Os achados de TCAR foram indicativos de fibrose em 74% dos casos, incluindo faveolamento, em 21%. Autoanticorpos relevantes foram detectados em 33% dos casos. Biópsia transbrônquica foi realizada em 23% dos pacientes, e biópsia pulmonar cirúrgica, em 17%. Os diagnósticos finais foram: DPI associada à doença do tecido conjuntivo (em 27%), PH (em 23%), fibrose pulmonar idiopática (em 14%), DPI não classificável (em 10%) e sarcoidose (em 6%). Os diagnósticos variaram significativamente entre os centros (c2 = 312,4; p < 0,001). Conclusões: Nossos achados mostram que DPI associada à doença do tecido conjuntivo é a DPI mais comum no Brasil, seguida pela PH. Esses resultados destacam a necessidade de uma estreita colaboração entre pneumologistas e reumatologistas, a importância de fazer perguntas detalhadas aos pacientes a respeito da potencial exposição a antígenos e a necessidade de campanhas de saúde pública destinadas a enfatizar a importância de evitar essa exposição.

Progressive fibrotic interstitial lung disease / Doença pulmonar intersticial fibrosante progressiva

ABSTRACT Many interstitial lung diseases (ILDs) share mechanisms that result in a progressive fibrosing phenotype. In Brazil, the most common progressive fibrosing interstitial lung diseases (PF-ILDs) are chronic hypersensitivity pneumonitis, idiopathic pulmonary fibrosis, unclassified ILD, and connective tissue diseases. PF-ILD is seen in approximately 30% of patients with ILD. Because PF-ILD is characterized by disease progression after initiation of appropriate treatment, a diagnosis of the disease resulting in fibrosis is critical. Different criteria have been proposed to define progressive disease, including worsening respiratory symptoms, lung function decline, and radiological evidence of disease progression. Although the time elapsed between diagnosis and progression varies, progression can occur at any time after diagnosis. Several factors indicate an increased risk of progression and death. In the last few years, antifibrotic drugs used in patients with idiopathic pulmonary fibrosis have been tested in patients with PF-ILD. The effects of nintedanib and placebo have been compared in patients with PF-ILD, a mean difference of 107.0 mL/year being observed, favoring nintedanib. The U.S. Food and Drug Administration and the Brazilian Health Regulatory Agency have approved the use of nintedanib in such patients on the basis of this finding. Pirfenidone has been evaluated in patients with unclassified ILD and in patients with other ILDs, the results being similar to those for nintedanib. More studies are needed in order to identify markers of increased risk of progression in patients with ILD and determine the likelihood of response to treatment with standard or new drugs.

RESUMO Muitas doenças pulmonares intersticiais (DPI) compartilham mecanismos que resultam em um fenótipo fibrosante progressivo. No Brasil, as doenças pulmonares intersticiais fibrosantes progressivas (DPI-FP) mais comuns são a pneumonite de hipersensibilidade crônica, a fibrose pulmonar idiopática, a DPI não classificada e as doenças do tecido conjuntivo. A DPI-FP é observada em aproximadamente 30% dos pacientes com DPI. Como a DPI-FP é caracterizada pela progressão da doença após o início do tratamento adequado, é fundamental diagnosticar a doença que resulta em fibrose. Diferentes critérios foram propostos para definir doença progressiva, incluindo piora dos sintomas respiratórios, declínio da função pulmonar e evidências radiológicas de progressão da doença. Embora o tempo decorrido entre o diagnóstico e a progressão varie, a progressão pode ocorrer a qualquer momento após o diagnóstico. Vários fatores indicam risco aumentado de progressão e morte. Nos últimos anos, antifibróticos usados em pacientes com fibrose pulmonar idiopática foram testados em pacientes com DPI-FP. Os efeitos do nintedanibe e placebo foram comparados em pacientes com DPI-FP, com diferença média de 107,0 mL/ano a favor do nintedanibe. A Food and Drug Administration (EUA) e a Agência Nacional de Vigilância Sanitária aprovaram o uso do nintedanibe em tais pacientes com base nesse achado. A pirfenidona foi avaliada em pacientes com DPI não classificada e em pacientes com outras DPI, e os resultados foram semelhantes aos do nintedanibe. Mais estudos são necessários para identificar marcadores de risco aumentado de progressão em pacientes com DPI e determinar a probabilidade de resposta ao tratamento com medicamentos-padrão ou novos.

Sleep parameters in patients with chronic hypersensitivity pneumonitis: a case-control study / Parâmetros do sono em pacientes com pneumonite de hipersensibilidade crônica: estudo de caso-controle

ABSTRACT Objective: To compare patients with chronic hypersensitivity pneumonitis (cHP) and controls with normal spirometry in terms of their sleep characteristics, as well as to establish the prevalence of obstructive sleep apnea (OSA) and nocturnal hypoxemia. Secondary objectives were to identify factors associated with OSA and nocturnal hypoxemia; to correlate nocturnal hypoxemia with the apnea-hypopnea index (AHI) and lung function, as well as with resting SpO2, awake SpO2, and SpO2 during exercise; and to evaluate the discriminatory power of sleep questionnaires to predict OSA. Methods: A total of 40 patients with cHP (cases) were matched for sex, age, and BMI with 80 controls, the ratio of controls to cases therefore being = 2:1. The STOP-Bang questionnaire, the Epworth Sleepiness Scale (ESS), the Pittsburgh Sleep Quality Index, the Berlin questionnaire and the Neck circumference, obesity, Snoring, Age, and Sex (NoSAS) score were applied to all cases, and both groups underwent full-night polysomnography. Results: The patients with cHP had longer sleep latency, lower sleep efficiency, a lower AHI, a lower respiratory disturbance index, fewer central apneas, fewer mixed apneas, and fewer hypopneas than did the controls. The patients with cHP had significantly lower nocturnal SpO2 values, the percentage of total sleep time spent below an SpO2 of 90% being higher than in controls (median = 4.2; IQR, 0.4-32.1 vs. median = 1.0; IQR, 0.1-5.8; p = 0.01). There were no significant differences between cases with and without OSA regarding the STOP-Bang questionnaire, NoSAS, and ESS scores. Conclusions: The prevalence of OSA in cHP patients (cases) was high, although not higher than that in controls with normal spirometry. In addition, cases had more hypoxemia during sleep than did controls. Our results suggest that sleep questionnaires do not have sufficient discriminatory power to identify OSA in cHP patients.

RESUMO Objetivo: Comparar pacientes com pneumonite de hipersensibilidade crônica (PHc) e controles com espirometria normal quanto às características do sono, bem como estabelecer a prevalência de apneia obstrutiva do sono (AOS) e hipoxemia noturna. Os objetivos secundários foram identificar fatores associados à AOS e hipoxemia noturna; correlacionar a hipoxemia noturna com o índice de apneias e hipopneias (IAH), função pulmonar, SpO2 em repouso, SpO2 em vigília e SpO2 durante o exercício; e avaliar o poder discriminatório de questionários do sono para predizer AOS. Métodos: Um total de 40 pacientes com PHc (casos) foram emparelhados por sexo, idade e IMC com 80 controles (2:1). O questionário STOP-Bang, a Escala de Sonolência de Epworth (ESE), o Índice de Qualidade do Sono de Pittsburgh, o questionário de Berlim e o escore Neck circumference, obesity, Snoring, Age, and Sex (NoSAS, circunferência do pescoço, obesidade, ronco, idade e sexo) foram aplicados a todos os casos, e ambos os grupos foram submetidos a polissonografia de noite inteira. Resultados: Os pacientes com PHc apresentaram maior latência do sono, menor eficiência do sono, menor IAH, menor índice de distúrbio respiratório, menos apneias centrais, menos apneias mistas e menos hipopneias do que os controles. Os pacientes com PHc apresentaram SpO2 noturna significativamente menor; a porcentagem do tempo total de sono com SpO2 < 90% foi maior que nos controles (mediana = 4,2; IIQ: 0,4-32,1 vs. mediana = 1,0; IIQ: 0,1-5,8; p = 0,01). Não houve diferenças significativas entre os casos com e sem AOS quanto à pontuação no questionário STOP-Bang, no NoSAS e na ESE. Conclusões: A prevalência de AOS em pacientes com PHc (casos) foi alta, embora não tenha sido maior que a observada em controles com espirometria normal. Além disso, os casos apresentaram mais hipoxemia durante o sono do que os controles. Nossos resultados sugerem que os questionários do sono não têm poder discriminatório suficiente para identificar AOS em pacientes com PHc.

Carbohydrate antigen 15-3 as a marker of disease severity in patients with chronic hypersensitivity pneumonitis* / Antígeno carboidrato 15-3 como marcador de gravidade da doença em pacientes com pneumonite de hipersensibilidade crônica

ABSTRACT Objective: Biomarkers associated with mucin 1, such as Krebs von den Lungen-6 and carbohydrate antigen (CA) 15-3, are increased in various interstitial lung diseases. Our aim was to determine whether CA 15-3 could be considered a biomarker of disease severity in patients with chronic hypersensitivity pneumonitis (cHP). Methods: This was a prospective observational study involving adult patients with cHP. Serum levels of CA 15-3 were measured and were correlated with variables related to disease severity and extension. HRCT scans were quantitatively analyzed using a computational platform and an image analysis tool (Computer Aided Lung Informatics for Pathology Evaluation and Rating). CA 15-3 levels were normalized by logarithmic transformation. Results: The sample comprised 41 patients. The mean age of the patients was 60.1 ± 11.6 years. The mean FVC in % of predicted was 70.3% ± 17.3%, and the median of the serum level of CA 15-3 was 48.1 U/mL. CA 15-3 levels inversely correlated with FVC in % of predicted (r = −0,30; p = 0,05), DLCO in % of predicted (r = −0,54; p < 0,01), and SpO2 at the end of a 4-min step test (r = −0,59; p < 0,01), but they directly correlated with total quantitative HRCT scores (r = 0,47; p = 0,004), especially regarding ground-glass opacities (r = 0.58; p < 0,001). Conclusions: CA 15-3 is likely to be a biomarker of disease severity of patients with cHP, particularly regarding gas exchange abnormalities.

RESUMO Objetivo: Biomarcadores associados à mucina-1, tais como Krebs von den Lungen-6 e carbohydrate antigen (CA, antígeno carboidrato) 15-3, encontram-se aumentados em diversas doenças pulmonares intersticiais. Nosso objetivo foi determinar se CA 15-3 poderia ser considerado um biomarcador de gravidade de doença em pacientes com pneumonite de hipersensibilidade crônica (PHc). Métodos: Estudo prospectivo observacional envolvendo pacientes adultos com PHc. Os níveis séricos de CA 15-3 foram medidos e correlacionados com variáveis relacionadas à gravidade e extensão da doença. As imagens de TCAR foram analisadas quantitativamente utilizando uma plataforma computacional e uma ferramenta de análise de imagem (Computer-Aided Lung Informatics for Pathology Evaluation and Rating). Os níveis de CA 15-3 foram normalizados por transformação logarítmica. Resultados: A amostra foi composta por 41 pacientes. A média de idade dos pacientes foi de 60,1 ± 11,6 anos. A média da CVF em % do previsto foi de 70,3% ± 17,3%, e a mediana do nível sérico de CA 15-3 foi de 48,1 U/mL. Os níveis de CA 15-3 se correlacionaram inversamente com CVF em % do previsto (r = −0,30; p = 0,05), DLCO em % do previsto (r = −0,54; p < 0,01) e SpO2 ao final de um teste de degrau de 4 minutos (r = −0,59; p < 0,01), mas se correlacionaram diretamente com a pontuação quantitativa total da TCAR (r = 0,47; p = 0,004), especialmente quanto a opacidades em vidro fosco (r = 0,58; p < 0,001). Conclusões: É provável que o CA 15-3 seja um biomarcador de gravidade de doença em pacientes com PHc, particularmente quanto a anormalidades nas trocas gasosas.

Enfermedades pulmonares intersticiales. Una perspectiva actual / Update on interstitial lung diseases

Interstitial lung diseases are a broad, diverse, challenging group of diseases, most of them chronic whose prognosis is not good. In the last two decades there have been considerable advances in the knowledge of the epidemiology, pathological and genetic bases and treatment of several of these diseases. This article summarizes and presents updated information about their classification, new knowledge on genetics and treatments in idiopathic pulmonary fibrosis, advances in the diagnosis and management of hypersensitivity pneumonitis and a review of the broad spectrum of interstitial diseases associated with connective tissue diseases. Several clinical trials are currently underway whose results will be available in the coming years and will provide more information and tools to improve the treatment of these patients.

Características clínicas, funcionais e sobrevida dos pacientes com pneumonia de hipersensibilidade do Ambulatório de Doenças Pulmonares Intersticiais do Hospital das Clinicas da Universidade Federal de Minas Gerais (HC-UFMG) / Clinical, functional and survival in patients with hypersensitivity pneumonia Center of Pulmonary Interstitial Disease of Hospital das Clínicas da Universidade Federal de Minas Gerais (HC- UFMG)

A pneumonia de hipersensibilidade (PH) constitui síndrome inflamatória causada pela resposta imune exagerada a partículas antigênicas inaladas. Objetivo: descrever características clínicas, radiológicas, funcionais esobrevida de pacientes com PH. Metodologia: estudo retrospectivo, envolvendo pacientes em acompanhamento no ambulatório de doenças pulmonares intersticiais do HC-UFMG no período de 2011 a 2015. Analisados dados clínicos, radiológicos, funcionais e morfológicos coletados através de um protocolo padronizado. Resultados: Dentre 139 pacientes com doenças intersticiais pulmonares, 34 (24%) tinham PH, com idade de 60,7 ± 18,1 anos. Exposição a mofo foi a etiologia mais frequente (19;55%). A forma crônica foi predominante (100% doas casos), assim como a presença de padrão reticular na tomografia de tórax (100%), com ou sem faveolamento. Observou-se distúrbio restritivo leve (CVF=69,00 ± 17,62L) associado a redução moderada da difusão de monóxido de carbono (59,20 ± 16,99%). O lavado broncoalveolar não auxiliou no diagnóstico e a biópsia transbrônquica foi diagnóstica em 5 (55%) casos e a biópsia cirúrgica foi conclusiva em 6 (85,7%). A sobrevida mediana foi de 75 meses. Conclusão: Nesta amostra de um ambulatório de referência, a PH respondeu por cerca de um quarto dos pacientes com doença intersticial pulmonar. A exposição a mofo foi a principal etiologia e a mortalidade significativa, o que reforça a importância da adoção de medidas preventivas através do reconhecimento precoce da exposição aos fatores de risco. (AU)

Hypersensitivity pneumonitis (HP) inflammatory is a syndrome caused by an excessive immune response to inhaled antigen particles. Objective:To describe clinical, radiological and functional characteristics and survival in patients with HP. Methodology: Retrospective study involving patients followed up at the pulmonary interstitial diseases clinic of the HC-UFMG from 2011 to 2015. Clinical, radiological, functional and morphological data were analysed from a standardized protocol. Results: Among 139 patients with interstitial lung disease, 34 (24%) had HP, aged 60.7 ± 18.1 years. Mold exposure was the most frequent cause (19; 55%). The chronic form predominated (100% donate cases), as well as the presence of reticular pattern on the chest tomography (100%), with or without honeycombing. There was mild restrictive lung disease (FVC = 69.00 ± 17,62L) associated with moderate reduction in carbon monoxide diffusion (59.20 ± 16.99%). Bronchoalveolar lavage did not help in the diagnosis and transbronchial biopsy was diagnostic in 5 (55%) cases; surgical biopsy was conclusive in 6 (85.7%). Median survival was 60 months. Conclusion: In this sample of a reference clinic, HP accounted for about a quarter of the patients with interstitial lung disease. The mold exposure was the main etiology and the mortality rate was significant, what reinforces the importance of adopting preventive measures through early recognition of exposure to risk factors. (AU)

Pleuroparenchymal fibroelastosis: report of two cases in Brazil / Fibroelastose pleuroparenquimatosa: relato de dois casos no Brasil

ABSTRACT Pleuroparenchymal fibroelastosis (PPFE) is a rare lung disease. It can be idiopathic or associated with any one of various conditions. To our knowledge, this is the first report of two cases of PPFE in Brazil. Our first patient presented with pleural and subpleural fibrosis in the upper lobes; a spiculated nodule in the left upper lobe; and a mild reticular pattern in the lower lobes. Surgical lung biopsy revealed PPFE in the upper lobes, including the nodule, and unclassified interstitial pneumonia in the left lower lobe. Our second patient had a history of exposure to domestic birds, indicating a risk of hypersensitivity pneumonitis, and presented with advanced lung disease, predominantly in the upper lobes, together with subpleural fibrosis.That patient underwent lung transplantation. In the explant specimen, PPFE and granulomas were identified, suggesting hypersensitivity pneumonitis as an associated cause.

RESUMO A fibroelastose pleuroparenquimatosa (FEPP) é uma doença pulmonar rara, podendo ser idiopática ou associada a diversas condições. Pelo que sabemos, este é o primeiro relato de dois casos de FEPP no Brasil. Nosso primeiro paciente apresentava fibrose pleural e subpleural nos lobos superiores, um nódulo espiculado no lobo superior esquerdo e um padrão reticular discreto nos lobos inferiores. A biópsia pulmonar cirúrgica demonstrou FEPP nos lobos superiores, incluindo no nódulo, e pneumonia intersticial não classificada no lobo inferior esquerdo. Nosso segundo paciente tinha história de exposição a aves domésticas, indicando um risco de pneumonite de hipersensibilidade, e doença pulmonar avançada predominando em lobos superiores, com fibrose subpleural. Esse paciente foi submetido a transplante pulmonar. No espécime do explante, FEPP e granulomas foram identificados, sugerindo pneumonite de hipersensibilidade como causa associada.

High-resolution computed tomography and histopathological findings in hypersensitivity pneumonitis: a pictorial essay / Aspectos tomográficos e histopatológicos da pneumonite por hipersensibilidade: ensaio iconográfico

Abstract Hypersensitivity pneumonitis is a diffuse interstitial and granulomatous lung disease caused by the inhalation of any one of a number of antigens. The objective of this study was to illustrate the spectrum of abnormalities in high-resolution computed tomography and histopathological findings related to hypersensitivity pneumonitis. We retrospectively evaluated patients who had been diagnosed with hypersensitivity pneumonitis (on the basis of clinical-radiological or clinical-radiological-pathological correlations) and had undergone lung biopsy. Hypersensitivity pneumonitis is clinically divided into acute, subacute, and chronic forms; high-resolution computed tomography findings correlate with the time of exposure; and the two occasionally overlap. In the subacute form, centrilobular micronodules, ground-glass opacities, and air trapping are characteristic high-resolution computed tomography findings, whereas histopathology shows lymphocytic inflammatory infiltrates, bronchiolitis, variable degrees of organizing pneumonia, and giant cells. In the chronic form, high-resolution computed tomography shows traction bronchiectasis, honeycombing, and lung fibrosis, the last also being seen in the biopsy sample. A definitive diagnosis of hypersensitivity pneumonitis can be made only through a multidisciplinary approach, by correlating clinical findings, exposure history, high-resolution computed tomography findings, and lung biopsy findings.

Resumo A pneumonite por hipersensibilidade é uma doença intersticial difusa, granulomatosa e de natureza inalatória, com inúmeros antígenos orgânicos e inorgânicos implicados. Nosso objetivo é ilustrar o espectro de anormalidades na tomografia de alta resolução do tórax e achados histopatológicos. Foram avaliadas, retrospectivamente, tomografias de alta resolução do tórax de pacientes com diagnóstico de pneumonite por hipersensibilidade estabelecido em correlação clínico-radiológica e clínico-radiológico-patológica em pacientes em que a biópsia esteve disponível. A pneumonite por hipersensibilidade é dividida, do ponto de vista clínico e didático, em aguda, subaguda e crônica, e as manifestações tomográficas da tomografia de alta resolução do tórax correlacionam-se com o tempo da evolução da doença, e por vezes se superpõem. Micronódulos centrolobulares, vidro fosco e aprisionamento aéreo são características tomográficas na manifestação subaguda, em que, histopatologicamente, se observam infiltrado inflamatório linfocítico, bronquiolite, graus variáveis de pneumonia em organização e células gigantes. Na fase crônica, a tomografia demonstra sinais de fibrose com bronquiolectasias de tração e eventualmente faveolamento, com predomínio superior, sendo observados também sinais de fibrose no estudo histopatológico. A abordagem multidisciplinar é definitiva no diagnóstico, que é realizado correlacionando-se as características clínicas, nexo causal de exposição, achados tomográficos e aspectos histopatológicos.

Neumonitis por hipersensibilidad asociado al cuidado de aves / Hypersensitivity pneumonitis associated to birds care

La neumonitis por hipersensibilidad asociada al cuidado de las aves es uno de los tipos más frecuentes de esta que se presentan. Aunque no se tienen datos epidemiológicos claros sobre su prevalencia, en los hospitales llegan casos de este tipo. No es una patología muy común; sin embargo, una muestra representativa de la población se encuentra expuesta a las aves y, consecuentemente, a los antígenos que causan la enfermedad. Su diagnóstico temprano puede significar para el paciente evitar daños, al dejar de exponerse al antígeno; por el contrario, si no se realiza un diagnóstico temprano, puede generarse un daño pulmonar irreversible. En este artículo, se presenta un caso clínico de neumonitis por hipersensibilidad al cuidado de aves.

Hypersensitivity pneumonitis associated to birds care, is one of the most common types of pneumonitis. Although there is no clear epidemiological data of prevalence, many cases of pneumonitis arrive to hospitals. It is a very rare disorder, however, much of the population is exposed to birds and consequently to antigens that cause this disease. The early diagnosis can mean a reversible damage to the patient if stop exposure to the antigen, but otherwise if the diagnosis isn't made early, can generate an irreversible lung damage. In this paper, it is presented a case of hypersensitivity pneumonitis in birds care.

The value of family history in the diagnosis of hypersensitivity pneumonitis in children / O valor da história familiar no diagnóstico de pneumonite de hipersensibilidade em crianças

Hypersensitivity pneumonitis (HP), or extrinsic allergic alveolitis, is an immunologically mediated disease resulting from the inhalation of organic substances that trigger an inflammatory response in the alveolar wall, bronchioles, and interstitium in susceptible individuals. Although HP is predominantly an occupational disease, seen in adulthood, cases in children have been described. The diagnosis of HP requires a high degree of suspicion. The treatment consists in avoiding contact with the antigen, and, in some cases, systemic corticosteroids might be necessary in order to prevent its progression to pulmonary fibrosis. We report the clinical cases of three children with a history of contact with birds and a family history of HP. All three patients presented with cough and dyspnea on exertion. The disease was diagnosed on the basis of the clinical history and ancillary diagnostic test results consistent with the diagnosis, including a predominance of lymphocytes (> 60%, CD8+ T lymphocytes in particular) in bronchoalveolar lavage fluid and a ground-glass pattern seen on HRCT of the chest. Early diagnosis is crucial in order to prevent HP from progressing to pulmonary fibrosis. Hereditary factors seem to influence the onset of the disease.

A pneumonite de hipersensibilidade (PH), ou alveolite alérgica extrínseca, é uma doença imunologicamente mediada, resultante da inalação de substâncias orgânicas que desencadeiam uma reação inflamatória na parede dos alvéolos, bronquíolos e interstício em indivíduos susceptíveis. Apesar de ser uma doença ocupacional de predomínio na idade adulta, estão descritos casos em crianças. O diagnóstico de PH requer grande suspeição, e seu tratamento consiste na ausência de contato com o antígeno e, em alguns casos, pode ser necessária corticoterapia sistêmica, evitando-se a progressão para fibrose pulmonar. Relatamos três casos clínicos de crianças com história de contato com aves e história familiar de PH. Todos os casos se apresentaram com tosse e dispneia aos esforços. O diagnóstico foi possível por história clínica e exames auxiliares de diagnóstico compatíveis, incluindo lavado broncoalveolar com predomínio de linfócitos (> 60%, especialmente linfócitos T CD8+) e TCAR de tórax com padrão em vidro fosco. O diagnóstico precoce é fundamental na PH para se prevenir a evolução para fibrose pulmonar. Fatores hereditários parecem influenciar seu aparecimento.

Perinatal Immunization With Vaccine-Grade Listeria monocytogenes Provides Protection Against Murine Th2 Airway Inflammation

PURPOSE: Asthma is a chronic respiratory disorder that leads to inflammation and narrowing of the airways. Its global prevalence has attained epidemic levels and treatment options that reach beyond temporary relief of symptoms are urgently needed. Since the processes leading to clinically symptomatic asthma start early in life, we set out to systematically evaluate a neonatal immunotherapeutic based on Listeria monocytogenes (Lm) for the control of allergic sensitization. METHODS: We modified Lm to express the model allergen, ovalbumin (OVA), and tested the ability of neonatal immunization with this strain to control allergic sensitization in a mouse model of OVA-induced asthma. Mice were immunized as newborns with live or heat killed LmOVA or live Lm, followed 6 weeks later by allergic sensitization with OVA. In order to determine whether the T(H)1-polarizing effect of this vaccine vector inadvertently may exacerbate development of certain T(H)1-driven allergic diseases, mice immunized as newborns were assessed in a model of adult hypersensitivity pneumonitis (HP). RESULTS: Both LmOVA and Lm-control vaccines were highly effective in providing long-lasting protection from airway inflammation after only one immunization given perinatally. Serum antibody levels and lung cytokine production suggest that this prophylactic strategy is associated with an allergen specific T(H)1-dominated response. Specifically, LmOVA vaccinated mice displayed significantly elevated OVA-specific serum IgG2a, but no difference in anti-OVA IgE antibodies and only slightly decreased anti-OVA IgG1 antibodies. Importantly, Lm-based neonatal vaccination did not exacerbate Th1/Th17 driven HP, arguing against broad spectrum immune skewing. CONCLUSIONS: Our findings highlight the promise of early life Lm-based immunomodulatory interventions as a prophylactic strategy for allergic asthma.

Perinatal Immunization With Vaccine-Grade Listeria monocytogenes Provides Protection Against Murine Th2 Airway Inflammation

PURPOSE: Asthma is a chronic respiratory disorder that leads to inflammation and narrowing of the airways. Its global prevalence has attained epidemic levels and treatment options that reach beyond temporary relief of symptoms are urgently needed. Since the processes leading to clinically symptomatic asthma start early in life, we set out to systematically evaluate a neonatal immunotherapeutic based on Listeria monocytogenes (Lm) for the control of allergic sensitization. METHODS: We modified Lm to express the model allergen, ovalbumin (OVA), and tested the ability of neonatal immunization with this strain to control allergic sensitization in a mouse model of OVA-induced asthma. Mice were immunized as newborns with live or heat killed LmOVA or live Lm, followed 6 weeks later by allergic sensitization with OVA. In order to determine whether the T(H)1-polarizing effect of this vaccine vector inadvertently may exacerbate development of certain T(H)1-driven allergic diseases, mice immunized as newborns were assessed in a model of adult hypersensitivity pneumonitis (HP). RESULTS: Both LmOVA and Lm-control vaccines were highly effective in providing long-lasting protection from airway inflammation after only one immunization given perinatally. Serum antibody levels and lung cytokine production suggest that this prophylactic strategy is associated with an allergen specific T(H)1-dominated response. Specifically, LmOVA vaccinated mice displayed significantly elevated OVA-specific serum IgG2a, but no difference in anti-OVA IgE antibodies and only slightly decreased anti-OVA IgG1 antibodies. Importantly, Lm-based neonatal vaccination did not exacerbate Th1/Th17 driven HP, arguing against broad spectrum immune skewing. CONCLUSIONS: Our findings highlight the promise of early life Lm-based immunomodulatory interventions as a prophylactic strategy for allergic asthma.

A Case of Occupational Hypersensitivity Pneumonitis Associated with Trichloroethylene / 결핵및호흡기질환

Trichloroethylene (TCE) is a toxic chemical commonly used as a degreasing agent, and it is usually found in a colorless or blue liquid form. TCE has a sweet, chloroform-like odor, and this volatile chlorinated organic chemical can cause toxic hepatitis, neurophysiological disorders, skin disorders, and hypersensitivity syndromes. However, the hypersensitivity pneumonitis (HP) attributed to TCE has rarely been reported. We hereby describe a case of HP associated with TCE in a 29-year-old man who was employed as a lead welder at a computer repair center. He was installing the capacitors on computer chip boards and had been wiped down with TCE. He was admitted to our hospital with complaints of dry coughs, night sweats, and weight losses for the past two months. HP due to TCE exposure was being suspected due to his occupational history, and the results of a video-associated thoracoscopic biopsy confirmed the suspicions. Symptoms have resolved after the steroid pulse therapy and his occupational change. TCE should be taken into consideration as a potential trigger of HP. Early recognition and avoidance of the TCE exposure in the future is important for the treatment of TCE induced HP.

Pulmão dos criadores de aves complicado por nocardiose pulmonar / Bird fancier's lung complicated by pulmonary nocardiosis

Relatamos o caso de um paciente de 84 anos que foi hospitalizado devido a tosse persistente e dispneia. A radiografia de tórax inicial revelou infiltrados pulmonares. Nocardia asteroides foi detectada no escarro, e o paciente foi tratado com antibióticos; entretanto, seus sintomas não melhoraram por completo. O paciente foi hospitalizado várias vezes, e os sintomas reapareceram após cada alta. Houve a suspeita de pneumonite de hipersensibilidade, sendo o paciente diagnosticado com pulmão dos criadores de aves. É provável que a nocardiose pulmonar se desenvolva em pacientes com doenças pulmonares crônicas, como DPOC, e em hospedeiros imunossuprimidos. Até onde sabemos, este é o primeiro relato de um caso de pulmão dos criadores de aves complicado por nocardiose pulmonar.

We report the case of an 84-year-old male who was admitted to the hospital with persistent cough and dyspnea. An initial chest X-ray revealed pulmonary infiltrates. Nocardia asteroides was detected in sputum, and the patient was treated with antibiotics. However, his symptoms did not completely resolve. He was admitted multiple times, and his symptoms relapsed after every discharge. He was finally suspected of having hypersensitivity pneumonitis and was diagnosed with bird fancier's lung. Pulmonary nocardiosis is likely to develop in patients with chronic pulmonary disorders, such as COPD, as well as in immunosuppressed hosts. To our knowledge, this is the first report of a case of bird fancier's lung complicated by pulmonary nocardiosis.

Zotarolimus-eluting stent-induced hypersensitivity pneumonitis

No abstract available.

A Case of Hypersensitivity Pneumonitis Caused by Mycobacterium terrae in a Fishery Worker / 대한내과학회지

Hypersensitivity pneumonitis caused by exposure to non-tuberculous mycobacteria in indoor hot tubs has been called "hot tub lung." Most of these cases of hypersensitivity pneumonitis were, in fact, caused by Mycobacterium avium complex. We describe a case of hypersensitivity pneumonitis caused by M. terrae. A 54-year-old man presented with a 4-month history of exertional dyspnea, cough, and sputum. The patient had been working in a fishery for 5 years. Approximately 3 months before the onset of symptoms, he began working at another fishery. His chest CT scans showed diffuse ground-glass opacities with multifocal air trappings and centrilobular nodules in both lungs. Transbronchial lung biopsy specimens revealed hypersensitivity pneumonitis. M. terrae was isolated from a mycobacterial culture of his sputum and the water at the fishery.

Neumonitis por hipersensibilidad / Pneumonitis related to hypersensitivity

Se presentó una paciente con antecedentes patológicos personales de asma bronquial leve persistente y de dermatitis atópica. Acudió por tener fiebre de 60 d de evolución, tos, disnea, anorexia y pérdida de peso, con empeoramiento progresivo. Se diagnosticó neumonitis por hipersensibilidad después de realizar estudios de imágenes e histológicos. Se describió la evolución clínica y radiológica.

Authors present the case of a woman with personal pathologic backgrounds of persistent light bronchial asthma and of an atopic dermatitis. She came to our service by fever of 60 days of evolution, cough, dyspnea, anorexia, and weight loss with a progressive worsening. A hypersensitivity pneumonitis was diagnosed after imaging and histological studies. Clinical and radiological course was described.

Diagnosis and Treatment of Hypersensitivity Pneumonitis

Hypersensitivity pneumonitis (HP), also known as extrinsic allergic alveolitis, is an immunologically mediated granulomatous, inflammatory disease of the lungs caused by repeated inhalation of various antigens. HP may occur in acute, subacute, or chronic forms. Chronic HP may be progressive, irreversible, and evolve to fibrotic interstitial lung disease. The diagnosis of HP can be made from a combination of clinical, laboratory, radiologic, and pathologic findings. A careful environmental and occupational history and establishment of exposure to a known inciting antigen are key factors in making the diagnosis of HP. Serum precipitating antibodies, bronchoalveolar lavage, and lung biopsy may be helpful in making the diagnosis. The pathology of HP is characterized by interstitial lymphocytic infiltration, poorlyformed noncaseating granulomas, cellular bronchiolitis, and fibrosis. In the pathogenesis of HP, recent studies showed that both type III and type IV hypersensitivity reactions are involved and are mediated by immune complexes and Th1 T cells, respectively. IFN-gamma is essential for the development of HP, and IL-10 appears to modulate the severity of the disease. TNF-alpha and TGF-beta have been implicated in development of the pulmonary fibrosis that is seen in chronic HP. Avoidance of organic antigen exposure is the most important factor for the management of HP. There is often an apparent beneficial response to corticosteroids in the cases of severe acute and subacute HP, and for chronic HP that is severe or progressive.

Pneumonite de hipersensibilidade / Hypersensitivity pneumonitis

Pneumonite de hipersensibilidade (PH) ou alveolite alérgica extrínseca é uma reação inflamatória imune que ocorre em indivíduos suscetíveis, devido à inalação de antígenos orgânicos e/ou inorgânicos. Esta patologia deve ser suspeitada quando houver relato de exposição a poeiras orgânicas. Relata-se um caso de PH em paciente masculino de 33 anos, com história de dispnéia, tosse, emagrecimento e febre, apresentando regressão da doença após interrupção da exposição a antígenos de aves. O diagnóstico geralmente é baseado na história e no exame clínico, confirmado pelo aparecimento de lesões típicas nos exames de imagem e pela biópsia pulmonar. O tratamento adequado resulta em melhora dos sintomas, do quadro imagético e do padrão espirométrico. O afastamento do agente causador usualmente regride a doença e a corticoterapia pode ser eficaz em reprimir a resposta inflamatória (AU)

Hypersensitivity pneumonitis (HP), or extrinsic allergic alveolitis, is an immune inflammatory reaction affecting susceptible individuals due to inhalation of organic and/or inorganic antigens. This pathology must be suspected if there is report of exposure to organic dusts. In this article a case of PH is reported in a 33-year-old male with history of dyspnea, coughing, weight loss, and fever, with regression of the disease after discontinuation of exposure to bird antigens. The diagnosis is usually based on history and clinical examination, confirmed by the appearance of typical lesions in imaging and pulmonary biopsy. Proper treatment results in improvement of symptoms, imaging picture, and spirometric pattern. The removal of the causal agent usually determines regression of the disease, and corticoid therapy may be effective in repressing the inflammatory response (AU)

A Case of Hypersensitivity Pneumonitis Caused by Penicillium species in a Home Environment

We report a case of hypersensitivity pneumonitis in a 30-yr-old female housewife caused by Penicillium species found in her home environment. The patient was diagnosed according to history, chest radiograph, spirometry, high-resolution chest CT, and transbronchial lung biopsy. To identify the causative agent, cultured aeromolds were collected by the open-plate method. From the main fungi cultured, fungal antigens were prepared, and immunoblot analysis with the patient's serum and each fungal antigen was performed. A fungal colonies were isolated from the patient's home. Immunoblotting analysis with the patient's sera demonstrated a IgG-binding fractions to Penicillium species extract, while binding was not noted with control subject. This study indicates that the patient had hypersensitivity pneumonitis on exposure to Penicillium species in her home environment.